FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Baudard, M Flotte, T Aran, JM Pastan, I Gottesman, MM AF Baudard, M Flotte, T Aran, JM Pastan, I Gottesman, MM TI Coordinate expression of the human multidrug resistance (MDRI) and the glucocerebrosidase (GC) cDNAs from a bicistronic adeno-associated vector: In vitro and in vivo delivery via liposomes. SO BLOOD LA English DT Meeting Abstract C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV HOSP,EUDOWOOD DIV PEDIAT RESP SCI,BALTIMORE,MD 21287. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2497 EP 2497 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002498 ER PT J AU Orlic, D Cline, AP Sidel, NE Girard, LJ Jordan, CT Bodine, DM AF Orlic, D Cline, AP Sidel, NE Girard, LJ Jordan, CT Bodine, DM TI The relative level of expression of retrovirus receptor mRNAs in mouse and human primitive hematopoietic stem cells predicts the efficiency of gene transfer. SO BLOOD LA English DT Meeting Abstract C1 NCHGR,LGT,BETHESDA,MD. SOMATIX CORP,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2498 EP 2498 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002499 ER PT J AU Be, TV Binh, TV Anderson, T Kaufman, DW Young, NS AF Be, TV Binh, TV Anderson, T Kaufman, DW Young, NS TI Epidemiology of aplastic anemia in Vietnam: Preliminary data from an incidence study in Ho Chi Minh city. SO BLOOD LA English DT Meeting Abstract C1 BLOOD TRANSFUS & HEMATOL CTR, SLONE EPIDEMIOL UNIT, HO CHI MINH CITY, 02215, VIETNAM. BOSTON UNIV, HEMATOL BRANCH, BOSTON, MA 20892 USA. NHLBI, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2525 EP 2525 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002526 ER PT J AU Dancis, A Stearman, R Yuan, D Klausner, RD AF Dancis, A Stearman, R Yuan, D Klausner, RD TI Genetics of iron uptake in Saccharomyces cerevisiae SO BLOOD LA English DT Meeting Abstract C1 NIH,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2528 EP 2528 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002529 ER PT J AU Yu, J Nagarajan, S Desai, S Liu, J Young, N Magnuson, T Colemanares, C Medof, ME AF Yu, J Nagarajan, S Desai, S Liu, J Young, N Magnuson, T Colemanares, C Medof, ME TI Neuronal differentiation in PIG-A knockout cell lines SO BLOOD LA English DT Meeting Abstract C1 CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. CLEVELAND CLIN RES FDN,CLEVELAND,OH. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2548 EP 2548 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002549 ER PT J AU Fairbanks, V Merritt, D Rodgers, D Thibodeau, S Steinberg, M Coleman, M Jones, R AF Fairbanks, V Merritt, D Rodgers, D Thibodeau, S Steinberg, M Coleman, M Jones, R TI A compound heterozygote with alpha-thalassemia-2 trait and hemoglobin Seal Rock simulating mild Hb H disease: DNA analysis proves the extended alpha chain mutation in Hb Seal Rock is TAA->GAA in the stop codon immediately 3' to codon 141 in the upstream alpha globin gene (alpha 2). SO BLOOD LA English DT Meeting Abstract C1 WASHINGTON UNIV,SCH MED,ST LOUIS,MO. NIH,BETHESDA,MD 20892. MAYO CLIN,ROCHESTER,MN. VET ADM MED CTR,JACKSON,MS. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2575 EP 2575 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002576 ER PT J AU Schwartz, GN Szabo, JM Gress, RE Perdue, JF AF Schwartz, GN Szabo, JM Gress, RE Perdue, JF TI Stimulatory effects of insulin-like growth factor II (IGF-II) on the maintenance and differentiation of committed and primitive hematopoietic progenitors from CD34+ bone marrow cells. SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. AMER RED CROSS,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2708 EP 2708 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002709 ER PT J AU Stefanova, I OShaughnessy, J Zujewski, J Cowan, K Reed, E Bolen, JB Wittes, RE Horak, ID AF Stefanova, I OShaughnessy, J Zujewski, J Cowan, K Reed, E Bolen, JB Wittes, RE Horak, ID TI Molecular mechanisms of cancer associated immunosuppression. Paradigm of T-cell regulation SO BLOOD LA English DT Meeting Abstract C1 NIH,NATL CANC INST,BETHESDA,MD 20892. DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2873 EP 2873 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002874 ER PT J AU Robertson, KD Manns, A Swinnen, LJ Hayward, SD Ambinder, RF AF Robertson, KD Manns, A Swinnen, LJ Hayward, SD Ambinder, RF TI Escape from Epstein-Barr virus (EBV)-specific cytotoxic T cell immune surveillance in neoplastic and non-neoplastic B cells is facilitated by methylation of a crucial site in the major viral latency promoter. SO BLOOD LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,DEPT ONCOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD. LOYOLA UNIV,DEPT MED,CHICAGO,IL 60611. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2949 EP 2949 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002950 ER PT J AU Haag, M Sutcliffe, M Wayne, A Dumont, D Saari, J Giusti, V Wall, J Favara, B AF Haag, M Sutcliffe, M Wayne, A Dumont, D Saari, J Giusti, V Wall, J Favara, B TI A rare case of interdigitating dendritic cell sarcoma (IDCS) in pediatrics: Cytogenetics, pathology and clinical correlation. SO BLOOD LA English DT Meeting Abstract C1 UNIV S FLORIDA, ALL CHILDRENS HOSP, DEPT PATHOL, ST PETERSBURG, FL 33701 USA. UNIV S FLORIDA, ALL CHILDRENS HOSP, DEPT IMMUNOL, ST PETERSBURG, FL 33701 USA. UNIV S FLORIDA, TAMPA, FL USA. MD ANDERSON CANC CTR, ORLANDO, FL USA. NIAID, HAMILTON, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 3241 EP 3241 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91003242 ER PT J AU Goad, K Killiany, B Rosenfeld, S Wesley, R Gross, J Macklin, L Singh, K Tucker, E Kramer, W Gralnick, HR Pucino, F AF Goad, K Killiany, B Rosenfeld, S Wesley, R Gross, J Macklin, L Singh, K Tucker, E Kramer, W Gralnick, HR Pucino, F TI Evaluation of a portable capillary prothrombin time monitor. SO BLOOD LA English DT Meeting Abstract C1 NIH,CTR CLIN,DEPT CLIN PATHOL,HEMATOL SECT,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 3474 EP 3474 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91003475 ER PT J AU FRANCHINI, G AF FRANCHINI, G TI MOLECULAR MECHANISMS OF HUMAN T-CELL LEUKEMIA/LYMPHOTROPIC VIRUS TYPE-I INFECTION SO BLOOD LA English DT Review ID LONG TERMINAL REPEAT; NF-KAPPA-B; LEUKEMIA-LYMPHOMA VIRUS; GROWTH-FACTOR RECEPTOR; TROPICAL SPASTIC PARAPARESIS; REX-RESPONSE ELEMENT; NON-HUMAN PRIMATES; PAPUA-NEW-GUINEA; PX MESSENGER-RNA; PAPILLOMAVIRUS-E5 TRANSFORMING PROTEIN RP FRANCHINI, G (reprint author), NCI,TUMOR CELL BIOL LAB,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. NR 319 TC 277 Z9 282 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 NOV 15 PY 1995 VL 86 IS 10 BP 3619 EP 3639 PG 21 WC Hematology SC Hematology GA TE585 UT WOS:A1995TE58500001 PM 7579327 ER PT J AU Schwartz, GN Szabo, JM Rose, WJ Halverson, D Hakim, FT Cepeda, R Zujewski, J OShaughnessy, J Cowan, KH Gress, RE Warren, MK AF Schwartz, GN Szabo, JM Rose, WJ Halverson, D Hakim, FT Cepeda, R Zujewski, J OShaughnessy, J Cowan, KH Gress, RE Warren, MK TI Early suppressive effects of chemotherapy on bone marrow megakaryocyte precursors. SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. OTSUKA AMER PHARMACEUT INC,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 3619 EP 3619 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91003620 ER PT J AU Bessudo, A Rassenti, L Feigal, E Kipps, TJ AF Bessudo, A Rassenti, L Feigal, E Kipps, TJ TI Immunoglobulin V-H gene repertoire of patients with AIDS SO BLOOD LA English DT Meeting Abstract C1 UCSD,SCH MED,DEPT MED,LA JOLLA,CA. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 3703 EP 3703 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91003703 ER PT J AU HE, RY REID, DM JONES, CE SHULMAN, NR AF HE, RY REID, DM JONES, CE SHULMAN, NR TI EXTRACELLULAR EPITOPES OF PLATELET GLYCOPROTEIN IB-ALPHA REACTIVE WITH SERUM ANTIBODIES FROM PATIENTS WITH CHRONIC IDIOPATHIC THROMBOCYTOPENIC PURPURA SO BLOOD LA English DT Article ID VONWILLEBRAND-FACTOR-BINDING; AMINO-ACID-SEQUENCES; ANTIGENIC DETERMINANTS; BLOOD PLATELETS; AUTOANTIBODIES; PLASMA; IIIA; IDENTIFICATION; PROTEINS; DOMAIN AB Glycoproteins (GPs) IIb/IIIa and Ib/IX are principal targets of autoantibodies (autoAbs) in idiopathic thrombocytopenic purpura (ITP), Platelet-associated Abs against GPIIb/IIIa primarily recognize discontinuous or nonlinear epitopes (Fujisawa et al, Blood 81:1284, 1993). This study focused on whether Abs against the extracellular domain of GPIb/IX might react with short linear amino acid (aa) sequences of GPIb alpha. Complementary DNAs (cDNAs) coding for two overlapping fragments of GPIb alpha were amplified, cloned into pFLAG.2 plasmids, and expressed in Escherichia coli DH5 alpha competent cells as FLAG fusion proteins, which were purified by anti-FLAG immunoaffinity chromatography. Of 16 selected ITP sera containing anti-GPIb/IX, 6 reacted in microtiter radioimmunoassays (RIAs) with recombinant protein fragment 2 (aas 240 to 485); 1 also with fragment 1 (aas 1 to 247), When synthetic peptides corresponding to 4 segments of fragment 2 with high antigenic indices (P1 to P4) were used as targets in RIAs, all 6 sera reacted with P2 (aas 326 to 346); 1 also reacted with P4 (aas 389 to 412). P2 was shown to be present on the surface of intact platelets by adsorption studies, and anti-P2 was detected in direct eluates of platelets from ITP patients. Glycocalicin in solution effectively competed with immobilized P2 for anti-P2; P2 in solution was a less effective competitor, Epitope scanning with a panel of synthetic 15-mer peptides localized the P2 epitope to the sequence, TKEQTTFPP. Epitope definition may offer insight into the pathophysiology of and more specific treatments for ITP. (C) 1995 by The American Society of Hematology. RP HE, RY (reprint author), NIDDK,CLIN HEMATOL BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 4D51,BETHESDA,MD 20892, USA. NR 40 TC 28 Z9 30 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 NOV 15 PY 1995 VL 86 IS 10 BP 3789 EP 3796 PG 8 WC Hematology SC Hematology GA TE585 UT WOS:A1995TE58500020 PM 7579346 ER PT J AU ZHU, QL ZHANG, M BLAESE, RM DERRY, JMJ JUNKER, A FRANCKE, U CHEN, SH OCHS, HD AF ZHU, QL ZHANG, M BLAESE, RM DERRY, JMJ JUNKER, A FRANCKE, U CHEN, SH OCHS, HD TI THE WISKOTT-ALDRICH SYNDROME AND X-LINKED CONGENITAL THROMBOCYTOPENIA ARE CAUSED BY MUTATIONS OF THE SAME GENE SO BLOOD LA English DT Article ID INACTIVATION; LYMPHOCYTES; PLATELETS AB The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, small platelets, eczema, recurrent infections, and immunodeficiency. Besides the classic WAS phenotype, there is a group of patients with congenital X-linked thrombocytopenia (XLT) who have small platelets but only transient eczema, if any, and minimal immune deficiency. Because the gene responsible for WAS has been sequenced, it was possible to correlate the WAS phenotypes with WAS gene mutations. Using a fingerprinting screening technique, we determined the approximate location of the mutation in 13 unrelated WAS patients with mild to severe clinical symptoms. Direct sequence analysis of cDNA and genomic DNA obtained from patient-derived cell lines showed 12 unique mutations distributed throughout the WAS gene, including insertions, deletions, and point mutations resulting in amino acid substitutions, termination, exon skipping, or splicing defects. Of 4 unrelated patients with the XLT phenotype, 3 had missense mutations affecting exon 2 and 1 had a splice-site mutation affecting exon 9. Patients with classic WAS had more complex mutations, resulting in termination codons, frameshift, and early termination. These findings provide direct evidence that XLT and WAS are caused by mutations of the same gene and suggest that severe clinical phenotypes are associated with complex mutations. (C) 1995 by The American Society of Hematology. C1 UNIV WASHINGTON,SCH MED,DEPT PEDIAT,SEATTLE,WA 98195. NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. STANFORD UNIV,MED CTR,BECKMAN CTR MOLEC & GENET MED,HOWARD HUGHES MED INST,STANFORD,CA 94305. UNIV BRITISH COLUMBIA,DEPT PEDIAT,VANCOUVER,BC V6T 1W5,CANADA. FU NICHD NIH HHS [HD17427] NR 25 TC 126 Z9 132 U1 1 U2 2 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 NOV 15 PY 1995 VL 86 IS 10 BP 3797 EP 3804 PG 8 WC Hematology SC Hematology GA TE585 UT WOS:A1995TE58500021 PM 7579347 ER PT J AU Evans, GL Chuah, MKL VandenDriessche, T Morgan, RA AF Evans, GL Chuah, MKL VandenDriessche, T Morgan, RA TI Development and analysis of retroviral vectors expressing human factor VIII as a potential gene therapy for hemophilia A SO BLOOD LA English DT Meeting Abstract C1 NIH,NCHGR,CLIN GENE THERAPY BRANCH,GENE TRANSFER TECHNOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 3976 EP 3976 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91003976 ER PT J AU Hallek, M Wendtner, CM Mangold, E Nolte, A BraunFalco, M Chiorini, JA Kotin, RM Maass, G Emmerich, B Winnacker, EL AF Hallek, M Wendtner, CM Mangold, E Nolte, A BraunFalco, M Chiorini, JA Kotin, RM Maass, G Emmerich, B Winnacker, EL TI Human lymphoid tumor cells transduced with recombinant adeno-associated virus (AAV) vectors containing B7-1 and B7-2 genes provide potent costimulatory signals for T cell proliferation. SO BLOOD LA English DT Meeting Abstract C1 TECH UNIV MUNCHEN WEIHENSTEPHAN,KLINIKUM INNENSTADT,MED KLIN,MUNICH,GERMANY. TECH UNIV MUNCHEN WEIHENSTEPHAN,GENZENTRUM,MUNICH,GERMANY. MEDIGENE GMBH,MARTINSRIED,GERMANY. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 3984 EP 3984 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91003984 ER PT J AU Li, F Linton, GF Malech, HL AF Li, F Linton, GF Malech, HL TI Comparison of G-CSF mobilized and steady-state peripheral blood CD34+ cells: Colony forming unit expansion and transduction efficiency. SO BLOOD LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 3992 EP 3992 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91003992 ER PT J AU Maples, PB Marx, JC Thimmapaya, R Bratten, WR Wolf, L TsengLaw, J Maruya, A Deans, RJ Carter, CS Wannebo, C WhitingTheobald, N Linton, GF Malech, HL AF Maples, PB Marx, JC Thimmapaya, R Bratten, WR Wolf, L TsengLaw, J Maruya, A Deans, RJ Carter, CS Wannebo, C WhitingTheobald, N Linton, GF Malech, HL TI Development of a closed system fluid path for CD34+ cell gene therapy. SO BLOOD LA English DT Meeting Abstract C1 BAXTER HLTHCARE CORP,DIV IMMUNOTHERAPY,ROUND LAKE,IL. BAXTER HLTHCARE CORP,DIV FENWAL,ROUND LAKE,IL. NIAID,HOST DEF LAB,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 3996 EP 3996 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91003996 ER PT J AU Munshi, NC Govindarajan, R Barlogie, B Drake, R Ding, LM Iyer, R Saylors, R Kornbluth, J Marcus, S Chiang, Y Ennist, D Reynolds, C Tricot, G AF Munshi, NC Govindarajan, R Barlogie, B Drake, R Ding, LM Iyer, R Saylors, R Kornbluth, J Marcus, S Chiang, Y Ennist, D Reynolds, C Tricot, G TI Thymidine kinase (TK) gene transduced human lymphocytes can be killed with ganciclovir - Preclinical studies. SO BLOOD LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. GENET THERAPY INC,GAITHERSBURG,MD. FREDERICK CANC RES & DEV CTR,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 4001 EP 4001 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91004001 ER PT J AU HENSON, DE RIES, LA AF HENSON, DE RIES, LA TI THE RELATIVE SURVIVAL RATE SO CANCER LA English DT Editorial Material RP HENSON, DE (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. NR 5 TC 99 Z9 99 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 NOV 15 PY 1995 VL 76 IS 10 BP 1687 EP 1688 DI 10.1002/1097-0142(19951115)76:10<1687::AID-CNCR2820761002>3.0.CO;2-I PG 2 WC Oncology SC Oncology GA TC718 UT WOS:A1995TC71800001 PM 8625034 ER PT J AU LIOTTA, LA AF LIOTTA, LA TI THE US-ITALY WORKSHOP ON THE MOLECULAR-GENETICS OF CANCER - INTRODUCTION SO CANCER LA English DT Editorial Material RP LIOTTA, LA (reprint author), NCI,PATHOL LAB,BLDG 10,ROOM 2A33,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1995 VL 76 IS 10 BP 1868 EP 1868 DI 10.1002/1097-0142(19951115)76:10<1868::AID-CNCR2820761029>3.0.CO;2-P PG 1 WC Oncology SC Oncology GA TC718 UT WOS:A1995TC71800028 PM 8625060 ER PT J AU BUDILLON, A AF BUDILLON, A TI MOLECULAR-GENETICS OF CANCER - ONCOGENES AND TUMOR-SUPPRESSOR GENES SO CANCER LA English DT Editorial Material RP BUDILLON, A (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,CELLULAR BIOCHEM SECT,BLDG 10,RM 5B05,BETHESDA,MD 20892, USA. OI Budillon, Alfredo/0000-0002-6330-6053 NR 3 TC 6 Z9 6 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 NOV 15 PY 1995 VL 76 IS 10 BP 1869 EP 1873 DI 10.1002/1097-0142(19951115)76:10<1869::AID-CNCR2820761030>3.0.CO;2-B PG 5 WC Oncology SC Oncology GA TC718 UT WOS:A1995TC71800029 PM 8625061 ER PT J AU ALESSANDRO, R KOHN, EC AF ALESSANDRO, R KOHN, EC TI MOLECULAR-GENETICS OF CANCER - TUMOR INVASION AND ANGIOGENESIS SO CANCER LA English DT Editorial Material ID METASTASIS RP ALESSANDRO, R (reprint author), NCI,SIGNAL TRANSDUCT & PREVENT UNIT,BLDG 10,RM 2A33,BETHESDA,MD 20892, USA. NR 13 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 1995 VL 76 IS 10 BP 1874 EP 1877 DI 10.1002/1097-0142(19951115)76:10<1874::AID-CNCR2820761031>3.0.CO;2-M PG 4 WC Oncology SC Oncology GA TC718 UT WOS:A1995TC71800030 PM 8625062 ER PT J AU BRONTE, V AF BRONTE, V TI MOLECULAR-GENETICS OF CANCER - GENE-THERAPY AND OTHER NOVEL THERAPEUTIC APPROACHES SO CANCER LA English DT Editorial Material RP BRONTE, V (reprint author), NCI,SURG BRANCH,BLDG 10,RM 2B46,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 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 NOV 15 PY 1995 VL 76 IS 10 BP 1878 EP 1881 DI 10.1002/1097-0142(19951115)76:10<1878::AID-CNCR2820761032>3.0.CO;2-7 PG 4 WC Oncology SC Oncology GA TC718 UT WOS:A1995TC71800031 PM 8625063 ER PT J AU SCHIFFMAN, MH BRINTON, LA AF SCHIFFMAN, MH BRINTON, LA TI THE EPIDEMIOLOGY OF CERVICAL CARCINOGENESIS SO CANCER LA English DT Article; Proceedings Paper CT 5th National Conference of the American-Cancer-Society on Gynecologic Cancers CY APR 06-08, 1995 CL WASHINGTON, DC SP Amer Canc Soc DE CERVIX; CARCINOMA; HUMAN PAPILLOMAVIRUS INFECTION; EPIDEMIOLOGY ID HUMAN PAPILLOMAVIRUS INFECTION; POLYMERASE CHAIN-REACTION; HIGH-INCIDENCE AREA; LOS-ANGELES-COUNTY; RISK-FACTORS; ORAL-CONTRACEPTIVES; INTRAEPITHELIAL NEOPLASIA; UTERINE CERVIX; CIGARETTE-SMOKING; YOUNG-WOMEN AB Epidemiologic and laboratory data suggest that cervical cancer typically arises from a series of causal steps, Each step can be studied separately in the hope of better etiologic understanding and improved cancer prevention. The earliest identified etiologic step is infection of young women with specific types of venereally transmissible human papillomaviruses (HPVs). Cervical HPV infections often lead to low grade squamous intraepithelial lesions (mildly abnormal Pap smears). Human papillomavirus infections and their associated lesions are extremely common among young, sexually active women. The infections typically resolve spontaneously even at the molecular level within months to a few years. Uncommonly, HPV infections and/or low grade lesions persist and progress to high grade lesions. The risk factors for progression are mainly unknown but include HPV type and intensity, cell-mediated immunity, and reproductive factors. Nutritional factors or co-infection with other pathogens may also be involved at this apparently critical etiologic step between common low grade and uncommon high grade intraepithelial lesions. Except for advancing age, no epidemiologic risk factors have been found for the next step between high grade intraepithelial lesions and invasive cancer. At the molecular level, invasion is associated with integration of viral DNA. Based on worldwide research, the steps in cervical carcinogenesis appear to be fundamentally the same everywhere, with a central role for HPV infection. The importance of etiologic cofactors like smoking, however, may vary by region. RP SCHIFFMAN, MH (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 165 TC 237 Z9 257 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 1995 VL 76 IS 10 SU S BP 1888 EP 1901 DI 10.1002/1097-0142(19951115)76:10+<1888::AID-CNCR2820761305>3.0.CO;2-H PG 14 WC Oncology SC Oncology GA TE563 UT WOS:A1995TE56300003 PM 8634980 ER PT J AU BELL, DA BADAWI, AF LANG, NP ILETT, KF KADLUBAR, FF HIRVONEN, A AF BELL, DA BADAWI, AF LANG, NP ILETT, KF KADLUBAR, FF HIRVONEN, A TI POLYMORPHISM IN THE N-ACETYLTRANSFERASE-1 (NAT1) POLYADENYLATION SIGNAL - ASSOCIATION OF NAT1-ASTERISK-10 ALLELE WITH HIGHER N-ACETYLATION ACTIVITY IN BLADDER AND COLON TISSUE SO CANCER RESEARCH LA English DT Note ID METABOLIC-ACTIVATION; MESSENGER-RNA; CARCINOGENS; GENE; EXPRESSION AB Exposures to carcinogens present in the diet, in cigarette smoke, or in the environment have been associated with increased risk of bladder and colorectal cancer, The aromatic amines and their metabolites, a class of carcinogen implicated in these exposures, can be N- or O-acetylated by the NAT1 and NAT2 enzymes. Acetylation may result in activation to DNA-reactive metabolites or, in some cases, detoxification. Many studies have focused on genetic variation in NAT2 and its potential as a risk factor in bladder and colorectal cancer; however, NAT1 activity is higher in bladder and colonic mucosa than NAT2, and the NAT1 enzyme also exhibits phenotypic variation among human tissue samples, We hypothesized that specific genetic variants in the polyadenylation signal of the NAT1 gene would alter tissue levels of NAT1 enzyme activity and used a PCR-based method to distinguish polymorphic NAT1 alleles in samples obtained from 45 individuals, When the NAT1 genotype was compared with the NAT1 phenotype in bladder and colon tissue samples (p-aminobenzoic acid activity), we observed a similar to 2-fold higher NAT1 enzyme activity in samples from individuals who inherited a variant polyadenylation signal (NAT1*10 allele). This is the first observation relating a genetic polymorphism in NAT1 to a rapid/slow NAT1 phenotype in humans. C1 NATL CTR TOXICOL RES,DIV MOLEC EPIDEMIOL,JEFFERSON,AR 72079. UNIV ARKANSAS,CANC RES CTR,LITTLE ROCK,AR 72205. UNIV WESTERN AUSTRALIA,DEPT PHARMACOL,NEDLANDS,WA 6009,AUSTRALIA. RP BELL, DA (reprint author), NIEHS,BIOCHEM RISK ANAL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 32 TC 213 Z9 221 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 NOV 15 PY 1995 VL 55 IS 22 BP 5226 EP 5229 PG 4 WC Oncology SC Oncology GA TD887 UT WOS:A1995TD88700022 PM 7585580 ER PT J AU BADAWI, AF HIRVONEN, A BELL, DA LANG, NP KADLUBAR, FF AF BADAWI, AF HIRVONEN, A BELL, DA LANG, NP KADLUBAR, FF TI ROLE OF AROMATIC AMINE ACETYLTRANSFERASES, NAT1 AND NAT2, IN CARCINOGEN-DNA ADDUCT FORMATION IN THE HUMAN URINARY-BLADDER SO CANCER RESEARCH LA English DT Article ID EXFOLIATED UROTHELIAL CELLS; DEPENDENT METABOLIC-ACTIVATION; ARYLAMINE N-ACETYLTRANSFERASE; HUMAN UROEPITHELIAL CELLS; HEMOGLOBIN ADDUCTS; CANCER; ACETYLATION; SUSCEPTIBILITY; PHENOTYPE; RISK AB The metabolic activation and detoxification pathways associated with the carcinogenic aromatic amines provide an extraordinary model of polymorphisms that can modulate human urinary bladder carcinogenesis, In this study, the metabolic N-acetylation of p-aminobenzoic acid (PABA) to N-acetyl-PABA (NAT1 activity) and of sulfamethazine (SMZ) to N-acetyl-SMZ (NAT2 activity), as well as the O-acetylation of N-hydroxy-4-aminobiphenyl (OAT activity; catalyzed by NAT1 and NAT2), were measured in tissue cytosols prepared from 26 different human bladder samples; then DNA was isolated for determination of NAT1 and NAT2 genotype and for analyses of carcinogen-DNA adducts. Both PABA and OAT activities were detected, with mean activities +/- SD of 2.9 +/- 2.3 mmol/min/mg protein and 1.4 +/- 0.7 pmol bound/mg DNA/min/mg protein, respectively, However, SMZ activities were below the assay limits of detection (< 10 pmol/min/mg protein), The levels of putative carcinogen-DNA adducts were quantified by P-32-postlabeling and averaged 2.34 +/- 2.09 adducts/10(8) deoxyribonucleotide phosphate (dNp). Moreover, the DNA adduct levels in these tissues correlated with their NAT1-dependent PABA activities (r = 0.52; P < 0.01) but not with their OAT activities, Statistical and probit analyses indicated that this NAT1 activity was not normally distributed and appeared bimodal, Applying the NAT1:OAT activity ratios (N:O ratio) allowed arbitrary designation of rapid and slow NAT1 phenotypes, with a cutpoint near the median value, Within each of these subgroups, NAT1 correlated with OAT (P < 0.05); DNA adduct levels were elevated 2-fold in individuals with the rapid NAT1 or NAT1/OAT phenotype. Examination of DNA sequence polymorphisms in the NAT1 gene by PCR have demonstrated that an NAT1 polyadenylation polymorphism is associated with differences in tissue NAT1 enzyme activity; accordingly, NAT1 activity in the bladder of individuals with the heterozygous NAT1*10 allele was 2-fold higher than in subjects homozygous for the putative wild-type NAT1*4 allele, Likewise, DIVA adduct levels in the mucosa of the urinary bladder were found to be 2-fold (P < 0.05) higher in individuals with the heterozygous NAT1*10 allele (3.5 +/- 2.1 adducts/10(8) dNp) as compared to NAT1*4 homozygous (1.8 +/- 1.9 adducts/10(8) dNp). Thus, these data provide strong support for the hypothesis that NAT1 activity in the urinary bladder mucosa represents a major bioactivation step that converts urinary N-hydroxy arylamines to reactive N-acetoxy esters that form covalent DNA adducts. Since previous studies have indicated that hepatic NAT2 activity is an important detoxification step for bladder carcinogenesis, one would predict that individuals who inherit slow NAT2 and rapid NAT1 (NAT1*10) genotypes would be at highest risk, Although our sample size was limited, this combined genotype indeed exhibited the highest adduct level (4.2 +/- 1.6 adducts/10(8) dNp) and the highest NAT1 activity (5.8 +/- 2.5 nnol/min/mg protein) among all other combined NAT1-NAT2 genotypes, Together, these data provide the first evidence that phenotypic and genotypic polymorphisms in both NAT1 and NAT2 are predictive of DNA adduct levels in human urinary bladder. C1 NATL CTR TOXICOL RES,DIV MOLEC EPIDEMIOL HFT100,JEFFERSON,AR 72079. NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. UNIV ARKANSAS,LITTLE ROCK,AR 72205. NR 74 TC 196 Z9 198 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1995 VL 55 IS 22 BP 5230 EP 5237 PG 8 WC Oncology SC Oncology GA TD887 UT WOS:A1995TD88700023 PM 7585581 ER PT J AU DUNNICK, JK ELWELL, MR RADOVSKY, AE BENSON, JM HAHN, FF NIKULA, KJ BARR, EB HOBBS, CH AF DUNNICK, JK ELWELL, MR RADOVSKY, AE BENSON, JM HAHN, FF NIKULA, KJ BARR, EB HOBBS, CH TI COMPARATIVE CARCINOGENIC EFFECTS OF NICKEL SUBSULFIDE, NICKEL-OXIDE, OR NICKEL SULFATE HEXAHYDRATE CHRONIC EXPOSURES IN THE LUNG SO CANCER RESEARCH LA English DT Article ID SULFIDE PARTICLES; INHALATION EXPOSURE; REGRESSION-ANALYSIS; CADMIUM COMPOUNDS; F344/N RATS; CELLS; PHAGOCYTOSIS; TOXICITY; WORKERS; MICE AB The relative toxicity and carcinogenicity of nickel sulfate hexahydrate (NiSO4 . 6H(2)O), nickel subsulfide (Ni3S2), and nickel oxide (NiO) were studied in F344/N rats and B6C3F(1) mice after inhalation exposure for 6 h/day, 5 days/week, for 2 years. Nickel subsulfide (0.15 and 1 mg/m(3)) and nickel oxide (1.25 and 2.5 mg/m(3)) caused an exposure-related increased incidence of alveolar/bronchiolar neoplasms and adrenal medulla neoplasms in male and female rats. Nickel oxide caused an equivocal exposure-related increase in alveolar/bronchiolar neoplasms in female mice. No exposure-related neoplastic responses occurred in rats or mice exposed to nickel sulfate or in mice exposed to nickel subsulfide. These findings are consistent with results from other studies, which show that nickel subsulfide and nickel oxide reach the nucleus in greater amounts than the do water-soluble nickel compounds such as nickel sulfate. It has been proposed that the more water-insoluble particles are phagocytized, whereas the vacuoles containing nickel migrate to the nuclear membrane, where they release nickel ions that effect DNA damage. The findings from these experimental studies show that chronic exposure to nickel can cause lung neoplasms in rats, and that this response is related to exposure to specific types of nickel compounds. C1 INHALAT TOXICOL RES INST, ALBUQUERQUE, NM 87185 USA. RP DUNNICK, JK (reprint author), NIEHS, RES TRIANGLE PK, NC 27709 USA. FU NIEHS NIH HHS [Y01-ES-30108] NR 44 TC 111 Z9 114 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1995 VL 55 IS 22 BP 5251 EP 5256 PG 6 WC Oncology SC Oncology GA TD887 UT WOS:A1995TD88700026 PM 7585584 ER PT J AU WAALKES, MP DIWAN, BA WARD, JM DEVOR, DE GOYER, RA AF WAALKES, MP DIWAN, BA WARD, JM DEVOR, DE GOYER, RA TI RENAL TUBULAR TUMORS AND ATYPICAL HYPERPLASIAS IN B6C3F(1) MICE EXPOSED TO LEAD ACETATE DURING GESTATION AND LACTATION OCCUR WITH MINIMAL CHRONIC NEPHROPATHY SO CANCER RESEARCH LA English DT Article ID RATS; CARCINOGENICITY; TOXICOLOGY; INDUCTION; PREGNANCY; PROMOTION; PHOSPHATE; LESIONS; ACID AB Lead is a high-priority hazardous substance in humans and a renal carcinogen in adult rodents. This study assessed the carcinogenic potential and toxicity of gestational and lactational lead exposure in (C57BL/6NCr x C3H/HeN)F-1 (hereafter called E6C3F(1)) mice. Effects of a renal tumor promoter [barbital sodium (BB)] on lead-initiated lesions were also studied. Pregnant female C57BL/6NCr mice (10-15/group) previously bred with C3H/HeN males were given lead acetate (0, 500, 750 and 1000 ppm lead) ad libitum in their drinking water, starting on gestation day 12 and continuing to 4 weeks postpartum. Offspring were then weaned and divided into same-sex groups of 23-25 and observed for a maximum of 112 weeks. Other groups received lead and then continuous BE (500 ppm) ad libitum in their drinking mater from weaning onward. In control male offspring (0 lead/0 BE), renal proliferative lesions [(RPLs); defined as atypical tubular hyperplasia or tumor] occurred rarely (1 lesion-bearing mouse/23 mice examined, 4%) and did not include tumors. RPLs increased in a dose-related fashion with lead exposure (500 lead/0 BE, 4/25, 16%; 750 lead/0 BE, 6/25, 24%; 1000 lead/0 BE, 12/25, 48%) in male offspring and mere often multiple. Ail lead-treated groups had renal tumors, including carcinoma, but these were most common at the highest dose (1000 lead/0 BE, 5/25). Lead-induced renal tumors arose in the absence of the extensive chronic nephropathy and lead inclusion bodies typically seen with lead carcinogenesis in rodents exposed chronically as adults. Postnatal BE exposure had no effect on RPL incidence (e.g., 1000 lead/500 BE, 8/25, 32%). Lead-treated female offspring also developed RPLs, including adenoma and carcinoma, but at a much lower rate than males. Thus, short-term lead exposure during the gestational/lactational period has carcinogenic potential in the mouse kidney. C1 NCI,FREDERICK CANC RES & DEV CTR,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. UNIV WESTERN ONTARIO,DEPT PATHOL,LONDON,ON N6A 3K7,CANADA. RP WAALKES, MP (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,INORGAN CARCINOGENESIS SECT,FREDERICK,MD 21702, USA. NR 49 TC 35 Z9 36 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1995 VL 55 IS 22 BP 5265 EP 5271 PG 7 WC Oncology SC Oncology GA TD887 UT WOS:A1995TD88700028 PM 7585586 ER PT J AU CHOI, CW LANG, L LEE, JT WEBBER, KO YOO, TM CHANG, HK LE, N JAGODA, E PAIK, CH PASTAN, I ECKELMAN, WC CARRASQUILLO, JA AF CHOI, CW LANG, L LEE, JT WEBBER, KO YOO, TM CHANG, HK LE, N JAGODA, E PAIK, CH PASTAN, I ECKELMAN, WC CARRASQUILLO, JA TI BIODISTRIBUTION OF F-18-LABELED AND I-125 LABELED ANTI-TAC DISULFIDE-STABILIZED FV FRAGMENTS IN NUDE-MICE WITH INTERLEUKIN 2-ALPHA RECEPTOR-POSITIVE TUMOR XENOGRAFTS SO CANCER RESEARCH LA English DT Article ID SINGLE-CHAIN-FV; MONOCLONAL-ANTIBODY; IMMUNOGLOBULIN FRAGMENTS; SELF-DISPLACEMENT; ESCHERICHIA-COLI; BINDING; PROTEINS; FORMS; RADIOIMMUNODETECTION; RADIOACTIVITY AB We evaluated the biodistribution, pharmacokinetics, and generation of catabolites of an F-18- and I-125-labeled anti-Tac disulfide-stabilized Pv fragment (dsFv) in tumor-bearing nude mice. This dsFv is genetically engineered from a murine monoclonal antibody that recognizes the alpha subunit of the interleukin 2 (IL-2 alpha) receptor. Labeling was performed with F-18 using N-succinimidyl 4-([F-18]fluoromethyl)benzoate or with I-125 using the Iodo-Gen method. The immunoreactivities of the radiolabeled anti-Tac dsFv were >82%. The biodistribution was evaluated (at 15, 45, and 90 min and 6 h) in athymic nude mice (similar to five/group) bearing s.c. tumor xenografts. Cell line A431 served as the IL-2 receptor-negative control tumor, whereas the ATAC4 cell line served as our IL-2 receptor-positive tumor. Animals received injections of F-18-labeled anti-Tac dsFv (0.7-1.4 megabecquerels/1.5-3 mu g) and I-125-labeled anti-Tac dsFv (0.1-0.4 megabecquerels/0.9-1 mu g). Blood clearance for both preparations was rapid, with <10% retained in the blood by 15 min. Maximum accumulation in ATAC4 tumors occurred between 45 and 90 min and peaked at a mean of 4.2% injected dose/g (F-18) and 5.6% of injected dose/g (I-125). At 6 h, the ATAC4 tumors contained 11 times more F-18 and 3 times more I-125 than did the A431 tumors. The ATAC4 tumor:blood ratios for the F-18 and I-125 were >12:1 and >1.4:1 at 6 h, respectively, whereas the ratios for the antigen-negative A431 tumor were less than 1. The kidneys were the major route of elimination. Catabolites appeared quickly and were identified as [I-125]iodide and predominantly N-epsilon-[F-18]4-nuoromethylbenzoyl(alpha-N-acetyl) lysine. This is the first study to evaluate the biodistribution of an F-18-labeled Fv fragment in vitro and irt vivo. In vivo, the dsFv was taken up rapidly by the kidneys, producing lysine-containing catabolites for F-18-labeled dsFv and [I-125]iodide for I-125-labeled dsFv. C1 NCI,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. NCI,DEPT NUCL MED,BETHESDA,MD 20892. NCI,DEPT POSITRON EMISS TOMOG,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 41 TC 50 Z9 51 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 NOV 15 PY 1995 VL 55 IS 22 BP 5323 EP 5329 PG 7 WC Oncology SC Oncology GA TD887 UT WOS:A1995TD88700037 PM 7585595 ER PT J AU TIAN, ZG LONGO, DL FUNAKOSHI, S ASAI, O FERRIS, DK WIDMER, M MURPHY, WJ AF TIAN, ZG LONGO, DL FUNAKOSHI, S ASAI, O FERRIS, DK WIDMER, M MURPHY, WJ TI IN-VIVO ANTITUMOR EFFECTS OF UNCONJUGATED CD30 MONOCLONAL-ANTIBODIES ON HUMAN ANAPLASTIC LARGE-CELL LYMPHOMA XENOGRAFTS SO CANCER RESEARCH LA English DT Article ID REED-STERNBERG CELLS; HODGKINS-DISEASE; KI-1 ANTIGEN; RECEPTOR; INVIVO; MALIGNANCIES; EXPRESSION AB CD30 is a M(r) 120,000 surface antigen identified originally by the Ki-l monoclonal antibody (moAb) against primary and cultured Reed-Sternberg cells present in Hodgkin's disease and anaplastic large-cell lymphomas (ALCLs). Examination of two ALCL cell Lines (Karpas 299 and Michel) demonstrated cell surface expression of CD30. Incubation of these lymphomas with two anti-CD30 moAbs that recognize the ligand-binding site (M44 or HeFi-1) resulted in significant growth inhibition in vitro, with significant decreases in cell viability. Another anti-CD30 moAb, Ber-H2, which recognizes a determinant not involved in ligand binding, had no effect on ALCL growth in vitro. When these human ALCL lines were transferred i.v. into mice with severe combined immune deficiency, the mice developed extensive metastasis in the s.c., brain, or eye tissues. The treatment of mice with either M44 or HeFi-1 anti-CD30 moAbs resulted in significant increases in survival, with some mice remaining disease free for more than 100 days. Thus, anti-CD30 treatment is efficacious for CD30(+) ALCL cell lines in vivo, and unconjugated anti-CD30 moAbs may be of potential clinical use. C1 NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. IMMUNEX RES & DEV CORP,SEATTLE,WA 98101. RI Tian, Zhigang/J-3512-2013 NR 24 TC 68 Z9 71 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 NOV 15 PY 1995 VL 55 IS 22 BP 5335 EP 5341 PG 7 WC Oncology SC Oncology GA TD887 UT WOS:A1995TD88700039 PM 7585597 ER PT J AU BREUNINGER, LM PAUL, S GAUGHAN, K MIKI, T CHAN, A AARONSON, SA KRUH, GD AF BREUNINGER, LM PAUL, S GAUGHAN, K MIKI, T CHAN, A AARONSON, SA KRUH, GD TI EXPRESSION OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN IN NIH/3T3 CELLS CONFERS MULTIDRUG-RESISTANCE ASSOCIATED WITH INCREASED DRUG EFFLUX AND ALTERED INTRACELLULAR DRUG DISTRIBUTION SO CANCER RESEARCH LA English DT Article ID P-GLYCOPROTEIN; TOPOISOMERASE-II; HL-60 CELLS; HL60 CELLS; LINES; GENE; ADRIAMYCIN; TRANSPORTER; MECHANISMS; ACCUMULATION AB Multidrug resistance is a major obstacle to cancer treatment. Using an expression cDNA library transfer approach to elucidating the molecular basis of non-P-glycoprotein-mediated multidrug resistance, we previously established that expression of multidrug resistance protein (MRP), an ATP-binding cassette superfamily transporter, confers multidrug resistance (G. D. Kruh et al., Cancer Res., 54: 1649-1652, 1994). In the present study, we generated NIH/3T3 MRP transfectants without using chemotherapeutic drugs to facilitate the pharmacological analysis of the MRP phenotype. MRP transfectants displayed increased resistance to several lipophilic drugs, including doxorubicin, daunorubicin, etoposide, actinomycin D, vincristine, and vinblastine. However, increased resistance was not observed for Taxol, a drug for which transfection of MDR1 confers high levels of resistance. Verapamil increased the sensitivity of MRP transfectants relative to control transfectants, but reversal was incomplete for doxorubicin and etoposide, the drugs for which MRP conferred the highest resistance levels. For the latter two drugs, MRP transfectants, which were similar to 8- and similar to 10-fold more sensitive than control cells in the absence of verapamil, exhibited 3.8- and 3.3-fold relative sensitization with 10 mu M verapamil, respectively, but remained similar to 2 and similar to 3-fold more resistant than control cells. Analysis of drug kinetics using radiolabeled daunorubicin revealed decreased accumulation and increased efflux in MRP transfectants. Confocal microscopic analysis of intracellular daunorubicin in MRP transfectants was consistent with reduced intracellular drug concentrations, and also revealed an altered pattern of intracellular drug distribution characterized by the initial accumulation of drug in a perinuclear location, followed by the development of a punctate pattern of drug scattered throughout the cytoplasm. This pattern was suggestive of a process of drug sequestration, possibly followed by vesicle transport. Both increased drug efflux and perinuclear drug accumulation are consistent with the reported localization of MRP in plasma and cytosolic membranes (N. Krishnamachary and M. S. Center, Cancer Res., 53: 3658-3663, 1993; hi. J. Flens et at, Cancer Res., 54: 4557-4563, 1994). These results thus indicate that the drug specificity of MRP is quite similar to that of,MDR1, but also suggest potential differences in Taxol specificity and the level of verapamil sensitivity. In addition, these results indicate that MRP functions to extrude drug from the cell, but additionally suggest the intriguing possibility that drug sequestration contributes to drug resistance by protecting cellular targets and/or contributing to drug efflux. C1 FOX CHASE CANC CTR,DEPT MED ONCOL,PHILADELPHIA,PA 19111. NIH,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. DERALD H RUTTENBERG CANC CTR,NEW YORK,NY 10029. FU NCI NIH HHS [R01 CA63173] NR 42 TC 204 Z9 208 U1 1 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 NOV 15 PY 1995 VL 55 IS 22 BP 5342 EP 5347 PG 6 WC Oncology SC Oncology GA TD887 UT WOS:A1995TD88700040 PM 7585598 ER PT J AU RIED, T JUST, KE HOLTGREVEGREZ, H DUMANOIR, S SPEICHER, MR SCHROCK, E LATHAM, C BLEGEN, H ZETTERBERG, A CREMER, T AUER, G AF RIED, T JUST, KE HOLTGREVEGREZ, H DUMANOIR, S SPEICHER, MR SCHROCK, E LATHAM, C BLEGEN, H ZETTERBERG, A CREMER, T AUER, G TI COMPARATIVE GENOMIC HYBRIDIZATION OF FORMALIN-FIXED, PARAFFIN-EMBEDDED BREAST-TUMORS REVEALS DIFFERENT PATTERNS OF CHROMOSOMAL GAINS AND LOSSES IN FIBROADENOMAS AND DIPLOID AND ANEUPLOID CARCINOMAS SO CANCER RESEARCH LA English DT Article ID MOLECULAR CYTOGENETIC ANALYSIS; NUCLEAR-DNA CONTENT; INSITU HYBRIDIZATION; SOLID TUMORS; SUPPRESSOR GENE; AMPLIFICATION; PROGNOSIS; CANCER; P53; ABNORMALITIES AB Comparative genomic hybridization serves as a screening test for regions of copy number changes in tumor genomes. We have applied the technique to map DNA gains and losses in 33 cases of formalin-fixed, paraffin-embedded primary breast tumors (13 fibroadenomas and 10 diploid and 10 aneuploid carcinomas). No genomic imbalances were found in fibroadenomas. Recurrent findings in adenocarcinomas include copy number increases for chromosomes 1q (14 of 20 samples), 8q (10 of 20), 17q (5 of 20), 6p (3 of 20), 13q (3 of 20), and 16p (3 of 20), and copy number decreases for chromosomes 22 (7 of 20), 17p (6 of 20), and 20 (3 of 20). Regional high level copy number increases were observed on chromosome bands 1q32, 8p11, 8q24, 10p, 11q13, 12p, 12q15, 17q11-12, and 17q22-24. The majority of the samples were studied for gene amplification of c-myc, c-erbB2, cycD1, and int-2 by means of Southern blot analysis. The comparison with DNA ploidy measurements revealed a different distribution and a significantly higher number of chromosomal C1 UNIV HEIDELBERG,INST HUMAN GENET,D-69120 HEIDELBERG,GERMANY. KAROLINSKA HOSP & INST,DEPT PATHOL,STOCKHOLM,SWEDEN. RP RIED, T (reprint author), NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BLDG 49,49 CONVENT DR,MSC 4470,BETHESDA,MD 20892, USA. RI Speicher, Michael/B-5362-2013 OI Speicher, Michael/0000-0003-0105-955X NR 40 TC 209 Z9 210 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 NOV 15 PY 1995 VL 55 IS 22 BP 5415 EP 5423 PG 9 WC Oncology SC Oncology GA TD887 UT WOS:A1995TD88700053 PM 7585611 ER PT J AU VANWAES, C SURH, DM CHEN, Z KIRBY, M RHIM, JS BRAGER, R SESSIONS, RB POORE, J WOLF, GT CAREY, TE AF VANWAES, C SURH, DM CHEN, Z KIRBY, M RHIM, JS BRAGER, R SESSIONS, RB POORE, J WOLF, GT CAREY, TE TI INCREASE IN SUPRABASILAR INTEGRIN ADHESION MOLECULE EXPRESSION IN HUMAN EPIDERMAL NEOPLASMS ACCOMPANIES INCREASED PROLIFERATION OCCURRING WITH IMMORTALIZATION AND TUMOR SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; BASEMENT-MEMBRANE; BIOCHEMICAL-CHARACTERIZATION; ALPHA-6-BETA-4 INTEGRIN; HUMAN KERATINOCYTES; LAMININ RECEPTOR; T-CELLS; ALPHA-2-BETA-1; SUBUNIT; LINES AB In a previous prospective study of SO patients with squamous cell carcinoma of the upper aerodigestive tract, a progressive increase in expression of the integrin cell adhesion molecule alpha(6) beta(4) in suprabasilar cell layers of the tumor parenchyma was associated with an increase in early recurrence after therapy, In this study, we determined the relationship of the altered expression pattern of the integrin to changes occurring during benign, invasive, or metastatic stages of tumor development, Suprabasilar expression of integrin alpha(6) beta(4) appeared with neoplastic transformation in benign squamous papillomas, but homogeneous expression occurred more frequently in the parenchyma of primary and metastatic squamous cell carcinomas, The variation in the extent of suprabasilar integrin expression among the tumors corresponded to the variation In the population undergoing proliferation as determined by two independent markers of proliferation, Integrin expression was quantified in primary, HPV 16 DNA-immortalized, and v-ki-ras oncogene-transformed keratinocytes, and the pattern of expression was compared with cell cycle progression. Primary keratinocyte lines showed a binodal distribution of integrin expression, with one population showing decreased integrin expression, cell size, and a block of cell cycle progression consistent with differentiation, whereas another population exhibited high integrin expression and full progression through the cell cycle, consistent with proliferation, HPV-immortalized and v-ki-ras-transformed cell lines undergoing continuous proliferation exhibited uniformly strong integrin expression, which was similar in intensity to that observed in the proliferating population of normal keratinocytes. Similar increases in expression of two additional integrins, alpha(2) beta(1) and alpha(3) beta(1), occurred along with integrin alpha(6) beta(4) in tissue specimens and cell lines derived from neoplasms, Thus, epidermal neoplasms display an increase in a population of cells exhibiting constitutive expression of a repertoire of integrins, which is similar to that found transiently in the acute phase of epidermal wound healing, a physiological response in which hyperproliferation, retention of multiple layers of proliferating cells, and migration occur, The association of a progressive increase in suprabasilar expression of these integrins with early tumor recurrence and advanced neoplasia suggests that constitutive expression and function of the same repertoire of integrins may be advantageous, rather than sufficient, for tumor progression. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NCI,MOLEC ONCOL LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT OTOLARYNGOL,WASHINGTON,DC. UNIV MICHIGAN,DEPT OTOLARYNGOL,ANN ARBOR,MI 48109. RP VANWAES, C (reprint author), NIDCD,HEAD & NECK SURG BRANCH,TUMOR BIOL SECT,ROOM 5D55,BLDG 10,MSC 1419,10 CTR DR,BETHESDA,MD 20892, USA. FU NIDCD NIH HHS [Z01-DC-00017] NR 44 TC 64 Z9 64 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 NOV 15 PY 1995 VL 55 IS 22 BP 5434 EP 5444 PG 11 WC Oncology SC Oncology GA TD887 UT WOS:A1995TD88700055 PM 7585613 ER PT J AU PIERUZZI, F ABASSI, ZA KEISER, HR AF PIERUZZI, F ABASSI, ZA KEISER, HR TI EXPRESSION OF RENIN-ANGIOTENSIN SYSTEM COMPONENTS IN THE HEART, KIDNEYS, AND LUNGS OF RATS WITH EXPERIMENTAL HEART-FAILURE SO CIRCULATION LA English DT Article DE HEART FAILURE; RENIN-ANGIOTENSIN SYSTEM ID ATRIAL-NATRIURETIC-PEPTIDE; II RECEPTOR SUBTYPES; TISSUE-SPECIFIC ACTIVATION; CONVERTING ENZYME; SODIUM; ALDOSTERONE; GENE; HYPERTROPHY; MECHANISMS; RETENTION AB Background Chronic activation of the renin-angiotensin system (RAS) plays an important role in the pathogenesis of heart failure. Increasing evidence indicates that other than the circulating RAS, a local RAS exists in several tissues, including the heart. The present study was carried out to quantify cardiac, renal, and pulmonary mRNA levels of renin, angiotensin-converting enzyme (ACE), and types 1 and 2 angiotensin II receptors (AT-1 and AT-2), in rats with different severities of heart failure. Methods and Results Heart failure was induced by the creation of an aortocaval fistula below the renal arteries. Rats with aortocaval fistula either compensate and maintain a normal sodium balance or decompensate and develop severe sodium retention. Six days after placement of the aortocaval fistula, heart weight (normalized to body weight) increased 35% (P<.05) in compensated and 65% in decompensated rats compared with control rats. Plasma renin activity increased 45% (P<.05) in rats in sodium balance and 127% in sodium-retaining rats. Total RNA was extracted from the heart, kidneys, and lungs, followed by reverse transcription-quantitative polymerase chain reaction. Renin mRNA levels in the heart, after 40 cycles, increased 68% (P<.01) and 140% in rats with either compensated or decompensated heart failure, respectively. Renal renin-mRNA levels also increased 130% (P<.05) in decompensated and only 52% (P<.05) in compensated animals. ACE-mRNA increased in a similar pattern in the heart but not in either the kidneys or lungs. Moreover, pulmonary, renal, and cardiac ACE immunoreactivity levels, assessed by Western blot analysis, showed the same trend. AT-1 receptor mRNA levels decreased 54% (P<.05) only in the myocardium of decompensated rats, whereas AT-2 receptor mRNA did not change in any tissue studied. Conclusions The development of heart failure is associated with a remarkable increase in the expression of a local RAS in the heart, which may contribute to the pathogenesis of this clinical syndrome. C1 NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. UNIV MILAN,OSPED MAGGIORE,CTR FISIOL CLIN & IPERTENS,MILAN,ITALY. NR 71 TC 115 Z9 119 U1 1 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 15 PY 1995 VL 92 IS 10 BP 3105 EP 3112 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TE203 UT WOS:A1995TE20300044 PM 7586282 ER PT J AU CLARKE, K VEECH, RL AF CLARKE, K VEECH, RL TI [F-18] FDG IN MEASURING MYOCARDIAL GLUCOSE-UPTAKE - RESPONSE SO CIRCULATION LA English DT Letter ID POSITRON EMISSION TOMOGRAPHY; HEART C1 NIAAA,METAB & MOLEC BIOL LAB,ROCKVILLE,MD 20852. RP CLARKE, K (reprint author), UNIV OXFORD,DEPT BIOCHEM,S PARKS RD,OXFORD OX1 3QU,ENGLAND. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 15 PY 1995 VL 92 IS 10 BP 3148 EP 3148 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TE203 UT WOS:A1995TE20300056 ER PT J AU CLARKE, K AF CLARKE, K TI METABOLIC COMPLEXITIES IN CARDIAC IMAGING - RESPONSE SO CIRCULATION LA English DT Letter RP CLARKE, K (reprint author), NIAAA,METAB & MOLEC BIOL LAB,ROCKVILLE,MD 20852, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 15 PY 1995 VL 92 IS 10 BP 3151 EP 3151 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TE203 UT WOS:A1995TE20300061 ER PT J AU HURLIN, PJ QUEVA, C KOSKINEN, PJ STEINGRIMSSON, E AYER, DE COPELAND, NG JENKINS, NA EISENMAN, RN AF HURLIN, PJ QUEVA, C KOSKINEN, PJ STEINGRIMSSON, E AYER, DE COPELAND, NG JENKINS, NA EISENMAN, RN TI MAD3 AND MAD4 - NOVEL MAX-INTERACTING TRANSCRIPTIONAL REPRESSORS THAT SUPPRESS C-MYC DEPENDENT TRANSFORMATION AND ARE EXPRESSED DURING NEURAL AND EPIDERMAL DIFFERENTIATION SO EMBO JOURNAL LA English DT Article DE DIFFERENTIATION; MAD FAMILY; MAX; MYC; TRANSCRIPTIONAL REPRESSION ID DNA-BINDING; N-MYC; CELL-DIFFERENTIATION; RAS COTRANSFORMATION; ONCOGENE EXPRESSION; NEOPLASTIC-CELLS; PROTEIN; MOUSE; GENE; DIMERIZATION AB The basic helix-loop-helix-leucine zipper (bHLHZip) protein Max associates with members of the Myc family, as well as with the related proteins Mad (Mad1) and Mxi1, Whereas both Myc:Max and Mad:Max heterodimers bind related E-box sequences, Myc:Max activates transcription and promotes proliferation while Mad:Max represses transcription and suppresses Myc dependent transformation, Here we report the identification and characterization of two novel Mad1-and Mxi1-related proteins, Mad3 and Mad4. Mad3 and Mad4 interact with both Max and mSin3 and repress transcription from a promoter containing CACGTG binding sites, Using a rat embryo fibroblast transformation assay, we show that both Mad3 and Mad4 inhibit c-Myc dependent cell transformation, An examination of the expression patterns of all mad genes during murine embryogenesis reveals that mad1, mad3 and mad4 are expressed primarily in growth-arrested differentiating cells. mxi1 is also expressed in differentiating cells, but is co-expressed with either c-myc, N-myc, or both in proliferating cells of the developing central nervous system and the epidermis, In the developing central nervous system and epidermis, downregulation of myc genes occurs concomitant with upregulation of mad family genes, These expression patterns, together with the demonstrated ability of Mad family proteins to interfere with the proliferation promoting activities of Myc, suggest that the regulated expression of Myc and Mad family proteins function in a concerted fashion to regulate cell growth in differentiating tissues. C1 FRED HUTCHINSON CANC RES CTR,DIV BASIC SCI,SEATTLE,WA 98104. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RI Koskinen, Paivi/G-8939-2014 FU NCI NIH HHS [N01-CO-46000, R01CA57138] NR 68 TC 241 Z9 251 U1 1 U2 4 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 NOV 15 PY 1995 VL 14 IS 22 BP 5646 EP 5659 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TG172 UT WOS:A1995TG17200021 PM 8521822 ER PT J AU Blaese, RM AF Blaese, RM TI Steps toward gene therapy .1. The initial trials SO HOSPITAL PRACTICE LA English DT Article AB Hopes for correcting the instruction tape in patients with genetic disease are being intensively explored. Initial efforts centered on monogenic immunodeficiency states, but in a pattern not wholly expected by researchers, the ''acquired genetic diseases'' of cancer and AIDS account for most ongoing clinical trials. Experience with adenosine deaminase deficiency shows the difficulties encountered in creating practical gene therapies. RP Blaese, RM (reprint author), NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD NOV 15 PY 1995 VL 30 IS 11 BP 33 EP 40 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA TK569 UT WOS:A1995TK56900014 PM 8557801 ER PT J AU KAWAMATA, H KAMEYAMA, S KAWAI, K TANAKA, Y NAN, L BARCH, DH STETLERSTEVENSON, WG OYASU, R AF KAWAMATA, H KAMEYAMA, S KAWAI, K TANAKA, Y NAN, L BARCH, DH STETLERSTEVENSON, WG OYASU, R TI MARKED ACCELERATION OF THE METASTATIC PHENOTYPE OF A RAT BLADDER-CARCINOMA CELL-LINE BY THE EXPRESSION OF HUMAN GELATINASE-A SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID BRONCHIAL EPITHELIAL-CELLS; IV COLLAGENASE; TISSUE INHIBITOR; METALLOPROTEINASE INHIBITOR; CANCER METASTASIS; ORGAN ENVIRONMENT; INVASION; TIMP-2; SECRETE; ASSAY AB Numerous studies have reported a correlation between the production of gelatinases A and B by cancer cells and invasive and metastatic potential. It has been suggested that the expression of gelatinase A (72-kDa type IV collagenase) is associated more closely with the metastatic phenotype of malignant cells in vitro and in vivo than that of gelatinase B (92-kDa type IV collagenase). We have established a rat bladder carcinoma cell line, MYU3L, which is tumorigenic and locally invasive but is not metastatic to the distal organs in nude mice. The MYU3L cell line secretes pro-gelatinase B but not any detectable level of pro-gelatinase A. We undertook the present study to determine whether over-expression of gelatinase A can affect the metastatic potential of MYU3L cells. We transfected MYU3L cells with an expression vector containing human pro-gelatinase A cDNA under the transcriptional control of the SR alpha promoter. Two stable transfectants over-expressing gelatinase A activity were isolated. We assessed the biological behavior of the transfectants by an orthotopic site (urinary bladder) inoculation and an i.v. injection in nude mice. Our results demonstrate that the induced expression of human gelatinase A enzyme markedly accelerates the metastatic phenotype of the rat bladder carcinoma cell line MYU3L. Our results suggest that gelatinase A produced by tumor cells plays a major role in the metastatic process. (C) 1995 Wiley-Liss, Inc. C1 NORTHWESTERN UNIV,SCH MED,DEPT PATHOL,CHICAGO,IL 60611. NORTHWESTERN UNIV,SCH MED,DEPT MED,CHICAGO,IL 60611. NORTHWESTERN UNIV,VET ADM LAKESIDE MED CTR,CHICAGO,IL 60611. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NCI NIH HHS [CA14649] NR 25 TC 58 Z9 63 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 NOV 15 PY 1995 VL 63 IS 4 BP 568 EP 575 DI 10.1002/ijc.2910630418 PG 8 WC Oncology SC Oncology GA TF625 UT WOS:A1995TF62500017 PM 7591268 ER PT J AU ESSMANN, U PERERA, L BERKOWITZ, ML DARDEN, T LEE, H PEDERSEN, LG AF ESSMANN, U PERERA, L BERKOWITZ, ML DARDEN, T LEE, H PEDERSEN, LG TI A SMOOTH PARTICLE MESH EWALD METHOD SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; RANGE ELECTROSTATIC INTERACTIONS; PERIODIC BOUNDARY-CONDITIONS; COMPUTER-SIMULATION; CONSTANT-PRESSURE; SOLVATED POLYPEPTIDES; DIELECTRIC-CONSTANT; MULTIPOLE METHOD; PAIR POTENTIALS; LATTICE SUMS AB The previously developed particle mesh Ewald method is reformulated in terms of efficient B-spline interpolation of the structure factors. This reformulation allows a natural extension of the method to potentials of the form 1/r(p) with p greater than or equal to 1. Furthermore, efficient calculation of the virial tensor follows. Use of B-splines in place of Lagrange interpolation leads to analytic gradients as well as a significant improvement in the accuracy. We demonstrate that arbitrary accuracy can be achieved, independent of system size N, at a cost that scales as N log(N). For biomolecular systems with many thousands of atoms this method permits the use of Ewald summation at a computational cost comparable to that of a simple truncation method of 10 angstroms or less. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP ESSMANN, U (reprint author), UNIV N CAROLINA,DEPT CHEM,CB 3290,CHAPEL HILL,NC 27599, USA. RI perera, Lalith/B-6879-2012; Pedersen, Lee/E-3405-2013; Cheng, Yushao/E-6256-2011 OI perera, Lalith/0000-0003-0823-1631; Pedersen, Lee/0000-0003-1262-9861; NR 67 TC 8217 Z9 8285 U1 55 U2 458 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD NOV 15 PY 1995 VL 103 IS 19 BP 8577 EP 8593 DI 10.1063/1.470117 PG 17 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA TE364 UT WOS:A1995TE36400026 ER PT J AU HALVORSON, MJ COLIGAN, JE AF HALVORSON, MJ COLIGAN, JE TI ENHANCEMENT OF VLA INTEGRIN RECEPTOR FUNCTION ON THYMOCYTES BY CAMP IS DEPENDENT ON THE MATURATION STAGE OF THE THYMOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; THYMIC STROMAL CELLS; PROTEIN-KINASE-C; EXTRACELLULAR-MATRIX; REGULATED EXPRESSION; IMMATURE THYMOCYTES; ARACHIDONIC-ACID; CROSS-LINKING; LYMPHOCYTES-T; BINDING-SITES AB A class of adhesion molecules, the VLA integrins, are expressed on thymocytes and have been shown to affect immature thymocyte differentiation in vitro. This study examines the ability of cAMP to regulate VLA receptor function in thymocytes. Pharmacologic agents that raise intracellular cAMP enhanced the binding of immature CD4(-) CD8(-) and CD4(+). CD8(+) thymocytes to fibronectin while having no effect on the binding of the more mature Jlld(-) thymocytes. PGE(2), a hormone produced by thymic epithelial cells and known to raise intracellular cAMP levels in thymocytes, also increased the binding of immature thymocytes to fibronectin. In contrast, activation of protein kinase C via PMA enhanced the binding of all three thymocyte subsets. The cAMP-induced binding was blocked by mAbs to the VLA integrin chains alpha(4) and alpha(5) and by the protein kinase A (PKA) inhibitor, (Rp)-cAMPS, indicating that activation of PKA enhances VLA-4 and VLA-5 receptor function. Activation of PKA was induced in all three thymocyte subsets following addition of cAMPa or forskolin, indicating that the inability of cAMP to enhance the binding of Jlld(-) thymocytes was not due to an inability to activate PKA. Thus, cAMP enhances integrin function in thymocytes in a maturation stage-specific manner. C1 NIAID,MOLEC STRUCT LAB,BETHESDA,MD 20852. NR 53 TC 16 Z9 16 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 NOV 15 PY 1995 VL 155 IS 10 BP 4567 EP 4574 PG 8 WC Immunology SC Immunology GA TD888 UT WOS:A1995TD88800008 PM 7594454 ER PT J AU HATHCOCK, KS PUCILLO, CEM LASZLO, G LAI, L HODES, RJ AF HATHCOCK, KS PUCILLO, CEM LASZLO, G LAI, L HODES, RJ TI ANALYSIS OF THYMIC SUBPOPULATIONS EXPRESSING THE ACTIVATION ANTIGEN GL7 - EXPRESSION, GENETICS, AND FUNCTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; MONOCLONAL-ANTIBODY; MOUSE THYMOCYTES; CD4+; DIFFERENTIATION; LYMPHOCYTES; SELECTION; DETERMINANTS; MATURATION; SUBSETS AB Previously, we reported an mAb, GL7, that defines an activation Ag expressed by in vitro-stimulated B and T cells as well as by a subpopulation of thymocytes. The current study analyzes the GL7-expressing populations of adult and fetal thymus and demonstrates that: 1) The majority of GL7(+) adult thymocytes are CD4(+)CD8(-) cells that are CD3 epsilon(high), TCR-alpha beta(high), HSA(low), and bimodal for CD69 expression. The 3G11(-)6C10(-) subset of CD4(+)CD8(-) thymocytes is enriched in GL7-expressing cells. 2) Strain differences exist in the expression of GL7 on adult CD4(+)CD8(-) thymocytes; 21.9 +/- 5.9% of BALB/c CD4(+)CD8(-) thymocytes are GL7(+), whereas 4.4 +/- 1.7% of C57BL/6 CD4(+)CD8(-) thymocytes are GL7(+). The low GL7 expression phenotype is dominant in CB6F1 thymocytes (7.0 +/- 2.0%), and analysis of BALB/c x CB6F1 mice suggests that low GL7 expression is determined by multiple genes. 3) CD4(+)CD8(-) GL7(+) thymocytes from BALB/c mice, but not C57BL/6 mice, are skewed toward a high proportion of V beta 8(+) cells. 4) Adult GL7(+) CD4(+)CD8(-) thymocytes can be activated by TCR-specific stimuli to proliferate and to secrete high amounts of IL-4. 5) Fetal thymocytes contain GL7(+) cells, which are predominantly CD4(-)CD8(-), HSA(low), CD69(-), and bimodal for TCR-gamma delta. Thus, GL7 expression defines a subpopulation of functionally competent TCR-alpha beta(+) CD4(+)CD8(-) thymocytes as well as TCR-gamma delta(+) and TCR(-) subpopulations of fetal CD4(-)CD8(-) thymocytes. C1 UNIV UDINE, SCH MED, DEPT BIOMED SCI & TECHNOL, IMMUNOL SECT, I-33100 UDINE, ITALY. EOTVOS LORAND UNIV, DEPT IMMUNOL, H-2131 GODOLLO, HUNGARY. PHARMINGEN, SAN DIEGO, CA 92121 USA. RP HATHCOCK, KS (reprint author), NCI, EXPTL IMMUNOL BRANCH, 900 ROCKVILLE PIKE, BLDG 10, ROOM 4B-10, BETHESDA, MD 20892 USA. RI Pucillo, Carlo/A-5515-2008; OI Pucillo, Carlo/0000-0002-4872-6156 NR 31 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1995 VL 155 IS 10 BP 4575 EP 4581 PG 7 WC Immunology SC Immunology GA TD888 UT WOS:A1995TD88800009 PM 7594455 ER PT J AU MEMON, SA MORENO, MB PETRAK, D ZACHARCHUK, CM AF MEMON, SA MORENO, MB PETRAK, D ZACHARCHUK, CM TI BCL-2 BLOCKS GLUCOCORTICOID-INDUCED BUT NOT FAS-INDUCED OR ACTIVATION-INDUCED APOPTOSIS IN A T-CELL HYBRIDOMA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; BETA-GALACTOSIDASE; DNA FRAGMENTATION; COWPOX VIRUS; CYCLE BLOCK; DEATH; PROTEIN; ANTIGEN; GENE; INVOLVEMENT AB Overexpression of Bcl-2 can prevent or markedly delay cell death induced by a variety of apoptotic stimuli. Although Fas and Fas ligand (FasL) interactions play a major role in the elimination of self-reactive T cells in the periphery, inhibition of Fas-mediated killing by Bcl-2 has not been consistently observed. The mouse T hybridoma 2B4.11 (2B4) has been a useful model to study glucocorticoid- and activation-induced apoptosis, which is mediated through Fas and FasL. Using both stable transfectants and transient transfections, overexpression of Bcl-2 or Bcl-x(L) readily blocked glucocorticoid-induced but not activation-induced apoptosis of 2B4 cells. Bcl-2 expression did not inhibit Fas-mediated cytotoxicity triggered by cells expressing Fast or by the transient transfection of human Fas. Similarly, overexpression of Bcl-2 in the mouse T hybridoma A1.1 did not block activation-induced/Fas-mediated apoptosis. In Jurkat cells, however, expression of Bcl-2 partially inhibited anti-fas-induced cell death. A Bcl-2-related protein that can interfere with anti-fas killing, the adenoviral E1B 19K, also did not block activation-induced/Fas-mediated apoptosis in 2B4 cells. In contrast, expression of CrmA, a cowpox virus protein that inhibits ICE-like protease activity, blocked activation-induced apoptosis in 2B4 cells but had little effect on Dex-mediated cytotoxicity. These results show that: 1) Bcl-2 can have strikingly different anti-cell death activity in the same cell depending upon the apoptotic stimulus, 2) distinct apoptosis signaling pathways may exist with differential sensitivity to Bcl-2 and ICE-like protease inhibitors. C1 NCI,BIOL RESPONSE MODIFIERS PROGRAM,IMMUNE CELL BIOL LAB,BETHESDA,MD 20892. RI Memon, Sarfraz/E-1198-2013 NR 83 TC 170 Z9 174 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 NOV 15 PY 1995 VL 155 IS 10 BP 4644 EP 4652 PG 9 WC Immunology SC Immunology GA TD888 UT WOS:A1995TD88800017 PM 7594463 ER PT J AU SUFFREDINI, AF REDA, D BANKS, SM TROPEA, M AGOSTI, JM MILLER, R AF SUFFREDINI, AF REDA, D BANKS, SM TROPEA, M AGOSTI, JM MILLER, R TI EFFECTS OF RECOMBINANT DIMERIC TNF RECEPTOR ON HUMAN INFLAMMATORY RESPONSES FOLLOWING INTRAVENOUS ENDOTOXIN ADMINISTRATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR GENE-EXPRESSION; SEPTIC SHOCK; FACTOR-ALPHA; MONOCLONAL-ANTIBODY; CARDIOVASCULAR-RESPONSE; FACTOR CACHECTIN; SEPSIS; MICE; EFFICACY AB Effects of dimeric TNF receptor (p80) Fc(TNFR:Fc) on acute phase responses were evaluated in 18 volunteers given endotoxin (4 ng/kg i.v.), Subjects were randomized to receive either placebo (n = 6), low dose TNFR:Fc (10 mg/m(2) i.v., n = 6), or high dose TNFR:Fc (60 mg/m(2) i.v., n = 6). TNFR:Fc blocked plasma TNF bioactivity (p = 0.001) and increased, in a dose-ordered fashion, TNF immunoactivity (p < 0.001). TNFR:Fc decreased secondary cytokine levels including IL-1 beta (p = 0.007), IL-8 (p < 0.001), IL-1 receptor antagonist(p < 0.001), granulocyte-CSF (p = 0.03), and growth regulated peptide-alpha(p = 0.001) but not macrophage inflammatory protein-1 alpha or IL-10. Low dose, but not high dose, TNFR:Fc blunted or delayed the release of epinephrine and cortisol (p less than or equal to 0.026). Despite the absence of plasma TNF bioactivity, high dose TNFR:Fc was less immunosuppressive than low dose TNFR:Fc as measured by cytokine and stress hormone responses. Endotoxin-related symptoms were not altered by TNFR:Fc and the febrile response was delayed but not diminished (p = 0.004). Increases in cardiac index (72 +/- 19%) and heart rate (60 +/- 10%) and decreases in systemic vascular resistance index (47 +/- 7%) were unaltered by TNFR:Fc. These data suggest that the inflammatory response to endotoxin can escape from high levels of circulating TNF-blocking activity and redundant pathways, independent of circulating TNF, can sustain inflammation and clinical responses caused by acute endotoxemia. C1 IMMUNEX CORP,SEATTLE,WA 98101. RP SUFFREDINI, AF (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BLDG 10,ROOM 7D-43,10 CTR DR,MSC-1662,BETHESDA,MD 20892, USA. NR 53 TC 153 Z9 158 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 NOV 15 PY 1995 VL 155 IS 10 BP 5038 EP 5045 PG 8 WC Immunology SC Immunology GA TD888 UT WOS:A1995TD88800066 PM 7594512 ER PT J AU PRASAD, JVNV LUNNEY, EA FERGUSON, D TUMMINO, PJ RUBIN, JR REYNER, EL STEWART, BH GUTTENDORF, RJ DOMAGALA, JM SUVOROV, LI GULNIK, SV TOPOL, IA BHAT, TN ERICKSON, JW AF PRASAD, JVNV LUNNEY, EA FERGUSON, D TUMMINO, PJ RUBIN, JR REYNER, EL STEWART, BH GUTTENDORF, RJ DOMAGALA, JM SUVOROV, LI GULNIK, SV TOPOL, IA BHAT, TN ERICKSON, JW TI HIV PROTEASE INHIBITORS POSSESSING A NOVEL, HIGH-AFFINITY, AND ACHIRAL P-1'/P-2' LIGAND WITH A UNIQUE PATTERN OF IN-VITRO RESISTANCE - IMPORTANCE OF A CONFORMATIONALLY-RESTRICTED TEMPLATE IN THE DESIGN OF ENZYME-INHIBITORS SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID HUMAN-SERUM ALBUMIN; MECHANISM; THERAPY; BINDING; SOLVENT AB Achiral pyran-2-one analogs possessing a 3-S-(2-alkylphenyl) group were determined to be high-affinity inhibitors for human immunodeficiency virus (HIV) protease (PR). Crystallographic, modeling, and structure-activity studies led to the 3-S-(2-tert-butylphenyl) moiety as an apparent optimal group to access the S-2'/S-1' pockets of the enzyme. Further optimization led to an inhibitor, 3-[(2-tert-butylphenyl)sulfanyl]-4-hydroxy-6-(3-methylphenyl)- pyran-2-one (14), possessing a K-i of 3 nM. An X-ray crystallographic structure of an inhibitor, 4-hydroxy-3-[(2-isopropylphenyl) sulfanyl]-6-phenylpyran-2-one (8), bound to HIV PR showed that the 3-S-(2-isopropylphenyl) group occupied the P-2' and P-1' pockets, while other crucial interactions were common to those found with other pyran-2-one analogs. The high potency observed for this series may be due, in part, to the restrictions on the intramolecular collapsibility of these molecules in aqueous solution, leading to a highly favorable hydrophobic effect on binding. Herein we report a novel P-2'/P-1' achiral ligand which results in a tight-binding inhibitor that occupies only three pockets in the enzyme and exhibits a unique pattern of in vitro resistance. C1 WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES DIV,DEPT BIOCHEM,ANN ARBOR,MI 48106. WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES DIV,DEPT PHARMACOKINET DRUG METAB,ANN ARBOR,MI 48106. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK BIOMED SUPERCOMP CTR,SAIC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,STRUCT BIOCHEM PROGRAM,SAIC,FREDERICK,MD 21702. RP PRASAD, JVNV (reprint author), WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES DIV,DEPT CHEM,2800 PLYMOUTH RD,ANN ARBOR,MI 48106, USA. NR 44 TC 33 Z9 33 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 15 PY 1995 VL 117 IS 45 BP 11070 EP 11074 DI 10.1021/ja00150a005 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA TE739 UT WOS:A1995TE73900005 ER PT J AU MADIGAN, MP ZIEGLER, RG BENICHOU, J BYRNE, C HOOVER, RN AF MADIGAN, MP ZIEGLER, RG BENICHOU, J BYRNE, C HOOVER, RN TI PROPORTION OF BREAST-CANCER CASES IN THE UNITED-STATES EXPLAINED BY WELL-ESTABLISHED RISK-FACTORS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ATTRIBUTABLE RISK AB Background: Few estimates of the fraction of cases of breast cancer attributable to recognized risk factors have been published, All estimates are based on selected groups, making their generalizability to the U.S. population uncertain, Purpose: our goal was to estimate the fraction of breast cancer cases in the United States attributable to well-established risk factors (i.e,, later age at first birth, nulliparity, higher family income, and first-degree family history of breast cancer), using data from the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study (NHEFS), the survey and follow-up of a probability sample of the U.S. population, Methods: From a cohort of 7508 female participants surveyed in the early 1970s, and followed up between 1982 and 1984 and again in 1987, 193 breast cancer cases were accrued for study. We calculated incidence rates, relative risks (RRs), and population attributable risks (PARs) for breast cancer risk factors and extended our results to the U.S. female population by using sample weights from the NHANES I survey, Results: Our PAR estimates suggest that later age at first birth and nulliparity accounted for a large fraction of U.S. breast cancer cases, 29.5% (95% confidence interval [CI] = 5.6%-53.3%); higher income contributed 18.9% (95% CI = -4.3% to 42.1%), and family history of breast cancer accounted for 9.1% (95% CI = 3.0%-15.2%). Taken together, these well-established risk factors accounted for approximately 47% (95% CI = 17%-77%) of breast cancer cases in the NHEFS cohort and about 41% (95% CI = 2%-80%) in the U.S. population, Conclusions: The RRs for most of these risk factors were modest, but their prevalence as a group was high, leading to estimates that suggest that a substantial proportion of breast cancer cases in the United States are explained by well-established risk factors, Implications: Elucidation of the determinants underlying recognized factors and study of other factors that may confer risk or protection are needed in efforts to advance understanding of breast cancer etiology and to aid in devising strategies for prevention. C1 NCI,DIV CANC ETIOL,BIOSTAT BRANCH,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. RP MADIGAN, MP (reprint author), NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,RM 443,BETHESDA,MD 20892, USA. RI Byrne, Celia/K-2964-2015 OI Byrne, Celia/0000-0001-8289-4252 NR 23 TC 374 Z9 383 U1 2 U2 11 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 NOV 15 PY 1995 VL 87 IS 22 BP 1681 EP 1685 DI 10.1093/jnci/87.22.1681 PG 5 WC Oncology SC Oncology GA TD409 UT WOS:A1995TD40900011 PM 7473816 ER PT J AU MAYBERRY, RM COATES, RJ HILL, HA CLICK, LA CHEN, VW AUSTIN, DF REDMOND, CK FENOGLIOPREISER, CM HUNTER, CP HAYNES, MA MUSS, HB WESLEY, MN GREENBERG, RS EDWARDS, BK AF MAYBERRY, RM COATES, RJ HILL, HA CLICK, LA CHEN, VW AUSTIN, DF REDMOND, CK FENOGLIOPREISER, CM HUNTER, CP HAYNES, MA MUSS, HB WESLEY, MN GREENBERG, RS EDWARDS, BK TI DETERMINANTS OF BLACK-WHITE DIFFERENCES IN COLON-CANCER SURVIVAL SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SOCIOECONOMIC-FACTORS; RACE AB Background: Blacks have lower survival rates for colon cancer than whites, possibly related to more advanced stages of disease at diagnosis and to socioeconomic differences between blacks and whites, White the black/white difference in colon cancer survival is well documented, the few studies that have investigated this difference have been limited by the modest number and type of explanatory factors that were considered, Purpose: We analyzed data from the National Cancer Institute Black/White Cancer Survival Study to determine 1) what characteristics might contribute to the racial difference in colon cancer survival and 2) if a survival disparity remained between black and white patients after adjustment was made for these characteristics. Methods: This prospective study included 454 blacks and a stratified random sample of 521 whites, aged 20-79 years, with cancer of the colon diagnosed from January 1, 1985, through December 31, 1986, and who were residents of the metropolitan areas of Atlanta, New Orleans, and San Francisco/Oakland, Follow-up was truncated on December 31, 1990, Cox proportional hazards regression was used to estimate the death rate among blacks relative to that among whites after adjustment for potential explanatory factors, including sociodemographic factors, concurrent (comorbid) medical conditions, stage at diagnosis, tumor characteristics, and treatment, All P values were calculated from two-tailed tests of statistical significance, Results: After adjustment for age, sex, and geographic area, the black-to-white mortality hazard ratio (HR) was 1.5 (95% confidence interval [CI] = 1.2-1.9), indicating that the risk of death among black patients was 50% higher than that among white patients, Further adjustment for stage reduced the excess cancer mortality to 20% (HR = 1.2; 95% CI = 1.0-1.5), decreasing the overall racial difference in excess mortality from 50% to 20% or to a 60% reduction in excess mortality, Although adjustment for poverty reduced the excess mortality by 20%, adjusting for both stage and poverty did not further reduce the racial difference, Among patients with stages II and III disease, blacks had lower survival rates than whites (HR = 1.8; 95% CI = 1.0-3.1 and HR = 1.5; 95% CI = 1.0-2.3, respectively), Among those patients with metastatic disease (stage IV), survival was similar for whites and blacks, Conclusions: Stage at diagnosis accounted for more than half of the excess colon cancer mortality observed among blacks, Poverty and other socioeconomic conditions, general health status, tumor characteristics, and general patterns of treatment did not further explain the remaining survival disadvantage among blacks, Implications: Because the racial disparity was confined to earlier stages, future studies should investigate whether blacks have more advanced disease at diagnosis and whether less aggressive treatment is provided because of understaging, C1 LOUISIANA STATE UNIV,MED CTR,DEPT PATHOL,NEW ORLEANS,LA 70112. OREGON STATE CANC REGISTRY,PORTLAND,OR. UNIV PITTSBURGH,SCH PUBL HLTH,DEPT BIOSTAT,PITTSBURGH,PA 15260. UNIV CINCINNATI,MED CTR,DEPT PATHOL & LAB MED,CINCINNATI,OH 45267. NIH,OFF RES WOMENS HLTH,OFF DIRECTOR,BETHESDA,MD 20892. CHARLES R DREW SCH MED & SCI,RANCHO PALOS VERDES,CA. WAKE FOREST UNIV,CTR COMPREHENS CANC,WINSTON SALEM,NC 27109. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP MAYBERRY, RM (reprint author), EMORY UNIV,ROLLINS SCH PUBL HLTH,DEPT EPIDEMIOL,1518 CLIFTON RD NE,ATLANTA,GA 30322, USA. NR 29 TC 166 Z9 168 U1 1 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 NOV 15 PY 1995 VL 87 IS 22 BP 1686 EP 1693 DI 10.1093/jnci/87.22.1686 PG 8 WC Oncology SC Oncology GA TD409 UT WOS:A1995TD40900012 PM 7473817 ER PT J AU WILSON, PWF AF WILSON, PWF TI CHOLESTEROL SCREENING - ONCE IS NOT ENOUGH SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID CORONARY HEART-DISEASE; PRIMARY-PREVENTION TRIAL; DYSLIPIDEMIA; RISK RP NHLBI, FRAMINGHAM HEART STUDY, 5 THURBER ST, FRAMINGHAM, MA 01701 USA. NR 25 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 13 PY 1995 VL 155 IS 20 BP 2146 EP 2147 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA TD267 UT WOS:A1995TD26700002 PM 7487235 ER PT J AU ANGLISTER, J REN, H KLEE, CB BAX, A AF ANGLISTER, J REN, H KLEE, CB BAX, A TI NMR IDENTIFICATION OF CALCINEURIN-B RESIDUES AFFECTED BY BINDING OF A CALCINEURIN-A PEPTIDE SO FEBS LETTERS LA English DT Article DE CALCINEURIN; NMR; CHAPS; PEPTIDE-PROTEIN ID TRIPLE-RESONANCE NMR; MULTIDIMENSIONAL NMR; CYCLOSPORINE-A; CENTRAL HELIX; PROTEIN; SPECTROSCOPY; COMPLEXES; SUBUNIT; TARGET; AMIDE AB Triple resonance 3D NMR methods have been used to study the interaction between calcineurin B and a peptide fragment of calcineurin A for which it has high affinity (K-D similar to 4 x 10(-7) M), Although calcineurin B aggregates at NMR concentrations of similar to 1 mM, in the presence of a target peptide fragment of calcineurin A it becomes monomeric and yields NMR spectra that are very similar to those reported previously for calcineurin B solubilized by the zwitterionic detergent CHAPS, Changes in chemical shifts between CHAPS- and peptide-solubilized calcineurin B are small which is indicative of no differences in secondary structure, Residues most affected by binding to target peptide are found primarily on the hydrophobic faces of the four helices, present in each of the two globular domains in calcineurin B, and in the loops connecting helices II and III, IV and V, and possibly in the C-terminal 12 residues, which also exhibit a change in mobility. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. WEIZMANN INST SCI,DEPT STRUCT CHEM,IL-76100 REHOVOT,ISRAEL. NR 30 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 13 PY 1995 VL 375 IS 1-2 BP 108 EP 112 DI 10.1016/0014-5793(95)01192-H PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TF351 UT WOS:A1995TF35100026 PM 7498455 ER PT J AU BAUMANN, MH MASH, DC STALEY, JK AF BAUMANN, MH MASH, DC STALEY, JK TI THE SEROTONIN AGONIST M-CHLOROPHENYLPIPERAZINE (MCPP) BINDS TO SEROTONIN TRANSPORTER SITES IN HUMAN BRAIN SO NEUROREPORT LA English DT Article DE M-CHLOROPHENYLPIPERAZINE; 5-HT TRANSPORTERS; [I-125] RTI-55; HUMAN BRAIN; D-FENFLURAMINE ID RAT-BRAIN; RECEPTORS; ARYLPIPERAZINES AB THE serotonin (5-HT) agonist m-chlorophenylpiperazine (mCPP) is commonly used as a neuroendocrine challenge agent in humans, and it is well accepted that its mechanism of action involves direct stimulation of postsynaptic 5-HT receptors. In the present work, we demonstrate that mCPP also displays appreciable affinity (IC50 = 230 nM) for 5-HT transporters labeled by [I-125]3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester ([I-125]RTI-55) in human occipital cortex. These data agree with reports that show mCPP increases extracellular 5-HT in rat brain via a mechanism involving 5-HT transporters. Our results indicate that mCPP may exhibit a presynaptic 5-HT action in man, and studies utilizing mCPP to assess 5-HT receptor sensitivity should be interpreted with caution. C1 UNIV MIAMI,SCH MED,DEPT NEUROL,MIAMI,FL 33101. RP BAUMANN, MH (reprint author), NIDA,DIV INTRAMURAL RES,CIN PSYCHOPHARMACOL SECT,POB 5180,BALTIMORE,MD 21224, USA. FU NIDA NIH HHS [DA O6227] NR 18 TC 43 Z9 44 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 NOV 13 PY 1995 VL 6 IS 16 BP 2150 EP 2152 DI 10.1097/00001756-199511000-00013 PG 3 WC Neurosciences SC Neurosciences & Neurology GA TH461 UT WOS:A1995TH46100012 PM 8595191 ER PT J AU WEISS, SRB LI, XL ROSEN, JB LI, H HEYNEN, T POST, RM AF WEISS, SRB LI, XL ROSEN, JB LI, H HEYNEN, T POST, RM TI QUENCHING - INHIBITION OF DEVELOPMENT AND EXPRESSION OF AMYGDALA-KINDLED SEIZURES WITH LOW-FREQUENCY STIMULATION SO NEUROREPORT LA English DT Article DE KINDLING; LONG-TERM DEPRESSION; DEPOTENTIATION; AMYGDALA; SEIZURE THRESHOLD; RATS ID POTENTIATION; MECHANISMS; EPILEPSY AB USING low frequency (quenching) stimulation parameters (1 Hz for 15 min), similar to those that induce long-term depression (LTD) in vitro, we attempted to alter amygdala kindling in vivo in rats. Quenching completely blocked the development and progression of afterdischarges and seizures in seven of eight animals. In fully kindled animals, once-daily quenching stimulation for one week (without concurrent kindling) suppressed the seizures when kindling stimulation was resumed. These effects of quenching probably resulted from the marked and long-lasting increases in the afterdischarge and seizure thresholds that were observed in these animals. These data indicate that quenching with low frequency electrical stimulation (which does not disrupt ongoing behavior) can have profound and long-lasting effects on seizure development, expression, and thresholds. The ultimate clinical applicability of low frequency stimulation in the treatment of seizures and related neuropsychiatric disorders remains to be explored. RP WEISS, SRB (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10-3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 132 Z9 137 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 NOV 13 PY 1995 VL 6 IS 16 BP 2171 EP 2176 DI 10.1097/00001756-199511000-00018 PG 6 WC Neurosciences SC Neurosciences & Neurology GA TH461 UT WOS:A1995TH46100017 PM 8595196 ER PT J AU STRUDLER, PK AF STRUDLER, PK TI NIH STUDY SECTIONS SO SCIENTIST LA English DT Letter RP STRUDLER, PK (reprint author), NIH,DIV RES GRANTS,RADIAT STUDY SECT,ROCKLEDGE II,ROOM 4144,MSC I804,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD NOV 13 PY 1995 VL 9 IS 22 BP 13 EP 13 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA TD483 UT WOS:A1995TD48300008 ER PT J AU RUSSIAN, DA KOVACS, JA AF RUSSIAN, DA KOVACS, JA TI PNEUMOCYSTIS-CARINII IN AFRICA - AN EMERGING PATHOGEN SO LANCET LA English DT Editorial Material ID HIV-INFECTION; PNEUMONIA; CHILDREN RP RUSSIAN, DA (reprint author), NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892, USA. NR 9 TC 21 Z9 21 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD NOV 11 PY 1995 VL 346 IS 8985 BP 1242 EP 1243 DI 10.1016/S0140-6736(95)91854-X PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA TE145 UT WOS:A1995TE14500002 PM 7475709 ER PT J AU FOSTER, WR AF FOSTER, WR TI IMPACT FACTOR AS THE BEST OPERATIONAL MEASURE OF MEDICAL JOURNALS SO LANCET LA English DT Letter RP FOSTER, WR (reprint author), NIH,BLDG 31-9A21,BETHESDA,MD 20892, USA. NR 4 TC 20 Z9 21 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD NOV 11 PY 1995 VL 346 IS 8985 BP 1301 EP 1301 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TE145 UT WOS:A1995TE14500057 PM 7475747 ER PT J AU KOONIN, EV ZHOU, SB LUCCHESI, JC AF KOONIN, EV ZHOU, SB LUCCHESI, JC TI THE CHROMO SUPERFAMILY - NEW MEMBERS, DUPLICATION OF THE CHROMO DOMAIN AND POSSIBLE ROLE IN DELIVERING TRANSCRIPTION REGULATORS TO CHROMATIN SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HETEROCHROMATIN-ASSOCIATED PROTEIN; DROSOPHILA-MELANOGASTER; MULTIPLE ALIGNMENT; BINDING PROTEIN; SEQUENCES; CLONING; GENE; LOCALIZATION; EXPRESSION; DATABASES AB Using computer methods for detecting conserved amino acid sequence motifs, we show that the chromatin organization modifier (chrome) domain that has been previously identified in several proteins involved in transcription down-regulation is present in a much larger group of (putative) chromatin-binding proteins, some of which are positive rather than negative regulators of transcription, The most interesting new members of the chrome superfamily are Drosophila male-specific lethal (MSL-3) protein involved in the X chromosome gene dosage compensation in the males and human retinoblastoma-binding protein RBP-1. We show that the chrome domain is duplicated in several chromatin-binding proteins and use this observation to interpret recent results on chromatin binding obtained with chimeric chrome domain- containing proteins, We hypothesize that the chrome domain may be a vehicle that delivers both positive and negative transcription regulators to the sites of their action on chromatin. C1 EMORY UNIV,DEPT BIOL,ATLANTA,GA 30322. RP KOONIN, EV (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 39 TC 157 Z9 162 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 11 PY 1995 VL 23 IS 21 BP 4229 EP 4233 DI 10.1093/nar/23.21.4229 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TG424 UT WOS:A1995TG42400002 PM 7501439 ER PT J AU ROSENBERG, HF DYER, KD AF ROSENBERG, HF DYER, KD TI HUMAN RIBONUCLEASE-4 (RNASE-4) - CODING SEQUENCE, CHROMOSOMAL LOCALIZATION AND IDENTIFICATION OF 2 DISTINCT TRANSCRIPTS IN HUMAN SOMATIC TISSUES SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EOSINOPHIL-DERIVED NEUROTOXIN; AMINO-ACID-SEQUENCE; BOVINE SEMINAL RIBONUCLEASE; POLYMERASE CHAIN-REACTION; MOLECULAR-CLONING; CATIONIC PROTEIN; PROMYELOCYTIC LEUKEMIA; MESSENGER-RNA; CELL-LINE; GENE AB We have isolated a unique genomic fragment encoding human ribonuclease 4 (RNase 4) of the mammalian ribonuclease gene family, whose members include pancreatic ribonuclease, eosinophil-derived neurotoxin, eosinophil cationic protein and angiogenin. We have determined that the coding sequence of RNase 4 resides on a single exon found on human chromosome 14, The mRNA encoding RNase 4 was detected by Northern analysis in a number of human somatic tissues, including pancreas, lung, skeletal muscle, heart, kidney and placenta, but not brain; liver represents the most abundant source, Interestingly, the mRNA encoding RNase 4 is similar to 2 kb in length, which is approximately twice as large as the mRNAs encoding other members of this gene family, A larger (similar to 2,4 kb), second transcript was detected in hepatic, pancreatic and renal tissues, The similar to 2 kb RNase 4 mRNA was detected in cells of the human promyelocytic leukemia line, HL-60, that had been treated with dibutyryl-cAMP to promote neutrophilic differentiation, In contrast, no mRNA encoding RNase 4 could be detected in cells treated with phorbol myristic acid (PMA), an agent promoting differentiation toward monocyte/macrophages, suggesting the existence of elements regulating tissue specific expression of this gene. RP ROSENBERG, HF (reprint author), NIAID,HOST DEF LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 36 TC 32 Z9 33 U1 1 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 11 PY 1995 VL 23 IS 21 BP 4290 EP 4295 DI 10.1093/nar/23.21.4290 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TG424 UT WOS:A1995TG42400011 PM 7501448 ER PT J AU BOURDI, M DEMADY, D MARTIN, JL JABBOUR, SK MARTIN, BM GEORGE, JW POHL, LR AF BOURDI, M DEMADY, D MARTIN, JL JABBOUR, SK MARTIN, BM GEORGE, JW POHL, LR TI CDNA CLONING AND BACULOVIRUS EXPRESSION OF THE HUMAN LIVER ENDOPLASMIC-RETICULUM P58 - CHARACTERIZATION AS A PROTEIN DISULFIDE-ISOMERASE ISOFORM, BUT NOT AS A PROTEASE OR A CARNITINE ACYLTRANSFERASE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE PROTEIN DISULFIDE ISOMERASE ISOFORM; PROTEASE; CARNITINE ACYLTRANSFERASE; BACULOVIRUS EXPRESSION SYSTEM; ENDOPLASMIC RETICULUM; HUMAN LIVER ID PHOSPHOLIPASE-C-ALPHA; RAT-LIVER; THIOREDOXIN; MICROSOMES; HALOTHANE; SEQUENCE; OXIDOREDUCTASE; PURIFICATION; DEGRADATION; METABOLITE AB The function of a 58-kDa liver microsomal protein (P58) is controversial. To help clarify the physiological function of this protein, particularly in humans, a full-length human liver cDNA clone was isolated, sequenced, and expressed in milligram quantities with the use of a baculovirus expression system, The deduced amino acid sequence of the mature protein contained two thioredoxin-like active site motifs (CGHC) and in its C-terminus a nuclear localization motif (KPKKKKK), and an ER-retention/retrieval motif (QEDL). The mature form of human P58 shared 95% amino acid sequence identity with the deduced amino acid sequences of a bovine liver cDNA, 93% with a murine B lymphocyte cDNA, and 91% with a rat basophilic leukemia cell cDNA, In contrast to reports on the activities of nonhuman forms of P58, the purified expressed human P58 showed no carnitine acyltransferase or protease activities. However, it did have protein disulfide isomerase activity, indicating that the physiological activity of human liver P58 may be attributed, at least in part, to this activity. (C) 1995 Academic Press, Inc. C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL,BALTIMORE,MD 21287. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RP BOURDI, M (reprint author), NHLBI,MOLEC IMMUNOL LAB,MOLEC & CELLULAR TOXICOL SECT,BLDG 10,ROOM 8N110,BETHESDA,MD 20892, USA. NR 34 TC 81 Z9 84 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 10 PY 1995 VL 323 IS 2 BP 397 EP 403 DI 10.1006/abbi.1995.0060 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TE643 UT WOS:A1995TE64300025 PM 7487104 ER PT J AU MIURA, Y TAM, T IDO, A MORINAGA, T MIKI, T HASHIMOTO, T TAMAOKI, T AF MIURA, Y TAM, T IDO, A MORINAGA, T MIKI, T HASHIMOTO, T TAMAOKI, T TI CLONING AND CHARACTERIZATION OF AN ATBF1 ISOFORM THAT EXPRESSES IN A NEURONAL DIFFERENTIATION-DEPENDENT MANNER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENHANCER-BINDING PROTEIN; ZINC-FINGER; GENE-EXPRESSION; HOMEODOMAIN; DROSOPHILA; ZFH-2; REPLICATION; GENOMES; MOTIFS; BOX AB The human ATBF1 cDNA reported previously, now termed ATBF1-B, encodes a 306-kDa protein containing 4 homeodomains and 18 zinc fingers including one pseudo zinc finger motif, Here, we report the isolation of a second ATBF1 cDNA, 12 kilobase pairs long, termed ATBF1-A. The deduced ATBF1-A protein is 404 kDa in size and differs from ATBF1-B by a 920-amino acid extention at the N terminus, Analysis of 5'-genomic sequences showed that the 5'-noneoding sequences specific to ATBF1-A and ATBF1-B transcripts were contained in distinct exons that could splice to a downstream exon common to the ATBF1-A and ATBF1-B mRNAs. The expression of ATBF1-A transcripts increased to high levels when P19 and NT2/D1 cells were treated with retinoic acid to induce neuronal. differentiation, Preferential expression of ATBF1-A transcripts was also observed in developing mouse brain. Transient transfection assays showed that the 5,5-kilobase pair sequence upstream of the ATBF1-A-specific exon (exon 2) supported expression of the linked chloramphenicol acetyltransferase gene in neuronal cells derived from P19 cells but not in undifferentiated P19 or in F9 cells, which do not differentiate into neurons. These results showed that ATBF1-A and ATBF1-B transcripts are generated by alternative promoter usage combined with alternative splicing and that the ATBF1-A-specific promoter is activated during neuronal differentiation. C1 UNIV CALGARY,FAC MED,DEPT MED BIOCHEM,CALGARY,AB T2N 4N1,CANADA. NAGASAKI UNIV,SCH MED,DEPT INTERNAL MED 1,NAGASAKI 852,JAPAN. SNOW BRAND MILK PROD CO LTD,LIFE SCI RES INST,ISHIBASHI,TOCHIGI 32905,JAPAN. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. HYOGO MED UNIV,DEPT GENET,NISHINOMIYA,HYOGO 659,JAPAN. NR 26 TC 60 Z9 64 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 NOV 10 PY 1995 VL 270 IS 45 BP 26840 EP 26848 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TE583 UT WOS:A1995TE58300026 PM 7592926 ER PT J AU EPIFANO, O LIANG, LF DEAN, J AF EPIFANO, O LIANG, LF DEAN, J TI MOUSE ZP1 ENCODES A ZONA-PELLUCIDA PROTEIN HOMOLOGOUS TO EGG ENVELOPE PROTEINS IN MAMMALS AND FISH SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OOCYTE-SPECIFIC EXPRESSION; SPERM RECEPTOR; DEVELOPMENTAL REGULATION; GENOMIC ORGANIZATION; BINDING-PROTEIN; GENES; DNA; SEQUENCE; ZP-2 AB Zp1 encodes one of the three major glycoproteins of the zona pellucida, an extracellular matrix that surrounds growing oocytes, ovulated eggs, and preimplantation embryos. The mouse gene is composed of 12 exons ranging in size from 82 to 364 base pairs and spans 6.5 kilobase pairs on chromosome 19 (2.13 +/- 1.5 centimorgans distal to D19Bir1), The Zp1 exon map is similar to ZPB, a human orthologue, and an E-box (CANNTG), implicated in oocyte-specific gene expression of mouse Zp2 and Zp3, is similarly located upstream of the transcription start site, The single copy Zp1 gene encodes a 623-amino acid protein, the carboxyl-terminal half of which is significantly similar to a corresponding region of mouse ZP2, The conservation of this same region in a fish egg;envelope protein suggests that not only has this protein domain been duplicated in mammals but that it has been conserved and used as an egg envelope protein in species that diverged 650 million years ago. RP EPIFANO, O (reprint author), NIDDK,CELLULAR & DEV BIOL LAB,BLDG 6,RM B1-26,6 CTR DR MSC 2715,BETHESDA,MD 20892, USA. NR 31 TC 73 Z9 77 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 NOV 10 PY 1995 VL 270 IS 45 BP 27254 EP 27258 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TE583 UT WOS:A1995TE58300084 PM 7592984 ER PT J AU GEORGE, KM YUAN, Y SHERMAN, DR BARRY, CE AF GEORGE, KM YUAN, Y SHERMAN, DR BARRY, CE TI THE BIOSYNTHESIS OF CYCLOPROPANATED MYCOLIC ACIDS IN MYCOBACTERIUM-TUBERCULOSIS - IDENTIFICATION AND FUNCTIONAL-ANALYSIS OF CMAS-2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; HOMOLOGOUS SERIES; SMEGMATIS; SYNTHASE; ENZYME; CHROMATOGRAPHY; ORGANIZATION; MEMBRANES; CLONING; LIPIDS AB The major mycolic acid produced by Mycobacterium tuberculosis contains two cis-cyclopropanes in the meromycolate chain. The gene whose product cyclopropanates the proximal double bond was cloned by homology to a putative cyclopropane synthase identified from the Mycobacterium leprae genome sequencing project. This gene, named cma2, was sequenced and found to be 52% identical to cma1 (which cyclopropanates the distal double bond) and 73% identical to the gene from M. leprae. Both cma genes were found to be restricted in distribution to pathogenic species of mycobacteria. Expression of cma2 in Mycobacterium smegmatis resulted in the cyclopropanation of the proximal double bond in the alpha(1), series of mycolic acids. Coexpression of both cyclopropane synthases resulted in cyclopropanation of both centers, producing a molecule structurally similar to the M; tuberculosis alpha-dicyclopropyl mycolates. Differential scanning calorimetry of purified cell walls and mycolic acids demonstrated that cyclopropanation of the proximal position raised the observed transition temperature by 3 degrees C. These results suggest that cyclepropanation contributes to the structural integrity of the cell wall complex. C1 NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,TB RES UNIT,HAMILTON,MT 59840. PATHOGENESIS CORP,TB & MOLEC MICROBIOL LAB,SEATTLE,WA 98119. RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11] NR 34 TC 129 Z9 134 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 10 PY 1995 VL 270 IS 45 BP 27292 EP 27298 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TE583 UT WOS:A1995TE58300090 PM 7592990 ER PT J AU BALER, R KLEIN, DC AF BALER, R KLEIN, DC TI CIRCADIAN EXPRESSION OF TRANSCRIPTION FACTOR FRA-2 IN THE RAT PINEAL-GLAND SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POST-TRANSLATIONAL MODIFICATION; IMMEDIATE-EARLY GENE; C-FOS; FACTOR AP-1; CROSS-TALK; PROTEINS; JUN; ACTIVATION; IMMUNOREACTIVITY; INDUCTION AB Physiological changes in Fos-like immunoreactivity in the rat pineal gland are shown here to be due primarily to changes in a 42/46-kDa Fos-related antigen (Era). Studies are presented that indicate this 42/46-kDa Fra is Fra-2, a poorly understood member of the Fos family of transcription factors. Both Fra-2 mRNA and protein are absent during the day and increase robustly at night on a circadian basis; organ culture studies indicate that regulation is mediated by an adrenergic --> cyclic AMP mechanism. AP-1 binding activity changes in parallel to changes in the level of Fra a protein. C1 NICHHD,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BETHESDA,MD 20892. NR 47 TC 86 Z9 87 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 NOV 10 PY 1995 VL 270 IS 45 BP 27319 EP 27325 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TE583 UT WOS:A1995TE58300094 PM 7592994 ER PT J AU Noga, JT Aylward, E Barta, PE Pearlson, GD AF Noga, JT Aylward, E Barta, PE Pearlson, GD TI Cingulate gyrus in schizophrenic patients and normal volunteers SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE magnetic resonance imaging; laterality; brain volume; hallucinations ID CEREBRAL BLOOD-FLOW; AUDITORY HALLUCINATIONS; PREFRONTAL CORTEX; BRAIN; MONKEY; DISORDER AB Comparable magnetic resonance imaging (MRI) sections of right and left anterior and posterior cingulate gyrus were measured blindly with a method developed by the authors in 14 patients with schizophrenia (by DSM-III-R criteria) and 14 normal volunteers individually matched to the patients for age, sex, education, and parental socioeconomic status. Interrater reliability met or exceeded 0.92 (kappa) on all cingulate structures measured. Brain volume in the two groups differed by 2%(normal > schizophrenia), but the difference was not significant. All cingulate gyri measures were nonsignificantly smaller in the patient group by 3-5%. There was an inverse correlation between left anterior cingulate size and severity of hallucinations that was, however, not significant after Bonferroni correction. Lateral asymmetry of the cingulate regions measured was the same in both groups, with the left being nonsignificantly smaller than the right for all regions. We demonstrate a reliable method, unreported thus far in the literature, to measure the cingulate gyrus on MRI; the results suggest that left cingulate gyrus size may be inversely related to severity of hallucinations in schizophrenia. C1 JOHNS HOPKINS UNIV HOSP,DEPT PSYCHIAT,NEUROIMAGING LAB,BALTIMORE,MD 21287. RP Noga, JT (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,2700 MARTIN L KING JR AVE SE,WASHINGTON,DC 20032, USA. NR 35 TC 64 Z9 64 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD NOV 10 PY 1995 VL 61 IS 4 BP 201 EP 208 DI 10.1016/0925-4927(95)02612-2 PG 8 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TK689 UT WOS:A1995TK68900002 PM 8748465 ER PT J AU PORTIER, C LUCIER, G DAMSTRA, T AF PORTIER, C LUCIER, G DAMSTRA, T TI DIOXIN RESEARCH IN VIETNAM SO SCIENCE LA English DT Letter RP PORTIER, C (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 10 PY 1995 VL 270 IS 5238 BP 901 EP 901 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TD878 UT WOS:A1995TD87800010 PM 7481783 ER PT J AU SMITH, ML CHEN, IT FORNACE, AJ AF SMITH, ML CHEN, IT FORNACE, AJ TI DOES THE P53 UP-REGULATED GADD45 PROTEIN HAVE A ROLE IN EXCISION-REPAIR - REPLY SO SCIENCE LA English DT Article RP SMITH, ML (reprint author), NCI,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892, USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 10 PY 1995 VL 270 IS 5238 BP 1005 EP 1006 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TD878 UT WOS:A1995TD87800056 ER PT J AU MCMILLAN, NAJ CHUN, RF SIDEROVSKI, DP GALABRU, J TOONE, WM SAMUEL, CE MAK, TW HOVANESSIAN, AG JEANG, KT WILLIAMS, BRG AF MCMILLAN, NAJ CHUN, RF SIDEROVSKI, DP GALABRU, J TOONE, WM SAMUEL, CE MAK, TW HOVANESSIAN, AG JEANG, KT WILLIAMS, BRG TI HIV-1 TAT DIRECTLY INTERACTS WITH THE INTERFERON-INDUCED, DOUBLE-STRANDED RNA-DEPENDENT KINASE, PKR SO VIROLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; TRANSLATIONAL CONTROL MECHANISM; HUMAN IMMUNODEFICIENCY VIRUS-1; GENE-EXPRESSION; HTLV-III; P68 KINASE; INITIATION FACTOR-2-ALPHA; FUNCTIONAL EXPRESSION; REPLICATION INVITRO; BINDING AB We present evidence that the HIV-I Tat protein and the RNA-dependent cellular protein kinase, PKR, interact with each other both in vitro and in vivo. Using GST fusion chromatography, we demonstrate that PKR, interacts directly with the HIV-1 Tat protein. The region in Tat sufficient for binding PKR maps within amino acids 20 to 72. In in vitro assays, the two-exon form of Tat (Tat 86) was phosphorylated by PKR, while the one exon form of Tat (Tat 72) inhibited PKR autophosphorylation and substrate phosphorylation. The ability of Tat to interact with PKR was demonstrated in both yeast and mammalian cells. Expression of PKR in yeast results in a growth suppressor phenotype which was reversed by coexpression of a one exon form of Tat. Expression of Tat 72 in HeLa cells resulted in direct interaction with PKR as detected by coimmunprecipitation with a Tat antibody. Tat and PKR also form a coimmunoprecipitable complex in cell-free extracts prepared from productively infected T lymphocytes. The interaction of Tat with PKR provides a potential mechanism by which HIV could suppress the interferon system. (C) 1995 Academic Press, Inc. C1 CLEVELAND CLIN FDN,DEPT CANC BIOL NN10,CLEVELAND,OH 44195. UNIV TORONTO,DEPT MED BIOPHYS,TORONTO,ON M4X 1K9,CANADA. UNIV TORONTO,ONTARIO CANC INST,AMGEN INST,TORONTO,ON M4X 1K9,CANADA. INST PASTEUR,VIROL & CELLULAR IMMUNOL UNIT,CNRS,UA 1157,F-75724 PARIS 15,FRANCE. UNIV CALIF SANTA BARBARA,DEPT BIOL SCI,SANTA BARBARA,CA 93106. NIH,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008; Williams, Bryan/A-5021-2009; Chun, Rene/A-9415-2010; OI Williams, Bryan/0000-0002-4969-1151; Chun, Rene/0000-0002-0190-0807; McMillan, Nigel/0000-0002-9471-1406; Siderovski, David/0000-0002-0688-8210 FU NIAID NIH HHS [R01 AI-34039, AI-20611] NR 64 TC 130 Z9 133 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 1995 VL 213 IS 2 BP 413 EP 424 DI 10.1006/viro.1995.0014 PG 12 WC Virology SC Virology GA TE732 UT WOS:A1995TE73200014 PM 7491766 ER PT J AU STAUBER, R GAITANARIS, GA PAVLAKIS, GN AF STAUBER, R GAITANARIS, GA PAVLAKIS, GN TI ANALYSIS OF TRAFFICKING OF REV AND TRANSDOMINANT REV PROTEINS IN LIVING CELLS USING GREEN FLUORESCENT PROTEIN FUSIONS - TRANSDOMINANT REV BLOCKS THE EXPORT OF REV FROM THE NUCLEUS TO THE CYTOPLASM SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL MESSENGER-RNA; RESPONSIVE ELEMENT RNA; HUMAN T-CELLS; HTLV-I REX; HIV-1 REV; TYPE-1 REV; GENE-EXPRESSION; TRANS-ACTIVATOR; NUCLEOLAR LOCALIZATION AB Expression of gag/pol and env genes of human immunodeficiency virus requires the viral Rev protein. Mutant Rev proteins, displaying a transdominant phenotype (TDRev), were shown to inhibit Rev function. To investigate the underlying mechanism of this inhibition, the green fluorescent protein (GFP) of Aequorea victoria was fused to Rev and TDRev, which allowed the study of their trafficking and interactions in living human cells. Both Rev-GFP and TDRev-GFP were shown to retain appropriate nucleolar localization and function. Upon actinomycin D treatment, Rev-GFP was transported to the cytoplasm within 1.5 hr, while TDRev, although partially dissociated from the nucleolus, was retained in the nucleus. Coexpression of Rev-GFP and TDRev in the same cell demonstrated that TDRev inhibited the transport of Rev-GFP from the nucleus to the cytoplasm. This inhibition was specific for Rev, since the export of the functionally analogous Rex protein of the human T-cell leukemia virus type I was not inhibited by TDRev. These results indicate that Rev and TDRev form heteromultimers in the nucleolus and that this interaction prevents Rev's export from the nucleus to the cytoplasm. In addition to providing a model for the function of TDRev, these results also demonstrate the successful application of protein fusions to GFP to study localization and trafficking of proteins in living mammalian cells. (C) 1995 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. OI Stauber, Roland/0000-0002-1341-4523 NR 95 TC 100 Z9 100 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 1995 VL 213 IS 2 BP 439 EP 449 DI 10.1006/viro.1995.0016 PG 11 WC Virology SC Virology GA TE732 UT WOS:A1995TE73200016 PM 7491768 ER PT J AU LENO, W HAGUE, BF TELLER, R KINDT, TJ AF LENO, W HAGUE, BF TELLER, R KINDT, TJ TI HIV-1 MEDIATES RAPID APOPTOSIS OF LYMPHOCYTES FROM HUMAN CD4 TRANSGENIC BUT NOT NORMAL RABBITS SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROGRAMMED CELL-DEATH; INFECTION; AIDS; INVIVO; MODEL AB Normal rabbit lymphocytes can be infected with HIV-1 although infection is much less efficient than in human lymphocytes. When peripheral blood mononuclear cells (PBMC) from rabbits transgenic for human CD4 (HuCD4) were exposed to HIV-1, enhanced infection and a rapid depletion of lymphocytes were observed. Cell death in the infected cultures occurred via apoptosis, but no similar effect was seen in nontransgenic rabbit PBMC cultures. induction of apoptosis in HuCD4-expressing cells required virus replication; heat-inactivated Virus or recombinant viral proteins had no effect on cell viability. Expression of the Fas antigen was increased in HIV-l-infected CD4(+) rabbit lymphocytes. Characterization of the infected PBMC cultures revealed that apoptosis occurs both in HuCD4(+) and HuCD4(-) cells, indicating that bystander cells are killed. These data define a requirement for HuCD4 in initiation, but not the spread, of HIV-1-induced apoptosis in rabbit PBMC and provide a model to probe mechanisms leading to lymphocyte depletion in HIV-1 infection. (C) 1995 Academic Press, Inc. C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. NR 21 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 1995 VL 213 IS 2 BP 450 EP 454 PG 5 WC Virology SC Virology GA TE732 UT WOS:A1995TE73200017 ER PT J AU BULLER, RML BURNETT, J CHEN, W KREIDER, J AF BULLER, RML BURNETT, J CHEN, W KREIDER, J TI REPLICATION OF MOLLUSCUM CONTAGIOSUM VIRUS SO VIROLOGY LA English DT Note ID VACCINIA VIRUS; GENE; CELLS AB Molluscum contagiosum virus (MCV) infects preadolescent children and sexually active adults, frequently causing a disfiguring cutaneous disease in immunosuppressed HIV-infected individuals. The development of an efficacious treatment regime has been hampered by the failure to replicate the virus in the laboratory. Here we report the first demonstration of MCV replication in an experimental system. In human foreskin grafts to athymic mice, MCV induced morphological changes which were indistinguishable from patient biopsies and included the development and migration of molluscum bodies containing mature virions to the epidermal surface. (C) 1995 Academic Press, Inc. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. UNIV MARYLAND,DEPT DERMATOL,BALTIMORE,MD 21201. PENN STATE UNIV,COLL MED,DEPT EXPTL PATHOL,HERSHEY,PA 17033. FU NCI NIH HHS [2RO1CA47622]; NIAID NIH HHS [N01-AI35138] NR 31 TC 39 Z9 39 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 1995 VL 213 IS 2 BP 655 EP 659 DI 10.1006/viro.1995.0037 PG 5 WC Virology SC Virology GA TE732 UT WOS:A1995TE73200037 PM 7491789 ER PT J AU SMITH, PB TIANO, HF NESNOW, S BOYD, MR PHILPOT, RM LANGENBACH, R AF SMITH, PB TIANO, HF NESNOW, S BOYD, MR PHILPOT, RM LANGENBACH, R TI 4-IPOMEANOL AND 2-AMINOANTHRACENE CYTOTOXICITY IN C3H/10T1/2 CELLS EXPRESSING RABBIT CYTOCHROME-P450 4B1 SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE CYTOCHROME P450 4B1; CYTOTOXICITY; AROMATIC AMINES; FURANS ID MOUSE EMBRYO FIBROBLASTS; METABOLIC-ACTIVATION; POSTCONFLUENCE INHIBITION; MUTAGENIC PRODUCTS; PULMONARY TOXICITY; ADDUCT FORMATION; GENE-TRANSFER; LUNG; DNA; LIVER AB In the present study, retroviral vectors were used to stably transfer and express the cDNA encoding rabbit CYP4B1 in mouse C3H/10T1/2 cells. The replication defective retroviral vector was packaged in the ecotropic packaging cell line, GP + E-86, with infectious titer of similar to 1 x 10(6) cfu/mL. Infection, followed by selection with G418, showed an infection efficiency of approximately 70% for the recipient C3H/10T1/2 cells. Analysis of ten G418 resistant clones showed that the number of vector inserts ranged from 4 to 13 copies per cell genome. Each clone was positive for microsomal CYP4B1 protein as determined by immunoblotting. Cytochrome P450 4B1 activity was assessed by the cytotoxicity of 4-ipomeanol, a known substrate for P450 4B1 and a model compound for chemical-induced injury to the lung. The initial clonigenic assays showed that 100% toxicity occurred in all the clones after a 96-hr exposure to 250 mu M 4-ipomeanol. Parental C3H/10T1/2 cells were resistant to 4-ipomeanol at concentrations as high as 1 mM. Two clones, designated No. 2 and No. 19, differing in levels of P450 4B1 protein, were characterized further for 4-ipomeanol and other chemical toxicities. A concentration-response study indicated 50% cytotoxicity at 4-ipomeanol concentrations of 1.5 mu g/mL for clone No. 2 and 2.5 mu g/mL for clone No. 19. A panel of agents representing the aromatic amines, some of which are known or suspected P450 4B1 substrates, were tested for cytotoxicity in clone No. 2. These agents included 2-aminoanthracene, 2-aminonaphthalene, 2-aminofluorene, 2-acetylaminofluorene and 4-aminobiphenyl. Only 2-aminoanthracene gave a clear cytotoxic response reducing the survival fraction of clone No. 2 to 50% at 0.2 mu g/mL while affecting parental cells minimally. In vitro expression of CYP4B1 provides a new experimental system for further elucidating the cytotoxic and mutagenic effects of P450 4B1 substrates. C1 NIEHS, RES TRIANGLE PK, NC 27709 USA. US EPA, HLTH EFFECTS RES LAB, CARCINOGENESIS & METAB BRANCH, RES TRIANGLE PK, NC 27711 USA. NCI, FREDERICK CANC RES & DEV CTR, DRUG DISCOVERY RES & DEV LAB, FREDERICK, MD 21702 USA. RP WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT BIOCHEM, MED CTR BLVD, WINSTON SALEM, NC 27157 USA. NR 51 TC 21 Z9 21 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 EI 1873-2968 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 9 PY 1995 VL 50 IS 10 BP 1567 EP 1575 DI 10.1016/0006-2952(95)02029-2 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TJ079 UT WOS:A1995TJ07900005 PM 7503758 ER PT J AU EHMANN, WC EYSTER, ME ALEDORT, LM GOEDERT, JJ AF EHMANN, WC EYSTER, ME ALEDORT, LM GOEDERT, JJ TI CAUSES OF DEATH IN HEMOPHILIA SO NATURE LA English DT Letter C1 CUNY MT SINAI SCH MED,DEPT MED,NEW YORK,NY 10029. NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD 20892. RP EHMANN, WC (reprint author), PENN STATE COLL MED,DEPT MED,DIV HEMATOL,HERSHEY,PA 17033, USA. NR 4 TC 6 Z9 6 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD NOV 9 PY 1995 VL 378 IS 6553 BP 124 EP 124 DI 10.1038/378124a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TD759 UT WOS:A1995TD75900017 PM 7477306 ER PT J AU PREISLER, RS CHEN, HH COLOMBO, MF CHOE, Y SHORT, BJ RAU, DC AF PREISLER, RS CHEN, HH COLOMBO, MF CHOE, Y SHORT, BJ RAU, DC TI THE B-FORM TO Z-FORM TRANSITION OF POLY(DG-M(5)DC) IS SENSITIVE TO NEUTRAL SOLUTES THROUGH AN OSMOTIC-STRESS SO BIOCHEMISTRY LA English DT Article ID Z-DNA; CONFORMATIONAL TRANSITIONS; PROTEIN SOLVATION; WATER; POLY(DG-DC).POLY(DG-DC); METHYLATION; POLY(DG-DC); HYDRATION; STABILITY; BINDING AB Several neutral solutes, ranging in size from methanol to a tetrasaccharide, stachyose, are shown to stabilize the left-handed Z form of the methylated polynucleotide poly(dG-m(5)dC). The action of these solutes is consistent with an osmotic stress, that is, with their effect on water chemical potentials coupled to a difference in the number of-associated water molecules between the B and Z conformations. The apparent difference in hydration between the two forms is, however, dependent on the particular solute used to probe the reaction. The effect of solutes is not consistent either with a direct binding of solute or with an indirect effect on electrostatics or ion binding through changes in the solution dielectric constant. The interplay of NaCl and neutral solute in modulating the B-Z transition suggests that salt also could be stabilizing the Z form through an osmotic stress. C1 TOWSON STATE UNIV,DEPT CHEM,BALTIMORE,MD 21204. GEORGE MASON UNIV,DEPT CHEM,FAIRFAX,VA 22030. UNESP,IBILCE,DEPT FIS,BR-15054000 S JOSE RIO PR,SP,BRAZIL. NIH,OFF DIRECTOR,BETHESDA,MD 20892. RI Colombo, Marcio/K-5229-2013 OI Colombo, Marcio/0000-0003-3035-3926 NR 42 TC 34 Z9 34 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 7 PY 1995 VL 34 IS 44 BP 14400 EP 14407 DI 10.1021/bi00044a017 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TD845 UT WOS:A1995TD84500017 PM 7578044 ER PT J AU POZSGAY, V ROBBINS, JB AF POZSGAY, V ROBBINS, JB TI SYNTHESIS OF A PENTASACCHARIDE FRAGMENT OF POLYSACCHARIDE-II OF MYCOBACTERIUM-TUBERCULOSIS SO CARBOHYDRATE RESEARCH LA English DT Article DE PENTASACCHARIDE; POLYSACCHARIDE II; MYCOBACTERIUM TUBERCULOSIS ID B STREPTOCOCCAL POLYSACCHARIDES; SHIGELLA-DYSENTERIAE TYPE-1; STEREOSELECTIVE SYNTHESIS; LINKED DISACCHARIDES; FACILE SYNTHESIS; BUILDING UNITS; OLIGOSACCHARIDES; ANTIGEN; THIOGLYCOSIDES; 2-AMINO-2-DEOXY-D-GLUCOPYRANOSE AB Stereocontrolled, stepwise synthesis of decyl glycosides of alpha-(1 --> 2)-linked di- to pentaglucosides (1-5) is described; these constitute fragments of Polysaccharide II of Mycobacterium tuberculosis, Phenyl 3,4,6-tri-O-acetyl-2-O-benzyl-1-thio-alpha-D-glucopyranoside (7) was used as the single key intermediate, obtained from 1,3,4,6-tetra-O-acetyl-2-O-benzyl-beta-D-glucopyranose (6) and PhSSiMe(3). Halogenolysis of 7 afforded the isolated beta bromide (10) and beta chloride (13). Solvolysis of 10 with decanol without heavy metal salts gave decyl 3,4,6-tri-O-acetyl-2-O-benzyl-alpha-D-glucopyranoside (14) in a highly stereoselective reaction, in high yield. Subsequent, iterative hydrogenolytic removal of the O-benzyl group and glycosylation with the beta-chloride 13 under catalysis by silver salts afforded the protected di- to penta-saccharide glycosides 16, 19, 21, and 23, which were conventionally deblocked. RP POZSGAY, V (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892, USA. NR 77 TC 12 Z9 12 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD NOV 7 PY 1995 VL 277 IS 1 BP 51 EP 66 DI 10.1016/0008-6215(95)00199-4 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA TE581 UT WOS:A1995TE58100005 PM 8548790 ER PT J AU POZSGAY, V COXON, B AF POZSGAY, V COXON, B TI STEREOSELECTIVE PREPARATION OF ALKYL GLYCOSIDES OF 2-ACETAMIDO-2-DEOXY-ALPHA-D-GLUCOPYRANOSE BY NONCLASSICAL HALIDE-ION CATALYSIS AND SYNTHESIS AND NMR-SPECTROSCOPY OF-ALPHA-D-GALP-(1-]3)-ALPHA-D-GLCPNAC-OME SO CARBOHYDRATE RESEARCH LA English DT Note DE ALKYL GLYCOSIDES; 2-ACETAMIDO-2-DEOXY-ALPHA-D-GLUCOPYRANOSE; A-D-GALP-(1-]3)-ALPHA-D-GLCPNAC-OME ID SHIGELLA-DYSENTERIAE TYPE-1; O-SPECIFIC POLYSACCHARIDE; OLIGOSACCHARIDES C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. NIST,DIV BIOTECHNOL,GAITHERSBURG,MD 20899. RP POZSGAY, V (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892, USA. NR 18 TC 14 Z9 14 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 NOV 7 PY 1995 VL 277 IS 1 BP 171 EP 178 DI 10.1016/0008-6215(95)00198-3 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA TE581 UT WOS:A1995TE58100013 PM 8548787 ER PT J AU POGUE, GP LEE, NS KOUL, S DWYER, DM NAKHASI, HL AF POGUE, GP LEE, NS KOUL, S DWYER, DM NAKHASI, HL TI IDENTIFICATION OF DIFFERENTIALLY EXPRESSED LEISHMANIA-DONOVANI GENES USING ARBITRARILY PRIMED POLYMERASE CHAIN-REACTIONS SO GENE LA English DT Article ID POLYMORPHISMS; CLONING; PROMASTIGOTES; AMASTIGOTES; MARKERS; ANTIGEN; FAMILY; RNA; PCR AB Arbitrarily primed polymerase chain reactions (AP-PCR) were used to amplify polymorphic DNA fragments from the genomes of a variety of geographic isolates of Leishmania donovani (Ld). From the latter, five polymorphic DNA fragments were cloned and sequence analysis identified 15 unique clones. Northern blot analysis showed that 13 of the 15 clones hybridized to transcribed RNAs isolated from Id. Eight of these 13 AP-PCR clones specifically hybridized to Ld RNAs that were differentially expressed in promastigote and 'amastigote' cells. Comparative Northern analysis of four differentially expressed AP-PCR clones indicated that two clones, LdS-14-14 and LdI-9-7, were expressed in Ld and several other Leishmania species. However, RNAs corresponding to two other AP-PCR clones, LdE-6-1 and LdI-9-5, were detected only in members of the Ld complex, and not in L. major (Lm) or L. tropica (Lt). Comparative Southern blot analysis of the LdS-14-14 locus revealed numerous restriction-fragment length polymorphisms (RFLP) distinguishing Lm and Lt from the Ld isolates and L. infantum. However, the LdS-14-14 loci were mapped to similar-sized chromosomes observed among all Old World Leishmania species tested, indicating that localized nucleotide divergence, not chromosomal rearrangement, was responsible for altered Southern blot patterns. These results demonstrate that AP-PCR is a very useful method for identifying expressed gene sequences in organisms of relatively low-complexity genomes. Interestingly, the majority of these sequences identified in this study correspond to differentially expressed genes. The value of this method lies in its ability to rapidly and randomly sample diverse portions of an organism's genome, in order to identify interesting and unique sequences. C1 US FDA,CTR BIOL EVALUAT & RES,DHP,LMP,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,CELL BIOL SECT,BETHESDA,MD 20892. NR 26 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 7 PY 1995 VL 165 IS 1 BP 31 EP 38 DI 10.1016/0378-1119(95)00461-E PG 8 WC Genetics & Heredity SC Genetics & Heredity GA TF524 UT WOS:A1995TF52400005 PM 7489912 ER PT J AU DAWES, SS CROUCH, RJ MORRIS, SL MIZRAHI, V AF DAWES, SS CROUCH, RJ MORRIS, SL MIZRAHI, V TI CLONING, SEQUENCE-ANALYSIS, OVERPRODUCTION IN ESCHERICHIA-COLI AND ENZYMATIC CHARACTERIZATION OF THE RNASE HI FROM MYCOBACTERIUM-SMEGMATIS SO GENE LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; THERMUS-THERMOPHILUS HB8; STABLE DNA-REPLICATION; RIBONUCLEASE-H; NUCLEOTIDE-SEQUENCE; DEFECTIVE MUTANTS; CRYSTAL-STRUCTURE; GENE; EXPRESSION; RESOLUTION AB Activity gel analysis of cell extracts from slow- and fast-growing mycobacteria confirmed the presence of several RNase H activities in both classes of organism. The rnhA gene from Mycobacterium smegmatis (Ms) was subsequently cloned using an internal gene segment probe [Mizrahi et al., Gene 136 (1993) 287-290]. The gene encodes a polypeptide of 159 amino acids that shares 50% identity with the RNase HI from Escherichia coli (Ec). However, unlike its counterparts from Gram(-) bacteria, Ms rnhA does not form an overlapping divergent transcriptional unit with dnaQ (encoding the epsilon (proofreading) subunit of DNA polymerase III), Ms RNase HI was overproduced in Ec as an enzymatically active maltose-binding protein (MBP) fusion protein which cleaved the RNA strand of an RNA . DNA hybrid with a similar site selectivity to that of its Ec homologue. C1 S AFRICAN INST MED RES,MOLEC BIOL UNIT,JOHANNESBURG 2000,SOUTH AFRICA. UNIV WITWATERSRAND,SCH MED,DEPT HAEMATOL,JOHANNESBURG 2193,SOUTH AFRICA. NIH,GENET MOLEC LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,MYCOBACTERIA LAB,BETHESDA,MD 20892. NR 28 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 7 PY 1995 VL 165 IS 1 BP 71 EP 75 DI 10.1016/0378-1119(95)00523-9 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA TF524 UT WOS:A1995TF52400012 PM 7489919 ER PT J AU ROPP, PA COPELAND, WC AF ROPP, PA COPELAND, WC TI CHARACTERIZATION OF A NEW DNA-POLYMERASE FROM SCHIZOSACCHAROMYCES-POMBE - A PROBABLE HOMOLOG OF THE SACCHAROMYCES-CEREVISIAE DNA-POLYMERASE-GAMMA SO GENE LA English DT Article DE POL-GAMMA; FISSION YEAST; REPLICATION; CHROMOSOME MAPPING; GENE REGULATION ID MITOCHONDRIAL-DNA; SUBUNIT STRUCTURE; YEAST; PURIFICATION; GENE; IDENTIFICATION; REPLICATION AB Mitochondrial (mt) DNA replication is carried out by the nuclear-encoded DNA polymerase-gamma (Pol-gamma). We have cloned a new DNA polymerase-encoding gene from Schizossaccharomyces pombe (Sp), which we believe encodes the homologue of the Saccharomyces cerevisiae (Sc) mt DNA polymerase (MIP1). The putative Sp poly gene expressed a transcript of approx. 4-kb that contained a 3-kb open reading frame encoding a polypeptide of 1018 amino acids (aa) (116kDa). This Sp Pol-gamma is 48% identical to the Sc MIP1 and contains uniquely conserved regions not found in the bacterial Poll-type DNA polymerases. The most notable difference between these two proteins is that the MIP1 product has a 236-aa C-terminal region beyond motif C that is not found in Sp Pol-gamma. Chromosomal mapping and genomic sequencing of the Sp poly places this gene on chromosome III downstream from the triose phosphate isomerase-encoding gene. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NR 26 TC 21 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 7 PY 1995 VL 165 IS 1 BP 103 EP 107 DI 10.1016/0378-1119(95)00412-Y PG 5 WC Genetics & Heredity SC Genetics & Heredity GA TF524 UT WOS:A1995TF52400018 PM 7489897 ER PT J AU HASENKRUG, KJ BROOKS, DM CHESEBRO, B AF HASENKRUG, KJ BROOKS, DM CHESEBRO, B TI PASSIVE IMMUNOTHERAPY FOR RETROVIRAL DISEASE - INFLUENCE OF MAJOR HISTOCOMPATIBILITY COMPLEX TYPE AND T-CELL RESPONSIVENESS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PRINCIPAL NEUTRALIZING DOMAIN; CYTOTOXIC LYMPHOCYTES-T; HOST GENETIC-CONTROL; FRIEND-VIRUS; MONOCLONAL-ANTIBODY; INDUCED LEUKEMIA; HIV-INFECTION; SPONTANEOUS-RECOVERY; IMMUNE-RESPONSE AB Administration of virus-specific antibodies is known to be an effective early treatment for some viral infections. Such immunotherapy probably acts by antibody-mediated neutralization of viral infectivity and is often thought to function independently of T-cell-mediated immune responses. In the present experiments, we studied passive antibody therapy using Friend murine leukemia virus complex as a model for an immunosuppressive retroviral disease in adult mice. The results showed that antibody therapy could induce recovery from a well-established retroviral infection. However, the success of therapy was dependent on the presence of both CD4(+) and CD8(+) T lymphocytes. Thus, cell-mediated responses were required for recovery from infection even in the presence of therapeutic levels of antibody. The major histocompatibility type of the mice was also an important factor determining the relative success of antibody therapy in this system, but it was less critical for low-dose than for high-dose infections. Our results imply that limited T-cell responsiveness as dictated by major histocompatibility genes and/or stage of disease may have contributed to previous immunotherapy failures in AIDS patients. Possible strategies to improve the efficacy of future therapies are discussed. RP HASENKRUG, KJ (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 65 TC 46 Z9 46 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 7 PY 1995 VL 92 IS 23 BP 10492 EP 10495 DI 10.1073/pnas.92.23.10492 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TD890 UT WOS:A1995TD89000010 PM 7479826 ER PT J AU NAGATA, H WOROBEC, AS OH, CK CHOWDHURY, BA TANNENBAUM, S SUZUKI, Y METCALFE, DD AF NAGATA, H WOROBEC, AS OH, CK CHOWDHURY, BA TANNENBAUM, S SUZUKI, Y METCALFE, DD TI IDENTIFICATION OF A POINT MUTATION IN THE CATALYTIC DOMAIN OF THE PROTOONCOGENE C-KIT IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS OF PATIENTS WHO HAVE MASTOCYTOSIS WITH AN ASSOCIATED HEMATOLOGIC DISORDER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PROTEIN TYROSINE KINASE; MUTATION ID HUMAN MAST-CELLS; BONE-MARROW; GROWTH-FACTOR; W-LOCUS; RECOMBINANT HUMAN; PROGENITOR CELLS; MYELODYSPLASTIC SYNDROMES; FETAL LIVER; EXPRESSION; RECEPTOR AB Both stem cells and mast cells express c-kif and proliferate after exposure to c-kit ligand. Mutations in c-kit may enhance or interfere with the ability of c-kit receptor to initiate the intracellular pathways resulting in cell proliferation. These observations suggested to us that mastocytosis might in some patients result from mutations in c-kif. cDNA synthesized from peripheral blood mononuclear cells of patients with indolent mastocytosis, mastocytosis with an associated hematologic disorder, aggressive mastocytosis, solitary mastocytoma, and chronic myelomonocytic leukemia unassociated with mastocytosis was thus screened for a mutation of c-kit. This analysis revealed that four of four mastocytosis patients with an associated hematologic disorder with predominantly myelodysplastic features had an A --> T substitution at nt 2368 of c-kit mRNA that causes an Asp-816 --> Val substitution. One of one patient examined who had mastocytosis with an associated hematologic disorder had the corresponding mutation in genomic DNA. Identical or similar amino acid substitutions in mast cell lines result in ligand-independent autophosphorylation of the c-kit receptor. This mutation was not identified in the patients within the other disease categories or in 67 of 67 controls. The identification of the point mutation Asp816Val in c-kit in patients with mastocytosis with an associated hematologic disorder provides insight not only into the pathogenesis of this form of mastocytosis but also into how hematopoiesis may become dysregulated and may serve to provide a means of confirming the diagnosis, assessing prognosis, and developing intervention strategies. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. NIDDKD,CTR CLIN,HEMATOL SECT,BETHESDA,MD 20892. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NR 33 TC 661 Z9 669 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 NOV 7 PY 1995 VL 92 IS 23 BP 10560 EP 10564 DI 10.1073/pnas.92.23.10560 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TD890 UT WOS:A1995TD89000024 PM 7479840 ER PT J AU BUDILLON, A CERESETO, A KONDRASHIN, A NESTEROVA, M MERLO, G CLAIR, T CHOCHUNG, YS AF BUDILLON, A CERESETO, A KONDRASHIN, A NESTEROVA, M MERLO, G CLAIR, T CHOCHUNG, YS TI POINT MUTATION OF THE AUTOPHOSPHORYLATION SITE OR IN THE NUCLEAR LOCATION SIGNAL CAUSES PROTEIN-KINASE-A RII(BETA) REGULATORY SUBUNIT TO LOSE ITS ABILITY TO REVERT TRANSFORMED FIBROBLASTS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMINO-ACID-SEQUENCE; BOVINE CARDIAC-MUSCLE; MURINE SARCOMA-VIRUS; HL-60 LEUKEMIA-CELLS; CYCLIC-AMP ANALOGS; CATALYTIC SUBUNIT; MOLECULAR-CLONING; HUMAN TESTIS; RII-BETA; ANTISENSE OLIGODEOXYNUCLEOTIDE AB The RII(beta) regulatory subunit of cAMP-dependent protein kinase (PKA) contains an autophosphorylation site and a nuclear location signal, KKRK. We approached the structure-function analysis of RII(beta) by using site-directed mutagenesis. Ser(114) (the autophosphorylation site) of human RII(beta) was replaced with Ala (RII(beta)-P) or Arg(264) of KKRK was replaced with Met (RII(beta)-K). ras-transformed NIH 3T3 (DT) cells were transfected with expression vectors for RII(beta), RII(beta)-P, and RII(beta)-K, and the effects on PKA isozyme distribution and transformation properties were analyzed. DT cells contained PKA-I and PKA-II isozymes in a 1:2 ratio. Over-expression of wild-type or mutant RII(beta) resulted in an increase in PKA-II and the elimination of PKA-I. Only wild-type RII(beta) cells demonstrated inhibition of both anchorage-dependent and -independent growth and phenotypic change. The growth inhibitory effect of RII(beta) overexpression was not due to suppression of ras expression but was correlated with nuclear accumulation of Rnp. DT cells demonstrated growth inhibition and phenotypic change upon treatment with 8-Cl-cAMP. RII(beta)-P or RII(beta)-K cells failed to respond to 8-Cl-cAMP. These data suggest that autophosphorylation and nuclear location signal sequences are integral parts of the growth regulatory mechanism of RII(beta). C1 NCI,TUMOR IMMUNOL & BIOL LAB,CELLULAR BIOCHEM SECT,BETHESDA,MD 20892. OI Budillon, Alfredo/0000-0002-6330-6053 NR 47 TC 38 Z9 38 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 NOV 7 PY 1995 VL 92 IS 23 BP 10634 EP 10638 DI 10.1073/pnas.92.23.10634 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TD890 UT WOS:A1995TD89000039 PM 7479855 ER PT J AU PU, LP VANLEEUWEN, FW TRACER, HL SONNEMANS, MAF LOH, YP AF PU, LP VANLEEUWEN, FW TRACER, HL SONNEMANS, MAF LOH, YP TI LOCALIZATION OF VASOPRESSIN MESSENGER-RNA AND IMMUNOREACTIVITY IN PITUICYTES OF PITUITARY STALK-TRANSECTED RATS AFTER OSMOTIC STIMULATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HYPEROSMOTIC STRESS; NEUROPEPTIDE; ASTROCYTES; IN SITU HYBRIDIZATION; IMMUNOCYTOCHEMISTRY ID FIBRILLARY ACIDIC PROTEIN; MESSENGER-RNA; CULTURED ASTROCYTES; BRATTLEBORO RAT; NEURAL LOBE; EXPRESSION; NEUROHYPOPHYSIS; PROENKEPHALIN; OXYTOCIN; NEURONS AB The presence of [arginine] vasopressin (AVP) mRNA and AVP immunoreactivity in pituicytes of the neural lobe (NL) of intact and pituitary stalk-transected rats, with and without osmotic stimulation, was examined, AVP mRNA was analyzed by Northern blotting, as well as by in situ hybridization in combination with immunocytochemistry using anti-glial fibrillary acidic protein (GFAP) as a marker for pituicytes, In intact rats, a poly(A) tail-truncated 0.62-kb AVP mRNA was detected in the NL and was found to increase 10-fold with 7 days of continuous salt loading. Morphological analysis of the NL of 7-day salt-loaded rats revealed the presence of AVP mRNA in a significant number of GFAP-positive pituicytes in the NL and in areas most probably containing nerve fibers, Eight days after pituitary stalk transection the NL AVP mRNA diminished in animals given water to drink, whereas in those given 2% saline for 18 h followed by 6 h of water, a treatment repeated on 6 successive days beginning 2 days after surgery, the 0.62-kb AVP mRNA was present, The AW mRNA in the pituitary stalk-transected, salt-loaded rats showed an exclusive cellular distribution in the NL, indicative of localization in pituicytes, Immunoelectron microscopy showed the presence of AW immunoreactivity in a subpopulation of pituicytes 7 and 10 days after pituitary stalk transection in salt-loaded animals, when almost all AVP fibers had disappeared from the NL. These data show that a subset of pituicytes in the NL is activated to synthesize AVP mRNA and AVP in response to osmotic stimulation. C1 NETHERLANDS INST BRAIN RES,1105 AZ AMSTERDAM,NETHERLANDS. RP PU, LP (reprint author), NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BETHESDA,MD 20892, USA. NR 33 TC 29 Z9 29 U1 1 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 NOV 7 PY 1995 VL 92 IS 23 BP 10653 EP 10657 DI 10.1073/pnas.92.23.10653 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TD890 UT WOS:A1995TD89000043 PM 7479859 ER PT J AU MIKOSHIBA, K FUKUDA, M MOREIRA, JE LEWIS, FMT SUGIMORI, M NIINOBE, M LLINAS, R AF MIKOSHIBA, K FUKUDA, M MOREIRA, JE LEWIS, FMT SUGIMORI, M NIINOBE, M LLINAS, R TI ROLE OF THE C2A DOMAIN OF SYNAPTOTAGMIN IN TRANSMITTER RELEASE AS DETERMINED BY SPECIFIC ANTIBODY INJECTION INTO THE SQUID GIANT SYNAPSE PRETERMINAL SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SYNAPTIC TRANSMISSION; VOLTAGE CLAMP; CALCIUM CURRENT ID BINDING AB Squid synaptotagmin (Syt) cDNA, including its open reading frame, was cloned and polyclonal antibodies were obtained in rabbits immunized with glutathione S-transferase (GST)-Syt-C2A. Binding assays indicated that the antibody, anti-Syt-C2A, recognized squid Syt and inhibited the Ca2+-dependent phospholipid binding to the C2A domain, This antibody, when injected into the preterminal at the squid giant synapse, blocked transmitter release in a manner similar to that previously reported for the presynaptic injection of members of the inositol high-polyphosphate series. The block was not accompanied by any change in the presynaptic action potential or the amplitude or voltage dependence of the presynaptic Ca2+ current, The postsynaptic potential was rather insensitive to repetitive presynaptic stimulation, indicating a direct effect of the antibody on the transmitter release system. Following block of transmitter release, confocal microscopical analysis of the preterminal junction injected with rhodamine-conjugated anti-Syt-C2A demonstrated fluorescent spots at the inner surface of the presynaptic plasmalemma next to the active zones. Structural analysis of the same preparations demonstrated an accumulation of synaptic vesicles corresponding in size and distribution to the fluorescent spots demonstrated confocally, Together with the finding that such antibody prevents Ca2+ binding to a specific receptor in the C2A domain, these results indicate that Ca2+ triggers transmitter release by activating the C2A domain of Syt. We conclude that the C2A domain is directly related to the fusion of synaptic vesicles that results in transmitter release. C1 NYU, MED CTR, DEPT PHYSIOL & NEUROSCI, NEW YORK, NY 10016 USA. OSAKA UNIV, INST PROT RES, SUITA, OSAKA 565, JAPAN. INST PHYS & CHEM RES, TSUKUBA LIFE SCI CTR, MOLEC NEUROBIOL LAB, TSUKUBA, IBARAKI 305, JAPAN. UNIV TOKYO, INST MED SCI, DEPT MOLEC NEUROBIOL, TOKYO 108, JAPAN. NATL INST HLTH, NINDS, NEUROBIOL LAB, BETHESDA, MD 20892 USA. MARINE BIOL LAB, WOODS HOLE, MA 02543 USA. RI Fukuda, MItsunori/I-1511-2015; Mikoshiba, Katsuhiko/N-7943-2015 FU NIA NIH HHS [NIAG09480]; NINDS NIH HHS [NS13742] NR 17 TC 113 Z9 113 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 NOV 7 PY 1995 VL 92 IS 23 BP 10703 EP 10707 DI 10.1073/pnas.92.23.10703 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TD890 UT WOS:A1995TD89000053 PM 7479868 ER PT J AU FUKUDA, M MOREIRA, JE LEWIS, FMT SUGIMORI, M NIINOBE, M MIKOSHIBA, K LLINAS, R AF FUKUDA, M MOREIRA, JE LEWIS, FMT SUGIMORI, M NIINOBE, M MIKOSHIBA, K LLINAS, R TI ROLE OF THE C2B DOMAIN OF SYNAPTOTAGMIN IN VESICULAR RELEASE AND RECYCLING AS DETERMINED BY SPECIFIC ANTIBODY INJECTION INTO THE SQUID GIANT SYNAPSE PRETERMINAL SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE INOSITOL HIGH-POLYPHOSPHATE SERIES; VESICULAR FUSION; VESICULAR RECYCLING ID EXOCYTOSIS AB Synaptotagmin (Syt) is an inositol high-polyphosphate series [IHPS inositol 1,3,4,5-tetrakisphosphate (IP4), inositol 1,3,4,5,6-pentakisphosphate, and inositol 1,2,3,4,5,6-hexakisphosphate] binding synaptic vesicle protein. A polyclonal antibody against the C2B domain (anti-Syt-C2B), an IHPS binding site, was produced. The specificity of this antibody to the C2B domain was determined by comparing its ability to inhibit IP4 binding to the C2B domain with that to inhibit the Ca2+/phospholipid binding to the C2A domain. Injection of the anti-Syt-C2B IgG into the squid giant presynapse did not block synaptic release, Coinjection of IP4 and anti-Syt-C2B IgG failed to block transmitter release, while IP4 itself was a powerful synaptic release blocker, Repetitive stimulation to presynaptic fiber injected with anti-Syt-C2B IgG demonstrated a rapid decline of the postsynaptic response amplitude probably due to its block of synaptic vesicle recycling. Electron microscopy of the anti-Syt-C2B-injected presynapse showed a 90% reduction of the numbers of synaptic vesicles, These results, taken together, indicate that the Syt molecule is central, in synaptic vesicle fusion by Ca2+ and its regulation by IHPS, as well as in the recycling of synaptic vesicles. C1 OSAKA UNIV, INST PROT RES, SUITA, OSAKA 565, JAPAN. INST PHYS & CHEM RES, TSUKUBA LIFE SCI CTR, MOLEC NEUROBIOL LAB, TSUKUBA, IBARAKI 305, JAPAN. UNIV TOKYO, INST MED SCI, DEPT MOLEC NEUROBIOL, MINATO KU, TOKYO 108, JAPAN. NATL INST HLTH, NINDS, NEUROBIOL LAB, BETHESDA, MD 20892 USA. MARINE BIOL LAB, WOODS HOLE, MA 02543 USA. NYU, MED CTR, DEPT PHYSIOL & NEUROSCI, NEW YORK, NY 10016 USA. RI Fukuda, MItsunori/I-1511-2015; Mikoshiba, Katsuhiko/N-7943-2015 FU NIA NIH HHS [NIAG09480]; NINDS NIH HHS [NS13742] NR 13 TC 140 Z9 142 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 NOV 7 PY 1995 VL 92 IS 23 BP 10708 EP 10712 DI 10.1073/pnas.92.23.10708 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TD890 UT WOS:A1995TD89000054 PM 7479869 ER PT J AU GINSBERG, L RAFIQUE, S XUEREB, JH RAPOPORT, SI GERSHFELD, NL AF GINSBERG, L RAFIQUE, S XUEREB, JH RAPOPORT, SI GERSHFELD, NL TI DISEASE AND ANATOMIC SPECIFICITY OF ETHANOLAMINE PLASMALOGEN DEFICIENCY IN ALZHEIMERS-DISEASE BRAIN SO BRAIN RESEARCH LA English DT Note DE ALZHEIMERS DISEASE; BRAIN; MEMBRANE; LIPID; ETHANOLAMINE PLASMALOGEN ID APOLIPOPROTEIN-E; FATTY-ACID; BILAYER; PHOSPHOLIPIDS; TEMPERATURE; INSTABILITY; SEPARATION; LIPIDS; ALLELE; STATE AB A significant and selective deficiency of ethanolamine plasmalogen (PPE) relative to phosphatidylethanolamine was identified in post mortem brain samples from patients with Alzheimer's disease (AD). This lipid defect showed anatomic specificity, being more marked at a site of neurodegeneration in AD brain than in a region relatively spared by the disease (mid-temporal cortex vs. cerebellum) and disease specificity for AD: it was not observed at the primary site of neurodegeneration in Huntington's disease (caudate nucleus) nor Parbinson's disease (substantia nigra). PPE deficiency parallels an inherent tendency towards membrane bilayer instability previously detected in AD brain which is necessarily due to a change in membrane lipid composition, and which may contribute to AD pathogenesis. C1 UNIV LONDON,INST NEUROL,DEPT CLIN NEUROL,LONDON WC1N 3BG,ENGLAND. UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE,ENGLAND. NIA,NEUROSCI LAB,BETHESDA,MD 20892. NIAMS,PHYS BIOL LAB,BETHESDA,MD. RP GINSBERG, L (reprint author), ROYAL FREE HOSP,SCH MED,DEPT CLIN NEUROSCI,ROWLAND HILL ST,LONDON NW3 2PF,ENGLAND. RI Ginsberg, Lionel/C-8704-2009 NR 29 TC 110 Z9 113 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 6 PY 1995 VL 698 IS 1-2 BP 223 EP 226 DI 10.1016/0006-8993(95)00931-F PG 4 WC Neurosciences SC Neurosciences & Neurology GA TD488 UT WOS:A1995TD48800031 PM 8581486 ER PT J AU SZIRAKI, I RAUHALA, P CHIUEH, CC AF SZIRAKI, I RAUHALA, P CHIUEH, CC TI NOVEL PROTECTIVE EFFECT OF MANGANESE AGAINST FERROUS CITRATE-INDUCED LIPID-PEROXIDATION AND NIGROSTRIATAL NEURODEGENERATION IN-VIVO SO BRAIN RESEARCH LA English DT Note DE MANGANESE; FERROUS CITRATE; LIPID PEROXIDATION; NEUROTOXICITY; DOPAMINE; NIGROSTRIATAL NEURON; FREE RADICAL; MN-SOD ID RAT-BRAIN; NEUROTOXICITY; DOPAMINE AB Earlier studies intranigrally infusing high doses of manganese (50-250 nmol) revealed a reversible oxidative injury to nigrostriatal dopaminergic neurons. In fact, intranigral infusion of lower dose manganese (4.2 nmol) in the present study did not significantly alter dopamine levels in rat striatum. Moreover, manganese completely suppressed both acute lipid peroxidation in substantia nigra and chronic degeneration of the nigrostriatal neurons induced by intranigral infusion of ferrous citrate (4.2 nmol). These in vivo data indicate that low dose manganese is a potent antioxidant which may activate antioxidative defense mechanisms to protect brain neurons against oxidative stress induced by iron complexes. C1 NIMH,CLIN SCI LAB,NEUROTOXICOL & NEUROPROTECT UNIT,BETHESDA,MD 20892. OI Rauhala, Pekka/0000-0003-2036-3522 NR 18 TC 28 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 6 PY 1995 VL 698 IS 1-2 BP 285 EP 287 DI 10.1016/0006-8993(95)01056-2 PG 3 WC Neurosciences SC Neurosciences & Neurology GA TD488 UT WOS:A1995TD48800043 PM 8581499 ER PT J AU MIZUUCHI, M BAKER, TA MIZUUCHI, K AF MIZUUCHI, M BAKER, TA MIZUUCHI, K TI ASSEMBLY OF PHAGE-MU TRANSPOSOSOMES - COOPERATIVE TRANSITIONS ASSISTED BY PROTEIN AND DNA SCAFFOLDS SO CELL LA English DT Article ID STRAND TRANSFER-REACTION; BACTERIOPHAGE-MU; B-PROTEIN; TRANSPOSITIONAL ENHANCER; INVITRO TRANSPOSITION; TN7 TRANSPOSITION; ESCHERICHIA-COLI; RIBONUCLEASE-H; TARGET DNA; A-PROTEIN AB Transposition of phage Mu takes place within higher order protein-DNA complexes called transpososomes. These complexes contain the two Mu genome ends synapsed by a tetramer of Mu transposase (MuA). Transpososome assembly is tightly controlled by multi pie protein and DNA sequence cofactors. We find that assembly can occur through two distinct pathways. One previously described pathway depends on an enhancer-like sequence element, the internal activation sequence (IAS). The second pathway depends on a MuB protein-target DNA complex. For both pathways, all four MuA monomers in the tetramer need to interact with an assembly-assisting element, either the IAS or MuB. However, once assembled, not all MuA monomers within the transpososome need to interact with MuB to capture MuB-bound target DNA. The multiple layers of control likely are used in vivo to ensure efficient rounds of DNA replication when needed, while minimizing unwanted transposition products. C1 MIT, HOWARD HUGHES MED INST, CAMBRIDGE, MA 02139 USA. MIT, DEPT BIOL, CAMBRIDGE, MA 02139 USA. RP MIZUUCHI, M (reprint author), NIDDKD, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. FU NIGMS NIH HHS [GM499224] NR 48 TC 39 Z9 40 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD NOV 3 PY 1995 VL 83 IS 3 BP 375 EP 385 DI 10.1016/0092-8674(95)90115-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TC977 UT WOS:A1995TC97700007 PM 8521467 ER PT J AU MCBLANE, JF VANGENT, DC RAMSDEN, DA ROMEO, C CUOMO, CA GELLERT, M OETTINGER, MA AF MCBLANE, JF VANGENT, DC RAMSDEN, DA ROMEO, C CUOMO, CA GELLERT, M OETTINGER, MA TI CLEAVAGE AT A V(D)J RECOMBINATION SIGNAL REQUIRES ONLY RAG1 AND RAG2 PROTEINS AND OCCURS IN 2 STEPS SO CELL LA English DT Article ID SITE-SPECIFIC RECOMBINATION; BROKEN DNA-MOLECULES; MOUSE THYMOCYTES; STRAND TRANSFER; MECHANISM; REARRANGEMENT; EXPRESSION; GENES; MICE AB Formation of double-strand breaks at recombination signal sequences is an early step in V(D)J recombination. Here we show that purified RAG1 and RAGS proteins are sufficient to carry out this reaction. The cleavage reaction can be divided into two distinct steps. First, a nick is introduced at the 5' end of the signal sequence, The other strand is then broken, resulting in a hairpin structure at the coding end and a blunt, 5'-phosphorylated signal end. The hairpin is made as a direct consequence of the cleavage mechanism. Nicking and hairpin formation each require the presence of a signal sequence and both RAG proteins. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RP MCBLANE, JF (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [GM48026] NR 32 TC 513 Z9 519 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 3 PY 1995 VL 83 IS 3 BP 387 EP 395 DI 10.1016/0092-8674(95)90116-7 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TC977 UT WOS:A1995TC97700008 PM 8521468 ER PT J AU MORHAM, SG LANGENBACH, R LOFTIN, CD TIANO, HF VOULOUMANOS, N JENNETTE, JC MAHLER, JF KLUCKMAN, KD LEDFORD, A LEE, CA SMITHIES, O AF MORHAM, SG LANGENBACH, R LOFTIN, CD TIANO, HF VOULOUMANOS, N JENNETTE, JC MAHLER, JF KLUCKMAN, KD LEDFORD, A LEE, CA SMITHIES, O TI PROSTAGLANDIN-SYNTHASE-2 GENE DISRUPTION CAUSES SEVERE RENAL PATHOLOGY IN THE MOUSE SO CELL LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ANTI-INFLAMMATORY DRUGS; ENDOPEROXIDE SYNTHASE; G/H SYNTHASE; INDUCIBLE CYCLOOXYGENASE; ALVEOLAR MACROPHAGES; MESSENGER-RNA; CDNA CLONING; EXPRESSION; INHIBITION AB The prostaglandin endoperoxide H synthase isoform 2, cyclooxygenase 2 (COX-2), is induced at high levels in migratory and other responding cells by proinflammatory stimuli. COX-2 is generally considered to be a mediator of inflammation. Its isoform, COX-1, is constitutively expressed in most tissues and is thought to mediate ''housekeeping'' functions. These two enzymes are therapeutic targets of the widely used nonsteroidal anti-inflammatory drugs (NSAIDs). To investigate further the different physiologic roles of these isoforms, we have used homologous recombination to disrupt the mouse gene encoding COX-2 (PtgsS). Mice lacking COX-2 have normal inflammatory responses to treatments with tetradecanoyl phorbol acetate or with arachidonic acid. However, the; develop severe nephropathy and are susceptible to peritonitis. C1 NIEHS,EXPTL CARCINOGENESIS & MUTAGENESIS LAB,RES TRIANGLE PK,NC 27709. NIEHS,EXPTL PATHOL LAB,RES TRIANGLE PK,NC 27709. RP MORHAM, SG (reprint author), UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27599, USA. FU NHLBI NIH HHS [HL49227]; NIGMS NIH HHS [GM20069] NR 60 TC 885 Z9 897 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 3 PY 1995 VL 83 IS 3 BP 473 EP 482 DI 10.1016/0092-8674(95)90125-6 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TC977 UT WOS:A1995TC97700017 PM 8521477 ER PT J AU LANGENBACH, R MORHAM, SG TIANO, HF LOFTIN, CD GHANAYEM, BI CHULADA, PC MAHLER, JF LEE, CA GOULDING, EH KLUCKMAN, KD KIM, HS SMITHIES, O AF LANGENBACH, R MORHAM, SG TIANO, HF LOFTIN, CD GHANAYEM, BI CHULADA, PC MAHLER, JF LEE, CA GOULDING, EH KLUCKMAN, KD KIM, HS SMITHIES, O TI PROSTAGLANDIN-SYNTHASE-1 GENE DISRUPTION IN MICE REDUCES ARACHIDONIC ACID-INDUCED INFLAMMATION AND INDOMETHACIN-INDUCED GASTRIC-ULCERATION SO CELL LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; IMMEDIATE-EARLY GENE; ENDOPEROXIDE SYNTHASE; MESSENGER-RNA; G/H SYNTHASE; COMPLEMENTARY-DNA; CDNA CLONING; COLON CANCER; ASPIRIN USE; CYCLOOXYGENASE AB Cyclooxygenases 1 and 2 (COX-1 and COX-2) are key enzymes in prostaglandin biosynthesis and the target enzymes for the widely used nonsteroidal anti-inflammatory drugs. To study the physiological roles of the individual isoforms, we have disrupted the mouse Ptgs1 gene encoding COX-1. Homozygous Ptgs1 mutant mice survive well, have no gastric pathology, and show less indomethacin-induced gastric ulceration than wild-type mice, even though their gastric prostaglandin E(2) levels are about 1% of wild type. The homozygous mutant mice have reduced platelet aggregation and a decreased inflammatory response to arachidonic acid, but not to tetradecanoyl phorbol acetate. Ptgs1 homozygous mutant females mated to homozygous mutant males produce few live offspring. COX-1-deficient mice provide a useful model to distinguish the physiological roles of COX-1 and COX-2. C1 NIEHS, BIOCHEM RISK ANAL LAB, RES TRIANGLE PK, NC 27709 USA. NIEHS, EXPTL PATHOL LAB, RES TRIANGLE PK, NC 27709 USA. NIEHS, REPROD & DEV TOXICOL LAB, RES TRIANGLE PK, NC 27709 USA. UNIV N CAROLINA, DEPT PATHOL, CHAPEL HILL, NC 27599 USA. RP NIEHS, EXPTL CARCINOGENESIS & MUTAGENESIS LAB, RES TRIANGLE PK, NC 27709 USA. FU NHLBI NIH HHS [HL49227]; NIGMS NIH HHS [GM20069] NR 82 TC 859 Z9 873 U1 2 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD NOV 3 PY 1995 VL 83 IS 3 BP 483 EP 492 DI 10.1016/0092-8674(95)90126-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TC977 UT WOS:A1995TC97700018 PM 8521478 ER PT J AU ANDERSSON, M WALLIN, H JONSSON, M NIELSEN, LL VISFELDT, J VYBERG, M BENNETT, WP DEBENEDETTI, VMG TRAVIS, LB STORM, HH AF ANDERSSON, M WALLIN, H JONSSON, M NIELSEN, LL VISFELDT, J VYBERG, M BENNETT, WP DEBENEDETTI, VMG TRAVIS, LB STORM, HH TI LUNG-CARCINOMA AND MALIGNANT MESOTHELIOMA IN PATIENTS EXPOSED TO THOROTRAST - INCIDENCE, HISTOLOGY AND P53 STATUS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CELL-LINES; PERITONEAL MESOTHELIOMA; URANIUM MINERS; RAS MUTATIONS; CANCER; INDUCTION; GENE AB In a previous registry-based survey of 999 patients injected with alpha-emitting (ThO2)-Th-232 (Thorotrast), we identified elevated risks for lung carcinoma and malignant mesothelioma. Since injected Thorotrast is retained lifelong mostly in liver, spleen and lymph nodes, the mesothelial surfaces of these organs are constantly irradiated. Thorotrast-administered patients also perpetually exhale Rn-220, a Th-232-daughter. Study of Thorotrast-exposed patients may, therefore, provide data with regard to carcinogenicity of radon exposure, a current public health concern, as well as the pathogenesis of malignant mesothelioma The incidence and histologic types of rung carcinoma and malignant mesothelioma within the cohort were examined by review of available histopathologic material and medical records. Further, mutations of the p53 gene were analyzed whenever possible as it has previously been suggested that radon-associated lung carcinomas exhibit specific mutational patterns. The cumulative risk for lung carcinoma reached 11.0% based on 20 confirmed cases. Nine were small cell rung cancer (SCLC), whereas the expected frequency was 18%. The risk for malignant mesothelioma reached 2.5% based on 7 cases. The actuarial risk of malignant mesothelioma for patients given more than 20 ml Thorotrast was 7.8% compared to 1.4% for patients administered smaller amounts. Seven lung carcinomas and 5 malignant mesotheliomas were analyzed for p53 mutations; only I (in a lung adenocarcinoma) was detected. A possible association between Thorotrast and SCLC is suggested. In addition, a possible dose-response gradient exists for Thorotrast and malignant mesothelioma. (C) 1995 Wiley-Liss, Inc. C1 DANISH CANC SOC,DIV CANC BIOL,DK-2100 COPENHAGEN,DENMARK. RIGSHOSP,NATL UNIV HOSP,DEPT ONCOL,COPENHAGEN,DENMARK. RIGSHOSP,NATL UNIV HOSP,DEPT PATHOL,COPENHAGEN,DENMARK. LUND UNIV,DEPT OCCUPAT & ENVIRONM MED,LUND,SWEDEN. AALBORG HOSP,INST PATHOL,AALBORG,DENMARK. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP ANDERSSON, M (reprint author), DANISH CANC SOC,DIV CANC EPIDEMIOL,BOX 839,49 STRANDBLVD,DK-2100 COPENHAGEN,DENMARK. RI Vyberg, Mogens/E-7576-2016; Wallin, Hakan/I-6459-2012 OI Vyberg, Mogens/0000-0002-6392-9517; Wallin, Hakan/0000-0001-7716-0166 NR 39 TC 30 Z9 32 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 3 PY 1995 VL 63 IS 3 BP 330 EP 336 DI 10.1002/ijc.2910630304 PG 7 WC Oncology SC Oncology GA TB576 UT WOS:A1995TB57600003 PM 7591226 ER PT J AU MOULD, AP AKIYAMA, SK HUMPHRIES, MJ AF MOULD, AP AKIYAMA, SK HUMPHRIES, MJ TI REGULATION OF INTEGRIN ALPHA-5-BETA-1-FIBRONECTIN INTERACTIONS BY DIVALENT-CATIONS - EVIDENCE FOR DISTINCT CLASSES OF BINDING-SITES FOR MN2+, MG2+, AND CA2+ SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-PLASMA FIBRONECTIN; CELL-ADHESION; LIGAND-BINDING; VITRONECTIN RECEPTOR; LEUKOCYTE ADHESION; PLATELET INTEGRIN; ALPHA-SUBUNIT; BETA-SUBUNIT; DOMAIN; IDENTIFICATION AB Integrin-ligand interactions are known to be dependent on divalent cations, although the precise role of cations in ligand binding is still unclear. Using the interaction between alpha 5 beta 1 and fibronectin as a model system, we have performed a comprehensive analysis of the effects of Mn2+, Mg2+, and Ca2+ on Ligand binding. Each cation had distinct effects on the ligand-binding capacity of alpha 5 beta 1:Mn2+ promoted high levels of Ligand binding, Mg2+ promoted low levels of binding, and Ca2+ failed to support binding Studies of the effects of different combinations of cations on Ligand binding indicated that the cation-binding sites within alpha 5 beta 1 are not all identical, or of broad specificity, but instead each site shows a distinct preference for one or more cations, Ca2+ strongly inhibited Mn2+-supported Ligand binding, but this inhibition was noncompetitive, suggesting that Ca2+ recognizes different cation-binding sites to Mn2+. In contrast, Ca2+ acted as a direct competitive inhibitor of Mg2+-supported Ligand binding, implying that Ca2+ can displace Mg2+ from the integrin. However, low concentrations of Ca2+ greatly increased the apparent affinity of Mg2+ for its binding site, suggesting the existence of a distinct high affinity Ca2+-binding site. Taken together, our results imply that the ligand-binding capacity of alpha 5 beta 1 can be regulated in a complex manner through separate classes of binding sites for Mn2+, Mg2+, and Ca2+. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP MOULD, AP (reprint author), UNIV MANCHESTER,SCH BIOL SCI,WELLCOME TRUST CTR CELL MATRIX RES,2 205 STOPFORD BLDG,OXFORD RD,MANCHESTER M13 9PT,LANCS,ENGLAND. FU Wellcome Trust NR 52 TC 208 Z9 215 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 NOV 3 PY 1995 VL 270 IS 44 BP 26270 EP 26277 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TC978 UT WOS:A1995TC97800042 PM 7592835 ER PT J AU SKOWYRA, D WICKNER, S AF SKOWYRA, D WICKNER, S TI GRPE ALTERS THE AFFINITY OF DNAK FOR ATP AND MG2+ - IMPLICATIONS FOR THE MECHANISM OF NUCLEOTIDE EXCHANGE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK PROTEINS; ESCHERICHIA-COLI; REPA MONOMERIZATION; REPLICATION; CHAPERONES; BINDING; ORIGIN; GROEL AB DnaK, DnaJ, and GrpE heat shock proteins of Escherichia coli activate site-specific DNA binding by the RepA replication initiator protein of plasmid P1 in a reaction dependent on ATP and Mg2+. We previously showed that GrpE is essential for in. vitro RepA activation specifically at about 1 mu m free Mg2+. In this paper, we demonstrate that GrpE lowers the requirement of DnaK ATPase for Mg2+, resulting in a large stimulation of ATP hydrolysis at about 1 mu M Mg2+ with and without DnaJ and RepA. In contrast to its effect on the Mg2+ requirement, GrpE increases the ATP requirement for DnaK ATPase and dramatically lowers the affinity of DnaK for ATP in the absence of Mg2+. We propose that GrpE not only lowers the affinity of DnaK for nucleotide but, by increasing affinity of DnaK for Mg2+, also weakens the interactions of Mg2+ with nucleotide prior to its release. RP SKOWYRA, D (reprint author), NCI, MOLEC BIOL LAB, BLDG 37, BETHESDA, MD 20892 USA. NR 30 TC 11 Z9 11 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 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 3 PY 1995 VL 270 IS 44 BP 26282 EP 26285 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TC978 UT WOS:A1995TC97800044 PM 7592837 ER PT J AU CANDI, E MELINO, G MEI, G TARCSA, E CHUNG, SI MAREKOV, LN STEINERT, PM AF CANDI, E MELINO, G MEI, G TARCSA, E CHUNG, SI MAREKOV, LN STEINERT, PM TI BIOCHEMICAL, STRUCTURAL, AND TRANSGLUTAMINASE SUBSTRATE PROPERTIES OF HUMAN LORICRIN, THE MAJOR EPIDERMAL CORNIFIED CELL-ENVELOPE PROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CROSS-LINKING; EXPRESSION; DIFFERENTIATION; INVOLUCRIN; KERATIN AB Loricrin is the major protein of the cornified cell envelope of terminally differentiated epidermal keratinocytes which functions as a physical barrier, In order to understand its properties and role in cornified cell envelope, we have expressed human loricrin from a full-length cDNA clone in bacteria and purified it to homogeneity. We have also isolated loricrin from newborn mouse epidermis. By circular dichroism and fluorescence spectroscopy, the in vivo mouse and bacterially expressed human loricrins possess no alpha or beta structure but have some organized structure in solution associated with their multiple tyrosines and can be reversibly denatured by either guanidine hydrochloride or temperature. The transglutaminase (TGase) 1, 2, and 3 enzymes expressed during epidermal differentiation utilized loricrin in vitro as a complete substrate, but the types of cross-linking were different. The TGase 3 reaction favored certain lysines and glutamines by forming mostly intrachain cross-links, whereas TGase 1 formed mostly large oligomeric complexes by interchain crosslinks involving different lysines and glutamines. Together, the glutamines and lysines used in vitro are almost identical to those seen in vivo. The data support a hypothesis for the essential and complementary roles of both TGase 1 and TGase 3 in cross-linking of loricrin in vivo. Failure to cross-link loricrin by TGase 1 may explain the phenotype of lamellar ichthyosis, a disease caused by mutations in the TGase 1 gene. C1 NIAMS,SKIN BIOL BRANCH,BETHESDA,MD 20892. NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. UNIV ROMA TOR VERGATA,IST DERMOPAT IMMACOLATA,DEPT EXPTL MED,BIOCHEM LABS,I-00167 ROME,ITALY. UNIV LAQUILA,DEPT BIOL,I-67100 LAQUILA,ITALY. NR 42 TC 127 Z9 128 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 NOV 3 PY 1995 VL 270 IS 44 BP 26382 EP 26390 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TC978 UT WOS:A1995TC97800059 PM 7592852 ER PT J AU CHAMULITRAT, W BLAZKA, ME JORDAN, SJ LUSTER, MI MASON, RP AF CHAMULITRAT, W BLAZKA, ME JORDAN, SJ LUSTER, MI MASON, RP TI TUMOR-NECROSIS-FACTOR-ALPHA AND NITRIC-OXIDE PRODUCTION IN ENDOTOXIN-PRIMED RATS ADMINISTERED CARBON-TETRACHLORIDE SO LIFE SCIENCES LA English DT Article DE HEPATOXICITY; CARBON TETRACHLORIDE; NITRIC OXIDE; LIVER TOXICITY; TUMOR NECROSIS FACTOR ID PROTEIN-SYNTHESIS; L-ARGININE; HEPATOCYTES; INVIVO; CYTOKINES; INDUCTION; BIOSYNTHESIS; CACHECTIN; SYNTHASE; INHIBIT AB Tumor necrosis factor-alpha (TNF alpha) is elevated in the sera of rats administered non-lethal doses of carbon tetrachloride (CCl4) followed by endotoxin. Elevated TNF alpha levels are correlated with the increased release of hepatic enzymes indicating hepatic damage. Under these conditions, nitric oxide (NO) was also produced in the liver as evidenced by the formation of nitrosyl complexes which were measured by electron paramagnetic resonance (EPR) spectroscopy. Decreased nitrosyl complex formation occurred in livers following treatment with either an inhibitor of macrophage activation (gadolinium trichloride; GdCl3), an inhibitor of cytokine responses (dexamethasone) or a NO synthase inhibitor (N-G-monomethyl-L-arginine; 1-NMA). GdCl3 or dexamethasone treatment decreased, while 1-NMA treatment increased, TNF alpha serum level. Taken together, these data suggest that TNF alpha and NO are induced following CCl4 and LPS exposure and may be important regulators in the hepatotoxicity of this liver injury model. C1 NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 30 TC 44 Z9 46 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD NOV 3 PY 1995 VL 57 IS 24 BP 2273 EP 2280 DI 10.1016/0024-3205(95)02220-D PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA TD162 UT WOS:A1995TD16200010 PM 7475981 ER PT J AU UNGERLEIDER, LG AF UNGERLEIDER, LG TI FUNCTIONAL BRAIN IMAGING STUDIES OF CORTICAL MECHANISMS FOR MEMORY SO SCIENCE LA English DT Review ID INFERIOR TEMPORAL CORTEX; POSITRON EMISSION TOMOGRAPHY; POSTERIOR CEREBRAL-LESIONS; HUMAN VISUAL-CORTEX; WORKING-MEMORY; MOTOR CORTEX; HIPPOCAMPAL-FORMATION; SENSORY STIMULATION; MACAQUE MONKEY; FRONTAL-CORTEX AB Recent functional brain imaging studies in humans indicate that learning and memory involve many of the same regions of the cortex that process sensory information and control motor output. The forms of perceptual and motor learning that can occur without conscious recollection are mediated in part by contractions and expansions of representations in the sensory and motor cortex. The same regions are also engaged during the conscious storage and retrieval of facts and events, but these types of memory also bring into play structures involved in the active maintenance of memories ''on line'' and in the establishment of associative links between the information stored in different sensory areas. Although the picture of memory that is emerging from functional imaging studies is consistent with current physiological accounts, there are puzzles and surprises that will be solved only through a combination of human and animal studies. RP UNGERLEIDER, LG (reprint author), NIMH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892, USA. NR 147 TC 344 Z9 348 U1 2 U2 13 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 3 PY 1995 VL 270 IS 5237 BP 769 EP 775 DI 10.1126/science.270.5237.769 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TC712 UT WOS:A1995TC71200031 PM 7481764 ER PT J AU RUSSELL, SM TAYEBI, N NAKAJIMA, H RIEDY, MC ROBERTS, JL AMAN, MJ MIGONE, TS NOGUCHI, M MARKERT, ML BUCKLEY, RH O'SHEA, JJ LEONARD, WJ AF RUSSELL, SM TAYEBI, N NAKAJIMA, H RIEDY, MC ROBERTS, JL AMAN, MJ MIGONE, TS NOGUCHI, M MARKERT, ML BUCKLEY, RH O'SHEA, JJ LEONARD, WJ TI MUTATION OF JAK3 IN A PATIENT WITH SCID - ESSENTIAL ROLE OF JAK3 IN LYMPHOID DEVELOPMENT SO SCIENCE LA English DT Article ID RECEPTOR GAMMA-CHAIN; FUNCTIONAL COMPONENT; IL-2 RECEPTOR AB Males with X-linked severe combined immunodeficiency (XSCID) have defects in the common cytokine receptor gamma chain (gamma(c)) gene that encodes a shared, essential component of the receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, and IL-15. The Janus family tyrosine kinase Jak3 is the only signaling molecule known to be associated with gamma(c), so it was hypothesized that defects in Jak3 might cause an XSCID-like phenotype. A girl with immunological features indistinguishable from those of XSCID was therefore selected for analysis. An Epstein-Barr virus (EBV)-transformed cell line derived from her lymphocytes had normal gamma(c) expression but lacked Jak3 protein and had greatly diminished Jak3 messenger RNA. Sequencing revealed a different mutation on each allele: a single nucleotide insertion resulting in a frame shift and premature termination in the Jak3 JH4 domain and a nonsense mutation in the Jak3 JH2 domain. The lack of Jak3 expression correlated with impaired B cell signaling, as demonstrated by the inability of IL-4 to activate Stat6 in the EBV-transformed cell line from the patient. These observations indicate that the functions of gamma(c) are dependent on Jak3 and that Jak3 is essential for lymphoid development and signaling. C1 NHLBI, MOLEC IMMUNOL LAB, BETHESDA, MD 20892 USA. NIMH, CLIN NEUROSCI BRANCH, CLIN GENET UNIT, BETHESDA, MD 20892 USA. NIAMSD, ARTHRITIS & RHEUMATISM BRANCH, BETHESDA, MD 20892 USA. DUKE UNIV, SCH MED, DEPT IMMUNOL, DURHAM, NC 27710 USA. DUKE UNIV, SCH MED, DEPT PEDIAT, DURHAM, NC 27710 USA. RI Russell, Sarah/B-9341-2009 OI Russell, Sarah/0000-0001-5826-9641 FU NCI NIH HHS [T32 CA09058]; NCRR NIH HHS [M01-RR30]; NIAID NIH HHS [R37AI18613-13] NR 31 TC 489 Z9 499 U1 2 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 3 PY 1995 VL 270 IS 5237 BP 797 EP 800 DI 10.1126/science.270.5237.797 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TC712 UT WOS:A1995TC71200040 PM 7481768 ER PT J AU ACS, P SZALLASI, Z KAZANIETZ, MG BLUMBERG, PM AF ACS, P SZALLASI, Z KAZANIETZ, MG BLUMBERG, PM TI DIFFERENTIAL ACTIVATION OF PKC ISOZYMES BY 14-3-3-ZETA-PROTEIN SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID KINASE-C-DELTA; BRAIN; PURIFICATION; EPSILON; LIGAND AB 14-3-3 proteins are ubiquitous in eukaryotes associated with many fundamental functions in signal transduction pathways and cell cycle regulation. Protein kinase C comprises a large family of serine/threonine protein kinases that are involved in cell growth and differentiation. Different protein kinase C isozymes have distinct roles in signal transduction pathways; protein kinase C epsilon is of particular interest because its overexpression leads to oncogenic transformation. The 14-3-3 protein has been reported to regulate the activity of protein kinase C, although the nature of its effect is equivocal. In this study we report the differential activation of various protein kinase C isoforms by 14-3-3 zeta protein. The classical isozymes show approximately a twofold activation, protein kinase C delta shows no significant increase in activity, whereas protein kinase C E, another novel isozyme, is highly activated. This activation shows strong positive cooperativity with a Hill coefficient of 6.1 +/- 0.2. (C) 1995 Academic Press, Inc. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOLEC MECH TUMOR PROMOT SECT,BETHESDA,MD 20892. NR 32 TC 41 Z9 42 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 2 PY 1995 VL 216 IS 1 BP 103 EP 109 DI 10.1006/bbrc.1995.2597 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TD653 UT WOS:A1995TD65300014 PM 7488074 ER PT J AU LI, BQ WANG, MH KUNG, HF RONSIN, C BREATHNACH, R LEONARD, EJ KAMATA, T AF LI, BQ WANG, MH KUNG, HF RONSIN, C BREATHNACH, R LEONARD, EJ KAMATA, T TI MACROPHAGE-STIMULATING PROTEIN ACTIVATES RAS BY BOTH ACTIVATION AND TRANSLOCATION OF SOS NUCLEOTIDE EXCHANGE FACTOR SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; TYROSINE KINASE-ACTIVITY; SCATTER FACTOR; SIGNAL TRANSDUCTION; SH3 DOMAIN; C-MET; GRB2; RECEPTOR; GENE; IDENTIFICATION AB Macrophage-stimulating protein (MSP) is a chemotactic factor that activates the receptor tyrosine kinase RON. The involvement of Ras in MSP-induced signal transduction was investigated. Here we demonstrate that, in RON-transfected MDCK cells, an active GTP-bound form of Ras was rapidly accumulated by MSP treatment and the Ras-guanine nucleotide exchange activity in SOS immunoprecipitates was concomitantly increased. GAP activity was not changed under the same conditions used. Furthermore, the SH2 domain of adaptor protein GRB2 but not Shc, associated with the activated RON-beta chain, and GRB2-SOS complexes translocated from the cytosol to the membrane upon MSP treatment. These results strongly suggest that MSP activates Ras through RON, and that MSP-induced activation of Pas might be controlled by both the enhancement of catalytic exchange activity of SOS and its translocation to the membrane where its target Ras is localized. (C) 1995 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702. CHR NANTES,INST BIOL,INSERM,U211,F-44035 NANTES 01,FRANCE. RP LI, BQ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOCHEM PHYSIOL LAB,SAIC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. RI Breathnach, Richard/K-7599-2015 NR 36 TC 37 Z9 38 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 2 PY 1995 VL 216 IS 1 BP 110 EP 118 DI 10.1006/bbrc.1995.2598 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TD653 UT WOS:A1995TD65300015 PM 7488076 ER PT J AU GOMEZ, DE YOSHIJI, H KIM, JC THORGEIRSSON, UP AF GOMEZ, DE YOSHIJI, H KIM, JC THORGEIRSSON, UP TI ULEX-EUROPAEUS-I LECTIN INDUCES ACTIVATION OF MATRIX-METALLOPROTEINASE-2 IN ENDOTHELIAL-CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MATRIX METALLOPROTEINASES; TISSUE INHIBITOR; COLLAGENASE; IDENTIFICATION; BINDING; EXPRESSION; GELATINASE; MOLECULES AB In this report, we show that the lectin Ulex europaeus agglutinin I (UEA I), which binds to alpha-linked fucose residues on the surface of endothelial cells, mediates activation of the 72-kDa matrix metalloproteinase-2 (MMP-2). A dose-dependent increase in the active 62-kDa form of MMP-2 was observed in conditioned medium from monkey aortic endothelial cells (MAEC) following incubation with concentrations of UEA I ranging from 2 to 100 mu g/ml. The increase in the 62-kDa MMP-2 gelatinolytic activity was not reflected by a rise in MMP-2 gene expression. The UEA I-mediated activation of MMP-2 was blocked by L-fucose, which competes with UEA I for binding to alpha-fucose. These findings may suggest that a similar in vivo mechanism exists, whereby adhesive interactions between tumor cell lectins and endothelial cells can mediate MMP-2 activation. (C) 1995 Academic Press, Inc. C1 NCI,DIV CANC ETIOL,OFF DIRECTOR,BETHESDA,MD 20892. OI Gomez, Daniel E/0000-0002-8629-0787 NR 24 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 2 PY 1995 VL 216 IS 1 BP 177 EP 182 DI 10.1006/bbrc.1995.2607 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TD653 UT WOS:A1995TD65300024 PM 7488085 ER PT J AU RANDAD, RS LUBKOWSKA, L BUJACZ, A NAIK, RH GULNIK, SV YU, B SILVA, A MUNSHI, S LYNCH, TM CLANTON, DJ BHAT, TN ERICKSON, JW AF RANDAD, RS LUBKOWSKA, L BUJACZ, A NAIK, RH GULNIK, SV YU, B SILVA, A MUNSHI, S LYNCH, TM CLANTON, DJ BHAT, TN ERICKSON, JW TI STRUCTURE-BASED DESIGN OF ACHIRAL ANTHRANILAMIDES AS P2/P2' SURROGATES FOR SYMMETRY-BASED HIV PROTEASE INHIBITORS - DESIGN, SYNTHESIS, X-RAY STRUCTURE, ENZYME-INHIBITION AND ANTIVIRAL ACTIVITY SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID AIDS AB Guided by the structure of HIV PR complexed with 2S,3R,4S,5S-2,5-bis[N,N'-((3-hydroxy-2-methylphenyl)carbonyl)amino] -3,4-dihydroxy-1,6-diphenyl hexane (1), a novel, achiral, non-peptidic anthranil (Ant) group was designed as a P2/P2' ligand. Symmetry-based inhibitors containing N-(2-pyridinylmethoxy-carbonyl)anthranil group are potent anti viral agents. Compounds 12 and 14 exhibited protease inhibitory activity of 60 and 70 pM, anti viral activity of 13 and 56 nM and cellular toxicity of >10 uM respectively. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,AIDS DRUG SCREENING & DEV LAB,FREDERICK,MD 21702. RP RANDAD, RS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702, USA. NR 10 TC 5 Z9 5 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 2 PY 1995 VL 5 IS 21 BP 2557 EP 2562 DI 10.1016/0960-894X(95)00449-4 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA TC828 UT WOS:A1995TC82800021 ER PT J AU BERN, C PHILEN, RM FREDMAN, D BOWMAN, BA NEWMAN, NJ GERR, F RIDEL, GM PENA, EZ MALILAY, J MILLER, DT SOWELL, AL MILLER, MA FLANDERS, WD FALTER, KH OLSON, DR KILBOURNE, EM SINKS, T ING, R STAEHLING, N BOYD, M GUNTER, EW PASCHAL, DC MUELLER, PW SPIERTO, FW NEEDHAM, LL HILL, RH ASHLEY, DL HANNON, WH MARQUEZ, AR FERNANDEZ, JRD HADAD, JH MILORD, DR CRISTIA, RP PEREZ, MAH VERDURA, CS ALBA, MAM HODELIN, MT GORBEA, MB DIAZ, ED HIORTLORENZEN, CLC CLUA, AM GUTIERREZ, PM ACOSTA, SJ CABRERA, A FERNANDEZ, MM FREIXAS, RS ESTRADA, R ARIAS, L MESTRE, PF PLA, E ROMERO, MC FERRET, AC LLANOS, G JIMENEZ, JS ROMAN, GC OBERMEYER, W CASTRO, MD RUIZ, CAP RICO, NS BETANCOURT, IP FUENTES, BEE CABRERA, AP CALDELLICEHIO, LET MEDINA, AG GOMEZ, N MOJARRIETA, MS VARA, JAC PORTALES, JMR HERNANDEZ, GR GINALY, SM GARCIA, PP GARCIA, M HERNANDEZ, CS DIAZ, EI RECIO, EM GARCIA, SH SANCHEZ, AL VALDES, P RODRIGUEZ, OM OLIVA, NB DIAZ, D PEREZ, MC HERNANDEZ, MCR GONEZ, JMR AMADO, SN DELLLANO, AC BREIJO, DH ACOSTA, AC GONZALEZ, MM ROMERO, RM CHAVEZ, OC VALDES, MH OTERO, GR CABALLERO, MM VALDES, AG OLIVERA, BR BENITEZ, EE BEADE, C LEON, LS MARIMON, FD ROMAN, AS RODRIGUEZ, R RODRIGUEZ, FD ALVAREZ, MR COLUMBE, MS MARRERO, A ZULUETA, D GARCIA, CR SANTOS, JPA PEDROSO, F RODRIGUEZ, HM VALDES, NM ACOSTA, MS CHOBEL, ER GODOY, MM LUGO, MM LOPEZ, LL DIAZ, EM MARTINEZ, JCB DELGADO, NA VALDES, MT MORENO, ARD SANCHEZ, SH HERNANDEZ, LEP VALDES, OM MARTINEZ, AO DOMINGUEZ, I DEARMAS, MR IGLESIAS, OR CASTELL, OR TRUJILLO, OG BEUNE, MDM RODRIGUEZ, FM MEDINA, RM RUIZCALDERON, JC FERNANDEZ, B BARROSO, EV MACHIN, JL ARMENTEROS, LR MENDEZ, CV PEREZ, JH CAMPOS, AC DIAZ, NA PEREZ, AO MILIAN, J LEON, OH CAPOTE, BR LEZCANOS, MR EZMORIZ, LP MOYA, O VITRIAGO, A MURGUIA, AU AF BERN, C PHILEN, RM FREDMAN, D BOWMAN, BA NEWMAN, NJ GERR, F RIDEL, GM PENA, EZ MALILAY, J MILLER, DT SOWELL, AL MILLER, MA FLANDERS, WD FALTER, KH OLSON, DR KILBOURNE, EM SINKS, T ING, R STAEHLING, N BOYD, M GUNTER, EW PASCHAL, DC MUELLER, PW SPIERTO, FW NEEDHAM, LL HILL, RH ASHLEY, DL HANNON, WH MARQUEZ, AR FERNANDEZ, JRD HADAD, JH MILORD, DR CRISTIA, RP PEREZ, MAH VERDURA, CS ALBA, MAM HODELIN, MT GORBEA, MB DIAZ, ED HIORTLORENZEN, CLC CLUA, AM GUTIERREZ, PM ACOSTA, SJ CABRERA, A FERNANDEZ, MM FREIXAS, RS ESTRADA, R ARIAS, L MESTRE, PF PLA, E ROMERO, MC FERRET, AC LLANOS, G JIMENEZ, JS ROMAN, GC OBERMEYER, W CASTRO, MD RUIZ, CAP RICO, NS BETANCOURT, IP FUENTES, BEE CABRERA, AP CALDELLICEHIO, LET MEDINA, AG GOMEZ, N MOJARRIETA, MS VARA, JAC PORTALES, JMR HERNANDEZ, GR GINALY, SM GARCIA, PP GARCIA, M HERNANDEZ, CS DIAZ, EI RECIO, EM GARCIA, SH SANCHEZ, AL VALDES, P RODRIGUEZ, OM OLIVA, NB DIAZ, D PEREZ, MC HERNANDEZ, MCR GONEZ, JMR AMADO, SN DELLLANO, AC BREIJO, DH ACOSTA, AC GONZALEZ, MM ROMERO, RM CHAVEZ, OC VALDES, MH OTERO, GR CABALLERO, MM VALDES, AG OLIVERA, BR BENITEZ, EE BEADE, C LEON, LS MARIMON, FD ROMAN, AS RODRIGUEZ, R RODRIGUEZ, FD ALVAREZ, MR COLUMBE, MS MARRERO, A ZULUETA, D GARCIA, CR SANTOS, JPA PEDROSO, F RODRIGUEZ, HM VALDES, NM ACOSTA, MS CHOBEL, ER GODOY, MM LUGO, MM LOPEZ, LL DIAZ, EM MARTINEZ, JCB DELGADO, NA VALDES, MT MORENO, ARD SANCHEZ, SH HERNANDEZ, LEP VALDES, OM MARTINEZ, AO DOMINGUEZ, I DEARMAS, MR IGLESIAS, OR CASTELL, OR TRUJILLO, OG BEUNE, MDM RODRIGUEZ, FM MEDINA, RM RUIZCALDERON, JC FERNANDEZ, B BARROSO, EV MACHIN, JL ARMENTEROS, LR MENDEZ, CV PEREZ, JH CAMPOS, AC DIAZ, NA PEREZ, AO MILIAN, J LEON, OH CAPOTE, BR LEZCANOS, MR EZMORIZ, LP MOYA, O VITRIAGO, A MURGUIA, AU TI EPIDEMIC OPTIC NEUROPATHY IN CUBA - CLINICAL CHARACTERIZATION AND RISK-FACTORS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID AMBLYOPIA AB Background. From 1991 to 1993, epidemic optic and peripheral neuropathy affected more than 50,000 people in Cuba. The number of new cases decreased after the initiation of vitamin supplementation in the population. In September 1993, Cuban and U.S. investigators conducted a study to characterize and identify risk factors for the optic form of the syndrome. Methods. We conducted ophthalmologic and neurologic examinations, assessed exposure to potential toxins, administered a semiquantitative food-frequency questionnaire, and assessed serum measures of nutritional status in 123 patients with severe optic neuropathy, matched for sex and age to randomly chosen normal subjects. Results. In the case patients, prominent clinical features were subacute loss of visual acuity with field defects, diminished color vision, optic-nerve pallor, and decreased sensitivity to vibration and temperature in the legs. Tobacco use, particularly cigar smoking, was associated with an increased risk of optic neuropathy. The risk was reduced among subjects with higher dietary intakes of methionine, vitamin B-12, riboflavin, and niacin and higher serum concentrations of antioxidant carotenoids, The risk was also reduced among subjects who raised chickens at home or had relatives living overseas - factors that may be indirect measures of increased food availability. Conclusions. The epidemic of optic and peripheral neuropathy in Cuba between 1991 and 1993 appears to be linked to reduced nutrient intake caused by the country's deteriorating economic situation and the high prevalence of tobacco use. C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. EMORY UNIV,ATLANTA,GA 30322. MINIST PUBL HLTH CUBA,HAVANA,CUBA. PAN AMER HLTH ORG,WASHINGTON,DC. NIH,BETHESDA,MD 20892. US FDA,ROCKVILLE,MD 20857. RI Needham, Larry/E-4930-2011; Hernandez Triana, Manuel/B-4513-2015 OI Hernandez Triana, Manuel/0000-0002-2752-2592 NR 38 TC 85 Z9 87 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 NOV 2 PY 1995 VL 333 IS 18 BP 1176 EP 1182 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA TB560 UT WOS:A1995TB56000003 ER PT J AU HENNINGFIELD, JE AF HENNINGFIELD, JE TI DRUG-THERAPY - NICOTINE MEDICATIONS FOR SMOKING CESSATION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED TRIAL; DOUBLE-BLIND TRIAL; TOBACCO WITHDRAWAL SYMPTOMS; TRANSDERMAL NICOTINE; CIGARETTE-SMOKING; CHEWING-GUM; REPLACEMENT THERAPY; PLACEBO GUM; SMOKERS; PATCH C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. RP HENNINGFIELD, JE (reprint author), NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,INTRAMURAL RES PROGRAM,POB 5180,BALTIMORE,MD 21224, USA. NR 102 TC 223 Z9 233 U1 1 U2 6 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 NOV 2 PY 1995 VL 333 IS 18 BP 1196 EP 1203 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA TB560 UT WOS:A1995TB56000007 PM 7565976 ER PT J AU SCALES, JB WINNING, RS RENAUD, CS SHEA, LJ SARGENT, TD AF SCALES, JB WINNING, RS RENAUD, CS SHEA, LJ SARGENT, TD TI NOVEL MEMBERS OF THE EPH RECEPTOR TYROSINE KINASE SUBFAMILY EXPRESSED DURING XENOPUS DEVELOPMENT SO ONCOGENE LA English DT Article DE EPH; RECEPTOR TYROSINE KINASE; XENOPUS; CEMENT GLAND ID DIFFERENTIAL EXPRESSION; GENE-EXPRESSION; PROTEIN; FAMILY; CLONING; LAEVIS; ELK; IDENTIFICATION; DROSOPHILA; HINDBRAIN AB Three cDNAs encoding receptor tyrosine kinases (RTKs) of the eph-subfamily have been identified based on their homology to Pagliaccio (Winning and Sargent, 1994, Mech. Dev. 46:219-229). These have been named TCK, Xelk (Xenopus homologue of elk), and PL7a (pag-like clone 7a). Each of these genes is expressed in a distinctive, tissue specific manner during early development. TCR is expressed in pre-semitic mesoderm, caudal somites, midbrain and cement gland, Xelk is expressed in the brain and spinal cord and in the first and fourth visceral arches. PL7a cDNA is expressed throughout the head and in the tip of the tab. All of the genes are represented in maternal mRNA, and are expressed in adult tissues. The Xelk cDNA encodes a protein which is 94% identical to rat elk and therefore is likely to represent the Xenopus homologue of this gene. TCK and PL7a are less related to previously identified eph-subfamily RTKs. The inability to unambiguously assign TCK and PL7a as Xenopus homologues of any previously identified eph RTK leads us to conclude that these cDNAs represent novel members of this family. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 41 TC 35 Z9 39 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 2 PY 1995 VL 11 IS 9 BP 1745 EP 1752 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TD094 UT WOS:A1995TD09400009 PM 7478602 ER PT J AU NAKAGAWA, K CONRAD, NK WILLIAMS, JP JOHNSON, BE KELLEY, MJ AF NAKAGAWA, K CONRAD, NK WILLIAMS, JP JOHNSON, BE KELLEY, MJ TI MECHANISM OF INACTIVATION OF CDKN2 AND MTS2 IN NON-SMALL-CELL LUNG-CANCER AND ASSOCIATION WITH ADVANCED-STAGE SO ONCOGENE LA English DT Article DE P16(INK4); CDKN2; P15(IMK4B); POINT MUTATION; LUNG NEOPLASM ID P53 GENE-MUTATIONS; LINES; IDENTIFICATION; FEATURES AB The CDKN2 tumor suppressor gene encodes an inhibitor of type D cyclin dependent kinases. CDKN2 is homozygously deleted in approximately 25% of nonsmall cell lung cancer (NSCLC) cell lines and these deletions are associated with advanced stage cancer. Conflicting reports of the frequency of CDKN2 alterations in NSCLC tumors prompted us to examine the relationship of these alterations and those of the related gene, MTS2, with patient stage and site of cancer. One hundred twenty-five NSCLC samples (71 cell lines and 54 tumors) were examined by PCR-SSCP. Twenty of 71 (28%) tumor cell lines had homozygous deletions, and six (8%) had point mutations compared to 4 (7%) with point mutations among 54 tumor samples. All mutations mere observed in tumors or cell lines from patients with stage III or IV disease. Two patients with no mutations in their primary tumor had a CDKN2 point mutation detected in a metastatic tumor. Point mutations were G:C to T:A transversion on the coding strand in five of 10 and resulted in nonsense mutations in seven of 10. Undetectable CDKN2 mRNA, in the absence of detectable genetic alteration, was noted in a similar fraction of cell lines derived from patients with stage I or IZ disease [two of seven (29%)] and stage Hi or TV disease [15 of 49 (31%)]. Homozygous deletion of MTS2 was found in 17 of 20 cell lines with CDKN2 deletions; no point mutations of MTS2 were identified by SSCP in the 125 samples. Thus, CDKN2 is a frequent target of genetic alterations at 9p21 in NSCLC. Both deletions and point mutations of CDKN2 are closely associated with tumor dissemination. C1 NATL CANC INST, NAVAL MED ONCOL BRANCH, BETHESDA, MD 20889 USA. NATL NAVAL MED CTR, DEPT LAB, BETHESDA, MD 20889 USA. NR 43 TC 69 Z9 70 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 2 PY 1995 VL 11 IS 9 BP 1843 EP 1851 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TD094 UT WOS:A1995TD09400020 PM 7478613 ER PT J AU CHOYKE, PL AF CHOYKE, PL TI IMAGING OF PROSTATE-CANCER SO ABDOMINAL IMAGING LA English DT Article DE PROSTATE NEOPLASMS; ULTRASOUND; DOPPLER ULTRASONOGRAPHY; RADIONUCLIDE STUDIES; COMPUTERIZED TOMOGRAPHY; MAGNETIC RESONANCE IMAGING; MONOCLONAL ANTIBODIES ID TRANSRECTAL ULTRASONOGRAPHY; ULTRASOUND; CARCINOMA; ANTIGEN; SR-89; COIL; IMPLANTATION; DIAGNOSIS; THERAPY; OVARIAN AB Prostate cancer diagnosis and treatment is fast emerging as a major health care issue in the United States. However, there are great uncertainties about the value of specific tests and therapies. Imaging modalities play a major role in the current management of patients with prostate cancer and this role is likely to expand in the future. Transrectal ultrasound is used to identify nonpalpable lesions, direct systematic biopsies, determine gland volume and stage prostate cancers. For staging skeletal metastases, the bone scan is acknowledged as the best method, however controversy surrounds its routine use in patients with low prostate specific antigen (PSA) values. Computed tomography (CT) and transrectal ultrasound have limited value in detecting extracapsular disease but CT can be used in conjunction with percutaneous biopsy to identify nodal metastases. The role of Endorectal coil MRT is currently evolving in the wake of a disappointing multiinstitutional trial but MRI still holds the most promise for accurately detecting local extent of prostate cancer. New radiolabeled techniques with monoclonal antibodies and peptide imaging are also having early but promising results. The role of imaging in prostate cancer is continuing to evolve as technology and knowledge about prostate cancer biology improves and health care economics force a more judicious use of imaging resources. RP CHOYKE, PL (reprint author), NIH,CTR CLIN,DEPT RADIOL,BLDG 10,ROOM 1C 660,BETHESDA,MD 20892, USA. NR 40 TC 14 Z9 14 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD NOV-DEC PY 1995 VL 20 IS 6 BP 505 EP 515 DI 10.1007/BF01256700 PG 11 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA TE944 UT WOS:A1995TE94400001 PM 8580742 ER PT J AU CLARK, NM NOTHWEHR, F GONG, M EVANS, D MAIMAN, LA HURWITZ, ME ROLOFF, D MELLINS, RB AF CLARK, NM NOTHWEHR, F GONG, M EVANS, D MAIMAN, LA HURWITZ, ME ROLOFF, D MELLINS, RB TI PHYSICIAN-PATIENT PARTNERSHIP IN MANAGING CHRONIC ILLNESS SO ACADEMIC MEDICINE LA English DT Editorial Material ID CONTINUING-EDUCATION PROGRAM; MEDICAL-EDUCATION; CONTROLLED TRIAL; CHRONIC DISEASE; MANAGEMENT; HYPERTENSION; ARTHRITIS; CARE C1 COLUMBIA UNIV,COLL PHYS & SURG,NEW YORK,NY. NICHHD,BETHESDA,MD. UNIV MICHIGAN,SCH PUBL HLTH,ANN ARBOR,MI. RP CLARK, NM (reprint author), UNIV MICHIGAN,SCH PUBL HLTH,ANN ARBOR,MI 48109, USA. FU NHLBI NIH HHS [R01 HL49976-02] NR 16 TC 59 Z9 62 U1 1 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD NOV PY 1995 VL 70 IS 11 BP 957 EP 959 DI 10.1097/00001888-199511000-00008 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA TF412 UT WOS:A1995TF41200012 PM 7575946 ER PT J AU TOCKMAN, MS QIAO, YL ZHAO, GZ SHARMA, R CAVENAUGH, LL EROZAN, YS AF TOCKMAN, MS QIAO, YL ZHAO, GZ SHARMA, R CAVENAUGH, LL EROZAN, YS TI SAFE SEPARATION OF SPUTUM CELLS FROM MUCOID GLYCOPROTEIN SO ACTA CYTOLOGICA LA English DT Article DE SPUTUM; FLOW CYTOMETRY; IMMUNOCYTOCHEMISTRY; DITHIOTHREITOL ID LUNG-CANCER DETECTION; PREVALENCE; DIAGNOSIS AB OBJECTIVE: To compare the safety and efficacy of homogenizing sputum with deoxyribonuclease I (DNAse I), dithiothreitol (DTT), N-acetyl-L-cysteine, sodium EDTA and trypsin against standard mechanical blending to provide mucus-free, single-cell suspensions for quantitative analysis. STUDY DESIGN: Clinical sputum specimens or cultured human bronchogenic carcinoma cells were preserved in 2% polyethylene glycol/50% ethanol, divided into aliquots, counted and stained (Papanicolaou and avidin-biotin complex immunostained) at baseline. Cells of each aliquot were separated from mucus by the standard physical blending method or by chemical or enzymatic mucus liquefaction. After staining, washing and resuspending in the original volume of polyethylene glycol/ethanol mixture, aliquots were again counted and stained. RESULTS: Cell counts, Papanicolaou staining and immunostaining showed that homogenization of induced, preserved sputum with 0.5 mM DTT is safe and provides mucus-free monolayers for immunocytochemistry and single-cell suspensions for flow cytometry. Mucolysis with 0.5 mM DTT resulted in a significant (16%) increase in cells available. In contrast, mechanical blending resulted in up to a 24% reduction in specimen cellularity. CONCLUSION: Homogenization with low-concentration DTT will probably facilitate the exploration of sputum for protein and gene markers of carcinogenesis. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,JOHN K FROST CTR,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,CYTOPATHOL LAB,BALTIMORE,MD 21205. NCI,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. CHINESE ACAD MED SCI,MED BIOL INST,DEPT IMMUNOL,KUNMING,PEOPLES R CHINA. CHINA MED UNIV,AFFILIATED HOSP 2,DEPT IMMUNOL,SHENYANG,PEOPLES R CHINA. RP TOCKMAN, MS (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH,615 N WOLF ST,BALTIMORE,MD 21205, USA. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 FU NCI NIH HHS [1P50 CA58184] NR 25 TC 19 Z9 19 U1 0 U2 3 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD NOV-DEC PY 1995 VL 39 IS 6 BP 1128 EP 1136 PG 9 WC Pathology SC Pathology GA TG082 UT WOS:A1995TG08200009 PM 7483987 ER PT J AU Yanovski, SZ AF Yanovski, SZ TI Biological correlates of binge eating SO ADDICTIVE BEHAVIORS LA English DT Article ID DEXAMETHASONE SUPPRESSION TEST; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; HORMONAL SECRETION; AFFECTIVE-DISORDER; CALORIC-INTAKE; WEIGHT; CORTISOL; ABNORMALITIES; WOMEN AB Eating disorders are associated with numerous biological perturbations; however, sorting out cause from effect is difficult. Neuroendocrine and metabolic abnormalities are seen in both anorexia nervosa and bulimia nervosa, but they have not been described in binge eating disorder, in which neither starvation nor compensatory behaviors are present. Although these findings may reflect biologic differences among subgroups of binge eaters, an alternative explanation is that many of the biological correlates of binge eating are the result of metabolic derangement secondary to starvation and/or purging. The identification of binge eating disorder provides an opportunity to study the causes and concomitants of binge eating in the absence of compensatory behaviors. RP Yanovski, SZ (reprint author), NIDDK,BETHESDA,MD 20892, USA. NR 46 TC 15 Z9 15 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD NOV-DEC PY 1995 VL 20 IS 6 BP 705 EP 712 DI 10.1016/0306-4603(96)00092-5 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA TW729 UT WOS:A1995TW72900003 PM 8820523 ER PT J AU WINDLE, C AF WINDLE, C TI FLUCTUATING SUPPORT SO ADMINISTRATION AND POLICY IN MENTAL HEALTH LA English DT Editorial Material C1 NIMH,BETHESDA,MD 20892. NR 12 TC 0 Z9 0 U1 0 U2 0 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD NOV PY 1995 VL 23 IS 2 BP 169 EP 174 DI 10.1007/BF02106728 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA TJ052 UT WOS:A1995TJ05200008 ER PT J AU RAGHEB, JA BRESSLER, P DAUCHER, M CHIANG, L CHUAH, MKL VANDENDRIESSCHE, T MORGAN, RA AF RAGHEB, JA BRESSLER, P DAUCHER, M CHIANG, L CHUAH, MKL VANDENDRIESSCHE, T MORGAN, RA TI ANALYSIS OF TRANSDOMINANT MUTANTS OF THE HIV TYPE-1 REV PROTEIN FOR THEIR ABILITY TO INHIBIT REV FUNCTION, HIV TYPE-1 REPLICATION, AND THEIR USE AS ANTI-HIV GENE THERAPEUTICS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID VIRAL MESSENGER-RNA; HUMAN T-CELLS; RETROVIRAL VECTORS; ENVELOPE PROTEIN; EXPRESSION; LYMPHOCYTES; ACTIVATOR; THERAPY; CD4; SEQUENCE AB The HIV-1 rev gene product facilitates the transport of singly spliced and unspliced HIV-1 transcripts and is necessary for productive HIV-1 infection. On the basis of the previously described trans-dominant Rev mutant M10, four point mutants and one frameshift mutant of the Rev protein were constructed. The mutants were inserted into retroviral expression vectors and analyzed for their ability to inhibit Rev-mediated gene expression. Transient transfection systems were used to screen these new mutants, and each was shown to inhibit expression of a Rev-dependent CAT reporter plasmid. Inhibition of HIV-1 envelope gene expression was tested in the HeLa-T4 cell line and was also shown to be inhibited by the trans-dominant Rev mutants. Retroviral vector producer cell lines were constructed and used to transduce Rev trans-dominant genes into the human T-cell line SupT1. The engineered SupT1 cell lines were then challenged with HIV-1 IIIB and HIV-1 expression was monitored by Northern blot analysis and in situ hybridization. SupT1 cells expressing either a Rev point mutant or the frameshift mutant showed greatly reduced HIV-1 mRNA accumulation and the Rev-dependent singly spliced and unspliced HIV-1 mRNAs were reduced. The kinetics of viral replication following challenge of Rev trans-dominant-engineered SupT1 cells with both HIV-1 IIIB and MN strains was significantly reduced and cells were protected from viral lysis. Viruses that emerge late in infection from Rev trans-dominant-engineered cultures are not resistant to Rev-mediated inhibition. Last, trans-dominant Rev-mediated protection of human CD4(+) lymphocytes from challenge with primary HIV-1 patient isolates confirms the potential utility of this system as an anti-HIV-1 gene therapy approach. C1 NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. NHLBI,BETHESDA,MD. NIAID,BETHESDA,MD. GENE THERAPY INC,GAITHERSBURG,MD. NR 53 TC 22 Z9 22 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 1995 VL 11 IS 11 BP 1343 EP 1353 DI 10.1089/aid.1995.11.1343 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA TG264 UT WOS:A1995TG26400004 PM 8573391 ER PT J AU VANCOTT, TC POLONIS, VR LOOMIS, LD MICHAEL, NL NARA, PL BIRX, DL AF VANCOTT, TC POLONIS, VR LOOMIS, LD MICHAEL, NL NARA, PL BIRX, DL TI DIFFERENTIAL ROLE OF V3-SPECIFIC ANTIBODIES IN NEUTRALIZATION ASSAYS INVOLVING PRIMARY AND LABORATORY-ADAPTED ISOLATES OF HIV TYPE-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; BIOSPECIFIC INTERACTION ANALYSIS; ENVELOPE GLYCOPROTEIN; ACID SEQUENCE; AIDS VIRUS; GP120; INFECTION; EPITOPE; PEPTIDE AB To identify epitopes important in neutralizing primary HIV-1 isolates, we have selectively depleted HIV-1 sera of antibodies specific for the third hypervariable region (V3) of the HIV-1 envelope glycoprotein gp120, and then assessed the functional consequences of such depletion in neutralization assays. The nucleotide sequence of the V3 loop region from HIV-1 PBMC DNA was determined for three HIV-1-infected patients, corresponding peptides were synthesized, and then subsequently used for V3 depletion of the patient sera. Depletion using a single clade B V3 peptide was capable of depleting > 98% of binding antibodies to multiple clade B V3 peptides, including those with changes within the GPG (X) under bar tip of the loop. Depleted and undepleted sera were studied for their ability to neutralize both laboratory-adapted HIV-1(MN) and two primary HIV-1 isolates with known V3 sequences, using a viral infectivity reduction assay. While the majority of HIV-1(MN) neutralization was lost on V3 depletion, the loss in neutralization capacity against primary isolates by these same V3-depleted sera was substantially less pronounced. This suggests that V3 peptide-specific antibodies within HIV-1 serum play a fundamentally different role in mediating neutralization in assays involving laboratory-adapted and primary isolates and implicates antibodies with epitope specificities outside of V3 as major determinants in neutralization assays involving primary isolates. C1 SRA TECHNOL,SHADY GROVE,MD 20850. HENRY M JACKSON FDN,ROCKVILLE,MD 20850. NCI,FREDERICK CANC RES & DEV CTR,TUMOR CELL BIOL LAB,FREDERICK,MD 21702. RP VANCOTT, TC (reprint author), WALTER REED ARMY INST RES,DIV RETROVIROL,13 TAFT CT,SUITE 200,ROCKVILLE,MD 20850, USA. NR 62 TC 95 Z9 95 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 1995 VL 11 IS 11 BP 1379 EP 1391 DI 10.1089/aid.1995.11.1379 PG 13 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA TG264 UT WOS:A1995TG26400009 PM 8573396 ER PT J AU WEXLER, P AF WEXLER, P TI TOXNET - THE NATIONAL-LIBRARY-OF-MEDICINE TOXICOLOGY DATABASE SO AMERICAN FAMILY PHYSICIAN LA English DT Letter RP WEXLER, P (reprint author), NATL LIB MED,TOXICOL & ENVIRONM HLTH INFORMAT PROGRAM,BETHESDA,MD 20209, USA. NR 0 TC 4 Z9 4 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 NOV 1 PY 1995 VL 52 IS 6 BP 1677 EP 1678 PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA TC869 UT WOS:A1995TC86900004 PM 7484674 ER PT J AU LIAO, DP BARNES, RW CHAMBLESS, LE SIMPSON, RJ SORLIE, P HEISS, G AF LIAO, DP BARNES, RW CHAMBLESS, LE SIMPSON, RJ SORLIE, P HEISS, G TI AGE, RACE, AND SEX-DIFFERENCES IN AUTONOMIC CARDIAC-FUNCTION MEASURED BY SPECTRAL-ANALYSIS OF HEART-RATE-VARIABILITY - THE ARIC STUDY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY DISEASE; NORMAL RANGES; MORTALITY; SEVERITY; TESTS; DEATH AB To investigate the distribution of heart rate variability (HRV) spectral power in an unselected sample of the population, and to ascertain the population correlates of HRV, we examined 1,984 healthy persons, aged 45 to 64 years, randomly selected from the Atherosclerosis Risk in Communities (ARIC) study cohort. Resting, supine, 2-minute, beat-to-beat heart rate data were collected between 7 A.M. and 12 noon. The race- and sex-adjusted geometric means of low-frequency component (LF, 0.025 to 0.15 Hz) were 4.00 and 3.13 (beats/min)(2); of high-frequency component (HF, 0.16 to 0.35 Hz), 1.65 and 1.21 (beats/min)(2); and of the HF/LF ratio, 0.41 and 0.39, for 45-to-54 and 55-to-64 years age groups, respectively (test of mean difference by age, p < 0.01, p < 0.01, and p = 0.11 for LF, HF, and HF/LF ratio, respectively). Comparing black with white examinees, the age- and sex-adjusted geometric means of LF were 3.06 and 3.70 (beats/ min)(2); of HF, 1.66 and 1.36 (beats/min)(2); of HF/LF, 0.54 and 0.37, respectively (test of mean difference by race, p < 0.01, p < 0.01, and p < 0.01). The age- and race-adjusted geometric means of LF for women and men were 3.12 and 4.10 (beats/min)(2); of HF, 1.46 and 1.38 (beats/min)(2); and of HF/LF, 0.47 and 0.34, respectively (test of mean difference, p < 0.01, p = 0.34, and p < 0.01). We conclude that HRV spectral indexes are associated with age, race, and sex. With increasing age, the parasympathetic and sympathetic spectral power components decrease. Black examinees have a lower LF, higher HF and higher HF/LF ratio than whites. Women have a lower LF, and a higher HF/LF ratio than men. C1 UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,SCH PUBL HLTH,DEPT BIOSTAT,CHAPEL HILL,NC 27599. ULTRASOUND READING CTR,ARIC,WINSTON SALEM,NC. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 28 TC 177 Z9 182 U1 2 U2 11 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 1995 VL 76 IS 12 BP 906 EP 912 DI 10.1016/S0002-9149(99)80260-4 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TC117 UT WOS:A1995TC11700012 PM 7484830 ER PT J AU LARSON, DE TATARANNI, PA FERRARO, RT RAVUSSIN, E AF LARSON, DE TATARANNI, PA FERRARO, RT RAVUSSIN, E TI LIBITUM FOOD-INTAKE ON A CAFETERIA DIET IN NATIVE-AMERICAN WOMEN - RELATIONS WITH BODY-COMPOSITION AND 24-H ENERGY-EXPENDITURE SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE OBESITY; MACRONUTRIENT INTAKE AND OXIDATION; RESPIRATORY CHAMBER; FOOD-SELECTION SYSTEM ID MIDDLE-AGED MEN; CALORIC-INTAKE; OBESE SUBJECTS; FAT OXIDATION; PIMA-INDIANS; WEIGHT-GAIN; CARBOHYDRATE; DETERMINANTS; BALANCE; IMPACT AB Epidemiologic studies consistently report associations between obesity and dietary fat but not total energy intake. We measured ad libitum food intake in a laboratory setting and evaluated its relation to body weight and composition, energy expenditure, and macronutrient utilization in 28 women of Pima-Papago heritage (aged 27 +/- 7 y, 85.3 +/- 19.0 kg, 44 +/- 6% body fat; ($) over bar x +/- SD). All women were studied during the follicular phase of the menstrual cycle. After a 4-d weight-maintenance period, the volunteers selected their food for 5 d from computerized vending machines offering a variety of familiar and preferred foods, ie, a ''cafeteria diet''. Twenty-four-hour energy expenditure and substrate oxidation were measured in a respiratory chamber on the 4th d of weight maintenance and the 5th d of ad libitum intake. Average ad libitum intake was 13 732 +/- 4238 kJ/d (11 +/- 1% protein, 40 +/- 1% fat, 49 +/- 4% carbohydrate), ie, moderate overeating by 27 +/- 37% above weight maintenance requirements (range: -27% to 124%). Percent body fat correlated with daily energy intake (r = 0.53, P < 0.01), the degree of overeating (r = 0.41, P < 0.05), and the selection of a diet higher in fat and lower in carbohydrate (r = 0.70 and r = -0.63, respectively, P < 0.001). Excess carbohydrate intake caused an increase in carbohydrate oxidation (r = 0.51, P < 0.01), whereas excess fat intake resulted in a decrease in fat oxidation (r = -0.53, P < 0.01) and thus a positive fat balance of 85 +/- 65 g/d. The positive relations among degrees of obesity, dietary fat intake and overeating, and the fact that dietary fat does not induce fat oxidation, support the hypothesis that dietary fat promotes obesity in women. C1 NIH,NIDDK,CLIN DIABET & NUTR SECT,PHOENIX,AZ. NR 36 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 1995 VL 62 IS 5 BP 911 EP 917 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TC135 UT WOS:A1995TC13500004 PM 7572735 ER PT J AU LANDS, WEM AF LANDS, WEM TI ALCOHOL AND ENERGY-INTAKE SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE ALCOHOL; BODY MASS INDEX; CYTOCHROME P-4502E1; CYP2E1; ETHANOL; FOOD ENERGY; GLUCONEOGENESIS; MICROSOMAL ETHANOL OXIDIZING SYSTEM; MEOS; MITOCHONDRIA; MITOCHONDRIAL DNA; UBIQUINONE ID RESEARCH CLINICS PREVALENCE; ETHANOL-OXIDIZING SYSTEM; FATTY LIVER; CARBOHYDRATE INTAKE; LIPID-PEROXIDATION; NUTRIENT INTAKE; BODY-WEIGHT; DIETARY-FAT; RAT-LIVER; METABOLISM AB One hundred years of research about the metabolism of alcohol have provided many details, but some general aspects of the physiologic value of alcohol remain uncertain or inadequately proven. Results from epidemiologic studies appear to be in conflict with interpretations based on results from indirect calorimetric studies. The apparent inability of body mass index to be maintained in women when alcohol is consumed with food may indicate impaired metabolic processes that need to be better understood. Current evidence on the effects of alcohol are summarized to identify experimental approaches that may provide information needed to resolve the current contradictions. C1 NIAAA, DIV BASIC RES, BETHESDA, MD USA. NR 55 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 1995 VL 62 IS 5 SU S BP 1101 EP 1106 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TD184 UT WOS:A1995TD18400012 ER PT J AU MASON, A SALLIE, R AF MASON, A SALLIE, R TI WHAT CAUSES FULMINANT HEPATIC-FAILURE OF UNKNOWN ETIOLOGY SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Editorial Material ID ACUTE LIVER-FAILURE; NON-B-HEPATITIS; NON-A; VIRUS-DNA; SERUM C1 NIH,LIVER UNIT,BETHESDA,MD. RP MASON, A (reprint author), ALTON OCHSNER MED INST,GASTROENTEROL & HEPATOL SECT,NEW ORLEANS,LA 70121, USA. RI Mason, Andrew/D-2938-2013 OI Mason, Andrew/0000-0002-0470-9522 NR 23 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD NOV PY 1995 VL 104 IS 5 BP 491 EP 494 PG 4 WC Pathology SC Pathology GA TB961 UT WOS:A1995TB96100002 PM 7572807 ER PT J AU CAPPUCCIO, FP ELLIOTT, P ALLENDER, PS PRYER, J FOLLMAN, DA CUTLER, JA AF CAPPUCCIO, FP ELLIOTT, P ALLENDER, PS PRYER, J FOLLMAN, DA CUTLER, JA TI EPIDEMIOLOGIC ASSOCIATION BETWEEN DIETARY CALCIUM INTAKE AND BLOOD-PRESSURE - A METAANALYSIS OF PUBLISHED DATA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BLOOD PRESSURE; CALCIUM; METAANALYSIS; NUTRITION; PUBLIC HEALTH ID CORONARY HEART-DISEASE; ALCOHOL INTAKE; HYPERTENSION; SODIUM; MEN; POPULATION; POTASSIUM; WOMEN; SUPPLEMENTATION; INDIVIDUALS AB The objectives of the study were to assess whether the epidemiologic data support a relation between dietary calcium intake and blood pressure, to obtain a quantitative estimate of the difference in blood pressure for a given difference in dietary calcium intake, and to assess the public health implications. A meta-analysis of published data (January 1983 to November 1993) that investigated the association between dietary calcium intake and blood pressure in different populations around the world was performed. Of 63 population studies identified, 23 were suitable for a quantitative overview (total n = 38,950). Unadjusted regression coefficients (95% confidence intervals) were obtained. Pooled unadjusted regression coefficients (95% confidence intervals) were then computed weighting each individual study by the inverse of its variance. Tests of heterogeneity and sensitivity analysis were carried out, and the possibility of publication bias was assessed. The regression coefficients ranged between -9.40 and 1.63 mmHg/100 mg calcium for systolic blood pressure and between -4.90 and 0.47 for diastolic blood pressure. in men (II studies, n = 7,271), the pooled regression coefficients were -0.010 and -0.009 mmHg/100 mg calcium for systolic and diastolic pressures, respectively (p < 0.001 and p < 0.05). In women (six studies, n = 8,507), they were -0.15 and -0.057 mmHg/100 mg calcium (p < 0.001 and p < 0.02), and in men and women combined (six studies, n = 23,172 for systolic pressure and four studies, n =3,215 for diastolic pressure) they were -0.061 and -0.061 mmHg/100 mg calcium (p < 0.001 and p < 0.05). In those studies that used the 24-hour recall method, the pooled regression coefficients were -0.06 and -0.09 mmHg/100 mg calcium (p < 0.005 and p = 0.07), whereas in those that used the food frequency questionnaire, they were -0.15 and -0.05 mmHg/100 mg calcium (p < 0.001 and p < 0.03). These data are consistent with an inverse association between dietary calcium intake and blood pressure. However, the size of the estimate, the observed heterogeneity among studies, and the possibility of confounding and publication bias indicate that an increase in calcium intake above the Recommended Dietary Allowance is not recommended at population level for the prevention and treatment of high blood pressure, C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP CAPPUCCIO, FP (reprint author), UNIV LONDON LONDON SCH HYG & TROP MED,DEPT PUBL HLTH & POLICY,ENVIRONM EPIDEMIOL UNIT,KEPPEL ST,LONDON WC1E 7HT,ENGLAND. RI Cappuccio, Francesco/D-3028-2009; OI Cappuccio, Francesco Paolo/0000-0002-7842-5493 NR 60 TC 110 Z9 117 U1 1 U2 2 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 1995 VL 142 IS 9 BP 935 EP 945 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TC545 UT WOS:A1995TC54500007 PM 7572974 ER PT J AU DAUSCH, JG STORY, M DRESSER, C GILBERT, GG PORTNOY, B KAHLE, LL AF DAUSCH, JG STORY, M DRESSER, C GILBERT, GG PORTNOY, B KAHLE, LL TI CORRELATES OF HIGH-FAT LOW-NUTRIENT-DENSE SNACK CONSUMPTION AMONG ADOLESCENTS - RESULTS FROM 2 NATIONAL-HEALTH SURVEYS SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Note ID PATTERNS C1 UNIV MINNESOTA,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. NCI,CANC CONTROL SCI PROGRAM,BETHESDA,MD 20892. UNIV MARYLAND,DEPT HLTH EDUC,COLLEGE PK,MD 20742. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RP DAUSCH, JG (reprint author), DAIRY COUNCIL GREATER METROPOLITAN WASHINGTON INC,1985 ISAAC NEWTON SQ S,SUITE 100,RESTON,VA 22090, USA. NR 12 TC 14 Z9 14 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD NOV-DEC PY 1995 VL 10 IS 2 BP 85 EP 88 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TE650 UT WOS:A1995TE65000002 PM 10160050 ER PT J AU KREBSSMITH, SM HEIMENDINGER, J PATTERSON, BH SUBAR, AF KESSLER, R PIVONKA, E AF KREBSSMITH, SM HEIMENDINGER, J PATTERSON, BH SUBAR, AF KESSLER, R PIVONKA, E TI PSYCHOSOCIAL FACTORS ASSOCIATED WITH FRUIT AND VEGETABLE CONSUMPTION SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE FRUIT; VEGETABLES; FOOD HABITS; DIET SURVEYS ID CANCER; MODEL AB Purpose. This study examined the relationship between various psychosocial factors and fruit and vegetable consumption. Design. The 5 A Day Baseline Survey, conducted in August 1991, just before the initiation of the 5 A Day for Better Health Program, obtained data on adults' intakes of, and their knowledge, perceptions, and attitudes regarding, fruits and vegetables. Setting. The survey was conducted by telephone. Subjects. Subjects were 2811 adults (response rate, 43%) aged 18 years and older in the 48 coterminous United States. Measures. Fruit and vegetable intake was measured as self-reported frequency of use; most of the psychosocial variables were measured using Likert scales. Results. This study estimates that only 8% of American adults thought that five or more servings of fruits and vegetables were needed for good health. Of the factors studied, the most important in determining someone's fruit and vegetable intake were the number of servings they thought they should have in a day, whether they liked the taste, and whether they had been in the habit of eating many fruits and vegetables since childhood. These few factors accounted for 15% more of the variation in fruit and vegetable consumption than did demographic variables alone (8%). Conclusions. Nutrition education should stress the need to eat five or more servings of fruits and vegetables per day because few adults are aware of this recommendation and such knowledge is strongly associated with increased intake. Furthermore, efforts to increase the palatability of fruits and vegetables, especially among children, should be promoted. C1 UNIV MICHIGAN,ANN ARBOR,MI 48109. PRODUCE BETTER HLTH FDN,NEWARK,DE. RP KREBSSMITH, SM (reprint author), NCI,DIV CANC PREVENT & CONTROL,9000 ROCKVILLE PIKE,EPN 313,BETHESDA,MD 20892, USA. NR 24 TC 127 Z9 130 U1 1 U2 12 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD NOV-DEC PY 1995 VL 10 IS 2 BP 98 EP 104 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TE650 UT WOS:A1995TE65000007 PM 10160052 ER PT J AU ALEX, S GUPTA, SL MINOR, JR TURCOVSKICORRALES, S GALLELLI, JF TAUB, D PISCITELLI, SC AF ALEX, S GUPTA, SL MINOR, JR TURCOVSKICORRALES, S GALLELLI, JF TAUB, D PISCITELLI, SC TI COMPATIBILITY AND ACTIVITY OF ALDESLEUKIN (RECOMBINANT INTERLEUKIN-2) IN PRESENCE OF SELECTED DRUGS DURING SIMULATED Y-SITE ADMINISTRATION - EVALUATION OF 3 METHODS SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE ADDITIVES; ALDESLEUKIN; ANTIINFECTIVE AGENTS; ANTICOAGULANTS; ANTIEMETICS; ANTINEOPLASTIC AGENTS; BIOASSAYS; DEXTROSE; DILUENTS; GANCICLOVIR SODIUM; GASTROINTESTINAL DRUGS; INCOMPATIBILITIES; INJECTIONS; LORAZEPAM; PENTAMIDINE ISETHIONATE; PROCHLORPERAZINE EDISYLATE; PROMETHAZINE HYDROCHLORIDE; SPECTROMETRY; STABILITY; STORAGE; SYMPATHOMIMETIC AGENTS ID NATURAL-KILLER; ADMIXTURES AB The compatibility and biological activity of aldesleukin (a form of recombinant interleukin-2) in the presence of selected i.v. drugs during simulated Y-site administration was studied. Five milliliters of aldesleukin 33,800 IU/mL in 5% dextrose injection was mixed in glass test tubes with 5 mt of each of 19 i.v. drugs prepared at concentrations used in routine clinical practice. The compatibility of the combinations was assessed by visual examination and spectrophotometry at 0, 0.5, 1, and 2 hours after preparation, and bioassays were conducted to determine the activity of aldesleukin in the combinations. Lorazepam was the only drug visually incompatible with aldesleukin. All the secondary drugs were spectrephotometrically compatible with aldesleukin. However, the bioassays showed that the following drugs reduced the activity of aldesleukin: ganciclovir sodium, lorazepam,pentamidine isethionate, prochlorperazine edisylate, and promethazine hydrochloride. Thus, aldesleukin became less biologically active when combined with four drugs for which visual examination suggested compatibility and when combined with five drugs for which spectrophotometry indicated compatibility. Aldesleukin 33,800 IU/mL in 5% dextrose injection lost significant biological activity in the presence of prochlorperazine edisylate, promethazine hydrochloride, lorazepam, ganciclovir sodium, and pentamidine isethionate during simulated Y-site administration. Visual assessment and spectrophotometry may not be valid methods for assessing possible changes in the biological activity of aldesleukin when combined with other agents. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,PHARMACEUT DEV SERV,CLIN PHARMACOKINET RES LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD. NR 11 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD NOV 1 PY 1995 VL 52 IS 21 BP 2423 EP 2426 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TC510 UT WOS:A1995TC51000008 PM 8564607 ER PT J AU AYLESWORTH, CA SMALLRIDGE, RC RICK, ME ALVING, BM AF AYLESWORTH, CA SMALLRIDGE, RC RICK, ME ALVING, BM TI ACQUIRED VON WILLEBRANDS DISEASE - A RARE MANIFESTATION OF POSTPARTUM THYROIDITIS SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Note DE VON WILLEBRANDS DISEASE; HYPOTHYROIDISM; POSTPARTUM THYROIDITIS ID VONWILLEBRANDS DISEASE; HYPOTHYROIDISM AB This report describes the diagnosis of acquired type I von Willebrand disease in a 30-year-old woman (G(5)P(5)) who presented with complaints of excessive bleeding in the postpartum period. The patient's additional complaints of fatigue, depression, and inability to lose weight resulted in laboratory testing that indicated hypothyroidism due to thyroiditis. Clinical symptoms and laboratory tests for von Willebrand disease and hypothyroidism normalized with L-thyroxine replacement, Thyroiditis resulting in symptomatic hypothyroidism occurs in 2-4 per cent of postpartum women. The possibility of underlying hypothyroidism should be considered for those patients, especially if they are parous women, who appear to have an acquired bleeding disorder suggestive of von Willebrand disease. (C) 1995 Wiley-Liss, Inc.* C1 WALTER REED ARMY MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20307. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DIV MED,WASHINGTON,DC 20307. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT HEMATOL & VASC BIOL,WASHINGTON,DC 20307. NIH,CTR CLIN,DEPT HEMATOL,BETHESDA,MD 20892. NR 10 TC 19 Z9 20 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD NOV PY 1995 VL 50 IS 3 BP 217 EP 219 DI 10.1002/ajh.2830500311 PG 3 WC Hematology SC Hematology GA TB942 UT WOS:A1995TB94200010 PM 7485084 ER PT J AU SMITH, TJ CULLEN, JW PECK, SD BROWN, KE YOUNG, NS AF SMITH, TJ CULLEN, JW PECK, SD BROWN, KE YOUNG, NS TI PANCYTOPENIA SECONDARY TO PARVOVIRUS B19 INFECTION IN A CHILD WITH ACUTE LYMPHOBLASTIC-LEUKEMIA, MIMICKING LEUKEMIC RELAPSE SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID ANEMIA C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. RP SMITH, TJ (reprint author), PRESBYTERIAN ST LUKES HOSP,ROCKY MT CHILDRENS CANC CTR,CHILDHOOD HEMATOL ONCOL ASSOCIATES,DENVER,CO, USA. NR 5 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD NOV PY 1995 VL 50 IS 3 BP 226 EP 227 DI 10.1002/ajh.2830500317 PG 2 WC Hematology SC Hematology GA TB942 UT WOS:A1995TB94200016 PM 7485090 ER PT J AU ROGERS, GR RIZZO, WB ZLOTOGORSKI, A HASHEM, N LEE, MJ COMPTON, JG BALE, SJ AF ROGERS, GR RIZZO, WB ZLOTOGORSKI, A HASHEM, N LEE, MJ COMPTON, JG BALE, SJ TI GENETIC HOMOGENEITY IN SJOGREN-LARSSON SYNDROME - LINKAGE TO CHROMOSOME 17P IN FAMILIES OF DIFFERENT NON-SWEDISH ETHNIC-ORIGINS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HUMAN ALDEHYDE DEHYDROGENASE; CULTURED FIBROBLASTS; FATTY ALCOHOL; OXIDOREDUCTASE AB Sjogren-Larsson syndrome (SLS) is a rare, autosomal recessive disorder that is characterized by congenital ichthyosis, mental retardation, and spastic diplegia or tetraplegia. Three United States families, three Egyptian families, and one Israeli Arab family were investigated for linkage of the SLS gene to a region of chromosome 17. Pairwise and multipoint linkage analysis with nine markers mapped the SLS gene to the same region of the genome as that reported in Swedish SLS pedigrees. Examination of recombinants by haplotype analysis showed that the gene lies in the region containing the markers D17S953, D17S805, D17S689, and D17S842. D17S805 is pericentromeric on 17p. Patients in two consanguineous Egyptian families were homozygous at the nine marker loci tested, and another patient from a third family was homozygous for eight of the nine, suggesting that within each of these families the region of chromosome 17 carrying the SLS gene is identical by descent. Linkage of the SLS gene to chromosome 17p in families of Arabic, mixed European, Native American, and Swedish descent provides evidence for a single SLS locus and should prove useful for diagnosis and carrier detection in worldwide cases. C1 NIAMSD,SKIN BIOL LAB,GENET STUDIES SECT,BETHESDA,MD 20892. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT HUMAN GENET & PEDIAT,RICHMOND,VA 23298. HEBREW UNIV JERUSALEM,HADASSAH MED CTR,DEPT DERMATOL,JERUSALEM,ISRAEL. AIN SHAMS MED GENET CLIN,CAIRO,EGYPT. RI Lee, Minjoo/A-9720-2008 OI Lee, Minjoo/0000-0002-3151-3808 NR 25 TC 21 Z9 22 U1 0 U2 0 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 NOV PY 1995 VL 57 IS 5 BP 1123 EP 1129 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA TA449 UT WOS:A1995TA44900019 PM 7485163 ER PT J AU DEAN, M ALLIKMETS, R AF DEAN, M ALLIKMETS, R TI CONTAMINATION OF CDNA LIBRARIES AND EXPRESSED-SEQUENCE-TAGS DATABASES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 6 TC 8 Z9 8 U1 0 U2 1 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 NOV PY 1995 VL 57 IS 5 BP 1254 EP 1255 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA TA449 UT WOS:A1995TA44900039 PM 7485181 ER PT J AU BIESECKER, LG DERENZO, EG AF BIESECKER, LG DERENZO, EG TI INTERNET SOLICITATION OF RESEARCH SUBJECTS FOR GENETIC-STUDIES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter C1 NIH,CTR CLIN,BIOETH PROGRAM,BETHESDA,MD. RP BIESECKER, LG (reprint author), NIH,NATL CTR HUMAN GENOME RES,BLDG 49,ROOM 4A80,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 1995 VL 57 IS 5 BP 1255 EP 1256 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA TA449 UT WOS:A1995TA44900040 PM 7485182 ER PT J AU FANAROFF, AA WRIGHT, LL STEVENSON, DK SHANKARAN, S DONOVAN, EF EHRENKRANS, RA YOUNES, N KORONES, SB STOLL, BJ TYSON, JE BAUER, CR OH, W LEMONS, JA PAPILE, LA VERTER, J AF FANAROFF, AA WRIGHT, LL STEVENSON, DK SHANKARAN, S DONOVAN, EF EHRENKRANS, RA YOUNES, N KORONES, SB STOLL, BJ TYSON, JE BAUER, CR OH, W LEMONS, JA PAPILE, LA VERTER, J TI VERY-LOW-BIRTH-WEIGHT OUTCOMES OF THE NATIONAL-INSTITUTE-OF-CHILD-HEALTH-AND-HUMAN-DEVELOPMENT NEONATAL RESEARCH NETWORK, MAY 1991 THROUGH DECEMBER 1992 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE VERY LOW BIRTH WEIGHT; MORBIDITY; MORTALITY; NICHD NEONATAL RESEARCH NETWORK ID GESTATIONAL-AGE; INFANTS; MORTALITY; GRAMS; SURFACTANT; LESS AB OBJECTIVES: Our goals were to determine the mortality risk for infants weighing 501 to 1500 gm according to gestational age, birth weight, and gender and to document birth weight-related changes in mortality and morbidity over a 5-year time period. STUDY DESIGN: In this observational study perinatal data were prospectively collected by the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network from May 1991 through December 1992 and compared with the corresponding data from 1987 through 1990. Standard definitions were used to record sociodemographic factors, perinatal events, and the neonatal course to 120 days of life, discharge, or death. RESULTS: The 1991 and 1992 cohort included 4279 in-born infants. Among their mothers 10% were <18 years old; 55% were black, 31% were white, and 11% were Hispanic; 14% had received no prenatal care; and 20% had received antenatal corticosteroids. Multiple gestations accounted for 20% of the births. Fifty percent of the infants were delivered by cesarean section. During 1991 and 1992 the overall survival for infants weighing 501 to 1500 gm at birth was 81%, compared with 74% in 1987 and 1988. Survival at birth weight 501 to 750 gm was 44%; it was 81% at 751 to 1000 gm, 92% at 1001 to 1250 gm, and 95% between 1251 and 1500 gm. Female infants had a significantly greater chance of surviving than male infants at similar birth weights and gestational ages. At any given gestational age, smaller infants were less likely to survive. Survival in all birth weight categories increased between 1987 and 1992, without accompanying increases in medical morbidity. Major morbidity increased with decreasing birth weight and included late-onset septicemia 22%, chronic lung disease (oxygen dependence at 36 weeks' corrected age) 18%, severe intraventricular hemorrhage (grades III and IV) 11%, and necrotizing enterocolitis 5%. Twelve percent of all infants were treated with corticosteroids for chronic lung disease, including 36% of infants who were oxygen dependent at age 28 days. The mean length of hospital stay was 69 days for survivors and 18 days for infants who died. CONCLUSIONS: Mortality for infants between 501 and 1500 gm at birth has declined over the past 5 years. There are interactions between birth weight, gestational age, gender, and survival rate. This increase in survival was not accompanied by an increase in medical morbidity. C1 CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. NICHHD,BETHESDA,MD 20892. STANFORD UNIV,PALO ALTO,CA 94304. YALE UNIV,NEW HAVEN,CT. WAYNE STATE UNIV,DETROIT,MI. GEORGE WASHINGTON UNIV,CTR BIOSTAT,WASHINGTON,DC. UNIV TENNESSEE,MEMPHIS,TN. EMORY UNIV,ATLANTA,GA 30322. UNIV TEXAS,SW MED CTR,DALLAS,TX. UNIV MIAMI,MIAMI,FL 33152. WOMEN & INFANTS HOSP RHODE ISL,PROVIDENCE,RI. INDIANA UNIV,INDIANAPOLIS,IN 46204. UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. FU NICHD NIH HHS [U10 HD21364, U10 HD21385, U10 HD27880] NR 17 TC 171 Z9 176 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 1995 VL 173 IS 5 BP 1423 EP 1431 DI 10.1016/0002-9378(95)90628-2 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA TH560 UT WOS:A1995TH56000014 PM 7503180 ER PT J AU SHAH, GK CANTRILL, HL HOLLAND, EJ AF SHAH, GK CANTRILL, HL HOLLAND, EJ TI VORTEX KERATOPATHY ASSOCIATED WITH ATOVAQUONE SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Note AB PURPOSE: We studied a case of vortex keratopathy that was associated with the use of atovaquone. METHOD: A patient with acquired immunodeficiency syndrome (AIDS) with pulmonary Pneumocystis carinii was treated with 750 mg of atovaquone three times a day. RESULTS: Similar to previous findings of drug induced vortex keratopathy, atovaquone vortex keratopathy is presumably caused by its lipophilic properties. This property is similar to that of other lipophilic agents such as amiodarone, chloroquine, chlorpromazine, quinacrine, and suramin. CONCLUSION: Atovaquone should be added to the list of agents causing vortex keratopathy involving the corneal epithelium. C1 NEI,CLIN BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,CYTOPATHOL SECT,BETHESDA,MD. RP SHAH, GK (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N103,10 CTR DR,MSC 1858,BETHESDA,MD 20892, USA. NR 5 TC 5 Z9 6 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 NOV PY 1995 VL 120 IS 5 BP 669 EP 671 PG 3 WC Ophthalmology SC Ophthalmology GA TD458 UT WOS:A1995TD45800014 PM 7485371 ER PT J AU CHAN, CC WHITCUP, SM SOLOMON, D NUSSENBLATT, RB AF CHAN, CC WHITCUP, SM SOLOMON, D NUSSENBLATT, RB TI INTERLEUKIN-10 IN THE VITREOUS OF PATIENTS WITH PRIMARY INTRAOCULAR LYMPHOMA SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Note AB PURPOSE: To find an accurate and simple method to diagnose primary intraocular lymphoma. METHODS: We prospectively analyzed concentrations of interleukin-10, interleukin-1, interleukin-2, interleukin-4, and interleukin-6 in vitrectomy specimens from three patients with primary intraocular lymphoma and five patients with uveitis by enzyme-linked immunosorbent assay. RESULTS: Interleukin-10 in the vitreous was detected in patients with primary intraocular lymphoma. Interleukin-10 levels correlated with clinical activity and the number of malignant cells. CONCLUSION: Concentrations of interleukin-10 in the vitreous may be a helpful clue to both clinicians and pathologists in diagnosing primary intraocular lymphoma. C1 NEI,CLIN BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,CYTOPATHOL SECT,BETHESDA,MD. RP CHAN, CC (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N103,10 CTR DR,MSC 1858,BETHESDA,MD 20892, USA. NR 5 TC 93 Z9 98 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 NOV PY 1995 VL 120 IS 5 BP 671 EP 673 PG 3 WC Ophthalmology SC Ophthalmology GA TD458 UT WOS:A1995TD45800015 PM 7485372 ER PT J AU BARCELLOSHOFF, MH EHRHART, EJ KALIA, M JIRTLE, R FLANDERS, K TSANG, MLS AF BARCELLOSHOFF, MH EHRHART, EJ KALIA, M JIRTLE, R FLANDERS, K TSANG, MLS TI IMMUNOHISTOCHEMICAL DETECTION OF ACTIVE TRANSFORMING GROWTH-FACTOR-BETA IN-SITU USING ENGINEERED TISSUE SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MOLECULAR-WEIGHT COMPLEX; HUMAN-PLATELETS; FACTOR-BETA-1; EXPRESSION; LOCALIZATION; GROWTH-FACTOR-BETA-1; PRECURSOR; CELLS; ANTIBODIES; REPAIR AB The biological activity of transforming growth factor-beta 1 (TGF-beta) is governed by dissociation from its latent complex. Immunohistochemical discrimination of active and latent TGF-beta could provide insight into TGF-beta activation in physiological and pathological processes, However, evaluation of immunoreactivity specificity in situ has been hindered by the lack of tissue in which TGF-beta status is known. To provide in situ analysis of antibodies to differentiate between these functional forms, we used xenografts of human tumor cells modified by transfection to overexpress latent TGF-beta or constitutively active TGF-beta This comparison revealed that, whereas most antibodies did not differentiate between TGF-beta activation status, the immunoreactivity of some antibodies was activation dependent. Two widely used peptide antibodies to the amino-terminus of TGF-beta, LC(1-30) and CC(1-30) showed marked preferential immunoreactivity with active TGF-beta versus latent TGP-beta in cryosections However, is formalin-fixed, paraffin-embedded tissue, discrimination of active TGF-beta by CC(1-30) was lost and immunoreactivity was distinctly extracellular, as previously reported for this antibody. Similar processing-dependent extracellular localization was found with a neutralizing antibody raised to recombinant TGF-beta. Antigen retrieval recovered cell-associated immunoreactivity of both antibodies. Two antibodies to peptides 78-109 showed mild to moderate preferential immunoreactivity with active TGF-beta only in paraffin sections LC(1-30) was the only antibody tested that discriminated active from latent TGF-beta in both frozen and paraffin-embedded tissue. Thus, in situ discrimination of active versus latent TGF-beta depends on both the antibody and tissue preparation. We propose that tissues engineered to express a specific form of a given protein provide a physiological setting in which to evaluate antibody reactivity with specific forms of a protein. C1 COLORADO STATE UNIV, DEPT RADIOL HLTH SCI, FT COLLINS, CO 80523 USA. DUKE UNIV, MED CTR, DEPT RADIAT ONCOL, DURHAM, NC USA. NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. R&D SYST INC, MINNEAPOLIS, MN USA. RP BARCELLOSHOFF, MH (reprint author), UNIV CALIF BERKELEY, LAWRENCE BERKELEY LAB,DIV LIFE SCI,BLDG 74,RM 157, 1 CYCLOTRON RD, BERKELEY, CA 94720 USA. NR 27 TC 71 Z9 71 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1995 VL 147 IS 5 BP 1228 EP 1237 PG 10 WC Pathology SC Pathology GA TD741 UT WOS:A1995TD74100008 PM 7485387 ER PT J AU MATRISIAN, LM TYKOCINSKI, ML PADARATHSINGH, M AF MATRISIAN, LM TYKOCINSKI, ML PADARATHSINGH, M TI LESSONS TO BE LEARNED FROM HEMATOPOIETIC MALIGNANCIES - WORKSHOP REPORT FROM THE DIVISION-OF-RESEARCH-GRANTS, NATIONAL-INSTITUTES-OF-HEALTH SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Editorial Material C1 CASE WESTERN RESERVE UNIV,DEPT PATHOL,CLEVELAND,OH 44106. NATL INST HLTH,DIV RES GRANTS,BETHESDA,MD. RP MATRISIAN, LM (reprint author), VANDERBILT UNIV,DEPT CELL BIOL,NASHVILLE,TN 37232, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1995 VL 147 IS 5 BP 1519 EP 1521 PG 3 WC Pathology SC Pathology GA TD741 UT WOS:A1995TD74100035 PM 7485414 ER PT J AU LI, YX KEIZER, J STOJILKOVIC, SS RINZEL, J AF LI, YX KEIZER, J STOJILKOVIC, SS RINZEL, J TI CA2+ EXCITABILITY OF THE ER MEMBRANE - AN EXPLANATION FOR IP3-INDUCED CA2+ OSCILLATIONS SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Review DE CALCIUM IONS; ENDOPLASMIC RETICULUM; INOSITOL; 1,4,5-TRISPHOSPHATE; CALCIUM PUMPS; PITUITARY CELLS; GONADOTROPIN-RELEASING HORMONE ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; PROTEIN-KINASE-C; INDUCED I OSCILLATIONS; INDUCED CALCIUM OSCILLATIONS; CYTOPLASMIC FREE CALCIUM; PAROTID ACINAR-CELLS; PITUITARY GONADOTROPHS; ENDOPLASMIC-RETICULUM; TRISPHOSPHATE RECEPTOR; CYTOSOLIC CA2+ AB Recent research dealing with experiments and theoretical models of Ca2+ excitability of the endoplasmic reticulum (ER) membrane induced by inositol 1,4,5-trisphosphate (IP3) is reviewed. Ca2+ excitability refers to the ability of a small increment of cytoplasmic Ca2+ concentration ([Ca2+](i)) to trigger a large [Ca2+](i) pulse or oscillations. Such nonlinear regenerative behavior is conferred by the existence of IP3 channels and Ca2+-ATPase transporters on the ER membrane, which extends throughout the cytoplasm. Ca2+ excitability resembles the plasma membrane electrical excitability of neurons and other cells: it is driven by the ionic concentration gradient across the ER membrane (higher Ca2+ concentration inside the ER); each [Ca2+](i) spike partially consumes the prestored energy that is reestablished through ATP-dependent active transport; and [Ca2+](i), the excitation variable, controls the nonlinear dynamic release rate of ER Ca2+. This review focuses on the kinetic models based on these features and on experiments dealing with the kinetic properties of [Ca2+](i)-dependent gating of the IP3 receptor channel. We summarize evidence in favor of two roles for [Ca2+](i) in gating the channel's opening: activation at a rapid time scale and inactivation an a slower time scale. Exploiting an analogy to the well-known Hodgkin-Huxley model for neuronal electrical excitability, we show how Ca2+ excitability of the ER membrane can be explained by these gating properties combined with the ER Ca2+ pump activity. The theory's ability to predict is illustrated by comparing calculated with experimental [Ca2+](i) responses for pituitary gonadotrophs under various stimulus conditions. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, BETHESDA, MD 20892 USA. UNIV CALIF DAVIS, INST THEORET DYNAM, DAVIS, CA 95616 USA. UNIV CALIF DAVIS, NEUROBIOL PHYSIOL & BEHAV SECT, DAVIS, CA 95616 USA. RP LI, YX (reprint author), NIDDK, MATH RES BRANCH, 9190 WISCONSIN AVE, SUITE 350, BETHESDA, MD 20814 USA. NR 102 TC 80 Z9 81 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD NOV PY 1995 VL 269 IS 5 BP C1079 EP C1092 PG 14 WC Cell Biology; Physiology SC Cell Biology; Physiology GA TE950 UT WOS:A1995TE95000001 ER PT J AU WANK, SA AF WANK, SA TI CHOLECYSTOKININ RECEPTORS SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Review DE GASTRIN; G PROTEIN-COUPLED RECEPTOR; EXPRESSION; GENE; COMPLEMENTARY DEOXYRIBONUCLEIC ACID; CHROMOSOME; HYBRIDIZATION; CLONING; PURIFICATION; SIGNAL TRANSDUCTION; NEUROPEPTIDE ID RAT PANCREATIC ACINI; GASTRIC PARIETAL-CELLS; SMOOTH-MUSCLE CELLS; HYPOTHALAMIC MAGNOCELLULAR NEURONS; BETA-ADRENERGIC-RECEPTOR; MOLECULAR-CLONING; GUINEA-PIG; FUNCTIONAL EXPRESSION; INOSITOL TRISPHOSPHATE; ENZYME-SECRETION AB The cholecystokinin (CCK) and gastrin families of peptides act as hormones and neuropeptides on central and peripheral CCK receptors to mediate secretion and motility in the gastrointestinal (GI) tract in the physiological response to a normal meal. CCK and its receptors are also widely distributed in the central nervous system (CNS) and contribute to the regulation of satiety, anxiety, analgesia, and dopamine-mediated behavior. Although the wide distribution, myriad number of functions, and reported pharmacological heterogeneity of CCK receptors would suggest a large number of receptor subtypes, the application of modern molecular biological techniques has identified two CCK receptors, CCK-A receptor (CCK-AR) and CCK-B receptor (CCK-BR), that mediate the actions of CCK and gastrin; gastrin receptors have been found to be identical to CCK-BR. CCK-AR, found predominantly in the GI system and select areas of the CNS, have high affinity for CCK and the nonpeptide antagonist L-364,718, whereas CCK-BR, found predominantly in the CNS and select areas of the GI system, have high affinity for CCK and gastrin and the nonpeptide antagonist L-365,260. Both CCK-AR and CCK-BR are highly conserved between species, although there is some tissue-specific variation in expression. Recombinant receptor expression faithfully reproduces the native receptor pharmacology and signal transduction pathways, allowing direct comparisons of receptor function between species as well as serving as a convenient source of receptor. Our present knowledge of the chromosomal localization, receptor gene structure, and primary sequence will allow further studies in disease association, receptor regulation, and structure-function analysis. RP NIDDKD, DIGEST DIS BRANCH, BLDG 10, RM 9C103, BETHESDA, MD 20892 USA. NR 250 TC 278 Z9 288 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 EI 1522-1547 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 1995 VL 269 IS 5 BP G628 EP G646 PG 19 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA TE645 UT WOS:A1995TE64500002 PM 7491953 ER PT J AU HANO, O BOGDANOV, KY SAKAI, M DANZIGER, RG SPURGEON, HA LAKATTA, EG AF HANO, O BOGDANOV, KY SAKAI, M DANZIGER, RG SPURGEON, HA LAKATTA, EG TI REDUCED THRESHOLD FOR MYOCARDIAL-CELL CALCIUM INTOLERANCE IN THE RAT-HEART WITH AGING SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE AGING HEART; SPONTANEOUS CYTOSOLIC CALCIUM OSCILLATIONS; SARCOPLASMIC RETICULUM AFTERCONTRACTIONS; VENTRICULAR FIBRILLATION ID SARCOPLASMIC-RETICULUM CA-2+-ATPASE; CARDIAC-MUSCLE; VENTRICULAR-FIBRILLATION; FATTY-ACIDS; NA+-CA2+ EXCHANGE; HAMSTER HEARTS; DIETARY-FAT; OSCILLATIONS; AGE; MODULATION AB To determine whether advancing age is accompanied by a reduced Ca2+ tolerance, we measured Ca2+-dependent diastolic pressure, prolonged relaxation and systolic functional deterioration, spontaneous sarcoplasmic reticulum (SR)-generated Ca2+ oscillations [detected as scattered laser light intensity fluctuations (SLIF)], aftercontractions, and ventricular fibrillation in isolated, isovolumic, atrioventricular-blocked intact hearts from 24- to 26-mo (old) and 6- to 8-mo (young) male Wistar rats. In enzymatically isolated single cardiac myocytes, the likelihood of the occurrence of spontaneous contractile waves driven by spontaneous SR Ca2+ release was also determined. In response to stepwise increases in perfusate Ca2+ concentration (Ca-0), a reduction in the maximum developed pressure accompanied by an elevation in end-diastolic pressure and a prolonged contraction duration was observed at lower Ca, in old vs. young hearts (P < 0.01 for each parameter). Furthermore, Ca2+-dependent ventricular fibrillation occurred during pacing in six old but in no young hearts (P < 0.01), aftercontractions were observed in seven old vs. one young heart (P < 0.01), and SLIF increased to a greater extent in old vs. young hearts. In single cardiac myocytes, spontaneous contractile waves occurred more frequently with increasing age (P < 0.01). These results indicate that aging is associated with an increased likelihood for the occurrence of SR-generated Ca2+ oscillations and functional abnormalities that result from these oscillations. C1 NIA, GERONTOL RES CTR, CARDIOVASC SCI LAB, BALTIMORE, MD 21224 USA. NR 47 TC 35 Z9 35 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD NOV PY 1995 VL 269 IS 5 BP H1607 EP H1612 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA TF258 UT WOS:A1995TF25800014 ER PT J AU ECELBARGER, CA TERRIS, J FRINDT, G ECHEVARRIA, M MARPLES, D NIELSEN, S KNEPPER, MA AF ECELBARGER, CA TERRIS, J FRINDT, G ECHEVARRIA, M MARPLES, D NIELSEN, S KNEPPER, MA TI AQUAPORIN-3 WATER CHANNEL LOCALIZATION AND REGULATION IN RAT-KIDNEY SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE COLLECTING DUCT; WATER PERMEABILITY; VASOPRESSIN; AQUAPORINS; WATER CHANNELS ID INTEGRAL MEMBRANE-PROTEIN; FAMILY; ATPASE AB The aquaporins are a family of water channels expressed in several water-transporting tissues, including the kidney. We have used a peptide-derived, affinity-purified polyclonal antibody to aquaporin-3 (AQP-3) to investigate its localization and regulation in the kidney. Immunoblotting experiments showed expression in both renal cortex and medulla, with greatest expression in the base of the inner medulla. Subcellular fractionation of membranes, using progressively higher centrifugation speeds, revealed that AQP-3 is present predominantly in the 4,000 and 17,000 g pellets and, in contrast to AQP-2, is virtually absent in the high-speed (200,000 g) pellet that contains small intracellular vesicles. Immunocytochemistry and immunofluorescence studies revealed that labeling is restricted to the cortical, outer medullary, and inner medullary collecting ducts. Within the collecting duct, principal cells were labeled, whereas intercalated cells were unlabeled. Consistent with previous immunofluorescence studies (K. Ishibashi, S. Sasaki, K. Fushimi, S. Uchida, M. Kuwahara, H. Saito, T. Furukawa, K. Nakajima, Y. Yamaguchi, T. Gojobori, and F. Marumo. Proc. Natl. Acad. Sci. USA 91: 6269-6273, 1994; T. Ma, A. Frigeri, H. Hasegawa, and A. S. Verkman. J. Biol. Chem. 269: 21845-21849, 1994), the labeling was confined to the basolateral domain. Immunoelectron microscopy, using the immunogold technique in ultrathin cryosections, demonstrated a predominant labeling of the basolateral plasma membranes. In contrast to previous findings with AQP-2, there was only limited AQP-3 labeling of intracellular vesicles, suggesting that this water channel is not regulated acutely through vesicular trafficking. Immunoblotting studies revealed that thirsting of rats for 48 h approximately doubled the amount of AQP-3 protein in the inner medulla. These studies are consistent with a role for AQP-3 in osmotically driven water absorption across the collecting duct epithelium and suggest that the expression of AQP-3 is regulated on a long-term basis. C1 NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BETHESDA, MD 20892 USA. CORNELL UNIV, COLL MED, DEPT PHYSIOL & BIOPHYS, NEW YORK, NY 10021 USA. AARHUS UNIV, INST ANAT, DEPT CELL BIOL, DK-8000 AARHUS, DENMARK. RI Echevarria Irusta, Miriam/E-6682-2010; IBIS, TERAPIA CELULA/P-3297-2015 OI Echevarria Irusta, Miriam/0000-0002-4758-9428; FU NIDDK NIH HHS [DK-11489, DK-08832] NR 26 TC 293 Z9 297 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrol. Physiol. PD NOV PY 1995 VL 269 IS 5 BP F663 EP F672 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA TE649 UT WOS:A1995TE64900007 PM 7503232 ER PT J AU KOPP, JB KLOTMAN, PE AF KOPP, JB KLOTMAN, PE TI TRANSGENIC ANIMAL-MODELS OF RENAL DEVELOPMENT AND PATHOGENESIS SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Review DE PROMOTER; HOMOLOGOUS RECOMBINATION; TRANSCRIPTION FACTOR; HOMEOBOX GENES; ONCOGENES; RENIN; ERYTHROPOIETIN; CYTOKINES; GROWTH HORMONE; TRANSFORMING GROWTH FACTOR-BETA; HUMAN IMMUNODEFICIENCY VIRUS 1 ID CELL-SPECIFIC EXPRESSION; ORNITHINE DECARBOXYLASE GENE; HUMAN ERYTHROPOIETIN GENE; EMBRYONIC STEM-CELLS; GROWTH FACTOR-I; N-MYC GENE; HUMAN ANGIOTENSINOGEN GENES; TISSUE-SPECIFIC EXPRESSION; POLYCYSTIC KIDNEY-DISEASE; HORMONE FUSION GENES AB The use of transgenic animals represents a powerful tool with which to address the role of particular gene products in vivo. Recent technical and biological advances have simplified the process of creating both transgenic mice and null-mutation mice. Increasing numbers of genetic control elements are available to direct transgene expression to particular renal cell types and to enhance the consistency of expression. These approaches have contributed significantly to our understanding of renal development and pathogenesis, in particular in the following areas: the roles of various oncogenes, homeobox genes, and growth factors in renal development and the pathogenesis of cystic renal diseases; the contribution of systemic and local expression of the renin-angiotensin system to blood pressure control; the role of growth factors and cytokines in progressive glomerular disease; the role of viral proteins in the pathogenesis of glomerular and tubular disease; and. mechanisms of immune-mediated renal disease. C1 CUNY MT SINAI SCH MED, DIV NEPHROL, NEW YORK, NY 10029 USA. RP KOPP, JB (reprint author), NIDDKD, METAB DIS BRANCH, KIDNEY DIS SECT, BLDG 10, RM 3N116, BETHESDA, MD 20892 USA. NR 218 TC 15 Z9 15 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 1995 VL 269 IS 5 BP F601 EP F620 PG 20 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA TE649 UT WOS:A1995TE64900001 PM 7503226 ER PT J AU MALONE, KM SZANTO, K CORBITT, EM MANN, JJ AF MALONE, KM SZANTO, K CORBITT, EM MANN, JJ TI CLINICAL-ASSESSMENT VERSUS RESEARCH METHODS IN THE ASSESSMENT OF SUICIDAL-BEHAVIOR SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 147th Annual Meeting of the American-Psychiatric-Association CY MAY 21-27, 1994 CL PHILADELPHIA, PA SP Amer Psychiat Assoc ID PSYCHIATRIC-PATIENTS; AFFECTIVE-DISORDERS; MEDICAL LETHALITY; INTENT SCALE; RISK-FACTORS; IDEATION; FOLLOW AB Objective: This study examined how accurately routine inpatient clinical assessments documented a history of overt suicidal behavior in inpatients with a diagnosis of major depressive episode. Secondary questions involved the exploration of possible factors influencing the quality of routine clinical documentation of suicidal behavior, such as lethality of attempts, axis II comorbidity, and presence of recent suicidal behavior. Method: Hospital records for 50 patients, known to have a history of suicidal behavior on the basis of research ratings, were reviewed to assess reporting of the number of lifetime suicide attempts, suicidal ideation and planning behavior, most medically lethal suicide attempt, and family history of suicidal behavior. These measures of suicidal behavior were compared with a comprehensive research assessment, completed concurrently and independently. Results: At admission clinicians failed to document a history of suicidal behavior in 12 of 50 patients identified by research assessment as depressed and as having attempted suicide. Fewer total suicide attempts were clinically reported than in research data. Documentation of suicidal behavior was least accurate in the physician discharge summary and was most accurate on hospital intake assessment, which employed a semistructured format for recording clinical information including suicidal behavior. Conclusions: A significant degree of past suicidal behavior is not recorded during routine clinical assessment, and the use of semistructured screening instruments may improve documentation and detection of lifetime suicidal behavior. The physician discharge summary must accurately document suicidal behavior, since it best identifies a high-risk population for outpatient clinicians responsible for follow-up. C1 NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY 10032. RP MALONE, KM (reprint author), COLUMBIA UNIV COLL PHYS & SURG,CLIN RES CTR STUDY SUICIDAL BEHAV,NIMH,722 W 168TH ST,BOX 28,NEW YORK,NY 10032, USA. RI Szanto, Katalin/B-8389-2014 FU NIMH NIH HHS [MH-48514, MH-46745] NR 39 TC 74 Z9 78 U1 6 U2 12 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1995 VL 152 IS 11 BP 1601 EP 1607 PG 7 WC Psychiatry SC Psychiatry GA TC543 UT WOS:A1995TC54300007 PM 7485622 ER PT J AU MAGRUDER, KM NORQUIST, GS FEIL, MB KOPANS, B JACOBS, D AF MAGRUDER, KM NORQUIST, GS FEIL, MB KOPANS, B JACOBS, D TI WHO COMES TO A VOLUNTARY DEPRESSION SCREENING-PROGRAM SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID GERIATRIC MEDICAL PATIENTS; ADDICTIVE-DISORDERS; SCALE AB Objective: The purpose of this study was to describe who comes to a voluntary depression screening program by analyzing findings from the 1992 National Depression Screening Day. Method: Survey results from 5,367 adult volunteers at 345 facilities were analyzed. The authors examined the prevalence of depression detected at the screening test and sociodemographic characteristics and treatment history of the respondents. They also estimated the percentage of these individuals who would actually have a diagnosis of major depression (positive predictive value). The main assessment measure was the Zung Self-Rating Depression Scale. Results: Of all participants, 76.6% (N=4,109) had at least minimal depressive symptoms (score of at least 50 on the Zung depression scale), 53.3% (N=2,859) had at least moderate symptoms (score of at least 60), and 22.6% (N=1,214) had severe symptoms (score of at least 70). Few of the depressed respondents were currently in treatment for a mental health problem. The positive predictive value of a screening test diagnosis of depression was between 92.5% and 95.5% when a cutoff score of 60 was used to indicate depression and between 88.7% and 92.3% when a cutoff score of 50 was used. Conclusions: Voluntary screening tests, as exemplified by results from the National Depression Screening Day, provide a good opportunity for identifying previously unidentified and untreated individuals with depression. RP MAGRUDER, KM (reprint author), NIMH,DIV EPIDEMIOL,RM 10C-06,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 25 TC 53 Z9 53 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1995 VL 152 IS 11 BP 1615 EP 1622 PG 8 WC Psychiatry SC Psychiatry GA TC543 UT WOS:A1995TC54300009 PM 7485624 ER PT J AU HARTSOCK, PI AF HARTSOCK, PI TI THE AVAILABILITY OF DISPOSABLE SYRINGES IN RUSSIA SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter RP HARTSOCK, PI (reprint author), NIDA,DIV EPIDEMIOL & PREVENT RES,COMMUNITY RES BRANCH,ROOM 9A-53,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 2 TC 2 Z9 2 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 1995 VL 85 IS 11 BP 1586 EP 1586 DI 10.2105/AJPH.85.11.1586 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TB493 UT WOS:A1995TB49300023 PM 7485678 ER PT J AU HEFFNER, JE BROWN, LK BARBIERI, CA HARPEL, KS DELEO, J AF HEFFNER, JE BROWN, LK BARBIERI, CA HARPEL, KS DELEO, J TI PROSPECTIVE VALIDATION OF AN ACUTE RESPIRATORY-DISTRESS SYNDROME PREDICTIVE SCORE SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID CRITICALLY ILL PATIENTS; ACUTE PHYSIOLOGY SCORE; ORGAN-SYSTEM FAILURE; CLINICAL PREDICTORS; LUNG INJURY; MORTALITY; MULTICENTER; THERAPY; EDEMA AB We derived an Acute Respiratory Distress Syndrome Score (ARDS Score) from previously described training set data. To validate its diagnostic accuracy for identifying a complicated course (early death or prolonged intubation) in acute lung injury, 50 patients were prospectively scored using an ARDS Score decision threshold of greater than or equal to 2.5 to discriminate between an uncomplicated (successful extubation after less than or equal to 14 d) and complicated course. Predictor factors incorporated in the ARDS Score were collected on Day 4 and Day 7 of ARDS and included Pa-O2/PA(O2). ratio, required positive end-expiratory pressure (PEEP), and chest radiograph progression. The diagnostic accuracy of the ARDS Score for determining a complicated course as well as overall survival was compared with three other available indices. Using receiver operating characteristic (ROC) analysis, the ARDS Score and Lung Injury Score (LIS) had the greatest diagnostic accuracy for determining a complicated course, but the Simplified Acute Physiology Score (SAPS Score) (score greater than or equal to 14) more accurately identified survival. The LIS components of static respiratory system compliance (C-rs) and chest radiograph description did not differ between patient groups. The interobserver concordance of the dynamic chest radiograph interpretation included in the ARDS Score was significant (p < 0.05). We conclude that the previously derived ARDS Score has valid diagnostic accuracy for identifying patients with ARDS who will follow a complicated course. C1 MED CTR,PHOENIX,AZ. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP HEFFNER, JE (reprint author), ST JOSEPHS HOSP,DEPT MED,CRIT CARE SECT,350 W THOMAS RD,PHOENIX,AZ 85013, USA. NR 34 TC 44 Z9 45 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV PY 1995 VL 152 IS 5 BP 1518 EP 1526 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA TC861 UT WOS:A1995TC86100015 PM 7582287 ER PT J AU LEVAV, M MIRSKY, AF CRUZ, ME CRUZ, I AF LEVAV, M MIRSKY, AF CRUZ, ME CRUZ, I TI NEUROCYSTICERCOSIS AND PERFORMANCE ON NEUROPSYCHOLOGIC TESTS - A FAMILY STUDY IN ECUADOR SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID LOS-ANGELES COUNTY; CYSTICERCOSIS AB Neurocysticercosis (NCC) is a common neurologic disorder in developing countries, where it may pose a major public health challenge. Recently, the disorder has become more commonly diagnosed in developed countries as a result of the influx of migrants from countries where the disease is endemic. The clinical syndrome associated with NCC includes neurologic, physical, and functional problems. Since the locus of the infection is mainly the central nervous system, there is a risk of neuropsychologic dysfunction. This study was conducted in Ecuador in a group of 123 subjects (49 males and 74 females, 9-62 years of age) from a community sample that was part of a larger neuroepidemiologic inquiry. A discriminant function procedure was used to select the tests that would be most sensitive at distinguishing between affected and nonaffected individuals. The results suggest that behavioral functions that include aspects of inhibitory control, motor, and visual-motor output are impaired in adolescent and adult subjects with NCC. C1 ACAD ECUATORIANA NEUROCIENCIAS, QUITO 605, ECUADOR. RP LEVAV, M (reprint author), NIMH, PSYCHOL & PSYCHOPATHOL LAB, CLIN & EXPTL NEUROPSYCHOL SECT, BLDG 10, ROOM 4C110, BETHESDA, MD 20892 USA. NR 32 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 1995 VL 53 IS 5 BP 552 EP 557 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA TH289 UT WOS:A1995TH28900018 PM 7485717 ER PT J AU BUELL, JF FRAKER, DL DOPPMAN, TL SHAWKER, TH SKARULIS, MC SPIEGEL, AM MARX, SJ ALEXANDER, R AF BUELL, JF FRAKER, DL DOPPMAN, TL SHAWKER, TH SKARULIS, MC SPIEGEL, AM MARX, SJ ALEXANDER, R TI HIGH CERVICAL INTRAVAGAL HYPERCELLULAR PARATHYROID-GLAND AS THE ETIOLOGY OF SEVERE PERSISTENT PRIMARY HYPERPARATHYROIDISM SO AMERICAN SURGEON LA English DT Article ID EXPLORATION; ADENOMA AB The preoperative localization and operative management of a high cervical intravagal parathyroid adenoma in a young woman with severe persistent primary hyperparathyroidism is presented. The etiology of persistent hyperparathyroidism is most frequently a missed adenoma that is often in an ectopic location; of these, undescended adenomas represent a small but important proportion. If clinical suspicion and preoperative localization procedures suggest an undescended gland, a direct surgical approach using a high cervical incision and a unilateral exploration is often successful. C1 NCI,SURG BRANCH,SURG METAB SECT,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,HENRY M JACKSON FDN,DEPT RADIOL,BETHESDA,MD 20892. NR 9 TC 8 Z9 8 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 1776 PEACHTREE RD, NW., SUITE 410N, ATLANTA, GA 30309-2352 SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD NOV PY 1995 VL 61 IS 11 BP 943 EP 946 PG 4 WC Surgery SC Surgery GA TA745 UT WOS:A1995TA74500003 PM 7486421 ER PT J AU ALDROUBI, A CHANG, HT ZAKHAROV, SF CHRAMBACH, A AF ALDROUBI, A CHANG, HT ZAKHAROV, SF CHRAMBACH, A TI DETERMINATION OF OPTIMALLY RESOLVING GEL CONCENTRATION AND MIGRATION TIME (PATH) IN GEL-ELECTROPHORESIS SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID EFFICIENCY AB The notion of a mathematically defined optimally resolving gel concentration for components of a pair of molecular species of any given size was developed by Rodbard et al. (Electrophoresis and Isoelectric Focusing on Polyacrylamide Gel, pp. 28-62, de Gruyter, Berlin, 1974) 21 years ago. The mathematical treatment was incorporated into a computer program (T-OPT) for mainframe computers which upon input of the slope and intercept on the mobility axis of the Ferguson plots of the two components, electrophoresis time and temperature, yielded plots of resolution vs gel concentration. The same algorithms were later incorporated into the program ELPHOFIT for personal computers. Ideality of diffusion spreading and zero initial zone width were assumed along with a Gaussian peak distribution and an equal area for both components. Moreover, these programs failed to respond to the practical question of the migration time (or path) required for the resolution at the optimal gel concentration, although an independent program predicting the course of resolution under the assumption of free diffusion band spreading in gels (DAR-001) had been devised by Rodbard for application in preparative elution-PAGE. The present work advances the technology for predicting resolving conditions by presenting a computer program which allows the user (i) to predict the gel concentration which is optimal for obtaining the desired degree of resolution at any migration time, (ii) to prescribe the minimal degree of resolution between two band distributions one wishes to achieve, and (iii) to predict the migration time (or path) required at the optimal gel concentration for the resolution of the two components. The program is written in MATLAB and can be used by any computer that supports MATLAB language. (C) 1995 Academic Press, Inc. C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892. RP ALDROUBI, A (reprint author), NICHHD,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. RI Aldroubi, Akram/J-7186-2012; OI Chang, Huan-Tsung/0000-0002-5393-1410 NR 13 TC 5 Z9 5 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 1 PY 1995 VL 231 IS 2 BP 432 EP 436 DI 10.1006/abio.1995.9976 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA TJ979 UT WOS:A1995TJ97900024 PM 8594996 ER PT J AU LEWISCH, SA LEVINE, RL AF LEWISCH, SA LEVINE, RL TI DETERMINATION OF 2-OXOHISTIDINE BY AMINO-ACID-ANALYSIS SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; GLUTAMINE-SYNTHETASE; SUPEROXIDE-DISMUTASE; ISCHEMIA-REPERFUSION; CATALYZED OXIDATION; HYDROGEN-PEROXIDE; FREE-RADICALS; ONE HISTIDINE; PROTEINS; INACTIVATION AB Oxidative modification of proteins has been implicated in aging, ischemia reperfusion, carcinogenesis, and other phenomena. Oxidation of the C-2 position of the imidazole ring of histidine converts the residue to 2-oxohistidine, a novel amino acid which may serve as a marker of oxidative modification of proteins (K. Uchida and S. Kawakishi, J. Biol. Chem. 269, 2405-2410, 1994). It has been identified in oxidatively modified proteins by electrochemical detection during reverse-phase high-pressure liquid chromatography, by mass spectrometry, and as the phenylthiohydantoin after Edman degradation, but not by amino acid analysis of protein hydrolysates. We now describe procedures for stabilizing 2-oxohistidine which allow its quantification by routine methods of amino acid analysis. These include classical ion exchange chromatography with postcolumn derivatization by o-phthaldialdehyde, reverse-phase chromatography with precolumn derivatization by o-phthaldialdehyde, and reverse-phase chromatography with precolumn derivatization by 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate. Using these techniques, a previously unidentified amino acid which appears during the oxidative inactivation of glutamine synthetase was shown to be 2-oxohistidine. One picomole of 2-oxohistidine was readily detected in a protein hydrolysate containing 1700 pmol total amino acids. RP LEWISCH, SA (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,ROOM 118,MSC 0320,BETHESDA,MD 20892, USA. RI Levine, Rodney/D-9885-2011 NR 27 TC 43 Z9 44 U1 1 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 1 PY 1995 VL 231 IS 2 BP 440 EP 446 DI 10.1006/abio.1995.9974 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA TJ979 UT WOS:A1995TJ97900026 PM 8594998 ER PT J AU MARTIN, JL PLEVAK, DJ FLANNERY, KD CHARLTON, M POTERUCHA, JJ HUMPHREYS, CE DERFUS, G POHL, LR AF MARTIN, JL PLEVAK, DJ FLANNERY, KD CHARLTON, M POTERUCHA, JJ HUMPHREYS, CE DERFUS, G POHL, LR TI HEPATOTOXICITY AFTER DESFLURANE ANESTHESIA SO ANESTHESIOLOGY LA English DT Note DE ANESTHETICS, VOLATILE, DESFLURANE; LIVER, HEPATOTOXICITY, IMMUNE-MEDIATED; TRIFLUOROACERYLATED ANTIGENS ID HALOTHANE HEPATITIS; ISOFLURANE ANESTHESIA; ENFLURANE HEPATITIS; METABOLIC BASIS; LIVER; BIOTRANSFORMATION; NEOANTIGENS; ANTIBODIES; NECROSIS; CHILDREN C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL CRIT CARE MED,BALTIMORE,MD 21205. MAYO CLIN & MAYO FDN,DEPT ANESTHESIOL & CRIT CARE MED,ROCHESTER,MN. MAYO CLIN & MAYO FDN,DEPT GASTROENTEROL,ROCHESTER,MN. LUTHER HOSP,MIDDLEFORD CLIN,EAU CLAIRE,WI. NHLBI,MOLEC IMMUNOL LAB,MOLEC & CELLULAR TOXICOL SECT,BETHESDA,MD. NR 30 TC 50 Z9 53 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 1995 VL 83 IS 5 BP 1125 EP 1129 DI 10.1097/00000542-199511000-00030 PG 5 WC Anesthesiology SC Anesthesiology GA TD723 UT WOS:A1995TD72300031 PM 7486167 ER PT J AU REISS, AL MAZZOCCO, MMM GREENLAW, R FREUND, LS ROSS, JL AF REISS, AL MAZZOCCO, MMM GREENLAW, R FREUND, LS ROSS, JL TI NEURODEVELOPMENTAL EFFECTS OF X-MONOSOMY - A VOLUMETRIC IMAGING STUDY SO ANNALS OF NEUROLOGY LA English DT Article ID TURNER SYNDROME; GRAY-MATTER; BRAIN; DEFICITS; BEHAVIOR; CHILDREN AB Thirty girls with Turner syndrome (TuS) were compared with 30 individually age-matched controls on volumetric brain measures derived from magnetic resonance imaging and on measures of psychological functioning. As expected, girls with TuS performed more poorly on visual-spatial and intellectual measures relative to controls, and were rated by their parents as having more significant problems in attention and social behaviors. Although no group differences in overall cerebral or subcortical volumes were observed, the regional distribution of gray and white matter differed across groups in both right and left parietal regions. Differences in total tissue volume ratios were seen for both right and left parietal areas, but differences in individual gray and white matter ratios were seen exclusively in the right parietal regions. In general, girls with TuS had a smaller proportion of tissue (gray and white) within the right and left parietal regions, and a larger proportion of tissue within the right inferior parietal-occipital region relative to girls in the control group. These data suggest a potentially important role for X chromosome genes and/or sex steroids in the development and specialization of brain structure and function. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. NICHHD,BETHESDA,MD. THOMAS JEFFERSON UNIV,DEPT PEDIAT,PHILADELPHIA,PA 19107. RP REISS, AL (reprint author), KENNEDY KRIEGER INST,BEHAV NEUROGENET & NEUROIMAGING RES CTR,707 N BROADWAY,BALTIMORE,MD 21205, USA. FU NICHD NIH HHS [HD25806, HD31715]; NIMH NIH HHS [MH01142] NR 29 TC 94 Z9 94 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1995 VL 38 IS 5 BP 731 EP 738 DI 10.1002/ana.410380507 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TE955 UT WOS:A1995TE95500006 PM 7486864 ER PT J AU CUNDY, KC BARDITCHCROVO, P WALKER, RE COLLIER, AC EBELING, D TOOLE, J JAFFE, HS AF CUNDY, KC BARDITCHCROVO, P WALKER, RE COLLIER, AC EBELING, D TOOLE, J JAFFE, HS TI CLINICAL PHARMACOKINETICS OF ADEFOVIR IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED PATIENTS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ANTIRETROVIRUS ACTIVITY; 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE; METABOLISM; INFECTION; INVIVO; AGENT; URINE AB The pharmacokinetics and bioavailability of adefovir [9-[2-(phosphonomethoxy)ethyl]adenine] were examined at two dose levels in three phase I/II studies in 28 human immunodeficiency type 1-infected patients. The concentrations of adefovir in serum following the intravenous infusion of 1.0 or 3.0 mg/kg of body weight were dose proportional and declined biexponentially, with an overall mean a standard deviation terminal half-life of 1.6 +/- 0.5 h (n = 28). Approximately 90% of the intravenous dose was recovered unchanged in the urine in 12 h, and more than 98% was recovered by 24 h postdosing. The overall mean a standard deviation total serum clearance of the drug (223 +/- 53 ml/h/kg; n = 25) approximated the renal clearance (205 +/- 78 ml/h/kg; n = 20), which was significantly higher (P < 0.01) than the baseline creatinine clearance in the same patients (88 +/- 18 ml/h/kg; n = 25). Since adefovir is essentially completely unbound in plasma or serum, these data indicate that active tubular secretion accounted for approximately 60% of the clearance of adefovir. The steady-state volume of distribution of adefovir (418 +/- 76 ml/kg; n = 28) suggests that the drug,vas distributed in total body water. Repeated daily dosing with adefovir at 1.0 mg/kg/day (n = 8) and 3.0 mg/kg/day (n = 4) for 22 days did not significantly alter the pharmacokinetics of the drug; there was no evidence of accumulation. The oral bioavailability of adefovir at a 3.0-mg/kg dose was < 12% (n = 5) on the basis of the concentrations in serum or 16.4% +/- 16.0% on the basis of urinary recovery. The subcutaneous bioavailability of adefovir at a 3.0-mg/kg dose was 102% +/- 8.3% (n = 5) on the basis of concentrations in serum or 84.8% +/- 28.5% on the basis of urinary recovery. These data are consistent with preclinical observations in various species. C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NIH,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,AIDS CLIN TRIALS UNIT,SEATTLE,WA 98122. RP CUNDY, KC (reprint author), GILEAD SCI INC,353 LAKESIDE DR,FOSTER CITY,CA 94404, USA. FU NCRR NIH HHS [RR-37] NR 23 TC 107 Z9 116 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 1995 VL 39 IS 11 BP 2401 EP 2405 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA TD129 UT WOS:A1995TD12900006 PM 8585716 ER PT J AU OJWANG, JO BUCKHEIT, RW POMMIER, Y MAZUMDER, A DEVREESE, K ESTE, JA REYMEN, D PALLANSCH, LA LACKMANSMITH, C WALLACE, TL DECLERCQ, E MCGRATH, MS RANDO, RF AF OJWANG, JO BUCKHEIT, RW POMMIER, Y MAZUMDER, A DEVREESE, K ESTE, JA REYMEN, D PALLANSCH, LA LACKMANSMITH, C WALLACE, TL DECLERCQ, E MCGRATH, MS RANDO, RF TI T30177, AN OLIGONUCLEOTIDE STABILIZED BY AN INTRAMOLECULAR GUANOSINE OCTET, IS A POTENT INHIBITOR OF LABORATORY STRAINS AND CLINICAL ISOLATES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID REVERSE-TRANSCRIPTASE; INFECTED-CELLS; HIV-1 ENTRY; REPLICATION; DNA; PHOSPHOROTHIOATE; LYMPHOCYTES; ACTIVATION; MECHANISM; BETA AB T30177, an oligonucleotide composed of only deoxyguanosine and thymidine, is 17 nucleotides in length and contains single phosphorothioate internucleoside linkages at its 5' and 3' ends for stability, This oligonucleotide does not share significant primary sequence homology with or possess any complementary (antisense) sequence motifs to the human immunodeficiency virus type 1 (HIV-1) genome, T30177 inhibited replication of multiple laboratory strains of HIV-1 in human T-cell lines, peripheral blood lymphocytes, and macrophages. T30177 was also found to be capable of inhibiting multiple clinical isolates of HIV-1 and preventing the cytopathic effect of HIV-1 in primary CD4(+) T lymphocytes, In assays with human peripheral blood lmphocytes there was no observable toxicity associated with T30177 at the highest concentration tested (100 mu M), while the median inhibitory concentration was determined to be in the range of 0.1 to 1.0 mu M for the clinical isolates tested, resulting in a high therapeutic index for this drug. In temporal studies, the kinetics of addition of T30177 to infected cell cultures indicated that, like the known viral adsorption blocking agents dextran sulfate and Chicago sky blue, T30177 needed to be added to cells during or very soon after viral infection, However, analysis of nucleic acids extracted at 12 h postinfection from cells treated with T30177 at the time of virus infection established the presence of unintegrated viral cDNA, including circular proviral DNA, in the treated cells, In vitro analysis of viral enzymes revealed that T30177 was a potent inhibitor of HIV-1 integrase, reducing enzymatic activity by 50% at concentrations in the range of 0.050 to 0.09 mu M. T30177 was also able to inhibit viral reverse transcriptase activity; however, the 50% inhibitory value obtained was in the range of 1 to 10 mu M, depending on the template used in the enzymatic assay, No observable inhibition of viral protease was detected at the highest concentration of T30177 used (10 mu M). In experiments in which T30177 mas removed from infected cell cultures at 4 days post-HIV-1 infection, total suppression of virus production was observed for more than 27 days, PCR analysis of DNA extracted from cells treated in this fashion was unable to detect the presence of viral DNA 11 days after removal of the drug from the infected cell cultures, The ability of T30177 to inhibit both laboratory and clinical isolates of HIV-1 and the experimental data which suggest that T30177 represents a novel class of integrase inhibitors indicate that this compound is a viable candidate for evaluation as a therapeutic agent against HIV-1 in humans. C1 TRIPLEX PHARMACEUT CORP,THE WOODLANDS,TX 77380. FREDERICK RES CTR,FREDERICK,MD 21701. NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. KATHOLIEKE UNIV LEUVEN,REGA INST MED RES,B-3000 LOUVAIN,BELGIUM. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO GEN HOSP,DEPT LAB MED,SAN FRANCISCO,CA 94110. RI Este, Jose/B-5509-2008 OI Este, Jose/0000-0002-1436-5823 NR 43 TC 108 Z9 108 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 1995 VL 39 IS 11 BP 2426 EP 2435 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA TD129 UT WOS:A1995TD12900011 PM 8585721 ER PT J AU SHIRASAKA, T CHOKEKIJCHAI, S YAMADA, A GOSSELIN, G IMBACH, JL MITSUYA, H AF SHIRASAKA, T CHOKEKIJCHAI, S YAMADA, A GOSSELIN, G IMBACH, JL MITSUYA, H TI COMPARATIVE-ANALYSIS OF ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ACTIVITIES OF DIDEOXYNUCLEOSIDE ANALOGS IN RESTING AND ACTIVATED PERIPHERAL-BLOOD MONONUCLEAR-CELLS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID PRIMARY LYMPHOCYTES; INVITRO; PHOSPHORYLATION; DIDEOXYCYTIDINE; AZIDOTHYMIDINE; DIDEOXYINOSINE; LEUKEMIA; THERAPY; KINASE; CYCLE AB We determined the anti-human immunodeficiency virus type 1 (anti-HIV-1) activities of various dideoxynucleoside analogs by using phytohemagglutinin-activated peripheral blood mononuclear cells (PHA-PBMs) and resting PBMs (R-PBMs) as target cells. The comparative order of anti-HIV-1 activity in PHA-PBMs was azidothymidine (AZT) > dideoxycytidine (ddC) > dideoxythymidinene (d4T) > dideoxyinosine (ddI) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) > 2'-beta-fluoro-dideoxyadenosine (F-ara-ddA), while that in R-PBMs was ddC > ddI, PMEA, and F-ara-ddA, >> AZT and d4T. A pronucleotide, bis-(S-acetylthioethanol)phosphotriester-ddAMP, which bypasses the anabolic monophosphorylation step for the intracellular delivery of ddAMP, was highly active both in PHA-PBMs and R-PBMs. These data may have basic and clinical relevance in the design of anti-HIV chemotherapy, particularly combination chemotherapy with dideoxynocleosides, and in the development of active pronucleotides. C1 NCI,DIV CANC TREATMENT,MED BRANCH,EXPTL RETROVIROL SECT,BETHESDA,MD 20892. UNIV MONTPELLIER 2,CHIM BIOORGAN LAB,CNRS,URA 488,F-34095 MONTPELLIER,FRANCE. NR 21 TC 45 Z9 45 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 1995 VL 39 IS 11 BP 2555 EP 2559 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA TD129 UT WOS:A1995TD12900034 PM 8585744 ER PT J AU WONG, JP SARAVOLAC, EG SABUDA, D LEVY, HB KENDE, M AF WONG, JP SARAVOLAC, EG SABUDA, D LEVY, HB KENDE, M TI PROPHYLACTIC AND THERAPEUTIC EFFICACIES OF POLY(IC-CENTER-DOT-LC) AGAINST RESPIRATORY INFLUENZA-A VIRUS-INFECTION IN MICE SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID POLYRIBOCYTIDYLIC ACID COMPLEX; RHESUS-MONKEYS; INTERFERON; FEVER AB Polyriboinosinic-polyribocytidylic acid [poly(IC . LC)] was evaluated for its prophylactic and therapeutic efficacies against respiratory influenza A virus infection in mice. Two doses of poly(IC . LC) (1 mg/kg of body weight per dose) administered intranasally within 12 days prior to infection with 10 50% lethal doses of mouse-adapted influenza A/PR/8 virus fully protected the mice against the infection. Determination of virus titers by hemagglutination and plaque assays showed more than a 2-log(10) decrease in virus titers in lung homogenates of pretreated mice compared with those in the lungs of the nonpretreated group. Treatment of infected mice with poly(IC . LC) resulted in a modest (40%) survival rate. These results suggest that poly(IC . LC) provides a highly effective prophylaxis against respiratory influenza A virus infection in mice. C1 NIAID,BETHESDA,MD 20892. USA,MED RES INST INFECT DIS,FT DETRICK,MD 21702. RP WONG, JP (reprint author), DEF RES ESTAB SUFFIELD,MED COUNTERMEASURES SECT,BOX 4000,MEDICINE HAT,AB T1A 8K6,CANADA. NR 14 TC 42 Z9 44 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 1995 VL 39 IS 11 BP 2574 EP 2576 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA TD129 UT WOS:A1995TD12900039 PM 8585749 ER PT J AU HOLLINGSHEAD, M ROBERSON, J DECKER, W BUCKHEIT, R ELDER, C MALSPEIS, L MAYO, J GREVER, M AF HOLLINGSHEAD, M ROBERSON, J DECKER, W BUCKHEIT, R ELDER, C MALSPEIS, L MAYO, J GREVER, M TI IN-VIVO DRUG SCREENING APPLICATIONS OF HIV-INFECTED CELLS CULTIVATED WITHIN HOLLOW FIBERS IN 2 PHYSIOLOGICAL COMPARTMENTS OF MICE SO ANTIVIRAL RESEARCH LA English DT Article DE ANIMAL MODEL; HUMAN IMMUNODEFICIENCY VIRUS (HIV); HOLLOW FIBER ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE RETROVIRUSES; INVIVO; MOUSE; GROWTH AB Previous studies demonstrated that human cell lines can be cultivated in hollow fibers in the subcutaneous and intraperitoneal compartment of mice. We have extended the range of cell lines to include cells infected with the human immunodeficiency virus (HIV). Furthermore, these HIV-infected cells have been shown to replicate in the hollow fibers located in both physiologic compartments (intraperitoneal and subcutaneous) of SCID mice. Treatment of the host mice with antiviral agents can suppress virus replication in these hollow fiber cultures. The potential use of this system for early in vivo screening of anti-HIV compounds is discussed. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK,MD 21702. SO RES INST,FREDERICK RES CTR,FREDERICK,MD 21701. NCI,FAIRVIEW CTR,DCT,DTP,PHARMACEUT CHEM LAB,FREDERICK,MD 21701. JOHNS HOPKINS UNIV,DIV HEMATOL MALIGNANCIES ONCOL 3127,BALTIMORE,MD 21287. RP HOLLINGSHEAD, M (reprint author), NCI,FAIRVIEW CTR,DCT,DTP,BIOL TESTING BRANCH,SUITE 205,1003 W 7TH ST,FREDERICK,MD 21701, USA. NR 21 TC 19 Z9 20 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD NOV PY 1995 VL 28 IS 3 BP 265 EP 279 DI 10.1016/0166-3542(95)00055-Q PG 15 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA TE636 UT WOS:A1995TE63600006 PM 8629818 ER PT J AU DIGIOVANNA, JJ SOLLITTO, RB ABANGAN, DL STEINBERG, SM REYNOLDS, JC AF DIGIOVANNA, JJ SOLLITTO, RB ABANGAN, DL STEINBERG, SM REYNOLDS, JC TI OSTEOPOROSIS IS A TOXIC EFFECT OF LONG-TERM ETRETINATE THERAPY SO ARCHIVES OF DERMATOLOGY LA English DT Article ID SKELETAL TOXICITY; AXIAL SKELETON; HYPEROSTOSIS; ISOTRETINOIN; ICHTHYOSIS AB Background and Design: Osteoporosis has been observed with chronic hypervitaminosis A but has not been established as a toxic effect of synthetic retinoid therapy in humans. This cross-sectional study was designed to assess bone mineral density (BMD) during long-term therapy with the retinoids etretinate or isotretinoin. Twenty-four patients were evaluated for osteoporosis with the standard techniques: single- and dual-photon absorptiometry. They received 50 g or more of etretinate (15 patients) or isotretinoin (nine patients) for 2 years or longer for the treatment of skin diseases (ichthyosis [nine patients], Darier's disease [six patients], xeroderma pigmentosum [four patients], skin cancer [three patients], or psoriasis [two patients]), In each of the two treatment groups, BMDs (measured in grams per square centimeter) were measured at five standard sites tie, lumbar spine, femoral neck, trochanter, Ward's triangle, and radius) and evaluated against a standardized database to control for age, sex, and weight. In addition, for each measurement site, BMDs (controlled for age, sex, and weight) were compared between the two groups, as a direct control for each other. Observations: Compared with those of the age-, sex-, and weight-matched controls, the BMD values of the etretinate group were significantly decreased at four of the five measurement sites: femoral neck (90.6%, P = .0001), Ward's triangle (87.8%, P = .0001), trochanter (87.8%, P = .0012), and radius (85.0% P = .039). In contrast, the BMDs in the isotretinoin group did not differ from control values except for an elevation at the lumbar spine (P = .039). When the two groups were compared, the mean BMDs were significantly lower in the etretinate group when measured at the lumbar spine, trochanter, and radius (P < .05). Conclusions: This study identified osteoporosis in patients who received long-term therapy with etretinate but not isotretinoin. Prospective studies of BMD would be useful to further define retinoid-associated osteoporosis. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. KING DREW MED CTR,DEPT DERMATOL,LOS ANGELES,CA. NR 33 TC 69 Z9 69 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD NOV PY 1995 VL 131 IS 11 BP 1263 EP 1267 DI 10.1001/archderm.131.11.1263 PG 5 WC Dermatology SC Dermatology GA TD681 UT WOS:A1995TD68100003 PM 7503569 ER PT J AU GERSHON, ES AF GERSHON, ES TI ANTISOCIAL-BEHAVIOR SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article RP GERSHON, ES (reprint author), NIMH,INTRAMURAL RES PROGRAM,10 CTR DR,MSC 1274,BETHESDA,MD 20892, USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 1995 VL 52 IS 11 BP 900 EP 901 PG 2 WC Psychiatry SC Psychiatry GA TD682 UT WOS:A1995TD68200002 PM 7487338 ER PT J AU SCULLY, RE HENSON, DE NIELSEN, ML RUBY, SG AF SCULLY, RE HENSON, DE NIELSEN, ML RUBY, SG TI PRACTICE PROTOCOL FOR THE EXAMINATION OF SPECIMENS REMOVED FROM PATIENTS WITH OVARIAN-TUMORS - A BASIS FOR CHECKLISTS SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PROGNOSTIC-SIGNIFICANCE; CELL TUMORS; CANCER; BORDERLINE; CARCINOMA C1 NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,BETHESDA,MD 20892. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HINSDALE HOSP,DEPT PATHOL & LAB MED,HINSDALE,IL. NR 41 TC 11 Z9 11 U1 0 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD NOV PY 1995 VL 119 IS 11 BP 1012 EP 1022 PG 11 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA TF276 UT WOS:A1995TF27600011 PM 7487401 ER PT J AU Balls, M Goldberg, AM Fentem, JH Broadhead, CL Burch, RL Festing, MFW Frazier, JM Hendriksen, CFM Jennings, M vanderKamp, MDO Morton, DB Rowan, AN Russell, C Russell, WMS Spielmann, H Stephens, ML Stokes, WS Straughan, DW Yager, JD Zurlo, J vanZutphen, BFM AF Balls, M Goldberg, AM Fentem, JH Broadhead, CL Burch, RL Festing, MFW Frazier, JM Hendriksen, CFM Jennings, M vanderKamp, MDO Morton, DB Rowan, AN Russell, C Russell, WMS Spielmann, H Stephens, ML Stokes, WS Straughan, DW Yager, JD Zurlo, J vanZutphen, BFM TI The three Rs: The way forward - The report and recommendations of ECVAM workshop 11 SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Editorial Material ID ANIMAL USE; DATA-BANK; VALIDATION; ALTERNATIVES; GUIDELINES; REDUCTION; TESTS; PAIN C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CAAT,BALTIMORE,MD 21202. FRAME,NOTTINGHAM NG1 4EE,ENGLAND. UNIV LEICESTER,MRC,TOXICOL UNIT,LEICESTER LE1 9HN,LEICS,ENGLAND. MANTECH ENVIRONM TECHNOL INC,TOX HAZARDS RES UNIT,DAYTON,OH 45431. RIVM,3721 MA BILTHOVEN,NETHERLANDS. RSPCA,DEPT RES ANIM,HORSHAM RH12 1HG,W SUSSEX,ENGLAND. NCA,3584 CL UTRECHT,NETHERLANDS. UNIV BIRMINGHAM,SCH MED,DEPT BIOMED SCI & ETH,BIRMINGHAM B15 2TJ,W MIDLANDS,ENGLAND. TUFTS UNIV,SCH VET MED,CTR ANIM & PUBL POLICY,N GRAFTON,MA 01536. UNIV READING,DEPT SOCIOL,READING RG6 2AA,BERKS,ENGLAND. ZEBET,BGVV,D-12277 BERLIN,GERMANY. HUMANE SOC UNITED STATES,WASHINGTON,DC 20037. NIEHS,NTP,RES TRIANGLE PK,NC 27709. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DIV TOXICOL SCI,BALTIMORE,MD 21205. UNIV UTRECHT,FAC VET MED,DEPT LAB ANIM SCI,3508 TD UTRECHT,NETHERLANDS. RP Balls, M (reprint author), JRC ENVIRONM INST,ECVAM,TP 580,I-21020 ISPRA,ITALY. NR 111 TC 128 Z9 132 U1 3 U2 9 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM, NOTTS, ENGLAND NG1 4EE SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD NOV-DEC PY 1995 VL 23 IS 6 BP 838 EP 866 PG 29 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TM529 UT WOS:A1995TM52900016 PM 11660368 ER PT J AU MASUR, H AF MASUR, H TI ALGORITHMIC APPROACH TO TREATMENT SO BAILLIERES CLINICAL INFECTIOUS DISEASES LA English DT Review ID PNEUMOCYSTIS-CARINII PNEUMONIA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HIV-INFECTED PATIENTS; TRIMETHOPRIM-SULFAMETHOXAZOLE; CONTROLLED TRIAL; AEROSOLIZED PENTAMIDINE; CLINDAMYCIN PRIMAQUINE; BRONCHOALVEOLAR LAVAGE; ADJUNCTIVE THERAPY; PROGNOSTIC FACTORS RP MASUR, H (reprint author), NIH,DEPT CRIT CARE MED,CLIN CTR BLDG 10,RM 7D-43,9000 ROCKVILLE PIKE BLV,BETHESDA,MD 20892, USA. NR 101 TC 2 Z9 2 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1071-6564 J9 BAILLIERE CLIN INF D JI Baillieres Clin. Infect. Dis. PD NOV PY 1995 VL 2 IS 3 BP 531 EP 549 PG 19 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TH397 UT WOS:A1995TH39700010 ER PT J AU MATHIS, C NEUMANN, PE GERSHENFELD, H PAUL, SM CRAWLEY, JN AF MATHIS, C NEUMANN, PE GERSHENFELD, H PAUL, SM CRAWLEY, JN TI GENETIC-ANALYSIS OF ANXIETY-RELATED BEHAVIORS AND RESPONSES TO BENZODIAZEPINE-RELATED DRUGS IN AXB AND BXA RECOMBINANT INBRED MOUSE STRAINS SO BEHAVIOR GENETICS LA English DT Article DE GENE MAPPING; ANXIETY; BETA-CARBOLINE; RECOMBINANT INBRED; EXPLORATORY ACTIVITY; SEIZURE; GAMMA-AMINOBUTYRIC ACID; BENZODIAZEPINE ID EXPLORATORY ACTIVITY; INDUCED SEIZURES; BETA-CARBOLINE; MICE; SUSCEPTIBILITY; DIAZEPAM; SENSITIVITY; C57BL-6J; BRAIN; MODEL AB Recombinant inbred (RI) strains derived from the C57BL/6J and A/J mouse strains were used for behavioral studies designed to estimate the number and location of chromosomal loci responsible for anxiety-related behaviors and differential sensitivity to agonists and inverse agonists of the gamma-aminobutyric acid(A) (GABA(A))/benzodiazepine receptor complex. The phenotypes of the parental inbred strains and of 28 Rl strains were characterized for the number of transitions in the light = dark exploratory model, anxiolytic response to diazepam, vertical and ambulatory activities in an open field, and sensitivity to the convulsant properties of methyl-beta-carboline-3-carboxylate (beta-CCM). The strain distribution patterns and estimates of the minimal number of loci obtained for each trait suggest that multiple chromosomal loci contribute to differences in anxiety-related behavioral phenotypes and the behavioral responses to diazepam and beta-CCM between C57BL/6J and A/J mice. The best probabilities of linkage were found between the variables characterizing response to diazepam and loci on chromosomes 1 (Xmv-41) and 10 (D10Mit2) and between the sensitivity to the convulsant actions of beta-CCM and locus D15Mit5 on chromosome 15. C1 NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL SECT,BETHESDA,MD 20892. DALHOUSIE UNIV,DEPT ANAT & NEUROBIOL,HALIFAX,NS B3H 4H7,CANADA. DALHOUSIE UNIV,DEPT PATHOL,DIV MOLEC PATHOL & MOLEC GENET,HALIFAX,NS B3H 4H7,CANADA. NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. RP MATHIS, C (reprint author), UNIV STRASBOURG 1,PSYCHOPHYSIOL LAB,CNRS,URA 1295,7 RUE UNIV,F-67000 STRASBOURG,FRANCE. RI MATHIS, CHANTAL/B-6399-2013 NR 56 TC 76 Z9 77 U1 0 U2 4 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 1995 VL 25 IS 6 BP 557 EP 568 DI 10.1007/BF02327579 PG 12 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA TC667 UT WOS:A1995TC66700006 PM 8540894 ER PT J AU SHEKELS, LL LYFTOGT, C KIELISZEWSKI, M FILIE, JD KOZAK, CA HO, SB AF SHEKELS, LL LYFTOGT, C KIELISZEWSKI, M FILIE, JD KOZAK, CA HO, SB TI MOUSE GASTRIC MUCIN - CLONING AND CHROMOSOMAL LOCALIZATION SO BIOCHEMICAL JOURNAL LA English DT Article ID MOLECULAR-CLONING; INTESTINAL MUCIN; O-GLYCOSYLATION; GENE-EXPRESSION; CDNA; RAT; ANTIBODIES; SEQUENCE; PROTEINS; GLYCOPROTEINS AB Mucins protect gastric epithelium by maintaining a favourable pH gradient and preventing autodigestion. The purpose of this study was to clone a mouse gastric mucin which would provide a foundation for analysis of mucin gene regulation. Mucin was purified from the glandular portion of gastric specimens and deglycosylated by HF solvolysis. Antibodies against native and deglycosylated mouse gastric mucin (MGM) were raised in chickens. Screening of a mouse stomach cDNA library with the anti-(deglycosylated MGM) antibody yielded partial clones containing a 48 bp tandem repeat and 768 bp of non-repetitive sequence. The 16-amino-acid tandem repeat has a consensus sequence of QTSSPNTGKTSTISTT with 25 % serine and 38 % threonine, The MGM tandem repeat sequence bears no similarity to previously identified mucins. The MGM non-repetitive region shares sequence similarity with human MUC5AC and, to a lesser extent, human MUC2 and rat intestinal mucin. Northern blot analysis reveals a polydisperse message beginning at 13.5 kb in mouse stomach with no expression in oesophagus, trachea, small intestine, large intestine, caecum, lung or kidney. Immunoreactivity of antibodies against deglycosylated MGM and against a synthetic MGM tandem repeat peptide was restricted to superficial mucous cells, antral glands and Brunner's glands in the pyloric-duodenal region. DNA analysis shows that MGM recognizes mouse and rat DNA but not hamster, rabbit or human DNA. The MGM gene maps to a site on mouse chromosome 7 homologous to the location of a human secretory mucin gene cluster on human chromosome 11p15. Due to sequence similarity and predominant expression in the stomach, the MGM gene may be considered a MUC5AC homologue and named Muc5ac. C1 VET ADM MED CTR,DEPT GASTROENTEROL 111D,MINNEAPOLIS,MN 55417. UNIV MINNESOTA,DEPT MED,MINNEAPOLIS,MN 55417. UNIV GEORGIA,COMPLEX CARBOHYDRATE RES CTR,ATHENS,GA 30602. NIH,BETHESDA,MD 20892. NR 59 TC 73 Z9 73 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 1 PY 1995 VL 311 BP 775 EP 785 PN 3 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TC563 UT WOS:A1995TC56300011 PM 7487932 ER PT J AU KOLE, HK SMYTH, MS RUSS, PL BURKE, TR AF KOLE, HK SMYTH, MS RUSS, PL BURKE, TR TI PHOSPHONATE INHIBITORS OF PROTEIN-TYROSINE AND SERINE THREONINE PHOSPHATASES SO BIOCHEMICAL JOURNAL LA English DT Article ID SKELETAL-MUSCLE; DIABETIC RATS; PHOSPHOTYROSINE; ACIDS; ACTIVATION; KINASES; TISSUES; ANALOGS AB In all, 15 aryl-containing phosphonates have been synthesized and tested for their effect on protein-tyrosine phosphatase (PTPase) activity. Two compounds, (naphth-2-yl) difluoroeffect on insulin-receptor autophosphorylation. Nine out of the 15 compounds potently inhibited serine/threonine phosphatase PP-2A activity without any effect on serine/threonine phosphatase PP-1 when tested at a concentration as high as 675 mu M. The most potent compounds acting toward PP-2A had IC,, values of 45-50 mu M. These PP-2A inhibitors could be useful tools for studying serine/threonine-phosphatase-mediated signal transduction. Two compounds, 12 and 13, inhibited both tyrosine phosphatase PTP-1B and serine/threonine phosphatase PP-2A with similar potency; IC50 values being 40-50 mu M in both cases. Details of the synthesis of compounds 10, 11 and 13 are given in Supplementary Publication SUP 50177 (6 pages), which has been deposited at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1995) 305, 9.methylphosphonic acid (12) and (napthy-1-yl) difluormethylphosphonic acid (13) have been found to inhibit dephosphorylation of [P-32]insulin receptors by PTP-1B, a protein tyrosine phosphatase (PTPase), with IC50 values of 40-50 mu M. Compound 12 competitively inhibited insulin-receptor dephosphorylation by PTP-B. Compound 12 also inhibited PTP-1B-catalysed dephosphorylation of a synthetic tyrosine phosphorylated substrate poly(Glu(80)-Tyr(20)) at the same potency, indicating that 12 acted via interaction with the PTPase. Additionally, 12 inhibited insulin-receptor PTPase(s) and epridermal-growth-factor-receptor PTPase(s) present in solubilized membranes from CHO (Chinese-hamster ovary)/HIRc and A431 cells respectively. IC50 values of 40-50 mu M were obtained in all cases with compound 12. Of note is the fact that these compounds did not have any C1 NCI,MED CHEM LAB,DEV THERAPEUT PROGRAM,DCT,BETHESDA,MD 20892. NIA,CLIN PHYSIOL LAB,DIABET UNIT,BALTIMORE,MD 21224. RI Burke, Terrence/N-2601-2014 NR 51 TC 71 Z9 74 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 NOV 1 PY 1995 VL 311 BP 1025 EP 1031 PN 3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TC563 UT WOS:A1995TC56300046 PM 7487920 ER PT J AU Couse, JF Curtis, SW Washburn, TF Eddy, EM Schomberg, DW Korach, KS AF Couse, JF Curtis, SW Washburn, TF Eddy, EM Schomberg, DW Korach, KS TI Disruption of the mouse oestrogen receptor gene: Resulting phenotypes and experimental findings SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 655th Meeting of the Biochemical-Society CY JUL 18-21, 1995 CL MANCHESTER, ENGLAND SP Biochem Soc ID EPIDERMAL GROWTH-FACTOR; ESTROGEN-RECEPTOR; PROGESTERONE-RECEPTOR; UTERUS; EXPRESSION; CELLS; LACTOTRANSFERRIN; ORGANIZATION; STIMULATION; PROTEIN C1 NATL INST ENVIRONM HLTH SCI, RECEPTOR BIOL SECT, RES TRIANGLE PK, NC 27709 USA. NATL INST ENVIRONM HLTH SCI, REPROD & DEV TOXICOL LAB, GAMETE BIOL SECT, RES TRIANGLE PK, NC 27709 USA. DUKE UNIV, MED CTR, DEPT OBSTET & GYNECOL, DURHAM, NC 27710 USA. DUKE UNIV, MED CTR, DEPT CELL BIOL, DURHAM, NC 27710 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 46 TC 45 Z9 45 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD NOV PY 1995 VL 23 IS 4 BP 929 EP 935 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TH865 UT WOS:A1995TH86500048 PM 8654869 ER PT J AU ElMohandes, AAE Rivas, RA Kiang, E Wahl, LM Katona, IM AF ElMohandes, AAE Rivas, RA Kiang, E Wahl, LM Katona, IM TI Membrane antigen and ligand receptor expression on neonatal monocytes SO BIOLOGY OF THE NEONATE LA English DT Article DE cord blood monocytes; membrane antigens; membrane receptors; flow microfluorometry; host defense ID PERIPHERAL-BLOOD MONOCYTES; FC-RECEPTORS; MONOCLONAL-ANTIBODIES; T-CELLS; INTERLEUKIN-2 RECEPTORS; MONONUCLEAR PHAGOCYTES; MACROPHAGES; INFECTION; SURFACE; CD4 AB The monocyte/macrophage cell lineage is an essential component of host defense. Functional deficiencies have been described in neonatal monocytes, but knowledge of membrane antigen and receptor ligand expression in neonatal monocytes is incomplete. In this study, antigen and receptor ligand expression of cord blood monocytes (CBM) was examined and compared to adult peripheral blood monocytes (PBM). Leu-M3 and Leu-M5 antigens were shown to be present on all CBM. Using dual fluorescence microfluorometry, the percentage and intensity of expression of HLA-DR, CD4 antigens, Fc gamma and IL-2 receptors (IL-2R) on Leu-M3(+) and Leu-M5(+) CBM were compared to PBM. A lower percentage of expression of HLA-DR(+) (87 +/- 3% vs, 95 +/- 1%, p = 0.02) and FC gamma RII(+) (96 +/- 1% vs. 99 +/- 0.2%, p = 0.04) was noted on CBM. CD4, FC gamma RI, and FC gamma RIII expression on CBM were comparable to PBM. LPS stimulation of CBM induced IL-2R expression and enhanced HLA-DR antigen expression as seen previously on PBM. These findings indicate that CBM are phenotypically comparable to adult PBM with deficiencies localized only to a few specific areas. C1 GEORGE WASHINGTON UNIV,MED CTR,NEWBORN SERV,WASHINGTON,DC 20037. UNIFORMED SERV UNIV HLTH SCI,F EDWARD HERBERT SCH MED,DEPT PEDIAT & MED,BETHESDA,MD 20814. NIDR,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. NR 42 TC 8 Z9 8 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0006-3126 J9 BIOL NEONATE JI Biol. Neonate PD NOV PY 1995 VL 68 IS 5 BP 308 EP 317 PG 10 WC Pediatrics SC Pediatrics GA TP636 UT WOS:A1995TP63600002 PM 8835085 ER PT J AU AgmonSnir, H AF AgmonSnir, H TI A novel theoretical approach to the analysis of dendritic transients SO BIOPHYSICAL JOURNAL LA English DT Article ID SIGNAL DELAY; NEURON MODEL; ARBITRARY GEOMETRY; CABLE PROPERTIES; SOMATIC SHUNT; ONE BRANCH; TREES; MOTONEURONS; POTENTIALS; SYNAPSES AB A novel theoretical framework for analyzing dendritic transients is introduced. This approach, called the method of moments, is an extension of Rall's cable theory for dendrites, It provides analytic investigation of voltage attenuation, signal delay, and synchronization problems in passive dendritic trees. In this method, the various moments of a transient signal are used to characterize the properties of the transient. The strength of the signal is measured by the time integral of the signal, its characteristic time is determined by its centroid (''center of gravity''), and the width of the signal is determined by a measure similar to the standard deviation in probability theory. Using these signal properties, the method of moments provides theorems, expressions, and efficient algorithms for analyzing the voltage response in arbitrary passive trees. The method yields new insights into spatiotemporal integration, coincidence detection mechanisms, and the properties of local interactions between synaptic inputs in dendritic trees. The method can also be used for matching dendritic neuron models to experimental data and for the analysis of synaptic inputs recorded experimentally. C1 HEBREW UNIV JERUSALEM, INST LIFE SCI, DEPT NEUROBIOL, IL-91904 JERUSALEM, ISRAEL. RP AgmonSnir, H (reprint author), NIDDK, NIH,MATH RES BRANCH,BSA,9190 WISCONSIN AVE, SUITE 350, BETHESDA, MD 20814 USA. NR 61 TC 14 Z9 14 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1995 VL 69 IS 5 BP 1633 EP 1656 PG 24 WC Biophysics SC Biophysics GA TV017 UT WOS:A1995TV01700002 PM 8580308 ER PT J AU Clay, JR AF Clay, JR TI Asymmetric modulation and blockade of the delayed rectifier in squid giant axons by divalent cations SO BIOPHYSICAL JOURNAL LA English DT Article ID POTASSIUM CHANNELS; SODIUM-CHANNELS; SURFACE-CHARGE; CALCIUM-IONS; K+ CHANNEL; INACTIVATION; KINETICS; BILAYERS AB The effects of intracellular magnesium ions and extracellular calcium and magnesium ions on the delayed rectifier potassium ion channel, I-K, were investigated from intracellularly perfused squid giant axons, Ca-o(+2) and Mg-o(+2) both blocked I-K in a voltage-independent manner with a K-D of similar to 100 and 500 mM, respectively. This effect was obscured at potentials in the vicinity of the resting potential (similar to-60 mV) by a rightward shift of the steady-state I-K inactivation curve along the voltage axis. The addition of either calcium or magnesium ions to the extracellular solution also produced the well known shift of the I-K activation curve along the voltage axis, Ca-o(+2) was approximately twice as effective in this regard as Mg-o(+2). The I-K activation kinetics were slowed by Ca-o(+2), but deactivation kinetics were not altered, as shown previously. Similar results were obtained with Mg-o(+2). The addition of magnesium ions to the intracellular perfusate shifted the activation curve along the voltage axis in the negative direction (without producing block) by approximately the same among as the Mg-o(+2) shift of this curve in the positive direction. Moreover, Mg-i(+2) substantially slowed the deactivation kinetics, whereas the effects of Mg-i(+2) on activation kinetics at strongly depolarized potentials were relatively minor. At modest depolarizations, Mg-i(+2) significantly reduced the delay before I-K activation. These results are essentially the mirror image of the effects on gating of extracellular divalent cations. C1 MARINE BIOL LAB,WOODS HOLE,MA 02543. RP Clay, JR (reprint author), NINCDS,NIH,NEUROPHYSIOL LAB,BLDG 36,ROOM 2C02,BETHESDA,MD 20892, USA. NR 25 TC 5 Z9 5 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1995 VL 69 IS 5 BP 1773 EP 1779 PG 7 WC Biophysics SC Biophysics GA TV017 UT WOS:A1995TV01700014 PM 8580320 ER PT J AU London, RE Gabel, SA AF London, RE Gabel, SA TI Fluorine-19 NMR studies of glucosyl fluoride transport in human erythrocytes SO BIOPHYSICAL JOURNAL LA English DT Article ID MAGNETIZATION TRANSFER; SELECTIVE INVERSION; EXCHANGE; F-19-NMR; SYSTEM AB Fluorine-19 magnetization transfer studies have been used to measure the transport rate of glucopyranosyl fluorides under equilibrium exchange conditions. Although rate constants and permeabilities could be determined for beta-D-glucopyranosyl fluoride, the exchange rate for alpha-D-glucopyranosyl fluoride was found to be too slow for determination using this method. The time-dependent decomposition of the beta-glucopyranosyl fluoride also limits the accuracy of the numerical results for this species; however, it is clear that the permeabilities of the alpha and beta forms differ significantly, i.e., P-beta > P-alpha. This observation is in contrast to recent observations for n-fluoro-n-deoxyglucose, for which P-alpha > P-beta for n = 2, 3, 4, or 6. The difference can be explained in terms of a simple alternating conformation model in which one of the conformations (with an external sugar-binding site) exhibits a preference for the beta form of the molecule, while the second conformation (with an internal sugar binding site) exhibits a preference for the alpha form. Fluorine/hydroxyl substitutions unmask these preferences by selectively reducing the binding to one of the conformations, depending on the specific site of fluorination. RP London, RE (reprint author), NIEHS,MOLEC BIOPHYS LAB,MD 17-05,BOX 12233,RES TRIANGLE PK,NC 27709, USA. NR 15 TC 11 Z9 11 U1 0 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1995 VL 69 IS 5 BP 1814 EP 1818 PG 5 WC Biophysics SC Biophysics GA TV017 UT WOS:A1995TV01700018 PM 8580324 ER PT J AU Clay, JR Ogbaghebriel, A Paquette, T Sasyniuk, BI Shrier, A AF Clay, JR Ogbaghebriel, A Paquette, T Sasyniuk, BI Shrier, A TI A quantitative description of the E-4031-sensitive repolarization current in rabbit ventricular myocytes SO BIOPHYSICAL JOURNAL LA English DT Article ID RECTIFIER K+-CURRENT; TRANSIENT OUTWARD CURRENT; DELAYED RECTIFIER; POTASSIUM CURRENT; DEPENDENT BLOCK; GUINEA-PIG; CELLS; HEART; MEMBRANE; CHANNELS AB We have measured the E-4031-sensitive repolarization current (I-Kr) in single ventricular myocytes isolated from rabbit hearts. The primary goal of this analysis was a description of the I-Kr kinetic and ion transfer properties. Surprisingly, the maximum time constant of this component was 0.8 s at 33-34 degrees C, which is significantly greater than the value of 0.18 s previously reported under similar conditions in the original measurements of I-Kr from guinea pig ventricular myocytes. The primary, novel feature of our analysis concerns the relationship of the bell-shaped curve that describes the voltage dependence of the kinetics and the sigmoidal curve that describes the activation of I-Kr. The midpoint of the latter occurred at approximately +10 mV on the voltage axis, as compared to -30 mV for the point on the voltage axis at which the maximum time constant occurred. Moreover, the voltage dependence of the kinetics was much broader than the steepness of the activation curve would predict. Taken together, these results comprise a gating current paradox that is not resolved by the incorporation of a fast inactivated state in the analysis. The fully activated current-voltage relation for I-Kr exhibited strong inward-going rectification, so much so that the current was essentially nil at +30 mV, even though the channel opens rapidly in this voltage range. This result is consistent with the lack of effect of E-4031 on the early part of the plateau phase of the action potential. Surprisingly, the reversal potential of I-Kr was similar to 15 mV positive to the potassium ion equilibrium potential, which indicates that this channel carries inward current during the latter part of the repolarization phase of the action potential. C1 NINCDS,NIH,NEUROPHYSIOL LAB,BETHESDA,MD 20897. MCGILL UNIV,DEPT PHYSIOL,MONTREAL,PQ H3G 1Y6,CANADA. MCGILL UNIV,DEPT PHARMACOL,MONTREAL,PQ H3G 1Y6,CANADA. NR 34 TC 42 Z9 42 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1995 VL 69 IS 5 BP 1830 EP 1837 PG 8 WC Biophysics SC Biophysics GA TV017 UT WOS:A1995TV01700020 PM 8580326 ER PT J AU Jacot, JL Glover, JP Robison, WG AF Jacot, JL Glover, JP Robison, WG TI Improved gold chloride procedure for nerve staining in whole mounts of rat corneas SO BIOTECHNIC & HISTOCHEMISTRY LA English DT Article DE cornea; innervation; whole mount; gold chloride; Descemet's membrane endothelium complex; rat ID REGENERATION; INNERVATION; EPITHELIUM; CAPSAICIN; BIRTH AB The purpose of this study was to modify the gold chloride procedure for studies of total innervation in corneal whole mounts to provide a decrease in nonspecific background staining and to eliminate the progressively deteriorating stain quality of standard gold chloride techniques, Modifications included use of cryoprotective agents, mechanical removal of Descemet's membrane-endothelium complex prior to fixation, treatment with alpha amylase, and halting the reduction of gold chloride to metallic gold using Kodak rapid fixer with hardener. Rat corneas were stored at -70 C in O.C.T. compound. The Descemet's membrane-endothelium complex was removed after thawing, and corneas were fixed in 4% NaPO4-buffered paraformaldehyde with 8% sucrose. Fixed corneas were incubated in NaPO4-buffered saline containing alpha amylase, placed in 100% lemon juice, then in 1% gold chloride solution, transferred to glacial acidic acid, placed in rapid fixer, rinsed in NaPO4-buffered saline, and dehydrated in graded alcohols, Flat mounts of whole corneas were examined using contralateral corneas as controls. Freezing corneas in O.C.T. compound, removal of the Descemet's membrane-endothelium complex, and treatment with alpha amylase reduced nonspecific background staining compared to controls, Treatment with Kodak rapid fixer prevented the deterioration of staining quality for at least 8 months, These improvements allow the gold chloride technique to be used with immunohistochemical procedures where the reaction products would be obscured by background staining. RP Jacot, JL (reprint author), NEI,PATHOPHYSIOL SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 23 TC 2 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1052-0295 J9 BIOTECH HISTOCHEM JI Biotech. Histochem. PD NOV PY 1995 VL 70 IS 6 BP 277 EP 284 DI 10.3109/10520299509108333 PG 8 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA TN423 UT WOS:A1995TN42300001 PM 9044655 ER PT J AU SATO, T SELLERI, C YOUNG, NS MACIEJEWSKI, JP AF SATO, T SELLERI, C YOUNG, NS MACIEJEWSKI, JP TI HEMATOPOIETIC INHIBITION BY INTERFERON-GAMMA IS PARTIALLY MEDIATED THROUGH INTERFERON REGULATORY FACTOR-I SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; SEQUENCE-BINDING-PROTEIN; NF-KAPPA-B; BONE-MARROW; FACTOR-I; MYELODYSPLASTIC SYNDROMES; ANTIGENIC ANALYSIS; PROGENITOR CELLS; INDUCIBLE GENES; APLASTIC-ANEMIA AB Biologic responses to cytokines are mediated by intracellular pathways involving induction of signaling and metabolic cascades. Interferon (IFN) regulatory factor-1 (IRF-1) is a major transcription factor induced not only by IFN-gamma but also by other cytokines including tumor necrosis factor-alpha (TNF-alpha). Possible IRF-1 binding sequence elements have been located in the promoter regions of several genes, including p53, inducible nitric oxide synthase, and cyclin D1. IFN-gamma and TNF-alpha can inhibit hematopoiesis in vitro and have been implicated in the pathophysiology of bone marrow (BM) failure. We investigated whether the inhibitory effects of these cytokines were intracellularly mediated through the expression of IRF-1 or -2 in target cells. In total BM cells, IRF-1 mRNA expression increased after stimulation with IFN-gamma and TNF-alpha; the stronger effect was observed with IFN-gamma. In contrast, IRF-2 mRNA expression was constitutive and not altered by cytokine stimulation. By gene amplification, low levels of IRF-1 mRNA were present in unstimulated, highly purified CD34(+) cells; on exposure to IFN-gamma and TNF-alpha, amplified IRF-1 mRNA showed a much stronger signal than control. When CD34(+) cells were treated with IFN-gamma and TNF-alpha, IRF-1 antisense oligodeoxynucleotide (ODN) partially reversed the suppressive effects on CD34(+) cell-derived colony formation by IFN-gamma but not those by TNF-alpha. In parallel experiments, IRF-1 antisense ODN decreased both IRF-1 protein and mRNA expression, The effects of ODN were sequence-specific and concentration-dependent. These results suggest that the inhibitory hematopoietic effects of IFN-gamma and TNF-alpha are mediated by different pathways. For IFN-gamma, IRF-1 is involved in the activation of cellular genes responsible for IFN-gamma suppressive effects. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 54 TC 44 Z9 45 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 NOV 1 PY 1995 VL 86 IS 9 BP 3373 EP 3380 PG 8 WC Hematology SC Hematology GA TB163 UT WOS:A1995TB16300013 PM 7579440 ER PT J AU IWAMA, A WANG, MH YAMAGUCHI, N OHNO, N OKANO, K SUDO, T TAKEYA, M GERVAIS, F MORISSETTE, C LEONARD, EJ SUDA, T AF IWAMA, A WANG, MH YAMAGUCHI, N OHNO, N OKANO, K SUDO, T TAKEYA, M GERVAIS, F MORISSETTE, C LEONARD, EJ SUDA, T TI TERMINAL DIFFERENTIATION OF MURINE RESIDENT PERITONEAL-MACROPHAGES IS CHARACTERIZED BY EXPRESSION OF THE STK PROTEIN-TYROSINE KINASE, A RECEPTOR FOR MACROPHAGE-STIMULATING PROTEIN SO BLOOD LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; OSTEOPETROTIC OP/OP MOUSE; GENE; IDENTIFICATION; FAMILY AB STK, a new member of the hepatocyte growth factor receptor family, is the receptor for macrophage-stimulating protein (MSP), which acts on murine resident peritoneal macrophages. We established polyclonal and monoclonal antibodies against STK and characterized the structure of STK protein and STK expression on cells of the mononuclear phagocyte system, Western blotting showed that the STK transcript is translated into a single-chain precursor and then cleaved into a 165-kD disulfide-linked heterodimer composed of a 35-kD alpha-chain and a 144-kD beta-chain. Western blotting detected STK protein on resident peritoneal macrophages, a target of MSP, and showed that it was autophosphorylated in cells stimulated by MSP. By flow cytometric analysis using a monoclonal anti-STK antibody, we showed that STK protein is expressed on restricted macrophage populations such as resident peritoneal macrophages, but not on exudate peritoneal macrophages or mononuclear phagocytes of the bone marrow, peripheral blood, spleen, or alveoli. Resident peritoneal macrophages were classified into two fractions according to their reactivity with an anti-STK antibody and a marker antibody for macrophages: STKhigh-F4/80(high) cells and STKnegative-F4/80(low) cells. Acute exudative macrophages were all STKnegative-F4/80(low), but they gradually became predominantly STKhigh-F4/80(high) several days after entrance into the peritoneal cavity. These results showed that after monocytes migrate into the peritoneal cavity, they undergo terminal differentiation in the peritoneal microenvironment, This is the first evidence of tissue-specific terminal differentiation of peritoneal macrophages, and this terminal differentiation can be characterized by the expression of STK receptor tyrosine kinase. (C) 1995 by The American Society of Hematology. C1 KUMAMOTO UNIV,SCH MED,INST MOLEC EMBRYOL & GENET,DEPT CELL DIFFERENTIAT,KUMAMOTO 860,JAPAN. KUMAMOTO UNIV,SCH MED,DEPT PATHOL 2,KUMAMOTO 860,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21701. TORAY INDUSTRIES LTD,BASIC RES LABS,KAMAKURA,KANAGAWA,JAPAN. MONTREAL GEN HOSP,CTR STUDY HOST RESISTANCE,MONTREAL,PQ H3G 1A4,CANADA. RI Suda, Toshio/H-6761-2013 OI Suda, Toshio/0000-0001-7540-1771 NR 34 TC 81 Z9 82 U1 1 U2 2 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 NOV 1 PY 1995 VL 86 IS 9 BP 3394 EP 3403 PG 10 WC Hematology SC Hematology GA TB163 UT WOS:A1995TB16300016 PM 7579443 ER PT J AU PATTERSONBUCKENDAHL, P KVETNANSKY, R FUKUHARA, K CIZZA, G CANN, C AF PATTERSONBUCKENDAHL, P KVETNANSKY, R FUKUHARA, K CIZZA, G CANN, C TI REGULATION OF PLASMA OSTEOCALCIN BY CORTICOSTERONE AND NOREPINEPHRINE DURING RESTRAINT STRESS SO BONE LA English DT Article DE OSTEOCALCIN; OSTEOBLAST FUNCTION; CORTICOSTERONE; NOREPINEPHRINE; HOMEOSTASIS; IMMOBILIZATION; MENTAL STRESS; SYMPATHETIC NEURAL HORMONES ID PARAVENTRICULAR NUCLEUS; IMMOBILIZATION STRESS; BONE; PROTEIN; RATS; CATECHOLAMINES; SERUM; 3,4-DIHYDROXYPHENYLALANINE; RESPONSES; WARFARIN AB Osteocalcin (OC), an extracellular calcium-binding protein of bone origin, is synthesized by osteoblasts and binds with high specificity to bone mineral crystals, A small, but relatively consistent portion of newly synthesized OC which is released to circulation has been well correlated with histological indices of osteoblastic activity, Synthesis of OC is regulated by numerous hormones including glucocorticoids. We previously reported that mild mental stressors such as cage change or cold exposure decreased rat plasma OC by up to 40% within 1 h. A similar response was induced in a time-and dose-related manner by injection of physiological levels of corticosterone (CS), the active glucocorticoid in rats, Prone immobilization by foot restraint of conscious rats for up to 2 h (IMMO) is a well-characterized model of classic ''fight-or-flight'' response, This model induces an immediate and prolonged elevation of CS, as well as the catecholamines epinephrine (E) and norepinephrine (NE), In marked contrast to milder stressors, immobilization induced an immediate increase of plasma OC, greater than 50% within 5-20 min, which returned toward normal after 2 h of restraint, Selective ablation of the hormones by adrenal medulectomy, adrenalectomy, or blockade of sympathetic ganglia did not abolish the initial rapid rise of plasma OC, Even before IMMO, plasma OC was increased by about 50% in the absence of sympathetic neural function or adrenal CS production, The presence of both CS and NE, but not E, was required to return plasma OC concentrations to basal levels, This strongly suggests interaction of CS and NE to regulate plasma OC and its release from bone, As expected, prior cold exposure lowered plasma OC, but did not abolish a subsequent increase in response to IMMO, nor did IMMO repeated daily for 7 days, The stimulus for the initial rapid elevation of OC is unknown, but likely to be of importance in the role OC plays in response to stress, Further investigation of the OC under mental stress should help to understand the function of this abundant and highly conserved bone protein. C1 SLOVAK ACAD SCI,INST EXPTL ENDOCRINOL,BRATISLAVA,SLOVAKIA. NINCDS,BETHESDA,MD 20892. NIMH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT RADIOL,SAN FRANCISCO,CA 94143. RP PATTERSONBUCKENDAHL, P (reprint author), RICHARD STOCKTON COLL,DIV NAT SCI & MATH,POMONA,NJ 08240, USA. NR 32 TC 21 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 8756-3282 J9 BONE JI Bone PD NOV PY 1995 VL 17 IS 5 BP 467 EP 472 DI 10.1016/8756-3282(95)00281-X PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TE424 UT WOS:A1995TE42400005 PM 8579958 ER PT J AU GRALNICK, HR VAIL, M MCKEOWN, LP MERRYMAN, P WILSON, O CHU, I KIMBALL, J AF GRALNICK, HR VAIL, M MCKEOWN, LP MERRYMAN, P WILSON, O CHU, I KIMBALL, J TI ACTIVATED PLATELETS IN PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE HEMOLYSIS; COMPLEMENT; CELL ACTIVATION; THROMBOSIS ID COMPLEMENT PROTEINS C5B-9; GLYCOPROTEIN-IIB-IIIA; BUDD-CHIARI SYNDROME; PLASMINOGEN-ACTIVATOR; PROCOAGULANT ACTIVITY; VONWILLEBRAND-FACTOR; ADHERENT PLATELETS; VENOUS THROMBOSIS; HEMOGLOBINURIA; RECEPTOR AB One of the major causes of morbidity and mortality in paroxysmal nocturnal haemoglobinuria (PNH) is venous thrombosis. We have studied fibrinolysis, coagulation and platelets in 11 patients with PNH in an attempt to identify the possible mechanism(s) of thrombosis in PNH. In this study we did not identify any fibrinolytic defects, evidence of coagulation activation, nor reduction in coagulation inhibitors. In contrast, in this cohort of 11 PNH patients we have identified varying degrees of platelet activation as defined by the surface expression of activation-dependent proteins and the binding of adhesive proteins to the platelet surface. The thrombotic events in PNH usually occur in the venous system. Our studies and previous experimental studies suggest that anti-platelet therapy may be efficacious in reducing the incidence and severity of venous thrombosis in PNH. RP GRALNICK, HR (reprint author), NCI,CTR CLIN,SERV HEMATOL,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2C390,BETHESDA,MD 20892, USA. NR 38 TC 62 Z9 66 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 1995 VL 91 IS 3 BP 697 EP 702 DI 10.1111/j.1365-2141.1995.tb05371.x PG 6 WC Hematology SC Hematology GA TD204 UT WOS:A1995TD20400029 PM 8555078 ER PT J AU HENRIKSEN, TB HEDEGAARD, M SECHER, NJ WILCOX, AJ AF HENRIKSEN, TB HEDEGAARD, M SECHER, NJ WILCOX, AJ TI STANDING AT WORK AND PRETERM DELIVERY - REPLY SO BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Letter C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP HENRIKSEN, TB (reprint author), AARHUS UNIV HOSP,DEPT OBSTET & GYNAECOL,PERINATAL EPIDEMIOL RES UNIT,DK-8000 AARHUS,DENMARK. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0306-5456 J9 BRIT J OBSTET GYNAEC JI Br. J. Obstet. Gynaecol. PD NOV PY 1995 VL 102 IS 11 BP 937 EP 937 DI 10.1111/j.1471-0528.1995.tb10894.x PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA TD487 UT WOS:A1995TD48700030 ER PT J AU CHOWDREY, HS LARSEN, PJ HARBUZ, MS JESSOP, DS AGUILERA, G ECKLAND, DJA LIGHTMAN, SL AF CHOWDREY, HS LARSEN, PJ HARBUZ, MS JESSOP, DS AGUILERA, G ECKLAND, DJA LIGHTMAN, SL TI EVIDENCE FOR ARGININE-VASOPRESSIN AS THE PRIMARY ACTIVATOR OF THE HPA AXIS DURING ADJUVANT-INDUCED ARTHRITIS SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE ARGININE VASOPRESSIN (AVP); CHRONIC STRESS; HPA-AXIS; ADJUVANT ARTHRITIS ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; STRESS ENHANCES VASOPRESSIN; RAT ANTERIOR-PITUITARY; FACTOR MESSENGER-RNA; PARVOCELLULAR NEUROSECRETORY NEURONS; HYPOPHYSEAL PORTAL BLOOD; FACTOR CRF RECEPTORS; MEDIAN-EMINENCE; ADRENOCORTICOTROPIN SECRETION AB 1 Adjuvant-induced arthritis (AA) is an experimental inflammation of the joints that results in chronic activation of the hypothalamo-pituitary-adrenal (HPA) axis. 2 In this study the role of hypothalamic corticotrophin-releasing factor (CRF) and arginine vasopressin (AVP) in the regulation of the HPA axis in this condition both in Sprague-Dawley (SD), and Piebald-Viral-Glaxo (PVG) rats has been further characterized. 3 The increase in AVP peptide content of portal blood (as early as day ii), just prior to the onset of arthritis is confirmed and further increases, peaking at day 16 are shown, coincident with the progression of inflammation in the PVG rats. 4 The increase in AVP is associated with a significant increase in the expression of AVP but not CRF mRNAs in the medial parvocellular division of the hypothalamic paraventricular nucleus (PVN) of arthritic SD rats. 5 In the presence of maximal inflammation of SD rats there was a significant decrease in the maximum binding of [I-125]-Tyr-oCRF to anterior pituitary membranes, whereas AVP receptor concentration in anterior pituitary membranes from both PVG and SD rats showed a significant increase with respect to controls. 6 The basal adrenocorticotrophin (ACTH) secretion in vitro was similar in both control and arthritic SD rats but that from arthritic PVG rat pituitaries was significantly greater than the respective controls (436 +/- 91 v 167 +/- 23 pg/tube). The ACTH response of pituitaries of arthritic PVG rats to CRF or the combination of CRF and AVP was significantly higher compared with the controls, although the ACTH response of arthritic SD rat pituitaries was unchanged. 7 The results are consistent with the view that activation of the parvocellular vasopressin system has an important role in the adaptation of the HPA axis to experimentally-induced chronic stress of arthritis. C1 UNIV GREENWICH,SCH CHEM & LIFE SCI,LONDON SE18 6PF,ENGLAND. UNIV COPENHAGEN,INST MED ANAT,DEPT B,COPENHAGEN,DENMARK. NICHHD,ENDOCRINE PHYSIOL SECT,BETHESDA,MD 20892. NORTHWICK PK HOSP & CLIN RES CTR,GLAXO GRP RES,CLIN PHARMACOL UNIT,HARROW HA1 3UJ,MIDDX,ENGLAND. RP CHOWDREY, HS (reprint author), UNIV BRISTOL,BRISTOL ROYAL INFIRM,DEPT MED,MARLBOROUGH ST,BRISTOL BS2 8HW,AVON,ENGLAND. NR 63 TC 93 Z9 93 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD NOV PY 1995 VL 116 IS 5 BP 2417 EP 2424 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TC075 UT WOS:A1995TC07500015 PM 8581278 ER PT J AU BOYER, JL OTUEL, JW FISCHER, B JACOBSON, KA HARDEN, TK AF BOYER, JL OTUEL, JW FISCHER, B JACOBSON, KA HARDEN, TK TI POTENT AGONIST ACTION OF 2-THIOETHER DERIVATIVES OF ADENINE-NUCLEOTIDES AT ADENYLYL CYCLASE-LINKED P-2Y-PURINOCEPTORS SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE P-2Y-PURINOCEPTORS; CYCLIC AMP ACCUMULATION; ADENYLYL CYCLASE INHIBITION; C6 RAT GLIOMA CELLS; 2-THIOETHER DERIVATIVES OF ADENINE NUCLEOTIDES ID PHOSPHOLIPASE-C; EXTRACELLULAR ATP; P2-PURINERGIC RECEPTORS; HL60 CELLS; ACTIVATION; MEMBRANES; CALCIUM; UTP AB 1 Analogues of adenine nucleotides inhibited beta-adrenoceptor-stimulated cyclic AMP accumulation in C6 rat glioma cells with a pharmacological selectivity consistent with that for involvement of a P-2Y-purinoceptor. 2 The inhibitory effect of adenine nucleotides was completely prevented by pretreatment of cells with pertussis toxin. 3 The capacity of a series of recently synthesized 2-thioether analogues of adenine nucleotides to inhibit cyclic AMP accumulation was examined. Several ATP analogues, e.g. 2-cyclohexylthio and 2-hexylthio ATP, inhibited cyclic AMP accumulation with EC(50) values of approximately 30 pM. These values represent 100,000 fold increases in potency over ATP. 4 Analogues of ADP exhibited the same remarkable increase in potency relative to their natural congener and diphosphates were at least as potent as the corresponding triphosphates at the C6 cell P-2Y-purinoceptor. 5 The relative potencies of a broad series of agonists at the C6 cell receptor did not correspond to the relative potencies of the same compounds for activation of P-2Y-purinoceptors on turkey erythrocyte membranes. Some agonists, particularly 2-thioether derivatives were more potent for stimulation of the C6 cell receptor, whereas other agonists were more potent in the turkey erythrocyte system. 6 These results add further support to the view that the adenylyl cyclase-linked P-2Y-purinoceptor of C6 rat glioma cells is a different subtype from the phospholipase C-linked P-2Y-purinoceptor of turkey erythrocyte membranes and several mammalian tissues C1 UNIV N CAROLINA,SCH MED,DEPT PHARMACOL,CHAPEL HILL,NC 27599. BAR ILAN UNIV,DEPT CHEM,IL-52900 RAMAT GAN,ISRAEL. NIDDK,MOLEC RECOGNIT SECT,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20, Z99 DK999999]; NHLBI NIH HHS [HL32322]; NIGMS NIH HHS [GM29536, GM38213] NR 28 TC 31 Z9 31 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD NOV PY 1995 VL 116 IS 6 BP 2611 EP 2616 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TF144 UT WOS:A1995TF14400012 PM 8590978 ER PT J AU KEMPNER, ES AF KEMPNER, ES TI THE MATHEMATICS OF RADIATION TARGET ANALYSES SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article ID SUBUNIT INTERACTIONS; IONIZING-RADIATION; SIZE DETERMINATION; ADENYLATE-CYCLASE; INACTIVATION; PROTEINS; ENZYMES; TEMPERATURE; SENSITIVITY AB Radiation target theory has been extended to complex biochemical systems. Mathematical analyses are presented for multiple forms of biological active proteins, for the presence of large inhibitors or activators, for compounds which regulate rate or affinity and for multiple-step reactions. Several predictions of these models have been verified experimentally. RP NIAMSD, PHYS BIOL LAB, BETHESDA, MD 20892 USA. NR 27 TC 15 Z9 15 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0092-8240 EI 1522-9602 J9 B MATH BIOL JI Bull. Math. Biol. PD NOV PY 1995 VL 57 IS 6 BP 883 EP 898 DI 10.1016/S0092-8240(95)80005-0 PG 16 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA TJ698 UT WOS:A1995TJ69800005 PM 8528160 ER PT J AU RUSH, ME RINZEL, J AF RUSH, ME RINZEL, J TI THE POTASSIUM A-CURRENT, LOW FIRING RATES AND REBOUND EXCITATION IN HODGKIN-HUXLEY MODELS SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article ID VOLTAGE-CLAMP ANALYSIS; NEOSTRIATAL NEURONS; HOPF-BIFURCATION; RELAY NEURONS; NERVE; MECHANISMS; PATTERN; APLYSIA; CELLS AB It is widely believed, following the work of Connor and Stevens (1971, J. Physiol. Lond. 214, 31-53) that the ability to fire action potentials over a wide frequency range, especially down to very low rates, is due to the transient, potassium A-current (I-A). Using a reduction of the classical Hodgkin-Huxley model, we study the effects of I-A on steady firing rate, especially in the near-threshold regime for the onset of firing. A minimum firing rate of zero corresponds to a homoclinic bifurcation of periodic solutions at a critical level of stimulating current. It requires that the membrane's steady-state current-voltage relation be N-shaped rather than monotonic. For experimentally based generic I-A parameters, the model does not fire at arbitrarily low rates, although it can for the more atypical I-A parameters given by Connor and Stevens for the crab axon. When the I-A inactivation rate is slow, we find that the transient potassium current can mediate more complex firing patterns, such as periodic bursting in some parameter regimes. The number of spikes per burst increases as g(A) decreases and as inactivation rate decreases. We also study how I-A affects properties of transient voltage responses, such as threshold and firing latency for anodal break excitation. We provide mathematical explanations for several of these dynamic behaviors using bifurcation theory and averaging methods. C1 CALIF STATE UNIV BAKERSFIELD,DEPT MATH,BAKERSFIELD,CA 93311. NIDDK,MATH RES BRANCH,BETHESDA,MD 20892. NR 40 TC 53 Z9 54 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD NOV PY 1995 VL 57 IS 6 BP 899 EP 929 DI 10.1016/S0092-8240(95)80006-9 PG 31 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA TJ698 UT WOS:A1995TJ69800006 PM 8528161 ER PT J AU HURTEAU, JA WOOLAS, RP JACOBS, IJ ORAM, DC KURMAN, CC RUBIN, LA NELSON, DL BERCHUCK, A BAST, RC MILLS, GB AF HURTEAU, JA WOOLAS, RP JACOBS, IJ ORAM, DC KURMAN, CC RUBIN, LA NELSON, DL BERCHUCK, A BAST, RC MILLS, GB TI SOLUBLE INTERLEUKIN-2 RECEPTOR-ALPHA IS ELEVATED IN SERA OF PATIENTS WITH BENIGN OVARIAN NEOPLASMS AND EPITHELIAL OVARIAN-CANCER SO CANCER LA English DT Article DE SOLUBLE INTERLEUKIN-2 RECEPTOR ALPHA; CA125; BENIGN OVARIAN NEOPLASMS; EPITHELIAL OVARIAN CANCER ID SOLID TUMORS; MARKERS AB Background. Previous studies have established that soluble interleukin-2 receptor alpha (sIL-2R alpha) levels are elevated in ascites and sera from individuals with advanced ovarian cancer (International Federation of Gynecology and Obstetrics [FIGO] Stage III/IV). This study was undertaken to evaluate sIL-2R alpha levels in individuals with benign ovarian neoplasms and early stage ovarian cancer (FIGO Stage I/II). Comparison with CA 125 levels was performed to assess screening potential. Methods. Sera from 92 healthy individuals, 61 with benign adnexal masses, 12 patients with FIGO Stage I/II ovarian cancers, and 27 patients with FIGO Stage III/IV ovarian cancers were assayed for sIL-2R alpha by enzyme-linked immunosorbent assay and CA 125 by radioimmunoassay. Results, The mean serum sIL-2R alpha levels for benign pelvic masses, and Stage I/II and Stage III/IV epithelial ovarian cancer were 1507 +/- 82, 1631 +/- 274, and 2596 +/- 384 U/ml, respectively. The difference between mean serum sIL-aR alpha levels in individuals with benign adnexal masses and Stage III/IV epithelial ovarian cancer was statistically significant (P < 0.05). In addition, of the four individuals with FIGO Stage I/II ovarian cancer who had CA125 levels below 35 U/ml, the accepted upper limit of normal, three patients had elevated serum sIL-2R alpha levels. Eleven of 12 patients (92%) with potentially curable Stage I/II disease had elevated serum levels of either sIL-2R alpha or CA125 and 8 of 12 (67%) had elevations of bath sIL-2R alpha and CA125. Sensitivity and specificity of a combination of CA 125 and soluble IL-2R alpha were 88.5% and 27.1%, respectively. Conclusion. Soluble interleukin-2 receptor alpha levels do not appear to differentiate between benign adnexal lesions and early malignancy; however, measurement of sIL-2R alpha levels in combination with CA125 warrants further evaluation to determine if together they will identify individuals with Stages I and II ovarian cancer. C1 TORONTO GEN HOSP,DIV ONCOL RES,TORONTO,ON,CANADA. UNIV TORONTO,DEPT OBSTET & GYNECOL,TORONTO,ON,CANADA. UNIV TORONTO,DEPT MED,TORONTO,ON,CANADA. UNIV TORONTO,DEPT IMMUNOL,TORONTO,ON,CANADA. NIH,BETHESDA,MD 20892. ROYAL LONDON HOSP,LONDON E1 1BB,ENGLAND. RP HURTEAU, JA (reprint author), DUKE UNIV,MED CTR,SCH MED,DURHAM,NC 27710, USA. RI Bast, Robert/E-6585-2011; Jacobs, Ian/F-1743-2013 OI Bast, Robert/0000-0003-4621-8462; Jacobs, Ian/0000-0002-8112-4624 NR 26 TC 15 Z9 16 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 NOV 1 PY 1995 VL 76 IS 9 BP 1615 EP 1620 DI 10.1002/1097-0142(19951101)76:9<1615::AID-CNCR2820760918>3.0.CO;2-G PG 6 WC Oncology SC Oncology GA TA524 UT WOS:A1995TA52400017 PM 8635066 ER PT J AU BRAUN, MM AHLBOM, A FLODERUS, B BRINTON, LA HOOVER, RN AF BRAUN, MM AHLBOM, A FLODERUS, B BRINTON, LA HOOVER, RN TI EFFECT OF TWINSHIP ON INCIDENCE OF CANCER OF THE TESTIS, BREAST, AND OTHER SITES (SWEDEN) SO CANCER CAUSES & CONTROL LA English DT Article DE BREAST CANCER; CANCER; HORMONES; PRENATAL EXPOSURE; SWEDEN; TESTIS CANCER; TWINS ID HUMAN CHORIONIC-GONADOTROPIN; TESTICULAR CANCER; RISK-FACTORS; PREGNANCIES; ESTROGEN; GESTATION; INUTERO AB It has been suggested that cancers of the testis and breast are associated with exposure to estrogens and other hormones in utero. Twin pregnancies have higher levels of pregnancy-associated hormones than singleton pregnancies, and these levels may be higher in dizygotic than in monozygotic twin pregnancies. Through a large population-based study of twins, we assessed the hypothesis that levels of pregnancy-associated hormones have etiologic importance for cancers of the testis, breast, and other sites. The incidence of all cancers among 46,767 members of the Swedish Twin Registry was compared with the incidence among the Swedish general population. We found testicular cancer excess among dizygotic twins (observed/expected [O/E] ratio = 1.6, 95 percent confidence interval [CI] = 1.0-2.6) that was greater for men younger than 35 years (O/E ratio = 2.3, CI = 1.1-4.2) compared with older men (O/E ratio = 1.2, CI = 0.5-2.4). In addition, a substantially elevated incidence of breast cancer was observed in dizygotic twin women aged 20 to 29 years (O/E = 6.7, CI = 2.9-13.1). None of the other age or zygosity groups showed notable elevations in incidence of testicular, breast, or other cancers. We conclude that dizygotic twinship may be associated with cancer of the breast and testis among young adults, These findings support the concept that pregnancy hormones are associated with risk of testicular and breast cancer, although non-hormonal aspects of twin pregnancy that vary with respect to zygosity cannot be excluded as explanatory factors. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. KAROLINSKA INST,INST ENVIRONM MED,S-10401 STOCKHOLM,SWEDEN. NATL INST OCCUPAT HLTH,DEPT NEUROMED,S-17184 SOLNA,SWEDEN. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 42 TC 115 Z9 116 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 1995 VL 6 IS 6 BP 519 EP 524 DI 10.1007/BF00054160 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA TG147 UT WOS:A1995TG14700008 PM 8580300 ER PT J AU CHEN, F KISHIDA, T DUH, FM RENBAUM, P ORCUTT, ML SCHMIDT, L ZBAR, B AF CHEN, F KISHIDA, T DUH, FM RENBAUM, P ORCUTT, ML SCHMIDT, L ZBAR, B TI SUPPRESSION OF GROWTH OF RENAL-CARCINOMA CELLS BY THE VON HIPPEL-LINDAU TUMOR-SUPPRESSOR GENE SO CANCER RESEARCH LA English DT Note ID CANCER; LINES AB Clear cell renal carcinomas are most frequently characterized by loss of function of both copies of the von Hippel-Lindau (VHL) disease gene, suggesting that the VHL gene product plays an important role in regulating renal cell proliferation. To directly assess the function of the VHL gene product, we transfected the wild-type VHL gene into two renal carcinoma cell lines that lacked normal expression of the gene. Expression of the wild-type VHL gene led to a dramatic suppression of growth in two renal carcinoma cell lines, A498 and UMRC6 in vitro, as measured by colony formation and direct cell counting. Transfection of a naturally occurring mutant VHL gene (nucleotide 713 G to A, Arg to Gln) did not lead to growth suppression of these renal carcinoma cells, nor did transfection of the wild-type VHL gene into two non-renal tumor cell Lines that expressed the endogenous wild-type VHL gene. Expression constructs, which included the first ATG at nucleotide 214, were sufficient to produce the strongest grow-th suppression. These experiments provide direct evidence that the VHL gene product functions to suppress the growth of renal carcinoma cells and also provide a model for mapping the domains of the VHL protein important in suppressing tumor growth. C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NR 20 TC 95 Z9 105 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1995 VL 55 IS 21 BP 4804 EP 4807 PG 4 WC Oncology SC Oncology GA TC468 UT WOS:A1995TC46800015 PM 7585510 ER PT J AU EWING, CM RU, N MORTON, RA ROBINSON, JC WHEELOCK, MJ JOHNSON, KR BARRETT, JC ISAACS, WB AF EWING, CM RU, N MORTON, RA ROBINSON, JC WHEELOCK, MJ JOHNSON, KR BARRETT, JC ISAACS, WB TI CHROMOSOME-5 SUPPRESSES TUMORIGENICITY OF PC3 PROSTATE-CANCER CELLS - CORRELATION WITH REEXPRESSION OF ALPHA-CATENIN AND RESTORATION OF E-CADHERIN FUNCTION SO CANCER RESEARCH LA English DT Note ID APC GENE-PRODUCT; TUMOR-CELLS; P-CADHERIN; ADHESION; PROTEIN; ESTABLISHMENT; ASSOCIATION; VINCULIN; GROWTH AB Considerable evidence now exists to support an important role for the E-cadherin-mediated cell-cell adhesion pathway as a suppressor of the invasive phenotype in adenocarcinoma cells. Previous studies have found that this pathway is frequently aberrant in prostate cancers, particularly those that are Likely to metastasize. In this study, we report on the effects of reestablishment of this pathway in a prostate cancer cell line, PC-3, in which this adhesion system is dysfunctional by virtue of a deletion of the gene that codes for alpha-catenin, an E-cadherin-associated protein necessary for normal E-cadherin function, Re-expression of alpha-catenin was accomplished either by transfection of PC-3 cells with a copy of the alpha-catenin cDNA under the control of a heterologous promoter or by microcell-mediated transfer of chromosome 5, which contains the alpha-catenin gene and its normal regulatory elements. In both cases, re-expression of alpha-catenin is associated with a similar, dramatic alteration in cell morphology, whereby extensive cell-cell contact is observed. In the case of transfection of the cDNA, this expression is only transient, because the transfected cells either cease to proliferate or, more commonly, revert to the parental phenotype with concomitant cessation of alpha-catenin expression. In contrast, tells containing one or more copies of microcell-transferred chromosome 5 express alpha-catenin in a stable manner and continue to proliferate. Upon injection into nude mice, these latter cells are no longer tumorigenic, or form only slowly growing tumors with greatly extended doubling times when compared to the parental PC-3 cells. During passage in culture, clones that contain only one transferred copy of chromosome 5 reproducibly revert to the parental phenotype. This reversion is associated with loss of the chromosome 5 region containing the alpha-catenin gene and consequent loss of alpha-catenin expression, as well as re-emergence of tumorigenicity. Transfer of chromosome 5 into prostate cancer cells that are E-cadherin negative does not result in either morphological transformation or suppression of tumorigenicity, suggesting that these effects of alpha-catenin expression are dependent upon concomitant expression of E-cadherin. These data demonstrate the tumor suppressive ability of chromosome 5 in the PC-3 prostate cancer cells and suggest that re-expression of alpha-catenin with resultant restoration of E-cadherin function plays a critical role in this process. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT UROL, BALTIMORE, MD 21287 USA. UNIV TOLEDO, DEPT BIOL, TOLEDO, OH 43606 USA. NIEHS, MOLEC CARCINOGENESIS LAB, RES TRIANGLE PK, NC 27709 USA. FU NCI NIH HHS [CA58236] NR 40 TC 113 Z9 114 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1995 VL 55 IS 21 BP 4813 EP 4817 PG 5 WC Oncology SC Oncology GA TC468 UT WOS:A1995TC46800017 PM 7585512 ER PT J AU KOSA, K JONES, CS DE LUCA, LM AF KOSA, K JONES, CS DE LUCA, LM TI THE H-RAS ONCOGENE INTERFERES WITH RETINOIC ACID SIGNALING AND METABOLISM IN NIH3T3 CELLS SO CANCER RESEARCH LA English DT Article ID HUMAN TERATOCARCINOMA CELLS; BINDING-PROTEIN; CRABP-I; TISSUE TRANSGLUTAMINASE; MOLECULAR-CLONING; ESCHERICHIA-COLI; GENE-EXPRESSION; DIFFERENTIATION; TRANSFORMATION; CONSTRUCTION AB We have previously shown that retinoic acid (RA) fails to induce transglutaminase C in H-ras transformed NIH-3T3 cells. Therefore, we investigated the effect of the H-ras oncogene on the metabolism of RA and on the expression of the cellular RA-binding protein I mRNA. HPLC analysis of the media and cell extracts demonstrated that H-ras-transformed cells metabolize RA to a much lesser extent than control cells, resulting in a higher concentration of RA in H-ras cells. Although inactive in endogenous transglutaminase induction, H-ras cell-associated RA was shown to be biologically available to induce activation of a reporter construct containing a retinoid response element and in stimulating transglutaminase activity in nontransfected cells. Cellular RA-binding protein I mRNA, supposedly involved in RA storage, was significantly increased in the H-ras-transformed cells. These data demonstrate that, even though H-ras-transformed cells accumulate up to 20 fold the concentration of RA as NIH-3T3 cells, they fail to show transglutaminase induction, suggesting that H-ras interferes with signal transduction by RA. C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. OI Kosa, Karolina/0000-0001-7867-2403 NR 29 TC 13 Z9 14 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1995 VL 55 IS 21 BP 4850 EP 4854 PG 5 WC Oncology SC Oncology GA TC468 UT WOS:A1995TC46800024 PM 7585519 ER PT J AU BEEBE, LE FORNWALD, LW DIWAN, BA ANVER, MR ANDERSON, LM AF BEEBE, LE FORNWALD, LW DIWAN, BA ANVER, MR ANDERSON, LM TI PROMOTION OF N-NITROSODIETHYLAMINE-INITIATED HEPATOCELLULAR TUMORS AND HEPATOBLASTOMAS BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN OR AROCLOR-1254 IN C57BL/6, DBA/2, AND B6D2F1 MICE SO CANCER RESEARCH LA English DT Article ID INDUCED LUNG-TUMORS; POLYCHLORINATED-BIPHENYLS; LIVER-TUMORS; SUSCEPTIBILITY; MOUSE; HEPATOCARCINOGENESIS; ACTIVATION; RATS AB To investigate the hypothesis that tumor promotion by chlorinated aromatic hydrocarbons involves Ah receptor occupation and subsequent induction of cytochromes P-450 1a-1, effects of Aroclor 1254 or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were examined in N-nitrosodiethylamine-initiated mice with different Ah receptor phenotype. Levels of cytochromes P-450 1a and 2b were measured by enzyme assay and Western immunoblots. Males of the C57BL/6, DBA/2, or (C57BL/6 x DBA/2)F-1 (hereafter referred to as ''B6D2F1'') strain were initiated with a single i.p. dose of N-nitrosodiethylamine (90 mg/kg body weight), followed by either multiple doses of TCDD (0.05 mu g/kg) weekly or Aroclor 1254 chronically in the diet (100 ppm) for 20 weeks, and then no treatment for 24 weeks. Lung tumor incidence or multiplicity was not altered by either of the promoters. Liver tumor incidence was similar among the three strains after N-nitrosodiethylamine alone (14, 21, and 21%, respectively). In DBA/2 mice, TCDD neither induced Cyp 1a nor promoted liver tumors. Aroclor caused an 8-fold induction of hepatic Cyp 2b, which was its maximum at the 12-week time point but did not promote tumors. Inductions of hepatic Cyp 1a by TCDD and la and 2b by Aroclor were similar in C57BL/6 and B6D2F1 mice, but tumor promotion responses were quite different. Dietary Aroclor significantly promoted Liver tumors in C57BL/6 mice (59 versus 14%) but not in B6D2F1 mice (24 versus 21%). Repeated TCDD promoted only in B6D2F1 mice (52 versus 21%) and not in C57BL/6 mice (19 versus 14%). Thus, whereas these data confirm that a functional Ah receptor is required for Liver tumor promotion, the degree of activation as measured by induction of Cyp 1a is not directly related to the degree of tumor-promoting capability, Other genetic factors must play a role in mediating the final tumor outcome. C1 NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP FREDERICK,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP FREDERICK,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. RP BEEBE, LE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP FREDERICK,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 28 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1995 VL 55 IS 21 BP 4875 EP 4880 PG 6 WC Oncology SC Oncology GA TC468 UT WOS:A1995TC46800028 PM 7585523 ER PT J AU ZIA, F FAGARASAN, M BITAR, K COY, DH PISEGNA, JR WANK, SA MOODY, TW AF ZIA, F FAGARASAN, M BITAR, K COY, DH PISEGNA, JR WANK, SA MOODY, TW TI PITUITARY ADENYLATE-CYCLASE ACTIVATING PEPTIDE RECEPTORS REGULATE THE GROWTH OF NON-SMALL-CELL LUNG-CANCER CELLS SO CANCER RESEARCH LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; GASTRIN-RELEASING PEPTIDE; HIGH-AFFINITY; FUNCTIONAL EXPRESSION; I RECEPTOR; POLYPEPTIDE; LINES; BOMBESIN; VIP; CARCINOMA AB We have identified pituitary adenylate cyclase activating peptide (PACAP) receptors on small cell lung cancer cell line NCI-N417 in a previous study. In this study, the role of PACAP in the growth and signal transduction of non-small cell lung cancer cells was investigated. Northern blot analysis with a full-length human PACAP receptor cDNA probe revealed a major 7.5-kb hybridizing transcript when total RNA extracted from NCI-H838 cells was used. PACAP bound with high affinity (K-d = 1 nM) to a single class of sites (B-max = 14,000/cell) when NCI-H838 cells were used. Specific I-125-labeled PACAP binding was inhibited with high affinity by PACAP-27 and PACAP-38, with moderate affinity by PACAP(6-38), and with low affinity by vasoactive intestinal polypeptide, PACAP(28-38), and PACAP(16-38). PACAP-27 elevated cAMP in a dose-dependent manner, and the increase in cAMP caused by PACAP was reversed by PACAP(6-38). PACAP-27, but not vasoactive intestinal polypeptide, elevated cytosolic Ca2+ in individual NCI-H838 cells, PACAP-27 stimulated arachidonic acid release, and the increase caused by PACAP was reversed by PACAP(6-38). PACAP-27 stimulated colony formation in NCI-H838 cells, whereas the PACAP antagonist PACAP(6-38) reduced colony formation in the absence or presence of exogenous PACAP-27. In nude mice bearing NCI-H838 xenografts, PACAP(6-38) slowed tumor growth significantly. These data suggest that biologically active type 1 PACAP receptors are present on human non-small cell lung cancer cells, which exhibit dual signal transduction pathways and regulate cell proliferation. C1 NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. GEORGE WASHINGTON UNIV,MED CTR,DEPT MICROBIOL,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,MED CTR,DEPT BIOCHEM,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,MED CTR,DEPT MOLEC BIOL,WASHINGTON,DC 20037. TULANE UNIV,SCH MED,DEPT MED,PEPTIDE RES LAB,NEW ORLEANS,LA 70112. NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK-36107] NR 32 TC 49 Z9 52 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1995 VL 55 IS 21 BP 4886 EP 4891 PG 6 WC Oncology SC Oncology GA TC468 UT WOS:A1995TC46800030 PM 7585525 ER PT J AU SILVERMAN, DT BROWN, LM HOOVER, RN SCHIFFMAN, M LILLEMOE, KD SCHOENBERG, JB SWANSON, GM HAYES, RB GREENBERG, RS BENICHOU, J SCHWARTZ, AG LIFF, JM POTTERN, LM AF SILVERMAN, DT BROWN, LM HOOVER, RN SCHIFFMAN, M LILLEMOE, KD SCHOENBERG, JB SWANSON, GM HAYES, RB GREENBERG, RS BENICHOU, J SCHWARTZ, AG LIFF, JM POTTERN, LM TI ALCOHOL AND PANCREATIC-CANCER IN BLACKS AND WHITES IN THE UNITED-STATES SO CANCER RESEARCH LA English DT Article ID RISK-FACTORS; ATTRIBUTABLE RISK; COFFEE; TOBACCO; MORTALITY; CONSUMPTION; DIET; DETERMINANTS; BEVERAGES; SMOKING AB A population-based, case-control study of pancreatic cancer based on direct interviews with 307 white and 179 black incident cases and 1164 white and 945 black population controls was conducted in three areas of the United States to determine the role alcohol drinking plays as a risk factor for pancreatic cancer and to estimate the extent to which it may explain the higher incidence of pancreatic cancer in blacks compared to whites. Our findings indicate that alcohol drinking at the Levels typically consumed by the general population of the United States is probably not a risk factor for pancreatic cancer. Our data suggest, however, that heavy alcohol drinking may be related to pancreatic cancer risk. Among men, blacks and whites who drank at least 57 drinks/week had odds ratios (ORs) of 2.2 [95% confidence interval (CI) = 0.9-5.6] and 1.4 (95% CI = 0.6-3.2), respectively. Among women, blacks who drank 8 to <21 drinks/week had an OR of 1.8 (95% CI = 0.8-4.0), and those who drank at least 21 drinks/week had an OR of 2.5 (95% CI = 1.02-5.9), but whites with the same levels of alcohol intake experienced no increased risk. Compared to whites, blacks had significantly higher ORs associated with heavy alcohol drinking (greater than or equal to 57 drinks/week) in men (P = 0.04) and with moderate-to-heavy drinking (greater than or equal to 8 drinks/week) in women (P = 0.03). Additional research is needed to determine whether heavy alcohol drinking is causally related to pancreatic cancer and whether the risk of alcohol-related pancreatic cancer is greater in blacks than in whites. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT SURG,BALTIMORE,MD 21205. NEW JERSEY STATE DEPT HLTH,SPECIAL EPIDEMIOL PROGRAM,TRENTON,NJ 08625. MICHIGAN STATE UNIV,COLL HUMAN MED,E LANSING,MI 48824. MED UNIV S CAROLINA,CHARLESTON,SC 29425. EMORY UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,ATLANTA,GA 30329. UNIV PITTSBURGH,SCH MED,DEPT CLIN EPIDEMIOL & FAMILY MED,PITTSBURGH,PA 15261. RP SILVERMAN, DT (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 418,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-51089, N01-CP-51090, N01-CP-51092] NR 49 TC 57 Z9 58 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1995 VL 55 IS 21 BP 4899 EP 4905 PG 7 WC Oncology SC Oncology GA TC468 UT WOS:A1995TC46800032 PM 7585527 ER PT J AU STANWELL, C BURKE, TR YUSPA, SH AF STANWELL, C BURKE, TR YUSPA, SH TI ERBSTATIN ANALOG METHYL 2,5-DIHYDROXYCINNAMATE CROSS-LINKS PROTEINS AND IS CYTOTOXIC TO NORMAL AND NEOPLASTIC EPITHELIAL-CELLS BY A MECHANISM INDEPENDENT OF TYROSINE KINASE INHIBITION SO CANCER RESEARCH LA English DT Article ID MOUSE EPIDERMAL-CELLS; RETINOIC ACID; DIFFERENTIATION; EXPRESSION; GROWTH; INVITRO; STAUROSPORINE; INDUCTION; ONCOGENE; GENE AB Differentiation therapy is an attractive option for the treatment of superficial, localized neoplastic lesions of the skin. Topical application of agents that induce differentiation could selectively inhibit tumor cell growth, inducing a program of cell death with the production of crosslinked protein envelopes as the terminal event of this process at the skin surface, effectively eliminating the neoplastic phenotype. The nonspecific kinase inhibitor staurosporine induces cornified envelope assembly in neoplastic keratinocytes and causes tumor regression (A. A. Dlugosz and S. H. Yuspa, Cancer Res., 51: 4677-4684, 1991). In pursuit of less toxic agents, specific tyrosine kinase inhibitors were tested for the ability to induce differentiation in keratinocyte-derived cells. Of a range of inhibitors tested, only MC was able to induce cross-linked protein and consequent cell death in mouse and hunan primary normal keratinocytes, 308 neoplastic mouse keratinocytes, HPV-18-infected immortalized human keratinocytes, and human lines SQCC-Y1 (squamous carcinoma) and A431 (epidermoid carcinoma). MC increased cross-linked protein in a dose-dependent manner (0.05-1 mM). To confirm differentiation, MC-treated mouse primary normal keratinocytes were tested for activation of the endogenous cross-linking enzyme transglutaminase, but no association was found between transglutaminase activity and MC-induced protein cross-linking. MC also induced protein cross-lining in the fibroblast cell line NIH3T3 and in B16 melanoma cells, in which cornified envelope assembly is not part of the differentiation process. This crass-linking occurred at 4 degrees C, suggesting a nonphysiological process. Western blot analysis of an in vitro assay with purified EGF receptor shelved that MC was able to cross-link the receptor. As in NIH3T3 cells, DTT inhibited cross-linking, suggesting that oxidation of MC or an acceptor group may be required for this effect. Thus, MC does not induce differentiation by a physiological mechanism in epithelial cells but causes chemical protein cross-linking into cornified envelope-like structures at high concentration. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NCI,MED CHEM LAB,BETHESDA,MD 20892. RI Burke, Terrence/N-2601-2014 NR 28 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1995 VL 55 IS 21 BP 4950 EP 4956 PG 7 WC Oncology SC Oncology GA TC468 UT WOS:A1995TC46800040 PM 7585535 ER PT J AU SALGALLER, ML AFSHAR, A MARINCOLA, FM RIVOLTINI, L KAWAKAMI, Y ROSENBERG, SA AF SALGALLER, ML AFSHAR, A MARINCOLA, FM RIVOLTINI, L KAWAKAMI, Y ROSENBERG, SA TI RECOGNITION OF MULTIPLE EPITOPES IN THE HUMAN-MELANOMA ANTIGEN GP100 BY PERIPHERAL-BLOOD LYMPHOCYTES STIMULATED IN-VITRO WITH SYNTHETIC PEPTIDES SO CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; T-CELL CLONES; PROLIFERATE INVIVO; MHC MOLECULES; IN-VITRO; IMMUNOTHERAPY; CANCER; INTERLEUKIN-2; INDUCTION; RESPONSES AB gp100 is a melanocyte lineage-specific antigen recognized by tumor-infiltrating lymphocytes whose adoptive transfer has been associated with tumor regression in patients with metastatic melanoma. The peripheral blood mononuclear cells of five melanoma patients were sensitized in vitro with synthetic peptides to elicit antigen-specific cytotoxic T lymphocyte (CTL) lines against four gp100 epitopes. These epitope-specific CTL lines were generated following weekly in vitro stimulation with the synthetic decamer G10(476) (V-L-Y-R-Y-G-S-F-S-V) or the nonamers G9(280) (Y-L-E-P-G-P-V-T-A), G9(154) (K-T-W-G-Q-Y-W-Q-V), or G9(209) (I-T-D-Q-V-P-F-S-V) pulsed onto autologous irradiated peripheral blood mononuclear cells. These Lines grew as long as 4 months in culture in low-dose interleukin 2 (30 IU/ml) and exhibited antigen-specific, MHC class I-restricted lysis of peptide-pulsed T2 cells and HLA-A2(+), gp100(+) established melanoma cell lines. G10(476)- and G9(280)-specific CTLs demonstrated specific release of granulocyte-macrophage-colony-stimulating factor and tumor necrosis factor a in response to T2 cells pulsed with relevant peptide, as well as to gp100(+) melanoma cell lines. These results demonstrate that several peptides derived from the gp100 protein are presented on the surface of melanoma cells and are sufficiently immunogenic to generate, in vitro, potent CTLs capable of cytolysis and the secretion of cytokines. Therefore, for HLA-A2(+) melanoma patients, these and possibly other gp100 peptides could represent good candidates for antigen-specific immunotherapy either singly or in a multivalent regimen. RP SALGALLER, ML (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B08,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 47 TC 120 Z9 121 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1995 VL 55 IS 21 BP 4972 EP 4979 PG 8 WC Oncology SC Oncology GA TC468 UT WOS:A1995TC46800043 PM 7585538 ER PT J AU CHUAQUI, RF SANZORTEGA, J VOCKE, C LINEHAN, WM SANZESPONERA, J ZHUANG, ZP EMMERTBUCK, MR MERINO, MJ AF CHUAQUI, RF SANZORTEGA, J VOCKE, C LINEHAN, WM SANZESPONERA, J ZHUANG, ZP EMMERTBUCK, MR MERINO, MJ TI LOSS OF HETEROZYGOSITY ON THE SHORT ARM OF CHROMOSOME-8 IN MALE BREAST CARCINOMAS SO CANCER RESEARCH LA English DT Article ID ANDROGEN RECEPTOR GENE; COLORECTAL-CANCER; DELETION; POLYMORPHISMS; PROSTATE; LOCI AB Identification of Loss of heterozygosity (LOH) at specific genetic loci in neoplastic cells suggests the presence of a tumor suppressor gene within the deleted region. LOH on chromosome 8p has been identified in colorectal, bladder, hepatocellular, and prostatic carcinomas. Little is currently known about the molecular events occurring during the development of male breast cancer. We studied LOB on chromosome 8p in 23 male breast carcinomas. Five polymorphic DNA markers were used: D8S136 and D8S137 on 8p12-21.3; and D8S254, D8S258, and D8S349 on 8p22. DNA was extracted from microdissected normal and tumor cells obtained from formalin-fixed, paraffin-embedded tissue sections and amplified by the PCR. LOH was identified in 19 of 23 cases (83%) with at Least one marker. Seven cases showed LOH only at 8p22, six cases showed LOH only at 8p12-21.3, and six cases showed LOH at both 8p22 and 8p12-21.3. In five of these last six cases, at Least one locus was retained between the two deleted regions; thus, the whole short arm of chromosome 8 was not Lost in these tumors. Our results show that there are two discrete areas of deletion on chromosome 8p in male breast cancer, suggesting the presence of one or more tumor suppressor genes that may play a role in the development or progression of the disease. C1 NCI,PATHOL LAB,ROCKVILLE,MD 20892. HOSP UNIV SAN CARLOS,DEPT ANAT PATOL,E-28040 MADRID,SPAIN. RI Sanz, Julian/G-5276-2013 NR 33 TC 35 Z9 36 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1995 VL 55 IS 21 BP 4995 EP 4998 PG 4 WC Oncology SC Oncology GA TC468 UT WOS:A1995TC46800046 PM 7585541 ER PT J AU RISHI, AK SHAO, ZM BAUMANN, RG LI, XS SHEIKH, MS KIMURA, S BASHIRELAHI, N FONTANA, JA AF RISHI, AK SHAO, ZM BAUMANN, RG LI, XS SHEIKH, MS KIMURA, S BASHIRELAHI, N FONTANA, JA TI ESTRADIOL REGULATION OF THE HUMAN RETINOIC ACID RECEPTOR CW GENE IN HUMAN BREAST-CARCINOMA CELLS IS MEDIATED VIA AN IMPERFECT HALF-PALINDROMIC ESTROGEN RESPONSE ELEMENT AND SP1 MOTIFS SO CANCER RESEARCH LA English DT Article ID CANCER CELLS; EXPRESSION; PROMOTER; INHIBITION; ACTIVATION; SEQUENCE; ABILITY; ALPHA AB Estrogen receptor (ER)-positive human breast carcinoma (HBC) cell lines express significantly higher levels of retinoic acid receptor alpha (RAR alpha) (isoform 1) mRNA than ER-negative HBCs. Estradiol enhances RAR alpha mRNA expression in different ER-positive HBCs by 2-13-fold, which in turn results in increased sensitivity of ER-positive HBCs to the growth inhibitory effects of retinoic acid. To investigate the regulatory mechanisms of estradiol-mediated enhancement of RAR alpha mRNA expression, the functional promoter for the human RAR alpha isoform 1 was cloned and used to assess estradiol-mediated promoter-dependent enhancement of firefly luciferase reporter gene activity in transiently transfected ER-positive (MCF-7 and T47D) and ER-negative (MDA-MB-231) HBCs. Deletional promoter constructs were obtained to further delineate the promoter region responsible for estradiol-mediated enhancement of promoter activity. Here, we present evidence that approximately 130 bp of the promoter fragment preceding the transcriptional start site are responsible for estradiol-mediated enhancement of hRAR alpha gene expression. The estradiol-mediated enhancement is dependent on ER binding. Further deletional analysis showed that a promoter sequence of 42 base pairs, located approximately 100 bases upstream of the transcriptional start site, contains elements for estradiol-mediated enhancement. Specific deletion of either the Sp1 motif or mutations in the imperfect half-palindromic estrogen response element motif of this fragment abolish its estradiol responsiveness in transient transfections. C1 UNIV MARYLAND,SCH MED,DEPT MED,DIV ONCOL,BALTIMORE,MD 21201. VET ADM MED CTR,BALTIMORE,MD 21218. UNIV MARYLAND,SCH DENT,DEPT BIOCHEM,BALTIMORE,MD 21201. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP RISHI, AK (reprint author), UNIV MARYLAND,SCH MED,CTR CANC,BRESSLER RES BLDG,ROON 9-031,655 W BALTIMORE ST,BALTIMORE,MD 21201, USA. FU NCI NIH HHS [CA-63335] NR 30 TC 82 Z9 82 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1995 VL 55 IS 21 BP 4999 EP 5006 PG 8 WC Oncology SC Oncology GA TC468 UT WOS:A1995TC46800047 PM 7585542 ER PT J AU MULLER, JR JANZ, S POTTER, M AF MULLER, JR JANZ, S POTTER, M TI DIFFERENCES BETWEEN BURKITTS LYMPHOMAS AND MOUSE PLASMACYTOMAS IN THE IMMUNOGLOBULIN HEAVY-CHAIN C-MYC RECOMBINATIONS THAT OCCUR IN THEIR CHROMOSOMAL TRANSLOCATIONS SO CANCER RESEARCH LA English DT Article ID VARIANT TRANSLOCATION; STRUCTURAL ALTERATIONS; GENE REARRANGEMENT; JOINING SIGNALS; CELL-LINES; B-CELL; REGION; ONCOGENE; LOCUS; BREAKPOINT AB Burkitt's lymphomas (BLs) and mouse plasmacytomas (MPs) are characterized by chromosomal translocations juxtaposing the c-myc oncogene to one of the immunoglobulin loci. Here we describe illegitimate recombinations and the DNA sequence at the junction between c-myc and immunoglobulin heavy chain (IgH) regions in these B-cell lineage tumors. In 15 BLs and in 29 MPs, recombination products were amplified by PCR and sequenced. Molecular analysis of the IgH/c-myc junctions revealed the following characteristics: (a) rearrangements in BLs represent nearly reciprocal exchanges between c-myc and IgH switch sequences, whereas in MPs, several hundred bp of c-myc may be duplicated or deleted; (b) short homologies of up to 5 bp between immunoglobulin and c-myc sequences can be found at most junction sites in both tumors; and (c) pentameric sequences typically found in switch regions and V(D)J recognition motifs also occur frequently at the sites of recombination in c-myc. RP MULLER, JR (reprint author), NCI,DIV CANC BIOL DIAG & CTR,BLDG 37,ROOM 2B-09,BETHESDA,MD 20892, USA. NR 45 TC 27 Z9 28 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1995 VL 55 IS 21 BP 5012 EP 5018 PG 7 WC Oncology SC Oncology GA TC468 UT WOS:A1995TC46800049 PM 7585544 ER PT J AU KUMAR, CC PROROCKROGERS, C KELLY, J DONG, ZG LIN, JJ ARMSTRONG, L KUNG, HF WEBER, MJ AFONSO, A AF KUMAR, CC PROROCKROGERS, C KELLY, J DONG, ZG LIN, JJ ARMSTRONG, L KUNG, HF WEBER, MJ AFONSO, A TI SCH-51344 INHIBITS RAS TRANSFORMATION BY A NOVEL MECHANISM SO CANCER RESEARCH LA English DT Article ID MUSCLE ALPHA-ACTIN; SIGNAL-TRANSDUCTION; KI-RAS; CELLS; CANCER; ONCOGENES; PROMOTER; FARNESYLATION; ACTIVATION; INDUCTION AB A pyrazolo-quinoline compound, 6-methoxy-4-[2-[(2-hydroxyethoxyl)ethyl]amino]-3-methy-1M -pyrazolo [3,4-b]quinoline (SCH 51344), was identified based on its ability to derepress human smooth muscle alpha-actin promoter activity in ras-transformed cells. In this study, we show that SCH 51344 reverts several key aspects of ms transformation, such as morphological changes, actin filament organization, and anchorage-independent growth, and also inhibits Val-12 Ras-induced maturation of Xenopus oocytes. SCH 51344 is also a potent inhibitor of the anchorage-independent growth of human tumor Lines known to contain multiple genetic alterations in addition to activated ms genes. We have sought to determine whether SCH 51344 disrupts the signaling pathway that activates mitogen-activated protein (MAP) kinase or extracellular signal-regulated kinase (ERK) in normal and ras-transformed fibroblast cells. NIH 3T3 cells transformed by different oncogenes, which have products that participate at different steps of the Ras signaling pathway, were tested in a soft-agar colony formation assay to determine which step of the pathway is Inhibited by SCH 51344. Our results indicate that SCH 51344 inhibits the ability of v-abl, v-mos, H-ras, v-raf, and mutant active MAP kinase kinase-transformed NIH 3T3 cells to grow in soft agar. Only v-fos-transformed cells were found to be resistant to the treatment of SCH 51344. SCH 51344 treatment had very little effect, if any, on the activation of MAP kinase kinase, MAP kinase, and p90(RSK) activity in response to growth factor stimulation. Treatment of ras-transformed cells with SCH 51334 led to stimulation of serum response factor DNA binding activity and activation of serum response element-dependent gene transcription, accounting for its ability to activate alpha-actin promoter activity in ras-transformed cells. Our results indicate that SCH 51344 inhibits ms transformation by a novel mechanism and acts at a point either downstream or parallel to extracellular signal-regulated kinase-dependent Ras signaling pathway. C1 SCHERING PLOUGH CORP,RES INST,DEPT MED CHEM,KENILWORTH,NJ 07033. UNIV VIRGINIA,HLTH SCI CTR,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. RP KUMAR, CC (reprint author), SCHERING PLOUGH CORP,RES INST,DEPT TUMOR BIOL,2015 GALLOPING HILL RD,KENILWORTH,NJ 07033, USA. FU NIGMS NIH HHS [GM 47332] NR 49 TC 25 Z9 25 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1995 VL 55 IS 21 BP 5106 EP 5117 PG 12 WC Oncology SC Oncology GA TC468 UT WOS:A1995TC46800064 PM 7585559 ER PT J AU MALARKEY, DE DEVEREUX, TR DINSE, GE MANN, PC MARONPOT, RR AF MALARKEY, DE DEVEREUX, TR DINSE, GE MANN, PC MARONPOT, RR TI HEPATOCARCINOGENICITY OF CHLORDANE IN B6C3F1 AND B6D2F1 MALE-MICE - EVIDENCE FOR REGRESSION IN B6C3F1 MICE AND CARCINOGENESIS INDEPENDENT OF RAS PROTOONCOGENE ACTIVATION SO CARCINOGENESIS LA English DT Article ID MOUSE-LIVER TUMORS; ORGANOCHLORINE PESTICIDES CHLORDANE; PROTOONCOGENE ACTIVATION; LUNG-TUMORS; NUCLEAR POLYPLOIDIZATION; METHYLENE-CHLORIDE; MUTATIONS; HEPTACHLOR; RESISTANT; DIELDRIN AB Logistic regression analysis of age-specific prevalences for neoplastic and non-neoplastic liver lesions was used to examine treatment responses for B6C3F1 and B6D2F1 male mice continuously exposed to chlordane (55 p.p.m.) and to determine whether neoplasms were dependent on continuous exposure in the B6C3F1 mice, In order to determine if ras oncogene activation plays a role in the carcinogenicity of chlordane and whether the activation is dependent on genetic background, liver tumors from chlordane-treated B6C3F1 and B6D2F1 mice were analyzed for the presence of activating mutations in the ras oncogene, The overall liver tumor prevalence at terminal killing was nearly 100% for both strains; however, the age-specific prevalence increased more rapidly in B6C3F1 mice than in B6D2F1 mice, Tumor-bearing B6C3F1 mice had an average of two more tumors per liver than B6D2F1 mice at their respective terminal killings (5.4 versus 3.3), When chlordane exposure was discontinued for a group of B6C3F1 mice ('stop' group) at 491 days of age, overall tumor multiplicity significantly decreased by 30% from an average of 4.4 per tumor-bearing-animal at 525 days to 3.1 at terminal killing (568 days), Over the same time period the prevalence of hepatocellular carcinomas significantly decreased from 80 to 54% and adenomas from 100 to 93% by terminal killing in B6C3F1 'stop-group' mice, Chlordane induced diffuse hepatocellular centrilobular hypertrophy, frequent multinucleate hepatocytes, toxic change and hepatoproliferative lesions composed predominantly of acidophilic hepatocytes in nearly 100% of both the B6C3F1 and B6D2F1 mice, The development of histological evidence of toxicity closely paralleled the temporal development of hepatocellular neoplasia and decreased in severity when the tumor burden was maximal. No H- or K-ras mutations were detected in the chlordane-induced hepatocellular tumors in B6C3F1 mice (15 adenomas and 15 carcinomas) or B6D2F1 mice (10 adenomas and 10 carcinomas), In conclusion, chlordane induced liver tumors in both B6C3F1 and B6D2F1 male mice by mechanisms independent of ras oncogene activation and 30% of both benign and malignant liver tumors in the B6C3F1 mice regressed after exposure was discontinued. C1 NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. NIEHS,ENVIRONM BIOL & MED PROGRAM,RES TRIANGLE PK,NC 27709. NIEHS,EXPTL PATHOL LABS,RES TRIANGLE PK,NC 27709. N CAROLINA STATE UNIV,COLL VET MED,DEPT MICROBIOL PATHOL & PARASITOL,RALEIGH,NC 27606. NR 58 TC 26 Z9 27 U1 5 U2 5 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1995 VL 16 IS 11 BP 2617 EP 2625 DI 10.1093/carcin/16.11.2617 PG 9 WC Oncology SC Oncology GA TG194 UT WOS:A1995TG19400003 PM 7586176 ER PT J AU GHOSHAL, A DAVIS, CD SCHUT, HAJ SNYDERWINE, EG AF GHOSHAL, A DAVIS, CD SCHUT, HAJ SNYDERWINE, EG TI POSSIBLE MECHANISMS FOR PHIP-DNA ADDUCT FORMATION IN THE MAMMARY-GLAND OF FEMALE SPRAGUE-DAWLEY RATS SO CARCINOGENESIS LA English DT Article ID METABOLIC-ACTIVATION; HETEROCYCLIC AMINES; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; ENVIRONMENTAL FACTORS; COVALENT BINDING; AROMATIC-AMINES; COOKED FOOD; MUTAGENICITY; CARCINOGEN; CANCER AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant heterocyclic amine in fried beef, is a mammary gland carcinogen in rats. Using the P-32-postlabeling method, PhIP-DNA adduct levels were measured in mammary epithelial cells isolated from female Sprague-Dawely rats given 10 daily doses of PhIP (75 mg/ kg, p.o.) according to a protocol previously shown to induce mammary gland cancer. At 24 h, 48 h, 1 week and 5 weeks after the last dose of PhIP, PhIP-DNA adduct levels [relative adduct labeling (RAL) x 10(7), mean +/- SD] were 10.2 +/- 0.7, 7.9 +/- 2.7, 2.2 +/- 0.6 and 0.9 +/- 0.03 respectively, When isolated rat mammary epithelial cells (from untreated rats) were incubated in vitro with N-hydroxy-PhIP (45 mu M, 1 h, 37 degrees C), PhIP-DNA adducts were detected in cell DNA (RAL = similar to 97 x 10(7)); however, no adducts were detected in cells incubated with PhIP (200 mu M, 15 h, 37 degrees C), Incubating cells with pentachlorophenol, an inhibitor of acetyltransferase, or incubating cells at 0-4 degrees C, reduced N-hydroxy-PhIP adduct levels by 45 and 75% respectively, indicating that formation of N-hydroxy-PhIP adducts was largely due to metabolic activation, Further studies showed that rat mammary gland microsomes had little capacity to N-hydroxylate PhIP, as assayed by the mutagenic activation of PhIP in the Ames Salmonella assay, In contrast, N-hydroxy-PhIP was metabolically activated by rat mammary gland O-acetyltransferase, as assayed by cytosol-catalyzed PhIP-DNA adduct formation to calf thymus DNA incubated in vitro with N-hydroxy-PhIP (2 mu M) in the presence of acetyl CoA, Notably, mammary cytosolic O-acetyltransferase activation of N-hydroxy-PhIP was similar to 16- to 17-fold higher than that observed with hepatic cytosol and at least two-fold higher than the mammary O-acetyltransferase activation of N-hydroxy-IQ or N-hydroxy-MeIQx, All three N-hydroxylamines were activated via cytosolic proline aminoacyl-tRNA synthetase and phosphorylase, although the activities of these enzymes were similar to 100-fold lower than O-acetyltransferase. No mammary cytosolic sulfotransferase activation could be detected with any of the N-hydroxylamines, Our results are consistent with the notion that PhIP-DNA adduct formation and initiation of carcinogenesis in the rat mammary gland may be associated with N-hydroxylation of PhIP outside the mammary gland, transport of the N-hydroxylamine to the mammary gland and subsequent in situ O-acetyltransferase-catalyzed activation of N-hydroxy-PhIP. C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43614. NR 57 TC 51 Z9 51 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1995 VL 16 IS 11 BP 2725 EP 2731 DI 10.1093/carcin/16.11.2725 PG 7 WC Oncology SC Oncology GA TG194 UT WOS:A1995TG19400019 PM 7586192 ER PT J AU TRITSCHER, AM CLARK, GC SEWALL, C SILLS, RC MARONPOT, R LUCIER, GW AF TRITSCHER, AM CLARK, GC SEWALL, C SILLS, RC MARONPOT, R LUCIER, GW TI PERSISTENCE OF TCDD-INDUCED HEPATIC CELL-PROLIFERATION AND GROWTH OF ENZYME-ALTERED FOCI AFTER CHRONIC EXPOSURE FOLLOWED BY CESSATION OF TREATMENT IN DEN INITIATED FEMALE RATS SO CARCINOGENESIS LA English DT Article ID FACTOR-ALPHA; HUMAN KERATINOCYTES; TUMOR PROMOTION; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN TCDD; MECHANISM; EXPRESSION; TOXICITY; LIVER; HEPATOCARCINOGENESIS; DIETHYLNITROSAMINE AB 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent tumor promoter in two-stage models of hepatocarcinogenesis, This study focuses on the persistence or reversibility of TCDD-mediated changes in livers after 30 weeks of treatment and cessation of treatment, Diethylnitrosamine (DEN) initiated animals (175 mg/kg) were promoted bi-weekly with TCDD at a dose equivalent to 125 ng/kg/day for 30 weeks without or with a following waiting period of 32 weeks before necropsy, 2,3,7,8-Tetrachlorodibenzo-p-dioxin liver concentration decreased 300-fold in the 32 week waiting period but was still five-fold above background, Induction of CYP1A1 dependent enzyme activity decreased according to TCDD tissue levels, In contrast, cell proliferation, as measured by BrdU-labeling index, was still 2.8-fold increased over controls in the TCDD group with waiting period compared to a 4-fold increase over controls at the end of the 30 week dosing period, Enzyme altered hepatic foci expressing the placental form of glutathione S-transferase decreased in number but the remaining foci were significantly increased in size and the percent of liver occupied by foci was higher at the end of the waiting period as compared to livers at the end of the dosing period, Liver tumor incidence at the end of the waiting period was 71% (5 of 7 animals) and the livers showed an increase in bile duct lesions with only mild toxicity. There was pronounced bile duct proliferation in DEN/TCDD treated animals after the waiting period with intense expression of TGF alpha in bile duct epithelial cells as detected by immunohistochemical methods, In comparison, at the end of the 30 week dosing period the livers showed more severe toxicity and only mild bile duct proliferation, Also, one small hepatocellular adenoma was observed, It is concluded that as opposed to CYP1A1 induction the more complex biological responses, cell proliferation and selective growth of certain preneoplastic foci, are persistent after prolonged TCDD treatment within the experimental framework of our study. C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 39 TC 28 Z9 28 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1995 VL 16 IS 11 BP 2807 EP 2811 DI 10.1093/carcin/16.11.2807 PG 5 WC Oncology SC Oncology GA TG194 UT WOS:A1995TG19400029 PM 7586202 ER PT J AU SINHA, R ROTHMAN, N MARK, SD MURRAY, S BROWN, ED LEVANDER, OA DAVIES, DS LANG, NP KADLUBAR, FF HOOVER, RN AF SINHA, R ROTHMAN, N MARK, SD MURRAY, S BROWN, ED LEVANDER, OA DAVIES, DS LANG, NP KADLUBAR, FF HOOVER, RN TI LOWER LEVELS OF URINARY 2-AMINO-3,8-DIMETHYLIMIDAZO[4,5-F]QUINOXALINE (MEIQX) IN HUMANS WITH HIGHER CYP1A2 ACTIVITY SO CARCINOGENESIS LA English DT Note ID HETEROCYCLIC AROMATIC-AMINES; METABOLIC-ACTIVATION; CARCINOGENS; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; 2-AMINO-3,4,8-TRIMETHYLIMIDAZO<4,5-F>QUINOXALINE; EXPOSURE; LIVER; BEEF; FOOD; RAT AB Heterocyclic aromatic amines (HAAs), such as 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), are metabolically activated by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2), We examined the relationship between CYP1A2 and NAT2 activity and the excretion of total unconjugated MeIQx in 66 healthy subjects, The subjects ate a controlled diet for 7 days containing lean ground beef cooked at low temperature. On day 8, they were tested for CYP1A2, and NAT2 activity by caffeine phenotyping, On the evening of day 8, subjects consumed lean ground beef cooked at high temperature containing 9.0 ng of MeIQx/g of meat. The subjects ate 3.1-4.0 g meat/kg body wt. Twelve-hour urine samples were collected and MeIQx was measured by gas chromatography-mass spectrometry, Using linear regression analyses, we found that higher CYP1A2 activity was associated with lower levels of total unconjugated MeIQx in the urine (P = 0.008) when adjusted for amount of meat eaten, while NAT2 activity showed no relationship with the latter, This suggests that a greater percentage of MeIQx is converted to metabolites such as the N-hydroxy derivative when CYP1A2 activity is higher, This finding supports the concept that interindividual variation in CYP1A2 activity may be relevant for cancers associated with exposure to HAAs. C1 ROYAL POSTGRAD MED SCH,DEPT CLIN PHARMACOL,LONDON W12 0NN,ENGLAND. USDA ARS,BELTSVILLE HUMAN NUTR RES CTR,NUTR REQUIREMENTS & FUNCT LAB,BELTSVILLE,MD 20705. UNIV ARKANSAS MED SCI HOSP,ARKANSAS CANC RES CTR,LITTLE ROCK,AR 72205. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP SINHA, R (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA N,RM 443,6130 EXECUT BLVD,ROCKVILLE,MD 20892, USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 17 TC 29 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1995 VL 16 IS 11 BP 2859 EP 2861 DI 10.1093/carcin/16.11.2859 PG 3 WC Oncology SC Oncology GA TG194 UT WOS:A1995TG19400037 PM 7586210 ER PT J AU SOINI, Y WELSH, JA ISHAK, KG BENNETT, WP AF SOINI, Y WELSH, JA ISHAK, KG BENNETT, WP TI P53 MUTATIONS IN PRIMARY HEPATIC ANGIOSARCOMAS NOT ASSOCIATED WITH VINYL-CHLORIDE EXPOSURE SO CARCINOGENESIS LA English DT Note ID CELL LUNG-CANCER; ESCHERICHIA-COLI; METABOLITE AB Angiosarcomas of the liver are rare, malignant cancers composed of neoplastic blood vessels, Human hepatic angiosarcomas have been associated with liver cirrhosis or exposure to vinyl chloride, Thorotrast or arsenic, A recent analysis of six hepatic angiosarcomas associated with vinyl chloride exposure found three mutations and all were A:T --> T:A transversions, which are otherwise uncommon in human cancers, To test the specificity of this mutation spectrum, we analyzed 21 hepatic angiosarcomas not associated with vinyl chloride exposure, Four cases were exposed to Thorotrast, none had a history of arsenic exposure and the rest were sporadic, Exons 5-8 of the p53 gene were amplified by polymerase chain reaction, and the products were sequenced directly, Two G:C --> A:T transitions were found in two tumors: TGC(cys) --> TAC(tyr) in codon 141 and CAA(gln) --> TAA(stop) in codon 136. Neither mutation was associated with Thorotrast exposure, These data indicate that p53 mutations are uncommon in sporadic hepatic angiosarcomas (2/21, 9%), and the mutational profile is consistent with endogenous mechanisms, Both features support the evidence linking vinyl chloride exposure to hepatic angiosarcomas containing an increased frequency of p53 mutations with a mutational spectrum (i.e. A:T --> T:A transversions) characteristic of chloroethylene oxide, a carcinogenic metabolite of vinyl chloride. C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV OULU,DEPT PATHOL,OULU,FINLAND. ARMED FORCES INST PATHOL,DEPT HEPAT & GASTROINTESTINAL PATHOL,WASHINGTON,DC 20306. NR 27 TC 44 Z9 45 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1995 VL 16 IS 11 BP 2879 EP 2881 DI 10.1093/carcin/16.11.2879 PG 3 WC Oncology SC Oncology GA TG194 UT WOS:A1995TG19400041 PM 7586214 ER PT J AU TAMOTSU, S SCHOMERUS, C STEHLE, JH ROSEBOOM, PH KORF, HW AF TAMOTSU, S SCHOMERUS, C STEHLE, JH ROSEBOOM, PH KORF, HW TI NOREPINEPHRINE-INDUCED PHOSPHORYLATION OF THE TRANSCRIPTION FACTOR CREB IN ISOLATED RAT PINEALOCYTES - AN IMMUNOCYTOCHEMICAL STUDY SO CELL AND TISSUE RESEARCH LA English DT Article DE PINEALOCYTES; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN (CREB); PHOSPHORYLATED CREB; BETA-ADRENERGIC RECEPTOR; S-ANTIGEN (ARRESTIN); TRANSCRIPTION FACTORS; CELL CULTURE (RAT, WISTAR) ID ADRENERGIC REGULATION; C-FOS AB In the present study we investigated whether norepinephrine, which stimulates melatonin biosynthesis in the mammalian pineal organ, causes phosphorylation of the cyclic AMP responsive element binding protein (CREB) in rat pinealocytes. Cells isolated from the pineal organ of adult male rats and cultured on coated coverslips were treated with norepinephrine, beta- or alpha(1)-adrenergic agonists for 1, 5, 10, 20, 30, 60 or 300 min and then immunocytochemically analyzed with an antibody against phosphorylated CREB (p-CREB). Treatment with norepinephrine or beta-adrenergic agonists resulted in a similar, time-dependent induction of p-CREB immunoreactivity, exclusively found in cell nuclei. The alpha(1)-adrenergic agonist phenylephrine did not induce p-CREB immunoreactivity at low doses (0.1 mu M) or when high doses (10 mu M) were applied in combination with a beta-antagonist (propranolol, 0.1 mu M). This indicates that induction of CREB phosphorylation is elicited by beta-adrenergic receptor stimulation. The response was first seen after 10 min and reached a maximum after 30 to 60 min when more than 90% of the cells displayed p-CREB immunoreactivity. The intensity of the p-CREB immunoreactivity showed marked cell-to-cell variation, but nearly all immunoreactive cells were identified as pinealocytes by double-labeling with an antibody against the S-antigen, a pinealocyte-specific marker. The results show that norepinephrine stimulation induces p-CREB immunoreactivity by acting upon beta-adrenergic receptors in virtually all rat pinealocytes. The findings support the notion that phosphorylation of CREB is a rather rapid and uniform response of pinealocytes to noradrenergic stimulation and thus is an important link between adrenoreceptor activation and subsequent gene expression in the rat pineal organ. C1 UNIV FRANKFURT,CTR MORPHOL,NEUROBIOL SECT,D-60590 FRANKFURT,GERMANY. NICHHD,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BETHESDA,MD 20892. NR 29 TC 60 Z9 60 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD NOV PY 1995 VL 282 IS 2 BP 219 EP 226 DI 10.1007/s004410050474 PG 8 WC Cell Biology SC Cell Biology GA TC845 UT WOS:A1995TC84500003 PM 8565052 ER PT J AU WOSIKOWSKI, K REGIS, JT ROBEY, RW ALVAREZ, M BUTERS, JTM GUDAS, JM BATES, SE AF WOSIKOWSKI, K REGIS, JT ROBEY, RW ALVAREZ, M BUTERS, JTM GUDAS, JM BATES, SE TI NORMAL P53 STATUS AND FUNCTION DESPITE THE DEVELOPMENT OF DRUG-RESISTANCE IN HUMAN BREAST-CANCER CELLS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID LYMPHOCYTIC-LEUKEMIA; GENE-EXPRESSION; CYCLE ARREST; APOPTOSIS; DEATH; BCL-2; PROTEIN; PROLIFERATION; CYTOTOXICITY; SENSITIVITY AB Loss of or mutations in p53 protein have been shown to decrease both radio- and chemosensitivity. The present study assessed the p53 gene status, ability to arrest in G(1) of the cell cycle, the functionality of the p53 transduction pathway, and apoptosis following treatment with radiation in a series of drug-resistant human breast cancer cells to determine whether p53 alterations occur during the development of drug resistance. We used 13 sublines derived from MCF-7, ZR75B, and T47D cells, which were resistant to doxorubicin, paclitaxel, vinblastine, cisplatin, etoposide, and amsacrine. Eleven of 12 drug-resistant sublines retained the parental p53 gene status, as determined by sequence analysis and functional yeast assay; only one subline was found to have acquired a mutation in the p53 gene. The MCF-7 TH subline was found to both acquire mutated p53 and to have major changes in p53 protein expression and function. In 12 other drug-resistant sublines, the G(1) checkpoint was conserved or only slightly impaired. A normal accumulation of p53, p21(Cip1/Waf1), and Mdm2 proteins and hypophosphorylation of Rb protein occurred in response to radiation with only small differences noted in the kinetics of p53 and p21(Cip1/Waf1) induction. Increased susceptibility to apoptosis was found in the ZR75B drug-resistant sublines, whereas no evidence for apoptosis was observed in the ZR75B, MCF-7, and T47D parentals and the MCF-7 and T47D drug-resistant sublines. This effect could not be explained by alterations in bcl-2 or bar expression. Our results demonstrate that alterations in: (a) p53 gene status; (b) ability to arrest in G(1); (c) induction of p53 protein and p53-dependent genes; and (d) decreased activation of apoptosis is not a requirement for the onset of drug resistance. The function of p53 appears to be dissociated from drug resistance in our model system. C1 NCI,DIV CANC TREATMENT,MED BRANCH,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Buters, Jeroen/G-5070-2011 NR 45 TC 69 Z9 70 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD NOV PY 1995 VL 6 IS 11 BP 1395 EP 1403 PG 9 WC Cell Biology SC Cell Biology GA TD037 UT WOS:A1995TD03700007 PM 8562478 ER PT J AU HOLMES, KL LANTZ, LM LEE, JS BEDIGIAN, HG TAUBENBERGER, JK AF HOLMES, KL LANTZ, LM LEE, JS BEDIGIAN, HG TAUBENBERGER, JK TI CHARACTERIZATION OF A NEW ANTIGEN EXPRESSED BY B-CELLS AND MYELOID LINEAGE CELLS IDENTIFIED BY THE MONOCLONAL-ANTIBODY LIP-6 SO CELLULAR IMMUNOLOGY LA English DT Article ID PRE-B; SURFACE ANTIGENS; GLYCOSYL-PHOSPHATIDYLINOSITOL; DIFFERENTIATION; REARRANGEMENT; LYMPHOMAS; ORIGIN; MICE; PB76 AB The LIP-6 MAb was produced against the undifferentiated cell line bh2-1 and recognizes an antigen expressed on all pre-B and B cell lines tested and some myeloid lineage lines. FAGS analysis of normal tissues showed that LIP-6 is expressed on B lineage cells at all stages of differentiation, from bone marrow pre-B to plasma cells, T cells and thymocytes are LIP-(6-), and splenic CD11b(+) cells are heterogeneous for LIP-6 expression. The LIP-6 MAb was shown to precipitate a major 75-kDa and a minor 85-kDa protein under reducing conditions and a large protein of >240 kDa under nonreducing conditions, Removal of N-linked sugars from the reduced lysates resulted in a single 65-kDa protein, suggesting that there is differential glycosylation of a single 65-kDa protein that forms disulfide-linked multimers. Finally, the LIP-6 antigen was shown not to be linked to the cell surface via a GPI linkage. (C) 1995 Academic Press, Inc. C1 NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. JACKSON LAB,BAR HARBOR,ME 04609. ARMED FORCES INST PATHOL,DEPT CELLULAR PATHOL,WASHINGTON,DC 20306. RP HOLMES, KL (reprint author), NIAID,MOLEC STRUCT LAB,BLDG 7,ROOM 301,7 CTR DR MSC 0760,BETHESDA,MD 20892, USA. NR 26 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV PY 1995 VL 166 IS 1 BP 131 EP 140 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA TE593 UT WOS:A1995TE59300015 PM 7585973 ER PT J AU COVITZ, W ESPELAND, M GALLAGHER, D HELLENBRAND, W LEFF, S TALNER, N AF COVITZ, W ESPELAND, M GALLAGHER, D HELLENBRAND, W LEFF, S TALNER, N TI THE HEART IN SICKLE-CELL-ANEMIA - THE COOPERATIVE STUDY OF SICKLE-CELL DISEASE (CSSCD) SO CHEST LA English DT Article DE CARDIAC DILATATION; ECHOCARDIOGRAPHY; HYPERTROPHY; SICKLE CELL DISEASE; SYSTOLIC FUNCTION ID LEFT-VENTRICULAR PERFORMANCE; ECHOCARDIOGRAPHIC MEASUREMENTS; M-MODE; CHILDREN; SIZE; RADIONUCLIDE AB The objective of this study was to obtain representative echocardiographic measurements of cardiac size and function in stable patients with sickle cell disease. This prospective, multicenter study utilized central reading of echocardiograms by an investigator blinded to other patient data, Stable outpatients from a balance of inner city and rural settings with SS phenotype and a broad age range were selected, because conflicting results from earlier studies were believed to be due to these patient selection criteria. Right and left ventricular dimensions and wall thickness, left atrial and aortic root dimensions, and systolic time intervals were measured, Body surface area indexed chamber dimensions and septal thickness were significantly increased from normal. Except for the right ventricle, chamber dimensions and wall thickness were inversely correlated with hemoglobin, The relationship between left ventricular dimension and hemoglobin was significantly dependent on age, Systolic time interval ratios were normal though left ventricular ejection time was prolonged, Shortening fraction was normal but velocity of circumferential fiber shortening was abnormally low, stable patients with sickle cell disease have dilated chambers, septal hypertrophy, and normal contractility. Though left ventricular dilatation was inversely related to hemoglobin, age (duration of illness) was an important factor in that relationship. No specific cardiomyopathy was associated with sickle cell anemia. C1 NHLBI,SICKLE CELL DIS BRANCH,BETHESDA,MD. NR 36 TC 82 Z9 85 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 NOV PY 1995 VL 108 IS 5 BP 1214 EP 1219 DI 10.1378/chest.108.5.1214 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA TD708 UT WOS:A1995TD70800014 PM 7587419 ER PT J AU GIBSON, KF AGUAYO, SM FLOWERS, JC FORD, JG JACKSON, JH LWEBUGAMUKASA, JS ROMAN, J SAMET, JM THOMAS, AV YOUNG, RC HURD AF GIBSON, KF AGUAYO, SM FLOWERS, JC FORD, JG JACKSON, JH LWEBUGAMUKASA, JS ROMAN, J SAMET, JM THOMAS, AV YOUNG, RC HURD TI RESPIRATORY-DISEASES DISPROPORTIONATELY AFFECTING MINORITIES SO CHEST LA English DT Article DE ETHNIC GROUPS; LUNG DISEASES; MINORITY GROUPS; RISK FACTORS ID OBSTRUCTIVE PULMONARY-DISEASE; SICKLE-CELL DISEASE; UNITED-STATES; NEW-MEXICO; LUNG-CANCER; ASTHMA HOSPITALIZATIONS; PNEUMOCOCCAL VACCINE; POPULATION-SAMPLE; CIGARETTE-SMOKING; AFRICAN-AMERICANS C1 NHLBI,DIV LUNG DIS,PULM DIS ADVISORY COMM,WORKING GRP,BETHESDA,MD 20892. NR 74 TC 28 Z9 28 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 NOV PY 1995 VL 108 IS 5 BP 1380 EP 1392 PG 13 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA TD708 UT WOS:A1995TD70800041 ER PT J AU FLACK, JM NEATON, J GRIMM, R SHIH, J CUTLER, J ENSRUD, K MACMAHON, S AF FLACK, JM NEATON, J GRIMM, R SHIH, J CUTLER, J ENSRUD, K MACMAHON, S TI BLOOD-PRESSURE AND MORTALITY AMONG MEN WITH PRIOR MYOCARDIAL-INFARCTION SO CIRCULATION LA English DT Article DE BLOOD PRESSURE; MYOCARDIAL INFARCTION; HEART DISEASES; MORTALITY ID CORONARY HEART-DISEASE; FACTOR INTERVENTION TRIAL; RISK-FACTORS; FOLLOW-UP; HYPERTENSION; REDUCTION; FRAMINGHAM; DEATH; SURVIVAL; SMOKING AB Background The purpose of the present study was to describe the relation between blood pressure (systolic [SEP] and diastolic [DBP]) and death from coronary heart disease (CHD) and all causes for men with a history of myocardial infarction (MI). Methods and Results The study cohort consisted of men aged 35 to 57 years screened for the Multiple Risk Factor Intervention Trial (MRFIT) in 1973 through 1975 and followed for survival for an average of 16 years through 1990. There were 5362 men who reported prior hospitalization for a heart attack of at least 2 weeks' duration at the initial screening of MRFIT. There was a J-shaped relation between SEP and DBP with both CHD and all-cause mortality during the first 2 years of follow-up in older (age, 45 to 57 years) men only. Risk nadirs for SEP were 152 and 145 mm Hg, respectively, for CHD death and air-cause mortality; corresponding DBP risk nadirs were 94 and 90 mm Hg. After the first 2 years, there was a positive association between SEP and death from CHD and all causes. By 15 years, cumulative CHD mortality percentages for men with screening SEP <120, 120 to 139, 140 to 159, and greater than or equal to 160 mm Hg were 19.7%, 21.3%, 27.5%, and 32.0%, respectively. When deaths only after year 2 were considered, although the linear DBP coefficient was significant, the quadratic term for DBP was no longer significant (P>.05). However, the relation still appeared J-shaped as cumulative mortality for those with DBP <70, 70 to 79, 80 to 89, 90 to 99, and greater than or equal to 100 mm Hg was 24.3%, 20.8%, 21.1%, 25.5%, and 29.7%, respectively. When the joint relation of SEP and DBP was considered, there were no survival differences among the four cohorts (SEP greater than or equal to 140 and DBP <80, SEP greater than or equal to 140 and DBP greater than or equal to 80, SEP greater than or equal to 140 and DBP <80, and SEP greater than or equal to 140 and DBP greater than or equal to 80) during the first 2 years. After 2 years, both CHD and all-cause mortality rates were approximately 40% higher for participants with SEP greater than or equal to 140 mm Hg versus <140 mm Hg regardless of DBP level (<80 or greater than or equal to 80 mm Hg). Conclusions In this large cohort of men with prior MI, the association of SEP and DBP with CHD and all-cause mortality varied over the 16-year follow-up period. During early followup, in older men only, J- or U-shaped relations were evident. However, after 2 years, these same relations had become positive and graded. Given the substantial excess mortality risk in this cohort associated with high blood pressure, particularly SEP, efforts to gradually lower blood pressure should receive high priority among hypertensive men with prior MI. C1 UNIV MINNESOTA,SCH PUBL HLTH,DIV BIOSTAT,MINNEAPOLIS,MN. UNIV MINNESOTA,SCH MED,DIV CARDIOL,MINNEAPOLIS,MN. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV MINNESOTA,VET ADM MED CTR,GEN MED SECT,MINNEAPOLIS,MN. UNIV AUCKLAND,DEPT MED,CLIN TRIALS RES UNIT,AUCKLAND,NEW ZEALAND. RP FLACK, JM (reprint author), BOWMAN GRAY SCH MED,CTR HYPERTENS,DIV HYPERTENS,CLIN SCI BLDG,ROOM 5180,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. FU NHLBI NIH HHS [N01-HV-487048, R01-HL-34767, R01-HL-46630-01A1] NR 41 TC 142 Z9 149 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 1 PY 1995 VL 92 IS 9 BP 2437 EP 2445 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TC796 UT WOS:A1995TC79600014 PM 7586343 ER PT J AU CORDA, S SPURGEON, HA LAKATTA, EG CAPOGROSSI, MC ZIEGELSTEIN, RC AF CORDA, S SPURGEON, HA LAKATTA, EG CAPOGROSSI, MC ZIEGELSTEIN, RC TI ENDOPLASMIC-RETICULUM CA2+ DEPLETION UNMASKS A CAFFEINE-INDUCED CA2+ INFLUX IN HUMAN AORTIC ENDOTHELIAL-CELLS SO CIRCULATION RESEARCH LA English DT Article DE CELL CALCIUM; ENDOTHELIUM; CAFFEINE; THAPSIGARGIN; INDO 1 ID MUSCLE SARCOPLASMIC-RETICULUM; RELEASE CHANNEL; CA-2+ MOBILIZATION; CALCIUM RELEASE; IONIC CURRENTS; THAPSIGARGIN; STORES; HISTAMINE; HOMEOSTASIS; INHIBITION AB Intracellular Ca2+ pools contribute to changes in cytosolic [Ca2+] ([Ca2+](i)), which play an important role in endothelial cell signaling. Recently, endothelial ryanodine sensitive Ca2+ stores were shown to regulate agonist-sensitive intracellular Ca2+ pools. Since caffeine binds the ryanodine Ca2+ release channel on the endoplasmic reticulum in a variety of cell types, we examined the effect of caffeine on [Ca2+](i) in human aortic endothelial cell monolayers loaded with the fluorescent probe indo 1. Under baseline conditions, 10 mmol/L caffeine induced a small increase in [Ca2+](i) from 86+/-10 to 115+/-17 nmol/L (mean+/-SEM); this effect was similar to that of 5 mu mol/L ryanodine and was unaffected by buffer Ca2+ removal. After depletion of an intracellular Ca2+ store by the irreversible endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin (1 mu mol/L), ryanodine did not affect [Ca2+](i). In contrast, caffeine induced a large rapid increase in [Ca2+](i) (176+/-19 to 338+/-35 nmol/L, P<.001) after thapsigargin exposure; this effect of caffeine was only observed when extracellular Ca2+ was present. A similar increase in [Ca2+](i) was induced by caffeine after depletion of ryanodine- and histamine-sensitive Ca2+ stores or after pretreatment with the endoplasmic reticulum Ca2+-ATPase inhibitor cyclopiazonic acid (10 mu mol/L). Thus, under baseline conditions the effect of caffeine on [Ca2+](i) is similar to that of ryanodine and appears to be due to the release of an intracellular store. However, after depletion of an endoplasmic reticulum Ca2+ store, caffeine, but not ryanodine, stimulates Ca2+ influx, resulting in a large increase in [Ca2+](i). The data suggest that caffeine-induced Ca2+ influx is controlled by the status of Ca2+ loading of intracellular Ca2+ stores in human aortic endothelial cells. C1 NIA, CARDIOVASC SCI LAB, BALTIMORE, MD 21224 USA. NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, DEPT MED, DIV CARDIOL, BALTIMORE, MD USA. NR 37 TC 27 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD NOV PY 1995 VL 77 IS 5 BP 927 EP 935 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA TB973 UT WOS:A1995TB97300008 PM 7554146 ER PT J AU BLUMENTHAL, MN BANKSSCHLEGEL, S BLEECKER, ER MARSH, DG OBER, C AF BLUMENTHAL, MN BANKSSCHLEGEL, S BLEECKER, ER MARSH, DG OBER, C TI COLLABORATIVE STUDIES ON THE GENETICS OF ASTHMA - NATIONAL HEART, LUNG AND BLOOD INSTITUTE SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article; Proceedings Paper CT Symposium on Recent Advances in the Genetics of Asthma and Allergy CY SEP 28-OCT 01, 1994 CL CANNES, FRANCE C1 NHLBI,AIRWAYS DIS BRANCH,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. UNIV CHICAGO,DEPT OBSTET & GYNAECOL,CHICAGO,IL 60637. RP BLUMENTHAL, MN (reprint author), UNIV MINNESOTA,DEPT MED,ALLERGY SECT,BOX 434 UMCH,420 DELAWARE ST SE,MINNEAPOLIS,MN 55455, USA. NR 0 TC 37 Z9 37 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD NOV PY 1995 VL 25 SU 2 BP 29 EP 32 DI 10.1111/j.1365-2222.1995.tb00416.x PG 4 WC Allergy; Immunology SC Allergy; Immunology GA TE570 UT WOS:A1995TE57000010 PM 8590337 ER PT J AU Bukh, J Miller, RH Purcell, RH AF Bukh, J Miller, RH Purcell, RH TI Biology and genetic heterogeneity of hepatitis C virus SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article; Proceedings Paper CT Conference on Hepatitis C Virus and Cryoglobulinemia CY OCT 13-14, 1994 CL MILAN, ITALY DE hepatitis; cryoglobulinemia; hepatocellular carcinoma; genotypes; quasispecies ID NON-B-HEPATITIS; POLYMERASE CHAIN-REACTION; NON-A; HYPERVARIABLE REGIONS; SEQUENCE-ANALYSIS; ENVELOPE; GLYCOPROTEIN; INFECTION; GENOTYPES; PROTEIN AB Hepatitis C virus (HCV) has a significant albeit varied, presence around the world. This virus is primarily transmitted parenterally, although sexual and perinatal transmission does appear to occur. However, no risk factor for transmission could be identified in a significant proportion of infected individuals. It was found that individuals became viremic early after the primary HCV infection, whereas seroconversion and hepatitis occurred several weeks later. It was demonstrated that less than 20% of patients cleared their viremia, with the majority of patients becoming chronically infected A significant proportion of chronically infected individuals developed chronic hepatitis and liver cirrhosis, and a strong association has been found with the development of hepatocellular carcinoma. Finally, HCV seems to be associated with autoimmune diseases and type II cryoglobulinemia. Thus, significant morbidity and mortality is caused by HCV infection worldwide. In a single infected individual the genome population of HCV has been found to comprise a quasispecies that consists of a number of identical sequences (i.e., the master sequence) and other closely related sequences. The master sequence of this quasispecies population changes during infection. In particular it has been found that the sequence of the hypervariable region 1 changes rapidly in infected individuals. It is possible that the quasispecies nature of HCV constitutes a mechanism by which HCV escapes immune surveillance and establishes a persistent infection in the host. It is now well established that HCV exists as distinct genotypes among different HCV isolates. According to the currently used classification these can be divided into a number of major genetic groups (or types) and subgroups (or subtypes). The extensive genetic heterogeneity of HCV has important implications for diagnosis, pathogenesis, treatment and vaccine development. C1 NIAID,NIH,DIV AIDS,BETHESDA,MD 20892. RP Bukh, J (reprint author), NIAID,NIH,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BLDG 7,ROOM 201,7 CTR DR MSC 0740,BETHESDA,MD 20892, USA. NR 42 TC 12 Z9 12 U1 0 U2 1 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 NOV-DEC PY 1995 VL 13 SU 13 BP S3 EP S7 PG 5 WC Rheumatology SC Rheumatology GA UF130 UT WOS:A1995UF13000002 PM 8730468 ER PT J AU Farci, P Orgiana, G Purcell, RH AF Farci, P Orgiana, G Purcell, RH TI Immunity elicited by hepatitis C virus SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article; Proceedings Paper CT Conference on Hepatitis C Virus and Cryoglobulinemia CY OCT 13-14, 1994 CL MILAN, ITALY DE hepatitis C virus; protective immunity; neutralizing antibodies; quasispecies; genetic heterogeneity ID NON-B-HEPATITIS; NON-A; SEQUENCE; GENOME; DONOR AB Hepatitis C virus (HCV), the major causative agent of post-transfusion and community-acquired non-A, non-B (NANB), is a single-stranded RNA virus characterized by a high degree of genetic heterogeneity. HCV is endemic worldwide and is a major cause of chronic liver disease and hepatocellular carcinoma. The development of a broadly reactive vaccine is a high priority for the control of HCV infection. In recent years, however, serious concerns have been raised regarding the degree of protective immunity elicited by HCV in the host. Several observations, both inpatients and in the chimpanzee model, have suggested a lack of protective immunity against HCV. Chronic HCV infection develops in more than 80% of patients, suggesting that in most cases the immune response of the host fails to mediate resolution of the infection. Cross-challenge studies demonstrated that convalescent chimpanzees are not protected against re-infection with homologous or heterologous HCV strains. Similar evidence has been obtained in polytransfused beta-thalassemic children, in whom re-infection with HCV was associated with multiple episodes of acute hepatitis. Although most of the evidence thus far accumulated suggests that HCV does not elicit a protective immune response, recent studies have provided experimental evidence, both in vitro and in vivo, that HCV infection induces a neutralizing antibody response in humans. However, such antibodies are isolate-restricted and ineffective against variant HCV strains emerging in vivo. Recently, using recombinant envelope proteins of HCV, a successful vaccination of chimpanzees against challenge with a homologous viral strain was reported Whether this vaccine can provide protection against challenge with a higher infectious dose of the homologous virus or against challenge with heterologous strains of HCV remains to be established. Overall, the data hitherto accumulated indicate that the genetic heterogeneity of HCV will be a major impediment for the development of a broadly reactive vaccine for the control of HCV infection. C1 NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. RP Farci, P (reprint author), UNIV CAGLIARI,IST MED INTERNA,VIA SAN GIORGIO 12,I-09100 CAGLIARI,ITALY. NR 29 TC 6 Z9 6 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 NOV-DEC PY 1995 VL 13 SU 13 BP S9 EP S12 PG 4 WC Rheumatology SC Rheumatology GA UF130 UT WOS:A1995UF13000003 PM 8730469 ER PT J AU Debinski, W Obiri, NI Powers, SK Pastan, I Puri, RK AF Debinski, W Obiri, NI Powers, SK Pastan, I Puri, RK TI Human glioma cells overexpress receptors for interleukin 13 and are extremely sensitive to a novel chimeric protein composed of interleukin 13 and Pseudomonas exotoxin SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTORS; HUMAN-MALIGNANT GLIOMA; FUSION PROTEINS; BRAIN-TUMORS; EXPRESSION; TOXIN; AERUGINOSA; GENE; MICE AB Recently, we have demonstrated that a spectrum of human adenocarcinoma cell lines express binding sites for interleukin 13 (IL-13). These cells are killed by a chimeric protein composed of human (h) IL-13 and a derivative of Pseudomonas exotoxin, PE38QQR (Debinski et al., J. Biol. Chem., 270: 16775-16780, 1995). The cell killing was hIL13- and hIL-4-specific, indicating that a common binding site for the two cytokines is present in several solid tumor cell lines. Herein, we report that an array of established glioma cell lines is killed by very low concentrations of hIL-13-PE38QQR, often reaching <1 ng/ml(<20 pM). Glioma cells express up to 30,000 molecules of IL-13 receptor/cell which has intermediate affinity toward hIL-13. hIL-13-PE38QQR is more active (up to 3 logs difference in cytotoxic activities) than are the corresponding chimeric toxins containing hIL-4 or hIL-6. The cytotoxic action of hIL-13-PE38QQR is blocked by an excess of hIL-13 on all cell lines studied, and it is not neutralized by hIL-4 on some of these cells. Our results show that human brain cancers richly express receptors for IL-13. Furthermore, the interaction detected previously between receptors for IL-13 and IL-4 on solid tumors cell lines is of a qualitatively different character in U-251 MG and U-373 MG glioma cells, The receptor for IL-13 may represent a new marker of brain cancers and an attractive target for anticancer therapies. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,MOLEC TUMOR BIOL LAB,BETHESDA,MD 20895. NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. RP Debinski, W (reprint author), PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT SURG,DIV NEUROSURG,BRB C3844,HERSHEY,PA 17033, USA. NR 33 TC 161 Z9 166 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1995 VL 1 IS 11 BP 1253 EP 1258 PG 6 WC Oncology SC Oncology GA TL086 UT WOS:A1995TL08600003 PM 9815919 ER PT J AU Brooks, D Taylor, C DosSantos, B Linden, H Houghton, A Hecht, TT Kornfeld, S Taetle, R AF Brooks, D Taylor, C DosSantos, B Linden, H Houghton, A Hecht, TT Kornfeld, S Taetle, R TI Phase Ia trial of murine immunoglobulin A antitransferrin receptor antibody 42/6 SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL-GROWTH-INVITRO; TRANSFERRIN RECEPTOR; MONOCLONAL-ANTIBODY; TUMOR-CELLS; EXPRESSION; LEUKEMIA; INVIVO; INHIBITION; RELEVANCE AB In preclinical in vitro and in vivo systems, mAbs to human transferrin (Tf) receptors blocked iron uptake from Tf and shelved antitumor activity, However, Tf receptors are also displayed by normal tissues, and a large, soluble pool of circulating serum Tf receptors has been detected, We report results of a Phase Ia trial of IgA monoclonal anti-Tf receptor antibody 42/6, Twenty-seven patients with advanced refractory cancer received 33 treatments with 42/6 administered as a 24-h infusion at doses ranging from 2.5 to 300 mg/m(2), 42/6 was generally well tolerated, although one patient receiving a second treatment experienced an allergic-type response associated with a human antimouse antibody response, Three patients with hematological cancers showed mixed tumor responses; there were no partial or complete remissions, Peak serum levels of antibody were obtained at the termination of the 24-h infusion, At doses greater than or equal to 25 mg/m(2), there was a linear relationship between the 42/6 dose and average peak serum 42/6 levels ranging from <1 to 36 mu g/ml. Serum Tf receptors showed a dose-dependent decrease during 42/6 infusion to 20-30% of baseline, and remained depressed for at least 48 h after terminating the infusion, Serum 42/6 levels rose in an inverse relationship to the drop in Tf receptors, 42/6 induced an increase in serum iron and Tf saturation consistent with blockade of peripheral iron uptake, and reduced Tf receptor display by bone marrow cells, Human antimouse antibody was detected in nine patients, Anti-Tf receptor antibody was well tolerated and mediated in vivo effects on iron uptake and Tf display, Antibody concentrations capable of inhibiting malignant blood cell growth were obtained without toxicity, This represents the first clinical trial of an IgA mouse mAb, and one of only a few trials in which an antibody reacting with a broad range of normal tissues has been administered, Additional clinical trials of anti-Tf receptor antibodies in blood cell cancers are indicated. C1 UNIV ARIZONA, ARIZONA CANC CTR, HEMATOL ONCOL SECT, TUCSON, AZ 85724 USA. UNIV ARIZONA, DEPT MED, TUCSON, AZ 85724 USA. UNIV ARIZONA, DEPT PATHOL, TUCSON, AZ 85724 USA. MEM SLOAN KETTERING INST CANC RES, NEW YORK, NY 10021 USA. NCI, BIOL RESPONSE MODIFIERS PROGRAM, FREDERICK, MD 21701 USA. FU NCI NIH HHS [CA37641, CA57535] NR 42 TC 34 Z9 38 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1995 VL 1 IS 11 BP 1259 EP 1265 PG 7 WC Oncology SC Oncology GA TL086 UT WOS:A1995TL08600004 PM 9815920 ER PT J AU Zea, AH Curti, BD Longo, DL Alvord, WG Strobl, SL Mizoguchi, H Creekmore, SP O'Shea, JJ Powers, GC Urba, WJ Ochoa, AC AF Zea, AH Curti, BD Longo, DL Alvord, WG Strobl, SL Mizoguchi, H Creekmore, SP O'Shea, JJ Powers, GC Urba, WJ Ochoa, AC TI Alterations in T cell receptor and signal transduction molecules in melanoma patients SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-BEARING MICE; TYROSINE PHOSPHORYLATION; SUPPRESSOR MACROPHAGES; HODGKINS-DISEASE; CLONAL ANERGY; KILLER-CELLS; ACTIVATION; CARCINOMA; LYMPHOCYTES; GENERATION AB We have recently described molecular changes in T cells from tumor-bearing patients that are associated with depressed immune function, The present work investigates changes in T-cell signal transduction proteins including the T-cell receptor-zeta (TCR-zeta) chain and receptor-associated tyrosine kinases in patients with metastatic malignant melanoma, A marked decrease in the expression of the TCR-zeta chain was observed in the peripheral blood T cells of 19 (43%) of 44 patients, Decreases in several tyrosine kinases were found in 12 (57%) of 21 patients tested, T cells from patients with diminished TCR-zeta chain expression also showed statistically significant differences in cytokine production pattern, with lower interleukin 2 and IFN-gamma production compared with normal subjects and melanoma patients with normal TCR-zeta chain status, The overall survival of melanoma patients with low TCR-zeta chain expression was significantly shorter than that of patients with normal TCR-zeta chain expression (P = 0.0013), TCR-zeta-deficient patients showed a trend toward having faster growing tumors, There was no correlation between the pretreatment TCR-zeta chain status and albumin or performance status, These findings suggest that alterations in T-cell function occur commonly in melanoma patients and may be independent predictors of clinical outcome. C1 NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, DIV CANC TREATMENT, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, IMMUNOTHERAPY LAB, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, SCI APPLICAT INT CORP, CLIN SERV PROGRAM, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, DATA MANAGEMENT SERV INC, FREDERICK, MD 21702 USA. NR 30 TC 171 Z9 175 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1995 VL 1 IS 11 BP 1327 EP 1335 PG 9 WC Oncology SC Oncology GA TL086 UT WOS:A1995TL08600012 PM 9815928 ER PT J AU Geoffroy, F Dahut, W Takimoto, CH Grem, JL AF Geoffroy, F Dahut, W Takimoto, CH Grem, JL TI Effects of 9-aminocamptothecin on newly synthesized DNA in patient bone marrow samples SO CLINICAL CANCER RESEARCH LA English DT Article ID STEP ALKALINE ELUTION; TOPOISOMERASE-I; CELLS-INVITRO; CAMPTOTHECIN; XENOGRAFTS; REGRESSION; CARCINOMA; MICE AB 9-Aminocamptothecin (9-AC) inhibited cell growth and DNA synthesis in HCT 116 human colon cancer cells in a concentration- and time-dependent manner, Interference with nascent DNA chain elongation was monitored using pH step alkaline elution, After a 3-day 9-AC exposure, 38% (10 nM) and 53% (50 nM) of the total [H-3]DNA eluted with pH steps 11.3-11.7, compared to 9% in control cells, Effects on nascent DNA integrity were also evaluated by fixed elution with pH 12.1 buffer, After a 3-day exposure to 9-AC, 27% (10 nM) and 82.5% (50 nM) of the total [H-3]DNA eluted relative to control, Paired bone marrow samples were then obtained in 10 patients before treatment and between 42 and 72 h of a continuous i.v. infusion of 9-AC (35-74 mu g/m(2)/h for 72 h), The mononuclear cells were incubated with [H-3]dThd for 2 or 4 h, and then analyzed using either pH step or fixed pH alkaline elution, respectively, In seven patients receiving greater than or equal to 47 mu g/m(2)/h 9-AC, 4% +/- 1.5% (mean +/- SE) of the total [H-3]DNA eluted with pH steps less than or equal to 11.7 in the pretreatment samples compared to 13% +/- 3.6% during 9-AC (P = 0.037), An altered fixed pH elution profile of nascent DNA was noted in two patients treated with 59 and 74 mu g/m(2)/h 9-AC compared to baseline, DNA synthesis was inhibited by 89% +/- 5% during infusion of greater than or equal to 59 mu g/m(2)/h 9-AC (n = 7), Since hematological toxicity is dose limiting on this 9-AC schedule, these cellular pharmacodynamic studies provide evidence of a DNA-directed cytotoxic effect of 9-AC in a sensitive host target tissue. C1 NCI,NATL NAVAL MED CTR,DIV CANC TREATMENT,NAVAL MED ONCOL BRANCH,CLIN ONCOL PROGRAM,BETHESDA,MD 20889. NR 24 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1995 VL 1 IS 11 BP 1345 EP 1351 PG 7 WC Oncology SC Oncology GA TL086 UT WOS:A1995TL08600014 PM 9815930 ER PT J AU TORRENCE, PF LI, GY XIAO, W AF TORRENCE, PF LI, GY XIAO, W TI TARGETED DESTRUCTION OF RNA - NOVEL CHIMERIC (2',5')-OLIGOADENYLATE-(3',5')-OLIGONUCLEOTIDES WITH PHOSPHODIESTERASE-RESISTANT STRUCTURES SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIDDK,MED CHEM LAB,BIOMED CHEM SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 1995 VL 41 IS 11 BP 12 EP 12 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA TD497 UT WOS:A1995TD49700044 ER PT J AU HRISTOVA, EN CECCO, S NIEMELA, JE REHAK, NN ELIN, RJ AF HRISTOVA, EN CECCO, S NIEMELA, JE REHAK, NN ELIN, RJ TI ANALYZER-DEPENDENT DIFFERENCES IN RESULTS FOR IONIZED CALCIUM, IONIZED MAGNESIUM, SODIUM, AND PH SO CLINICAL CHEMISTRY LA English DT Article DE ELECTROLYTES; ION-SELECTIVE ELECTRODES; REFERENCE INTERVAL ID ELECTRODES; PLASMA; SERUM AB We compared two ion-selective analyzers (AVL 988-4 and NOVA CRT) for determining ionized calcium (iCa(2+)), ionized magnesium (iMg(2+)), sodium (Na+), and pH in serum specimens from healthy and diseased individuals. For assays of three levels of protein-based control materials, total imprecision (CV) was <3% for all analytes except iMg(2+) (less than or equal to 6.5% on NOVA, and less than or equal to 4.9% on AVL). We found a significant difference between the analyzers (P < 0.001) for the mean iMg(2+) concentration in patients but no significant correlation (r = 0.253) between the analyzers for iMg(2+) in specimens from healthy volunteers, even though the mean iMg(2+) concentration did not differ significantly between these groups. The reference interval (central 95 percentiles) for iMg(2+) with AVL (0.44-0.60 mmol/L) was contained within that of NOVA (0.39-0.64 mmol/L). The AVL gave higher values for iCa(2+) (P < 0.001) and lower values for pH (P < 0.001) in specimens from normal volunteers and patients. The mean value for Na+ in patients' samples was significantly higher by the NOVA (P < 0.01) than by the AVL analyzer. Thus, we found significant differences between these two analyzers for all four analytes. RP HRISTOVA, EN (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,CLIN CHEM SERV,BLDG 10,ROOM 2C-407,BETHESDA,MD 20892, USA. RI Chorbadzhiyska, Elitsa/F-2161-2014; OI Niemela, Julie/0000-0003-4197-3792 NR 20 TC 42 Z9 44 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 1995 VL 41 IS 11 BP 1649 EP 1653 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA TD497 UT WOS:A1995TD49700017 PM 7586557 ER PT J AU RAO, VH BRIDGE, JA NEFF, JR SCHAEFER, GB BUEHLER, BA VISHWANATHA, JK POLLOCK, RE NICOLSON, GL YAMAMOTO, M GOKASLAM, ZL STETLERSTEVENSON, WG SAWAYA, R RAO, JS AF RAO, VH BRIDGE, JA NEFF, JR SCHAEFER, GB BUEHLER, BA VISHWANATHA, JK POLLOCK, RE NICOLSON, GL YAMAMOTO, M GOKASLAM, ZL STETLERSTEVENSON, WG SAWAYA, R RAO, JS TI EXPRESSION OF 72 KDA AND 92 KDA TYPE-IV COLLAGENASES FROM HUMAN GIANT-CELL TUMOR OF BONE SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE INVASION; METALLOPROTEINASES; METASTASIS; TISSUE INHIBITORS OF METALLOPROTEINASES ID MATRIX METALLOPROTEINASES; STROMAL CELLS; METASTASIS; TISSUE; STROMELYSIN; MACROPHAGES; INHIBITORS AB Basement membrane forms widespread barriers to tumor invasion, It has been shown that tumor-secreted, basement membrane-degrading enzymes, namely metalloproteinases (MMPs) play an important role in tumor invasion and metastasis. In this study,we determined the enzymatic activity, content, and mRNA of both the 72 kDa (MMP-2) and 92 kDa (MMP-9) MMPs in primary cultures of human giant-cell tumor of bone (GCT) in vitro and in tissue extracts (in vivo). Gelatin zymography showed the presence of lytic bands at M(r) 121000, 92000, and 72000, and these enzymatic activities were inhibited by EDTA, an inhibitor of MMPs. Western blots with antibodies specific for MMP-2 and MMP-9 confirmed the presence of MMP-2 and MMP-9 both in vitro and in vivo, but GCT cells at late passage showed only MMP-2. Northern blots using labeled cDNA probes specific for these molecules revealed the presence of 3.1 kb transcript for MMP-2 and a 2.9 kb transcript for MMP-9. Using specific antibodies to 72 kDa and 92 kDa type IV collagenases, we studied their cellular distribution by immunohistochemical means, Stronger immunoreactivity was found for 92 kDa type IV collagenase than 72 kDa type IV collagenase in the giant cells, It appears, therefore, that MMP-9 may play an important role in the malignant behavior of GCTs and suggests a potential therapeutic role for protease inhibitors in attempting to minimize the invasive behavior of GCTs. C1 UNIV NEBRASKA,MED CTR,DEPT PEDIAT,MATRIX RES LAB,OMAHA,NE 68198. UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE 68198. UNIV NEBRASKA,MED CTR,DEPT ORTHOPED SURG,OMAHA,NE 68198. UNIV NEBRASKA,MED CTR,DEPT BIOCHEM,OMAHA,NE 68198. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT SURG ONCOL,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT TUMOR BIOL,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT NEUROSURG,HOUSTON,TX 77030. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NCI NIH HHS [CA 56792] NR 37 TC 23 Z9 23 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD NOV PY 1995 VL 13 IS 6 BP 420 EP 426 DI 10.1007/BF00118181 PG 7 WC Oncology SC Oncology GA TD040 UT WOS:A1995TD04000002 PM 7586800 ER PT J AU Rao, PR Jones, S Sun, Z Hosmane, RS Abugo, O Rifkind, J AF Rao, PR Jones, S Sun, Z Hosmane, RS Abugo, O Rifkind, J TI Aspirin analogues and flow of erythrocytes through narrow capillaries SO CLINICAL HEMORHEOLOGY LA English DT Article DE erythrocytes; deformability; salicylates; aspirin; lipophilicity; capillary ID ANESTHETICS AB We demonstrate that in vitro incubation of erythrocytes from normal human adults in a series of aspirin analogues of increasing lipophilicity leads to a correspondingly decreased resistance (apparent viscosity) to their flow in narrow capillaries. No particular trend was observed in mean cell volume and morphologic characteristics of the cells. These observations demonstrate that erythrocyte flow characteristics are affected even before any observable changes occur in morphologic and geometric characteristics. We suggest that other changes occur in the membrane constitution which lead to a decreased membrane elastic stiffness and shear viscosity. These changes are greater with more lipophilic salicylates, perhaps, because they are adsorbed to a greater degree in the lipid bilayer and they disrupt the constitution of the membrane to a greater extent. C1 UNIV MARYLAND,DEPT CHEM & BIOCHEM,BALTIMORE,MD 21228. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP Rao, PR (reprint author), UNIV MARYLAND,DEPT MECH ENGN,BALTIMORE,MD 21228, USA. NR 14 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 0271-5198 J9 CLIN HEMORHEOL JI Clin. Hemorheol. PD NOV-DEC PY 1995 VL 15 IS 6 BP 877 EP 887 PG 11 WC Hematology SC Hematology GA TL503 UT WOS:A1995TL50300009 ER PT J AU MOFENSON, LM KORELITZ, J PELTON, S MOYE, J NUGENT, R BETHEL, J AF MOFENSON, LM KORELITZ, J PELTON, S MOYE, J NUGENT, R BETHEL, J TI SINUSITIS IN CHILDREN INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS - CLINICAL CHARACTERISTICS, RISK-FACTORS, AND PROPHYLAXIS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INTRAVENOUS IMMUNOGLOBULIN; OTITIS-MEDIA AB The clinical presentation, radiological and laboratory evaluation, treatment, and risk factors of sinusitis in a cohort of 376 human immunodeficiency virus (HIV)-infected children from a placebo-controlled clinical trial of intravenous immunoglobulin (MG) as prophylaxis for infections were examined. Ninety-five episodes of sinusitis were described in 60 patients; one-third of the patients had two or more episodes. Sinusitis episodes were commonly associated with nonspecific, chronic symptoms (67.4%, persistent nasal discharge; 54.7%, nocturnal or persistent cough), whereas symptoms more specific to acute sinusitis were less frequent (17.9%, headache or facial pain; 9.5%, periorbital swelling; 25.3%, temperature of greater than or equal to 102 degrees F; 9%, total white blood cell count of >15,000/mm(3)). The sinuses primarily involved were the maxillary sinus (85.9%) and the ethmoidal sinus (42.3%); 36% of episodes involved two or more sinuses. Preceding respiratory infections did not appear to increase the risk of sinusitis, and CD4(+) lymphocyte counts in children with and without sinusitis did not differ. Neither monthly IVIG prophylaxis nor three times weekly trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii pneumonia decreased the risk of sinusitis. Sinusitis in HIV-infected children is most often subacute and recurrent. Evaluations of new modalities for prophylaxis for sinusitis are needed. C1 WESTAT CORP,ROCKVILLE,MD 20850. BOSTON CITY HOSP,DIV PEDIAT INFECT DIS,BOSTON,MA 02118. RP MOFENSON, LM (reprint author), NICHHD,CTR RES MOTHERS & CHILDREN,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,EXECUT BLDG,BETHESDA,MD 20892, USA. OI Mofenson, Lynne/0000-0002-2818-9808; moye, john/0000-0001-9976-8586 NR 30 TC 13 Z9 15 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV PY 1995 VL 21 IS 5 BP 1175 EP 1181 DI 10.1093/clinids/21.5.1175 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TC172 UT WOS:A1995TC17200016 PM 8589139 ER PT J AU ROSS, JP HOLLAND, SM GILL, VJ DECARLO, ES GALLIN, JI AF ROSS, JP HOLLAND, SM GILL, VJ DECARLO, ES GALLIN, JI TI SEVERE BURKHOLDERIA (PSEUDOMONAS) GLADIOLI INFECTION IN CHRONIC GRANULOMATOUS-DISEASE - REPORT OF 2 SUCCESSFULLY TREATED CASES SO CLINICAL INFECTIOUS DISEASES LA English DT Note ID RESPIRATORY-TRACT; CYSTIC-FIBROSIS; CEPACIA; PNEUMONIA AB Chronic granulomatous disease (CGD) is characterized by a defect in phagocytic cells that leads to recurrent superficial and deep pyogenic infections. Burkholderia (Pseudomonas) gladioli is a gram-negative bacillus in the pseudomallei group of pseudomonads that is known primarily as a plant pathogen. We report two cases of pneumonia, one accompanied by septicemia, caused by B. gladioli in patients with CGD and their successful treatment with antibiotics. We believe these represent the first reports of human disease caused by this organism. We conclude that B. gladioli should be considered a potential pathogen in patients with CGD. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD 20892. NR 17 TC 57 Z9 58 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV PY 1995 VL 21 IS 5 BP 1291 EP 1293 DI 10.1093/clinids/21.5.1291 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TC172 UT WOS:A1995TC17200035 PM 8589158 ER PT J AU Harlow, E Tlsty, T Courtneidge, S McCormick, F Tocque, B Yaniv, M Woude, GV Herlich, P Bohmann, D Howley, P Levine, A Prives, C Lane, D Oren, M Kimchi, A Thomas, G Feuteun, J AF Harlow, E Tlsty, T Courtneidge, S McCormick, F Tocque, B Yaniv, M Woude, GV Herlich, P Bohmann, D Howley, P Levine, A Prives, C Lane, D Oren, M Kimchi, A Thomas, G Feuteun, J TI Cancer: The translation of advances in basic science to human therapy. 22-27 July, 1995 - La fondation des Treilles, Tourtour, France - Discussion SO COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE III-SCIENCES DE LA VIE-LIFE SCIENCES LA English DT Discussion C1 INST PASTEUR,PARIS,FRANCE. MGH,CTR CANC,BOSTON,MA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. EMBL,HEIDELBERG,GERMANY. SUGEN,REDWOOD CITY,CA. ONYX PHARMACEUT,RICHMOND,CA. RHONE POULENC RORER,CTR RECH,VITRY,FRANCE. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. GENET INST INC,KARLSRUHE,GERMANY. PRINCETON UNIV,PRINCETON,NJ 08544. COLUMBIA UNIV,NEW YORK,NY. UNIV DUNDEE,DUNDEE DD1 4HN,SCOTLAND. WEIZMANN INST SCI,IL-76100 REHOVOT,ISRAEL. INST CURIE,PARIS,FRANCE. INST GUSTAVE ROUSSY,VILLEJUIF,FRANCE. RP Harlow, E (reprint author), HARVARD MED SCH,BOSTON,MA, USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 0764-4469 J9 CR ACAD SCI III-VIE JI Comptes Rendus Acad. Sci. Ser. III-Sci. Vie-Life Sci. PD NOV PY 1995 VL 318 IS 11 BP 1173 EP 1179 PG 7 WC Biology; Multidisciplinary Sciences SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics GA TN012 UT WOS:A1995TN01200011 ER PT J AU ChoChung, YS Pepe, S Clair, T Budillon, A Nesterova, M AF ChoChung, YS Pepe, S Clair, T Budillon, A Nesterova, M TI cAMP-dependent protein kinase: Role in normal and malignant growth SO CRITICAL REVIEWS IN ONCOLOGY/HEMATOLOGY LA English DT Review ID CYCLIC-AMP-BINDING; ADENOSINE 3'-5'-CYCLIC MONOPHOSPHATE; HL-60 LEUKEMIA-CELLS; AMINO-ACID-SEQUENCE; MAMMARY EPITHELIAL-CELLS; REGULATORY SUBUNIT RII; BOVINE CARDIAC-MUSCLE; TYROSINE-SPECIFIC PHOSPHORYLATION; MICROTUBULE-ASSOCIATED PROTEIN-2; DIRECT CYTOCHEMICAL-LOCALIZATION RP ChoChung, YS (reprint author), NCI,DCBDC,TUMOR IMMUNOL & BIOL LAB,CELLULAR BIOCHEM SECT,BLDG 10,ROOM 5B05,BETHESDA,MD 20892, USA. OI Budillon, Alfredo/0000-0002-6330-6053 NR 304 TC 117 Z9 119 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD NOV PY 1995 VL 21 IS 1-3 BP 33 EP 61 DI 10.1016/1040-8428(94)00166-9 PG 29 WC Oncology; Hematology SC Oncology; Hematology GA TT707 UT WOS:A1995TT70700003 PM 8822496 ER PT J AU BURGIN, AB NASH, HA AF BURGIN, AB NASH, HA TI SUICIDE SUBSTRATES REVEAL PROPERTIES OF THE HOMOLOGY-DEPENDENT STEPS DURING INTEGRATIVE RECOMBINATION OF BACTERIOPHAGE-LAMBDA SO CURRENT BIOLOGY LA English DT Article ID SITE-SPECIFIC RECOMBINATION; GENETIC-RECOMBINATION; PHAGE-LAMBDA; DNA; PROTEIN; MIGRATION; SYNAPSIS; CLEAVAGE AB Background: A fundamental feature of bacteriophage lambda site-specific recombination is the strict requirement for a region of sequence identity between recombining DNA duplexes. It has been difficult to understand how the recombination machinery identities and responds to non-homologies as subtle as a single base-pair substitution, because the reaction intermediates are transient and there are likely to be several different homology-dependent steps. In order to understand better how the recombination machinery compares parental sequences, we have used the recently developed 'suicide substrates' - DNA containing 5'-bridging phosphorothioate linkages - to monitor the timing of homology-sensing relative to the strand cleavage reactions. Results: The cleavage reactions for the two different strands of attB, the bacterial recombination locus for lambda integration, show very different degrees of dependence on homology with the partner locus, attP. Strand cleavage at the B binding site for Int recombinase is insensitive to homology. In contrast, cleavage at the B' binding site strongly depends an homology in the three base pairs adjacent to the B site. Strand cleavage at the B site is apparently required for the readout of this homology but, surprisingly, joining of the cleaved B site to a partner is not. Conclusions: Our finding that cleavage at the B site is insensitive to homology shows that effective synapsis between partners does not depend on sequence matching. Cleavage at the B' site provides the earliest positive signal for a homology-dependent switch in the lambda recombination machinery. Because this switch can occur in the absence of strand joining, the results argue against models that invoke strand ligation as the critical element of homology-sensing. Alternative mechanisms are presented that involve varieties of non-covalent strand swapping. A synthesis of the present results and other recent experiments highlights the importance of the disannealing of complementary strands and their reannealing to new partners, a process traditionally described as branch migration. The reversibility of branch migration and its bias away from mismatched combinations are proposed to be the major mechanisms of homology-sensing during lambda integration. C1 NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 30 TC 45 Z9 46 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 NOV 1 PY 1995 VL 5 IS 11 BP 1312 EP 1321 DI 10.1016/S0960-9822(95)00258-2 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TD858 UT WOS:A1995TD85800021 PM 8574589 ER PT J AU MORI, K LIZAK, MJ CECKLER, TL BALABAN, RS KADOR, PF AF MORI, K LIZAK, MJ CECKLER, TL BALABAN, RS KADOR, PF TI MAGNETIC-RESONANCE-IMAGING OF THE GALACTOSEMIC DOG EYE USING MAGNETIZATION-TRANSFER CONTRAST SO CURRENT EYE RESEARCH LA English DT Article DE DOG; LENS; MAGNETIC RESONANCE IMAGING (MRI); MAGNETIZATION TRANSFER CONTRAST (MTC); SUGAR CATARACTS ID ALDOSE REDUCTASE; SUGAR CATARACT; RABBIT LENS; WATER; SPECTROSCOPY; DIFFUSION; INVIVO AB Magnetization transfer contrast (MTC) enhanced magnetic resonance (MR) imaging is a technique that generates high contrast images based on characteristic tissue differences resulting from the interaction of water and macromolecules. In this study, the feasibility of applying this technique to documenting the progression of osmotic sugar cataract formation was investigated in male beagles, initially 6 or 24 month old, fed a diet containing 30% galactose. MTC enhanced magnetic resonance imaging was periodically conducted on these animal's eyes at 2-Tesla. The lens MR images were compared to photographs obtained by photo-slit lamp and retroillumination photography. The MTC technique provided improved image details of the lens and anterior segment that documented osmotic changes from initial cortical vacuole formation to cortical and nuclear changes associated with advanced sugar cataracts. The latter could not be observed by photo-slit lamp or retroillumination photography. C1 NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. NEI,OCULAR THERAPEUT LAB,BETHESDA,MD 20892. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 19 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD NOV PY 1995 VL 14 IS 11 BP 1035 EP 1040 DI 10.3109/02713689508998527 PG 6 WC Ophthalmology SC Ophthalmology GA TG200 UT WOS:A1995TG20000009 PM 8585933 ER PT J AU ROSENBAUM, T BOISSY, YL KOMBRINCK, K BRANNAN, CI JENKINS, NA COPELAND, NG RATNER, N AF ROSENBAUM, T BOISSY, YL KOMBRINCK, K BRANNAN, CI JENKINS, NA COPELAND, NG RATNER, N TI NEUROFIBROMIN-DEFICIENT FIBROBLASTS FAIL TO FORM PERINEURIUM IN-VITRO SO DEVELOPMENT LA English DT Article DE NEUROFIBROMATOSIS; NF1; FIBROBLAST; NEUROFIBROMA; PERINEURIUM; RAS; TRANSGENIC MICE; SCHWANN CELL ID BASAL LAMINA DEPOSITION; TYPE-1 GENE-PRODUCT; SCHWANN-CELLS; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; SACCHAROMYCES-CEREVISIAE; PROTEIN PRODUCT; S-100 PROTEIN; RAS GTPASE; CULTURE; TUMOR AB To identify cell type(s) that might contribute to nerve sheath tumors (neurofibromas) in patients with neurofibromatosis type 1, we generated cell cultures. containing neurons, Schwann cells and fibroblasts from transgenic mouse embryos in which the type 1 neurofibromatosis gene was disrupted by homologous recombination (Brannan et al. (1994) Genes Development, 8,1019-1029). Normal fascicle formation by perineurial cells failed to occur in the absence of neurofibromin. Fascicles were reduced in number and showed abnormal morphology when normal neurons and Schwann cells were cultured up to 37 days with fibroblasts lacking neurofibromin. Proliferation was increased in a majority of fibroblast cell strains analyzed from embryos lacking neurofibromin. These observations suggest that mutations in the neurofibromatosis type 1 gene affect fibroblast behavior that might contribute to neurofibroma formation in patients with neurofibromatosis type 1. C1 UNIV CINCINNATI,COLL MED,DEPT CELL BIOL NEUROBIOL & ANAT,CINCINNATI,OH 45267. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NINDS NIH HHS [R01 NS028840, R01 NS028840-09, NS 28840]; PHS HHS [N01-C0-46000] NR 71 TC 35 Z9 37 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 1995 VL 121 IS 11 BP 3583 EP 3592 PG 10 WC Developmental Biology SC Developmental Biology GA TF896 UT WOS:A1995TF89600010 PM 8582272 ER PT J AU JONES, CM KUEHN, MR HOGAN, BLM SMITH, JC WRIGHT, CVE AF JONES, CM KUEHN, MR HOGAN, BLM SMITH, JC WRIGHT, CVE TI NODAL-RELATED SIGNALS INDUCE AXIAL MESODERM AND DORSALIZE MESODERM DURING GASTRULATION SO DEVELOPMENT LA English DT Article DE NODAL; AXIAL MESODERM; DORSALIZATION; GASTRULATION; TGF-BETA; XENOPUS ID BONE MORPHOGENETIC PROTEIN-4; XENOPUS-LAEVIS EMBRYOS; SPEMANN ORGANIZER; TRANSFORMING GROWTH-FACTOR-BETA-2; VENTRALIZING FACTOR; CRYSTAL-STRUCTURE; MOUSE; GENE; SUPERFAMILY; CELLS AB Mouse embryos homozygous for a null mutation in nodal arrest development at early gastrulation and contain little or no embryonic mesoderm. Here, two Xenopus nodal-related genes (Xnr-1 and Xnr-2) are identified and shown to be expressed transiently during embryogenesis, first within the vegetal region of late blastulae and later in the marginal zone during gastrulation, with enrichment in the dorsal lip. Xnrs and mouse nodal function as dose-dependent dorsoanterior and ventral mesoderm inducers in whole embryos and explanted animal caps. Using a plasmid vector to produce Xnr proteins during gastrulation,,ve show that, in contrast to activin and other TGF beta-like molecules, Xnr-1 and Xnr-2 can dorsalize ventral marginal zone explants and induce muscle differentiation, Xnr signalling also rescues a complete embryonic axis in UV-ventralized embryos. The patterns of Xnr expression, the activities of the proteins and the phenotype of mouse nodal mutants, all argue strongly that a signaling pathway involving nodal, or nodal-related peptides, is an essential conserved element in mesoderm differentiation associated with vertebrate gastrulation and axial patterning. C1 VANDERBILT UNIV,SCH MED,DEPT CELL BIOL,NASHVILLE,TN 37232. NATL INST MED RES,DEV BIOL LAB,LONDON NW7 1AA,ENGLAND. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP JONES, CM (reprint author), VANDERBILT UNIV,SCH MED,HOWARD HUGHES MED INST,221 KIRKLAND HALL,NASHVILLE,TN 37232, USA. RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 FU NICHD NIH HHS [HD-28062] NR 64 TC 341 Z9 348 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 1995 VL 121 IS 11 BP 3651 EP 3662 PG 12 WC Developmental Biology SC Developmental Biology GA TF896 UT WOS:A1995TF89600016 PM 8582278 ER PT J AU VILLAR, AJ EDDY, EM PEDERSEN, RA AF VILLAR, AJ EDDY, EM PEDERSEN, RA TI DEVELOPMENTAL REGULATION OF GENOMIC IMPRINTING DURING GAMETOGENESIS SO DEVELOPMENTAL BIOLOGY LA English DT Article ID GROWTH FACTOR-II; MOUSE EMBRYOS; TGF-ALPHA; METHYLATION; GENE; EMBRYOGENESIS; EXPRESSION; TRANSGENE; CHROMATIN; ALLELE AB Successful mammalian development requires both the male and female genomes. This is due in part to genomic imprinting, which results in offspring inheriting only one functional copy of a gene from either the mother or the father. Evidence suggests that this specialization of the parental genomes is established during gametogenesis when the imprint pattern inherited from the parent is switched to reflect the sex of the progeny. We used reverse transcription-PCR to analyze the allele-specific expression of Igf-2 Igf-2r, and H19 in the testes and ovaries of mice derived from an interspecies cross between Mus musculus and Mus spretus. Because of genomic imprinting, Igf-2 is expressed only from the paternal allele and Igf-2r and H19 only from the maternal allele, in most tissues. Although allele-specific expression was maintained in the neonatal testis and ovary, relaxation of imprinting was detected by 7 days after birth in the male and continued during testis development. In the female, relaxation of the Igf-2 and Igf-2r parental imprints was observed in the adult ovary and oocyte. These results (1) indicate that imprinted expression is relaxed during gametogenesis, presumably as a consequence or prerequisite of the imprinting mechanism, and (2) predict a subsequent imprinting event after which the allele-specific expression of Igf-2 Igf-2r, and H19 reflects the parent of origin. (C) 1995 Academic Press, Inc. C1 UNIV CALIF SAN FRANCISCO,RADIOBIOL & ENVIRONM HLTH LAB,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT ANAT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT OBSTET GYNECOL & REPROD SCI,SAN FRANCISCO,CA 94143. NIEHS,REPROD & DEV TOXICOL LAB,GAMETE BIOL SECT,RES TRIANGLE PK,NC 27709. FU NICHD NIH HHS [HD26732] NR 38 TC 37 Z9 39 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV PY 1995 VL 172 IS 1 BP 264 EP 271 DI 10.1006/dbio.1995.0021 PG 8 WC Developmental Biology SC Developmental Biology GA TD804 UT WOS:A1995TD80400021 PM 7589806 ER PT J AU MALIN, DH LAKE, JR SMITH, DA JONES, JA MOREL, J CLAUNCH, AE STEVENS, PA PAYZA, K HO, KK LIU, J HAM, I BURGESS, K AF MALIN, DH LAKE, JR SMITH, DA JONES, JA MOREL, J CLAUNCH, AE STEVENS, PA PAYZA, K HO, KK LIU, J HAM, I BURGESS, K TI SUBCUTANEOUS INJECTION OF AN ANALOG OF NEUROPEPTIDE FF PREVENTS NALOXONE-PRECIPITATED MORPHINE ABSTINENCE SYNDROME SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE NEUROPEPTIDE FF; ANTIOPIATE PEPTIDES; OPIATE DEPENDENCE; OPIATE ABSTINENCE SYNDROME; MORPHINE; NALOXONE; DANSYL COMPOUNDS ID ENHANCED ANTIOPIATE ACTIVITY; PHASE PEPTIDE-SYNTHESIS; CENTRAL-NERVOUS-SYSTEM; RAT SPINAL-CORD; MODULATING PEPTIDE; OPIATE-WITHDRAWAL; INDUCED ANALGESIA; FMRFAMIDE; FLFQPQRFAMIDE; RECEPTORS AB There is evidence that neuropeptide FF (NPFF) has antiopiate activity and may play a role in opiate dependence and subsequent abstinence syndrome. A fragment of NPFF was modified at the C-terminal in an effort to convert it to an NPFF antagonist. It was also dansylated at the N-terminal in an effort to render it more lipophilic and increase its penetration of the blood-brain barrier. Third ventricle administration of the resulting compound, dansyl-PQRamide (0.75 mu g and 1 mu g), dose-dependently antagonized the quasi-morphine abstinence activity of NPFF (10 mu g) in opiate-naive rats. Subcutaneous injection of dansyl-PQRamide (13 mg/kg) in chronically morphine-infused rats attenuated opiate dependence as indicated by prevention of naloxone-precipitated abstinence syndrome. Dansyl-PQRamide displaced radiolabelled ligand from NPFF receptors in a concentration-dependent manner with a K-i of 13 mu M, and had a half-life over 300 times longer than NPFF under aminopeptidase digestion. C1 NIMH, WASHINGTON, DC 20032 USA. TEXAS A&M UNIV, DEPT CHEM, COLLEGE STN, TX 77843 USA. RP MALIN, DH (reprint author), UNIV HOUSTON CLEAR LAKE, BOX 237, HOUSTON, TX 77058 USA. RI Burgess, Kevin/B-5372-2015 OI Burgess, Kevin/0000-0001-6597-1842 FU NIDA NIH HHS [DA06554] NR 36 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD NOV PY 1995 VL 40 IS 1 BP 37 EP 42 DI 10.1016/0376-8716(95)01178-1 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA TJ856 UT WOS:A1995TJ85600005 PM 8746922 ER PT J AU CHANG, HT YEUNG, ES AF CHANG, HT YEUNG, ES TI DYNAMIC CONTROL TO IMPROVE THE SEPARATION PERFORMANCE IN CAPILLARY ELECTROPHORESIS SO ELECTROPHORESIS LA English DT Article DE CAPILLARY ELECTROPHORESIS; DYNAMIC CONTROL; REPRODUCIBILITY ID ELECTROOSMOTIC FLOW-CONTROL; EXTERNAL ELECTRIC-FIELD; APPLIED RADIAL VOLTAGE; ZONE ELECTROPHORESIS; PH GRADIENT; GEL-ELECTROPHORESIS; TEMPERATURE; MANIPULATION; GENERATION; OPTION AB Dynamic control in capillary electrophoresis (CE) is able to provide better resolution, shorter separation time, reduced band broadening and better reproducibility for the separations of organic and inorganic ions and large molecules such as proteins and DNA. This article provides an overview of dynamic control in CE by several techniques: pH, temperature, external electric field, and field amplification. These techniques take advantage of the changes in electroosmotic flow coefficient, electrophoretic mobilities of the analytes due to changes in equilibrium, viscosity of the buffer solution, and/or electric field strength. The basic theories and applications to the improvement of the separation performance for standard samples in CE by using these dynamic control techniques are presented. Finally, the advantages and shortcomings of these techniques and the future trends of dynamic control for the separations of real samples are discussed. C1 IOWA STATE UNIV SCI & TECHNOL,DEPT CHEM,AMES,IA 50011. NICHHD,MACROMOLEC ANAL SECT,THEORET & PHYS BIOL LAB,BETHESDA,MD. US DOE,AMES LAB,AMES,IA 50011. RI Chang, Huan-Tsung/C-1183-2011 NR 52 TC 6 Z9 8 U1 1 U2 8 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD NOV PY 1995 VL 16 IS 11 BP 2069 EP 2073 DI 10.1002/elps.11501601336 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA TJ765 UT WOS:A1995TJ76500011 PM 8748737 ER PT J AU KRYLOV, D OLIVE, M VINSON, C AF KRYLOV, D OLIVE, M VINSON, C TI EXTENDING DIMERIZATION INTERFACES - THE BZIP BASIC REGION CAN FORM A COILED-COIL SO EMBO JOURNAL LA English DT Article DE BZIP; COILED COIL; DNA BINDING; DOMINANT-NEGATIVE; HETERODIMER; PROTEIN DESIGN; LEUCINE ZIPPER ID LEUCINE ZIPPER PROTEINS; DNA-BINDING; TRANSCRIPTION FACTOR; ALPHA-HELICES; GENE; RECOGNITION; SPECIFICITY; ENHANCER; FAMILY; C/EBP AB We appended a rationally designed acidic amphipathic protein sequence to the N-terminus of a leucine zipper. Circular dichroism data indicate that this engineered polypeptide sequence can 'zipper' up the basic region of a bZIP monomer into a heterodimeric coiled coil. This propagation of the leucine zipper dimerization interface into the basic region can proceed for up to four heptads and stabilizes the heterodimer complex 2.5 kcal/mol or >100-fold. The acidic nature of the extension is the most critical component of the design, suggesting that the extension is acting as a DNA mimetic. The dimerization prevents the basic region in this heterodimeric coiled coil structure from binding to DNA, Gel-shift, fluorescence and transient transfection assays indicate that the acidic extension appended to a leucine zipper can inactivate the DNA-binding and transactivation properties of the bZIP protein C/EBP. The three bZIP basic regions examined in this study dimerize with similar stability with the acidic extension, suggesting that this N-terminal extension can be used to develop dominant-negatives to other bZIP transcription factors. C1 NATL INST HLTH,NATL CANC INST,BIOCHEM LAB,BETHESDA,MD 20892. NR 33 TC 76 Z9 76 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 1 PY 1995 VL 14 IS 21 BP 5329 EP 5337 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TF681 UT WOS:A1995TF68100019 PM 7489722 ER PT J AU IWAI, K KLAUSNER, RD ROUAULT, TA AF IWAI, K KLAUSNER, RD ROUAULT, TA TI REQUIREMENTS FOR IRON-REGULATED DEGRADATION OF THE RNA-BINDING PROTEIN, IRON REGULATORY PROTEIN-2 SO EMBO JOURNAL LA English DT Article DE CYSTEINE; IRON; IRON-RESPONSIVE ELEMENT; PROTEASOME; PROTEIN DEGRADATION ID SULFUR CLUSTER; ACONITASE ACTIVITY; OXIDATION AB Iron regulatory proteins (IRPs) regulate the expression of genes involved in iron metabolism whose transcripts contain RNA stem-loop moths known as iron-responsive elements (IREs), When iron concentrations are low, IRPs bind to IREs in the 5' untranslated region (UTR) of transcripts where they repress translation, or the 3' UTR of transcripts where they inhibit degradation, The RNA binding activities of the homologous proteins IRP1 and IRP2 are both regulated posttranslationally. The binding activity of IRP2 is regulated by the degradation of the protein when cells are iron-replete, Here, we demonstrate that a 73 amino acid sequence that corresponds to a unique exon in IRP2 contains a sequence required for rapid degradation in iron-replete cells, The deletion of this sequence eliminates the rapid turnover of IRP2, whereas the transfer of this sequence to the corresponding position in the homologous protein IRP1 confers the capacity for iron-dependent degradation upon IRP1, Site-directed mutagenesis has demonstrated that specific cysteines within the IRP2 exon are required for iron-dependent degradation, The degradation of IRP2 appears to be mediated by the proteasome in iron-replete cells, When degradation is prevented, the RNA binding activity of IRP2 is not regulated by iron concentration, Thus, degradation is required for the regulation of the RNA binding activity of IRP2. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NR 34 TC 158 Z9 158 U1 0 U2 0 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 NOV 1 PY 1995 VL 14 IS 21 BP 5350 EP 5357 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TF681 UT WOS:A1995TF68100021 PM 7489724 ER PT J AU ZHANG, Y OCONNOR, JP SIOMI, MC SRINIVASAN, S DUTRA, A NUSSBAUM, RL DREYFUSS, G AF ZHANG, Y OCONNOR, JP SIOMI, MC SRINIVASAN, S DUTRA, A NUSSBAUM, RL DREYFUSS, G TI THE FRAGILE-X MENTAL-RETARDATION SYNDROME PROTEIN INTERACTS WITH NOVEL HOMOLOGS FXR1 AND FXR2 SO EMBO JOURNAL LA English DT Article DE FRAGILE X MENTAL RETARDATION SYNDROME; FXR1; FXR2; PROTEIN-PROTEIN INTERACTION; RNA-BINDING PROTEINS ID RNA-BINDING; FMR-1 GENE; CGG REPEAT; K-PROTEIN; REGION; SITE; IDENTIFICATION; HYBRIDIZATION; INSTABILITY; EXPRESSION AB Fragile X Mental Retardation Syndrome is the most common form of hereditary mental retardation, and is caused by defects in the FMR1 gene, FMR1 is an RNA-binding protein and the syndrome results from lack of expression of FMRI or expression of a mutant protein that is impaired in RNA binding, The specific function of FMR1 is not known, As a step towards understanding the function of FMR1 we searched for proteins that interact with it in vivo, We have cloned and sequenced a protein that interacts tightly with FMR1 in vivo and in vitro, This novel protein, FXR2, is very similar to FMR1 (60% identity), FXR2 encodes a 74 kDa protein which, like FMR1, contains two KH domains, has the capacity to bind RNA and is localized to the cytoplasm, The FXR2 gene is located on human chromosome 17 at 17p13.1, In addition, FMR1 and FXR2 interact tightly with the recently described autosomal homolog FXR1, Each of these three proteins is capable of forming heteromers with the others, and each can also form homomers, FXR1 and FXR2 are thus likely to play important roles in the function of FMR1 and in the pathogenesis of the Fragile X Mental Retardation Syndrome. C1 UNIV PENN,SCH MED,HOWARD HUGHES MED INST,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT BIOCHEM & BIOPHYS,PHILADELPHIA,PA 19104. NATL INST HLTH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 36 TC 218 Z9 231 U1 0 U2 6 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 NOV 1 PY 1995 VL 14 IS 21 BP 5358 EP 5366 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TF681 UT WOS:A1995TF68100022 PM 7489725 ER PT J AU PACAK, K PALKOVITS, M KVETNANSKY, R MATERN, P HART, C KOPIN, IJ GOLDSTEIN, DS AF PACAK, K PALKOVITS, M KVETNANSKY, R MATERN, P HART, C KOPIN, IJ GOLDSTEIN, DS TI CATECHOLAMINERGIC INHIBITION BY HYPERCORTISOLEMIA IN THE PARAVENTRICULAR NUCLEUS OF CONSCIOUS RATS SO ENDOCRINOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; IMMOBILIZATION STRESS; GLUCOCORTICOID RECEPTOR; TYROSINE HYDROXYLATION; MONOAMINE-OXIDASE; BRAIN; NOREPINEPHRINE; SECRETION; NEURONS; CORTICOSTERONE AB Administration of glucocorticoids decreases the release of corticotropin-releasing hormone and in vitro turnover of norepinephrine (NE) in the paraventricular nucleus (PVN) of the hypothalamus, and immobilization (IMMO) markedly increases NE release and stimulates corticotropin-releasing hormone neurons in the PVN. This study assessed whether hypercortisolemia affects in vivo indexes of catecholaminergic activation in the PVN. Microdialysis was used to simultaneously measure PVN microdialysate concentrations of NE, the neuronal NE metabolite dihydroxyphenylglycol, the extraneuronal NE metabolite methoxyhydroxyphenylglycol, and the dopamine metabolite dihydroxyphenylacetic acid before, during, and after 2 h of IMMO. Catecholamine synthesis was examined based on elevations of 3,4-dihydroxyphenylalanine levels after local perfusion with NSD-1015, an inhibitor of L-aromatic acid decarboxylase. Cortisol (CORT; 25 mg/kg . day) or vehicle (VEH; saline) was infused sc for 7 days via an osmotic minipump. CORT-treated rats had lower basal NE, dihydroxyphenylglycol, methoxyhydroxyphenylglycol, and dihydroxyphenylacetic acid levels and significantly smaller levels of all these compounds during IMMO than VEH-treated rats. CORT-treated rats also had less NSD-1015-induced accumulation of microdialysate 3,4-dihydroxyphenylalanine at baseline and during IMMO than VEH-treated rats. Basal and IMMO-induced plasma ACTH and corticosterone responses were reduced in CORT-treated rats. The results indicate that chronic hypercortisolemia decreases basal levels and stress-induced increments in indexes of release, metabolism, turnover, and synthesis of catecholamines in the PVN and suggest that-glucocorticoids restrain the limit of hypothalamo-pituitary-adrenocortical axis activation during stress by attenuating catecholamine synthesis and release in the PVN. C1 NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. NINCDS, CLIN NEUROSCI BRANCH, BETHESDA, MD 20892 USA. NIAMSD, ARTHRIT & RHEUMATISM BRANCH, BETHESDA, MD 20892 USA. SLOVAK ACAD SCI, INST EXPTL ENDOCRINOL, BRATISLAVA, SLOVAKIA. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 31 TC 35 Z9 35 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1995 VL 136 IS 11 BP 4814 EP 4819 DI 10.1210/en.136.11.4814 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TB983 UT WOS:A1995TB98300013 PM 7588211 ER PT J AU WANG, YH EGAN, JM RAYGADA, M NADIV, O ROTH, J MONTROSERAFIZADEH, C AF WANG, YH EGAN, JM RAYGADA, M NADIV, O ROTH, J MONTROSERAFIZADEH, C TI GLUCAGON-LIKE PEPTIDE-1 AFFECTS GENE-TRANSCRIPTION AND MESSENGER-RIBONUCLEIC-ACID STABILITY OF COMPONENTS OF THE INSULIN SECRETORY SYSTEM IN RIN-1046-38 CELLS SO ENDOCRINOLOGY LA English DT Article ID PANCREATIC BETA-CELLS; GLUCOSE-TRANSPORTER; SIGNAL TRANSDUCTION; EXPRESSION; HORMONE; LINE; GLUCOKINASE; HYPERGLYCEMIA; BIOSYNTHESIS; HEXOKINASE AB It has been previously demonstrated that the enteric hormone glucagon-like peptide-1 (7-36 amide) (GLP-1) has acute effects on glucose-induced insulin secretion by RIN 1046-38 cells. In this study, we investigated the effects of extended exposure of RIN 1046-38 cells to GLP-1 and examine the mechanism by which GLP-1 synergizes with glucose in stimulating insulin secretion. Compared with cells cultured with glucose alone, incubation of cells with glucose plus 1 or 10 nM GLP-1 for 12 or 24 h significantly increased insulin release by about 3-fold, intracellular insulin content by 1.5-fold, and insulin messenger RNA (mRNA) by almost 2.5-fold. The insulinotropic effects of GLP-1 on RIN 1046-38 cells were accompanied by an up-regulation of both glucose transporter-1 (GLUT-1) and hexokinase I mRNA by about 2-fold. mRNA levels of GLUT-2 and glucokinase, which were low in controls, were unchanged by GLP-1 treatment. Treatment of cells with a transcription inhibitor, actinomycin D, demonstrated that elevated insulin mRNA levels after a GLP-1 exposure are mainly due to stabilization of the mRNA. In contrast, the elevated mRNA levels of GLUT-1 and hexokinase I are the result of increased transcription stimulated by GLP-1 exposure. Actinomycin D blunted the GLP-1 effect on insulin release but did not affect GLP-1-mediated elevation of insulin mRNA. This suggests that actinomycin D inhibits the transcription of the proteins necessary for insulin biosynthesis and insulin release, such as GLUT-1 and hexokinase I. Our study suggests that the mechanisms by which extended exposure of RIN 1046-38 cells to GLP-1 increases glucose-stimulated insulin secretion include significant up-regulation of glucose-sensing elements. C1 NIA, CTR GERONTOL RES, CLIN PHYSIOL LAB, DIABET UNIT, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, SCH MED, DIV GERIATR MED & GERONTOL, BALTIMORE, MD 21224 USA. NR 38 TC 70 Z9 72 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1995 VL 136 IS 11 BP 4910 EP 4917 DI 10.1210/en.136.11.4910 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TB983 UT WOS:A1995TB98300026 PM 7588224 ER PT J AU STANNARD, B BLAKESLEY, V KATO, H ROBERTS, CT LEROITH, D AF STANNARD, B BLAKESLEY, V KATO, H ROBERTS, CT LEROITH, D TI SINGLE TYROSINE SUBSTITUTION IN THE INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR INHIBITS LIGAND-INDUCED RECEPTOR AUTOPHOSPHORYLATION AND INTERNALIZATION, BUT NOT MITOGENESIS SO ENDOCRINOLOGY LA English DT Article ID KINASE DOMAIN AUTOPHOSPHORYLATION; SIGNAL TRANSDUCTION; SPECIFICITY; REPLACEMENT; PHOSPHORYLATION; PHENYLALANINE; REGIONS; HORMONE; FAMILY AB The tyrosine kinase domains of the insulin and insulin-like growth factor I (IGF-I) receptors play an essential role in signal transduction. After ligand binding, these receptors undergo autophosphorylation, with a cluster of three tyrosines (residues 1131, 1135, and 1136 in the IGF-I receptor) being the first to be phosphorylated. Mutation of the ATP-binding site or substitution of this triple tyrosine cluster in the catalytic domain blocks essentially all of the functions of these receptors. Using stably transfected NIH-3T3 cell lines, we studied the effect of a mutation of tyrosine 1131 of the triple tyrosine cluster of the IGF-I receptor to phenylalanine. This mutation significantly reduced IGF-I-induced beta-subunit autophosphorylation, whereas phosphorylation of the endogenous substrate IRS-1 was unaffected. Despite the reduction in autophosphorylation and receptor internalization, IGF-I-induced thymidine incorporation and cellular proliferation were unaffected. Thus, the extent of receptor autophosphorylation and internalization does not appear to be a limiting factor for IGF-I-stimulated mitogenesis. C1 NIDDKD, DIABET BRANCH, MOLEC & CELLULAR PHYSIOL SECT, BETHESDA, MD 20892 USA. OI Roberts, Charles/0000-0003-1756-5772 NR 34 TC 18 Z9 18 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1995 VL 136 IS 11 BP 4918 EP 4924 DI 10.1210/en.136.11.4918 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TB983 UT WOS:A1995TB98300027 PM 7588225 ER PT J AU LEE, CY RECHLER, MM AF LEE, CY RECHLER, MM TI PURIFIED RAT ACID-LABILE SUBUNIT AND RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR (IGF)-BINDING PROTEIN-3 CAN FORM A 150-KILODALTON BINARY COMPLEX IN-VITRO IN THE ABSENCE OF IGFS SO ENDOCRINOLOGY LA English DT Article ID FACTOR-BINDING-PROTEINS; FACTOR-I; HUMAN-SERUM; HORMONE; HYPOGLYCEMIA AB Insulin-like growth factors (IGFs) circulate in plasma mainly as part of a 150-kilodalton (kDa) complex with 40- to 45-kDa IGF-binding protein-3 (IGFBP-3) and an approximately 85-kDa acid-labile subunit (ALS) that does not bind IGFs directly. This complex sequesters IGFs in plasma, thereby providing a potential reservoir of the growth factors for tissues while constraining their potential hypoglycemic effects. Although it has been thought that IGFBP-3 must brst bind IGF-I or IGF-II before it can complex with ALS to form the 15O-kDa complex, we recently showed that unoccupied 150-kDa binary complexes of IGFBP-3 and ALS are abundant in adult rat serum. We now demonstrate that IGFBP-3 and rat (r)ALS can form 150-kDa complexes in the absence of IGFs. ALS was purified from rat serum by anion exchange chromatography and affinity chromatography on an IGF-I-Sepharose column to which human (h) IGFBP-3 had been noncovalently bound. The preparation contained less than 0.1 ng IGF-I/mu Lg purified ALS. In the absence of IGF, radiolabeled rALS and recombinant hIGFBP-3 formed complexes that could be immunoprecipitated by antiserum to hIGFBP-3; these complexes were identified by direct quantitation of the precipitated radioactivity or by sodium dodecyl sulfate-polyaclylamide gel electrophoresis (SDS-PAGE). Inclusion of IGF-I in the incubation increased complex formation. Complex formation also was demonstrated by incubation of unlabeled rALS with hTGFBP-3, followed by affinity cross-linking. Complexes were fractionated by SDS-PAGE, blotted, and shown to contain unoccupied IGF-binding sites by their ability to bind radioiodinated IGF-II. In addition, when rALS was subjected to SDS-PAGE and blotted, radioiodinated recombinant hIGFBP-3 bound to the 85-kDa protein. In this experiment, IGFBP-3 binding was slightly increased by coincubation with IGF-I. Thus, purified rALS can form a 150-kDa complex with hIGFBP-3 in the absence of IGF in vitro. The efficiency of complex formation was increased to variable extents by coincubation with IGF-I depending on the assay method. RP LEE, CY (reprint author), NIDDKD, MOLEC & CELLULAR ENDOCRINOL BRANCH, GROWTH & DEV SECT,BLDG 10, ROOM 8D14, MSC 1758, BETHESDA, MD 20892 USA. NR 26 TC 18 Z9 19 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1995 VL 136 IS 11 BP 4982 EP 4989 DI 10.1210/en.136.11.4982 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TB983 UT WOS:A1995TB98300034 PM 7588232 ER PT J AU BIDWELL, MC EITZMAN, BA WALMER, DK MCLACHLAN, JA GRAY, KD AF BIDWELL, MC EITZMAN, BA WALMER, DK MCLACHLAN, JA GRAY, KD TI ANALYSIS OF MESSENGER-RIBONUCLEIC-ACID AND PROTEIN FOR THE LIGANDS AND RECEPTORS OF THE PLATELET-DERIVED GROWTH-FACTOR SIGNALING PATHWAY IN THE PLACENTA, EXTRAEMBRYONIC MEMBRANES, AND UTERUS DURING THE LATTER HALF OF MURINE GESTATION SO ENDOCRINOLOGY LA English DT Article ID FACTOR-A-CHAIN; SMOOTH-MUSCLE CELLS; INSULIN-LIKE; FACTOR PDGF; EXPRESSION; GENE; PURIFICATION; ACTIVATION; INVITRO; EMBRYOS AB Previous investigation of ligand and receptor messenger RNA (mRNA) expression implicated the platelet-derived growth factor (PDGF) pathway as a participant in the maintenance of pregnancy and fetal development during the first half of murine gestation. We extended these studies using Northern and in situ RNA hybridization and immunohistochemical detection of protein to evaluate the expression kinetics and cell-specific localization of PDGF-A, PDGF-B, PDGF alpha-receptor, and PDGF beta-receptor in mouse placenta, extraembryonic membranes, and uterus during the second half of gestation (days 9.5-18.5). Northern blotting experiments reveal that mRNAs for the PDGF signaling components exhibit unique time-dependent and tissue-specific expression in the placenta and uterus, being progressively and coordinately up-regulated as gestation proceeds. Cell-specific localization of mRNA and protein by in situ hybridization and immunohistochemistry demonstrates widespread expression in multiple cell types of the placenta, gravid uterus, and extraembryonic membranes. Abundant PDGF protein and mRNA expression is exhibited in the nucleated fetal erythroid progenitor cells that originate in the extraembryonic membranes and circulate throughout the developing conceptus. Our data together with those of previous studies demonstrate that PDGF ligands and receptors are globally expressed in many cell types within fetal and maternal tissues during murine gestation and, thus, imply a potential role for PDGF in fetal development and maternal-fetal interactions. C1 NIEHS, REPROD & DEV TOXICOL LAB, RES TRIANGLE PK, NC 27709 USA. DUKE UNIV, MED CTR, DEPT OBSTET & GYNECOL, DIV REPROD ENDOCRINOL & INFERTIL, DURHAM, NC 27710 USA. NR 40 TC 16 Z9 17 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1995 VL 136 IS 11 BP 5189 EP 5201 DI 10.1210/en.136.11.5189 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TB983 UT WOS:A1995TB98300060 PM 7588258 ER PT J AU OCARROLL, AM KREMPELS, K AF OCARROLL, AM KREMPELS, K TI WIDESPREAD DISTRIBUTION OF SOMATOSTATIN RECEPTOR MESSENGER RIBONUCLEIC-ACIDS IN RAT PITUITARY SO ENDOCRINOLOGY LA English DT Note ID MOLECULAR-CLONING; GROWTH-HORMONE; NERVOUS-SYSTEM; EXPRESSION; SECRETION; IDENTIFICATION; AFFINITY; FAMILY; BRAIN AB The expression of five somatostatin receptor subtypes, rsstr1-5, was examined in rat pituitary by in situ hybridization histochemistry. The anterior lobe of the pituitary expressed mRNA encoding all five rsstr subtypes. Relatively high levels of rsstr3 mRNA expression were also observed in the intermediate lobe of the pituitary. If all five rsstr proteins are expressed in the pituitary, the effects of somatostatin and somatostatin-28 on pituitary function may therefore represent the composite-activation of more than one sstr. Co-localization studies on the same pituitary sections revealed a widespread distribution of rsstr mRNA in the major endocrine cell groups. Somatotrophs showed a relatively high level of rsstr4 and -5 mRNA expression while thyrotrophs predominantly expressed rsstr2 mRNA. These data may point to the potential roles for sstr subtypes in mediating SRIF physiology in the pituitary. C1 NINCDS, CLIN NEUROSCI BRANCH, BETHESDA, MD 20892 USA. RP OCARROLL, AM (reprint author), NIMH, CELL BIOL LAB, BLDG 36, ROOM 3A-17, BETHESDA, MD 20892 USA. NR 22 TC 90 Z9 91 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1995 VL 136 IS 11 BP 5224 EP 5227 DI 10.1210/en.136.11.5224 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TB983 UT WOS:A1995TB98300063 PM 7588261 ER PT J AU Zahm, SH Fraumeni, JF Davis, DL AF Zahm, SH Fraumeni, JF Davis, DL TI The avoidable causes of cancer - Introduction SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NCI, Rockville, MD 20850 USA. US Dept HHS, Off Assistant Secretary Hlth, Washington, DC 20201 USA. RP Zahm, SH (reprint author), NCI, Rockville, MD 20850 USA. RI Zahm, Shelia/B-5025-2015 NR 0 TC 1 Z9 1 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1995 VL 103 SU 8 BP 129 EP 129 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA V42AT UT WOS:000202841100002 ER PT J AU Shopland, DR AF Shopland, DR TI Tobacco use and its contribution to early cancer mortality with a special emphasis on cigarette smoking SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cigarette smoking; tobacco use; tobacco consumption; lung cancer; cessation of smoking; smoking prevalence; pipe and cigar smoking; smokeless tobacco; environmental tobacco smoke; changes in smoking by birth cohort, race, and gender differences in smoking behavior; race and gender differences in lung cancer death rates ID UNITED-STATES VETERANS; MALE BRITISH DOCTORS; LUNG-CANCER; PASSIVE-SMOKING; RISK; SMOKERS; DEATH; STATISTICS; TRENDS AB This paper provides an overview of the relationship between tobacco use and early cancer mortality. It presents a retrospective examination of trends in smoking behavior and how these trends affected the national lung cancer mortality pattern during this century. Information on smoking prevalence is presented for black and white men and women for each 5-year birth cohort between 1885 and 1969. The author argues that the lung cancer mortality pattern observed in the United States since 1950 is entirely compatible with changes in smoking behavior among the various birth cohorts examined. The paper also reviews our current scientific knowledge about the etiological relationship between cigarette smoking and site-specific cancer mortality, with particular emphasis on lung cancer. Data on other forms of tobacco use and cancer mortality risks are included as are data on environmental tobacco smoke exposures and nonsmokers' lung cancer risk. Data are presented to demonstrate that cigarette use alone will be responsible for nearly one-third of the U.S. cancer deaths expected in the United States in 1995, or 168,000 premature cancer deaths. Among males, 38% of all cancer deaths are cigarette related, while among women 23% of all cancer deaths are due to cigarettes. These totals, however, include neither the cancer deaths that could reasonably be attributed to pipe, cigar, and smokeless tobacco use among males nor the estimated 3000 to 6000 environmental tobacco smoke-related lung cancer deaths that occur annually in nonsmokers. It is concluded that tobacco use, particularly the practice of cigarette smoking, is the single greatest cause of excess cancer mortality in U.S. populations. C1 NCI, Smoking & Tobacco Control Program, Bethesda, MD 20892 USA. RP Shopland, DR (reprint author), NCI, Smoking & Tobacco Control Program, Execut Plaza N,Room 241,6130 Execut Blvd,MSC 7337, Bethesda, MD 20892 USA. NR 75 TC 130 Z9 131 U1 0 U2 6 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1995 VL 103 SU 8 BP 131 EP 142 DI 10.2307/3432300 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA V42AT UT WOS:000202841100003 PM 8741773 ER PT J AU Schatzkin, A Dorgan, J Swanson, C Potischman, N AF Schatzkin, A Dorgan, J Swanson, C Potischman, N TI Diet and cancer: Future etiologic research SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE antioxidants; breast cancer; cancer; colon cancer; diet; fat; lung cancer; nutrition; prevention; prostate cancer ID IOWA WOMENS HEALTH; LARGE-BOWEL CANCER; BREAST-CANCER; COLON-CANCER; BETA-CAROTENE; EPIDEMIOLOGIC EVIDENCE; ANTIOXIDANT VITAMINS; COLORECTAL ADENOMA; PREVENTION TRIALS; MEASUREMENT ERROR AB In light of several credible diet and cancer hypotheses, we suggest strategies for advancing our understanding in this area. Two conceptual approaches can be taken in defining dietary exposure: the decompositional approach focuses on specific nutrients and other chemical constituents of food, whereas the integrative approach emphasizes the action of whole foods or food patterns (cuisines). Diet-cancer hypotheses can be organized according to this conceptual framework. We review four types of scientific investigation available to us for advancing the diet and cancer field: metabolic (clinical nutrition) studies; animal studies; observational epidemiologic investigations; and clinical trials. Each of these designs has its strengths and limitations, Observational epidemiologic studies and trials have the particular advantage of examining explicit cancer end points in humans. Results from metabolic and animal research, however, can complement the findings from epidemiologic studies and trials. Finally, we briefly review strategies for evaluating promising hypotheses linking diet to cancers of the large bowel, lung, breast, and prostate. C1 NCI, Canc Prevent Studies Branch, Div Canc Prevent & Control, Bethesda, MD 20892 USA. NCI, Div Canc Etiol, Bethesda, MD 20892 USA. RP Schatzkin, A (reprint author), NCI, Canc Prevent Studies Branch, Div Canc Prevent & Control, 9000 Rockville Pike,EPN 211, Bethesda, MD 20892 USA. EM schatzka@dcpcepn.nci.nih.gov NR 55 TC 9 Z9 9 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1995 VL 103 SU 8 BP 171 EP 175 DI 10.2307/3432306 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA V42AT UT WOS:000202841100009 PM 8741779 ER PT J AU Hulka, BS Brinton, LA AF Hulka, BS Brinton, LA TI Hormones and breast and endometrial cancers: Preventive strategies and future research SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE prevention; hormones; neoplasms; endometrium; breast ID ORAL-CONTRACEPTIVE USE; ESTROGEN REPLACEMENT THERAPY; RISK-FACTORS; CONJUGATED ESTROGENS; POSTMENOPAUSAL WOMEN; UNITED-STATES; SEX-HORMONES; REDUCED RISK; BENEFITS; ASSOCIATION AB A number of hormonal approaches for prevention of endometrial and breast cancers have been proposed. Because of the hormonal responsiveness of both tumors, much attention has focused on effects of exogenous hormone use. Although estrogens in hormone replacement therapy increase the risk of endometrial cancer, the disease is substantially reduced by long-term use of oral contraceptives. The issues with breast cancer are more complex, mainly because of a variety of unresolved effects. Long-term estrogen use is associated with some increase in breast cancer risk, and certain patterns of oral contraceptives appear to predispose to early-onset disease. With respect to estrogens, preventive approaches for both tumors would include use for as limited periods of time as possible. Addition of a progestin appears to lower estrogen-associated endometrial disease, but its effect on breast cancer risk remains less clear. Additional studies on effects of detailed usage parameters should provide useful insights into etiologic mechanisms. Other preventive approaches for endometrial cancer that may work through hormonal mechanisms include staying thin, being physically active, and maintaining a vegetarian diet. Breast cancer risk may possibly be reduced by extended periods of breastfeeding, restriction of intake of alcoholic beverages, remaining thin later in life, and being physically active. Additional research is needed to clarify the biologic mechanisms of these associations. The bridging of epidemiology with the biologic sciences should clarify many unresolved issues and lead to better preventive approaches. C1 NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. RP Brinton, LA (reprint author), NCI, Environm Epidemiol Branch, EPN 443,6130 Execut Blvd,MSC 7374, Bethesda, MD 20892 USA. EM BrintonL@EPNDCE.NCI.NIH.GOV RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 49 TC 15 Z9 15 U1 1 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1995 VL 103 SU 8 BP 185 EP 189 DI 10.2307/3432308 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA V42AT UT WOS:000202841100011 PM 8741781 ER PT J AU Stolley, PD Zahm, SH AF Stolley, PD Zahm, SH TI Nonhormonal drugs and cancer SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE acetaminophen; alkylating agents; antihistamines; arsenicals; cancer; chemotherapy; drugs; cyclophosphamide; nonsteroidal antiinflammatory drugs; phenacetin; thorotrast ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RENAL-CELL CARCINOMA; FETAL HYDANTOIN SYNDROME; FAMILIAL ADENOMATOUS POLYPOSIS; NON-HODGKINS-LYMPHOMA; SOFT-TISSUE SARCOMAS; FATAL COLON-CANCER; LARGE-BOWEL CANCER; BREAST-CANCER; RISK-FACTORS AB Nonhormonal drugs probably account for only a small proportion of human cancer but have contributed many valuable insights into carcinogenic mechanisms. The antineoplastics, radiopharmaceuticals, and a few other agents account for most of the known drug-induced cancer. A number of other agents are under suspicion, usually due to studies in laboratory animals or to preliminary clinical or epidemiologic observations. This group includes some drugs in widespread use such as clofibrate and cimetidine. For a few drugs that are carcinogenic in animals, such as dapsone and isoniazid, epidemiologic studies have shown lite to no evidence of carcinogenicity. Recent experimental studies have shown tumor promotion by the commonly used antidepressants amitriptyline and fluoxetine and some antihistamines, which deserve epidemiologic investigation of cancer risk. Some drugs may also protect against cancer, as suggested by the lower risk of colorectal cancer among regular users of nonsteroidal antiinflammatory drugs. Pharmacoepidemiologic studies must take into account possible confounding by the original conditions for which drugs were taken and the typically long latency period of drug-induced cancer. Improved postmarketing surveillance, continued routine case-control surveillance, and ad hoc case-control and cohort studies are needed to evaluate drugs already in use as well as newly introduced agents. C1 NCI, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. RP Zahm, SH (reprint author), NCI, Epidemiol & Biostat Program, EPN 418, Bethesda, MD 20892 USA. EM zahms@epndce.nci.nih.gov RI Zahm, Shelia/B-5025-2015 NR 114 TC 6 Z9 6 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1995 VL 103 SU 8 BP 191 EP 196 DI 10.2307/3432309 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA V42AT UT WOS:000202841100012 PM 8741782 ER PT J AU Blair, A Zahm, SH AF Blair, A Zahm, SH TI Agricultural exposures and cancer SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE agriculture; farmers; farmworkers; cancer; pesticides; review; exposures ID NON-HODGKINS-LYMPHOMA; SOFT-TISSUE SARCOMA; BREAST-CANCER; TRANSPLANT RECIPIENTS; PESTICIDE USE; RISK; MORTALITY; FARMERS; WOMEN; MEN AB The purpose of this report is to review the literature on cancer among persons employed in agriculture, to characterize the value of this line of research, and to recommend future directions. Farmers, despite a generally favorable mortality, appear to experience elevated rates for several cancers, including leukemia, non-Hodgkin's lymphoma, multiple myeloma, soft-tissue sarcoma, and cancers of the skin, lip, stomach, brain, and prostate. The rates for several of these tumors (i.e., non-Hodgkin's lymphoma, multiple myeloma, skin, brain, and prostate) appear to be increasing in the general population. No set of established etiologic factors explains all the cancer excesses observed among farmers, although several are associated with naturally occurring or medically induced immunodeficiencies. This suggests that there may be factors in the agricultural environment that introduce immune system deficiencies. Farmers are exposed to a variety of substances that could operate through this mechanism, including pesticides, engine exhausts, solvents, dusts, and zoonotic microbes. Studies to further characterize the cancer risk among farmers, their dependents, and farm laborers, and to identify the exposures that may be involved would not only be useful in providing a safe work environment in agriculture but may furnish considerable insight into the causes for a number of tumors that are rising in incidence in the general population. C1 NCI, Occupat Studies Sect, Bethesda, MD 20892 USA. RP Blair, A (reprint author), NCI, Occupat Studies Sect, Execut Plaza N,Room 418, Bethesda, MD 20892 USA. EM Blaira@epndce.nci.nih.gov RI Zahm, Shelia/B-5025-2015 NR 39 TC 148 Z9 153 U1 0 U2 8 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1995 VL 103 SU 8 BP 205 EP 208 DI 10.2307/3432311 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA V42AT UT WOS:000202841100014 PM 8741784 ER PT J AU Darby, SC Inskip, PD AF Darby, SC Inskip, PD TI Ionizing radiation: Future etiologic research and preventive strategies SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE radiation; ionizing; cancer etiology ID LUNG-CANCER MORTALITY; RADON DAUGHTER EXPOSURE; URANIUM MINERS; COHORT; WORKERS; PROGENY; P53; CHERNOBYL; RISK AB Estimates of cancer risks following exposure to ionizing radiation traditionally have been based on the experience of populations exposed to substantial (and known) doses delivered over short periods of time. Examples include survivors of the atomic bombings at Hiroshima and Nagasaki, and persons treated with radiation for benign or malignant disease. Continued follow-up of these populations is important to determine the long-term effects of exposure in childhood, to characterize temporal patterns of excess risk for different types of cancer, and to understand better the interactions between radiation and other host and environmental factors. Most population exposure to radiation occurs at very low dose rates. For low linear energy transfer (LET) radiations, it offer has been assumed that cancer risks per unit dose are lower following protracted exposure than following acute exposure. Studies of nuclear workers chronically exposed over a working lifetime provide data that can be used to test this hypothesis, and preliminary indications are that the risks per unit dose for most cancers other than leukemia are similar to those for acute exposure. However, these results are subject to considerable uncertainty, and further information on this question is needed. Residential radon is the major source of population exposure to high-LET radiation. Current estimates of the risk of lung cancer due to residential exposure to radon and radon daughters are based on the experience of miners exposed to much higher concentrations. Data indicate that lung cancer risk among miners is inversely associated with exposure rate, and also is influenced by the presence of other lung carcinogens such as arsenic in the mine environment. Further study of populations of radon-exposed miners would be informative, particularly those exposed at below-average levels. More direct evidence on the effects of residential exposure to radon also is desirable but might be difficult to come by, as risks associated with radon levels found in most homes might be too low to be quantified accurately in epidemiological studies. C1 NCI, Radiat Epidemiol Branch, Epidemiol & Biostat Program, Rockville, MD 20852 USA. Univ Oxford, Imperial Canc Res Fund, Canc Epidemiol Unit, Oxford, England. RP Inskip, PD (reprint author), NCI, Radiat Epidemiol Branch, Epidemiol & Biostat Program, Execut Plaza N,Room 408,6130 Execut Blvd, Rockville, MD 20852 USA. NR 29 TC 3 Z9 3 U1 1 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1995 VL 103 SU 8 BP 245 EP 249 DI 10.2307/3432319 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA V42AT UT WOS:000202841100022 PM 8741792 ER PT J AU de The, G AF de The, G TI Viruses and human cancers: Challenges for preventive strategies SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE human papilloma virus; Epstein-Barr virus; infectious mononucleosis; Burkitt's lymphorna; nasopharyngeal carcinoma; hepatitis B virus; cancer; vaccination ID EPSTEIN-BARR-VIRUS; NASOPHARYNGEAL CARCINOMA; EPIDEMIOLOGY AB Virus-associated human cancers provide unique opportunities for preventive strategies. The role of human papilloma viruses (HPV 16 and 18), hepatitis B virus (HBV), Epstein-Barr herpes virus (EBV), and retroviruses (human immunodeficiency virus [HIV] and human T-cell leukemia/lymphoma virus [HTLV]) in the development of common carcinomas and lymphomas represents a major cancer threat, particularly among individuals residing in developing countries, which account for 80% of the world's population. Even though these viruses are not the sole etiological agents of these cancers (as would be the case for infectious diseases), different approaches can be implemented to significantly decrease the incidence of virus-associated malignancies. The first approach is vaccination, which is available for HEN and possibly soon for EBV. The long delay between primary viral infection and development of associated tumors as well as the cost involved with administering vaccinations detracts from the feasibility of such an approach within developing countries. The second approach is to increase efforts to detect pre-cancerous lesions or early tumors using immunovirological means. This would allow early diagnosis and better treatment. The third strategy is [irked to the existence of disease susceptibility genes, and suggests that counseling be provided for individuals carrying these genes to encourage them to modify their lifestyles and other conditions associated with increased cancer risks (predictive oncology). Specific recommendations include: a) increase international studies that explore the causes of the large variations in prevalence of common cancers throughout the world; b) conduct interdisciplinary studies involving laboratory investigation and social sciences, which may suggest hypotheses that may then be tested experimentally; and c) promote more preventive and health enhancement strategies in addition to curative and replacement therapies. C1 Inst Pasteur, Unit Epidemiol Oncogen Viruses, F-75724 Paris 15, France. Natl Inst Hlth, Fogarty Int Ctr, Bethesda, MD USA. RP de The, G (reprint author), Inst Pasteur, Unit Epidemiol Oncogen Viruses, 28 Rue Dr Roux, F-75724 Paris 15, France. EM dethe@pasteur.fr NR 22 TC 8 Z9 11 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1995 VL 103 SU 8 BP 269 EP 273 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA V42AT UT WOS:000202841100027 PM 8741797 ER PT J AU Walker, B Figgs, LW Zahm, SH AF Walker, B Figgs, LW Zahm, SH TI Differences in cancer incidence, mortality, and survival between African Americans and whites SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE African Americans; breast cancer; cancer; cervical cancer; colorectal cancer; ethnicity; multiple myeloma; oropharyngeal cancer; prostate cancer; race ID HUMAN LUNG-CANCER; BREAST-CANCER; UNITED-STATES; RACIAL-DIFFERENCES; PROSTATE-CANCER; MULTIPLE-MYELOMA; P53 POLYMORPHISM; WOMEN; RISK; PATTERNS AB This report highlights selected evidence of different cancer patterns among African Americans and whites and considers potential risk factors associated with these cancers. During the years 1987 to 1991, African Americans experienced higher incidence and mortality rates than whites for multiple myeloma and for cancers of the oropharynx, colorectum, lung and bronchus, cervix, and prostate. African Americans had lower incidence and mortality for cancer of the urinary bladder. The incidence of breast cancer was higher among white women, but mortality was higher among African American women. Five-year relative survival for the period 1983 to 1990 was generally lower among African Americans than whites for cancers of the oropharynx, colorectum, cervix, prostate, and female breast but slightly higher for multiple myeloma. From 1973 to 1991, there were significant declines in cervical cancer incidence among women of both races, oropharyngeal cancer mortality among whites, and bladder cancer mortality for whites and African Americans. Risk factors for the more prominent cancers suggest that efforts aimed at changing lifestyles, achieving socioeconomic parity, and insuring environmental equity are likely to relieve African Americans of much of their disproportionate cancer burden. C1 Howard Univ, Univ Canc Ctr, Washington, DC 20060 USA. NCI, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. RP Walker, B (reprint author), Howard Univ, Univ Canc Ctr, 2041 Georgia Ave NW, Washington, DC 20060 USA. RI Zahm, Shelia/B-5025-2015 NR 64 TC 58 Z9 60 U1 1 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1995 VL 103 SU 8 BP 275 EP 281 DI 10.2307/3432325 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA V42AT UT WOS:000202841100028 PM 8741798 ER PT J AU Zahm, SH Fraurneni, JF AF Zahm, SH Fraurneni, JF TI Racial, ethnic, and gender variations in cancer risk: Considerations for future epidemiologic research SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE alcohol; biomarkers; cancer; epidemiology; ethnicity; genetics; occupation; minorities; race; smoking ID CAFFEINE URINARY METABOLITES; BREAST-CANCER; LUNG-CANCER; PUERTO-RICAN; SOCIOECONOMIC-FACTORS; BORN POPULATION; SOUTH FLORIDA; UNITED-STATES; NEW-YORK; WOMEN AB There is no question that the risk of many cancers varies substantially by race, ethnic group, and gender. Although important clues to cancer etiology may come from investigating the differences in risk across subgroups of the population, epidemiologic research has often focused on white men. More descriptive and analytic studies are needed to identify and explain variations in risk among population subgroups. Especially important are studies to clarify the role of differential exposures, susceptibility, and diagnostic factors in cancer incidence, although differences in treatment may contribute to variations in cancer mortality. Improvements in classification of ethnicity, assessment of carcinogenic exposures in various subpopulations, and measures of host susceptibility states should augment future epidemiologic research designed to better understand mechanisms underlying the racial, ethnic, and gender differences in cancer risk. C1 NCI, Epidemiol & Biostat Program, Div Canc Etiol, Bethesda, MD 20892 USA. RP Zahm, SH (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Etiol, EPN 418, Bethesda, MD 20892 USA. EM zahms@epndce.nci.nih.gov RI Zahm, Shelia/B-5025-2015 NR 48 TC 24 Z9 25 U1 3 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1995 VL 103 SU 8 BP 283 EP 286 DI 10.2307/3432326 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA V42AT UT WOS:000202841100029 PM 8741799 ER PT J AU Rothman, N Hayes, RB AF Rothman, N Hayes, RB TI Using biomarkers of genetic susceptibility to enhance the study of cancer etiology SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cancer; genetic susceptibility; genetic polymorphisms ID GLUTATHIONE-S-TRANSFERASE; GSTM1 NULL GENOTYPE; UPPER AERODIGESTIVE TRACT; POLYMERASE-CHAIN-REACTION; OCCUPATIONAL CASE-CONTROL; SQUAMOUS-CELL CARCINOMA; TRANS-STILBENE OXIDE; LUNG-CANCER; BLADDER-CANCER; HUMAN-LIVER AB There has been increasing interest in the interaction of genetic susceptibility and xenobiotic exposures in cancer etiology. Study of gene-environment interactions may increase our ability to characterize relatively low population risks if a substantial proportion of the population cancer burden is attributed to high risk among a smaller group of genetically susceptible members. Further, these studies may provide insight into the mechanism of carcinogenesis, which can help establish the biologic plausibility of an exposure-cancer relationship. Biologic processes important in tumorigenesis that exhibit substantial interindividual differences may function as susceptibility factors. Potential examples include polymorphic enzymes, which activate and detoxify procarcinogens and carcinogens (e.g., certain P450 enzymes, N-acetyltransferase [NAT2], glutathione S-transferase M1), and variation in the capacity to repair DNA. Biologic assays are now available to evaluate many of these functions at the DNA and phenotype level and can be readily incorporated into studies of cancer etiology. C1 NCI, Environm Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Rothman, N (reprint author), NCI, Environm Epidemiol Branch, NIH, EPN 418, Bethesda, MD 20892 USA. EM rothmann@epndce.nci.nih.gov NR 74 TC 16 Z9 17 U1 1 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1995 VL 103 SU 8 BP 291 EP 295 DI 10.2307/3432328 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA V42AT UT WOS:000202841100031 PM 8741801 ER PT J AU GOYER, RA AF GOYER, RA TI CHELATION OF TOXIC METALS - CURRENT INTERESTS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Note RP GOYER, RA (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 18 TC 8 Z9 8 U1 1 U2 2 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1995 VL 103 IS 11 BP 988 EP 989 DI 10.2307/3432622 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TE822 UT WOS:A1995TE82200007 PM 8605861 ER PT J AU WEINBERG, CR AF WEINBERG, CR TI POTENTIAL FOR BIAS IN EPIDEMIOLOGIC STUDIES THAT RELY ON GLASS-BASED RETROSPECTIVE ASSESSMENT OF RADON SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID INDOOR RADON; PO-210; PRODUCTS; EXPOSURE AB Retrospective assessment of exposure to radon remains the greatest challenge in epidemiologic efforts to assess lung cancer risk associated with residential exposure. An innovative technique based on measurement of alpha-emitting, long-lived daughters embedded by recoil into household glass may one day provide improved radon dosimetry. Particulate air pollution is known, however, to retard the plate-out of radon daughters. This would be expected to result in a differential effect on dosimetry, where the calibration curve relating the actual historical radon exposure to the remaining alpha-activity in the glass would be different in historically smoky and nonsmoky environments. The resulting ''measurement confounding'' can distort inferences about the effect of random and can also produce spurious evidence for synergism between random exposure and cigarette smoking. RP WEINBERG, CR (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 18 TC 6 Z9 6 U1 1 U2 2 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1995 VL 103 IS 11 BP 1042 EP 1046 DI 10.2307/3432633 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TE822 UT WOS:A1995TE82200028 PM 8605854 ER PT J AU GOYER, RA CHERIAN, MG JONES, MM REIGART, JR AF GOYER, RA CHERIAN, MG JONES, MM REIGART, JR TI ROLE OF CHELATING-AGENTS FOR PREVENTION, INTERVENTION, AND TREATMENT OF EXPOSURES TO TOXIC METALS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID LEAD SEQUESTERING AGENTS; X-RAY-FLUORESCENCE; DIMERCAPTOPROPANE SULFONATE; EXPOSED RATS; CADMIUM; MOBILIZATION; INTOXICATION; MANAGEMENT; COMPLEXES; MERCURY C1 UNIV WESTERN ONTARIO,LONDON,ON N6A 5C1,CANADA. VANDERBILT UNIV,NASHVILLE,TN 37235. MED UNIV S CAROLINA,CHARLESTON,SC 29425. RP GOYER, RA (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 40 TC 57 Z9 61 U1 1 U2 8 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1995 VL 103 IS 11 BP 1048 EP 1052 DI 10.2307/3432634 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TE822 UT WOS:A1995TE82200029 PM 8605855 ER PT J AU COOPER, GS BAIRD, DD AF COOPER, GS BAIRD, DD TI THE USE OF QUESTIONNAIRE DATA TO CLASSIFY PERIMENOPAUSAL AND PREMENOPAUSAL STATUS SO EPIDEMIOLOGY LA English DT Note DE MENOPAUSAL STATUS; QUESTIONNAIRE ASSESSMENT; METHODOLOGY AB We assessed how well questionnaire data could classify peri- vs premenopausal status in 280 women, ages 38-49 years. Sixty-seven per cent of those who reported use of hormone replacement therapy begun when menstrual periods were irregular, or who had hot flashes at least once a day, or whose last menstrual period was at least 60 days in length, were perimenopausal by hormonal assay (early follicular phase serum follicle-stimulating hormone greater than or equal to 15 international units per liter), with a sensitivity of 0.56 [95% confidence interval (CI) = 0.41-0.72] and a specificity of 0.95 (95% CI = 0.93-0.98). In the classification of premenopausal status, the criterion of no menstrual cycle length changes in the past 5 years yielded the highest sensitivity (0.61; 95% CI = 0.54-0.67) and specificity (0.81; 95% CI = 0.68-0.93). With these few items, researchers can improve the classification of peri- and premenopausal status when longitudinal or hormonal assessments cannot be obtained. RP COOPER, GS (reprint author), NIEHS,EPIDEMIOL BRANCH A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NCI NIH HHS [5-T32-CA09330]; NCRR NIH HHS [RR00046] NR 0 TC 13 Z9 13 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 1995 VL 6 IS 6 BP 625 EP 628 DI 10.1097/00001648-199511000-00011 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TA290 UT WOS:A1995TA29000011 PM 8589095 ER PT J AU THEODORE, WH ALBERT, P STERTZ, B MALOW, B KO, D WHITE, S FLAMINI, R KETTER, T AF THEODORE, WH ALBERT, P STERTZ, B MALOW, B KO, D WHITE, S FLAMINI, R KETTER, T TI FELBAMATE MONOTHERAPY - IMPLICATIONS FOR ANTIEPILEPTIC DRUG DEVELOPMENT SO EPILEPSIA LA English DT Article DE FELBAMATE; MONOTHERAPY; EPILEPSY; ANTIEPILEPTIC DRUG DEVELOPMENT ID PARTIAL-ONSET SEIZURES; EPILEPTIC PATIENTS; CONTROLLED TRIAL; CLINICAL-TRIAL; CARBAMAZEPINE; WITHDRAWAL; ANTICONVULSANT; PHENYTOIN; METABOLITES; FREQUENCY AB We studied the effect of felbamate (FBM) monotherapy on seizure rate in patients with partial and secondarily generalized seizures undergoing presurgical monitoring at a single site. The study design was a double-blind placebo-controlled parallel monotherapy trial. Forty patients whose seizures had not been controlled by standard antiepileptic drugs (AEDs) were randomized. Seizure type was confirmed by video-EEG monitoring. All baseline AEDs were discontinued, and patients were drug-free for 5.3 +/- 2.4 days before randomization to FBM or placebo. After a 4-day titration, seizures were counted for 14 days. Patients receiving FBM had significantly lower seizure rates, whether all randomized patients, patients who survived titration, or study completers were compared. Eight of 19 placebo patients randomized to placebo, as compared with 13 of 21 receiving FBM, completed the 18-day study. Two FBM patients dropped out due to seizures, and 6 dropped out due to side effects, including anxiety, difficulty sleeping, abdominal discomfort, acute psychosis, and orobuccal dyskinesias. Ten placebo patients met the criteria for premature discontinuation owing to seizures, and 1 had an episode of panic, There was no evidence of hepatic or hematologic toxicity. FBM reduces seizure frequency in patients with localization-related epilepsy. RP THEODORE, WH (reprint author), NIH,NIH BLDG 10,ROOM 5C-205,BETHESDA,MD 20892, USA. NR 35 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 1995 VL 36 IS 11 BP 1105 EP 1110 DI 10.1111/j.1528-1157.1995.tb00468.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA TC203 UT WOS:A1995TC20300006 PM 7588454 ER PT J AU PERKINS, JR TOMER, KB AF PERKINS, JR TOMER, KB TI CHARACTERIZATION OF THE LOWER-MOLECULAR-MASS FRACTION OF VENOMS FROM DENDROASPIS-JAMESONI-KAIMOSAE AND MICRURUS-FULVIUS USING CAPILLARY-ELECTROPHORESIS ELECTROSPRAY MASS-SPECTROMETRY SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE CAPILLARY ELECTROPHORESIS; ELECTROSPRAY MASS SPECTROMETRY; SNAKE VENOMS ID NAJA-MOSSAMBICA-MOSSAMBICA; MAGNETIC-RESONANCE SPECTRUM; LASER-DESORPTION IONIZATION; BLACK MAMBA VENOM; POLYLEPIS-POLYLEPIS; LIQUID-CHROMATOGRAPHY; SECONDARY STRUCTURE; CARDIOTOXIN-CTXIIB; ALPHA-NEUROTOXIN; AQUEOUS-SOLUTION AB Capillary electrophoresis (CE) with electrospray ionization (ESI) and selected ion-monitoring mass-spectrometric (SIM-MS) detection has been used to provide as much information as possible about the lower molecular-mass fraction (peptides of molecular masses up to 8500 Da) of the venoms of Dendroaspis jamesoni kaimosae (Jameson's Mamba) and Micrurus fulvius (Eastern Coral Snake). Method development was based on the venom of D. jamesoni kaimosae,which contains some previously described peptides, with subsequent application to the completely unknown venom of M. fulvius. CE-ESI-SIM-MS provides a rapid and extremely sensitive method for the detection and molecular-mass determination of peptides present in venoms. It has been utilized to provide molecular masses and thus, by inference, confirmation of the peptide compositions for those toxins which have been previously described in the literature. Our methodology indicates the presence of 83 peptides in the venom of D. jamesoni kaimosae and 49 peptides in the venom of M. fulvius in the molecular-mass range 6000-8500 Da. C1 NIEHS,MOLEC BIOPHYS LAB,BETHESDA,MD. RI Tomer, Kenneth/E-8018-2013 NR 46 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD NOV 1 PY 1995 VL 233 IS 3 BP 815 EP 827 DI 10.1111/j.1432-1033.1995.815_3.x PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TD243 UT WOS:A1995TD24300016 PM 8521847 ER PT J AU WALLACE, KK BAO, ZY DAI, H DIGATE, R SCHULER, G SPEEDIE, MK REYNOLDS, KA AF WALLACE, KK BAO, ZY DAI, H DIGATE, R SCHULER, G SPEEDIE, MK REYNOLDS, KA TI PURIFICATION OF CROTONYL-COA REDUCTASE FROM STREPTOMYCES-CALLINUS AND CLONING, SEQUENCING AND EXPRESSION OF THE CORRESPONDING GENE IN ESCHERICHIA-COLI SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE CROTONYL-COA REDUCTASE; BUTYRATE METABOLISM; STREPTOMYCES; FATTY ACID BIOSYNTHESIS ID TRANS-2-ENOYL-COA REDUCTASE; MYCOBACTERIUM-SMEGMATIS; MOLECULAR-CLONING; CARBON SKELETON; CHICKEN LIVER; DNA-SEQUENCE; CODON USAGE; COENZYME-A; IDENTIFICATION; BINDING AB A crotonyl-CoA reductase (EC 1.3.1.38, acyl-CoA:NADP(+) trans-2-oxidoreductase) catalyzing the conversion of crotonyl-CoA to butyryl-CoA has been purified and characterized from Streptomyces collinus. This enzyme, a dimer with subunits of identical mass (48 kDa), exhibits a K-m = 18 mu M for crotonyl-CoA and 15 mu M for NADPH. The enzyme was unable to catalyze the reduction of any other enoyl-CoA thioesters or to utilize NADH as an electron donor. A highly effective inhibition by straight-chain fatty acids (K-i = 9.5 mu M for palmitoyl-(CoA) compared with branched-chain fatty acids (K-i > 400 mu M for isopalmitoyl-CoA) was observed. All of these properties are consistent with a proposed role of the enzyme in providing butyryl-CoA as a starter unit for straight-chain fatty acid biosynthesis. The crotonyl-CoA reductase gene was cloned in Escherichia coli. This gene, with a proposed designation of ccr is encoded in a 1344-bp open reading frame which predicts a primary translation product of 448 amino acids with a calculated molecular mass of 49.4 kDa. Several dispersed regions of highly significant sequence similarity were noted between the deduced amino acid sequence and various alcohol dehydrogenases and fatty acid synthases, including one region that contains a putative NADPH binding site. The ccr gene product was expressed in E. coli and the induced crotonyl-CoA reductase was purified tenfold and shown to have similar steady-state kinetics and electrophoretic mobility on sodium dodecyl sulfate/polyacrylamide to the native protein. C1 UNIV MARYLAND, SCH PHARM, DEPT PHARMACEUT SCI, BALTIMORE, MD 21201 USA. UNIV MARYLAND, MARYLAND BIOTECHNOL INST, CTR MED BIOTECHNOL, BALTIMORE, MD 21201 USA. NIH, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20892 USA. FU NIGMS NIH HHS [GM-50542002] NR 60 TC 52 Z9 55 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD NOV 1 PY 1995 VL 233 IS 3 BP 954 EP 962 DI 10.1111/j.1432-1033.1995.954_3.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TD243 UT WOS:A1995TD24300033 PM 8521864 ER PT J AU Korn, WM DuManoir, S Otto, T Schmidt, U Seeber, S Becher, R AF Korn, WM DuManoir, S Otto, T Schmidt, U Seeber, S Becher, R TI Conventional and molecular cytogenetic analysis of testicular germ cell tumors SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 UNIV ESSEN GESAMTHSCH,W GERMAN CANC RES CTR,DEPT INTERNAL MED CANC RES,ESSEN,GERMANY. NIH,BETHESDA,MD 20892. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 1995 VL 31A SU 5 BP 901 EP 901 PG 1 WC Oncology SC Oncology GA TH919 UT WOS:A1995TH91900899 ER PT J AU Salomon, DS AF Salomon, DS TI EGF-related peptides in cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI,TUMOR IMMUNOL & BIOL LAB,TUMOR GROWTH FACTOR SECT,BETHESDA,MD 20892. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 1995 VL 31A SU 5 BP 1012 EP 1012 PG 1 WC Oncology SC Oncology GA TH919 UT WOS:A1995TH91901009 ER PT J AU Steward, WP Dunlop, DJ Cameron, C Talbot, DC Kleisbauer, JL Thomas, P Guerin, JC Perol, M Sanson, C Dabouis, G Lacroix, H AF Steward, WP Dunlop, DJ Cameron, C Talbot, DC Kleisbauer, JL Thomas, P Guerin, JC Perol, M Sanson, C Dabouis, G Lacroix, H TI Gemcitabine combined with cisplatin in non-small cell lung cancer (NSCLC): A phase I/II study SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 BEATSON ONCOL CTR,GLASGOW,LANARK,SCOTLAND. NCI,CLIN TRIALS UNIT,KINGSTON,ON,CANADA. IMPERIAL CANC RES FUND,CLIN ONCOL UNIT,OXFORD,ENGLAND. HOP RENE & GUILLAUME LAENNEC,NANTES,FRANCE. HOP ST MARGUERITE,MARSEILLE,FRANCE. HOP CROIX ROUSSE,F-69317 LYON,FRANCE. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 1995 VL 31A SU 5 BP 1081 EP 1081 PG 1 WC Oncology SC Oncology GA TH919 UT WOS:A1995TH91901076 ER PT J AU Crosson, K AF Crosson, K TI A network of educators for cancer clinical trials SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 1995 VL 31A SU 5 BP 1350 EP 1350 PG 1 WC Oncology SC Oncology GA TH919 UT WOS:A1995TH91901345 ER PT J AU Berger, DP Herbstritt, L Hellerich, U SChulzke, S Dengler, WA Gallo, M Pastan, I Mertelsmann, R Fiebig, HH AF Berger, DP Herbstritt, L Hellerich, U SChulzke, S Dengler, WA Gallo, M Pastan, I Mertelsmann, R Fiebig, HH TI Cytotoxicity of TGF alpha-PE40 and correlation to expression of epidermal growth factor receptor SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE growth factors; TGF alpha; TGF alpha-PE40; recombinant toxins; nude mice; xenografts; clonogenic assay ID FACTOR-ALPHA; PSEUDOMONAS EXOTOXIN; FUSION PROTEIN; TUMOR XENOGRAFTS; IMMUNOTOXINS; CARCINOMAS; CANCER; TISSUES; OVARIAN; CELLS AB TGF alpha-PE40 is a chimeric protein composed of transforming growth factor alpha (TGF alpha) linked to a modified Pseudomonas exotoxin (PE40). We tested the in vitro cytotoxicity of TGF alpha-PE40 on 23 different solid human tumour xenografts established in nude mice and human bone marrow cells from healthy donors, utilising a modified clonogenic assay. In order to distinguish non-specific toxicity from the targeted effects of TGF alpha-PE40, epidermal growth factor receptor (EGFR) expression of the tumours studied was assessed by Northern blot, slot blot and immunohistochemistry. TGF alpha-PE40 demonstrated differential cytotoxicity on human tumour xenografts in the clonogenic assay. No toxicity on human bone marrow cells was observed. In vitro activity of TGF alpha-PE40 showed a significant correlation with the expression of EGF receptors as determined by immunohistochemistry and slot blot. Further studies will be performed in order to determine the in vivo activity of this compound in tumour-bearing nude mice. C1 UNIV FREIBURG,INST PATHOL,FREIBURG,GERMANY. NATL CANC INST,BETHESDA,MD. RP Berger, DP (reprint author), UNIV FREIBURG,MED CTR,DEPT INTERNAL MED 1,HUGSTETTER STR 55,D-79106 FREIBURG,GERMANY. NR 29 TC 0 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 1995 VL 31A IS 12 BP 2067 EP 2072 DI 10.1016/0959-8049(95)00422-X PG 6 WC Oncology SC Oncology GA TM406 UT WOS:A1995TM40600037 PM 8562167 ER PT J AU TANG, PZ GANNON, MJ ANDREW, A MILLER, D AF TANG, PZ GANNON, MJ ANDREW, A MILLER, D TI EVIDENCE FOR ESTROGENIC REGULATION OF HEAT-SHOCK PROTEIN EXPRESSION IN HUMAN ENDOMETRIUM AND STEROID-RESPONSIVE CELL-LINES SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; PROGESTERONE RECEPTORS; NUCLEOTIDE-SEQUENCE; ESTROGEN-RECEPTOR; MENSTRUAL-CYCLE; BREAST-CANCER; MESSENGER-RNA; GENE; 90-KDA AB Gene amplification with target-specific primers (reverse-transcription polymerase chain reaction (RT-PCR)) was used to monitor the relative expression of oestrogen and progesterone receptor mRNAs alongside the mRNAs for heat shock proteins HSP 90 alpha, HSP 90 beta and HSP 70a in normal samples of human endometrial tissue oner the whole menstrual cycle and in short-term cultures of steroid-responsive (T47-D) and unresponsive (HRT-18) cell lines exposed to oestradiol and progesterone over a 24-h incubation period. In endometrium, oestrogen and progesterone receptors followed the expected patterns of expression at the protein level during the menstrual cycle and also showed a positive correlation of expression with each other throughout (r=0.514), Of the HSPs only HSP 90 alpha expression correlated positively with oestrogen receptor (r=0.687), while HSP 70a expression, which peaked in the late secretory stage, displayed a significantly inverse correlation with HSP 90 beta expression (r=-0.526). All p values < 0.05. In T47-D cell cultures, oestrogen receptor expression was stimulated transiently by oestradiol (10(-7) mol/l) and more persistently by progesterone (10(-7) mol/l). Progesterone receptor expression was depressed by progesterone and weakly stimulated by oestradiol. HSP 70a and HSP 90 alpha expression were stimulated by oestradiol, Progesterone generally depressed HSP 90 alpha expression and simultaneous addition of both oestradiol and progesterone to the culture medium was antagonistic to HSP 90 alpha expression. No clear effect of agonist addition on HSP mRNA expression was apparent in the HRT-18 cultures. A possible mechanism for observed oestrogenic effects on HSP expression is put forward. C1 UNIV LEEDS,INST PATHOL,DEPT CLIN MED,LEEDS LS2 9JT,W YORKSHIRE,ENGLAND. LEEDS GEN INFIRM,ACAD UNIT OBSTET & GYNAECOL,LEEDS,W YORKSHIRE,ENGLAND. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NR 31 TC 30 Z9 31 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD NOV PY 1995 VL 133 IS 5 BP 598 EP 605 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TD531 UT WOS:A1995TD53100015 PM 7581991 ER PT J AU TURCOVSKICORRALES, SM FENTON, RG PELTZ, G TAUB, DD AF TURCOVSKICORRALES, SM FENTON, RG PELTZ, G TAUB, DD TI CD28-B7 INTERACTIONS PROMOTE T-CELL ADHESION SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE ADHESION; T LYMPHOCYTES; CD28; B7; PHOSPHATIDYLINOSITOL-3-KINASE; CTLA-4 ID MONOCLONAL-ANTIBODIES; ACTIVATION PATHWAY; COUNTER-RECEPTOR; CYCLOSPORINE-A; CROSS-LINKING; B-CELLS; PROLIFERATION; ANTIGEN; LIGATION; ANERGY AB CD28 activation by antibody-mediated ligation has been shown to provide an important co-stimulatory signal for T cell adhesion to purified protein ligands. However, the effect of CD28 ligation by one of its natural ligands, B7.1, on T cell adhesion to other cells has not been studied. Therefore, in the present manuscript, we characterized the adhesive interactions between human T cells and B7.1-transfected major histocompatibility complex class II+ and class II- melanoma cells. In our studies, human T cells and T cell clones adhered to B7.1-transfected melanoma cells, but not to untransfected parental cells. The adhesive reaction in this model was rapid, occurring within 15 min, and was inhibited by anti-B7.1 antibody and soluble CTLA-4 immunoglobubulin. Antibody inhibition studies demonstrated that adhesion between T cells and B7.1-transfected melanoma cells was mediated by interactions between LFA-1:ICAM-1 and CD2:LFA-3. Inhibition by pharmacological agents demonstrated that the CD28-induced adhesion required specific intracellular signaling events. A protein kinase C inhibitor, staurosporin, significantly inhibited T cell binding to transfected melanoma cells, while cyclosporin A and wortmannin, an inhibitor of phosphatidylinositol-3-kinase, did not. These results suggest that the presence of B7 on various cell populations may activate lymphocytes to adhere better, thus promoting activation, cytolysis, and migration. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,CLIN SERV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL MODIFIERS PROGRAM,FREDERICK,MD 21702. SYNTEX INC,PALO ALTO,CA 94304. NR 40 TC 31 Z9 31 U1 0 U2 2 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 1995 VL 25 IS 11 BP 3087 EP 3093 DI 10.1002/eji.1830251115 PG 7 WC Immunology SC Immunology GA TE647 UT WOS:A1995TE64700014 PM 7489747 ER PT J AU ORBAN, GA SAUNDERS, RC VANDENBUSSCHE, E AF ORBAN, GA SAUNDERS, RC VANDENBUSSCHE, E TI LESIONS OF THE SUPERIOR TEMPORAL CORTICAL MOTION AREAS IMPAIR SPEED DISCRIMINATION IN THE MACAQUE MONKEY SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE VISUAL CORTEX; ABLATION; MOTION; PRIMATES; PERCEPTUAL DEFICITS; BEHAVIOR ID VISUAL RESPONSE PROPERTIES; VELOCITY DISCRIMINATION; DIRECTION SELECTIVITY; FUNCTIONAL-PROPERTIES; MOVEMENT VISION; STRIATE CORTEX; BLIND PATIENT; RHESUS-MONKEY; BRAIN-DAMAGE; NEURONS AB The effects of circumscribed lesions of the superior temporal cortical motion areas on speed discrimination were tested in three macaque monkeys using both moving random-textured patterns and moving bars. The lesions, which included the middle temporal visual area, the adjacent medial superior temporal visual area and the fundus superior temporal visual area, produced a severe and lasting deficit in speed discrimination when tested with the random patterns. In contrast, deficits were smaller when tested with moving bars. Control lesions of the inferior temporal cortex in two monkeys had little effect on speed discrimination. There was no clear deficit following inferior temporal or superior temporal sulcus lesions on a vernier acuity task. These experiments indicate that the middle temporal and adjacent areas play a crucial role in speed discrimination and that lesion effects depend on the cues available to the animals. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,CEREBRAL MECHANISMS UNIT,BETHESDA,MD 20892. RP ORBAN, GA (reprint author), CATHOLIC UNIV LEUVEN,SCH MED,NEURO & PSYCHOFYSIOL LAB,CAMPUS GASTHUISBERG,B-3000 LOUVAIN,BELGIUM. NR 65 TC 53 Z9 54 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV 1 PY 1995 VL 7 IS 11 BP 2261 EP 2276 DI 10.1111/j.1460-9568.1995.tb00647.x PG 16 WC Neurosciences SC Neurosciences & Neurology GA TF392 UT WOS:A1995TF39200008 PM 8563975 ER PT J AU BARKER, WC ANDRICH, MP ALEXANDER, HR FRAKER, DL AF BARKER, WC ANDRICH, MP ALEXANDER, HR FRAKER, DL TI CONTINUOUS INTRAOPERATIVE EXTERNAL MONITORING OF PERFUSATE LEAK USING I-131 HUMAN SERUM-ALBUMIN DURING ISOLATED PERFUSION OF THE LIVER AND LIMBS SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PERFUSION, REGIONAL; TUMOR NECROSIS FACTOR; IODINE RADIOISOTOPES; INTRAOPERATIVE MONITORING ID MALIGNANT-MELANOMA; BLOOD LEAKAGE; MELPHALAN; GAMMA AB Regional isolated perfusion using tumor necrosis factor (TNF) shows significant promise for treatment of cancer which is limited to limbs or organs. The high toxicity of TNF requires very sensitive real time monitoring of leakage in order to avoid serious patient complications, Human serum albumin labeled with iodine-131 is used with an externally mounted and collimated NaI(Tl) detector to track the leakage of blood from the isolated perfusion blood circuit into the general systemic vascular space. Blood activity levels measured using the monitor demonstrated a very good correlation with blood serum samples taken concurrently with external monitoring. External monitoring can reduce the risks of perfusion leakage intraoperatively with the precision necessary to safely perform isolated perfusion using TNF. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. RP BARKER, WC (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892, USA. NR 18 TC 35 Z9 35 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD NOV PY 1995 VL 22 IS 11 BP 1242 EP 1248 DI 10.1007/BF00801607 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TE842 UT WOS:A1995TE84200004 PM 8575471 ER PT J AU MCCRAE, RR COSTA, PT AF MCCRAE, RR COSTA, PT TI TRAIT EXPLANATIONS IN PERSONALITY PSYCHOLOGY SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Article; Proceedings Paper CT Symposium on Structure and Causality in Personality and Behavior, at the 7th European Conference on Personality CY JUL 12-16, 1994 CL MADRID, SPAIN ID 5-FACTOR MODEL; CONSISTENCY; PHILOSOPHY; CONSTRUCTS; BEHAVIOR; PEOPLE AB Recent debates on the status of contemporary trait psychology (Pervin, 1994) have revived old questions about the role of traits in the explanation of behavior: are traits mere descriptions of behavior, or do they offer one legitimate and useful form of explanation? We review the logic of trait explanation and present a general model of the person in which personality traits are hypothetical constructs regarded as basic dispositions. In interaction with external influences-notably shared meaning systems-traits contribute causally to the development of habits, attitudes; skills, and other characteristic adaptations. In this model, action and experience can be explained directly or proximally in terms of the interaction of the immediate situation with the individual's characteristic adaptations, and indirectly or distally in terms of underlying personality traits. RP MCCRAE, RR (reprint author), NIA,CTR GERONTOL RES,PERSONAL STRESS & COPING SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 85 TC 147 Z9 152 U1 22 U2 38 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD NOV PY 1995 VL 9 IS 4 BP 231 EP 252 DI 10.1002/per.2410090402 PG 22 WC Psychology, Social SC Psychology GA TE980 UT WOS:A1995TE98000001 ER PT J AU LI, Q PENG, B WHITCUP, SM JANG, SU CHAN, CC AF LI, Q PENG, B WHITCUP, SM JANG, SU CHAN, CC TI ENDOTOXIN-INDUCED UVEITIS IN THE MOUSE - SUSCEPTIBILITY AND GENETIC-CONTROL SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE ENDOTOXIN INDUCED UVEITIS (EIU); MOUSE; LIPOPOLYSACCHARIDE RESPONSE GENE; H-2 HAPLOTYPES; MAST CELL; EYE; INFLAMMATION ID MAST-CELLS; RATS AB Endotoxin induced uveitis in the mouse provides a useful animal model for acute anterior uveitis in humans, We have investigated the susceptibility of endotoxin-induced uveitis among various mouse strains, and have examined the relationship between genetic background and the resultant inflammatory response to endotoxin. We studied ten strains with differing major histocompatibility-2 genes, lipopolysaccharide response gene, and strains with mast cell depletion and its sham control. Anterior uveitis was induced by injecting 300 mu g of Salmonella typhimurium endotoxin into one hind footpad. Mice were then killed 8, 12, 16, 20, 24, 48 and 72 hr after endotoxin injection, and vertical sections of the eyes through the pupil-optic nerve axis were evaluated for ocular inflammation. C3H/HeN mice developed severe uveitis, In contrast, C3H/HeJ mice (lipopolysaccharide response gene(-)) did not develop uveitis even though it has the same genetic background and shares the same major histocompatibility-2 haplotype with C3H/HeN mice (lipopolysaccharide response gene). The strain that was mast-cell deficient (W/W-v) developed minimal uveitis; however, W/+ mice, with mast cells, developed more inflammation at 48 and 72 hr after endotoxin injection. C3H.SW and FVB/N mice also developed severe uveitis, and BALB/C, CBA/J, and B10.A developed mild uveitis. In conclusion, there is a wide variation in the magnitude and susceptibility to endotoxin among mouse strains. Multiple factors appear to influence this variability, including non-histocompatibility-2 genetic background, the lipopolysaccharide response gene, and the presence of mast cells. (C) 1995 Academic Press Limited C1 NEI,CLIN BRANCH,BETHESDA,MD 20892. UNIV MICHIGAN,SCH ART & SCI,ANN ARBOR,MI 48109. RP LI, Q (reprint author), NEI,IMMUNOL LAB,BLDG 10,ROOM 10N103,10 CTR DR,MSC 1858,BETHESDA,MD 20892, USA. NR 21 TC 64 Z9 69 U1 0 U2 2 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD NOV PY 1995 VL 61 IS 5 BP 629 EP 632 DI 10.1016/S0014-4835(05)80056-9 PG 4 WC Ophthalmology SC Ophthalmology GA TC973 UT WOS:A1995TC97300011 PM 8654505 ER PT J AU WISTOW, G JAWORSKI, C RAO, PV AF WISTOW, G JAWORSKI, C RAO, PV TI A NONLENS MEMBER OF THE BETA-GAMMA-CRYSTALLIN SUPERFAMILY IN A VERTEBRATE, THE AMPHIBIAN CYNOPS SO EXPERIMENTAL EYE RESEARCH LA English DT Letter ID X-RAY-ANALYSIS; MYXOCOCCUS-XANTHUS; PROTEIN-S; EYE LENS; DIFFERENTIATION; EVOLUTION; FAMILY; CDNA RP WISTOW, G (reprint author), NEI,BLDG 6,ROOM 222,BETHESDA,MD 20892, USA. NR 23 TC 35 Z9 39 U1 0 U2 1 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD NOV PY 1995 VL 61 IS 5 BP 637 EP 639 DI 10.1016/S0014-4835(05)80058-2 PG 3 WC Ophthalmology SC Ophthalmology GA TC973 UT WOS:A1995TC97300013 PM 8654507 ER PT J AU Colman, E Katzel, LI Sorkin, J Coon, PJ Engelhardt, S Rogus, E Goldberg, AP AF Colman, E Katzel, LI Sorkin, J Coon, PJ Engelhardt, S Rogus, E Goldberg, AP TI The role of obesity and cardiovascular fitness ln the impaired glucose tolerance of aging SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE obesity; impaired glucose tolerance and aging ID BODY-FAT DISTRIBUTION; DIABETES-MELLITUS; ABDOMINAL FAT; ORAL GLUCOSE; INSULIN; AGE; INTOLERANCE; POPULATION; ASSOCIATION; MEN AB The prevalence of impaired glucose tolerance (IGT) increases with aging. Although some data suggest that age is independently associated with IGT, other studies suggest that age-associated changes in body composition and reduced cardiovascular fitness are responsible for the development of IGT. We, therefore, examined the relationship of age, total and regional adiposity, and level of fitness (VO(2)max) to the presence of IGT in 155 healthy, nondiabetic, nonsmoking, older community dwelling men. Sixty-two of 155 men (40%) had IGT, while 93 men (60%) had normal glucose tolerance (WHO criteria). The subjects with IGT were of similar age (61.0 +/- 1.0 vs. 59.0 +/- 0.7 years, p = 0.49) and had the same maximal aerobic capacity, (VO(2)max) (42 0 +/- 1.0 vs. 44.0 +/- 0.8 mL/kg ffm/min, p = 0.42), but had a higher waist to hip ratio (WHR) (0.98 +/- 0.01 vs. 0.96 +/- 0.01, p = 0.005) and percent body fat (30.0 +/- 0.4 vs. 26.0 +/- 0.6, p = 0.004) than the men with normal glucose tolerance. In univariate analysis, the 2-h glucose level correlated positively with percent body fat (r = 0.30, p = 0.0002), WHR (0.24, p = 0.002), and age (r = 0.17, p = 0.03) and negatively with VO(2)max (r = -0.23, p = 0.005). In both multiple logistic and linear regression analyses, percent body fat was the only independent predictor of IGT (p = 0.002). These results suggest that the age-associated increase in total adiposity is a major contributor to the development of IGT in middle-aged and older men. Thus, lifestyle modifications that reduce body fat should reduce the risk for IGT and the development of noninsulin-dependent diabetes mellitus in the elderly. C1 UNIV MARYLAND,SCH MED,DEPT MED,DIV GERONTOL,BALTIMORE,MD 21201. VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,BALTIMORE,MD. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. FU NIA NIH HHS [KO8 AG-00347, 5-K08-AG00497, R01 AG07660-03] NR 37 TC 8 Z9 8 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD NOV-DEC PY 1995 VL 30 IS 6 BP 571 EP 580 DI 10.1016/0531-5565(95)00015-1 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA TL510 UT WOS:A1995TL51000002 PM 8867526 ER PT J AU OSTROWSKI, LE NETTESHEIM, P AF OSTROWSKI, LE NETTESHEIM, P TI INHIBITION OF CILIATED CELL-DIFFERENTIATION BY FLUID SUBMERSION SO EXPERIMENTAL LUNG RESEARCH LA English DT Article DE CILIA; DIFFERENTIATION; TRACHEA; AIR-LIQUID INTERFACE ID TRACHEAL EPITHELIAL-CELLS; HUMAN NASAL EPITHELIUM; EXTRACELLULAR-MATRIX; CULTURE; EXPRESSION; GROWTH; GENE; REGENERATION; CILIOGENESIS AB Rat tracheal epithelial (RTE) cells, plated at low density on collagen gel-coated membranes, differentiate into a mucociliary epithelium when cultured at an air-liquid interface (ALI). However, when RTE cells are cultured submerged in media, ciliated cell differentiation is drastically reduced. This study examined possible mechanisms for the inhibition of ciliated cell differentiation by submersion. Ciliated cell differentiation was measured using a monoclonal antibody specific for rat ciliated cells. Removing growth stimulatory compounds from both the basal and apical media increased ciliated cell differentiation in submerged cultures, indicating that submersion inhibits, but does not prevent, ciliogenesis. However, the effect of submersion was independent of the composition of the apical media. The depth of apical fluid was important, with depths greater than or equal to 1 mm causing almost complete inhibition of ciliated cell differentiation, while a depth Of 0.5 mm allowed significant ciliogenesis. Submersion appeared to block ciliated cell differentiation al mr early step, because ciliated cell development required several days following creation of an ALI. Once ciliogenesis was initiated in ALI cultures, submersion did not reverse or inhibit the development off ciliated cells. These studies have provided new information on the inhibition of ciliated cell differentiation by fluid submersion. RP OSTROWSKI, LE (reprint author), NIEHS, PULM PATHOBIOL LAB, AIRWAY CELL BIOL GRP, POB 12233, MAIL DROP D2-01, RES TRIANGLE PK, NC 27709 USA. NR 29 TC 35 Z9 35 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD NOV-DEC PY 1995 VL 21 IS 6 BP 957 EP 970 DI 10.3109/01902149509031773 PG 14 WC Respiratory System SC Respiratory System GA TE977 UT WOS:A1995TE97700009 PM 8591796 ER PT J AU Barreau, C Touray, M Pimenta, PF Miller, LH Vernick, KD AF Barreau, C Touray, M Pimenta, PF Miller, LH Vernick, KD TI Plasmodium gallinaceum: Sporozoite invasion of Aedes aegypti salivary glands is inhibited by anti-gland antibodies and by lectins SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Plasmodium; sporozoite; mosquito; insect vector; basal lamina; vector competence ID EXTRACELLULAR-MATRIX; ANOPHELES-STEPHENSI; DROSOPHILA; BERGHEI; MOSQUITOS; KNOWLESI; BINDING AB There is evidence which suggests that malaria sporozoites recognize mosquito salivary glands by specific receptor-ligand interactions. We are interested in identifying the putative salivary gland receptor(s) for sporozoite invasion. We used an in vivo bioassay for sporozoite invasion of salivary glands. In this assay, purified sporozoites from mature oocysts of Plasmodium gallinaceum were injected into Aedes aegypti mosquitoes and salivary glands were dissected at different time points after injection. One half of the maximum invasion of salivary glands by sporozoites occurred by 6 hr, and salivary gland sporozoite load did not increase further after 24 hr postinjection. This assay was used to determine the effect of experimental treatments with antibodies and lectins at 24 hr postinjection. We raised a rabbit polyclonal antiserum against female Ae. aegypti salivary glands which recognized tissue-specific determinants in the basal lamina of salivary glands. Purified IgG antibody fraction of the immune serum blocked sporozoite invasion in vivo. We tested a panel of 19 lectins and found 7 which bound to salivary glands. Of these 7, succinylated wheat germ agglutinin and wheat germ agglutinin completely blocked sporozoite invasion; Pisum sativum agglutinin and soybean agglutinin partially blocked; and concanavalin A, Dolichos biflorus agglutinin, and Phaseolus vulgaris erythroagglutinin did not block. Our results suggest that sporozoites interact with glycosylated salivary gland surface molecules which serve as receptors for invasion, and which may be in the salivary,oland basal lamina. Because the putative sporozoite receptors contain immunogenic determinants, it is feasible to identify them by an immunological strategy. (C) 1995 Academic Press, Inc. RP Barreau, C (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 23 TC 56 Z9 56 U1 1 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD NOV PY 1995 VL 81 IS 3 BP 332 EP 343 DI 10.1006/expr.1995.1124 PG 12 WC Parasitology SC Parasitology GA TK431 UT WOS:A1995TK43100012 PM 7498430 ER PT J AU Shahabuddin, M Kaidoh, T Aikawa, M Kaslow, DC AF Shahabuddin, M Kaidoh, T Aikawa, M Kaslow, DC TI Plasmodium gallinaceum: Mosquito peritrophic matrix and the parasite-vector compatibility SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE chitinase; host-parasite relationship; vector; polyoxin D; malaria ID AEDES-AEGYPTI; CALLIPHORA-ERYTHROCEPHALA; MEMBRANES; INFECTIVITY; MALARIA; PROTEASE; INSECTA; DIPTERA; CHITIN AB Transmission of malaria parasites occurs by relatively few species of mosquitoes. One proposed mechanism of refractoriness is an inability of certain Plasmodium spp. to cross the peritrophic matrix (PM) in the midgut of an incompatible mosquito. We have tested this hypothesis by studying sporogonic development of Plasmodium gallinaceum in susceptible (Aedes aegypti and Anopheles gambiae G3) and refractory (Anopheles stephensi) mosquito species in the presence and absence of the PM. In the presence of the PM the number of oocysts that developed in A. gambiae G3 was about 20% of that in A. aegypti, whereas no oocysts developed in A. stephensi. To disrupt PM formation we added, to an infectious bloodmeal, either exogenous fungal chitinase or polyoxin D, the latter being a potent inhibitor of chitin synthase. The absence of the PM did not increase the susceptibility of A. aegypti and A. gambiae nor did it make A. stephensi susceptible to P. gallinaceum infection. The data indicate that the PM is not the primary determinant of P, gallinaceum compatibility in these mosquitoes and suggest that determinant(s) of refractoriness occurs after the parasite crosses the mosquito PM. (C) 1995 Academic Press, Inc. C1 CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. RP Shahabuddin, M (reprint author), NIAID,LPD,MOLEC ENTOMOL SECT,MALARIA VACCINES SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI-10645-22] NR 26 TC 31 Z9 32 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD NOV PY 1995 VL 81 IS 3 BP 386 EP 393 DI 10.1006/expr.1995.1129 PG 8 WC Parasitology SC Parasitology GA TK431 UT WOS:A1995TK43100017 PM 7498435 ER PT J AU WONG, JM SHI, YB WOLFFE, AP AF WONG, JM SHI, YB WOLFFE, AP TI A ROLE FOR NUCLEOSOME ASSEMBLY IN BOTH SILENCING AND ACTIVATION OF THE XENOPUS TR-BETA-A GENE BY THE THYROID-HORMONE RECEPTOR SO GENES & DEVELOPMENT LA English DT Article DE NUCLEOSOME ASSEMBLY; XENOPUS; THYROID HORMONE RECEPTOR GENE; TRANSCRIPTION ID RETINOID-X-RECEPTOR; TRANSCRIPTION FACTOR ACCESS; YEAST ALPHA-2 REPRESSOR; TUMOR VIRUS PROMOTER; RNA POLYMERASE-II; NUCLEAR RECEPTORS; PHO5 PROMOTER; AMPHIBIAN METAMORPHOSIS; POSITIONED NUCLEOSOMES; CHROMATIN STRUCTURE AB We have assembled the thyroid hormone-inducible promoter of the Xenopus thyroid hormone receptor (TR)beta A gene into chromatin using replication-coupled and -independent assembly pathways in vivo. We establish that heterodimers of TR and 9-cis retinoic acid receptors (RXR) can bind to their recognition sites within chromatin both in vivo and in vitro and alternately repress or activate transcription dependent on the absence or presence of thyroid hormone. Maximal transcriptional repression requires the presence of unliganded TR/RXR heterodimers during replication-coupled chromatin assembly. We demonstrate an increase in transcription directed by the TR beta A promoter of over two orders of magnitude in vivo, following the addition of thyroid hormone. This increase in transcription involves the relief of the repressed state that is established by the unliganded TR/RXR heterodimer during replication-coupled chromatin assembly. The association of thyroid hormone with the chromatin-bound TR/RXR heterodimer leads to the disruption of local chromatin structure in a transcription-independent process. Thus, chromatin structure has multiple roles in the regulation of TR beta A gene expression in vivo: The TR/RXR heterodimer recognizes the response element within chromatin, TR/RXR makes use of the chromatin assembly process to silence transcription more efficiently, and TR/RXR directs the disruption of local chromatin structure in response to thyroid hormone. C1 NICHHD,MOLEC EMBRYOL LAB,MOLEC BIOL SECT,BETHESDA,MD 20892. RP WONG, JM (reprint author), NICHHD,MOLEC MORPHOGENESIS UNIT,BETHESDA,MD 20892, USA. NR 85 TC 173 Z9 174 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 1 PY 1995 VL 9 IS 21 BP 2696 EP 2711 DI 10.1101/gad.9.21.2696 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA TD885 UT WOS:A1995TD88500011 PM 7590246 ER PT J AU LANE, TF DENG, CX ELSON, A LYU, MS KOZAK, CA LEDER, P AF LANE, TF DENG, CX ELSON, A LYU, MS KOZAK, CA LEDER, P TI EXPRESSION OF BRCA1 IS ASSOCIATED WITH TERMINAL DIFFERENTIATION OF ECTODERMALLY AND MESODERMALLY DERIVED TISSUES IN MICE SO GENES & DEVELOPMENT LA English DT Article DE BRCA1 EXPRESSION; MOUSE HOMOLOG; EMBRYONIC DEVELOPMENT; TERMINAL DIFFERENTIATION; TRANSCRIPTION; MAMMARY GLAND; RING FINGER ID MYC TRANSGENIC MICE; ZINC-FINGER; PROTEIN; GENE; ACID; SEQUENCE; STEP; IDENTIFICATION; RECEPTOR; BINDING AB We have isolated genomic and cDNA clones of Brca1, a mouse homolog of the recently cloned breast cancer-associated gene, BRCA1. Brca1 encodes an 1812-amino-acid protein with a conserved zinc finger domain and significant homology to the human protein. Brca1 maps to Chromosome 11 within a region of conserved synteny with human chromosome 17, consistent with the mapping of the human gene to 17q21. Brca1 transcripts are expressed in a variety of cultured cells but reveal a specific and dynamic expression pattern during embryonic development. for example, expression is observed first in the otic vesicle of embryonic day 9.5 (E9.5) embryos. This expression diminishes and is replaced by expression in the neuroectoderm at E10.5. By E11-12.5, higher levels are observed in differentiating keratinocytes and in whisker pad primordia. Transcripts also become evident in epithelial cells of the E14-17 kidney. Brca1 expression occurs in differentiating epithelial cells of several adult organs as well, suggesting a general role in the functional maturation of these tissues. Consistent with this, Brca1 transcripts are expressed in both alveolar and ductal epithelial cells of the mammary gland. During pregnancy, there is a large increase in Brca1 mRNA in mammary epithelial cells, an increase that parallels their functional differentiation. Because high rates of breast cancer are associated with loss of BRCA1 in humans, it is possible that this gene provides an important growth regulatory function in mammary epithelial cells. In addition, increased transcription of mammary Brca1 during pregnancy might contribute, in part, to the reduced cancer risk associated with exposure to pregnancy and lactation. C1 HOWARD HUGHES MED INST,BOSTON,MA 02115. NIAID,BETHESDA,MD 20892. RP LANE, TF (reprint author), HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115, USA. RI deng, chuxia/N-6713-2016 NR 46 TC 171 Z9 173 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 1 PY 1995 VL 9 IS 21 BP 2712 EP 2722 DI 10.1101/gad.9.21.2712 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA TD885 UT WOS:A1995TD88500012 PM 7590247 ER PT J AU JOHNSON, EW IYER, LM RICH, SS ORR, HT GILNAGEL, A KURTH, JH ZABRAMSKI, JM MARCHUK, DA WEISSENBACH, J CLERICUZIO, CL DAVIS, LE HART, BL GUSELLA, JF KOSOFSKY, BE LOUIS, DN MORRISON, LA GREEN, ED WEBER, JL AF JOHNSON, EW IYER, LM RICH, SS ORR, HT GILNAGEL, A KURTH, JH ZABRAMSKI, JM MARCHUK, DA WEISSENBACH, J CLERICUZIO, CL DAVIS, LE HART, BL GUSELLA, JF KOSOFSKY, BE LOUIS, DN MORRISON, LA GREEN, ED WEBER, JL TI REFINED LOCALIZATION OF THE CEREBRAL CAVERNOUS MALFORMATION GENE (CCM1) TO A 4-CM INTERVAL OF CHROMOSOME 7Q CONTAINED IN A WELL-DEFINED YAC CONTIG SO GENOME RESEARCH LA English DT Article ID DINUCLEOTIDE REPEAT POLYMORPHISMS; NATURAL-HISTORY; HUMAN GENOME; LINKAGE MAP; YEAST; CONSTRUCTION; LIBRARIES; ANGIOMAS; VECTORS; LOCI AB Cerebral cavernous malformations (CCM) are vascular lesions present in some 20 million people worldwide that are responsible for seizures, migraine, hemorrhage, and other neurologic problems. Familial cases of CCM can be inherited as an autosomal dominant disorder with variable expression. A gene for CCM (CCM1) was recently mapped to a 33-cM segment of chromosome 7q in a large Hispanic family (Dubovsky et al. 1995). Here, the collection of several new short tandem repeat polymorphisms (STRPs) within the region of interest on 7q and the refinement of the marker order in this region using both linkage analysis in CEPH families and especially YAC-based STS content mapping are described. Affected members of three Hispanic families share allele haplotypes indicating a common ancestral mutation within these families. Using the shared haplotype information along with analysis of crossovers in affected individuals from both the Hispanic and Caucasian families, the region likely to contain the CCM1 gene has been reduced to a 4-cM segment of 7q between D7S2410 and D7S689. All markers within the refined chromosomal segment were located on a single YAC contig estimated to be -2 Mb in size. Four potential candidate genes have been mapped to this region. C1 NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT PUBL HLTH SCI & NEUROL, WINSTON SALEM, NC 27157 USA. UNIV MINNESOTA, MINCEP, MINNEAPOLIS, MN 55455 USA. UNIV MINNESOTA, INST HUMAN GENET, MINNEAPOLIS, MN 55455 USA. UNIV MINNESOTA, DEPT LAB MED & PATHOL, MINNEAPOLIS, MN 55455 USA. UNIV MINNESOTA, DEPT NEUROL, MINNEAPOLIS, MN 55455 USA. BARROW NEUROL INST, PHOENIX, AZ 85026 USA. DUKE UNIV, MED CTR, DEPT GENET, DURHAM, NC 27710 USA. GENETHON, F-91000 EVRY, FRANCE. UNIV NEW MEXICO, SCH MED, DEPT PEDIAT, ALBUQUERQUE, NM 87131 USA. UNIV NEW MEXICO, SCH MED, DEPT NEUROL, ALBUQUERQUE, NM 87131 USA. UNIV NEW MEXICO, SCH MED, DEPT RADIOL, ALBUQUERQUE, NM 87131 USA. MASSACHUSETTS GEN HOSP, MOLEC NEUROGENET UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, NEUROL SERV, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP MARSHFIELD MED RES FDN, CTR MED GENET, MARSHFIELD, WI 54449 USA. OI Morrison, Leslie/0000-0002-0092-193X FU NINDS NIH HHS [NS16308] NR 45 TC 45 Z9 45 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD NOV PY 1995 VL 5 IS 4 BP 368 EP 380 DI 10.1101/gr.5.4.368 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA TK367 UT WOS:A1995TK36700005 PM 8750196 ER PT J AU LEE, CH COPELAND, NG GILBERT, DJ JENKINS, NA WEI, LN AF LEE, CH COPELAND, NG GILBERT, DJ JENKINS, NA WEI, LN TI GENOMIC STRUCTURE, PROMOTER IDENTIFICATION, AND CHROMOSOMAL MAPPING OF A MOUSE NUCLEAR ORPHAN RECEPTOR EXPRESSED IN EMBRYOS AND ADULT TESTES SO GENOMICS LA English DT Article ID MOLECULAR-CLONING; STEROID-RECEPTOR; GAMMA-GENE; VITAMIN-A; ORGANIZATION; ACID AB We have isolated and characterized overlapping genomic clones containing the complete transcribed region of a newly isolated mouse cDNA encoding an orphan receptor expressed specifically in midgestation embryos and adult testis. This gene spans a distance of more than 50 kb and is organized into 13 exons. The transcription initiation site is located at the 158th nucleotide upstream from the translation initiation codon. All the exon/intron junction sequences follow the GT/AG rule. Based upon Northern blot analysis and the size of the transcribed region of the gene, its transcript was determined to be approximately 2.5 kb. Within approximately 500 bp upstream hom the transcription initiation site, several immune response regulatory elements were identified but no TATA box was located. This gene was mapped to the distal region of mouse chromosome 10 and its locus has been designated Tr2-11. Immunohistochemical studies show that the Tr2-11 protein is present mainly in advanced germ cell populations of mature testes and that Tr2-11 gene expression is dramatically decreased in vitamin A-depleted animals. (C) 1995 Academic Press, Inc. C1 UNIV MINNESOTA,DEPT PHARMACOL,MINNEAPOLIS,MN 55455. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-46000]; NIDDK NIH HHS [DK46866-01] NR 23 TC 32 Z9 33 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 1 PY 1995 VL 30 IS 1 BP 46 EP 52 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TC727 UT WOS:A1995TC72700007 PM 8595902 ER PT J AU NICHOLS, RC PAI, SI GE, Q TARGOFF, IN PLOTZ, PH LIU, P AF NICHOLS, RC PAI, SI GE, Q TARGOFF, IN PLOTZ, PH LIU, P TI LOCALIZATION OF 2 HUMAN AUTOANTIGEN GENES BY PCR SCREENING AND IN-SITU HYBRIDIZATION - GLYCYL-TRANSFER-RNA SYNTHETASE LOCATES TO 7P15 AND ALANYL-TRANSFER-RNA SYNTHETASE LOCATES TO 16Q22 SO GENOMICS LA English DT Note ID TRANSFER-RNA-SYNTHETASE; AUTOANTIBODIES; LIBRARY; DNA C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,BETHESDA,MD 20892. OKLAHOMA MED RES FDN,ARTHRIT IMMUNOL SECT,OKLAHOMA CITY,OK 73104. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 10 TC 3 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 1 PY 1995 VL 30 IS 1 BP 131 EP 132 DI 10.1006/geno.1995.0028 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TC727 UT WOS:A1995TC72700028 PM 8595897 ER PT J AU LUTZ, RJ EPSTEIN, AH COOK, JA DEDRICK, RL AF LUTZ, RJ EPSTEIN, AH COOK, JA DEDRICK, RL TI AN IN-VITRO FLOW MODEL TO STUDY STREAMING DURING PELVIC INTRAARTERIAL DRUG INFUSIONS SO GYNECOLOGIC ONCOLOGY LA English DT Article ID RADIATION-THERAPY; INVITRO MODEL; BLOOD-FLOW; IODODEOXYURIDINE; DELIVERY; PHARMACOLOGY; CHEMOTHERAPY; IRRADIATION AB Regional delivery of suitable drugs by intra-arterial infusion may offer a therapeutic advantage, High concentrations in the tumor are sought with reduced systemic toxicity, Adequate mixing of drug solutions with perfusing blood is essential to provide uniform distribution of drug to tumor-bearing tissue distal to the infusion site, Using a glass model of the iliofemoral and pelvic arteries, we have demonstrated that a streaming phenomenon occurs, Laminar ''streamers'' of slowly infused drug solution originate at the catheter tip and proceed nonuniformly into distal arterial branches, The intensity of streaming and the pattern of distribution are highly sensitive to catheter tip placement acid quite unpredictable. The consequence of regional therapy under streaming conditions is severe maldistribution of drug in the infused tissues with potentially high levels delivered to normal tissues and simultaneous subtherapeutic levels delivered to tumor, Our in vitro model Fan be used to test appropriate infusion techniques that enhance mixing such as pulsed infusions and novel catheter designs. C1 NCI,DIV CANC TREATMENT,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,RADIAT BIOL BRANCH,BETHESDA,MD 20892. RP LUTZ, RJ (reprint author), NCI,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3N17,13 S DR MSC 5766,BETHESDA,MD 20892, USA. NR 38 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 1995 VL 59 IS 2 BP 288 EP 296 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA TD649 UT WOS:A1995TD64900024 PM 7590489 ER PT J AU WINGATE, S AF WINGATE, S TI QUALITY-OF-LIFE FOR WOMEN AFTER A MYOCARDIAL-INFARCTION SO HEART & LUNG LA English DT Article AB Objectives: To assess the level of quality of life and to determine the relationship of selected variables to quality of life in a sample of women after a myocardial infarction (MI). Design: Ex post facto, one-group, correlational survey. Setting: Offices of cardiologists in private practice. Participants: Consecutive sample of 96 women who had a diagnosis of MI, and who had not undergone cardiac surgery. Results: The mean quality of life score was 21.6. Significant variables in the regression equation were employment status (p < 0.01), social support (p < 0.01), and self-esteem (p = 0.04), and these three variables accounted for 45% of the variance in quality of life. Conclusions: The quality of life scores in this sample were higher than expected and similar to those of healthy populations. Those women in the sample who returned to their former employment status and had higher levels of social support and self-esteem had higher levels of quality of life. C1 NATL INST HLTH,BETHESDA,MD. NR 0 TC 26 Z9 26 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0147-9563 J9 HEART LUNG JI Heart Lung PD NOV-DEC PY 1995 VL 24 IS 6 BP 467 EP 473 DI 10.1016/S0147-9563(95)80024-7 PG 7 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA TF363 UT WOS:A1995TF36300005 PM 8582822 ER PT J AU YANOVSKI, JA YANOVSKI, SZ HARRINGTON, L GOLD, PW CHROUSOS, GP AF YANOVSKI, JA YANOVSKI, SZ HARRINGTON, L GOLD, PW CHROUSOS, GP TI DIFFERENCES IN THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS OF BLACK-AND-WHITE MEN SO HORMONE RESEARCH LA English DT Article DE CORTICOTROPIN-RELEASING HORMONE; ADRENOCORTICOTROPIC HORMONE; CORTISOL; RACIAL DIFFERENCES ID DEXAMETHASONE SUPPRESSION TEST; RACIAL-DIFFERENCES; WOMEN; CORTICOTROPIN; ALDOSTERONE; DIAGNOSIS; OBESITY AB We previously found that, following intravenous administration of ovine corticotropin-releasing hormone (CRH), the plasma ACTH concentrations of Black women were approximately twice as high as those of White women; however, there were no corresponding differences in cortisol response. To determine whether this difference in ACTH secretion is also present in men, we studied the hypothalamic-pituitary-adrenal axis of 10 Black and 10 White weight-, age-, and education-matched men. Waist-to-hip ratio, 24-hour urine free cortisol excretion, and ACTH and cortisol responses to 1 mu g/kg ovine CRH were determined. There were no racial differences in waist-to-hip ratio, 24-hour urine free cortisol excretion, baseline free or total plasma cortisol and ACTH concentrations, or plasma cortisol response to CRH. However, CRH-stimulated plasma ACTH concentrations, measured in an extraction polyclonal radioimmunoassay, were significantly greater in Blacks than in Whites at all time points between 30 and 180 min after administration of CRH (area under curve (AUG) 1,796 +/- 245 pmol/l . min in Blacks vs. 1,278 +/- 121 pmol/ l . min in Whites, p < 0.001). Neither cortisol nor ACTH AUCs were significantly correlated with Body Mass Index in Black or White men. We conclude that there are differences in the HPA axis of Black and White men similar to those found previously in women. The physiology underlying these differences remains to be understood. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NIDDK,DIV DIGEST DIS & NUTR,BETHESDA,MD. RP YANOVSKI, JA (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,MSC 1862,BLDG 10,ROOM 10N262,900 ROCKVILLE PK,BETHESDA,MD 20892, USA. OI Yanovski, Jack/0000-0001-8542-1637 NR 30 TC 12 Z9 12 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PD NOV PY 1995 VL 44 IS 5 BP 208 EP 212 DI 10.1159/000184627 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TG634 UT WOS:A1995TG63400003 PM 8582712 ER PT J AU CHUAH, MKL VANDENDRIESSCHE, T MORGAN, RA AF CHUAH, MKL VANDENDRIESSCHE, T MORGAN, RA TI DEVELOPMENT AND ANALYSIS OF RETROVIRAL VECTORS EXPRESSING HUMAN FACTOR-VIII AS A POTENTIAL GENE-THERAPY FOR HEMOPHILIA-A SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED TRANSFER; RNA; CELLS; REGION; FIBROBLASTS; SEQUENCES; INVITRO; LINE; MICE AB To develop a potential gene therapy strategy for the treatment of hemophilia A, we constructed several retroviral vectors expressing a B-domain-deleted factor WI (FVIII) cDNA, We confirmed previous reports that when the FVIII cDNA is inserted into a retroviral vector, the vector mRNA is decreased resulting in significantly (100- to 1,000-fold) lower vector titers. In an attempt to overcome this inhibition we pursued two independent strategies, First, site-directed mutagenesis was employed to change the structure of a putative 1.2-kb FVIII RNA inhibitory sequence (INS), Second, the FVIII gene was transcribed from a retroviral vector containing a 5' intron, Results demonstrated that the intron increased FVIII expression up to 20-fold and viral titer up to 40-fold but conservative mutagenesis of the putative FVIII WS region failed to yield a significant increase in FVIII expression or titer, Using the improved FVIII splicing vector, we transduced a variety of cell types and were able to demonstrate relatively high FVIII expression (10-60 ng of FVIII/10(6) cells/24 hr), These results underscore the usefulness of these transduced cell types for potential in vivo delivery of FVIII. C1 NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,GENE TRANSFER TECHNOL SECT,BETHESDA,MD 20892. GENET THERAPY INC,GAITHERSBURG,MD 20878. NR 39 TC 71 Z9 73 U1 0 U2 6 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 1995 VL 6 IS 11 BP 1363 EP 1377 DI 10.1089/hum.1995.6.11-1363 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA TE486 UT WOS:A1995TE48600002 PM 8573610 ER PT J AU NASH, MA PLATSOUCAS, CD WONG, BY WONG, PMC COTTLERFOX, M OTTO, E FREEDMAN, RS AF NASH, MA PLATSOUCAS, CD WONG, BY WONG, PMC COTTLERFOX, M OTTO, E FREEDMAN, RS TI TRANSDUCTION OF RIL-2 EXPANDED CD4(+) AND CD8(+) OVARIAN TIL-DERIVED T-CELL LINES WITH THE G1NA (NEO(R)) REPLICATION-DEFICIENT RETROVIRAL VECTOR SO HUMAN GENE THERAPY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; MEDIATED GENE-TRANSFER; MONOCLONAL-ANTIBODIES; THERAPY; EXPRESSION; VEHICLES; MELANOMA AB We have expanded ovarian tumor-infiltrating lymphocytes (TIL) in low concentrations of recombinant interleukin-2 (rIL-2) to conduct intraperitoneal adoptive immunotherapy trials in patients with ovarian cancer, We have previously demonstrated that certain T cell lines and clones derived from ovarian Tn, exhibit in vitro autologous tumor-specific cytotoxicity and/or cytokine production (interferon-gamma, tumor necrosis factor-alpha) preferentially in response to autologous tumor cells. Studies that utilize a marker gene introduced into the DNA of TIL can provide useful information on specific uptake or localization of TIL at tumor sites and on the survival of TIL in vivo, We have conducted a series of preclinical experiments in which we have successfully transfected TIL with G1Na, which encodes the gene for neomycin phosphotransferase (neo(R)), Neo(R) was detected in at least 10% of CD8(+) cells (mean = 10.4%) and between 2.5 and 20% of CD4(+) TIL (mean = 8.5%), Transduction of ovarian TIL with G1Na caused no substantial changes to the T cell phenotypes or in vitro cytotoxicities against ovarian and hematogenous tumor cell targets, or on the rIL-2 requirements of TIL for growth and proliferation, In addition, the intact G1Na provirus in transduced TIL cells was rescuable by replication-competent retrovirus and was transferred into the genome of NIH-3T3 fibroblasts, which were rendered resistant to G418, An enhanced polymerase chain reaction (PCR) procedure utilizing detection by ethidium bromide staining was developed, The enhanced PCR detected 1 in 100,000 neo(R)-labeled cells. Furthermore, detection of the G1Na genome in transduced TIL by in situ hybridization with an RNA probe provided evidence for expression of the neo(R) gene in transduced TIL. Results obtained from these studies suggest that ovarian TIL-derived T cell lines transduced with the neo(R) gene post infection with the G1Na retroviral vector can be utilized to examine the in vivo trafficking pattern of ovarian TIL-derived T cell lines expanded in low concentrations of rIL-2 and their survival. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT OBSTET GYNECOL,EXPTL GYNECOL SECT,HOUSTON,TX 77030. TEMPLE UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19140. TEMPLE UNIV,SCH MED,FELS INST CANC RES & MOLEC BIOL,PHILADELPHIA,PA 19140. NIH,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892. GENET THERAPY INC,GAITHERSBURG,MD 20878. FU NCI NIH HHS [CA-57884, CA-52308, CA-64943-01] NR 33 TC 1 Z9 1 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 1995 VL 6 IS 11 BP 1379 EP 1389 DI 10.1089/hum.1995.6.11-1379 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA TE486 UT WOS:A1995TE48600003 PM 8573611 ER PT J AU MUHLHAUSER, J PILI, R MERRILL, MJ MAEDA, H PASSANITI, A CRYSTAL, RG CAPOGROSSI, MC AF MUHLHAUSER, J PILI, R MERRILL, MJ MAEDA, H PASSANITI, A CRYSTAL, RG CAPOGROSSI, MC TI IN-VIVO ANGIOGENESIS INDUCED BY RECOMBINANT ADENOVIRUS VECTORS CODING EITHER FOR SECRETED OR NONSECRETED FORMS OF ACIDIC FIBROBLAST GROWTH-FACTOR SO HUMAN GENE THERAPY LA English DT Article ID BASEMENT-MEMBRANE; FACTOR FAMILY; FACTOR-I; HEPARIN; CELLS AB In vivo gene transfer of angiogenic growth factors represents a potential approach to the treatment of ischemic diseases, The present study examined the in vitro and in vivo effects of two replication-deficient recombinant adenovirus (Ad) vectors coding for human acidic fibroblast growth factor (aFGF(1-154)). One vector codes for the nonsecreted form of the peptide (AdCMV.aFGF(1-154)), and the other vector codes for a recombinant, secreted form (AdCMV.sp+aFGF(1-154)). AdCMV.NLS beta gal, an adenovirus vector coding for beta-galactosidase (beta-Gal), was used as a control, Assessment of proliferation of starved human umbilical vein endothelial cells infected with AdCMV.aFGF(1-154) and AdCMV.sp+aFGF(1-154) (20 pfu/cell) showed approximately 6- and 10-fold increase in cell number over control, respectively, Infection with AdCMV.sp+aFGF(1-154) and with AdCMV.aFGF(1-154) enhanced endothelial cell differentiation into capillary-like structures in vitro, However, this effect was significantly more pronounced with AdCMV.sp+aFGF(1-154) than with AdCMV.aFGF(1-154). Angiogenesis in vivo was assessed by injecting subcutaneously into mice 750 mu l of reconstituted basement membrane proteins (Matrigel) and the Ad vectors (2 x 10(8) pfu), After 14 days, there was histologic evidence of neovascularization in the animal's tissue surrounding the Matrigel plugs with AdCMV.aFGF(1-154) and AdCMV.sp+aFGF(1-154). Further, the hemoglobin content of the Matrigel plugs with AdCMV.aFGF(1-154) and with AdCMV.sp+aFGF(1-154) was, respectively, 2.3- and 2.6-fold higher than with AdCMV.NLS beta gal. Together, these observations support the concept that adenovirus vectors coding for various forms of acidic FGF(1-154) may be used to induce angiogenesis in vivo and may provide a new therapeutic approach to ischemic diseases. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,GENE THERAPY UNIT,BALTIMORE,MD 21224. NIA,BIOL CHEM LAB,BALTIMORE,MD 21224. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NHLBI,PULM BRANCH,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. IST DERMOPATICO IMMACOLATA,PATOL VASC LAB,ROME,ITALY. NR 23 TC 50 Z9 54 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 1995 VL 6 IS 11 BP 1457 EP 1465 DI 10.1089/hum.1995.6.11-1457 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA TE486 UT WOS:A1995TE48600010 PM 8573618 ER PT J AU LI, L HAMER, DH AF LI, L HAMER, DH TI RECOMBINATION AND ALLELIC ASSOCIATION IN THE XQ/YQ HOMOLOGY REGION SO HUMAN MOLECULAR GENETICS LA English DT Article ID HUMAN SEX-CHROMOSOMES; HUMAN X-CHROMOSOME; Y-CHROMOSOME; PSEUDOAUTOSOMAL REGION; PAIRING REGION; DNA-SEQUENCES; GENE; INACTIVATION; EVOLUTION; PROPHASE AB The ends of the long arms of the human X and Y chromosomes contain a homologous region that can undergo sequence exchange. We have developed new polymorphic markers to analyze the genetic behavior of this region in the three-generation CEPH reference families. These Xq/Yq markers undergo crossovers in approximately 2% of male meioses in a pattern consistent with reciprocal recombination rather than gene conversion. Although the rate of recombination in males is significantly higher than in females or in autosomal sequences, it is more than an order of magnitude lower than in the short arm pseudoautosomal region at Xp/Yp. The Xq/Yq markers exhibit allelic association with one another, but not with markers in the X-specific or Y-specific regions of the sex chromosomes. Hence the Xq/Yq homology region displays behavior that is intermediate between sex-linked and true pseudoautosomal, and is unlikely to be essential for proper chromosome segregation. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 20 TC 21 Z9 21 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1995 VL 4 IS 11 BP 2013 EP 2016 DI 10.1093/hmg/4.11.2013 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA TD659 UT WOS:A1995TD65900002 PM 8589676 ER PT J AU SAVITSKY, K SFEZ, S TAGLE, DA ZIV, Y SARTIEL, A COLLINS, FS SHILOH, Y ROTMAN, G AF SAVITSKY, K SFEZ, S TAGLE, DA ZIV, Y SARTIEL, A COLLINS, FS SHILOH, Y ROTMAN, G TI THE COMPLETE SEQUENCE OF THE CODING REGION OF THE ATM GENE REVEALS SIMILARITY TO CELL-CYCLE REGULATORS IN DIFFERENT SPECIES SO HUMAN MOLECULAR GENETICS LA English DT Article ID ATAXIA-TELANGIECTASIA; DROSOPHILA-MELANOGASTER; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; SCHIZOSACCHAROMYCES-POMBE; IONIZING-RADIATION; DNA-DAMAGE; MEIOTIC RECOMBINATION; V(D)J RECOMBINATION; SCID MUTATION AB Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immuno-deficiency, radiation sensitivity, and cancer predisposition. A-T heterozygotes are moderately cancer prone. The A-T gene, designated ATM, was recently identified in our laboratory by positional cloning, and a partial cDNA clone was found to encode a polypeptide with a PI-3 kinase domain. We report here the molecular cloning of a cDNA contig spanning the complete open reading frame of the ATM gene. The predicted protein of 3056 amino acids shows significant sequence similarities to several large proteins in yeast, Drosophila and mammals, ail of which share the PI-3 kinase domain. Many of these proteins are involved in the detection of DNA damage and the control of cell cycle progression. Mutations in their genes confer a variety of phenotypes with features similar to those observed in human A-T cells. The complete sequence of the ATM gene product provides useful clues to the function of this protein, and furthers understanding of the pleiotropic nature of the A-T mutations. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN GENET,IL-69978 RAMAT AVIV,ISRAEL. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. FU NINDS NIH HHS [NS31763] NR 84 TC 400 Z9 409 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1995 VL 4 IS 11 BP 2025 EP 2032 DI 10.1093/hmg/4.11.2025 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA TD659 UT WOS:A1995TD65900004 PM 8589678 ER PT J AU NAGLE, DL KOZAK, CA MANO, H CHAPMAN, VM BUCAN, M AF NAGLE, DL KOZAK, CA MANO, H CHAPMAN, VM BUCAN, M TI PHYSICAL MAPPING OF THE TEC AND GABRB1 LOCI REVEALS THAT THE W-SH MUTATION ON MOUSE CHROMOSOME-5 IS ASSOCIATED WITH AN INVERSION SO HUMAN MOLECULAR GENETICS LA English DT Article ID CELL GROWTH-FACTOR; C-KIT RECEPTOR; TYROSINE KINASE RECEPTOR; PROTO-ONCOGENE; HEMATOPOIETIC-CELLS; GENETIC-ANALYSIS; HUMAN PIEBALDISM; MUTANT MICE; T-COMPLEX; SI-LOCUS AB In the mouse, mutations in the c-Kit proto-oncogene, a member of the receptor tyrosine kinase (RTK) gene family, have pleiotropic effects on hematopoiesis, pigmentation and fertility (dominant spotting, W). However, in the W-sh allele the defect is confined to abnormal pigmentation caused by the disruption of 5' regulatory sequences of Kit leaving an intact structural gene. In this report, the previously published physical map around the Pdgfra-Kit-Flk1 RTK loci is extended by mapping the loci encoding the GABA(A) (gamma-aminobutyric acid) receptor subunit beta 1, Gabrb1 and a cytoplasmic kinase (Tec) 3 Mb proximal to Kit. PFGE analysis of the wild-type (C57BL/6J) chromosome demonstrates the following gene order: cen-Gabrb1-Tec-Pdgfra-Kit, whereas the analysis of W-sh/W-sh DNA is consistent with the order: cen-Gabrb1-Pdgfra-Tec-Kit. This altered physical map can be explained by an inversion on the W-sh chromosome located proximally to the Kit locus and spanning the 2.8 Mb Pdgfra-Tec chromosomal segment. This high resolution physical mapping study identifies large DNA fragments that span the two inversion breakpoints and potentially carry Kit upstream regulatory elements involved in the control of Kit expression during embryonic development. C1 UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. NIAID,BETHESDA,MD 20892. JICHI MED SCH,DEPT BIOL MOLEC,MINAMI KAWACHI,TOCHIGI,JAPAN. ROSWELL PK CANC INST,DEPT MOLEC & CELLULAR BIOL,BUFFALO,NY 14623. FU NHGRI NIH HHS [HG00170]; NICHD NIH HHS [HD 28410]; NIGMS NIH HHS [GM33160] NR 45 TC 34 Z9 34 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1995 VL 4 IS 11 BP 2073 EP 2079 DI 10.1093/hmg/4.11.2073 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA TD659 UT WOS:A1995TD65900009 PM 8589683 ER PT J AU RICHARDS, FM PAYNE, SJ ZBAR, B AFFARA, NA FERGUSONSMITH, MA MAHER, ER AF RICHARDS, FM PAYNE, SJ ZBAR, B AFFARA, NA FERGUSONSMITH, MA MAHER, ER TI MOLECULAR ANALYSIS OF DE-NOVO GERMLINE MUTATIONS IN THE VON HIPPEL-LINDAU DISEASE GENE SO HUMAN MOLECULAR GENETICS LA English DT Article ID VONRECKLINGHAUSEN NEUROFIBROMATOSIS; DINUCLEOTIDE; ORIGIN AB VHL disease is a dominantly inherited familial cancer syndrome with variable expression and age-dependent penetrance. The diagnosis of isolated cases is often delayed compared with familial cases, and estimates of the new mutation rate have varied more than 20-fold. To investigate the frequency and origin of de novo VHL gene mutations we have analysed: (i) families with identical mutations to determine if there is a common haplotype, and (ii) apparent new mutation cases to determine whether the clinical diagnosis of such cases is reliable and to define the parental origin of de novo VHL gene mutations. Haplotyping of 12 VHL mutations occurring in two or more families (total 42 kindreds) revealed that for most mutations there was no evidence of a founder effect. A marked bias for a paternal origin of new mutations has been reported in other familial cancer syndromes such as neurofibromatosis type 1 (NF1), multiple endocrine neoplasia (MEN) 2B and bilateral retinoblastoma, but it is unclear whether this bias results from a greater susceptibility for mutagenesis during male gametogenesis because of the larger number of cell divisions compared with that in oogenesis, or from genomic imprinting effects. Analysis of 13 de novo VHL mutations in which the parent of origin could be established, showed no evidence for a bias for a paternal origin (seven paternal, six maternal), and differed significantly from that reported in NF1, MEN2B and bilateral retinoblastoma. This result demonstrates that an increased susceptibility to paternal allele mutation is not a universal finding in autosomal genetic diseases and that the origin of new mutations may be influenced by both genomic imprinting effects and the increased number of cell divisions in spermatogenesis compared with oogenesis. C1 UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE CB2 1QP,ENGLAND. ADDENSBROOKE NHS TRUST,MOLEC GENET LAB,CAMBRIDGE,ENGLAND. NCI,IMMUNOBIOL LAB,FREDERICK,MD 21701. RI MAHER, EAMONN/A-9507-2008 OI MAHER, EAMONN/0000-0002-6226-6918 NR 33 TC 77 Z9 79 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1995 VL 4 IS 11 BP 2139 EP 2143 DI 10.1093/hmg/4.11.2139 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA TD659 UT WOS:A1995TD65900018 PM 8589692 ER PT J AU BAGROV, AY FEDOROVA, OV AUSTINLANE, JL DMITRIEVA, RI ANDERSON, DE AF BAGROV, AY FEDOROVA, OV AUSTINLANE, JL DMITRIEVA, RI ANDERSON, DE TI ENDOGENOUS MARINOBUFAGENIN-LIKE IMMUNOREACTIVE FACTOR AND NA+,K+ ATPASE INHIBITION DURING VOLUNTARY HYPOVENTILATION SO HYPERTENSION LA English DT Article DE HYPOVENTILATION; NA+,K+-EXCHANGING ATPASE; BUFANOLIDES; HYPERTENSION ID DIGITALIS-LIKE-FACTOR; VOLUME-EXPANDED DOGS; SODIUM-TRANSPORT; ESSENTIAL-HYPERTENSION; CIRCULATING INHIBITOR; HUMAN-PLASMA; DIGOXIN; NA,K-ATPASE; ANTIBODIES; ERYTHROCYTES AB In previous studies investigators found that conditioned hypoventilatory breathing potentiated a sodium-sensitive form of hypertension in dogs that was not mediated by sympathetic nervous system arousal. Our study investigated effects of 30 minutes of voluntary hypoventilation, maintained by a respiratory gas monitor and feedback procedure, in 16 normotensive humans of both sexes on (1) plasma concentrations of endogenous digitalis-like factors (ouabain-like and marinobufagenin-like immunoreactivity), (2) activity of erytherocyte Na+,K+-ATPase, (3) inhibitory activity of plasma Na+,K+-ATPase, and (4) blood pressure. Increased end tidal Pco(2) (41+/-0.78 mm Hg versus 37.6+/-1.03 mm Hg) was associated with (1) an increase in plasma marinobufagenin-like immunoreactivity (1.23+/-0.47 versus 4.96+/-1.19 nmol/L), (2) an inhibition of Na+,K+-ATPase in red blood cells (3.68+/-0.22 versus 2.15+/-0.25 mmol P-i . mL(-1). h(-1); P<.01), (3) increase in plasma Na+,K+-ATPase inhibitory activity (34.9+/-4.0% versus 48.8+/-2.1%, P<.02), and (4) increases in systolic (112.4+/-2.6 versus 107.6+/-1.8 mm Hg) and diastolic (73.5+/-2.1 versus 68.8+/-2.1 mm Hg) blood pressures. Plasma levels of ouabain-like immunoreactivity did not increase significantly. Incubation of erythrocytes obtained during hypoventilation with antidigoxin antibody restored the Na+,K+-ATPase activity (3.99+/-0.34 mmol P-i . mL(-1). h(-1)). Cessation of hypoventilation was associated with decreases in diastolic blood pressure (70.5+/-2.2 mm Hg) and restoration of Na+,K+-ATPase activity in erythrocytes (2.99+/-0.43 mmol P-i . mL(-1). h(-1)). On the basis of organic extraction and thin-layer chromatography followed by separation with the use of reverse-phase high-performance liquid chromatography, the material coeluting with marinobufagenin was separated from human urine. This material cross-reacted with anti-marinobufagenin antibody. These results demonstrate the presence of a bufadienolide-like Na+,K+-ATPase inhibitor in human plasma and support the view that breathing pattern may participate in blood pressure control via release of a rapidly acting circulating Na+,K+-ATPase inhibitor. C1 IM SECHENOV EVOLUT PHYSIOL & BIOCHEM INST,PHARMACOL LAB,ST PETERSBURG,RUSSIA. RP BAGROV, AY (reprint author), NIA,BEHAV SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Dmitrieva, Renata/0000-0002-3073-7914 NR 44 TC 91 Z9 91 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 1995 VL 26 IS 5 BP 781 EP 788 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TD294 UT WOS:A1995TD29400010 PM 7591018 ER PT J AU OSTELL, JM AF OSTELL, JM TI INTEGRATED ACCESS TO HETEROGENEOUS DATA FROM NCBI SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article RP OSTELL, JM (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,INFORMAT ENGN BRANCH,8600 ROCKVILLE PIKE,3BA B2N12,BETHESDA,MD 20894, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD NOV-DEC PY 1995 VL 14 IS 6 BP 730 EP 736 DI 10.1109/51.473267 PG 7 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA TE830 UT WOS:A1995TE83000016 ER PT J AU UNSER, M AF UNSER, M TI TEXTURE CLASSIFICATION AND SEGMENTATION USING WAVELET FRAMES SO IEEE TRANSACTIONS ON IMAGE PROCESSING LA English DT Article ID ORTHONORMAL BASES; GABOR FUNCTIONS; TRANSFORMS; DISCRIMINATION; REPRESENTATION AB This paper describes a new approach to the characterization of texture properties at multiple scales using the wavelet transform, The analysis uses an overcomplete wavelet decomposition, which yields a description that is translation invariant. It is shown that this representation constitutes a tight frame of l(2) and that it has a fast iterative algorithm, A texture is characterized by a set of channel variances estimated at the output of the corresponding filter bank, Classification experiments with 12 Brodatz textures indicate that the discrete wavelet frame (DWF) approach is superior to a standard (critically sampled) wavelet transform feature extraction, These results also suggest that this approach should perform better than most traditional single resolution techniques (co-occurrences, local linear transform, and the like). A detailed comparison of the classification performance of various orthogonal and biorthogonal wavelet transforms is also provided. Finally, the DWF feature extraction technique is incorporated into a simple multicomponent texture segmentation algorithm, and some illustrative examples are presented. RP UNSER, M (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. RI Unser, Michael/A-1550-2008; anzhi, yue/A-8609-2012 NR 36 TC 808 Z9 874 U1 4 U2 54 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 1057-7149 J9 IEEE T IMAGE PROCESS JI IEEE Trans. Image Process. PD NOV PY 1995 VL 4 IS 11 BP 1549 EP 1560 DI 10.1109/83.469936 PG 12 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA TC628 UT WOS:A1995TC62800008 PM 18291987 ER PT J AU NAKAJIMA, PB MENETSKI, JP ROTH, DB GELLERT, M BOSMA, MJ AF NAKAJIMA, PB MENETSKI, JP ROTH, DB GELLERT, M BOSMA, MJ TI V-D-J REARRANGEMENTS AT THE T-CELL RECEPTOR DELTA-LOCUS IN MOUSE THYMOCYTES OF THE ALPHA-BETA LINEAGE SO IMMUNITY LA English DT Article ID GAMMA-DELTA; ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODIES; GENE REARRANGEMENTS; GENOMIC ORGANIZATION; V(D)J RECOMBINATION; CD4+8+ THYMOCYTES; TRANSGENIC MICE; CHAIN GENES; SCID MICE AB The T cell receptor (TCR) delta locus lies within the TCR alpha locus and is excised from the chromosome by V alpha-J alpha rearrangement. We show here that delta sequences persist in a large fraction of the DNA from mature CD4(+)CD8(-)alpha beta(+) mouse thymocytes. Virtually all delta loci in these cells are rearranged and present in extrachromosomal DNA. In immature alpha beta lineage thymocytes (CD3(-/lo)CD4(+)CD8(+)) and in CD4(+)CD8(-)alpha beta(+) thymocytes expressing a transgene-encoded alpha beta receptor, rearranged delta genes are present both in chromosomal and extrachromosomal DNA. Thus, contrary to earlier proposals, commitment to the alpha beta lineage does not require recombinational silencing of the delta locus or its deletion by a site-specific mechanism prior to V alpha-J alpha rearrangement. C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. RP NAKAJIMA, PB (reprint author), FOX CHASE CANC CTR,INST CANC RES,7701 BURHOLME AVE,PHILADELPHIA,PA 19111, USA. FU NCI NIH HHS [CA-04946]; NCRR NIH HHS [RR-05539]; NIAID NIH HHS [AI-13323] NR 68 TC 35 Z9 35 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 1995 VL 3 IS 5 BP 609 EP 621 DI 10.1016/1074-7613(95)90132-9 PG 13 WC Immunology SC Immunology GA TG281 UT WOS:A1995TG28100009 PM 7584151 ER PT J AU KING, LB VACCHIO, MS DIXON, K HUNZIKER, R MARGULIES, DH ASHWELL, JD AF KING, LB VACCHIO, MS DIXON, K HUNZIKER, R MARGULIES, DH ASHWELL, JD TI A TARGETED GLUCOCORTICOID RECEPTOR ANTISENSE TRANSGENE INCREASES THYMOCYTE APOPTOSIS AND ALTERS THYMOCYTE DEVELOPMENT SO IMMUNITY LA English DT Article ID T-CELLS; MESSENGER-RNA; BETA-CHAIN; GENE-EXPRESSION; WILD-TYPE; MICE; ACTIVATION; IMMATURE; INDUCTION; DEATH AB The exquisite sensitivity of thymocytes to steroid-induced apoptosis, the steroidogenic potential of thymic epithelial cells, and the ability of steroid synthesis inhibitors to enhance antigen-specific deletion of thymocytes in fetal thymic organ cultures suggest a role for glucocorticoids in thymocyte development. To address this further, transgenic mice that express antisense transcripts to the glucocorticoid receptor (GR) specifically in immature thymocytes were generated. The consequent hyporesponsiveness of thymocytes to glucocorticoids was accompanied by a reduction in thymic size, primarily owing to a decrease in the number of CD4(+)CD8(+) cells. While an enhanced susceptibility to T cell receptor (TCR)-mediated apoptosis appeared to be partially responsible for this reduction, thymocyte loss could also be detected before thymocytes progressed to the CD4(+)CD8(+) TCR alpha beta-expressing stage, These results suggest that glucocorticoids are necessary for survival and maturation of thymocytes, and are consistent with a role for steroids in both the transition from CD4(-)CD8(-) to CD4(+)CD8(+) cells and the survival of CD4(+)CD8(+) cells stimulated via the TCR. C1 NIAID, IMMUNOL LAB, BETHESDA, MD 20892 USA. RP KING, LB (reprint author), NCI, IMMUNE CELL BIOL LAB, BETHESDA, MD 20892 USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 FU NCI NIH HHS [CA09162] NR 56 TC 166 Z9 167 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 1995 VL 3 IS 5 BP 647 EP 656 DI 10.1016/1074-7613(95)90135-3 PG 10 WC Immunology SC Immunology GA TG281 UT WOS:A1995TG28100012 PM 7584154 ER PT J AU LIAO, J NICKERSON, KG BYSTRICKY, S ROBBINS, JB SCHNEERSON, R SZU, SC KABAT, EA AF LIAO, J NICKERSON, KG BYSTRICKY, S ROBBINS, JB SCHNEERSON, R SZU, SC KABAT, EA TI CHARACTERIZATION OF A HUMAN MONOCLONAL IMMUNOGLOBULIN-M (IGM) ANTIBODY (IGM(BEN)) SPECIFIC FOR VI CAPSULAR POLYSACCHARIDE OF SALMONELLA-TYPHI SO INFECTION AND IMMUNITY LA English DT Article ID ESCHERICHIA-COLI K1; DENATURED DNA; POLYNUCLEOTIDES; ANTIGEN; FEVER; ACID AB A search for human monoclonal antibodies to protective antigens of bacteria revealed an immunoglobulin M lambda chain [IgM(lambda); designated IgM(BEN)] reactive with the Vi capsular polysaccharide of Salmonella typhi. Vi, a linear homopolymer of alpha(1-->4)GalApNAc that is O acetylated at C-3, is a licensed vaccine for typhoid fever. Immunologic properties of IgM(BEN) were compared to those of burro globulin prepared by intravenous injections of S. typhi (B339-340). IgM(BEN) and B339-340 yielded identical precipitin lines with Vi by double immunodiffusion. IgM(BEN) and B339-340 produced similar precipitation results with Vi and its derivatives prepared by de-O-acetylation, carboxyl reduction, and removal or replacement of the N-acetyl at C-2 with O-acetyl. B339-340 yielded maximal precipitation with Vi (0.41 mg of antibody per ml with 1.4 mu g of Vi); next was carboxyl-reduced, O-acetylatecl Vi, which precipitated 0.325 mg of antibody per mi with 2.5 mu g of Vi. IgM(BEN) yielded maximal precipitation,vith de-O-acetylated, carboxyl-reduced Vi (similar to 11.0 mg of antibody per mi with similar to 1.3 mu g of antigen); next were de-O-acetylated Vi (9.89 mg/ml) and Vi (9.19 mg/ml). The precipitin curves and equivalence points of these three antigens were similar. Pneumococcus type 1, which contains GalApNAc, did not precipitate with Vi or its derivatives. These slight differences in specificity between IgM(BEN) and B339-340 were related to our proposed structure of Vi. We plan to use IgM(BEN) as a reference for measurement of vaccine-induced Vi antibodies. C1 COLUMBIA UNIV,COLL PHYS & SURG,DEPT MICROBIOL & NEUROL,NEW YORK,NY 10032. COLUMBIA UNIV,COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032. NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [5RO1-AI-27508, 5RO1-AI19042, 5RO1-AI-25616] NR 32 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1995 VL 63 IS 11 BP 4429 EP 4432 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TB400 UT WOS:A1995TB40000033 PM 7591081 ER PT J AU ALPUCHEARANDA, CM BERTHIAUME, EP MOCK, B SWANSON, JA MILLER, SI AF ALPUCHEARANDA, CM BERTHIAUME, EP MOCK, B SWANSON, JA MILLER, SI TI SPACIOUS PHAGOSOME FORMATION WITHIN MOUSE MACROPHAGES CORRELATES WITH SALMONELLA SEROTYPE PATHOGENICITY AND HOST SUSCEPTIBILITY SO INFECTION AND IMMUNITY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INNATE RESISTANCE; TYPHIMURIUM INVASION; NATURAL-RESISTANCE; EPITHELIAL-CELLS; INFECTION; MICE; VIRULENCE; GENE; EXPRESSION AB Light microscopic studies indicated a correlation between the virulence for mice of different Salmonella serotypes and the ability to form or maintain spacious phagosomes (SP) within mouse macrophages. Although Salmonella typhimurium induced membrane ruffling, macropinocytosis, and SP formation in macrophages from BALB/c mice, serotypes which are nonpathogenic for mice produced markedly fewer SP. SP formation correlated with both serotype survival within mouse macrophages and reported lethality for mice. Time-lapse video microscopy demonstrated that the human pathogen S. typhi induced generalized macropinocytosis and SP formation in human monocyte-derived macrophages, indicating a similar morphology for the initial phases of this host-pathogen interaction. In contrast to bone marrow-derived macrophages from BALB/c mice, macrophages from S. typhimurium-resistant outbred (CD-1) and inbred (CBA/HN) mice did not initiate generalized macropinocytosis after bacterial infection and formed markedly fewer SP. These deficiencies were not due to the Ity resistance genotype of these mice, as macrophages from mice that were congenic except for the Ity locus demonstrated equal SP formation in response to S. typhimurium. The observation that S. typhimurium-resistant CD-1 and CBA/HN mice are deficient in the ability to form and/or maintain SP indicates that a variable host component is important for SP formation and suggests that the ability to induce or form SP affects susceptibility to S. typhimurium. When serotypes nonpathogenic for mice were used to infect BALB/c macrophages, or when CD-1 or CBA/HN mouse macrophages were infected by S. typhimurium, some of the SP that formed shrank within seconds. This rapid shrinkage suggests that SP maintenance is also important for S. typhimurium survival within macrophages. These studies indicate that both host and bacterial factors contribute to SP formation and maintenance, which correlate with Salmonella intracellular survival and the ability to cause lethal enteric (typhoid) fever. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NCI,GENET LAB,BETHESDA,MD 20892. RI Swanson, Joel/P-4362-2014 OI Swanson, Joel/0000-0003-0900-8212 FU NIAID NIH HHS [AI 35950, AI34504] NR 41 TC 65 Z9 65 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1995 VL 63 IS 11 BP 4456 EP 4462 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TB400 UT WOS:A1995TB40000037 PM 7591085 ER PT J AU STEVENSON, B SCHWAN, TG ROSA, PA AF STEVENSON, B SCHWAN, TG ROSA, PA TI TEMPERATURE-RELATED DIFFERENTIAL EXPRESSION OF ANTIGENS IN THE LYME-DISEASE SPIROCHETE, BORRELIA-BURGDORFERI SO INFECTION AND IMMUNITY LA English DT Note ID IXODES-DAMMINI; PROTEIN; TICKS; ANTIBODIES AB Previous studies have demonstrated that Borrelia burgdorferi in the midguts of infected ticks shows increased expression of the antigenic outer surface protein OspC after the ticks have ingested a blood meal. This differential expression is at least partly due to a change in temperature, as an increase in OspC levels is also observed when cultures are shifted from 23 to 35 degrees C. Immunoblotting of bacterial lysates with sera from infected mice indicated that the levels of several additional antigens were also increased in bacterial cultures shifted to 35 degrees C; we have identified one antigen as OspE. We have also observed differential expression of OspF, which has been proposed to be coexpressed in an operon with the gene encoding OspE. RP STEVENSON, B (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 30 TC 256 Z9 257 U1 0 U2 5 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 NOV PY 1995 VL 63 IS 11 BP 4535 EP 4539 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TB400 UT WOS:A1995TB40000051 PM 7591099 ER PT J AU Pippin, CG McMurry, TJ Brechbiel, MW McDonald, M Lambrecht, R Milenic, D Roselli, M Colcher, D Gansow, OA AF Pippin, CG McMurry, TJ Brechbiel, MW McDonald, M Lambrecht, R Milenic, D Roselli, M Colcher, D Gansow, OA TI Lead(II) complexes of 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate: Solution chemistry and application to tumor localization with Pb-203 labeled monoclonal antibodies SO INORGANICA CHIMICA ACTA LA English DT Article DE kinetics and mechanism; thermodynamics; lead complexes; aza macrocycle complexes; monoclonal antibodies ID CARCINOMA XENOGRAFTS; GLYCOPROTEIN TAG-72; B72.3; RADIOIMMUNOTHERAPY; AGENT; MACROCYCLES; STABILITY; ANTIGEN; DOTA AB The aqueous solution chemistry of lead(II) complexes of DOTA (DOTA(4-)=1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate) has been investigated in the course of developing Pb-203 radiolabeled monoclonal antibodies as imaging agents. The stability and protonation constant of the 1:1 complex of Pb(DOTA)(2-) were estimated to be 10(24.3+/-0.2) and 10(3.3+/-0.1) at 25 degrees C, I=0.10 M (NaClO4), respectively. Formation reaction kinetics between Pb(II) and DOTA were investigated by stopped-flow methods. Possible mechanisms developed for the reaction involve (i) the rapid formation of a protonated intermediate which subsequently loses a proton during the rate-limiting step and (ii) formation of a rapid 'dead-end' equilibrium, with reactants reacting by a second-order process to give products. Dissociation of Pb(DOTA)(2-) to form the aquo Pb(II) cation and protonated DOTA was studied in perchloric acid. These results, when applied to the radiolabeling of monoclonal antibody B72.3 conjugates of DOTA with Pb-203, led to, the biological evaluation of the Pb-203(DOTA)-B72.3 radioimmunoconjugate in mice, Biodistribution studies reported here suggest that Pb-203(DOTA) labeled monoclonal antibodies may be useful for tumor localization of Pb(II) radionuclides. C1 NATL CANC INST,CHEM SECT,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,TUMOR BIOL LAB,BETHESDA,MD 20892. KING FAISAL SPECIALIST HOSP & RES CTR,DEPT RADIONUCLIDE & CYCLOTRON OPERAT,RIYADH 11211,SAUDI ARABIA. UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE 68198. NR 36 TC 28 Z9 28 U1 0 U2 6 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 0020-1693 J9 INORG CHIM ACTA JI Inorg. Chim. Acta PD NOV PY 1995 VL 239 IS 1-2 BP 43 EP 51 DI 10.1016/0020-1693(95)04708-5 PG 9 WC Chemistry, Inorganic & Nuclear SC Chemistry GA TL875 UT WOS:A1995TL87500008 ER PT J AU GOMEZ, DE KASSIM, A OLIVERO, OA AF GOMEZ, DE KASSIM, A OLIVERO, OA TI PREFERENTIAL INCORPORATION OF 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE (AZT) IN TELOMERIC SEQUENCES OF CHO CELLS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE ANTICANCER DRUGS; AZT; CHO; TELOMERASE; TELOMERE ID VIRUS REVERSE-TRANSCRIPTASE; HUMAN FIBROBLASTS; DNA-POLYMERASES; CELLULAR DNA; 3'-AZIDO-3'-DEOXYTHYMIDINE; 5'-TRIPHOSPHATE; TRIPHOSPHATE; PHARMACOLOGY; SENESCENCE AB 3'-Azido-2',3'-dideoxythymidine (AZT), the thymidine analogue used against human immunodeficiency virus 1 (HIV-1), exhibits bone marrow and blood toxicity in humans, presumably as the result of genotoxic mechanisms induced by incorporation of AZT into eukaryotic DNA. Preferential incorporation of AZT into telomeric regions of DNA of Chinese hamster ovary (CHO) cells has been previously demonstrated by immunofluorescence using anti-AZT antibodies. We quantitatively compared the amount of [H-3]-AZT bound to telomeric and non-telomeric sequences of CHO cell DNA. DNA from cells exposed to [H-3]-AZT was digested by a mixture of restriction enzymes, frequent cutters in the overall genome, without restriction sites in the telomeric repeat. As a result, the telomeric fraction (TF): isolated by separation columns, comprised longer sequences (> 2 kb) than the non-telomeric fraction (NTF). Radioactivity associated with each fraction revealed a three fold increase in [H-3]-AZT incorporated in the TF compared with the NTF. No preferential telomeric binding was detected for [H-3]-thymidine (Tdr) or [H-3]-5'bromodeoxyuridine (BrdU) in similar experiments or in DNA of AZT-treated mouse primary fibroblasts, cells with large telomeric repeats that lack telomerase. When the chromosomal ends of high molecular weight [H-3]-AZT-DNA were digested with Pal 31, the radioactivity was double in the TF compared with the NTF. Therefore incorporation of AZT in CHO immortalized cells but not in primary fibroblasts (that lack telomerase) indirectly shows that AZT incorporation could be telomerase-mediated. C1 NCI,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. OI Gomez, Daniel E/0000-0002-8629-0787 NR 24 TC 27 Z9 28 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 NOV PY 1995 VL 7 IS 5 BP 1057 EP 1060 PG 4 WC Oncology SC Oncology GA TA190 UT WOS:A1995TA19000006 PM 21552931 ER PT J AU OKUNIEFF, P AF OKUNIEFF, P TI TOWARDS NONINVASIVE HUMAN TUMOR PHYSIOLOGICAL MEASUREMENTS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID INVIVO RP OKUNIEFF, P (reprint author), NCI,RADIAT ONCOL BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM B3B69,BETHESDA,MD 20892, USA. NR 7 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 1995 VL 33 IS 4 BP 961 EP 962 DI 10.1016/0360-3016(95)02142-0 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA TE826 UT WOS:A1995TE82600027 PM 7591910 ER PT J AU ROBISON, WG LAVER, NM JACOT, JL GLOVER, JP AF ROBISON, WG LAVER, NM JACOT, JL GLOVER, JP TI SORBINIL PREVENTION OF DIABETIC-LIKE RETINOPATHY IN THE GALACTOSE-FED RAT MODEL SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE ALDOSE REDUCTASE; COMPUTER MORPHOMETRY; DIABETIC RETINOPATHY; GALACTOSE-FED RAT MODEL; RETINAL VASCULATURE ID ALDOSE REDUCTASE INHIBITOR; RETINAL VESSEL CHANGES; FED DOGS; CATARACT; TOLRESTAT; COMPLICATIONS; CAPILLARIES; MELLITUS AB Purpose, To determine if the retinal microangiopathies of the galactose-fed rat model of diabetic retinopathy can be prevented with the aldose reductase inhibitor sorbinil. Methods. Sprague-Dawley rats were fed 50% d-galactose with or without sorbinil (0.05% wt/ wt), mixed biweekly with fresh diet. Rats in each group were examined frequently by slit lamp and were killed after 8, 16, and 24 months. Computer-assisted morphometry was performed on wholemounts of elastase retinal digest preparations. Results, Cataracts developed in all galactose-fed untreated rats within 3 weeks but not in the sorbinil-treated rats even after 24 months. At 8 months, the galactose-fed untreated rats exhibited statistically significant increases in the mean capillary width, the percent of retinal area occupied by capillaries (capillary density), and the percent of microvascular area with capillaries >20 mu m wide (dilated channels), compared to controls. At 16 months, the galactose-fed untreated rats showed statistically significant increases over controls in both total mean capillary length and density, and two of the four rats examined had microaneurysms. At 24 months, all the galactose-fed untreated rats had microaneurysms and extensive areas with hypercellular meshworks composed of dilated channels characteristic of intraretinal microvascular abnormalities (IRMA). By contrast, galactose-fed, sorbinil-treated rats, at 24 months, had no IRMA and showed no statistically significant differences from control rats in any of the parameters measured morphometrically. Conclusions, Ail the galactose-induced retinal microangiopathies were prevented with sorbinil. Aldose reductase inhibitors may be beneficial in ameliorating the similar vascular lesions characteristic of human diabetic retinopathy, though the mechanism remains obscure. RP ROBISON, WG (reprint author), NEI,9000 ROCKVILLE PIKE,BLDG 6,ROOM 316,BETHESDA,MD 20892, USA. NR 43 TC 33 Z9 33 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 1995 VL 36 IS 12 BP 2368 EP 2380 PG 13 WC Ophthalmology SC Ophthalmology GA TD020 UT WOS:A1995TD02000009 PM 7591626 ER PT J AU LU, SC SUN, WM NAGINENI, CN HOOKS, JJ KANNAN, R AF LU, SC SUN, WM NAGINENI, CN HOOKS, JJ KANNAN, R TI BIDIRECTIONAL GLUTATHIONE TRANSPORT BY CULTURED HUMAN RETINAL-PIGMENT EPITHELIAL-CELLS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE GLUTATHIONE (GSH) EFFLUX; GLUTATHIONE (GSH) UPTAKE; HUMAN RETINAL PIGMENT EPITHELIAL CELLS; RCGSHT; TSGSHT ID BLOOD-BRAIN-BARRIER; RAT HEPATOCYTES; HEPATIC GLUTATHIONE; INHIBITION; PROTECTION; KINETICS; EFFLUX AB Purpose. To characterize glutathione (GSH) transport by cultured human retinal pigment epithelial (HRPE) cells. Methods. Cultured HRPE cells were pretreated with acivicin for GSH efflux and with buthionine sulfoximine for GSH uptake to prevent the breakdown and resynthesis of GSH. Efflux was measured by the linear rate of accumulation of GSH in the supernatant; uptake was measured using [S-35] GSH plus varying concentrations of GSH. Molecular forms were verified by high-performance liquid chromatography. HRPE cell mRNA was probed for the presence of the two recently cloned rat sinusoidal and canalicular GSH transporters, (RsGshT and RcGshT), by Northern blot analysis. Results. Glutathione efflux was temperature dependent (undetectable at 4 degrees C), and it averaged 23 +/- 3.3 pmol/10(6) cells/minute or 10% of the total GSH effluxed per hour (total cell GSH = 13.6 +/- 1.5 nmol/10(6) cells). Efflux was not influenced by dithiothreitol or sulfobromophthalein-reduced GSH adduct, agents known to affect liver sinusoidal GSH transport. Glutathione uptake tvas linear up to 45 minutes and was temperature dependent. The difference between 37 degrees C and 4 degrees C uptake values represented true uptake. Glutathione uptake (2 mu Ci/ml + 1 mM mass) was Na independent and was inhibited significantly by phenol-3,6-dibromphthaleim disulfonate. The kinetics of GSH uptake was assessed by measuring uptake with S-35-GSH and 0.05 to 40 mM extracellular GSH for 30 minutes. Uptake was saturable with V-max = 18.7 +/- 1.7 nmol/10(6) cells/30 minutes, K-m = 12.1 +/- 1.9 mM, n (binding site) = 1. On Northern blot analysis, HRPE cells express mRNA for RcGshT but not for RsGshT. Conclusions. The similarities in functional characteristics of GSH transport and the presence of RcGshT-like mRNA suggest GSH transport in HRPE cells is mediated by a RcGshT homolog. Although the transporter can operate bidirectionally, it is expected to be a net efflux pump under normal physiologic conditions because the intracellular GSH concentration is much higher. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. OUTPATIENT CLIN,DEPT VET AFFAIRS,LOS ANGELES,CA. RP LU, SC (reprint author), UNIV SO CALIF,SCH MED,DEPT MED,DIV GASTROINTESTINAL & LIVER DIS,MUDD ROOM 410,1333 SAN PABLO ST,LOS ANGELES,CA 90033, USA. FU NIDDK NIH HHS [DK-45334] NR 30 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 1995 VL 36 IS 12 BP 2523 EP 2530 PG 8 WC Ophthalmology SC Ophthalmology GA TD020 UT WOS:A1995TD02000025 PM 7591642 ER PT J AU SLOAND, EM PITT, E KLEIN, HG AF SLOAND, EM PITT, E KLEIN, HG TI SAFETY OF THE BLOOD-SUPPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; T-CELL LEUKEMIA; HTLV-II INFECTION; NON-B HEPATITIS; TRANSFUSION-ASSOCIATED HEPATITIS; POLYMERASE CHAIN-REACTION; INTRAVENOUS-DRUG-USERS; LYMPHOTROPIC VIRUS; TRYPANOSOMA-CRUZI C1 NIH, WARREN GRANT MAGNUSON CLIN CTR, BETHESDA, MD 20892 USA. RP SLOAND, EM (reprint author), NHLBI, 31 CTR DR, MSC 2490, BLDG 31, ROOM 4A11, BETHESDA, MD 20892 USA. NR 107 TC 65 Z9 68 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 1 PY 1995 VL 274 IS 17 BP 1368 EP 1373 DI 10.1001/jama.274.17.1368 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TB278 UT WOS:A1995TB27800028 PM 7563562 ER PT J AU DESFORGES, JF ATHARI, F COOPER, ES JOHNSON, CS LEMON, SM LINDSAY, KL MCCULLOUGH, J MCINTOSH, K ROSS, RK WHITSETT, CF WITTES, J WRIGHT, TL AF DESFORGES, JF ATHARI, F COOPER, ES JOHNSON, CS LEMON, SM LINDSAY, KL MCCULLOUGH, J MCINTOSH, K ROSS, RK WHITSETT, CF WITTES, J WRIGHT, TL TI INFECTIOUS-DISEASE TESTING FOR BLOOD-TRANSFUSIONS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB Objective.-To provide physicians and other transfusion medicine professionals with a current consensus on infectious disease testing for blood transfusions. Participants.-A nonfederal, nonadvocate, 12-member consensus panel representing the fields of hematology, infectious disease, transfusion medicine, epidemiology, and biostatistics and a public representative. In addition, 23 experts in hematology, cardiology, transfusion medicine, infectious disease, and epidemiology presented data to the consensus panel and a conference audience of 450. Evidence.-The literature was searched through MEDLINE and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature, Scientific evidence was given precedence over clinical anecdotal experience. Consensus.-The panel, answering predefined consensus questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. Consensus Statement.-The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. Conclusions.-The serum alanine aminotransferase test should be discontinued as a surrogate marker for blood donors likely to transmit posttransfusion non-A, non-B hepatitis infection since specific hepatitis C antibody testing has eliminated more than 85% of these cases. Antibody to hepatitis B core antigen testing should continue as it may prevent some cases of posttransfusion hepatitis B; it may also act as a surrogate marker for human immunodeficiency virus (HIV) infection in donors and may prevent a small number of cases of transfusion-transmitted HIV infection, Syphilis testing should continue until adequate data can determine its effect on the rarity of transfusion-transmitted syphilis. Vigilant public health surveillance is critical in responding to emerging infectious disease threats to the blood supply. C1 FAIRFAX HOSP,DEPT PATHOL,BLOOD BANK,FALLS CHURCH,VA. FAIRFAX HOSP,DEPT PATHOL,DONOR SERV,FALLS CHURCH,VA. OCHSNER TRANSPLANT CTR,NEW ORLEANS,LA. UNIV SO CALIF,SCH MED,DEPT MED,DIV HEMATOL,LOS ANGELES,CA 90033. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC. UNIV SO CALIF,DEPT MED,DIV GASTROINTESTINAL & LIVER DIS,LOS ANGELES,CA. UNIV MINNESOTA HOSP,DIV LAB MED,MINNEAPOLIS,MN 55455. UNIV MINNESOTA HOSP,TRANSFUS MED SECT,MINNEAPOLIS,MN 55455. HARVARD UNIV,SCH MED,BOSTON,MA. CHILDRENS HOSP,DIV INFECT DIS,BOSTON,MA. DEPT HLTH SERV,SAN DIEGO,CA. EMORY UNIV,SCH MED,DEPT PATHOL & LAB MED,ATLANTA,GA. STAT COLLABORAT INC,WASHINGTON,DC. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA. NHLBI,BONE MARROW TRANSPLANTAT BRANCH,BETHESDA,MD 20892. NHLBI,TRANSFUS MED BRANCH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,OFF BLOOD RES & REVIEW,DIV TRANSFUS TRANSMITTED DIS,HEPATITIS LAB,ROCKVILLE,MD. AMER RED CROSS,HOLLAND LAB,DEPT TRANSMISSIBLE DIS,ROCKVILLE,MD. NIH,OFF MED APPLICAT RES,BETHESDA,MD. UNIV CALIF DAVIS,MED CTR,DIV HEMATOL ONCOL,DAVIS,CA 95616. SACRAMENTO MED FDN,CTR BLOOD,SACRAMENTO,CA. NIAID,DIV MICROBIOL & INFECT DIS,ENTER DIS BRANCH,BETHESDA,MD. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. NHLBI,OFF DIRECTOR,BETHESDA,MD 20892. NHLBI,OFF PREVENT EDUC & CONTROL,COMMUN & PUBL INFORMAT BRANCH,BETHESDA,MD 20892. RP DESFORGES, JF (reprint author), TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02111, USA. NR 0 TC 32 Z9 32 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 NOV 1 PY 1995 VL 274 IS 17 BP 1374 EP 1379 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TB278 UT WOS:A1995TB27800029 ER PT J AU Ong, KC Wen, H Chesnick, AS Duewell, S Jaffer, FA Balaban, RS AF Ong, KC Wen, H Chesnick, AS Duewell, S Jaffer, FA Balaban, RS TI Radiofrequency shielding of surface coils at 4.0 T SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE radiofrequency coil; radiofrequency shield; surface coil; radiation losses; inductive losses; dielectric losses; dielectric currents AB Because radiation loss associated with a radiofrequency (RF) coil increases as roughly the fourth power of the frequency, this loss mechanism may become important in high-held studies above 2.0 T. In this study, the contribution of radiation losses at 4.0 T were determined in a rectangular surface coil using an RF shield to modify the radiation losses. The effect of this shield was determined on coil Q, B-1 distribution, and signal to noise as a function of distance between the coil and the shield, Phantoms and human tissue were evaluated to characterize the loss mechanisms. The results demonstrate a large radiation loss in the unshielded surface coil, However, the radiation losses in vivo were not dominant owing to a large inductive loss occurring from dielectric currents in the body at 170 MHz. C1 NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. RI Balaban, Robert/A-7459-2009; Wen, Han/G-3081-2010; OI Balaban, Robert/0000-0003-4086-0948; Wen, Han/0000-0001-6844-2997; Jaffer, Farouc/0000-0001-7980-384X NR 0 TC 16 Z9 16 U1 0 U2 0 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD NOV-DEC PY 1995 VL 5 IS 6 BP 773 EP 777 DI 10.1002/jmri.1880050626 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TL103 UT WOS:A1995TL10300025 PM 8748501 ER PT J AU KAAYA, EE PARRAVICINI, C ORDONEZ, C GENDELMAN, R BERTI, E GALLO, RC BIBERFELD, P AF KAAYA, EE PARRAVICINI, C ORDONEZ, C GENDELMAN, R BERTI, E GALLO, RC BIBERFELD, P TI HETEROGENEITY OF SPINDLE CELLS IN KAPOSIS-SARCOMA - COMPARISON OF CELLS IN LESIONS AND IN CULTURE SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE KAPOSIS SARCOMA; HIV INFECTION; SPORADIC; ENDEMIC; EPIDEMIC; HETEROGENEITY; REACTIVE ID FACTOR GENE-EXPRESSION; WEIBEL-PALADE BODIES; SMOOTH MUSCLE ACTIN; ENDOTHELIAL-CELL; MONOCLONAL-ANTIBODIES; BASEMENT-MEMBRANE; DNA-SEQUENCES; STROMAL CELLS; AIDS; PROTEIN AB The immunophenotype of spindle cells in epidemic, endemic, and classic (sporadic) Kaposi's sarcoma (KS) lesions was defined by the demonstration of various cell markers and compared with that of KS-derived cell lines. No significant histological or immunophenotypic differences were observed between the three clinical types of KS at comparable stages. The spindle-cell compartment of the different KS types was composed predominantly of a mixture of proliferating CD45 + /CD68 + bone-marrow-derived monocytes and TE7 + /collagen + fibroblastic cells with varying expression of EN4/PAL-E/CD31/CD34/CD36 endothelial-associated antigens and/or smooth-muscle-specific alpha-actin (alpha-actin). The latter cells appeared to represent transitional forms of fibroendothelial and fibromyocytic cells. The in vitro cultured KS-derived cell lines (KS-3, KS-6, and KS-8) expressed the fibroblastic antigen TE7 and smooth-muscle-specific alpha-actin but not leukocytic or endothelial-associated antigens consistent with the phenotype of fibromyoid spindle cells of primary lesions. Neither HIV antigen nor provirus DNA was demonstrable in the epidemic KS lesions. The observed heterogeneity of the spindle-cell compartment further substantiates the view that Kaposi's sarcoma, irrespective of clinical setting, expresses salient features more compatible with reactive, tumor-like lesion than clonal sarcoma. C1 KAROLINSKA INST,IMMUNOPATHOL LAB,STOCKHOLM,SWEDEN. SACCO HOSP,DEPT PATHOL,MILAN,ITALY. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RI Berti, Emilio/F-5256-2012 NR 61 TC 73 Z9 73 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD NOV 1 PY 1995 VL 10 IS 3 BP 295 EP 305 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TA586 UT WOS:A1995TA58600001 PM 7552491 ER PT J AU POWELL, DM ZHANG, MJ KONINGS, DAM WINGFIELD, PT STAHL, SJ DAYTON, ET DAYTON, AI AF POWELL, DM ZHANG, MJ KONINGS, DAM WINGFIELD, PT STAHL, SJ DAYTON, ET DAYTON, AI TI SEQUENCE SPECIFICITY IN THE HIGHER-ORDER INTERACTION OF THE REV PROTEIN OF HIV-1 WITH ITS TARGET SEQUENCE, THE RRE SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV-1; REV; RRE ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANS-ACTIVATOR GENE; VIRAL MESSENGER-RNA; RESPONSIVE ELEMENT; HTLV-III; EXPRESSION REQUIRES; SECONDARY STRUCTURE; VIRION EXPRESSION; BINDING-SITE; REPLICATION AB The Rev protein of human immunodeficiency virus type 1 (HIV-1) multimerizes along RNAs containing the Rev target sequence, the RRE. Although sequence-specific information is recognized in the high affinity or initial interaction, it is not known what role RNA-contained information plays in higher-order binding events. We have quantitatively studied the binding of Rev protein to the primary Rev binding domain (II + III) of wild-type and mutant RREs. RRE mutations that retain the basic secondary structure of wild type can separately and differentially alter the Kds for formation of the first, second, and third ReV/RRE complexes (C1, C2, and C3). The data suggest that Rev recognizes sequence-specific information in the RRE when it forms higher-order complexes. However, the formation of higher-order complexes is not as dependent on sequence-specific information as the first or lower order binding iteraction, which involves recognition of the high-affinity site. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. UNIV COLORADO,BOULDER,CO 80309. NIH,OFF DIRECTOR,PROT EXPRESS LAB,BETHESDA,MD 20892. NR 41 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD NOV 1 PY 1995 VL 10 IS 3 BP 317 EP 323 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TA586 UT WOS:A1995TA58600003 PM 7552493 ER PT J AU Santelli, JS Rosenfeld, WD DuRant, RH Dubler, N Morreale, M English, A Rogers, AS AF Santelli, JS Rosenfeld, WD DuRant, RH Dubler, N Morreale, M English, A Rogers, AS TI Guidelines for adolescent health research - A position paper of the Society for Adolescent Medicine SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article; Proceedings Paper CT Consensus Conference on Guidelines for Adolescent Health Research CY MAY 19-20, 1994 CL ALEXANDRIA, VA DE adolescents; health research; research protection ID SOCIALLY SENSITIVE RESEARCH; AIDS; INTERVENTION; COMMUNITY; PROGRAMS; BEHAVIOR; LEGAL AB Their ambiguous legal and ethical status has become a barrier to adolescents' appropriate involvement in research from which they may benefit and which is needed to improve adolescent health care and to inform health policy. Involvement of adolescents in research should be based on a scientific and empathetic understanding of their developing capabilities and a careful assessment of risks and benefits. The important role of parents and communities as protectors of adolescents should be respected and enhanced as we acknowledge and respect developing adolescent autonomy, These guidelines provide a framework to interpret the federal regulations for protection of human subjects in light of the unique legal, ethical, developmental, contextual, and racial issues that affect adolescents. The guidelines are designed to protect individual adolescent research subjects and to facilitate important youth research that would promote the health of adolescents. C1 MORRISTOWN MEM HOSP,ADOLESCENT SERV,MORRISTOWN,NJ. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV ADOLESCENT YOUNG ADULT MED,CAMBRIDGE,MA 02138. MONTEFIORE MED CTR,DEPT SOCIAL MED,BRONX,NY. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BALTIMORE,MD 21218. NICHHD,MATERNAL AIDS BRANCH,BETHESDA,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MATERNAL & CHILD HLTH,BALTIMORE,MD 21218. NR 50 TC 47 Z9 47 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD NOV PY 1995 VL 17 IS 5 BP 270 EP 276 DI 10.1016/1054-139X(95)00181-Q PG 7 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA TK532 UT WOS:A1995TK53200004 PM 8924431 ER PT J AU Jenkins, RR Parron, D AF Jenkins, RR Parron, D TI Guidelines for adolescent health research: Issues of race and class SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article; Proceedings Paper CT Consensus Conference on Guidelines for Adolescent Health Research CY MAY 19-20, 1994 CL ALEXANDRIA, VA ID PSYCHOLOGY; ETHNICITY C1 HOWARD UNIV,COLL MED,WASHINGTON,DC 20059. NIMH,ROCKVILLE,MD 20857. NR 43 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD NOV PY 1995 VL 17 IS 5 BP 314 EP 322 PG 9 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA TK532 UT WOS:A1995TK53200009 PM 8924436 ER PT J AU DELAGLIO, F GRZESIEK, S VUISTER, GW ZHU, G PFEIFER, J BAX, A AF DELAGLIO, F GRZESIEK, S VUISTER, GW ZHU, G PFEIFER, J BAX, A TI NMRPIPE - A MULTIDIMENSIONAL SPECTRAL PROCESSING SYSTEM BASED ON UNIX PIPES SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE MULTIDIMENSIONAL NMR; DATA PROCESSING; FOURIER TRANSFORMATION; LINEAR PREDICTION; MAXIMUM ENTROPY; UNIX ID MAXIMUM-ENTROPY METHOD; NUCLEAR MAGNETIC-RESONANCE; IMPROVED LINEAR PREDICTION; DIMENSIONAL NMR-SPECTRA; TIME-DOMAIN DATA; SENSITIVITY IMPROVEMENT; IMAGE-RECONSTRUCTION; PHASE; SPECTROSCOPY; SIGNALS AB The NMRPipe system is a UNIX software environment of processing, graphics, and analysis tools designed to meet current routine and research-oriented multidimensional processing requirements, and to anticipate and accommodate future demands and developments. The system is based on UNIX pipes, which allow programs running simultaneously to exchange streams of data under user control. In an NMRPipe processing scheme, a stream of spectral data flows through a pipeline of processing programs, each of which performs one component of the overall scheme, such as Fourier transformation or linear prediction. Complete multidimensional processing schemes are constructed as simple UNIX shell scripts. The processing modules themselves maintain and exploit accurate records of data sizes, detection modes, and calibration information in all dimensions, so that schemes can be constructed without the need to explicitly define or anticipate data sizes or storage details of real and imaginary channels during processing. The asynchronous pipeline scheme provides other substantial advantages, including high flexibility, favorable processing speeds, choice of both all-in-memory and disk-bound processing, easy adaptation to different data formats, simpler software development and maintenance, and the ability to distribute processing tasks on multi-CPU computers and computer networks. C1 UNIV UTRECHT,BIJVOET CTR BIOMOLEC RES,3584 CH UTRECHT,NETHERLANDS. HONG KONG UNIV SCI & TECHNOL,DEPT BIOCHEM,KOWLOON,HONG KONG. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP DELAGLIO, F (reprint author), NIDDK,CHEM PHYS LAB,BLDG 5 B2-31,5 CTR DR MSC 0505,BETHESDA,MD 20892, USA. NR 55 TC 8397 Z9 8433 U1 38 U2 325 PU ESCOM SCI PUBL BV PI LEIDEN PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD NOV PY 1995 VL 6 IS 3 BP 277 EP 293 DI 10.1007/BF00197809 PG 17 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA TH725 UT WOS:A1995TH72500006 PM 8520220 ER PT J AU GRZESIEK, S BAX, A AF GRZESIEK, S BAX, A TI SPIN-LOCKED MULTIPLE-QUANTUM COHERENCE FOR SIGNAL ENHANCEMENT IN HETERONUCLEAR MULTIDIMENSIONAL NMR EXPERIMENTS SO JOURNAL OF BIOMOLECULAR NMR LA English DT Note DE MULTIDIMENSIONAL NMR; LINE NARROWING; RELAXATION; MULTIPLE QUANTUM COHERENCE; ROESY; PROTEIN; CALMODULIN ID PRACTICAL ASPECTS; PROTEINS AB For methine sites the relaxation rate of C-13-H-1 two-spin coherence is generally slower than the relaxation rate of the individual C-13 and H-1 single spin coherences. The slower decay of two-spin coherence can be used to increase the sensitivity and resolution in heteronuclear experiments, particularly those that require correlation of H-alpha and C alpha chemical shifts. To avoid dephasing of the two-spin coherence caused by H-1-H-1 J-couplings, the H-1 spin is locked by the application of a weak rf field, resulting in a spin-locked multiple quantum coherence. For a sample of calcium-free calmodulin, use of the multiple quantum approach yields significant signal enhancement over the conventional constant-rime 2D HSQC experiment. The approach is applicable to many multidimensional NMR experiments, as demonstrated for a 3D C-13-separated ROESY CT-HMQC spectrum. RP GRZESIEK, S (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA. NR 19 TC 52 Z9 52 U1 1 U2 5 PU ESCOM SCI PUBL BV PI LEIDEN PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD NOV PY 1995 VL 6 IS 3 BP 335 EP 339 PG 5 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA TH725 UT WOS:A1995TH72500012 PM 8520225 ER PT J AU BRODER, S KARP, JE AF BRODER, S KARP, JE TI PROGRESS AGAINST CANCER SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE CANCER; CARCINOGENESIS ID FIBROBLAST GROWTH-FACTOR; NONPOLYPOSIS COLORECTAL-CANCER; FREQUENT ALLELIC LOSS; HUMAN PROSTATE-CANCER; BREAST-CANCER; CELL-CYCLE; LYMPHOBLASTIC-LEUKEMIA; ATAXIA-TELANGIECTASIA; EXTRACELLULAR-MATRIX; HOMOZYGOUS DELETION RP BRODER, S (reprint author), NCI,BETHESDA,MD 20892, USA. NR 133 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-5216 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD NOV PY 1995 VL 121 IS 11 BP 633 EP 647 DI 10.1007/BF01218521 PG 15 WC Oncology SC Oncology GA TE360 UT WOS:A1995TE36000003 PM 7593127 ER PT J AU MIYAMOTO, S TERAMOTO, H COSO, OA GUTKIND, JS BURBELO, PD AKIYAMA, SK YAMADA, KM AF MIYAMOTO, S TERAMOTO, H COSO, OA GUTKIND, JS BURBELO, PD AKIYAMA, SK YAMADA, KM TI INTEGRIN FUNCTION - MOLECULAR HIERARCHIES OF CYTOSKELETAL AND SIGNALING MOLECULES SO JOURNAL OF CELL BIOLOGY LA English DT Article ID FIBRONECTIN RECEPTOR; TYROSINE PHOSPHORYLATION; EXTRACELLULAR-MATRIX; FOCAL ADHESIONS; CELL-ADHESION; BINDING; TRANSDUCTION; MIGRATION AB Integrin receptors play important roles in organizing the actin-containing cytoskeleton and in signal transduction from the extracellular matrix. The initial steps in integrin function can be analyzed experimentally using beads coated with ligands or anti-integrin antibodies to trigger rapid focal transmembrane responses. A hierarchy of transmembrane actions was identified in this study. Simple integrin aggregation triggered localized transmembrane accumulation of 20 signal transduction molecules, including RhoA, Rac1, Ras, Raf, MEK, ERK, and JNK. In contrast, out of eight cytoskeletal molecules tested, only tensin coaccumulated. Integrin aggregation alone was also sufficient to induce rapid activation of the JNK pathway, with kinetics of activation different from those of ERK. The tyrosine kinase inhibitors herbimycin A or genistein blocked both the accumulation of 19 out of 20 signal transduction molecules and JNK- and ERK-mediated signaling. Cytochalasin D had identical effects, whereas three other tyrosine kinase inhibitors did not. The sole exception among signaling molecules was the kinase pp125(FAK) which continued to coaggregate with alpha(5) beta(1) integrins even in the presence of these inhibitors. Tyrosine kinase inhibition also failed to block the ability of ligand occupancy plus integrin aggregation to trigger transmembrane accumulation of the three cytoskeletal molecules talin, alpha-actinin, and vinculin; these molecules accumulated even in the presence of cytochalasin D. However, it was necessary to fulfill all four conditions, i.e., integrin aggregation, integrin occupancy, tyrosine kinase activity, and actin cytoskeletal integrity, to achieve integrin-mediated focal accumulation of other cytoskeletal molecules including F-actin and paxillin. Integrins therefore mediate a transmembrane hierarchy of molecular responses. C1 NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RP MIYAMOTO, S (reprint author), NIDR,DEV BIOL LAB,BLDG 30,ROOM 421,BETHESDA,MD 20892, USA. RI Gutkind, J. Silvio/A-1053-2009; Burbelo, Peter/B-1027-2009; OI Yamada, Kenneth/0000-0003-1512-6805 NR 45 TC 1031 Z9 1040 U1 5 U2 56 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV PY 1995 VL 131 IS 3 BP 791 EP 805 DI 10.1083/jcb.131.3.791 PG 15 WC Cell Biology SC Cell Biology GA TC101 UT WOS:A1995TC10100019 PM 7593197 ER PT J AU DELLAMBRA, E PATRONE, M SPARATORE, B NEGRI, A CECILIANI, F BONDANZA, S MOLINA, F CANCEDDA, FD DELUCA, M AF DELLAMBRA, E PATRONE, M SPARATORE, B NEGRI, A CECILIANI, F BONDANZA, S MOLINA, F CANCEDDA, FD DELUCA, M TI STRATIFIN, A KERATINOCYTE SPECIFIC 14-3-3-PROTEIN, HARBORS A PLECKSTRIN HOMOLOGY (PH) DOMAIN AND ENHANCES PROTEIN-KINASE-C ACTIVITY SO JOURNAL OF CELL SCIENCE LA English DT Article DE KERATINOCYTE; PROTEIN KINASE C; PH DOMAIN; 14-3-3 PROTEIN; SIGNAL TRANSDUCTION; EPIDERMIS; MELANOCYTE ID PERFORMANCE LIQUID-CHROMATOGRAPHY; HUMAN EPIDERMAL-KERATINOCYTES; CALCIUM-DEPENDENT EXOCYTOSIS; ADRENAL CHROMAFFIN CELLS; SIGNALING PROTEINS; MOLECULAR-CLONING; EPITHELIAL-CELLS; GROWTH-FACTOR; DIFFERENTIATION; EXPRESSION AB The intrinsic signal(s) responsible for the onset of human keratinocyte terminal differentiation is not yet fully understood. Evidence has been recently accumulated linking the phospholipase-mediated activation of protein kinase C to the coordinate changes in gene expression occurring during keratinocyte terminal differentiation. Here we report the purification of a keratinocyte-derived protein enhancing protein kinase C enzymatic activity. The stimulator eluted as a peak with estimated molecular mass of approximately 70 kDa, while analysis by SDS-PAGE showed a 30 kDa protein migrating as a distinct doublet, suggesting the formation of a 30 kDa homodimer. The amino acid sequence analysis allowed the unambigous identification of the protein kinase C stimulator as a mixture of the highly homologous sigma (stratifin) and zeta isoforms of 14-3-3 proteins, which are homodimers of identical 30 kDa subunits. Mono Q anion exchange chromatography and immunoblot analysis further confirmed that stratifin enhances protein kinase C activity. Stratifin was originally sequenced from a human keratinocyte protein database, but its function was unknown. The pleckstrin homology domain has been recently related to protein translocation to the cell membrane as well as to functional interactions of intracellular proteins involved in signal transduction. We show here that stratifin (and 14-3-3 zeta) harbors a pleckstrin homology domain, and the consequent functional implications will be discussed. C1 NATL CANC INST,CTR ADV BIOTECHNOL,I-16132 GENOA,ITALY. UNIV GENOA,INST BIOL CHEM,GENOA,ITALY. UNIV MILAN,INST VET PHYSIOL & BIOCHEM,MILAN,ITALY. INT INST GENET & BIOPHYS,I-80125 NAPLES,ITALY. RI Dellambra, Elena/A-4005-2014; De Luca, Michele/N-5883-2014; OI Dellambra, Elena/0000-0002-4329-3312; De Luca, Michele/0000-0002-0850-8445; PATRONE, Mauro/0000-0002-7740-2396 FU Telethon [A.008] NR 81 TC 57 Z9 58 U1 1 U2 2 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 NOV PY 1995 VL 108 BP 3569 EP 3579 PN 11 PG 11 WC Cell Biology SC Cell Biology GA TD619 UT WOS:A1995TD61900022 PM 8586668 ER PT J AU KATZ, J WEISS, H GOLDMAN, B KANETY, H STANNARD, B LEROITH, D SHEMER, J AF KATZ, J WEISS, H GOLDMAN, B KANETY, H STANNARD, B LEROITH, D SHEMER, J TI CYTOKINES AND GROWTH-FACTORS MODULATE CELL-GROWTH AND INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEIN SECRETION BY THE HUMAN SALIVARY CELL-LINE (HSG) SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HUMAN-BREAST-CANCER; I IGF-I; RETINOIC ACID; GENE-EXPRESSION; GLAND AB The human salivary cell line (HSG) was investigated for the effect of various growth factors and cytokines on cellular proliferation and on the production of insulin-like growth factor binding proteins (ICFBPs). IGF-l increased cell growth by approximately 25%, and induced the appearances of three distinct protein bands on ligand blot of the cell culture. Two bands with molecular weights of 43 and 45 Kda, respectively, proved to be ICFBP-3 using a specific antibody, and the third was a 24 Kda species (probably, IGFBP-4). Similar IGFBPs were released by the cells following stimulation by EGF and insulin as well as following incubation with the IGF-I receptor antibody alpha IR3. Retinoic acid had an inhibitory effect (50%) on IGF-I-induced cellular proliferation and an attenuative effect on the 24 Kda band when it was combined with IGF-I, and to a lesser effect EGF; however, it enhanced ICFBP-3 production when incubated with IGF-I. The IGF-I receptor antibody had an agonistic effect on ICFBPs production when applied alone or together with IGF-I. TN F-alpha and INF-gamma had minimal effects on cell growth when added alone but when applied in combination, a marked inhibition of cellular proliferation was noted. These cytokines caused increased accumulation of IGFBP-3, -4, and -5. Addition of IGF-I to these cytokines enhanced the expression of these bands. These data demonstrate that growth factors and cytokines which modulate HSG cell growth, induce specific ICFBPs which may play a role in their effects on cell growth. (C) 1995 Wiley-Liss, Inc. C1 NIDDK,DIABET BRANCH,BETHESDA,MD 20892. HELLER INST MED RES,TEL AVIV,ISRAEL. CHAIM SHEBA MED CTR,INST ENDOCRINOL,TEL AVIV,ISRAEL. TEL AVIV UNIV,SACKLER SCH MED,IL-69978 TEL AVIV,ISRAEL. NR 13 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 1995 VL 165 IS 2 BP 223 EP 227 DI 10.1002/jcp.1041650202 PG 5 WC Cell Biology; Physiology SC Cell Biology; Physiology GA TB806 UT WOS:A1995TB80600001 PM 7593199 ER PT J AU SHIMAOKA, S TSUBOI, R JINDO, T IMAI, R TAKAMORI, K RUBIN, JS OGAWA, H AF SHIMAOKA, S TSUBOI, R JINDO, T IMAI, R TAKAMORI, K RUBIN, JS OGAWA, H TI HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR EXPRESSED IN FOLLICULAR PAPILLA CELLS STIMULATES HUMAN HAIR-GROWTH IN-VITRO SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HUMAN SKIN FIBROBLASTS; EPITHELIAL-CELLS; INVITRO; CULTURE; FOLLICLES; ALPHA; KERATINOCYTES; SECRETION; INDUCTION; MOTILITY AB Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional polypeptide which acts as mitogen, motogen, or morphogen. In this study, we examined the effect of HGF/SF on human hair growth using organ and cell culture systems. HGF/SF was found to stimulate hair length and DNA synthesis in hair follicles at increasing concentrations up to 10 ng/ml (P < 0.05 and P < 0.01, respectively). HGF/SF stimulated [H-3]thymidine incorporation by hair bulb-derived keratinocytes with the strongest response at 30 ng/ml of HGF/SF (P < 0.05). Cultured follicular papilla cells secreted HGF/SF, measured by an enzyme-linked immuno-assay, in response to interleukin 1-alpha(IL1-alpha, 10 ng/ml), tumor necrosis factor-alpha (TNF-alpha, 10 ng/ml), or tetradecanoylphorbolacetate (100 nM) at levels ranging from 0.2 to 0.3 ng/mg protein/48 h. HGF/SF mRNA expressions, measured by the reverse transcription-polymerase chain reaction, were detected in follicular papilla cells, and were also stimulated by the three reagents. Transforming growth factor-beta(10 ng/ml) suppressed both protein and mRNA levels. These results suggest that hair follicle elongation induced by HGF/SF in organ culture occurs partly due to the mitogenic activity of HGF/SF expressed in follicular papilla cells on hair bulb-derived keratinocytes. (C) 1995 Wiley-Liss, Inc. C1 JUNTENDO UNIV,SCH MED,DEPT DERMATOL,BUNKYO KU,TOKYO 113,JAPAN. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 45 TC 45 Z9 47 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 1995 VL 165 IS 2 BP 333 EP 338 DI 10.1002/jcp.1041650214 PG 6 WC Cell Biology; Physiology SC Cell Biology; Physiology GA TB806 UT WOS:A1995TB80600013 PM 7593211 ER PT J AU KIMONIS, VE TROENDLE, J ROSE, SR YANG, ML MARKELLO, TC GAHL, WA AF KIMONIS, VE TROENDLE, J ROSE, SR YANG, ML MARKELLO, TC GAHL, WA TI EFFECTS OF EARLY CYSTEAMINE THERAPY ON THYROID-FUNCTION AND GROWTH IN NEPHROPATHIC CYSTINOSIS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DEPLETION; PHOSPHOCYSTEAMINE; INSUFFICIENCY; TRANSPORT; FRACTIONS; CHILDREN; PATIENT AB Primary hypothyroidism is a known complication of nephropathic cystinosis, a lysosomal storage disorder characterized by renal failure as well as deterioration of other organs. The drug cysteamine depletes lysosomes of cystine and helps preserve renal function and enhance growth in cystinosis patients. To determine whether cysteamine also prevents hypothyroidism, we retrospectively divided 101 patients into group A (n = 28; well treated), group B (n = 26; partially treated), and group C (n = 47; poorly treated). Lifetable analysis indicated a significantly higher probability of remaining free of L-T-4 replacement in group A vs. group B (P = 0.09) or group C (P = 0.004). Cysteamine therapy also improved mean height z-scores (-2.17 in group A, -3.04 in group B, and -4.07 in group C) and reduced the bone age deficit (i.e. chronological age minus bone age) by 1.5 yr for every 10 yr of previous cysteamine therapy. We conclude that in addition to its other salutary effects, oral cysteamine therapy helps prevent hypothyroidism and enhances growth in patients with nephropathic cystinosis. C1 NICHHD, HUMAN GENET BRANCH, HUMAN BIOCHEM GENET SECT, BETHESDA, MD 20892 USA. NICHHD, DIV EPIDEMIOL STAT & PREVENT RES, BIOMETRY & MATH STAT BRANCH, BETHESDA, MD 20892 USA. NIAMSD, BETHESDA, MD 20892 USA. UNIV TENNESSEE, DEPT PEDIAT, MEMPHIS, TN 38103 USA. VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, DEPT PEDIAT, RICHMOND, VA 23298 USA. NR 31 TC 69 Z9 72 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1995 VL 80 IS 11 BP 3257 EP 3261 DI 10.1210/jc.80.11.3257 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TD909 UT WOS:A1995TD90900028 PM 7593434 ER PT J AU GOULET, M DULAR, R TULLY, JG BILLOWES, G KASATIYA, S AF GOULET, M DULAR, R TULLY, JG BILLOWES, G KASATIYA, S TI ISOLATION OF MYCOPLASMA-PNEUMONIAE FROM THE HUMAN UROGENITAL TRACT SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SEROLOGICAL CROSS-REACTIONS; GENITALIUM AB Mycoplasma pneumoniae is. a common etiologic agent of lower respiratory tract infections in humans. However, it has been reported previously that the organism has occasionally been isolated from sites other than the oropharynx and respiratory tract. We report the isolation of 24 strains of M. pneumoniae from urogenital specimens obtained from 22 female patients. Most isolates were of cervical origin from patients attending several local gynecological clinics over a 2-year period. Strains were also isolated from the urethra of one of three healthy male sexual partners of female patients positive for the organism. Single serum specimens obtained from three female patients and three different male sexual partners showed antibody levels suggestive bf either recent respiratory infection or genital tract colonization with M. pneumoniae. Although there is nd apparent definitive explanation for the localized outbreak of the organism at these unusual sites, the possible transfer through sexual and/or orogenital contact remains the most likely mode of transmission. The occurrence of an organism with obvious pathogenicity for human epithelial tissue in the urogenital tract Suggests such transfer could play a role in genital tract infection. C1 OTTAWA PUBL HLTH LAB,OTTAWA,ON K1G 54A,CANADA. MONFORT HOSP,OTTAWA,ON,CANADA. UNIV OTTAWA,FAC MED,DEPT MICROBIOL & IMMUNOL,OTTAWA,ON K1H 8M5,CANADA. NIAID,FREDERICK CANC RES & DEV CTR,MYCOPLASMA SECT,FREDERICK,MD. NR 21 TC 33 Z9 38 U1 0 U2 1 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 NOV PY 1995 VL 33 IS 11 BP 2823 EP 2825 PG 3 WC Microbiology SC Microbiology GA TA461 UT WOS:A1995TA46100004 PM 8576326 ER PT J AU HOFFMAN, WH PLUTA, RM FISHER, AQ WAGNER, MB YANOVSKI, JA AF HOFFMAN, WH PLUTA, RM FISHER, AQ WAGNER, MB YANOVSKI, JA TI TRANSCRANIAL DOPPLER ULTRASOUND ASSESSMENT OF INTRACRANIAL HEMODYNAMICS IN CHILDREN WITH DIABETIC-KETOACIDOSIS SO JOURNAL OF CLINICAL ULTRASOUND LA English DT Article DE TRANSCRANIAL DOPPLER; DIABETIC KETOACIDOSIS,; INSULIN-DEPENDENT DIABETES MELLITUS; DOPPLER ULTRASONOGRAPHY ID CEREBRAL BLOOD-FLOW; BRAIN; ARTERY; EDEMA; VELOCITY; MELLITUS; HYPERGLYCEMIA; PRESSURE; ISCHEMIA; DAMAGE AB The pathophysiology of acute neurological complications of diabetic ketoacidosis (DKA) in children and adolescents is not completely understood. We sought to establish whether transcranial Doppler (TCD) was able to monitor the changes of cerebral blood flow regulatory mechanisms, as measured by cerebral blood velocities (CBF-V), Gosling's pulsatility index (PI), and cerebral vascular reactivity (VR), prior to and during treatment of DKA. The increased values of PI suggested an increase of intracranial pressure (ICP) due to the existence of cerebral vasoparalysis, based on the low values of VR prior to treatment and 6 hours after initiation of treatment. At 24 hours, the correction of hematocrit and pH was associated with a significant decrease of PI, suggesting a decrease of ICP, likely due to a return of vascular tone in response to the low PaCO2. This was further supported by an increase of VR in all patients. At 48 hours, when PaCO2 returned to normal, the PI remained low and the VR increased further, suggesting a complete reversal of vasoparalysis and a return of cerebral blood flow regulatory mechanisms. (C) 1995 John Wiley & Sons, Inc. C1 NIH,SURG NEUROL BRANCH,BETHESDA,MD 20892. MED COLL GEORGIA,DEPT NEUROL,AUGUSTA,GA 30912. MED COLL GEORGIA,DEPT SURG,EMERGENCY SERV,AUGUSTA,GA 30912. NIH,DEV ENDOCRINOL BRANCH,BETHESDA,MD. RP HOFFMAN, WH (reprint author), MED COLL GEORGIA,DEPT PEDIAT,CK-151,AUGUSTA,GA 30912, USA. NR 37 TC 31 Z9 31 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0091-2751 J9 J CLIN ULTRASOUND JI J. Clin. Ultrasound PD NOV-DEC PY 1995 VL 23 IS 9 BP 517 EP 523 DI 10.1002/jcu.1870230903 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA TA444 UT WOS:A1995TA44400002 PM 8537473 ER PT J AU Lee, SK Chi, JG Jeon, YJ Park, SC Mori, M Chung, SI AF Lee, SK Chi, JG Jeon, YJ Park, SC Mori, M Chung, SI TI Expression of transglutaminase C during the prenatal development of human submandibular glands SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE prenatal development; salivary gland; transglutaminase ID MAJOR SALIVARY-GLANDS; RAT PAROTID-GLAND; TISSUE TRANSGLUTAMINASE; CELLULAR TRANSGLUTAMINASE; LIVER TRANSGLUTAMINASE; MORPHOGENESIS; FIBRINOGEN; PROTEINS; CELLS; DEATH AB The involvement of transglutaminase C (TGase C) in morphogenesis and cytodifferentiation during glandular tubule formation was addressed by immunolocalization of the protein at different stages of prenatal human submandibular gland development in 100 fetuses and 20 adult salivary glands. Immunocytochemical detection was carried out using a monospecific antibody to TGase C. The results showed TGase C reactivity in both acini and ducts early in development (from 10 to 14 weeks), followed by a marked increase in ductal activity and a decline in acinar activity up to 32 weeks. During the peak of reactivity at 25 to 32 weeks, staining was concentrated in the apical ends of the columnar cells. In the adult, staining was weakly and diffusely distributed in the striated and excretory ducts. Western blot analysis of the cellular extracts of pooled samples from various stages of salivary gland development showed a single strong band at 76 kDa early in development. This band became weaker after 32 weeks of prenatal development and in the adult. These findings of transient high expression of TGase C, which coincide with the development of tubulo-alveolar structure, suggest that TGase C may play a role in morphogenesis in human salivary gland development. C1 SEOUL NATL UNIV,COLL MED,DEPT BIOCHEM,SEOUL 151,SOUTH KOREA. ASAHI UNIV,SCH DENT,DEPT ORAL & MAXILLOFACIAL SURG,GIFU,JAPAN. NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. SEOUL NATL UNIV,DEPT PATHOL,SEOUL 151,SOUTH KOREA. RI Chi, Je Geun/G-4989-2011; OI Chi, Je-Geun/0000-0002-9950-2072 NR 39 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 1995 VL 74 IS 11 BP 1812 EP 1816 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TP412 UT WOS:A1995TP41200015 PM 8530745 ER PT J AU JINDO, T TSUBOI, R IMAI, R TAKAMORI, K RUBIN, JS OGAWA, H AF JINDO, T TSUBOI, R IMAI, R TAKAMORI, K RUBIN, JS OGAWA, H TI THE EFFECT OF HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR ON HUMAN HAIR FOLLICLE GROWTH SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Note DE HEPATOCYTE GROWTH FACTOR; CYTOKINE; ORGAN CULTURE; HUMAN HAIR GROWTH ID ORGAN-CULTURE; MITOGEN AB The effect of hepatocyte growth factor/scatter factor (HGF/SF) on human hair follicle growth was examined using: a serum-free organ culture system. The DNA synthesis in human hair follicles and elongation of the hair shaft were measured subsequent to the follicle isolation and culture at 31 degrees C in 95%, O-2-5%, CO2 for 72 h. Results showed that HGF/SF significantly increased H-3-thymidine (P < 0.001) incorporation and hair follicle length (P < 0.05). The effect of HGF/SF was dose-dependent with a maximal stimulation at 10 ng/ml. C1 JUNTENDO UNIV,SCH MED,DEPT DERMATOL,BUNKYO KU,TOKYO 113,JAPAN. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 19 TC 32 Z9 34 U1 0 U2 4 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD NOV PY 1995 VL 10 IS 3 BP 229 EP 232 DI 10.1016/0923-1811(95)00429-V PG 4 WC Dermatology SC Dermatology GA TK244 UT WOS:A1995TK24400008 PM 8593266 ER PT J AU MONTEIROLEAL, LH FARINA, M BENCHIMOL, M KACHAR, B DESOUZA, W AF MONTEIROLEAL, LH FARINA, M BENCHIMOL, M KACHAR, B DESOUZA, W TI COORDINATED FLAGELLAR AND CILIARY BEATING IN THE PROTOZOAN TRITRICHOMONAS-FETUS SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE FLAGELLATE; VIDEO MICROSCOPY ID MICROTUBULE BUNDLE; AXOSTYLE; SACCINOBACULUS; MOTILITY AB Tritrichomonas foetus is a flagellated protozoon found in urogenital tract of cattle. Its free movement in liquid medium is powered by the coordinated movement of three flagella projecting towards the anterior region of the cell, and one recurrent flagellum that forms a junction with the cell body and ends as a free projection in the posterior region of the cell. We have used video microscopy and digital image processing to analyze the relationships between the movements of these flagella. The anterior flagella beat in a ciliary type pattern displaying effective and recovery strokes, while the recurrent flagellum beats in a typical flagellar wave form. One of the three anterior flagella has a distinctive pattern of beating. It beats straight in its forward direction as opposed to the ample beats performed by the others. Frequency measurements obtained from cells swimming in a viscous medium shows that the beating frequency of the recurrent flagellum is approximate twice the frequency for the three anterior flagella. We also observed that the costa and the axostyle do not show any active motion. On the contrary, they form a cytoskeletal base for the anchoring and orientation of the flagella. C1 UNIV FED RIO DE JANEIRO,INST BIOFIS CARLOS CHAGAS FILHO,LAB ULTRAESTRUTURA CELULAR HERTHA MEYER,BR-21949900 RIO JANEIRO,BRAZIL. UNIV ESTADUAL NORTE FLUMINENSE,CTR BOICIENCIAS & BIOTECNOL,BIOL CELULAR & TECIDUAL LAB,BR-28015620 S JOSE CAMPOS,RJ,BRAZIL. NATL INST DEAFNESS & OTHER COMMUN DISORDERS,CELLULAR BIOL LAB,BETHESDA,MD 20892. RI Farina, Marcos/I-3744-2014 NR 25 TC 15 Z9 15 U1 0 U2 1 PU SOC PROTOZOOLOGISTS PI POTOMAC PA 12263 GREENLEAF AVE, POTOMAC, MD 20854 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD NOV-DEC PY 1995 VL 42 IS 6 BP 709 EP 714 DI 10.1111/j.1550-7408.1995.tb01621.x PG 6 WC Microbiology SC Microbiology GA TF125 UT WOS:A1995TF12500011 PM 8520587 ER PT J AU DIAMOND, LS AF DIAMOND, LS TI IN-MEMORIAM - WALLACE,FRANKLIN,GERHARD (1909-1995) SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Item About an Individual RP DIAMOND, LS (reprint author), NIH,PARASIT DIS LAB,BLDG 4,RM 126,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI POTOMAC PA 12263 GREENLEAF AVE, POTOMAC, MD 20854 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD NOV-DEC PY 1995 VL 42 IS 6 BP 753 EP 754 PG 2 WC Microbiology SC Microbiology GA TF125 UT WOS:A1995TF12500018 ER PT J AU JONES, K RIVERA, C SGADARI, C FRANKLIN, J MAX, EE BHATIA, K TOSATO, G AF JONES, K RIVERA, C SGADARI, C FRANKLIN, J MAX, EE BHATIA, K TOSATO, G TI INFECTION OF HUMAN ENDOTHELIAL-CELLS WITH EPSTEIN-BARR-VIRUS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LATENT GENE-EXPRESSION; LYMPHOPROLIFERATIVE DISORDERS; HODGKINS-DISEASE; LYMPHOCYTES-B; GROWTH-FACTOR; T-CELLS; INTERLEUKIN-6; EPITOPE; INTERFERON; BLOOD AB Interleukin-6 (IL-6) promotes growth and tumorigenicity of Epstein-Barr virus (EBV)-immortalized B cells, and is abnormally elevated in the serum of solid organ transplant recipients who develop EBV-positive posttransplant lymphoproliferative disease (PTLD), but not in control transplant recipients. Endothelial cells derived from PTLD lesions were found to secrete spontaneously high levels of IL-6 in vitro for up to 4 mo. We examined possible mechanisms for sustained IL-6 production by endothelial cells. Here, we show that EBV can infect endothelial cells in vitro. After 3-4 wk incubation with lethally irradiated EBV-positive, but not EBV-negative cell lines, a proportion of human umbilical cord-derived endothelial cells (HUVECs) expressed in situ the EBV-encoded small RNAs (EBER). Southern blot analysis after polymerase chain reaction showed EBV DNA in HUVEC that had been incubated with lethally irradiated EBV-positive cells, but not in the controls. Exposure of HUVECs to lethally irradiated EBV-positive but not EBV-negative cell lines induced IL-6 production that was sustained for up to 120 d of culture. These studies identify endothelial cells as targets for EBV infection and raise the possibility that this infection may be important in the life cycle and pathology of EBV. C1 NCI,PEDIAT ONCOL BRANCH,BETHESDA,MD 20892. RP JONES, K (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BLDG 29A,ROOM 2D06,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 40 TC 50 Z9 50 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1995 VL 182 IS 5 BP 1213 EP 1221 DI 10.1084/jem.182.5.1213 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TB894 UT WOS:A1995TB89400004 PM 7595192 ER PT J AU NEURATH, MF FUSS, I KELSALL, BL STUBER, E STROBER, W AF NEURATH, MF FUSS, I KELSALL, BL STUBER, E STROBER, W TI ANTIBODIES TO INTERLEUKIN-12 ABROGATE ESTABLISHED EXPERIMENTAL COLITIS IN MICE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; RECEPTOR MUTANT MICE; IMMUNE INTERFERON; T-CELLS; EXPRESSION; CYTOKINE; MODEL; RATS AB In this study, we describe a novel murine model of chronic intestinal inflammation induced by the hapten reagent 2,4,6-trinitrobenzene sulfonic acid (TNBS). Rectal application of low doses of TNBS in BALB/c and SJL/J mice resulted in a chronic transmural colitis with severe diarrhea, weight loss, and rectal prolapse, an illness that mimics some characteristics of Crohn's disease in humans. The colon of TNBS-treated mice on day 7 was marked by infiltration of CD4(+) T cells; furthermore, in situ polymerase chain reaction studies revealed high levels of interferon (IFN)-gamma mRNA in diseased colons. Isolated lamina propria (LP) CD4(+) T cells from TNBS-treated mice stimulated with anti-CD3 and anti-CD28 antibodies exhibited a Th1 pattern of cytokine secretion: a 20-50-fold increase in IL-2 and IFN-gamma levels and a 5-fold decrease in IL-4 levels as compared with those of stimulated LP CD4(+) T cells from control BALB/c mice. Administration of monoclonal anti-IL-12 antibodies to the TNBS-treated mice both early (at 5 d) and late (at 20 d) after induction of colitis led to a striking improvement in both the clinical and histopathological aspects of the disease and frequently abrogated the established colitis completely. Furthermore, LP CD4(+) T cells isolated from anti-IL-12-treated mice failed to secrete IFN-gamma upon in vitro stimulation. In summary, the data demonstrate the pivotal role of IL-12 and IFN-gamma in a TNBS-induced murine model of chronic intestinal inflammation. Furthermore, they suggest the potential utility of anti-IL-12 antibodies in patients with Crohn's disease. C1 NIAID,MUCOSAL IMMUN SECT,LCI,BETHESDA,MD 20892. NR 30 TC 956 Z9 985 U1 1 U2 12 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1995 VL 182 IS 5 BP 1281 EP 1290 DI 10.1084/jem.182.5.1281 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TB894 UT WOS:A1995TB89400011 PM 7595199 ER PT J AU LIAO, F RABIN, RL YANNELLI, JR KONIARIS, LG VANGURI, P FARBER, JM AF LIAO, F RABIN, RL YANNELLI, JR KONIARIS, LG VANGURI, P FARBER, JM TI HUMAN MIG CHEMOKINE - BIOCHEMICAL AND FUNCTIONAL-CHARACTERIZATION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CD3/T-CELL RECEPTOR COMPLEX; PLATELET FACTOR-IV; T-LYMPHOCYTES; BETA-THROMBOGLOBULIN; IMMATURE THYMOCYTES; SECONDARY STRUCTURE; FREE CALCIUM; INTERLEUKIN-8; PROTEINS; CELLS AB Mig is a chemokine of the CXC subfamily that was discovered by differential screening of a cDNA library prepared from lymphokine-activated macrophages. The mig gene is inducible in macrophages and in other cells in response to interferon (IFN)-gamma. We have transfected Chinese hamster ovary (CHO) cells with cDNA encoding human Mig and we have derived CHO cell lines from which we have purified recombinant human Mig (rHuMig). rHuMig induced the transient elevation of [Ca2+](i) in human tumor-infiltrating T lymphocytes (TIL) and in cultured, activated human peripheral blood-derived lymphocytes. No responses were seen in human neutrophils, monocytes, or Epstein-Barr virus-transformed B lymphoblastoid cell lines. rHuMig was chemotactic for TIL by a modified Boyden chamber assay but rHuMig was not chemotactic for neutrophils or monocytes. The CHO cell lines, IFN-gamma-treated human peripheral-blood monocytes, and IFN-gamma-treated cells of the human monocytic cell Line THP-1 all secreted multiple and identical HuMig species as revealed by SDS-PAGE. Using the CHO-derived rHuMig, we have shown that the species' heterogeneity is due to proteolytic cleavage at basic carboxy-terminal residues, and that the proteolysis occurs before and not after rHuMig secretion by the CHO cells. The major species of secreted rHuMig ranged from 78 to 103 amino acids in length, the latter corresponding to the full-length secreted protein predicted from the HuMig cDNA. Carboxy-terminal-truncated forms of rHuMig were of lower specific activity compared to full-length rHuMig in the calcium flux assay, and the truncated species did not block the activity of the full-length species. It is likely that HuMig plays a role in T cell trafficking and perhaps in other aspects of the physiology of activated T cells. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. FU NCI NIH HHS [CA-48059, CA-52001] NR 69 TC 291 Z9 296 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1995 VL 182 IS 5 BP 1301 EP 1314 DI 10.1084/jem.182.5.1301 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TB894 UT WOS:A1995TB89400013 PM 7595201 ER PT J AU MARCHESE, C CHEDID, M DIRSCH, OR CSAKY, KG SANTANELLI, F LATINI, C LAROCHELLE, WJ TORRISI, MR AARONSON, SA AF MARCHESE, C CHEDID, M DIRSCH, OR CSAKY, KG SANTANELLI, F LATINI, C LAROCHELLE, WJ TORRISI, MR AARONSON, SA TI MODULATION OF KERATINOCYTE GROWTH-FACTOR AND ITS RECEPTOR IN REEPITHELIALIZING HUMAN SKIN SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CELL-PROLIFERATION; EXPRESSION; DIFFERENTIATION; GENE; KGF; FAMILY; SINGLE AB We investigated the expression and distribution of keratinocyte growth factor (FGF) (FGF-7) and its receptor (KGFR) during reepithelialization of human skin. KGF mRNA levels increased rapidly by 8-10-fold and remained elevated for several days. In contrast, KGFR transcript levels decreased early but were significantly elevated by 8-9 d. A KGF-immunoglobulin G fusion protein (KGF-HFc), which specifically and sensitively detects the KGFR, localized the receptor to differentiating keratinocytes of control epidermis, but revealed a striking decrease in receptor protein expression during the intermediate period of reepithelization. Suramin, which blocked KGF binding and stripped already bound KGF from its receptor, failed to unmask KGFRs in tissue sections from the intermediate phase of wound repair. The absence of KGFR protein despite increased KGFR transcript levels implies functional receptor downregulation in the presence of increased KGF. This temporal modulation of KGF and KGFRs provides strong evidence for the functional involvement of KGF in human skin reepithelialization. C1 MT SINAI SCH MED,DERALD H RUTTENBERG CANC CTR,NEW YORK,NY 10029. UNIV ROMA LA SAPIENZA,NATL INST CANC RES,BIOTECHNOL SECT,I-00161 ROME,ITALY. NEI,IMMUNOL LAB,BETHESDA,MD 20892. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV ROMA LA SAPIENZA,DEPT PLAST SURG & RECONSTRUCT,I-00161 ROME,ITALY. UNIV ROMA LA SAPIENZA,DEPT EXPTL MED & PATHOL,I-00161 ROME,ITALY. NR 29 TC 135 Z9 138 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1995 VL 182 IS 5 BP 1369 EP 1376 DI 10.1084/jem.182.5.1369 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TB894 UT WOS:A1995TB89400019 PM 7595207 ER PT J AU WIZEL, B HOUGHTEN, RA PARKER, KC COLIGAN, JE CHURCH, P GORDON, DM BALLOU, WR HOFFMAN, SL AF WIZEL, B HOUGHTEN, RA PARKER, KC COLIGAN, JE CHURCH, P GORDON, DM BALLOU, WR HOFFMAN, SL TI IRRADIATED SPOROZOITE VACCINE INDUCES HLA-B8-RESTRICTED CYTOTOXIC T-LYMPHOCYTE RESPONSES AGAINST 2 OVERLAPPING EPITOPES OF THE PLASMODIUM-FALCIPARUM SPOROZOITE SURFACE PROTEIN-2 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MALARIA PARASITE; CIRCUMSPOROZOITE PROTEIN; PEPTIDE BINDING; CELL EPITOPES; ANCHOR RESIDUES; SPECIFICITY; MOLECULES; SEQUENCE; ANTIGEN AB Vaccines designed to protect against malaria by inducing CD8(+) cytotoxic T lymphocytes (CTL) in individuals of diverse HLA backgrounds must contain multiple conserved epitopes from various preerythrocytic-stage antigens. Plasmodium falciparum sporozoite surface protein 2 (PfSSP2) is considered an important antigen for inclusion in such vaccines, because CD8(+) CTL against the P. yoelii SSP2 protect mice against malaria by eliminating infected hepatocytes. To develop PfSSP2 as a component of malaria vaccines, we investigated the presence of anti-PfSSP2 CTL in two HLA-B8(+) volunteers immunized with irradiated P. falciparum sporozoites and characterized their CTL responses using PfSSP2-derived 15-amino acid peptides bearing the HLA-B8-binding motif. Peripheral blood mononuclear cells from both volunteers stimulated with recombinant vaccinia expressing PfSSP2 displayed antigen-specific, genetically restricted, CD8(+) T cell-dependent CTL activity against autologous target cells expressing PfSSP2. Of the five HLA-B8 motif-bearing 15-mers identified in the PfSSP2 sequence, two peptides sharing a 10-amino acid overlap sensitized HLA-B8-matched target cells from both volunteers for lysis by peptide-stimulated effector;. The CTL activity was HLA-B8 restricted and dependent on CD8(+) T cells. Analysis of the three shorter peptides representing HLA-B8 motif-bearing sequences within the two positive peptides for their ability to bind to HLA-B8 in vitro, and to sensitize target cells for lysis by effecters stimulated with the 15-mers, identified two overlapping HLA-B8-restricted CTL epitopes. Available data indicate that the sequence of one CTL epitope is conserved and the other is variant among P. falciparum isolates. Circulating activated CTL against the conserved epitope could be directly identified in one of the two volunteers. The identification of two HLA-B8-restricted CTL epitopes on PfSSP2 provides data critical to developing an epitope-based anti-liver stage malaria vaccine. C1 USN,MED RES INST,MALARIA PROGRAM,BETHESDA,MD 20889. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MOLEC MICROBIOL & IMMUNOL,BALTIMORE,MD 21205. TORREY PINES INST MOLEC STUDIES,SAN DIEGO,CA 92121. HOUGHTEN PHARMACEUT INC,SAN DIEGO,CA 92121. NIAID,MOLEC STRUCT LAB,ROCKVILLE,MD 20852. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT IMMUNOL,WASHINGTON,DC 20307. OI Parker, Kenneth/0000-0002-6282-2478 NR 64 TC 66 Z9 66 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1995 VL 182 IS 5 BP 1435 EP 1445 DI 10.1084/jem.182.5.1435 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TB894 UT WOS:A1995TB89400026 PM 7595214 ER PT J AU PACELLI, R WINK, DA COOK, JA KRISHNA, MC DEGRAFF, W FRIEDMAN, N TSOKOS, M SAMUNI, A MITCHELL, JB AF PACELLI, R WINK, DA COOK, JA KRISHNA, MC DEGRAFF, W FRIEDMAN, N TSOKOS, M SAMUNI, A MITCHELL, JB TI NITRIC-OXIDE POTENTIATES HYDROGEN PEROXIDE-INDUCED KILLING OF ESCHERICHIA-COLI SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID GEL-ELECTROPHORESIS; DNA DAMAGE; MACROPHAGES; SUPEROXIDE; PEROXYNITRITE; CYTOTOXICITY; SYNTHASE; BACTERIA; CLONING; INVITRO AB Previously, we reported that nitric oxide (NO) provides significant protection to mammalian cells from the cytotoxic effects of hydrogen peroxide (H2O2). Murine neutrophils and activated macrophages, however, produce NO, H2O2, and other reactive oxygen species to kill microorganisms, which suggests a paradox. In this study, we treated bacteria (Escherichia coli) with NO and H2O2 for 30 min and found that exposure to NO resulted in minimal toxicity, but greatly potentiated (up to 1,000-fold) H2O2-mediated killing, as evaluated by a clonogenic assay. The combination of NO/H2O2 induced DNA double strand breaks in the bacterial genome, as shown by field-inverted gel electrophoresis, and this increased DNA damage may correlate with cell killing. NO was also shown to alter cellular respiration and decrease the concentration of the antioxidant glutathione to a residual level of 15-20% in bacterial cells. The iron chelator desferrioxamine did not stop the action of NO on respiration and glutathione decrease, yet it prevented the NO/H2O2 synergistic cytotoxicity, implicating metal ions as critical participants in the NO/H2O2 cytocidal mechanism. Our results suggest a possible mechanism of modulation H2O2-mediated toxicity, and we propose a new key role in the antimicrobial macrophagic response for NO. C1 NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,SCH MED,DEPT MOLEC BIOL,IL-91010 JERUSALEM,ISRAEL. NR 47 TC 182 Z9 185 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1995 VL 182 IS 5 BP 1469 EP 1479 DI 10.1084/jem.182.5.1469 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TB894 UT WOS:A1995TB89400029 PM 7595217 ER PT J AU SMITH, LC MEIRELLES, FV BUSTIN, M CLARKE, HJ AF SMITH, LC MEIRELLES, FV BUSTIN, M CLARKE, HJ TI ASSEMBLY OF SOMATIC HISTONE H1 ONTO CHROMATIN DURING BOVINE EARLY EMBRYOGENESIS SO JOURNAL OF EXPERIMENTAL ZOOLOGY LA English DT Article ID MESSENGER-RNA; EMBRYOS; STAGE; FERTILIZATION; NUCLEAR; MOUSE AB We have examined the distribution of somatic histone H1 in bovine oocytes and preimplantation embryos, using an antibody that recognizes histone H1 subtypes present in somatic cells. Immunoreactive H1 was not detectable on the chromosomes of metaphase II of meiosis nor in the nuclei of early cleavage-stage embryos. In most embryos, immunoreactive H1 was assembled onto embryonic chromatin during the fourth to sixth cell cycle after fertilization. No immunoreactive somatic histone H1 was detected, however, when embryos were incubated in the presence of a-amanitin beginning early during the fourth cell cycle. These results indicate that somatic subtypes of histone H1 are assembled onto embryonic chromatin in a developmentally regulated manner that requires embryonic transcription. Aphidicolin, an inhibitor of DNA replication, also inhibited the assembly of somatic histone H1 onto chromatin when present at early stages of the 4th cell cycle. It is suggested that, because the bulk of histone gene expression in proliferating cells occurs during DNA replication, expression of genes encoding immunoreactive H1 is inhibited in embryos blocked before or soon after entering the S-phase. These findings on the control of somatic histone H1 assembly onto chromatin in cattle show a remarkable similarity to those found in the mouse. Such evolutionary conservation suggests that the somatic histone H1 complement of chromatin may regulate critical aspects of chromatin activity during mammalian oogenesis or early embryogenesis. (C) 1995 Wiley-Liss, Inc. C1 MCGILL UNIV,DEPT OBSTET & GYNECOL,MONTREAL,PQ H3A 1A1,CANADA. MCGILL UNIV,DEPT BIOL,MONTREAL,PQ H3A 1A1,CANADA. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP SMITH, LC (reprint author), UNIV MONTREAL,FAC MED VET,CTR RECH REPROD ANIM,ST HYACINTHE,PQ J2S 7C6,CANADA. RI Meirelles, Flavio/B-5048-2010; Smith, Lawrence/K-4658-2012; Bustin, Michael/G-6155-2015 OI Meirelles, Flavio/0000-0003-0372-4920; NR 26 TC 18 Z9 18 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 0022-104X J9 J EXP ZOOL JI J. Exp. Zool. PD NOV 1 PY 1995 VL 273 IS 4 BP 317 EP 326 DI 10.1002/jez.1402730406 PG 10 WC Zoology SC Zoology GA TH316 UT WOS:A1995TH31600005 PM 8530913 ER PT J AU CHEN, BH NIE, JY SINGH, M PIKE, VW KIRK, KL AF CHEN, BH NIE, JY SINGH, M PIKE, VW KIRK, KL TI SYNTHESIS OF 2-FLUORO AND 6-FLUORO ANALOGS OF THREO-3-(3,4-DIHYDROXYPHENYL) SERINE (2-FLUORO-THREO-DOPS AND 6-FLUORO-THREO-DOPS) SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article DE SYNTHESIS; FLUORO-THREO-DOPS; NMR SPECTROSCOPY; MASS SPECTROMETRY ID ORTHOSTATIC HYPOTENSION; DL-THREO-3,4-DIHYDROXYPHENYLSERINE; L-THREO-3,4-DIHYDROXYPHENYLSERINE AB 2-Fluoro- and 6-fluoro-threo-dihydroxyphenylserine (2-F- and 6-F-threo-DOPS) have the potential, after crossing the blood-brain barrier, of functioning in the central nervous system as biological precursors of 2- and 6-fluoronorepinephrine (2- and 6-F-NE). Since 2-F-NE is a selective beta-adrenergic agonist and 6-F-NE is a selective alpha-adrenergic agonist, subsequent selective actions at beta- and alpha-adrenergic receptors could be beneficial for both clinical and pharmacological studies. We have prepared 2- and 6-F-threo-DOPS by the ZnCl2-catalyzed reaction of a protected glycine trimethylsilylketene acetal with benzyl-protected 2- and 6-fluoroprocatechuealdehyde. Other enantio- and diastereoselective approaches to these analogues either gave no product or produced predominantly the erythro diastereomer, apparently formed during work-up by acid-promoted racemization of the benzylic OH group in compounds possessing an unprotected catechol. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,MRC,CTR CLIN SCI,PET,METHODOL GRP,LONDON W12 0NN,ENGLAND. NR 18 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD NOV PY 1995 VL 75 IS 1 BP 93 EP 101 DI 10.1016/0022-1139(95)98347-6 PG 9 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA TG230 UT WOS:A1995TG23000012 ER PT J AU LIU, RH FOSTER, G CONE, EJ KUMAR, SD AF LIU, RH FOSTER, G CONE, EJ KUMAR, SD TI SELECTING AN APPROPRIATE ISOTOPIC INTERNAL STANDARD FOR GAS-CHROMATOGRAPHY MASS-SPECTROMETRY ANALYSIS OF DRUGS OF ABUSE - PENTOBARBITAL EXAMPLE SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE TOXICOLOGY; BARBITURATES; GC/MS; INTERNAL STANDARD; PENTOBARBITAL AB Internal standards are commonly used for the quantitative determination of drugs of abuse and their metabolites (drug/metabolite) in biological fluids and tissues by the selective ion monitoring (SIM) gas chromatography/mass spectrometry (GC/MS) procedure. Analogs of drugs/metabolites that are labeled with three or more deuterium atoms (isotopic analog) at appropriate positions are considered to be the most effective internal standards for these applications. Before a specific deuterated analog can be adopted as an internal standard in a GC/MS assay, the mass spectrum of the compound or its derivative must be evaluated along with the corresponding spectrum from the parent drug/metabolite. There should be an adequate number of sufficiently high-mass ions (typically three for the drug/metabolite and two for the isotopic analog) that can be attributed to each analyte, and these ions should be sufficiently free of interference from the other analyte of the pair (cross-contribution). Interferences may be caused by the presence of an isotopic impurity in the deuterated analog (extrinsic factor) or may be due to the ion fragmentation characteristics of the compound (intrinsic factor). The extrinsic factor may be corrected by the manufacturer with different synthetic methods and purification procedures, while the intrinsic factor may be partially or wholly corrected through the use of different chemical derivatives (sample preparation stage) or different ionization (GC/MS assay stage) procedures. In this study, pentobarbital/d(5)-pentobarbital is used as the exemplar analyte/deuterated analog pair to illustrate the ion selection and evaluation procedures. Full-scan mass spectra were employed for preliminary ion selection. SIM data were then used to calculate the extent, if any, of cross-contributions. SIM ion chromatograms obtained under a lower GC oven temperature were used to differentiate sources (ion fragmentation mechanism versus isotopic impurity) of cross-contributions. C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. RADIAN CORP,AUSTIN,TX. RP LIU, RH (reprint author), UNIV ALABAMA,DEPT CRIMINAL JUSTICE,GRAD PROGRAM FORENS SCI,BIRMINGHAM,AL 35294, USA. NR 6 TC 27 Z9 27 U1 1 U2 4 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD NOV PY 1995 VL 40 IS 6 BP 983 EP 989 PG 7 WC Medicine, Legal SC Legal Medicine GA TH095 UT WOS:A1995TH09500018 PM 8522930 ER PT J AU MELIKYAN, GB NILES, WD RATINOV, VA KARHANEK, M ZIMMERBERG, J COHEN, FS AF MELIKYAN, GB NILES, WD RATINOV, VA KARHANEK, M ZIMMERBERG, J COHEN, FS TI COMPARISON OF TRANSIENT AND SUCCESSFUL FUSION PORES CONNECTING INFLUENZA HEMAGGLUTININ EXPRESSING CELLS TO PLANAR MEMBRANES SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID VIRAL ENVELOPE PROTEIN; PATCH-CLAMP; CAPACITANCE MEASUREMENTS; EXOCYTOSIS; VESICLE AB Time-resolved admittance measurements were used to investigate the evolution of fusion pores formed between cells expressing influenza virus hemagglutinin (HA) and planar bilayer membranes. The majority of fusion pores opened in a stepwise fashion to semistable conductance levels of several nS. About 20% of the pores had measurable rise times to nS conductances; some of these opened to conductances of similar to 500 pS where they briefly lingered before opening further to semistable conductances. The fall times of closing were statistically similar to the rise times of opening. All fusion pores exhibited semistable values of conductance, varying from similar to 2-20 nS; they would then either close or fully open to conductances on the order of 1 mu S. The majority of pores closed; similar to 10% fully opened. Once within the semistable stage, all fusion pores, even those that eventually closed, tended to grow. Statistically, however, before closing, transient fusion pores ceased to grow and reversed their conductance pattern: conductances decreased with a measurable time course until a final drop to closure. In contrast, pore enlargement to the fully open state tended to occur from the largest conductance values attained during a pore's semistable stage. This final enlargement was characterized by a stepwise increase in conductance. The density of HA on the cell surface did not strongly affect pore dynamics. But increased proteolytic treatment of cell surfaces did lead to faster growth Within the semistable range. Transient pores and pores that fully opened had indistinguishable initial conductances and statistically identical time courses of early growth, suggesting they were the same upon formation. We suggest that transient and fully open pores evolved from common structures with stochastic factors determining their fate. C1 RUSH MED COLL,DEPT MOLEC BIOPHYS & PHYSIOL,CHICAGO,IL 60612. NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM 27367] NR 32 TC 31 Z9 31 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD NOV PY 1995 VL 106 IS 5 BP 803 EP 819 DI 10.1085/jgp.106.5.803 PG 17 WC Physiology SC Physiology GA TJ406 UT WOS:A1995TJ40600002 PM 8648293 ER PT J AU Slattery, JP OBrien, SJ AF Slattery, JP OBrien, SJ TI Molecular phylogeny of the red panda (Ailurus fulgens) SO JOURNAL OF HEREDITY LA English DT Article ID DIMENSIONAL PROTEIN ELECTROPHORESIS; MITOCHONDRIAL-DNA SEQUENCE; RELATIVE EFFICIENCIES; MAXIMUM-LIKELIHOOD; GENETIC-DISTANCE; GIANT PANDA; CARNIVORES; EVOLUTION; DIVERGENCE; PARSIMONY AB The phylogenetic placement of the red panda (Ailurus fulgens) and the giant panda (Ailuropoda melanoleuca) has been an evolutionary enigma since their original descriptions in the nineteenth century, A series of recent molecular analyses led to a consensus that the giant panda's ancestors were derived from early bears (Ursidae), but left unsettled the phylogenetic relationship of the red panda, Previous molecular and morphological phylogenies were inconclusive and varied among placement of the red panda within the raccoon family (Procyonidae), within the bear family (Ursidae), or in a separate family of carnivores equidistant between the two, To examine a relatively ancient (circa 20-30 million years before the present, MYBP) phylogenetic divergence, we used two slowly evolving genetic markers: mitochondrial 12S rRNA sequence and 592 fibroblast proteins resolved by two dimensional gel electrophoresis. Four different carnivore outgroup species, including dog (Canidae: Canis familiaris), cat (Felidae: Felis catus), fanaloka (Viverridae: Fossa fossa), and mongoose (Herpestidae: Galidia elegans), were selected to identify the root of the phylogenetic topologies. Phylogenetic reconstruction by distance-based methods, maximum parsimony, and maximum likelihood clearly indicate a distinct bifurcation forming the Ursidae and the Procyonidae, Further, our data consistently place the red panda as an early divergence within the Procyonidae radiation and confirm the inclusion of giant panda in the Ursidae lineage. RP Slattery, JP (reprint author), NCI, VIRAL CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. NR 53 TC 33 Z9 41 U1 1 U2 28 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 EI 1465-7333 J9 J HERED JI J. Hered. PD NOV-DEC PY 1995 VL 86 IS 6 BP 413 EP 422 PG 10 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA TL747 UT WOS:A1995TL74700001 PM 8568209 ER PT J AU RAJAGOPALAN, S WINTER, CC WAGTMANN, N LONG, EO AF RAJAGOPALAN, S WINTER, CC WAGTMANN, N LONG, EO TI THE IG-RELATED KILLER-CELL INHIBITORY RECEPTOR BINDS ZINC AND REQUIRES ZINC FOR RECOGNITION OF HLA-C ON TARGET-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Note ID HUMAN GROWTH-HORMONE; NK CLONES; MONOCLONAL-ANTIBODIES; EXPRESSION; ALLELES; LYSIS; SPECIFICITY; PROTECTION; PRODUCTS; LINE AB Members of the Ig superfamily ave predominantly receptors that mediate interactions between cells or provide signals to cells when binding specific ligands. Here we describe an Ig-related receptor that requires zinc for its function, Killer cell inhibitory receptors (KIR) belonging to the Ig superfamily mediate inhibition of NK cells upon recognition of HLA-C molecules on target cells. An abundance of histidine residues in the first extracellular domain of KIR, including the signature zinc binding motif HEXXH, suggested that this receptor may bind zinc. Two distinct KIR molecules that mediate recognition of HLA-Cw4 and -Cw8, respectively, bound specifically to zinc affinity columns. Furthermore, addition of the zinc chelator 1,10-phenanthroline during chromium release assays reversed the inhibition of killing by NK clones specific for HLA-Cw4 or HLA-Cw8, demonstrating that zinc is necessary for the inhibitory function of KIR. Such functionally relevant zinc binding has not been described for other members of the Ig superfamily and may represent a novel regulatory mechanism for pg receptor-ligand interactions. C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 27 TC 62 Z9 62 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 NOV 1 PY 1995 VL 155 IS 9 BP 4143 EP 4146 PG 4 WC Immunology SC Immunology GA TB468 UT WOS:A1995TB46800003 PM 7594568 ER PT J AU ENGLAND, RD KULLBERG, MC CORNETTE, JL BERZOFSKY, JA AF ENGLAND, RD KULLBERG, MC CORNETTE, JL BERZOFSKY, JA TI MOLECULAR ANALYSIS OF A HETEROCLITIC T-CELL RESPONSE TO THE IMMUNODOMINANT EPITOPE OF SPERM WHALE MYOGLOBIN - IMPLICATIONS FOR PEPTIDE PARTIAL AGONISTS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I H-2K(B); RECEPTOR LIGAND; ANTIGENIC SITES; VIRAL PEPTIDES; MHC MOLECULE; RECOGNITION; CLONES; BINDING; IDENTIFICATION AB We have investigated the molecular basis for binding and Ag presentation of an immunodominant Th cell determinant of sperm whale myoglobin, a prototype amphipathic helical structure in the native protein. A series of peptides with three different substitutions at each position were evaluated for binding to the class II MHC molecule I-A(d) and for activation of two T cell clones with distinct fine specificity, to determine the role of each residue. The assignment of MHC binding and TCR binding residues is consistent with a peptide bound as a twisted beta-strand, with 130 degrees twist similar to that of the influenza hemagglutinin peptide crystallized in the groove of HLA-DR1. This twist gives the peptide amphipathicity, with a periodicity similar to an alpha-helix without its being a helix. Two substituted peptides were discovered to be heteroclitic, but by different molecular mechanisms, one involving gain of a favorable residue and one involving loss of an unfavorable one. Complexes of both peptides with I-A(d) had enormously higher affinity for the TCR, but peptide affinity for the MHC molecule was not increased, such that the wild-type peptide acted as a partial agonist and inhibited the response to the heteroclitic ones. Moreover, the magnitude of response was elevated in a way that could not be mimicked by the wild-type peptide even at higher concentration. These results suggest a TCR dwell time requirement for optimal signal transduction that may help explain the mechanism of partial agonism. C1 NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. IOWA STATE UNIV SCI & TECHNOL,DEPT MATH,AMES,IA 50011. NR 63 TC 23 Z9 23 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 NOV 1 PY 1995 VL 155 IS 9 BP 4295 EP 4306 PG 12 WC Immunology SC Immunology GA TB468 UT WOS:A1995TB46800023 PM 7594588 ER PT J AU KONDO, A SIDNEY, J SOUTHWOOD, S DELGUERCIO, MF APPELLA, E SAKAMOTO, H CELIS, E GREY, HM CHESNUT, RW KUBO, RT SETTE, A AF KONDO, A SIDNEY, J SOUTHWOOD, S DELGUERCIO, MF APPELLA, E SAKAMOTO, H CELIS, E GREY, HM CHESNUT, RW KUBO, RT SETTE, A TI PROMINENT ROLES OF SECONDARY ANCHOR RESIDUES IN PEPTIDE BINDING TO HLA-A24 HUMAN CLASS-I MOLECULES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SELF-PEPTIDES; OVALBUMIN PEPTIDE; T-CELLS; MHC; HLA; MOTIFS; IDENTIFICATION AB The binding capacity of large sets of peptides corresponding to naturally occurring sequences and carrying previously defined A24-specific motifs was analyzed. It was found that only a minority (9-25%) of the motif-carrying peptides bound the relevant HLA-A molecule with good affinity (IC 50% less than or equal to 50 nM) while the majority of them bound only weakly or not at all (IC 50% greater than or equal to 500 nM). By correlating the presence of specific residue types at each position along the peptide sequence with average binding affinity, the prominent influence of specific secondary interactions (secondary anchor residues) was revealed. Moreover, secondary interactions appeared to be size-dependent in that the specific effects detected differed in 9-mer and 10-mer peptide sets. Based on these observations, A24-specific refined motifs were also established for both 9-mer and 10-mer ligands, and their merit was verified by testing the binding capacity of independent sets of synthetic peptides. Such refined motifs should facilitate accurate prediction of potential A24-restricted peptide epitopes, it was also noted that certain crucial secondary interactions appear to be remarkably similar in the case of A24 and other HLA-A molecules previously analyzed (A*0201, A3, A11, and others). This may reflect contributions to binding affinity of relatively invariant residues located within the polymorphic pockets of the HLA binding groove. C1 CYTEL CORP,SAN DIEGO,CA 92121. TAKARA SHUZO CO LTD,SHIGA,JAPAN. LA JOLLA INST ALLERGY & IMMUNOL,SAN DIEGO,CA 92037. NCI,BETHESDA,MD 20892. RI Sakamoto, Hiroshi/A-3181-2011 NR 30 TC 73 Z9 74 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 NOV 1 PY 1995 VL 155 IS 9 BP 4307 EP 4312 PG 6 WC Immunology SC Immunology GA TB468 UT WOS:A1995TB46800024 PM 7594589 ER PT J AU Marincola, FM Shamamian, P Rivoltini, L Salgaller, M Cormier, J Restifo, NP Simonis, TB Venzon, D White, DE Parkinson, DR AF Marincola, FM Shamamian, P Rivoltini, L Salgaller, M Cormier, J Restifo, NP Simonis, TB Venzon, D White, DE Parkinson, DR TI HLA associations in the antitumor response against malignant melanoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE HLA; malignant melanoma; NAC patients ID TUMOR-NECROSIS-FACTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; I ANTIGEN EXPRESSION; INFILTRATING LYMPHOCYTES; FACTOR-ALPHA; CANCER-PATIENTS; FACTOR TNF; INTERLEUKIN-2; IMMUNOTHERAPY; CELLS AB In this study we analyzed the human leukocyte antigen (HLA) pattern of North American Caucasian patients with metastatic melanoma as compared with the North American Caucasian (NAG) population. We also investigated whether the HLA type of melanoma patients had an effect on their tolerance and response to interleukin-2 (IL-2)-based therapy. Four hundred twelve serologic phenotypes of Caucasian melanoma patients referred to the National Cancer Institute, National Institutes of Health, from February 1989 through December 1993 were collected by typing the patient's peripheral blood lymphocytes. Furthermore, 74 melanoma patients were typed for HLA class II by high-resolution sequence specific primer-polymerase chain reaction. Response rate and treatment-related toxicity in those patients receiving IL-2-based treatment (N = 272) were compared with HLA serologic types. The frequency of four HLA-B alleles was significantly different in the melanoma compared with the NAC population: Of these, HLA-BS, -B8, and -B15 had a frequency falling between the NAC and the Northern European population. No other significant differences between melanoma patients and NAC population were noted for other HLA loci. A correlation was noted between HLA-DR3 and -DR4 alleles and decreased tolerance to IL-2, whereas homozygosity for HLA-DR decreased the chance of response, There were no significant associations between HLA type and response. It is unlikely that the associations noted between some HLA-B alleles and melanoma bear significantly on the etiology of the disease. The differences seen between American melanoma patients and the NAC population are probably best explained by geographical ancestry. The association between HLA-DR and tolerance to IL-2 therapy noted in this study may offer insight toward the understanding of mechanisms regulating the cascade of events after the systemic administration of IL-2. C1 NCI,DEPT TRANSFUS MED,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RP Marincola, FM (reprint author), NCI,SURG BRANCH,DIV CANC TREATMENT,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. RI Restifo, Nicholas/A-5713-2008; Venzon, David/B-3078-2008; OI Restifo, Nicholas P./0000-0003-4229-4580; Rivoltini, Licia/0000-0002-2409-6225 FU Intramural NIH HHS [Z99 TW999999, NIH0010139353, Z01 BC010763-01] NR 53 TC 23 Z9 26 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV PY 1995 VL 18 IS 4 BP 242 EP 252 DI 10.1097/00002371-199511000-00005 PG 11 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA UA137 UT WOS:A1995UA13700005 PM 8680652 ER PT J AU Yannelli, JR McConnell, S Parker, L Nishimura, M Robbins, P Yang, J ElGamil, M Kawakami, Y AF Yannelli, JR McConnell, S Parker, L Nishimura, M Robbins, P Yang, J ElGamil, M Kawakami, Y TI Melanoma tumor-infiltrating lymphocytes derived from four distinct anatomic sites obtained from a single patient: Comparison of functional reactivity and melanoma antigen recognition SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE TIL; MART-1; immunotherapy; cytotoxicity; melanoma ID NECROSIS-FACTOR-ALPHA; AUTOLOGOUS TUMOR; CYTOKINE SECRETION; ADVANCED CANCER; INTERLEUKIN-2; RELEASE; CELLS; LYSIS AB Tumor-infiltrating lymphocytes (TILs) were grown from four distinct anatomic sites from a patient with metastatic melanoma. The metastatic sites included a tumor-involved lymph node, a subcutaneous lesion obtained from the chest wall, a portion of bowel, and adrenal gland. TILs grown from each anatomic site over the course of 20 days in the presence of 6,000 IU/ml recombinant interleukin-2 exhibited comparable growth rates. Between days 30 and 45, the TILs were a mixture of CD3(+) CD4(+) and CD3(+) CD8(+) lymphocytes expressing the alpha beta form of the T-cell receptor. TILs derived from each anatomic site specifically lysed autologous tumor obtained from all four anatomic sites. In fine specificity analysis, the TILs exhibited human leukocyte antigen (HLA-A2)-restricted lysis of fresh tumor targets and cultured melanoma cell lines. Each TIL recognized a product of the MART-1 gene, and specifically, the monomer peptide MART-1(27-35). Thus lymphocytes reactive with the MART-1 melanoma antigen appeared to be widely distributed in diverse metastases in this patient. This information, along with previous data on the reactivity of multiple patients to this antigen, attests to its dominance in the immune reactivity of humans to melanoma. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NR 30 TC 6 Z9 6 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV PY 1995 VL 18 IS 4 BP 263 EP 271 DI 10.1097/00002371-199511000-00007 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA UA137 UT WOS:A1995UA13700007 PM 8680654 ER PT J AU Krouse, RS Royal, RE Heywood, G Weintraub, BD White, DE Steinberg, SM Rosenberg, SA Schwartzentruber, DJ AF Krouse, RS Royal, RE Heywood, G Weintraub, BD White, DE Steinberg, SM Rosenberg, SA Schwartzentruber, DJ TI Thyroid dysfunction in 281 patients with metastatic melanoma or renal carcinoma treated with interleukin-2 alone SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE Il-2; hypothyroidism; hyperthyroidism; renal carcinoma; melanoma ID RECOMBINANT INTERLEUKIN-2; THERAPY; HYPOTHYROIDISM; IMMUNOTHERAPY; INTERFERON; CANCER AB The purpose of this prospective study was to determine the incidence of thyroid dysfunction in cancer patients receiving immunotherapy with interleukin-2 (IL-2) alone, and to assess the relationship of hypothyroidism to clinical response. A cohort of 281 consecutive patients with metastatic melanoma or renal carcinoma were treated with IL-2 alone from July 1, 1989 until June 30, 1993. The majority (n = 216) received high-dose IL-2 and the remainder (n = 65) received low-dose therapy. Thyroid function was measured before, during, and after immunotherapy. Forty-one percent of initially euthyroid patients developed thyroid dysfunction after starting high-dose IL-2-alone therapy. The most common abnormality was hypothyroidism, occurring in 35% of patients, although moderate or severe hypothyroidism requiring thyroid hormone replacement occurred in 9% of patients. Hypothyroidism was related to duration of IL-2 therapy and was not associated with clinical response. Hyperthyroidism developed in 7% of previously euthyroid patients receiving high-dose IL-2. Overall, the incidence of thyroid dysfunction was similar in the high- and low-dose IL-2 regimens. In conclusion, thyroid dysfunction is a common sequela of IL-2 therapy. Thyroid function should be measured routinely in cancer patients receiving IL-2-based treatment. It is recommended that thyroid hormone replacement be given to patients with moderate or severe hypothyroidism. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,NIH,BETHESDA,MD 20892. NIDDKD,BETHESDA,MD 20892. NR 23 TC 48 Z9 48 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV PY 1995 VL 18 IS 4 BP 272 EP 278 DI 10.1097/00002371-199511000-00008 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA UA137 UT WOS:A1995UA13700008 PM 8680655 ER PT J AU HAUBRICH, RH FLEXNER, C LEDERMAN, MM HIRSCH, M PETTINELLI, CP GINSBERG, R LIETMAN, P HAMZEH, FM SPECTOR, SA RICHMAN, DD HAMMER, S COOLEY, T GULICK, R SULLIVAN, M SPINA, C FRASER, A LATHEY, J BASSIAKOS, Y CHANCE, M DROBNES, C CORUELL, E GRUE, L RAINES, C KUWAHARA, S MCPHERSON, J AF HAUBRICH, RH FLEXNER, C LEDERMAN, MM HIRSCH, M PETTINELLI, CP GINSBERG, R LIETMAN, P HAMZEH, FM SPECTOR, SA RICHMAN, DD HAMMER, S COOLEY, T GULICK, R SULLIVAN, M SPINA, C FRASER, A LATHEY, J BASSIAKOS, Y CHANCE, M DROBNES, C CORUELL, E GRUE, L RAINES, C KUWAHARA, S MCPHERSON, J TI A RANDOMIZED TRIAL OF THE ACTIVITY AND SAFETY OF RO-24-7429 (TAT ANTAGONIST) VERSUS NUCLEOSIDE FOR HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PLACEBO-CONTROLLED TRIAL; TUMOR-NECROSIS-FACTOR; TRANS-ACTIVATOR GENE; DOUBLE-BLIND; REPLICATION; ZIDOVUDINE; TYPE-1; INHIBITION; EFFICACY; AZT AB Ro 24-7429, a Tat antagonist, dosed at 75, 150, or 300 mg/day, was compared with nucleoside analogue (zidovudine or didanosine) for 12 weeks in 96 human immunodeficiency virus (HIV)infected patients to assess safety and activity. The primary adverse effect of Ro 24-7429 was rash, which necessitated treatment discontinuation in 6 of 71 patients. Nucleoside analogue treatment produced an average increase in CD4 cell count of 28 cells/mm(3) at week 8 versus a decrease of 27 cells/mm(3) in recipients of Ro 24-7429 (P < .001). Serum HIV p24 antigen levels decreased by an average of 111 pg/mL in nucleoside recipients at week 8 compared with an increase of 41 pg/mL in recipients of Ro 24-7429 (P = .007). Nucleoside-treated patients had a mean 0.66 log(10) reduction in infectious peripheral blood mononuclear cells, while Ro 24-7429 recipients had a mean 0.02 log(10) reduction (P = .02). No dose-response relationships were observed in the Ro 24-7429 groups. In this study, Ro 24-7429 treatment showed no evidence of antiviral activity. C1 UNIV CALIF SAN DIEGO,DEPT PATHOL,SAN DIEGO,CA 92103. UNIV CALIF SAN DIEGO,DEPT PEDIAT,SAN DIEGO,CA 92103. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. CASE WESTERN RESERVE UNIV,SCH MED,DEPT MED,CLEVELAND,OH 44106. HARVARD UNIV,MASSACHUSETTS GEN HOSP,BOSTON,MA. NIAID,DIV AIDS,BETHESDA,MD 20892. HOFFMANN LA ROCHE AG,NUTLEY,NJ. RP HAUBRICH, RH (reprint author), UNIV CALIF SAN DIEGO,CTR TREATMENT,DEPT MED,2760 5TH AVE,SUITE 300,SAN DIEGO,CA 92103, USA. FU NCRR NIH HHS [RR-00722, RR-00035]; NIAID NIH HHS [AI-27670] NR 22 TC 22 Z9 23 U1 0 U2 2 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 NOV PY 1995 VL 172 IS 5 BP 1246 EP 1252 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TA552 UT WOS:A1995TA55200010 PM 7594660 ER PT J AU BECERRA, LR GERFEN, GJ BELLEW, BF BRYANT, JA HALL, DA INATI, SJ WEBER, RT UN, S PRISNER, TF MCDERMOTT, AE FISHBEIN, KW KREISCHER, KE TEMKIN, RJ SINGEL, DJ GRIFFIN, RG AF BECERRA, LR GERFEN, GJ BELLEW, BF BRYANT, JA HALL, DA INATI, SJ WEBER, RT UN, S PRISNER, TF MCDERMOTT, AE FISHBEIN, KW KREISCHER, KE TEMKIN, RJ SINGEL, DJ GRIFFIN, RG TI A SPECTROMETER FOR DYNAMIC NUCLEAR-POLARIZATION AND ELECTRON-PARAMAGNETIC-RESONANCE AT HIGH-FREQUENCIES SO JOURNAL OF MAGNETIC RESONANCE SERIES A LA English DT Article ID C-13 NMR-SPECTROSCOPY; HIGH-RESOLUTION NMR; EPR SPECTROSCOPY; 95 GHZ; SOLIDS; GYROTRON; SPINS; 5-T AB A high-frequency dynamic nuclear polarization (DNP)/electron paramagnetic resonance spectrometer operating at 211 MHz for H-1 and 140 GHz for g = 2 paramagnetic centers (5 T static field) is described. The salient feature of the instrument is a cyclotron-resonance maser (gyrotron) which generates high-frequency, high-power microwave radiation, This gyrotron, which under conventional operation produces millisecond pulses at kilowatt powers, has been adapted to operate at similar to 100 W for 1 to 20 s pulses and in the continuous wave mode at the 10 W power level, Experiments combining DNP with magic-angle spinning (MAS) nuclear magnetic resonance were performed on samples consisting of 2% by weight of the free radical BDPA doped into polystyrene, Room-temperature DNP enhancement factors of 10 for H-1 and 40 for C-13 were obtained in the NMR-MAS spectra, Static DNP NMR has also been performed on samples containing nitroxides dissolved in water:glycerol solvent mixtures, Enhancements of approximately 200 have been obtained for low-temperature (14 K) H-1 NMR. A pulsed/CW EPR spectrometer operating at 140 GHz has been developed in conjunction with the DNP spectrometer, Microwave sources include Gunn-diode oscillators which provide low-power (20 mW) radiation, and the gyrotron, which has been used to deliver higher power levels in pulsed experiments, Results using this spectrometer are presented for continuous-wave and echo-detected EPR, electron spin-echo-envelope modulation (ESEEM), and Fourier-transform EPR. (C) 1995 Academic Press, Inc. C1 MIT,CTR PLASMA FUS,CAMBRIDGE,MA 02139. BRUKER INSTRUMENTS INC,DIV EPR,BILLERICA,MA 01821. CENS,SERV BIOPHYS,F-91191 GIF SUR YVETTE,FRANCE. FREE UNIV BERLIN,FACHBEREICH PHYS,D-14195 BERLIN,GERMANY. COLUMBIA UNIV,DEPT CHEM,NEW YORK,NY 10027. NIH,INST AGING,BALTIMORE,MD 21224. MONTANA STATE UNIV,DEPT CHEM,BOZEMAN,MT 59715. RP BECERRA, LR (reprint author), MIT,DEPT CHEM,FRANCIS BITTER NATL MAGNET LAB,CAMBRIDGE,MA 02139, USA. OI Fishbein, Kenneth/0000-0002-6353-4603; McDermott, Ann/0000-0002-9249-1649 NR 43 TC 105 Z9 106 U1 6 U2 49 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1858 J9 J MAGN RESON SER A JI J. Magn. Reson. Ser. A PD NOV PY 1995 VL 117 IS 1 BP 28 EP 40 PG 13 WC Physics, Atomic, Molecular & Chemical SC Physics GA TE637 UT WOS:A1995TE63700004 ER PT J AU WILLIAMSONKRUSE, L BIESECKER, LG AF WILLIAMSONKRUSE, L BIESECKER, LG TI PFEIFFER TYPE CARDIOCRANIAL SYNDROME - A 3RD CASE-REPORT SO JOURNAL OF MEDICAL GENETICS LA English DT Note AB Pfeiffer-type cardiocranial syndrome is a rare condition reported previously in three patients, two of whom were sibs. All three patients shared features that included growth and developmental retardation, sagittal synostosis, hypertelorism, low set ears, micrognathia with mandibular ankylosis, congenital heart defects, and genital anomalies. The purposes of this report are to present a fourth patient with features of the Pfeiffer-type cardiocranial syndrome, to expand the clinical phenotype of this condition, and to present evidence that supports the concept that this phenotype represents a distinct nosological entity. C1 NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,BETHESDA,MD 20892. UNIV MISSOURI,DEPT CHILD HLTH,DIV MED GENET,COLUMBIA,MO 65201. NR 5 TC 5 Z9 5 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD NOV PY 1995 VL 32 IS 11 BP 901 EP 903 DI 10.1136/jmg.32.11.901 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA TC962 UT WOS:A1995TC96200016 PM 8592338 ER PT J AU BORDIN, S BOSCHERO, AC CARNEIRO, EM ATWATER, I AF BORDIN, S BOSCHERO, AC CARNEIRO, EM ATWATER, I TI IONIC MECHANISMS INVOLVED IN THE REGULATION OF INSULIN-SECRETION BY MUSCARINIC AGONISTS SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE MUSCARINIC AGONIST; BETA-CELL ELECTRICAL ACTIVITY; INSULIN SECRETION; K+-PERMEABILITY; CRAC; CHARYBDOTOXIN; MOUSE ID PANCREATIC BETA-CELLS; INDUCED ELECTRICAL-ACTIVITY; CALCIUM ENTRY; B-CELLS; CA2+ INFLUX; GLUCOSE; MEMBRANE; RELEASE; ISLETS; ACETYLCHOLINE AB The effects of the muscarinic agonist oxotremorine-m (oxo-m) on insulin secretion, K+-permeability and electrical activity from isolated mouse pancreatic islets were studied. Oxo-m potentiated glucose-induced insulin secretion in a dose-dependent manner, saturating at ca. 10 mu M. At 11.2 mM glucose, oxo-m (0.1 and 10 mu M) had two distinct effects on beta-cell electrical activity. Both concentrations increased the steadystate burst frequency, however, at 10 mu M an initial and transient polarization was measured, and the subsequent activity was accompanied by a slight depolarization. The polarizing effect of oxo-m was almost completely suppressed by charybdotoxin (ChTX), a blocker of the large conductance (maxi) [Ca2+](i)-activated potassium channel (K-(Ca)). In the presence of 11.2 mM glucose, oxo-m (50 mu M) provoked a significant and transient increase in the Rb-86 efflux from perifused islets. This effect was inhibited by ChTX. ChTX also potentiated oxo-m stimulated insulin secretion in the presence of glucose. Finally, the balance between the polarizing and depolarizing effects of oxo-m was variable in different islets and depended on glucose concentration. Insulin secretion stimulated by oxo-m in the presence of glucose was more closely correlated to the agonist induced increase in burst frequency than to an increase in plateau fraction. We conclude that muscarinic stimulation has at least two effects on beta-cell electrical activity, an initial hyperpolarization, owing to activation of K-(Ca) channels, followed by depolarization and high-frequency bursts, proposed to reflect the activation of a current sensitive to the depletion of intracellular Ca2+ stores (CRAC). C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. UNIV CAMPINAS,INST BIOL,DEPT FISIOL & BIOFIS,BR-13081 CAMPINAS,BRAZIL. RI Carneiro, Everardo /D-4758-2012; Boschero, Antonio/O-7525-2014 OI Boschero, Antonio/0000-0003-3829-8570 NR 38 TC 47 Z9 47 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD NOV PY 1995 VL 148 IS 2 BP 177 EP 184 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA TG474 UT WOS:A1995TG47400007 PM 8606366 ER PT J AU HUNT, RA CIUFFO, GM SAAVEDRA, JM TUCKER, DC AF HUNT, RA CIUFFO, GM SAAVEDRA, JM TUCKER, DC TI SYMPATHETIC INNERVATION MODULATES THE EXPRESSION OF ANGIOTENSIN-II RECEPTORS IN EMBRYONIC RAT-HEART GRAFTED IN OCULO SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE ANGIOTENSIN II; SYMPATHETIC NERVOUS SYSTEM; QUANTITATIVE AUTORADIOGRAPHY; AT(1) RECEPTOR; AT(2) RECEPTOR; CARDIAC DEVELOPMENT ID CARDIAC FIBROBLASTS; NEURONAL CULTURES; PROTEIN-SYNTHESIS; GROWTH; INOCULO; CELLS; CATECHOLAMINES; STIMULATION; HYPERTROPHY; INFARCTION AB Angiotensin II acts as a cardiac growth factor, and causes both inotropic and chronotropic changes within the heart. In the present study, we used an in oculo model system to examine the effects of sympathetic innervation on the density of cardiac angiotensin II receptors. Quantitative autoradiography was used to determine the density of angiotensin II receptors in embryonic rat hearts grafted into either sympathetically innervated or sympathetically denervated eye chambers of adult host rats. The density of specific binding to angiotensin II receptors was nearly three-fold higher in sympathetically non-innervated compared to sympathetically innervated heart grafts (30.8 +/- 4.2 v 11.5 +/- 3.2 fmol/mg protein). Specific binding to angiotensin II receptors in heart grafts was displaced by addition of the AT(1) receptor antagonist losartan, but not by addition of the AT(2) receptor competitor PD 123177. Thus, only AT(1) receptors were present in sympathetically innervated and sympathetically non-innervated embryonic rat hearts grafted in oculo. We conclude that changes in sympathetic innervation caused changes in the density of cardiac angiotensin II receptors in the present study. Our results may have implications for growth and function not only during cardiac development, but also during cardiac disease. (C) 1995 Academic Press Limited C1 UNIV ALABAMA, DEPT PSYCHOL, BIRMINGHAM, AL 35294 USA. NIMH, CLIN SCI LAB, PHARMACOL SECT, BETHESDA, MD 20892 USA. FU NHLBI NIH HHS [HL 42258, HL 39048] NR 36 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD NOV PY 1995 VL 27 IS 11 BP 2445 EP 2452 DI 10.1006/jmcc.1995.0232 PG 8 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA TD002 UT WOS:A1995TD00200003 PM 8596195 ER PT J AU NARITSIN, DB SAITO, K MARKEY, SP CHEN, CY HEYES, MP AF NARITSIN, DB SAITO, K MARKEY, SP CHEN, CY HEYES, MP TI METABOLISM OF L-TRYPTOPHAN TO KYNURENATE AND QUINOLINATE IN THE CENTRAL-NERVOUS-SYSTEM - EFFECTS OF 6-CHLOROTRYPTOPHAN AND 4-CHLORO-3-HYDROXYANTHRANILATE SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE MACROPHAGES; ASTROCYTES; KYNURENINE AMINOTRANSFERASE; 4-CHLOROKYNURENINE; 7-CHLOROKYNURENATE; NONHUMAN PRIMATES ID PERFORMANCE LIQUID-CHROMATOGRAPHY; D-ASPARTATE RECEPTOR; RAT-BRAIN; CEREBROSPINAL-FLUID; PATHWAY METABOLISM; IMMUNE ACTIVATION; ACID FORMATION; AMINOTRANSFERASE; IDENTIFICATION; QUANTIFICATION AB The metabolism of L-tryptophan to the neuroactive kynurenine pathway metabolites, L-kynurenine, kynurenate and quinolinate, and the effects of two inhibitors of quinolinate synthesis (6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate) were investigated by mass spectrometric assays in cultured cells and in vivo. Cell lines obtained from astrocytoma, neuroblastoma, macrophage/monocytes, lung, and liver metabolized L-[C-13(6)]tryptophan to L-[C-13(6)]kynurenine and [C-13(6)]kynurenate, particularly after indoleamine-2,3-dioxygenase induction by interferon-gamma. Kynurenine aminotransferase activity was measurable in all cell types examined but was unaffected by interferon-gamma. These results suggest that many cell types can be sources of kynurenate following immune activation. In vivo synthesis of L-[C-13(6)]kynurenine and [C-13(6)]kynurenate from L-[C-13(6)]tryptophan was studied in the CSF of macaques infected with poliovirus, as a model of inflammatory neurologic disease. The effects of 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate on the synthesis of kynurenate were different. 6-Chlorotryptophan attenuated formation of L-[C-13(6)]kynurenine and [C-13(6)]kynurenate and was converted to 4-chlorokynurenine and 7-chlorokynurenate It may be an effective prodrug for the delivery of 7-chlorokynurenate, which is a potent antagonist of NMDA receptors. In contrast, 4-chloro-3-hydroxyanthranilate did not reduce accumulation of L-[C-13(6)]kynurenine and [C-13(6)]kynurenate. 6-Chlorotryptophan and 4-chloro-3-hydroxyanthranilate are useful tools to manipulate concentrations of quinolinate and kynurenate in the animal models of neurologic disease to evaluate physiological roles of these neuroactive metabolites. RP NARITSIN, DB (reprint author), NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BLDG 10,ROOM 3D40,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 39 TC 23 Z9 23 U1 0 U2 6 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1995 VL 65 IS 5 BP 2217 EP 2226 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TA742 UT WOS:A1995TA74200038 PM 7595510 ER PT J AU BERGQVIST, PBF HEYES, MP BUGGE, M BENGTSSON, F AF BERGQVIST, PBF HEYES, MP BUGGE, M BENGTSSON, F TI BRAIN QUINOLINIC ACID IN CHRONIC EXPERIMENTAL HEPATIC-ENCEPHALOPATHY - EFFECTS OF AN EXOGENOUS AMMONIUM ACETATE CHALLENGE SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE AMMONIA TOXICITY; COMA; KYNURENINES; PORTACAVAL-SHUNTED RATS; TRYPTOPHAN METABOLISM ID RAT-BRAIN; PORTACAVAL ANASTOMOSIS; BLOOD; FAILURE; QUANTIFICATION; SEROTONIN; REGIONS; BARRIER; PLASMA; RABBIT AB Elevated brain concentrations of the neurotoxin and NMDA receptor agonist quinolinic acid (QUIN) have been demonstrated in portacaval-shunted (PCS) rats, a chronic hepatic encephalopathy (HE) model. Increased brain QUIN levels have also been shown in acute hyperammonemic rats. In the present study, the plasma and brain (neocortical) QUIN levels in chronic PCS rats were investigated. The study also included a single exogenous ammonium acetate (NH4Ac; 5.2 mmol/kg, i.p.) challenge to precipitate a reversible hepatic coma. Compared with sham-operated controls, chronic PCS rats exhibited decreased rather than increased plasma and brain QUIN levels. The plasma-to-brain QUIN ratio was not found to be altered. The NH4Ac administration induced coma in all of the PCS rats 20-25 min after the challenge, and this coma was resolved within 60-75 min. No relevant temporal relationship between changes in brain QUIN levels and the neurological status in the PCS rats was observed. Therefore, our results do not support the contention that increased brain QUIN levels per se are involved in the pathogenesis of HE. C1 UNIV LUND HOSP,DEPT CLIN PHARMACOL,S-22185 LUND,SWEDEN. GOTHENBURG UNIV,DEPT THORAC SURG,GOTHENBURG,SWEDEN. NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. NR 28 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1995 VL 65 IS 5 BP 2235 EP 2240 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TA742 UT WOS:A1995TA74200040 PM 7595512 ER PT J AU GRANGE, E DEUTSCH, J SMITH, QR CHANG, M RAPOPORT, SI PURDON, AD AF GRANGE, E DEUTSCH, J SMITH, QR CHANG, M RAPOPORT, SI PURDON, AD TI SPECIFIC ACTIVITY OF BRAIN PALMITOYL-COA POOL PROVIDES RATES OF INCORPORATION OF PALMITATE IN BRAIN PHOSPHOLIPIDS IN AWAKE RATS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE PALMITATE INCORPORATION; ACYLCOA; BRAIN; PHOSPHOLIPID METABOLISM; RAT; FATTY ACIDS ID FREE FATTY-ACIDS; DENSITY LIPOPROTEIN RECEPTOR; ACYL-COENZYME-A; PROTEIN-SYNTHESIS; SUBCELLULAR-FRACTIONS; PHOSPHATIDIC-ACID; IN-VIVO; ESTERS; TRANSPORT; PLASMA AB In vivo rates of palmitate incorporation into brain phospholipids were measured in awake rats following programmed intravenous infusion of unesterified [9,10-H-3] palmitate to maintain constant plasma specific activity. Animals were killed after 2-10 min of infusion by microwave irradiation and analyzed for tracer distribution in brain phospholipid and phospholipid precursor, i.e., brain unesterified palmitate and palmitoyl-CoA, pools. [9,10-H-3]Palmitate incorporation into brain phospholipids was linear with time and rapid, with >50% of brain tracer in choline-containing glycerophospholipids at 2 min of infusion. However, tracer specific activity in brain phospholipid precursor pools was low and averaged only 1.6-1.8% of plasma unesterified palmitate specific activity. Correction for brain palmitoyl-CoA specific activity increased the calculated rate of palmitate incorporation into brain phospholipids (0.52 nmol/s/g) by similar to 60-fold. The results suggest that palmitate incorporation and turnover in brain phospholipids are far more rapid than generally assumed and that this rapid turnover dilutes tracer specific activity in brain palmitoyl-CoA pool owing to release and recycling of unlabeled fatty acid from phospholipid breakdown. RP GRANGE, E (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C-103,BETHESDA,MD 20892, USA. NR 56 TC 61 Z9 61 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1995 VL 65 IS 5 BP 2290 EP 2298 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TA742 UT WOS:A1995TA74200046 PM 7595518 ER PT J AU HILL, RM LEDGERWOOD, EC BRENNAN, SO PU, LP LOH, YP CHRISTIE, DL BIRCH, NP AF HILL, RM LEDGERWOOD, EC BRENNAN, SO PU, LP LOH, YP CHRISTIE, DL BIRCH, NP TI COMPARISON OF THE MOLECULAR-FORMS OF THE KEX2/SUBTILISIN-LIKE SERINE PROTEASES SPC2, SPC3, AND FURIN IN NEUROENDOCRINE SECRETORY VESICLES REVEALS DIFFERENCES IN CARBOXYL-TERMINUS TRUNCATION AND MEMBRANE ASSOCIATION SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE PROHORMONE CONVERTASES; PROHORMONE PROCESSING; NEUROENDOCRINE; ADRENAL MEDULLA; PITUITARY ID MEDULLARY CHROMAFFIN GRANULES; PROCESSING ENDOPEPTIDASE; KEX2-RELATED PROTEASES; HORMONE BIOSYNTHESIS; SUBTILISIN FAMILY; INTERMEDIATE LOBE; CELL-LINE; PROHORMONE; IDENTIFICATION; PITUITARY AB The molecular forms and membrane association of SPC2, SPC3, and furin were investigated in neuroendocrine secretory vesicles from the anterior, intermediate, and neural lobes of bovine pituitary and bovine adrenal medulla. The major immunoreactive form of SPC2 was the full-length enzyme with a molecular mass of 64 kDa. The major immunoreactive form of SPC3 was truncated at the carboxyl terminus and had a molecular mass of 64 kDa. Full-length 86-kDa SPC3 with an intact carboxyl terminus was found only in bovine chromaffin granules. Immunoreactive furin was also detected in secretory vesicles. The molecular masses of 80 and 76 kDa were consistent with carboxyl-terminal truncation of furin to remove the transmembrane domain. All three enzymes were distributed between the soluble and membrane fractions of secretory vesicles although the degree of membrane association was tissue specific and, in the case of SPC3, dependent on the molecular form of the enzyme. Significant amounts of membrane-associated and soluble forms of SPC2, SPC3, and furin were found in pituitary secretory vesicles, whereas the majority of the immunoreactivity in chromaffin granules was membrane associated. More detailed analyses of chromaffin granule membranes revealed that 86-kDa SPC3 was more tightly associated with the membrane fraction than the carboxyl terminus-truncated 64-kDa form. C1 UNIV AUCKLAND,SCH BIOL SCI,AUCKLAND,NEW ZEALAND. CHRISTCHURCH HOSP,MOLEC PATHOL LAB,CHRISTCHURCH,NEW ZEALAND. NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. RI Christie, David/C-8065-2009; Birch, Nigel/H-2498-2011; OI Birch, Nigel/0000-0002-8417-3587; Ledgerwood, Elizabeth/0000-0002-4956-6043 NR 53 TC 33 Z9 33 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1995 VL 65 IS 5 BP 2318 EP 2326 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TA742 UT WOS:A1995TA74200049 PM 7595521 ER PT J AU DUTTON, EK UHM, CS SAMUELSSON, SJ SCHAFFNER, AE FITZGERALD, SC DANIELS, MP AF DUTTON, EK UHM, CS SAMUELSSON, SJ SCHAFFNER, AE FITZGERALD, SC DANIELS, MP TI ACETYLCHOLINE-RECEPTOR AGGREGATION AT NERVE-MUSCLE CONTACTS IN MAMMALIAN CULTURES - INDUCTION BY VENTRAL SPINAL-CORD NEURONS IS SPECIFIC TO AXONS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE NEUROMUSCULAR JUNCTION; ACH RECEPTOR; SKELETAL MUSCLE; SYNAPSE; SPINAL CORD NEURON; CELL CULTURE; AXON; DENDRITE ID DEVELOPING NEUROMUSCULAR-JUNCTIONS; MICROTUBULE-ASSOCIATED PROTEINS; NEWLY FORMED SYNAPSES; RAT MYOTUBES; BASAL LAMINA; SKELETAL-MUSCLE; PERICELLULAR PROTEOLYSIS; SYNAPTIC ULTRASTRUCTURE; MONOCLONAL-ANTIBODIES; PLASMINOGEN-ACTIVATOR AB We used a novel mammalian coculture system to study ACh receptor (AChR) redistribution and synaptic structure at nerve-muscle contacts, Ventral spinal cord (VSC) neurons were plated on cultures containing extensive myotubes but few fibroblasts, Neurite-induced redistribution of AChRs occurred within 6 hr after plating neurons and was maximal between 36-48 hr, This AChR redistribution appeared in two patterns: (1) AChR density at sites directly apposed to the neurite where neurites crossed preexisting AChR patches was sharply reduced, (2) Newly aggregated AChRs formed swaths lateral to the neurite path. VSC neurons induced more AChR aggregation than hippocampal, superior cervical ganglion and dorsal root ganglion neurons. The 43 and 58 kDa postsynaptic proteins were colocalized with AChR-enriched domains in all VSC neurite-induced aggregates whereas the colocalization of laminin was variable. Electron microscopy of regions with neurite-induced AChR aggregation showed postsynaptic membrane specializations characteristic of developing synapses and, in older cultures, features of more mature synaptic structure, Thus, the coculture system is useful for studying early stages of neuromuscular junction (NMJ) formation. Neurites in these cocultures were identified as axons or dendrites by morphological criteria and by their immunoreactivity for synaptophysin and phosphorylated heavy neurofilament subunits or for microtubule associated protein 2 (MAP2), respectively, Axons showed a 10-fold higher induction of AChR aggregation than did dendrites, Thus, at least one essential signaling molecule necessary for the induction-of AChR aggregation at sites of interaction with muscle appears to be expressed in a polarized fashion in developing VSC neurons. C1 NHLBI,BIOCHEM GENET LAB,BETHESDA,MD 20892. NINCDS,NEUROPHYSIOL LAB,BETHESDA,MD 20892. NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. NR 76 TC 25 Z9 26 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV PY 1995 VL 15 IS 11 BP 7401 EP 7416 PG 16 WC Neurosciences SC Neurosciences & Neurology GA TF264 UT WOS:A1995TF26400039 PM 7472493 ER PT J AU Schaffner, AE Barker, JL Stenger, DA Hickman, JJ AF Schaffner, AE Barker, JL Stenger, DA Hickman, JJ TI Investigation of the factors necessary for growth of hippocampal neurons in a defined system SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE neuronal culture; hippocampus; rat embryo; X-ray photoelectron spectroscopy; surface; serum-free medium; protein adsorption ID COPLANAR MOLECULAR ASSEMBLIES; SERUM-FREE; CULTURE; MONOLAYERS; SURFACES; CELLS; FIBRONECTIN; ATTACHMENT; OUTGROWTH; GUIDANCE AB We have developed an in vitro system that combines the use of a defined medium with a chemically defined surface for the differentiation of embryonic rat hippocampal neurons. Cells were grown on silica substrates modified with two chemically distinct molecules: poly-D-lysine and an amine-containing organosilane. Cells were dissociated by mechanical or enzymatic methods and grown in serum-containing versus serum-free medium on these surfaces. Our results demonstrate that optimal survival and growth in serum-free medium occurs on the artificial surfaces. X-ray photoelectron spectroscopy (XPS) was used to analyze the surfaces both before and after cell culture. In addition, surface properties such as elemental composition, the initial thickness of the substrate material, and the thickness of material deposited during the course of cell culture were quantified after cell removal. Taken together, the results from the cell culture and surface analysis demonstrate that the media, proteins deposited from the media onto the surface, surface composition, and properties intrinsic to neuronal membranes all interact in a complex fashion to determine whether or not the cells will adhere and survive in culture. In particular,the role of material deposited from the medium onto the culture substratum may be more important than has been previously appreciated. This system allows for the study of neuronal differentiation in a well-defined environment. C1 USN,RES LAB,CTR BIOMOLEC SCI & ENGN,WASHINGTON,DC 20375. SCI APPLICAT INT CORP,MCLEAN,VA 22102. RP Schaffner, AE (reprint author), NATL INST HLTH,NINDS,NEUROPHYSIOL LAB,BLDG 36,ROOM 2C02,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NICHD NIH HHS [R0I-HD31457-2] NR 35 TC 63 Z9 64 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD NOV PY 1995 VL 62 IS 1-2 BP 111 EP 119 DI 10.1016/0165-0270(95)00063-1 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TL549 UT WOS:A1995TL54900015 PM 8750092 ER PT J AU MAHER, F AF MAHER, F TI IMMUNOLOCALIZATION OF GLUT1 AND GLUT3 GLUCOSE TRANSPORTERS IN PRIMARY CULTURED NEURONS AND GLIA SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE MONOSACCHARIDE TRANSPORT PROTEINS; IMMUNOFLUORESCENCE; COCULTURE ID MICROTUBULE-ASSOCIATED PROTEIN-2; CEREBELLAR GRANULE CELL; GENE-EXPRESSION; HIPPOCAMPAL-NEURONS; XENOPUS OOCYTES; SCHWANN-CELLS; BRAIN; ISOFORMS; GALACTOCEREBROSIDE; OLIGODENDROCYTES AB Immunofluorescence analysis was used to study the cellular localization of glucose transporters 1 and 3 (GLUT1 and GLUT3) in primary rat neuronal and glial cultures. In primary cultured cerebellar granule neurons and cortical neurons, GLUT3 was detected in a pattern consistent with a generalized cell surface distribution. GLUT3 distribution corresponded most closely with the neural cell adhesion molecule (NCAM), and showed overlapping but distinct distributions compared to synaptophysin, microtubule-associated protein 2 (MAP2), neurofilament protein, and growth-associated protein (GAP43). Culture of neurons in the presence of glia did not alter the cellular localization of GLUT3. GLUT1 was detectable in primary cerebellar granule neurons both at the cell surface and in the cytoplasm, and appeared decreased in neurons cocultured with glia. GLUT1, but not GLUT3, was detected in glial fibrillary acidic protein (GFAP)-positive astrocytes present in mixed neuronal-glial cultures derived from cerebellum and cerebral cortex, as well as in cortical astrocyte cultures. GLUT1, but not GLUT3, was also detected in microglia and oligodendrocytes present in these cultures. This study indicates a generalized cell surface expression of the glucose transporters expressed in neurons and glia, rather than selective targeting to different cellular domains or subcellular locations. (C) 1995 Wiley-Liss, Inc. C1 NIDDK,BETHESDA,MD. NR 38 TC 42 Z9 42 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV 1 PY 1995 VL 42 IS 4 BP 459 EP 469 DI 10.1002/jnr.490420404 PG 11 WC Neurosciences SC Neurosciences & Neurology GA TC837 UT WOS:A1995TC83700003 PM 8568932 ER PT J AU GILMAN, AL SLOAND, E WHITE, JG SACHER, R AF GILMAN, AL SLOAND, E WHITE, JG SACHER, R TI A NOVEL HEREDITARY MACROTHROMBOCYTOPENIA SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE PLATELET; THROMBOCYTOPENIA; HEARING LOSS; HEREDITY; GLYCOPHORIN ID BERNARD-SOULIER PLATELETS; LEUKOCYTE INCLUSIONS; MONOCLONAL-ANTIBODY; MEMBRANE SYSTEMS; GLYCOPROTEIN-IB; THROMBOCYTOPENIA; NEPHRITIS; COLLAGEN; DEAFNESS; DISEASE AB Purpose: A family is described in which macrothrombocytopenia and hearing loss are transmitted in an autosomal-dominant fashion. Patients and Methods: Several members of the family were studied extensively. Review of blood smears, coagulation studies, platelet function testing, and electron microscopy were performed. Platelet membrane glycoproteins were examined using flourescein-conjugated antibodies and flow cytometry. Results: Platelet counts ranged from 50,000 to 123,000/mu l. Both mean platelet diameter and volume were increased. No leukocyte inclusions were noted by light or electron microscopy. Platelet aggregation was normal with adenosine diphosphate (ADP), collagen, and ristocetin but diminished with epinephrine and arachidonic acid. Flow cytometry showed normal platelet membrane glycoproteins and the unusual expression of glycophorin A on 40-60% of the giant platelets. Conclusions: This family's syndrome of macrothrombocytopenia and late-onset hearing loss appears to represent a novel giant platelet disorder. The expression of glycophorin A suggests disordered megakaryocytopoiesis with the early release of immature platelets. C1 GEORGETOWN UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC. GEORGETOWN UNIV,SCH MED,DEPT PATHOL & MED,WASHINGTON,DC. NHLBI,BETHESDA,MD. UNIV MINNESOTA,SCH MED,DEPT LAB MED PATHOL & PEDIAT,MINNEAPOLIS,MN. NR 37 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD NOV PY 1995 VL 17 IS 4 BP 296 EP 305 DI 10.1097/00043426-199511000-00004 PG 10 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA TB916 UT WOS:A1995TB91600004 PM 7583384 ER PT J AU FALLETTA, JM WOODS, GM VERTER, JI BUCHANAN, GR PEGELOW, CH IYER, RV MILLER, ST HOLBROOK, CT KINNEY, TR VICHINSKY, E BECTON, DL WANG, W JOHNSTONE, HS WETHERS, DL REAMAN, GH DEBAUN, MR GROSSMAN, NJ KALINYAK, K JORGENSEN, JH BJORNSON, A THOMAS, MD REID, C AF FALLETTA, JM WOODS, GM VERTER, JI BUCHANAN, GR PEGELOW, CH IYER, RV MILLER, ST HOLBROOK, CT KINNEY, TR VICHINSKY, E BECTON, DL WANG, W JOHNSTONE, HS WETHERS, DL REAMAN, GH DEBAUN, MR GROSSMAN, NJ KALINYAK, K JORGENSEN, JH BJORNSON, A THOMAS, MD REID, C TI DISCONTINUING PENICILLIN PROPHYLAXIS IN CHILDREN WITH SICKLE-CELL-ANEMIA SO JOURNAL OF PEDIATRICS LA English DT Article ID POLYVALENT PNEUMOCOCCAL VACCINE; STREPTOCOCCUS-PNEUMONIAE; ANTIMICROBIAL RESISTANCE; BACTERIAL-INFECTION; WALL POLYSACCHARIDE; ANTIBODY AB Objective: To evaluate the consequences of discontinuing penicillin prophylaxis at 5 years of age in children with sickle cell anemia who had received prophylactic penicillin for much of their lives. Design: Randomized, double-blind, placebo-controlled trial. Setting Eighteen teaching hospitals throughout the United States. Patients: Children with sickle cell anemia (hemoglobin SS or hemoglobin S beta(0)-thalassemia) who had received prophylactic penicillin therapy for at least 2 years immediately before their fifth birthday and had received the 23-valent pneumococcal vaccine between 2 and 3 years of age and again at the time of randomization. Of 599 potential candidates, 400 were randomly selected and followed for an average of 3.2 years. Interventions: After randomization, patients received the study medication twice daily-either penicillin V potassium, 250 mg, or an identical placebo tablet. Patients were either seen in the clinic or contacted every 3 months thereafter for an interval history and dispensing of the study drug. A physical examination was scheduled every 6 months. Main outcome measures: The primary end point was a comparison of the incidence of bacteremia or meningitis caused by Streptococcus pneumoniae in children continuing penicillin prophylaxis versus those receiving the placebo. Results: Six children had a systemic infection caused by 5. pneumoniae, four in the placebo group (2.0%; 95% confidence interval 0.5%, 5.0%) and two in the continued penicillin prophylaxis group (1.0%; 95% confidence interval 0.1%, 3.6%), with a relative risk of 0.5 (95% confidence interval 0.1, 2.7). All invasive isolates were either serotype 6(A or B) or serotype 23F. Four of the isolates were penicillin susceptible, and two (one from each treatment group) were penicillin and multiply antibiotic resistant. Adverse effects of the study drug were reported for three patients (nausea, vomiting, or both), one of whom was in the placebo group. Conclusion: Children with sickle cell anemia who have not had a prior severe pneumococcal infection or a splenectomy and are receiving comprehensive care may safely stop prophylactic penicillin therapy at 5 years of age. Parents must be aggressively counseled to seek medical attention for all febrile events in children with sickle cell anemia. C1 CHILDRENS MERCY HOSP, DEPT PEDIAT, HEMATOL ONCOL SECT, KANSAS CITY, MO 64108 USA. GEORGE WASHINGTON UNIV, CTR BIOSTAT, WASHINGTON, DC USA. UNIV TEXAS, SW MED CTR, DEPT PEDIAT, DALLAS, TX USA. UNIV MIAMI, DEPT PEDIAT, MIAMI, FL 33152 USA. UNIV MISSISSIPPI, DEPT PEDIAT, DIV HEMATOL ONCOL, UNIVERSITY, MS 38677 USA. SUNY HLTH SCI CTR, BROOKLYN, NY USA. CHILDRENS HOSP EASTERN N CAROLINA, DIV PEDIAT HEMATOL ONCOL, GREENVILLE, NC USA. CHILDRENS HOSP OAKLAND, DEPT HEMATOL, OAKLAND, CA 94609 USA. ARKANSAS CHILDRENS HOSP, DIV PEDIAT HEMATOL ONCOL, LITTLE ROCK, AR 72202 USA. ST JUDE CHILDRENS RES HOSP, DIV PEDIAT HEMATOL, MEMPHIS, TN 38105 USA. UNIV ILLINOIS, DEPT PEDIAT, URBANA, IL USA. ST LUKES ROOSEVELT HOSP, CTR SICKLE CELL, NEW YORK, NY USA. NATL CHILDRENS HOSP, MED CTR, DIV HEMATOL ONCOL, WASHINGTON, DC USA. WASHINGTON UNIV, SCH MED, DIV PEDIAT HEMATOL ONCOL, ST LOUIS, MO 63110 USA. COLUMBUS CHILDRENS HOSP, DIV PEDIAT HEMATOL ONCOL, COLUMBUS, OH USA. CHILDRENS HOSP, MED CTR, CINCINNATI COMPREHENS SICKLE CELL CTR, CINCINNATI, OH USA. UNIV TEXAS, HLTH SCI CTR, DEPT PATHOL, HOUSTON, TX USA. JAMES N GAMBLE INST MED RES, DIV IMMUNOL, CINCINNATI, OH USA. NHLBI, SICKLE CELL DIS BRANCH, BETHESDA, MD 20892 USA. RP FALLETTA, JM (reprint author), DUKE UNIV, MED CTR, DUKE COMPREHENS SICKLE CELL CTR, DIV PEDIAT HEMATOL ONCOL, BOX 2916, DURHAM, NC 27710 USA. NR 25 TC 93 Z9 95 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 1995 VL 127 IS 5 BP 685 EP 690 DI 10.1016/S0022-3476(95)70154-0 PG 6 WC Pediatrics SC Pediatrics GA TD931 UT WOS:A1995TD93100003 PM 7472817 ER PT J AU IVY, SP MACKALL, CL GORE, L GRESS, RE HARTLEY, A AF IVY, SP MACKALL, CL GORE, L GRESS, RE HARTLEY, A TI DEMODICIDOSIS IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA - AN OPPORTUNISTIC INFECTION OCCURRING WITH IMMUNOSUPPRESSION SO JOURNAL OF PEDIATRICS LA English DT Note ID DEMODEX-FOLLICULORUM AB We report demodicidosis in 11 children with acute lymphoblastic leukemia and a mildly pruritic, erythematous papular dermatitis that developed in areas rich in sebaceous glands. Demodex eruptions were safely and effectively treated with 5% permethrin. Proliferation of commensal parasites of the skin, Demodex folliculorum and Demodex brevis may be an opportunistic infection of the skin in the immunocompromised host; the expected abrogation of cell-mediated immunity secondary to lymphocyte depletion predisposes some children given chemotherapy for leukemia to mite proliferation. C1 CHILDRENS NATL MED CTR, DEPT PEDIAT, HEMATOL ONCOL SECT, WASHINGTON, DC 20010 USA. CHILDRENS NATL MED CTR, DEPT PEDIAT, DERMATOL SECT, WASHINGTON, DC 20010 USA. GEORGE WASHINGTON UNIV, SCH MED & HLTH SCI, WASHINGTON, DC 20052 USA. NCI, DIV CANC BIOL DIAG & CTR, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. RP IVY, SP (reprint author), CHILDRENS NATL MED CTR, DEPT HEMATOL ONCOL, 111 MICHIGAN AVE NW, WASHINGTON, DC 20010 USA. NR 10 TC 35 Z9 37 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 1995 VL 127 IS 5 BP 751 EP 754 DI 10.1016/S0022-3476(95)70168-0 PG 4 WC Pediatrics SC Pediatrics GA TD931 UT WOS:A1995TD93100017 PM 7472831 ER PT J AU CHEN, H LI, H CHUANG, DM AF CHEN, H LI, H CHUANG, DM TI ROLE OF 2ND-MESSENGERS IN AGONIST UP-REGULATION OF 5-HT2A(5-HT2) RECEPTOR-BINDING SITES IN CEREBELLAR GRANULE NEURONS - INVOLVEMENT OF CALCIUM INFLUX AND A CALMODULIN-DEPENDENT PATHWAY SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RAT CEREBRAL-CORTEX; PHOSPHOLIPASE-C; HOMOLOGOUS DESENSITIZATION; PHOSPHOINOSITIDE TURNOVER; ARACHIDONIC-ACID; 5-HT2 RECEPTORS; CELLS; EXPRESSION; INHIBITOR; SYSTEM AB The present study was undertaken to examine the involvement of 5-HT2A receptor-mediated second messengers in the agonist-induced up-regulation of 5-HT2A receptors in cerebellar granule cells. Stimulation of these cells with a 5-HT2A/5-HT2C agonist, (+/-)-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane for 16 hr resulted in a marked increase in [H-3]ketanserin binding to 5-HT2A receptors in intact cells. (+/-)-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane up-regulated, but not basal levels of 5-HT2A binding sites, were largely attenuated by actinomycin D and cycloheximide, suggesting an essential role for de novo RNA and protein synthesis in this up-regulation process. This receptor up-regulation was 5-HT2A receptor-mediated but was unaffected by short-term pretreatment with phorbol dibutyrate to attenuate (+/-)-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane-induced phosphoinositide hydrolysis or by treatment with staurosporine to inhibit protein kinase C. In contrast, blockade of Ca2+ channels by LaCl3 or SK&F 96365 and depletion of extracellular Ca2+ by EGTA preferentially decreased the upregulated 5-HT2A receptor levels, suggesting a role of Ca2+ influx in the receptor up-regulation. The (+/-)-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane up-regulation was also prevented by inhibitors of calmodulin, calmidazolium and W-7. Moreover, the effect of (+/-)-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane was blocked by KN-62, a selective Ca2+/calmodulin kinase inhibitor and by H-7 and staurosporine at concentrations high enough to be nonselective for a specific type of protein kinase. Taken together, these results strongly suggest that agonist-induced up-regulation of 5-HT2A receptors requires receptor-mediated Ca2+ influx and a CaM-activated pathway, possibly involving Ca2+/CaM kinase activation. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BETHESDA,MD 20892. NR 35 TC 20 Z9 21 U1 0 U2 2 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 NOV PY 1995 VL 275 IS 2 BP 674 EP 680 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TE743 UT WOS:A1995TE74300020 PM 7473154 ER PT J AU POPIK, P LAYER, RT FOSSOM, LH BENVENISTE, M GETERDOUGLASS, B WITKIN, JM SKOLNICK, P AF POPIK, P LAYER, RT FOSSOM, LH BENVENISTE, M GETERDOUGLASS, B WITKIN, JM SKOLNICK, P TI NMDA ANTAGONIST PROPERTIES OF THE PUTATIVE ANTIADDICTIVE DRUG, IBOGAINE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INDUCED LOCOMOTOR STIMULATION; MORPHINE-TOLERANCE; RECEPTOR COMPLEX; BEHAVIORAL SENSITIZATION; PARASAGITTAL ZONES; RAPID TOLERANCE; BINDING-SITES; D-SERINE; MK-801; MICE AB Both anecdotal reports in humans and preclinical studies indicate that ibogaine interrupts addiction to a variety of abused substances including alcohol, opiates, nicotine and stimulants. Based on the similarity of these therapeutic claims to recent preclinical studies demonstrating that N-methyl-D-aspartate (NMDA) antagonists attenuate addiction-related phenomena, we examined the NMDA antagonist properties of ibogaine. Pharmacologically relevant concentrations of ibogaine produce a voltage-dependent block of NMDA receptors in hippocampal cultures (K-i, 2.3 mu M at -60 mV). Consistent with this observation, ibogaine competitively inhibits [H-3]1-[1-(2-thienyl)-cyclohexyl]piperidine binding to rat forebrain homogenates (K-i, 1.5 mu M) and blocks glutamate-induced cell death in neuronal cultures (IC50, 4.5 mu M). Moreover, at doses previously reported to interfere with drug-seeking behaviors, ibogaine substitutes as a discriminative stimulus (ED(50), 64.9 mg/kg) in mice trained to discriminate the prototypic voltage-dependent NMDA antagonist, dizocilpine (0.17 mg/kg), from saline. Consistent with previous reports, ibogaine reduced naloxone-precipitated jumping in morphine-dependent mice (ED(50), 72 mg/kg). Although pretreatment with glycine did not affect naloxone-precipitated jumping in morphine-dependent mice, it abolished the ability of ibogaine to block naloxone-precipitated jumping. Taken together, these findings link the NMDA antagonist actions of ibogaine to a putative ''antiaddictive'' property of this alkaloid, its ability to reduce the expression of morphine dependence. C1 NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. ADDICT RES CTR,NATL INST DRUG ABUSE,PSYCHOBIOL SECT,DRUG DEV GRP,BALTIMORE,MD. POLISH ACAD SCI,INST PHARMACOL,PL-31343 KRAKOW,POLAND. RI Popik, Piotr/R-5383-2016 OI Popik, Piotr/0000-0003-0722-1263 NR 95 TC 69 Z9 69 U1 0 U2 4 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 NOV PY 1995 VL 275 IS 2 BP 753 EP 760 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TE743 UT WOS:A1995TE74300029 PM 7473163 ER PT J AU ZHANG, L MCBAIN, CJ AF ZHANG, L MCBAIN, CJ TI VOLTAGE-GATED POTASSIUM CURRENTS IN STRATUM ORIENS-ALVEUS INHIBITORY NEURONS OF THE RAT CA1 HIPPOCAMPUS SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID ADULT GUINEA-PIG; K+ CHANNEL; OUTWARD CURRENTS; MAMMALIAN BRAIN; CELLS; CLAMP; CONDUCTANCE; EXPRESSION; SLICES AB 1. Voltage-activated K+ currents mere recorded from visually identified inhibitory interneurones of the CA1 stratum oriens-alveus region in neonatal rat hippocampal slices using outside-out patch and whole-cell voltage clamp techniques. 2. Outward currents comprised both a transient and a sustained component when elicited from a holding potential of -90 mV. Tail current analysis of current reversal potentials showed that outward currents were carried by potassium ions. 3. The transient current, I-A, was activated with a time to peak within 5 ms, inactivated with a time constant of similar to 15 ms at 0 mV and possessed half-activation at -14 mV. Half-inactivation of the transient current occurred at -71 mV. At -90 mV, the transient current recovered from inactivation with a time constant of 142 ms. 4. Activation of currents from a holding potential of -50 mV permitted isolation of the sustained current, I-K. In Ca2+-free conditions the sustained current showed rapid activation, reaching about 80% of its maximum within 1.5 ms, and showed little inactivation during Is depolarizing steps. The majority of sustained outward currents showed no voltage-dependent inactivation. In similar to 20% of cells, a slow time-dependent inactivation of the sustained current was observed, suggesting the presence of a second type of sustained current in these cells. 5. A Ca2+-dependent K+ current comprised a significant portion of the total sustained current; this current was activated at voltages positive to -30 mV and showed no time-dependent inactivation over a 1 s depolarizing step. This current component was removed in Ca2+-free conditions or by iberiotoxin. 6. Low concentrations of 4-AP (50 mu m) attenuated both the transient and sustained current components recorded in a Ca2+-free solution. Higher concentrations of 4-AP (<10 mM) were without further effect on the sustained current but completely blocked the transient current with an IC50 of 1.8 mM. TEA blocked the sustained current with an IC50 of 7.9 mM without significantly reducing the transient current. Both current components were resistant to dendrotoxin (500 nM). C1 NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,CELLULAR & SYNAPT PHYSIOL UNIT,BETHESDA,MD 20892. NR 34 TC 57 Z9 58 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV 1 PY 1995 VL 488 IS 3 BP 647 EP 660 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA TG262 UT WOS:A1995TG26200009 PM 8576855 ER PT J AU ZHANG, L MCBAIN, CJ AF ZHANG, L MCBAIN, CJ TI POTASSIUM CONDUCTANCES UNDERLYING REPOLARIZATION AND AFTERHYPERPOLARIZATION IN RAT CA1 HIPPOCAMPAL INTERNEURONS SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID AFTER-HYPERPOLARIZATION; PYRAMIDAL CELLS; ORIENS-ALVEUS; NEURONS; CHANNELS; APAMIN; CURRENTS; BINDING; INVITRO; REGION AB 1. The roles of multiple potassium conductances underlying action potential repolarization and after-hyperpolarization (AHP) in visually identified st. oriens-alveus (st.O-A) inhibitory interneurones of neonatal rat CA1 hippocampal slices were determined using whole-cell patch clamp techniques. 2. 4-Aminopyridine dose-dependently prolonged the action potential repolarization. The effects of 4-AP persisted in Ca2+-free conditions. Action potentials evoked from hyper polarized potentials possessed an increased rate of repolarization. These data suggest an involvement of the rapidly activating transient current, I-A, in spike repolarization. 3. Action potential duration was increased in the presence of Ca2+-free, Cd2+-containing solution, iberiotoxin or 1 mM TEA. The fast component of the AHP was attenuated by these agents suggesting that the Ca2+-activated K+ conductance, I-C, underlies both the spike repolarization and fast AHP. 4. In Ca2+-free conditions, TEA (>1 mM) dose-dependently prolonged the action potential duration by blocking a late conductance in action potential repolarization, suggesting a role for the sustained current, I-K. 5. The slow AHP was attenuated by Ca2+ free medium, apamin or the Ca2+ chelator EGTA, suggesting a role for the Ca2+-activated K+ conductance, I-AHP. 6. We conclude that action potential repolarization and AHP of st. O-A interneurones result from the activation of pharmacologically distinct, temporally overlapping potassium conductances. These findings are discussed with reference to the voltage clamp data presented in the preceding manuscript. C1 NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,CELLULAR & SYNAPT PHYSIOL UNIT,BETHESDA,MD 20892. NR 27 TC 147 Z9 147 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV 1 PY 1995 VL 488 IS 3 BP 661 EP 672 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA TG262 UT WOS:A1995TG26200010 PM 8576856 ER PT J AU Monaco, R Chen, JM Friedman, FK BrandtRauf, P Chung, D Pincus, MR AF Monaco, R Chen, JM Friedman, FK BrandtRauf, P Chung, D Pincus, MR TI Structural effects of the binding of GTP to the wild-type and oncogenic forms of the ras-gene-encoded p21 proteins SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE oncogenic p21 proteins; molecular dynamics; GTP; changes in conformation; effector domains ID AMINO-ACID-RESIDUES; RAS-P21 PROTEIN; GAP; DOMAIN; IDENTIFICATION; MATURATION; INTERACTS; MUTANTS; REGION AB Molecular dynamics calculations have been performed to determine the average structures of ras-gene-encoded p21 proteins bound to GTP, i.e., the normal (wild-type) protein and two oncogenic forms of this protein, the Val 12- and Leu 61-p21 proteins. We find that the average structures for all of these proteins exhibit low coordinate fluctuations (which are highest for the normal protein), indicating convergence to specific structures. From previous dynamics calculations of the average structures of these proteins bound to GDP, major regional differences were found among these proteins [Monaco et nl. (1995), J. Protein Chem., in press]. We now find that the average structures of the oncogenic proteins are more similar to one another when the proteins are bound to GTP than when they are bound to GDP [Monaco er al. (1995), J. Protein Chem., in press]. However, they still differ in structure at specific amino acid residues rather than in whole regions, in contradistinction to the results found for the p21-GDP complexes. Two exceptions are the regions 25-32, in an cu-helical region, and 97-110. The two oncogenic (Val 12- and Leu 61-) proteins have similar structures which differ significantly in the region of residues 97-110. This region has recently been identified as being critical in the interaction of p21 with kinase target proteins. The differences in structure between the oncogenic proteins suggest the existence of more than one oncogenic form of the p21 protein that can activate different signaling pathways. C1 VET AFFAIRS MED CTR,DEPT PATHOL & LAB MED,BROOKLYN,NY 11209. NYU,DEPT CHEM,NEW YORK,NY 10003. SUNY HLTH SCI CTR,DEPT PATHOL,BROOKLYN,NY 11203. DUPONT AGR PROD,STINE HASKELL RES CTR,NEWARK,DE 19714. NIH,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. COLUMBIA UNIV,COLL PHYS & SURG,DIV ENVIRONM SCI,NEW YORK,NY 10016. LONG ISL UNIV,DEPT CHEM,BROOKLYN,NY 11201. RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [CA 42500] NR 32 TC 17 Z9 17 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD NOV PY 1995 VL 14 IS 8 BP 721 EP 730 DI 10.1007/BF01886911 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TM175 UT WOS:A1995TM17500010 PM 8747433 ER PT J AU PANDO, JA GOURLEY, MF WILDER, RL CROFFORD, LJ AF PANDO, JA GOURLEY, MF WILDER, RL CROFFORD, LJ TI HORMONAL SUPPLEMENTATION AS TREATMENT FOR CYCLICAL RASHES IN PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS SO JOURNAL OF RHEUMATOLOGY LA English DT Note DE SEX HORMONES; ORAL CONTRACEPTIVES; SKIN DISEASES; SLE ID RHEUMATIC DISEASES; SEX-HORMONES; STEROIDS; SLE AB Skin involvement is common in patients with SLE, and in some cases is related to the menstrual period. We describe the clinical course of 3 patients with menstrual related rashes who experienced a significant improvement from their skin disease after the initiation of oral contraceptives. The potential role of hormones in the manifestations of SLE is discussed. RP PANDO, JA (reprint author), NIAMS,BLDG 10,ROOM 9,S 205,BETHESDA,MD 20892, USA. RI Crofford, Leslie/J-8010-2013 NR 16 TC 16 Z9 16 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 NOV PY 1995 VL 22 IS 11 BP 2159 EP 2162 PG 4 WC Rheumatology SC Rheumatology GA TC847 UT WOS:A1995TC84700027 PM 8596162 ER PT J AU FINGER, DR PLOTZ, PH HEYWOOD, G AF FINGER, DR PLOTZ, PH HEYWOOD, G TI MYOSITIS FOLLOWING TREATMENT WITH HIGH-DOSE INTERLEUKIN-2 FOR MALIGNANCY SO JOURNAL OF RHEUMATOLOGY LA English DT Letter C1 NIAMS,BETHESDA,MD. NCI,BETHESDA,MD 20892. RP FINGER, DR (reprint author), WILLIAM BEAUMONT ARMY MED CTR,EL PASO,TX 79920, USA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 1995 VL 22 IS 11 BP 2188 EP 2188 PG 1 WC Rheumatology SC Rheumatology GA TC847 UT WOS:A1995TC84700038 PM 8596171 ER PT J AU JEWELL, CM WEBSTER, JC BURNSTEIN, KL SAR, M BODWELL, JE CIDLOWSKI, JA AF JEWELL, CM WEBSTER, JC BURNSTEIN, KL SAR, M BODWELL, JE CIDLOWSKI, JA TI IMMUNOCYTOCHEMICAL ANALYSIS OF HORMONE MEDIATED NUCLEAR TRANSLOCATION OF WILD-TYPE AND MUTANT GLUCOCORTICOID RECEPTORS SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article ID DNA-BINDING; ANTIPEPTIDE ANTIBODIES; PROGESTERONE RECEPTORS; MONOCLONAL-ANTIBODIES; ANTAGONIST RU-486; LOCALIZATION; INVITRO; CELLS; ACTIVATION; MULTIPLE AB We have analyzed structural and functional features of the human glucocorticoid receptor (hGR) for their effects on receptor subcellular distribution. COS 1 cells transiently transfected with wild type and mutant hGR cDNAs were assessed immunocytochemically using well-characterized antipeptide antibodies to the hGR. The effect of administration of steroid hormones (and the antiglucocorticoid RU486) on receptor localization was evaluated. Unliganded wild type receptors expressed in COS 1 cells were predominately cytoplasmic. Addition of glucocorticoids or the glucocorticoid receptor antagonist, RU486, resulted in complete translocation of these receptors into the nucleus whereas non-glucocorticoid steroids or dibutyryl cAMP were not effective in promoting nuclear translocation. Thus, nuclear translocation was specific for steroids capable of high affinity binding to the hGR. To elucidate the potential role of receptor domains in receptor localization, COS 1 cells transiently transfected with various receptor cDNA mutants were analyzed in a similar manner. Translocation of an hGR deletion mutant lacking the majority of the amino terminus (deletion of amino acids 77-262) was identical to the wild type receptor despite the absence of a transactivation domain. Receptors in which the DNA binding domain was either partially or totally deleted showed an impaired capacity to undergo hormone-inducible nuclear translocation. Deletion of the hinge region of the hGR (which also contains part of the nuclear localization signal, NL1) resulted in receptor localization in the cytoplasm. Mutants in the ligand binding domain exhibited two localization phenotypes, exclusively nuclear or cytoplasmic. Receptor mutants truncated after amino acid 550 were found in the nucleus in the presence and absence of hormone consistent with the existence of nuclear localization inhibitory sequences in the ligand binding domain of the receptor. However, a linker insertion mutant (at amino acid 582) which results in a receptor deficient in ligand binding did not undergo nuclear translocation indicating that nuclear localization inhibitory sequences were intact in this mutant. The role of receptor phosphorylation on hormone induced nuclear translocation was also examined. Mouse glucocorticoid receptors which contained mutations of certain hormone inducible phosphorylation sites exhibited translocation properties similar to wild type mGR indicating that these phosphorylation sites on the receptor do not play a major role in hormone inducible nuclear translocation. C1 NIEHS,INTEGRAT BIOL LAB,MOLEC ENDOCRINOL GRP,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CHAPEL HILL,NC 27599. DARTMOUTH COLL SCH MED,DEPT PHYSIOL,LEBANON,NH 03756. NR 29 TC 50 Z9 50 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid. Biochem. Mol. Biol. PD NOV PY 1995 VL 55 IS 2 BP 135 EP 146 DI 10.1016/0960-0760(95)00174-X PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA TJ070 UT WOS:A1995TJ07000001 PM 7495692 ER PT J AU ARNOLD, SF OBOURN, JD JAFFE, H NOTIDES, AC AF ARNOLD, SF OBOURN, JD JAFFE, H NOTIDES, AC TI PHOSPHORYLATION OF THE HUMAN ESTROGEN-RECEPTOR BY MITOGEN-ACTIVATED PROTEIN-KINASE AND CASEIN KINASE-II - CONSEQUENCE ON DNA-BINDING SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article ID CHICKEN PROGESTERONE-RECEPTOR; MOUSE GLUCOCORTICOID RECEPTOR; THYROID-HORMONE RECEPTOR; TRANSCRIPTIONAL ACTIVATION; NUCLEAR RECEPTOR; INTACT-CELLS; IDENTIFICATION; SITES; ESTRADIOL; INVITRO AB We determined the amino acid and radiolabel sequences of tryptic [P-32]phosphopeptides of the purified human estrogen receptor (hER) from MCF-7 cells and Sf9 cells. Serine 118 was identified as a site that was phosphorylated independently of estradiol-binding in MCF-7 cells. Proline is on the carboxy terminus of serine 118, which suggests that the serine-proline may be a consensus phosphorylation site motif for either the mitogen-activated protein (MAP) kinase or p34(cdc2) kinase. MAP kinase selectively phosphorylated the recombinant hER in vitro on serine 118 independent of estradiol-binding, whereas p34(cdc2) did not phosphorylate the hER. We demonstrated previously that serine 167 of the hER was phosphorylated in an estradiol-dependent manner. We therefore compared the consequence of hER phosphorylation at serine 118 by MAP kinase and phosphorylation at serine 167 by casein kinase II on the receptor's affinity for specific DNA binding. The binding of the hER to an estrogen response element was not altered by phosphorylation with MAP kinase at serine 118 but was significantly increased when phosphorylated at serine 167 by casein kinase II. These data suggest that phosphorylation of the hER by MAP kinase(s) pathways may influence receptor action by a mechanism other than the estradiol-dependent phosphorylation of hER by casein kinase II. C1 UNIV ROCHESTER, SCH MED & DENT, DEPT ENVIRONM MED, ROCHESTER, NY 14622 USA. UNIV ROCHESTER, SCH MED & DENT, DEPT BIOPHYS, ROCHESTER, NY 14622 USA. NINDS, LNC, PROT PEPTIDE SEQUENCING FACIL, BETHESDA, MD 20892 USA. FU NICHD NIH HHS [HD 06707]; NIEHS NIH HHS [ES 01247, T32ES 07026] NR 40 TC 83 Z9 85 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD NOV PY 1995 VL 55 IS 2 BP 163 EP 172 DI 10.1016/0960-0760(95)00177-2 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA TJ070 UT WOS:A1995TJ07000004 PM 7495695 ER PT J AU Montoya, ID Hess, JM Preston, KL Gorelick, DA AF Montoya, ID Hess, JM Preston, KL Gorelick, DA TI A model for pharmacological research-treatment of cocaine dependence SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE clinical trials; cocaine; dependence; pharmacotherapy; model ID METHADONE-MAINTAINED PATIENTS; LONGITUDINAL DATA; DESIPRAMINE; AMANTADINE; TRIALS AB Major problems for research on pharmacological treatments for cocaine dependence are lack of comparability of results from different treatment research programs and poor validity and/or reliability of results. Double-blind, placebo-controlled, random assignment, experimental designs, using standard intake and assessment procedures help to reduce these problems. Cessation or reduction of drug use and/or craving, retention in treatment, and medical and psychosocial improvement are some of the outcome variables collected in treatment research programs. A model to be followed across different outpatient clinical trials for pharmacological treatment of cocaine dependence is presented here. This model represents an effort to standardize data collection to make results more valid and comparable. RP Montoya, ID (reprint author), NIDA,DIV INTRAMURAL RES,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural NIH HHS [Z99 DA999999] 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 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD NOV-DEC PY 1995 VL 12 IS 6 BP 415 EP 421 DI 10.1016/0740-5472(95)02017-9 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA TM346 UT WOS:A1995TM34600003 PM 8749725 ER PT J AU LEONARD, HL MEYER, MC SWEDO, SE RICHTER, D HAMBURGER, SD ALLEN, AJ RAPOPORT, JL TUCKER, E AF LEONARD, HL MEYER, MC SWEDO, SE RICHTER, D HAMBURGER, SD ALLEN, AJ RAPOPORT, JL TUCKER, E TI ELECTROCARDIOGRAPHIC CHANGES DURING DESIPRAMINE AND CLOMIPRAMINE TREATMENT IN CHILDREN AND ADOLESCENTS SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE CLOMIPRAMINE; DESIPRAMINE; ELECTROCARDIOGRAM; TRICYCLIC ANTIDEPRESSANTS; SUDDEN DEATH ID OBSESSIVE-COMPULSIVE DISORDER; SUDDEN-DEATH; TRICYCLIC ANTIDEPRESSANT; PLASMA-LEVELS; IMIPRAMINE; 2-HYDROXYDESIPRAMINE; NORTRIPTYLINE; TERFENADINE; NORPRAMIN; CHANNELS AB Objective: With the increased use of tricyclic antidepressants in children, and several reports of several sudden deaths associated with desipramine (DMI) treatment, systematic study of their cardiac effects is indicated. In the present study, DMI's and clomipramine's (CMI) short-term effects on the electrocardiogram (EGG) were compared, as well as the long-term effects of CMI. Method: The ECGs of 47 children and adolescents in treatment trials were examined at baseline, after 5 weeks of CMI and of DMI treatment, and during CMI maintenance (mean duration 24.6 months). Results: At 5 weeks of CMI and of DMI treatment, the heart rate, PR, QRS, and QT-corrected (QT(c)) intervals on ECG were significantly increased from baseline (p<.05); DMI increased PR and QRS intervals more than CMI (p<.05), and CMI increased QT(c) more (p<.05). Tachycardia was the most common change (36%). More patients experienced an incomplete intraventricular conduction delay during DMI treatment (23%, 9/39) than during CMI (2%, 1/47) (p<.05). four patients (9%) acutely developed a prolonged QT(c) during either DMI or CMI. Long-term maintenance ECGs during CMI treatment (n=25) were not significantly different from that at week 5, although some individuals developed or resolved specific ECG changes. Conclusion: CMI and DMI both produced ECG changes typically reported for tricyclic antidepressants, and they differed on specific ECG changes. Changes in ECG measures for individuals from short to long term suggest that continued monitoring is required. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. RP LEONARD, HL (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 52 TC 46 Z9 46 U1 0 U2 0 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 NOV PY 1995 VL 34 IS 11 BP 1460 EP 1468 DI 10.1097/00004583-199511000-00012 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA TB165 UT WOS:A1995TB16500012 PM 8543513 ER PT J AU JENSEN, PS WATANABE, HK RICHTERS, JE CORTES, R ROPER, M LIU, S AF JENSEN, PS WATANABE, HK RICHTERS, JE CORTES, R ROPER, M LIU, S TI PREVALENCE OF MENTAL DISORDER IN MILITARY CHILDREN AND ADOLESCENTS - FINDINGS FROM A 2-STAGE COMMUNITY SURVEY SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE DIAGNOSTIC INTERVIEW SCHEDULE FOR CHILDREN; CHILD BEHAVIOR CHECKLIST; MILITARY CHILDREN; MILITARY FAMILIES; PREVALENCE; MENTAL DISORDER; PSYCHOPATHOLOGY ID FAMILY SYNDROME; POPULATION; RISK AB Objective: Because previous reports have suggested that children of military families are at greater risk for psychopathology, this study examines the levels of psychopathology in an epidemiological community sample of military children all living on a military post. Method: Standardized psychopathology rating scales and a structured diagnostic interview (the Diagnostic interview Schedule for Children [DISC], version 2.1) were used in a multimethod, multistage survey; 294 six- to seventeen-year-old military children and their parents participated in the study. Results: Parent- and child-administered structured DSM-III-R DISC interviews indicated that children's levels of psychopathology were at levels consistent with studies of other normal samples. In addition, parents' and children's symptom checklist ratings of children were at national norms, as were parents' ratings of their own symptoms. Conclusions: Overall results do not support the notion that levels of psychopathology are greatly increased in military children. Further studies of military families should address the effects of rank and socioeconomic status, housing, and the current impact of life stressors on the parents as well as the children, in order to avoid drawing erroneous conclusions about parts or all of the military community. C1 WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT MIL PSYCHIAT,DIV NEUROPSYCHIAT,WASHINGTON,DC 20307. NIMH,DIV EPIDEMIOL & SERV RES,EPIDEMIOL & PSYCHOPATHOL RES BRANCH,ROCKVILLE,MD 20857. RP JENSEN, PS (reprint author), NIMH,DIV CLIN & TREATMENT RES,CHILD & ADOLESCENT DISORDERS RES BRANCH,ROOM 18C-17,ROCKVILLE,MD 20857, USA. OI Richters, John/0000-0002-6780-1828; Jensen, Peter/0000-0003-2387-0650 NR 23 TC 60 Z9 61 U1 3 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 1995 VL 34 IS 11 BP 1514 EP 1524 DI 10.1097/00004583-199511000-00019 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA TB165 UT WOS:A1995TB16500019 PM 8543520 ER PT J AU VANHORN, L BUJNOWSKI, M SCHWABA, J MATHIEUHARRIS, M DONATO, K CLEEMAN, J AF VANHORN, L BUJNOWSKI, M SCHWABA, J MATHIEUHARRIS, M DONATO, K CLEEMAN, J TI DIETITIANS CONTRIBUTIONS TO CHOLESTEROL EDUCATION - A DECADE OF PROGRESS SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Editorial Material ID PHYSICIAN C1 AMER DIETET ASSOC,HLTH CARE FINANCING TEAM,CHICAGO,IL. NHLBI,BETHESDA,MD 20892. RP VANHORN, L (reprint author), NORTHWESTERN UNIV,SCH MED,DEPT PREVENT MED,680 N LAKE SHORE DR,SUITE 1102,CHICAGO,IL 60611, USA. NR 27 TC 3 Z9 3 U1 0 U2 0 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD NOV PY 1995 VL 95 IS 11 BP 1263 EP 1267 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TC872 UT WOS:A1995TC87200006 PM 7594121 ER PT J AU PAHOR, M GURALNIK, JM CORTI, MC FOLEY, DJ CARBONIN, P HAVLIK, RJ AF PAHOR, M GURALNIK, JM CORTI, MC FOLEY, DJ CARBONIN, P HAVLIK, RJ TI LONG-TERM SURVIVAL AND USE OF ANTIHYPERTENSIVE MEDICATIONS IN OLDER PERSONS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID MYOCARDIAL-INFARCTION; CARDIOVASCULAR HEALTH; DRUG-THERAPY; NIFEDIPINE; HYPERTENSION; TRIAL AB OBJECTIVE: To determine whether older persons with hypertension who use specific calcium antagonists and ACE inhibitors have a different risk of mortality than those using beta-blockers. DESIGN: A prospective cohort study continuing from 1988 through 1992. SETTING: Three communities of the Established Populations for Epidemiologic Studies of the Elderly. PARTICIPANTS: Hypertensive participants aged greater than or equal to 71 years (n = 906) who had no evidence of congestive heart failure and who were using either beta-blockers (n = 515), verapamil (n = 77), diltiazem (n = 92), nifedipine (n = 74), or ACE inhibitors (n = 148). Nifedipine was of the short acting variety. MEASUREMENTS: The main outcome measure was all-cause mortality. Age, gender, smoking, HDL-cholesterol, blood pressure, intake of digoxin and diuretics, physical disability, self-perceived health, and comorbid conditions were examined as confounders. RESULTS: During 3538 person-years of follow-up, 188 participants died (53 deaths per 1000 person-years). Compared with beta-blockers, after adjusting for age, gender, comorbid conditions and other health-related factors, the relative risks (95% confidence interval) for mortality associated with use of verapamil, diltiazem, nifedipine, and ACE inhibitors were 0.8 (0.4-1.4), 1.3 (0.8-2.1), 1.7 (1.1-2.7), and 0.9 (0.6-1.4), respectively. The results were unchanged after excluding participants with other potential contraindications to beta-blockers and after stratifying on coronary heart disease and use of diuretics. Higher doses of nifedipine were associated with higher mortality. CONCLUSION: Compared with beta-blockers, use of short acting nifedipine was associated with decreased survival in older hypertensive persons. However, selective factors influencing the use of specific drugs in higher risk patients could not be completely discounted, and final conclusions will depend on clinical trials. C1 CATHOLIC UNIV ROME,DEPT INTERNAL MED & GERIATR,ROME,ITALY. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. NR 49 TC 240 Z9 243 U1 1 U2 2 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 NOV PY 1995 VL 43 IS 11 BP 1191 EP 1197 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA TD463 UT WOS:A1995TD46300001 PM 7594151 ER PT J AU GLOTH, FM SMITH, CE HOLLIS, BW TOBIN, JD AF GLOTH, FM SMITH, CE HOLLIS, BW TOBIN, JD TI FUNCTIONAL IMPROVEMENT WITH VITAMIN-D REPLENISHMENT IN A COHORT OF FRAIL, VITAMIN-D-DEFICIENT OLDER-PEOPLE SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Note ID OSTEOMALACIA; RADIOIMMUNOASSAY; POPULATION; SUNLIGHT; CALCIUM; MUSCLE AB OBJECTIVE: To evaluate functional improvement in a population of frail, homebound older persons with low vitamin D status as vitamin D stores improve. DESIGN: Randomized, controlled intervention study. SETTING: Subjects' homes and a nursing facility in Baltimore, Maryland. PARTICIPANTS: The first 32 subjects (community-dwelling, homebound older subjects from the Johns Hopkins Elder Housecall Program and nursing home residents from the Johns Hopkins Geriatrics Center) entered in a longitudinal study of vitamin D replacement. MEASUREMENTS: Baseline 25-hydroxyvitamin D levels were measured and repeated at least 1 month after therapy with either placebo or vitamin D (ergocalciferol). Subjects were also administered the Frail Elderly Functional Assessment (FEFA) questionnaire, an instrument demonstrated to be reliable, valid, and sensitive to small increments of functional change in this population. MAIN RESULTS: All subjects started with 25-hydroxyvitamin D levels less than 15 ng/mL. Those subjects whose levels improved by at least 3 ng/mL (> assay coefficient of variation) also demonstrated improvement in FEFA score. Regression analysis between change in FEFA score compared with change in 25-hydroxyvitamin D was significant (r = .4; P = .02). CONCLUSIONS: In this cohort of homebound older people, improvement in vitamin D status was associated with functional improvement as measured by the FEFA questionnaire. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV GERIATR MED & GERONTOL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,BAYVIEW MED CTR,BALTIMORE,MD 21218. MED UNIV S CAROLINA,CHILDRENS HOSP,DEPT PEDIAT,CHARLESTON,SC 29425. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP GLOTH, FM (reprint author), UNION MEM HOSP,DEPT MED,DIV GERIATR,201 E UNIV PKWY,BALTIMORE,MD 21218, USA. FU NIA NIH HHS [5 T32 AG00120-03]; NIAMS NIH HHS [AR 38460] NR 28 TC 71 Z9 74 U1 0 U2 6 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 NOV PY 1995 VL 43 IS 11 BP 1269 EP 1271 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA TD463 UT WOS:A1995TD46300012 PM 7594162 ER PT J AU LINDBERG, DAB AF LINDBERG, DAB TI MEDICAL COMPUTING HIGH AND LOW SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Editorial Material RP LINDBERG, DAB (reprint author), NATL LIB MED,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV-DEC PY 1995 VL 2 IS 6 BP 337 EP 341 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA TE152 UT WOS:A1995TE15200001 PM 8581549 ER PT J AU FELSTED, RL GLOVER, CJ HARTMAN, K AF FELSTED, RL GLOVER, CJ HARTMAN, K TI PROTEIN N-MYRISTOYLATION AS A CHEMOTHERAPEUTIC TARGET FOR CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID TYROSINE KINASE-ACTIVITY; HUMAN-COLON-CARCINOMA; MEMBRANE ASSOCIATION; ACYLATION; MYRISTOYLTRANSFERASE; TRANSFORMATION; ENZYMOLOGY; P60SRC; ACID RP FELSTED, RL (reprint author), NCI,DIV BASIC SCI,BIOL CHEM LAB,BLDG 37,RM 5D02,BETHESDA,MD 20892, USA. NR 24 TC 34 Z9 34 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 NOV 1 PY 1995 VL 87 IS 21 BP 1571 EP 1573 DI 10.1093/jnci/87.21.1571 PG 3 WC Oncology SC Oncology GA TB162 UT WOS:A1995TB16200001 PM 7563194 ER PT J AU INSKIP, PD EKBOM, A GALANTI, MR GRIMELIUS, L BOICE, JD AF INSKIP, PD EKBOM, A GALANTI, MR GRIMELIUS, L BOICE, JD TI MEDICAL DIAGNOSTIC X-RAYS AND THYROID-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BREAST-CANCER; RISK; RADIATION; LEUKEMIA; WOMEN; RADIOGRAPHY; EXPOSURE; CHINA AB Background: Diagnostic x rays are the largest man-made source of exposure to ionizing radiation for the general population, Whether there are meaningful cancer risks associated with such exposures is unclear. Most previous case-control studies have relied on recalled histories of x rays, and there is concern that completeness and accuracy of recall might differ between cancer case and control subjects. Purpose: The present study used information recorded prospectively in hospital charts to address the relationship between medical diagnostic x rays and risk of thyroid cancer. Methods: The Swedish Cancer Registry and the Uppsala-Orebro Regional Cancer Registry were used to identify persons with papillary or follicular thyroid cancer diagnosed from January 1, 1980, through December 31, 1992, among residents of the Uppsala Health Care Region. After histopathologic review, there were 484 such case subjects available for study. An equal number of age-, sex-, and county of residence-matched control subjects from the general population were randomly selected on the basis of the Swedish Registry of the Total Population. Lifetime residential histories were compiled, and radiology records were searched at all Swedish hospitals serving regions where study subjects ever maintained an official residence, Approximate radiation doses to the thyroid gland for specific types of x-ray examinations were assigned on the basis of mean values of measurements made in Sweden in 1973-1975 and in the United States in 1970, Odds ratios were used to evaluate the association between diagnostic radiography and risk of thyroid cancer, Results: A total of 3853 medical diagnostic x rays mere ascertained among thyroid cancer case subjects and 4039 among the matched control subjects, There was no tendency for case subjects to have had more of the types of x-ray procedure associated with higher radiation dose to the thyroid gland (i.e., those involving the head or neck area), This finding was true even when analysis was restricted to x rays occurring before 1960, when doses likely were higher than in more recent years, and for examinations occurring in childhood and adolescence, when susceptibility to radiation-induced thyroid cancer is greatest. The relative risk of thyroid cancer was not significantly associated with estimated cumulative dose to the thyroid gland from diagnostic x rays (two-sided P for trend = .80). Conclusion: These data indicate that the risk of thyroid cancer due to medical diagnostic x rays, if any, is very small. C1 UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,S-75185 UPPSALA,SWEDEN. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. NR 36 TC 38 Z9 45 U1 2 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 NOV 1 PY 1995 VL 87 IS 21 BP 1613 EP 1621 DI 10.1093/jnci/87.21.1613 PG 9 WC Oncology SC Oncology GA TB162 UT WOS:A1995TB16200011 PM 7563204 ER PT J AU BYRNE, C SCHAIRER, C WOLFE, J PAREKH, N SALANE, M BRINTON, LA HOOVER, R HAILE, R AF BYRNE, C SCHAIRER, C WOLFE, J PAREKH, N SALANE, M BRINTON, LA HOOVER, R HAILE, R TI MAMMOGRAPHIC FEATURES AND BREAST-CANCER RISK - EFFECTS WITH TIME, AGE, AND MENOPAUSE STATUS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PARENCHYMAL PATTERNS; COMPUTER-PROGRAM; DENSITIES; WOMEN AB Background: Mammographic images from women with a high proportion of epithelial and stromal breast tissues are described as showing high-density parenchymal patterns. Most past studies that noted an increase in breast cancer risk associated with mammographic parenchymal patterns showing high density either 1) lacked information on other breast cancer risk factors, 2) were too small, or 3) included insufficient follow-up time to adequately resolve persisting doubts whether mammographic features are ''independent'' measures of breast cancer risk and not a detection artifact, Purpose: The purpose of this study was twofold: 1) to evaluate the associations between mammographic features and other breast cancer risk factors and 2) to assess effects of mammographic features on breast cancer risk by time, age, and menopause status, Methods: To address these questions, we analyzed detailed information from a large, nested case-control study with 16 years of follow-up, This study used information from both screening and follow-up phases of the Breast Cancer Detection Demonstration Project, a nationwide program that offered annual breast cancer screening for more than 280 000 women from 1973 to 1980, Mammographic features were assessed from the base-line screening mammographic examination for 1880 incident case subjects and 2152 control subjects, Control subjects were randomly selected from women of the same age and race as each case subject, Control subjects attended the same screening center as the case subject and were free of breast cancer at the case subject's date of diagnosis, Odds ratios (ORs) with 95% confidence intervals (CIs) provided estimates of the relative risk of breast cancer, Results: Mammographic features were associated with known breast cancer risk factors, However, the high-density parenchymal pattern effects were independent of family history, age at first birth, alcohol consumption, and benign breast disease, The increased risk for women with Wolfe's two high-density parenchymal patterns, P2 (OR = 3.2; 95% CI = 2.5-4.0) and Dy (OR = 2.9; 95% CI = 2.2-3.9), was explained primarily by measured percent of the breast with dense mammographic appearance, Compared with women with no visible breast density, women who had a breast density of 75% or greater had an almost fivefold increased risk of breast cancer (95% CI = 3.6-7.1), These effects persisted for 10 or more years and were noted for both premenopausal and postmenopausal women of all ages. Conclusions: Of the breast cancer risk factors assessed in the participants, high-density mammographic parenchymal patterns, as measured by the proportion of breast area composed of epithelial and stromal tissue, had the greatest impact on breast cancer risk, Of the breast cancers in this study, 28% were attributable to having 50% or greater breast density. C1 NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,LOS ANGELES,CA 90024. HUTZEL HOSP,DEPT RADIOL,DETROIT,MI 48201. RI Brinton, Louise/G-7486-2015; Byrne, Celia/K-2964-2015 OI Brinton, Louise/0000-0003-3853-8562; Byrne, Celia/0000-0001-8289-4252 NR 39 TC 546 Z9 552 U1 4 U2 15 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 NOV 1 PY 1995 VL 87 IS 21 BP 1622 EP 1629 DI 10.1093/jnci/87.21.1622 PG 8 WC Oncology SC Oncology GA TB162 UT WOS:A1995TB16200012 PM 7563205 ER PT J AU MARTINEZ, RA POINTER, A VEREEN, D MARKS, SF AF MARTINEZ, RA POINTER, A VEREEN, D MARKS, SF TI NATIONAL-MEDICAL-ASSOCIATION-NATIONAL-INSTITUTES-OF-HEALTH WORKSHOP ON VIOLENCE AND THE CONDUCT OF RESEARCH - WORKGROUP PROCEEDINGS, JUNE 1-2, 1994 SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE VIOLENCE; AFRICAN-AMERICAN COMMUNITIES AB The physical, economic, and mental toll caused by violence in the United States has put tremendous pressure on American medical, political, religious, and social institutions. The impact in urban neighborhoods has been especially harrowing, forcing African-American organizations to address this domestic problem with ideas and suggestions unique to their philosophies and collective talents. This article contains general perspectives and commentary from physicians and social science experts who participated in a workshop sponsored by the National Medical Association, the National Institute of Drug Abuse, and the National Institute of Mental Health to discuss topics on violence, its health consequences, and the conduct of research in the African-American community. RP MARTINEZ, RA (reprint author), NIH,5600 FISHERS LANE,RM 18-103,ROCKVILLE,MD 20857, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD NOV PY 1995 VL 87 IS 11 BP 797 EP 802 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TD905 UT WOS:A1995TD90500005 PM 8907813 ER PT J AU HEYES, MP SAITO, K MILSTIEN, S SCHIFF, SJ AF HEYES, MP SAITO, K MILSTIEN, S SCHIFF, SJ TI QUINOLINIC ACID IN TUMORS, HEMORRHAGE AND BACTERIAL-INFECTIONS OF THE CENTRAL-NERVOUS-SYSTEM IN CHILDREN SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE KYNURENINE PATHWAY; NEUROTOXIN; MACROPHAGE; CSF SHUNT; CYTOKINES ID KYNURENINE PATHWAY METABOLISM; HUMAN-IMMUNODEFICIENCY-VIRUS; CEREBROSPINAL-FLUID; RAT-BRAIN; L-TRYPTOPHAN; DISEASE; SERUM; MYELOMENINGOCELE; MACROPHAGES; MENINGITIS AB A potential mechanism that may contribute to neurological deficits following central nervous system infection in children was investigated. Quinolinic acid (QUIN) is a neurotoxic metabolite of the kynurenine pathway that accumulates within the central nervous system following immune activation. The present study determined whether the levels of QUIN are increased in the cerebrospinal fluid of children with infections of the CNS, hydrocephalus, tumors or hemorrhage. Extremely high QUIN concentrations were found in patients with bacterial infections or the CNS, despite treatment with antimicrobial agents. CSF QUIN levels were also elevated to a lesser degree in patients with hydrocephalus or tumors. CSF L-kynurenine levels increased in parallel to the accumulations in QUIN, which is consistent with increased activity of the first enzyme of the kynurenine pathway, indoleamine-2,3-dioxygenase. The CSF levels of neopterin, a marker of immune and macrophage activation, were also increase in patients with infections. The cytokines tumor necrosis factor-ct and interleukin-6 were also detected in some patients' samples, and were highest in patients with infection. These results suggest that QUIN is a sensitive marker of the presence of immune activation within the CNS. Further studies of QUIN as a potential contributor to neurologic dysfunction and neurodegeneration in children with CNS inflammation are warranted. C1 NIMH,NEUROCHEM LAB,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT NEUROSURG,WASHINGTON,DC 20010. RP HEYES, MP (reprint author), NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BLDG 10,ROOM 3D40,BETHESDA,MD 20892, USA. NR 34 TC 40 Z9 42 U1 1 U2 5 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 NOV PY 1995 VL 133 IS 1-2 BP 112 EP 118 DI 10.1016/0022-510X(95)00164-W PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TE600 UT WOS:A1995TE60000016 PM 8583213 ER PT J AU NIMS, RW LUBET, RA AF NIMS, RW LUBET, RA TI INDUCTION OF CYTOCHROME-P-450 IN THE NORWAY RAT, RATTUS-NORVEGICUS, FOLLOWING EXPOSURE TO POTENTIAL ENVIRONMENTAL CONTAMINANTS SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Review ID POLYCHLORINATED-BIPHENYLS PCBS; ARYL-HYDROCARBON HYDROXYLASE; HEPATIC MICROSOMAL-ENZYMES; PERFORMANCE LIQUID-CHROMATOGRAPHY; MONOCLONAL-ANTIBODIES; LIVER-MICROSOMES; MESSENGER-RNAS; DEVELOPMENTAL EXPRESSION; STEROID HYDROXYLATIONS; PHENOBARBITAL-TYPE AB Cytochrome P-450 (CYP) induction (consisting of increases in cellular RNA and protein content and associated catalytic activities) occurs predominantly in the liver, but also in small intestine, lung, kidney, and placenta, of Norway rats (Rattus norvegicus) exposed to certain types of potential environmental contaminants. The specific isoform(s) induced in the rat and the magnitudes of the increases observed depend upon the chemical nature of the xenobiotic. For instance, the predominant isoforms induced by nonhalogenated polycyclic aromatic hydrocarbons, such as petroleum derivatives and coal-tar constituents such as the benzopyrenes and the anthracenes, are those of the CYP1A subfamily. Poly halogenated aromatic hydrocarbons, such as the halogenated dibenzodioxins, dibenzofurans, and biphenyls, may cause the induction of predominantly the CYP1A subfamily, predominantly the CYP2B subfamily, or mixed CYP1A- and CYP2B-type induction, depending upon the halogen substitution pattern. In contrast, the chlorinated hydrocarbon pesticides, such as DDT, dieldrin, chlordane, and mirex, cause almost exclusively the induction of isoforms of the CYP2B (and to a lesser extent the CYP3A) subfamilies. The commonly employed plasticizing agent di-(2-ethylhexyl)phthalate elicits predominantly induction of the CYP4A subfamily. Those xenobiotics that would be expected to be the most pervasive environmental contaminants are typically those that have also been found to cause the most profound CYP induction responses. Such chemicals are extremely lipophilic and tend to accumulate in animal tissues, especially fatty tissues such as the liver. The hepatic CYP induction response to such potential environmental contaminants is typical of the animals' response to lipophilic xenobiotics in general, and serves as a mechanism by which the excretion of such compounds from the body is facilitated. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP NIMS, RW (reprint author), MICROBIOL ASSOCIATES INC,INVITRO TOXICOL,9900 BLACKWELL RD,ROCKVILLE,MD 20850, USA. NR 138 TC 56 Z9 57 U1 1 U2 6 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD NOV PY 1995 VL 46 IS 3 BP 271 EP 292 PG 22 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TE194 UT WOS:A1995TE19400002 PM 7473857 ER PT J AU GONCALVES, LF SHERER, DM ROMERO, R SILVA, M AMUNDSON, GM TREADWELL, MC AF GONCALVES, LF SHERER, DM ROMERO, R SILVA, M AMUNDSON, GM TREADWELL, MC TI PRENATAL SONOGRAPHIC FINDINGS OF AGENESIS OF THE RIGHT AND LEFT PORTAL VEINS AND ASSOCIATED INTRAHEPATIC PORTOSYSTEMIC SHUNTS SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Note ID PATENT DUCTUS VENOSUS; CONGENITAL ABSENCE; VENOUS SHUNT; VENA-CAVA; DIAGNOSIS; ANEURYSM; TRANSPLANTATION; ULTRASOUND; FISTULA; CHILD C1 GEORGETOWN UNIV,MED CTR,DEPT GYNECOL & OBSTET,NICHD,DIV INTRAMURAL,PERINATOL RES FACIL,WASHINGTON,DC 20007. HUTZEL HOSP,DEPT OBSTET & GYNECOL,DETROIT,MI 48201. CHILDRENS HOSP MICHIGAN,DEPT RADIOL,DETROIT,MI 48201. WAYNE STATE UNIV,DETROIT,MI. NR 23 TC 11 Z9 11 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD NOV PY 1995 VL 14 IS 11 BP 849 EP 852 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA TB384 UT WOS:A1995TB38400009 PM 8551551 ER PT J AU KYOSTIO, SRM WONDERLING, RS OWENS, RA AF KYOSTIO, SRM WONDERLING, RS OWENS, RA TI NEGATIVE REGULATION OF THE ADENOASSOCIATED VIRUS (AAV) P-5 PROMOTER INVOLVES BOTH THE P-5 REP BINDING-SITE AND THE CONSENSUS ATP-BINDING MOTIF OF THE AAV REP68 PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSCRIPTION START SITE; LARGE T-ANTIGEN; GENE-EXPRESSION; HUMAN CYTOMEGALOVIRUS; DNA-REPLICATION; MAMMALIAN-CELLS; GENOME; SEQUENCE; COMPLEX; ELEMENT AB Transcript levels from the P-5 promoter of adeno-associated virus type 2 (AAV) are negatively regulated by the AAV Rep78 and Rep68 proteins in the absence of helper virus. We have identified a Rep-responsive negative cis element of the P-5 prompter between the P-5 TATA box and transcription start site by using 5' and 3' deletions of the P-5 promoter fused to the chloramphenicol acetyltransferase gene, This element contains four imperfect GAGC repeats similar to the Rep recognition sequences (RRSs) in the AAV inverted terminal repeats and in the AAV preferred integration locus in chromosome 19. Band shift analyses showed that human 293 cell nuclear extracts containing Rep68 or Rep68/K340H, a putative nucleoside triphosphate (NTP)-binding-site mutant of Rep68, formed Rep-specific complexes with this P-5 RRS DNA. Within the P-5 RRS, mutation of a cytosine at position 273 in the AAV Sequence to guanine abolished Rep68 binding to the DNA. A mutation in the P-5 RRS within a full-length AAV genome, which abolished Rep binding, resulted in a 40 to 50% reduction in the ability of wild-type Rep68 to inhibit the accumulation of P-5 transcripts in vivo, In contrast, the Rep68/K340H mutant was unable to down-regulate this mutated promoter. These results indicate that there are at least two mechanisms involved in the negative regulation of P-5 transcript levels by Rep68; one involves Rep68 binding to the P-5 RRS, and another requires the region of Rep68 containing the consensus NTP-binding motif, Furthermore, our studies of AAV genomes containing mutated RRS- and/or YY1-binding elements suggest that transcription factor YY1 binding to the transcription start site of P-5 interferes with Rep68 repression of the P-5 promoter. C1 NIDDKD,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. NR 58 TC 82 Z9 82 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1995 VL 69 IS 11 BP 6787 EP 6796 PG 10 WC Virology SC Virology GA RZ100 UT WOS:A1995RZ10000022 PM 7474090 ER PT J AU HUANG, MJ ORENSTEIN, JM MARTIN, MA FREED, EO AF HUANG, MJ ORENSTEIN, JM MARTIN, MA FREED, EO TI P6(GAG) IS REQUIRED FOR PARTICLE-PRODUCTION FROM FULL-LENGTH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MOLECULAR CLONES EXPRESSING PROTEASE SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE-LEUKEMIA-VIRUS; ROUS-SARCOMA VIRUS; PFIZER MONKEY VIRUS; OPEN READING FRAME; MATRIX PROTEIN; GAG-POLYPROTEIN; HIV-1 PROTEASE; INTRACELLULAR-TRANSPORT; NUCLEOCAPSID PROTEIN; MUTATIONAL ANALYSIS AB The human immunodeficiency virus type 1 (HIV-1) Gag protein precursor, Pr55(gag), contains at its C-terminal end a proline-rich, 6-kDa domain designated ph. Two functions have been proposed for ph: incorporation of the HIV-1 accessory protein Vpr into virus particles and virus particle production, To characterize the role of ph in the HIV-1 life cycle and to map functional domains within p6, we introduced a number of nonsense and single and multiple amino acid substitution mutations into ph. Following the introduction of the mutations into the full-length HIV-1 molecular clone pNL4-3, the effects on Gag protein expression and processing, virus particle production, and virus infectivity were analyzed. The production of mutant virus particles was also examined by transmission electron microscopy. The results indicate that (i) ph is required for efficient virus particle production from a full-length HIV-1 molecular clone; (ii) a Pro-Thr-Ala-Pro sequence, located between residues 7 and 10 of ph, is critical for virus particle production; (iii) mutations outside the Pro Thr-Ala Pro motif have little or no effect on virus assembly and release; (iv) the ph defect is manifested at a late stage in the budding process; and (v) mutations in ph that severely reduce virion production in HeLa cells also block or significantly delay the establishment of a productive infection in the CEM(12D-7) T-cell line. We further demonstrate that mutational inactivation of the viral protease reverses the ph defect, suggesting a functional linkage between ph and the proteolytic processing of the Gag precursor protein during the budding of progeny virions. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT PATHOL,WASHINGTON,DC 20037. NR 75 TC 337 Z9 341 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1995 VL 69 IS 11 BP 6810 EP 6818 PG 9 WC Virology SC Virology GA RZ100 UT WOS:A1995RZ10000025 PM 7474093 ER PT J AU LU, YL BENNETT, RP WILLS, JW GORELICK, R RATNER, L AF LU, YL BENNETT, RP WILLS, JW GORELICK, R RATNER, L TI A LEUCINE TRIPLET REPEAT SEQUENCE (LXX)(4) IN P6(GAG) IS IMPORTANT FOR VPR INCORPORATION INTO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PARTICLES SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; ROUS-SARCOMA VIRUS; OPEN READING FRAME; VIRAL PROTEIN-R; GAG PROTEIN; PRODUCTIVE INFECTION; MUTATIONAL ANALYSIS; CELLS; EXPRESSION; GENE AB Incorporation of Vpr into human immunodeficiency virus type 1 (HIV-1) virions is mediated by the Gag protein, independently of other viral components. We have coexpressed Vpr and Gag constructs in a vaccinia virus expression system in order to map the region of Gag involved in Vpr packaging. Deletion of the carboxyl-terminal p6 region of Gag impaired the ability of Gag to package Vpr. To confirm the role of p6 in Vpr packaging, Rous sarcoma virus (RSV)-HIV chimeras containing HIV-1 p6 were constructed. Although RSV Gag does not package Vpr into virus particles, a chimera containing HIV-1 p6 is sufficient for Vpr incorporation. To map the region of p6 involved in Vpr packaging, a series of p6 point mutations and deletion mutations was analyzed. Mutations in the N-terminal p6 proline-rich domain, for which preliminary evidence shows a marked decrease in virion incorporated RNA, did not affect Vpr incorporation. Deletion of residues 1 to 31 of HIV-1 p6 did not affect Vpr packaging, but residues 35 to 47, including an (LXX)(4) domain, were required for Vpr incorporation into virus particles. C1 WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MOLEC MICROBIOL,ST LOUIS,MO 63110. PENN STATE UNIV,COLL MED,DEPT IMMUNOL & MICROBIOL,HERSHEY,PA 17033. NCI,FREDERICK CANC RES & DEV CTR,SAIC,AIDS VACCINE PROGRAM,FREDERICK,MD 21701. FU NCI NIH HHS [CA47482]; NIAID NIH HHS [AI24745, AI34736] NR 49 TC 113 Z9 116 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 NOV PY 1995 VL 69 IS 11 BP 6873 EP 6879 PG 7 WC Virology SC Virology GA RZ100 UT WOS:A1995RZ10000034 PM 7474102 ER PT J AU DUENSING, TD FANG, H DORWARD, DW PINCUS, SH AF DUENSING, TD FANG, H DORWARD, DW PINCUS, SH TI PROCESSING OF THE ENVELOPE GLYCOPROTEIN GP160 IN IMMUNOTOXIN-RESISTANT CELL-LINES CHRONICALLY INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID ENDOPROTEOLYTIC CLEAVAGE; TRIMMING GLUCOSIDASE; PARTICLES LACKING; AIDS PATIENTS; PROTEIN; HIV; CD4; INFECTIVITY; TRANSPORT; GLYCOSYLATION AB We describe the isolation and characterization of variant cell lines which are chronically infected with the human immunodeficiency virus (HIV) and resistant to the action of immunotoxins directed against the HIV envelope protein, These variants all produce normal levels of HN proteins, budding virions, and the envelope protein precursor gp160. Two of the variants, 10E and 11E, contain a mutation within the env gene which results in the production of a truncated precursor and altered processing and transport of the protein to the fell surface, Variants B9 and G4 are defective in gp160 cleavage and do not efficiently transport the envelope protein to the cell surface, There are no mutations in the expressed viruses of B9 and G4, These cell lines express higher levels of CD4 protein and mRNA than H9/NL4-3. Thus 10E, 11E, B9, and G4 have escaped immunotoxin action by downmodulating the envelope protein from their cell surfaces, None of these variants produce infectious HIV. Two other immunotoxin-resistant variants, E9-3 and 41-17, produce normal levels of gp160, efficiently transport the cleaved and processed subunits to the cell surface, and secrete infectious HIV. These studies identify alterations in gp160 processing that underscore the importance of the relationship between HIV and the cell that it infects. C1 NIAID,ROCKY MT LABS,MICROSCOPY BRANCH,HAMILTON,MT 59840. RP DUENSING, TD (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,903 S 4TH,HAMILTON,MT 59840, USA. NR 43 TC 5 Z9 5 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 NOV PY 1995 VL 69 IS 11 BP 7122 EP 7131 PG 10 WC Virology SC Virology GA RZ100 UT WOS:A1995RZ10000064 PM 7474132 ER PT J AU LIAO, XB BUCHBERG, AM JENKINS, NA COPELAND, NG AF LIAO, XB BUCHBERG, AM JENKINS, NA COPELAND, NG TI EVI-5, A COMMON SITE OF RETROVIRAL INTEGRATION IN AKXD T-CELL LYMPHOMAS, MAPS NEAR GFI-1 ON MOUSE CHROMOSOME-5 SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; RECOMBINANT INBRED MICE; FOCUS-FORMING VIRUSES; AKR/J MICE; VIRAL INTEGRATION; POLYTROPIC MULVS; TRANSGENIC MICE; DNA; IDENTIFICATION; PROVIRUSES AB We have identified a novel common site of retroviral integration, Evi-5, in AKXD T-cell lymphomas, All proviruses located at Evi-5 are clustered within a 7-kb genomic region and, where determined, are oriented in the same transcriptional direction. Interspecific backcross analysis localized Evi-5 to mouse chromosome 5, where it cosegregated with another common viral integration site, Gfi-l. Gfi-l encodes a novel zinc finger transcription factor whose expression is thought to be important for interleukin-2 signaling. Physical mapping studies showed that Evi-5 is located approximately 18 kb upstream of Gfi-l, and Southern analysis showed that Gfi-l, like Evi-5, is a common integration site in AKXD T-cell tumors. With one exception, Evi-5 and Gfi-l integrations were mutually exclusive, Ten of the tumors with Evi-5 or Gfi-l integrations also harbored viral integrations at other common integration sites causally associated with T-cell disease, These results are consistent with the hypothesis that T-cell lymphomagenesis is a multistep disease and that viral integration at Evi-5 or Gfi-l is causally associated with this disease process. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. OI Buchberg, Arthur/0000-0002-0543-5631 NR 50 TC 36 Z9 36 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 NOV PY 1995 VL 69 IS 11 BP 7132 EP 7137 PG 6 WC Virology SC Virology GA RZ100 UT WOS:A1995RZ10000065 PM 7474133 ER PT J AU CHO, BC SHAUGHNESSY, JD LARGAESPADA, DA BEDIGIAN, HG BUCHBERG, AM JENKINS, NA COPELAND, NG AF CHO, BC SHAUGHNESSY, JD LARGAESPADA, DA BEDIGIAN, HG BUCHBERG, AM JENKINS, NA COPELAND, NG TI FREQUENT DISRUPTION OF THE NF1 GENE BY A NOVEL MURINE AIDS VIRUS-RELATED PROVIRUS IN BXH-2 MURINE MYELOID LYMPHOMAS SO JOURNAL OF VIROLOGY LA English DT Article ID INDUCED IMMUNODEFICIENCY SYNDROME; TERMINAL REPEAT SEQUENCES; B-CELL LINEAGE; LEUKEMIA-VIRUS; DEFECTIVE VIRUS; INBRED STRAINS; T-CELLS; MICE; NEUROFIBROMATOSIS; TYPE-1 AB Evi-2, a common site of viral integration in BXH-2 myeloid lymphomas, is located within a large intron of the Nfl tumor suppressor gene, Viral integration at Evi-5 appears to induce disease by disrupting normal Nfl expression, During our attempts to characterize the nature of the proviruses located at Evi-2, we found that approximately half of the proviruses were defective nonecotropic proviruses (A. M. Buchberg, H. G. Bedigian, N. A. Jenkins, and N. G. Copeland, Mol. Cell, Biol, 10:4658-4666, 1990). This was surprising, since most proviruses characterized at other BXH-2 common integration sites are full-length ecotropic viruses. In the studies described here, we found that this defective provirus carries two large deletions, one in pol and one in env, and is structurally related to another murine retrovirus, the murine AIDS retrovirus. By using oligonucleotide probes specific for this defective provirus, designated MRV, we showed that MRV-related proviruses are carried as endogenous germ line proviruses in most inbred strains, In addition, we identified the endogenous MRV provirus that gives rise to the defective proviruses identified at Evi-2. We present a model that accounts for the positive selection of MRV proviruses at Evi-2, which may allow selective identification of common viral integration sites harboring tumor suppressor genes. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. JACKSON LAB,BAR HARBOR,ME 04609. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107. RI Largaespada, David/C-9832-2014; OI Buchberg, Arthur/0000-0002-0543-5631 FU NCI NIH HHS [CA31102, N01-CO-46000] NR 54 TC 28 Z9 28 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 NOV PY 1995 VL 69 IS 11 BP 7138 EP 7146 PG 9 WC Virology SC Virology GA RZ100 UT WOS:A1995RZ10000066 PM 7474134 ER PT J AU PINCUS, SH COLE, R IRELAND, R MCATEE, F FUJISAWA, R PORTIS, J AF PINCUS, SH COLE, R IRELAND, R MCATEE, F FUJISAWA, R PORTIS, J TI PROTECTIVE EFFICACY OF NONNEUTRALIZING MONOCLONAL-ANTIBODIES IN ACUTE INFECTION WITH MURINE LEUKEMIA-VIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 INFECTION; CORE PROTEIN; RETROVIRUS; CELLS; MICE; ERYTHROLEUKEMIA; IDENTIFICATION; REPLICATION; CHIMPANZEES; IMMUNITY AB We have used an experimental retrovirus infection to study the roles played by different antibodies in resistance to both infection and disease, A molecularly cloned chimeric murine leukemia virus was used to induce acute lethal neurological disease in neonatal mice, A panel of monoclonal antibodies directed against the Gag and Env proteins was tested for protective efficacy, In vitro neutralization assays demonstrated that anti-Env antibodies gave different degrees of neutralization, while no anti-Gag neutralized the virus, In vivo experimental endpoints mere onset of clinical signs and premoribund condition. As expected, different anti-Env antibodies demonstrated different degrees of protection which correlated with their neutralizing abilities. Surprisingly, anti-Gag antibodies directed against both p15 (MA protein) and p30 (CA protein) were also protective, significantly delaying the onset of disease, No protection was seen with either of two control antibodies. The protection with anti-Gag was dose related and time dependent and was also produced viith Fab fragments. Treatment with anti-Gag did not prevent viremia but resulted in a slight slowing in viremia kinetics and decreased levels of virus in the central nervous systems of mice protected from disease, These data indicate that nonneutralizing antiretroviral antibodies can influence the outcome of retroviral disease. The data also suggest functional role for cell surface expression of Gag proteins on murine leukemia virus-infected cells. C1 NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840. NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 36 TC 21 Z9 21 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 NOV PY 1995 VL 69 IS 11 BP 7152 EP 7158 PG 7 WC Virology SC Virology GA RZ100 UT WOS:A1995RZ10000068 PM 7474136 ER PT J AU BROWN, CR NAKAMURA, MS MOSCA, JD HAYWARD, GS STRAUS, SE PERERA, LP AF BROWN, CR NAKAMURA, MS MOSCA, JD HAYWARD, GS STRAUS, SE PERERA, LP TI HERPES-SIMPLEX VIRUS TRANSREGULATORY PROTEIN ICP27 STABILIZES AND BINDS TO 3'-ENDS OF LABILE MESSENGER-RNA SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR VIRUS; IMMEDIATE-EARLY GENE; MESSENGER-RNA; ALPHA PROTEIN-ICP27; POSTTRANSCRIPTIONAL MECHANISM; EQUINE HERPESVIRUS-1; EARLY TRANSCRIPTION; DELETION MUTANTS; TYPE-1 ICP27; EXPRESSION AB Previous work demonstrated that a herpes simplex virus type 1 (HSV-1) immediate-early function upregulates beta interferon but not chloramphenicol acetyltransferase reporter genes driven by the strong simian virus 40 (SV40) or cytomegalovirus promoter-enhancer regions in both transient assays and stable cell lines. The different 3' mRNA stabilization and RNA-processing signals from these two reporter genes appeared to be primarily responsible for this phenomenon. We now report that the HSV-1 ICP27 itself is sufficient to stimulate both steady-state accumulation and increased half-life of beta interferon reporter gene mRNA. Furthermore, the ability to respond directly to cotransfected ICP27 can be transferred to chloramphenicol acetyltransferase reporter genes by replacement of their SV40 derived splicing and poly(A) signals with the 3' AU-rich and poly(A) RNA-processing signals from the normally highly labile beta interferon and c-myc mRNA species. ICP27 expressed in bacteria bound specifically to in vitro-generated RNA from both the beta interferon and c-myc intronless AU-rich 3' RNA-processing regions, but not to the SV40-derived early-region splice signal and poly(A) sequences. By site-specific mutagenesis, we also show that individual ICP27 C-terminal amino acid residues that are positionally conserved in ICP27 homologs in other herpesviruses (D-357, E-358, H-479, C-400, C-483 and C-488) are critical for trans-regulatory activity. Importantly, several of these positions match mutations that are known to be essential for the role of ICP27 in the early-to-late switch during the virus lytic cycle. Therefore, our findings support the notion that HSV ICP27 modulates gene expression posttranscriptionally in part by targeting RNA. C1 NIAID,CLIN INVEST LAB,MED VIROL SECT,BETHESDA,MD 20892. HENRY M JACKSON FDN,RETROVIRUS RES LAB,ROCKVILLE,MD 20850. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205. FU NCI NIH HHS [R01 CA22130] NR 71 TC 69 Z9 71 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 NOV PY 1995 VL 69 IS 11 BP 7187 EP 7195 PG 9 WC Virology SC Virology GA RZ100 UT WOS:A1995RZ10000072 PM 7474140 ER PT J AU RAGHEB, JA YU, H HOFMANN, T ANDERSON, WF AF RAGHEB, JA YU, H HOFMANN, T ANDERSON, WF TI THE AMPBOTROPIC AND ECOTROPIC MURINE LEUKEMIA-VIRUS ENVELOPE TM SUBUNITS ARE EQUIVALENT MEDIATORS OF DIRECT MEMBRANE-FUSION - IMPLICATIONS FOR THE ROLE OF THE ECOTROPIC ENVELOPE AND RECEPTOR IN SYNCYTIUM FORMATION AND VIRAL ENTRY SO JOURNAL OF VIROLOGY LA English DT Article ID HOST RANGE; RETROVIRUS RECEPTOR; NUCLEOTIDE-SEQUENCE; MOUSE FIBROBLASTS; GLYCOPROTEIN; INFECTION; GENE; PROTEINS; CELLS; RECOMBINATION AB The murine leukemia virus (MuLV) envelope protein was examined to determine which sequences are responsible for the differences in direct membrane fusion observed with the ecotropic and amphotropic MuLV subtypes. These determinants were studied by utilizing amphotropic ecotropic chimeric envelope proteins that have switched their host range but retain their original fusion domain (TM subunit). Fusion was tested both in rodent cells and in 293 cells bearing the human homolog of the ecotropic MuLV receptor. The results demonstrate that the amphotropic TM is able to mediate cell-to cell fusion to an extent equivalent to that mediated by the ecotropic TM, indicating that their fusion domains are equivalent, The ''murinized'' human homolog of the ecotropic receptor supports syncytium formation as well as the native murine receptor. These findings suggest that interactions between the ecotropic envelope protein and conserved sequences in the ecotropic receptor are the principal determinants of syncytium formation. The relationship of the fusion phenotype to pa-dependent infection and the route of viral entry was examined by studying virions bearing the chimeric envelope proteins. Such virions appear to enter cells via a pathway that is directed by the host range determining region of their envelope rather than by sequences that confer pH dependence. Therefore, the pH dependence of infection may not reflect the initial steps in viral entry. Thus, it appears that both the syncytium phenotype and the route of viral entry are properties of the viral receptor, the amino-terminal half of the ecotropic envelope protein, or the interaction between the two. C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. NR 49 TC 21 Z9 21 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 NOV PY 1995 VL 69 IS 11 BP 7205 EP 7215 PG 11 WC Virology SC Virology GA RZ100 UT WOS:A1995RZ10000074 PM 7474142 ER PT J AU FALGOUT, B MARKOFF, L AF FALGOUT, B MARKOFF, L TI EVIDENCE THAT FLAVIVIRUS NS1-NS2A CLEAVAGE IS MEDIATED BY A MEMBRANE-BOUND HOST PROTEASE IN THE ENDOPLASMIC-RETICULUM SO JOURNAL OF VIROLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; SIGNAL PEPTIDE; NONSTRUCTURAL PROTEINS; STRUCTURAL PROTEINS; VIRUS; IDENTIFICATION; TRANSLOCATION; NS3; EXPRESSION; NS2B AB Previous deletion mutagenesis studies have shown that the flavivirus NS1-NS2A cleavage requires the eight C-terminal residues of NS1, constituting the cleavage recognition sequence, and sequences in NS2A far downstream of the cleavage site. We now demonstrate that replacement of all of NS1 upstream of the cleavage recognition sequence with prM sequences still allows cleavage in vivo. Thus, other than the eight C-terminal residues, NS1 is dispensable for NS1-NS2A cleavage. However, deletion of the N-terminal signal sequence abrogated cleavage, suggesting that entry into the exocytic pathway is required, Cleavage in vivo was not blocked by brefeldin A, and cleavage could occur in vitro in the presence of dog pancreas microsomes, indicating that NS1-NS2A cleavage occurs in the endoplasmic reticulum, Four in-frame deletions in NS2A were cleavage defective in vitro, as were two mutants in which NS4A-NS4B sequences were substituted for NS2A, suggesting that most of NS2A is required, A series of substitution mutants were constructed in,which all Asp, Cys, Glu, His, and Ser residues in NS2A were collectively replaced; all standard proteases require at least one of these residues in their active sites, No single mutant was cleavage defective, suggesting that NS2A is not a protease, Fractionation of the microsomes indicated that the lumenal contents were not required for NS1-NS2A cleavage, It seems most likely that NS1-NS2A cleavage is effected by a host membrane-bound endoplasmic reticulum-resident protease, quite possibly signalase, and that NS2A is required to present the cleavage recognition sequence in the correct conformation to the host enzyme for cleavage. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RP FALGOUT, B (reprint author), US FDA,CTR BIOL EVALUAT & RES,VECTOR BORNE VIRAL DIS LAB,1401 ROCKVILLE PIKE HFM-451,ROCKVILLE,MD 20852, USA. NR 47 TC 89 Z9 93 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 NOV PY 1995 VL 69 IS 11 BP 7232 EP 7243 PG 12 WC Virology SC Virology GA RZ100 UT WOS:A1995RZ10000077 PM 7474145 ER PT J AU BESSEN, RA LYNCH, WP PORTIS, JL AF BESSEN, RA LYNCH, WP PORTIS, JL TI INHIBITION OF MURINE RETROVIRUS-INDUCED NEURODEGENERATION IN THE SPINAL-CORD BY EXPLANT CULTURE SO JOURNAL OF VIROLOGY LA English DT Note ID INDUCED SPONGIFORM ENCEPHALOPATHY; CENTRAL-NERVOUS-SYSTEM; ORGANOTYPIC CULTURES; LEUKEMIA-VIRUS; HIPPOCAMPAL SLICE; NMDA RECEPTOR; KAINIC ACID; NEUROTOXICITY; DISEASE; NEURONS AB The neurovirulent chimeric mouse ecotropic retrovirus FrCas(E) causes a rapid neurodegenerative disease of the central nervous system (CNS) characterized by the appearance of spongiform lesions in motor areas 10 days after neonatal inoculation. To study the details of the pathogenic process, we examined the ability of an ex vivo spinal cord model to recapitulate disease. Organotypic spinal cord slice cultures were established from IRW mice 7 days after neonatal inoculation. This corresponds to a time when virus expression in the CNS is first detectable but spongiform changes have yet to evolve. Infectivity associated with these cultures peaked at 7 days in vitro and persisted at this level for 6 weeks, FrCas(E) infection of the spinal cord slices was primarily found associated with microglial cells. Infection of neurons, astrocytes, oligodendroglia, and endothelial cells was not observed; however, significant astrogliosis was found. Despite the presence of extensive microglial infection in close association with spinal motor neurons in organotypic cultures, no virus-specific spongiform degenerative changes were observed. These results suggest that removal of motor neurons from the developing CNS, despite maintaining the local cytoarchitectural relationships, prevents the virus from eliciting its pathological effects. Possible reasons for the interruption of lesion development are discussed. C1 HARVARD UNIV,SCH MED,BWH,DEPT PATHOL,BOSTON,MA 02115. RP BESSEN, RA (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 36 TC 3 Z9 3 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 NOV PY 1995 VL 69 IS 11 BP 7300 EP 7303 PG 4 WC Virology SC Virology GA RZ100 UT WOS:A1995RZ10000090 PM 7474158 ER PT J AU CHIORINI, JA YANG, L SAFER, B KOTIN, RM AF CHIORINI, JA YANG, L SAFER, B KOTIN, RM TI DETERMINATION OF ADENOASSOCIATED VIRUS REP68 AND REP78 BINDING-SITES BY RANDOM SEQUENCE OLIGONUCLEOTIDE SELECTION SO JOURNAL OF VIROLOGY LA English DT Note ID ADENOASSOCIATED VIRUS; TERMINAL REPEAT; DNA; REPLICATION; INTEGRATION; PROTEINS AB To further define the canonical binding site for the P-5-promoted Rep proteins of the adeno-associated virus, a modified random oligonucleotide selection procedure was performed, using purified recombinant Rep protein. These results may explain the effects of Rep on cellular gene expression. C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. RI kotin, robert/B-8954-2008 NR 19 TC 50 Z9 51 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 NOV PY 1995 VL 69 IS 11 BP 7334 EP 7338 PG 5 WC Virology SC Virology GA RZ100 UT WOS:A1995RZ10000097 PM 7474165 ER PT J AU TRUS, BL HOMA, FL BOOY, FP NEWCOMB, WW THOMSEN, DR CHENG, NQ BROWN, JC STEVEN, AC AF TRUS, BL HOMA, FL BOOY, FP NEWCOMB, WW THOMSEN, DR CHENG, NQ BROWN, JC STEVEN, AC TI HERPES-SIMPLEX VIRUS CAPSIDS ASSEMBLED IN INSECT CELLS INFECTED WITH RECOMBINANT BACULOVIRUSES - STRUCTURAL AUTHENTICITY AND LOCALIZATION OF VP26 SO JOURNAL OF VIROLOGY LA English DT Note ID EQUINE HERPESVIRUS-1; IDENTIFICATION; MICROSCOPY; SYMMETRY; PENTONS; TYPE-1 AB Recently, recombinant baculoviruses have been used to show that expression of six herpes simplex virus type 1 genes results in the formation of capsid-like particles. We have applied cryoelectron microscopy and three-dimensional image reconstruction to establish their structural authenticity to a resolution of similar to 2.7 nm. By comparing capsids assembled with and without the expression of gene UL35, we have confirmed the presence of six copies of its product, VP26 (12 kDa), around each hexon tip. However, VP26 is not present on pentons, indicating that the conformational differences between the hexon and penton states of the major capsid protein, VP5, extend to the VP26 binding site. C1 NIAMSD,STRUCT BIOL LAB,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,COMPUTAT BIOSCI & ENGN LAB,BETHESDA,MD 20892. UPJOHN CO,MOLEC BIOL RES,KALAMAZOO,MI 49001. UNIV VIRGINIA,HLTH SCI CTR,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,CTR CANC,CHARLOTTESVILLE,VA 22908. NR 28 TC 85 Z9 85 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 NOV PY 1995 VL 69 IS 11 BP 7362 EP 7366 PG 5 WC Virology SC Virology GA RZ100 UT WOS:A1995RZ10000102 PM 7474170 ER PT J AU HEINEMAN, TC COHEN, JI AF HEINEMAN, TC COHEN, JI TI THE VARICELLA-ZOSTER VIRUS (VZV) OPEN-READING-FRAME-47 (ORF47) PROTEIN-KINASE IS DISPENSABLE FOR VIRAL REPLICATION AND IS NOT REQUIRED FOR PHOSPHORYLATION OF ORF63 PROTEIN, THE VZV HOMOLOG OF HERPES-SIMPLEX VIRUS ICP22 SO JOURNAL OF VIROLOGY LA English DT Note ID GENE; HERPESVIRUSES; CELLS AB To investigate the role of varicella-zoster virus (VZV) open reading frame 47 (ORF47) protein kinase during infection, a VZV mutant was generated in which two contiguous stop codons were introduced into ORF47, thus eliminating expression of the ORF47 kinase. ORF47 kinase was not essential for the growth of VZV in cultured cells, and the growth rate of the VZV mutant lacking ORF47 protein was indistinguishable from that of parental VZV. Nuclear extracts from cells infected with parental VZV contained several phosphorylated proteins which were not detected in extracts from cells infected with the ORF47 mutant. The herpes simplex virus type 1 (HSV-1) UL13 protein (the homolog of VZV ORF47 protein) is responsible for the posttranslational processing associated with phosphorylation of HSV-1 ICP22 (the homolog of VZV ORF63 protein). Immunoprecipitation of P-32-labeled proteins from cells infected with parental virus and those infected with ORF47 mutant virus yielded similar amounts of the VZV phosphoproteins encoded by ORF4, ORF62, ORF63, and ORF68 (VZV gE), and the electrophoretic migration of these proteins was not affected by the lack of ORF 47 kinase. Therefore, while the VZV ORF47 protein is capable of phosphorylating several cellular or viral proteins, it is not required for phosphorylation of the ORF63 protein in virus-infected cells. C1 NIAID,CLIN INVEST LAB,MED VIROL SECT,BETHESDA,MD 20892. NR 20 TC 56 Z9 57 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 NOV PY 1995 VL 69 IS 11 BP 7367 EP 7370 PG 4 WC Virology SC Virology GA RZ100 UT WOS:A1995RZ10000103 PM 7474171 ER PT J AU DUTTA, C HADLEY, EC AF DUTTA, C HADLEY, EC TI THE SIGNIFICANCE OF SARCOPENIA IN OLD-AGE SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT Workshop on Sarcopenia - Muscle Atrophy in Old Age CY SEP 19-21, 1994 CL AIRLIE, VA SP NIA ID STRENGTH; WOMEN AB Our knowledge of the significance of sarcopenia in old age is limited by a lack of epidemiologic data, an incomplete assessment of the pathophysiologic consequences of age-related decrements in muscle mass and quality, and poor understanding of the underlying mechanisms responsible for these decrements. These gaps prevent us from fully appreciating the extent of the public health burden that sarcopenia poses, and present major obstacles to the elucidation of therapies to prevent or reverse sarcopenia in the elderly. The National Institute on Aging convened the Workshop on Sarcopenia to address these issues. The primary questions explored at the workshop included: (a) What research is needed to determine the clinical and functional significance of sarcopenia? (I?) What research is needed to understand its etiology? and (c) What opportunities are there for determining the efficacy of current or potential interventions to prevent or retard tire development of sarcopenia? The research recommendations from the workshop underscored the need for more dialogue between researchers in different fields (e.g., endocrinology, exercise physiology, bone biology) and for multidisciplinary approaches in order to gain greater insight into sarcopenia. The summary of the research directions which follows has been organized according to the primary questions of the workshop. RP DUTTA, C (reprint author), NIA,GERIATR PROGRAM,GATEWAY BLDG,SUITE 3E-327,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 13 TC 135 Z9 135 U1 0 U2 5 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 1995 VL 50 SI SI BP 1 EP 4 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA TE567 UT WOS:A1995TE56700002 PM 7493199 ER PT J AU HOLLOSZY, JO AF HOLLOSZY, JO TI WORKSHOP ON SARCOPENIA - MUSCLE ATROPHY IN OLD-AGE - PREFACE SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material RP HOLLOSZY, JO (reprint author), NIA,MUSCULOSKELETAL RES GERIATR PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 4 Z9 4 U1 0 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 1995 VL 50 SI SI BP R9 EP R9 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA TE567 UT WOS:A1995TE56700001 ER PT J AU NOIRI, E ROMANOV, V FOREST, T GAILIT, J DIBONA, GF MILLER, F SOM, P OSTER, ZH GOLIGORSKY, MS AF NOIRI, E ROMANOV, V FOREST, T GAILIT, J DIBONA, GF MILLER, F SOM, P OSTER, ZH GOLIGORSKY, MS TI PATHOPHYSIOLOGY OF RENAL TUBULAR OBSTRUCTION - THERAPEUTIC ROLE OF SYNTHETIC RGD PEPTIDES IN ACUTE-RENAL-FAILURE SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID CELL SUBSTRATE ADHESION; EXTRACELLULAR-MATRIX; FOCAL ADHESION; ALPHA-ACTININ; INTERCELLULAR-ADHESION; MONOCLONAL-ANTIBODIES; INTEGRIN RECEPTORS; TYROSINE KINASE; POTENTIAL ROLE; NITRIC-OXIDE C1 SUNY STONY BROOK,DEPT PHYSIOL & BIOPHYS,STONY BROOK,NY 11794. SUNY STONY BROOK,DEPT PATHOL,STONY BROOK,NY 11794. SUNY STONY BROOK,DEPT NUCL MED,STONY BROOK,NY 11794. BROOKHAVEN NATL LAB,UPTON,NY 11973. NCI,FREDERICK,MD 21701. IOWA MED COLL,DEPT INTERNAL MED,IOWA CITY,IA. RP NOIRI, E (reprint author), SUNY STONY BROOK,DEPT MED,STONY BROOK,NY 11794, USA. FU NIDDK NIH HHS [DK-45695] NR 91 TC 32 Z9 33 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 1995 VL 48 IS 5 BP 1375 EP 1385 DI 10.1038/ki.1995.426 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA TA830 UT WOS:A1995TA83000001 PM 8544393 ER PT J AU STRIKER, GE HE, CJ LIU, ZH YANG, DCW ZALUPS, RK ESPOSITO, C STRIKER, LJ AF STRIKER, GE HE, CJ LIU, ZH YANG, DCW ZALUPS, RK ESPOSITO, C STRIKER, LJ TI PATHOGENESIS OF NONIMMUNE GLOMERULOSCLEROSIS - STUDIES IN ANIMALS AND POTENTIAL APPLICATIONS TO HUMANS SO LABORATORY INVESTIGATION LA English DT Article ID GROWTH FACTOR-I; DEPENDENT DIABETES-MELLITUS; BASEMENT-MEMBRANE COLLAGEN; FOCAL GLOMERULAR SCLEROSIS; TRANSGENIC MICE; MESANGIAL CELLS; MESSENGER-RNA; DIFFERENTIAL EXPRESSION; EXTRACELLULAR-MATRIX; HORMONE RECEPTOR C1 MERCER UNIV,SCH MED,DIV BASIC MED SCI,MACON,GA 31207. RP STRIKER, GE (reprint author), NIDDK,METAB DIS BRANCH,RENAL CELL BIOL SECT,BETHESDA,MD 20892, USA. FU NIEHS NIH HHS [ES-05157] NR 93 TC 31 Z9 32 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 NOV PY 1995 VL 73 IS 5 BP 596 EP 605 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TH832 UT WOS:A1995TH83200002 PM 7474933 ER PT J AU EASTHAM, JA TRUONG, LD ROGERS, E KATTAN, M FLANDERS, KC SCARDINO, PT THOMPSON, TC AF EASTHAM, JA TRUONG, LD ROGERS, E KATTAN, M FLANDERS, KC SCARDINO, PT THOMPSON, TC TI TRANSFORMING GROWTH-FACTOR-BETA-1 - COMPARATIVE IMMUNOHISTOCHEMICAL LOCALIZATION IN HUMAN PRIMARY AND METASTATIC PROSTATE-CANCER SO LABORATORY INVESTIGATION LA English DT Article DE TGF-BETA-1; PROSTATE CANCER; PROGRESSION; METASTASIS ID MESENCHYMAL EPITHELIAL INTERACTIONS; PROGRAMMED CELL-DEATH; FACTOR-BETA; MESSENGER-RNA; PROLIFERATION; EXPRESSION; CARCINOMA; ANGIOGENESIS; INDUCTION; INVITRO AB BACKGROUND: We have shown previously that primary prostate cancer demonstrates significant extracellular accumulation of transforming growth factor-beta 1 (TGF-beta 1). To further investigate the potential role of TGF-beta 1 in prostate cancer progression, we evaluated an expanded series of primary prostatic carcinomas and associated lymph node metastases. EXPERIMENTAL DESIGN: Prostate tissue samples from 37 patients were examined. Three were organ donors, all less than 30 years of age, whose prostates were included as normal controls. Eighteen had undergone radical prostatectomy and pelvic lymph node dissection. Eleven were without evidence of metastasis, whereas seven were found to have prostate cancer within at least one of their pelvic lymph nodes. Sixteen had undergone transurethral resection of the prostate for benign disease, yet all had prostate cancer within the resected specimen (15 were stage T1b; 1 was stage Tla). Twelve of the patients with stage T1b disease underwent pelvic lymph node dissection and implantation of radioactive gold seeds. All 12 had prostate cancer in at least one lymph node. All specimens were examined for the level of expression and localization of TGF-beta 1 by immunohistochemistry using Ab that distinguish intracellular from extracellular TGF-beta 1. RESULTS: Normal prostate tissue and benign prostatic hyperplasia demonstrated negative or weak intracellular and extracellular staining for TGF-beta 1. By comparison, 29 of 34 primary prostate cancers showed extensive extracellular TGF-beta 1 staining with pronounced intracellular accumulation within epithelial cells in 13 of 34 patients. There was no difference in the staining pattern for extracellular TGF-beta 1 between primary cancers with and without pelvic lymph node metastases. However, in primary cancers without pelvic lymph node metastases, only 1 of 15 patients showed strong intracellular staining for TGF-beta 1 compared with 12 of 19 primary tumors with metastatic disease. In addition, only 2 of 19 lymph node metastases demonstrated weak extracellular TGF-beta 1 staining, but all 19 contained intracellular TGF-beta 1. CONCLUSIONS: These findings confirm our previous observation that prostate cancer exhibits enhanced intracellular and extracellular accumulation of TGF-beta 1 relative to normal prostate tissue and benign prostatic hyperplasia. In addition, our study documented a significantly more pronounced accumulation of intracellular TGF-beta 1 in primary prostate cancer with metastasis than in primary tumors without metastasis. Moreover, although the pattern of intracellular TGF-beta 1 staining observed in the primary tumor is maintained in the metastasis, a lack of extracellular accumulation of TGF-beta 1 in the metastatic site was noted. This differential pattern may be biologically important and could conceivably reflect a role for TGF-beta 1 in disease progression. C1 MATSUNAGA CONTE PROSTATE CANC RES CTR,HOUSTON,TX. SCOTT DEPT UROL,HOUSTON,TX. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT PATHOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. METHODIST HOSP,HOUSTON,TX 77030. VET AFFAIRS MED CTR,UROL RES LAB,HOUSTON,TX 77030. FU NCI NIH HHS [CA50588, P50-CA58204] NR 39 TC 87 Z9 92 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 NOV PY 1995 VL 73 IS 5 BP 628 EP 635 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TH832 UT WOS:A1995TH83200005 PM 7474936 ER PT J AU RADLER, J STREY, H SACKMANN, E AF RADLER, J STREY, H SACKMANN, E TI PHENOMENOLOGY AND KINETICS OF LIPID BILAYER SPREADING ON HYDROPHILIC SURFACES SO LANGMUIR LA English DT Article ID PHOSPHOLIPID-BILAYERS; POROUS-MEDIA; MEMBRANES; MONOLAYERS; REFLECTION; INTERFACES; VESICLES; MODEL AB We studied the spreading of phospholipid bilayer membranes and the conditions for the formation of continuous bilayers on rough (glass, glass-MgF2, glass-MgF2-SiO2) and smooth (mica) solids using reflection interference contrast microscopy as an analytical tool. We show that two fundamentally different spreading mechanisms are possible: (i) The sliding of a single bilayer on a thin lubricating water film and (ii) the rolling of thin lobes of two juxtaposed bilayers in: a tank. tread type motion. In the first mechanism the spreading velocity of a straight interface exhibits a square root behavior, v similar to t-(1/2), allowing an estimate of the frictional coupling of the membrane to the substrate. On smooth surfaces (e.g., freshly cleaved mica) the dissipation is dominated by shear flow in the ultrathin water film separating the bilayer from the substrate. On rough surfaces in contrast (e.g., glass) friction is caused by two-dimensional flow of pinning centers through the spreading membrane. In the latter case the advancing front exhibits a self-similar interface roughness which grows with time. The growth of the roughness is analyzed, and a static roughness exponent xi = 0.61 +/- 0.04 is found. The rolling of membranes occurs On dehydrated solid-bilayer interfaces with the substrate adjacent bilayer being immobilized. In this case a viscous fingering type spreading pattern is observed. From a practical point of view the rolling motion results in separated lipid patches with intermediate uncovered spots, while spreading by membrane sliding leads to continuous substrate-supported bilayers. C1 NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892. TECH UNIV MUNICH,DEPT PHYS E22,BIOPHYS LAB,D-85474 GARCHING,GERMANY. RP RADLER, J (reprint author), UNIV CALIF SANTA BARBARA,DEPT MAT,SANTA BARBARA,CA 93106, USA. RI Strey, Helmut/B-5456-2009 NR 34 TC 213 Z9 214 U1 4 U2 43 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0743-7463 J9 LANGMUIR JI Langmuir PD NOV PY 1995 VL 11 IS 11 BP 4539 EP 4548 PG 10 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA TF282 UT WOS:A1995TF28200058 ER PT J AU BROWN, ED MORRIS, VC RHODES, DG SINHA, R LEVANDER, OA AF BROWN, ED MORRIS, VC RHODES, DG SINHA, R LEVANDER, OA TI URINARY MALONDIALDEHYDE-EQUIVALENTS DURING INGESTION OF MEAT COOKED AT HIGH OR LOW-TEMPERATURES SO LIPIDS LA English DT Note ID LIPID-PEROXIDATION; MALONALDEHYDE; EXCRETION; CARCINOGENS; MUTAGENS; FOOD; RATS AB Excretion of malondialdehyde (MDA)-generating substances in the urine has been suggested as an indicator of in vivo lipid peroxidation. However, MDA in the urine also reflects the amount of lipid peroxidation products consumed in the diet. We determined MDA as the thiobarbituric acid (TBA)-MDA complex in urine of 19 healthy adults (10 male and 9 female) fed large quantities (3.6-4.1 g/kg body weight) of ground beef cooked at a low or a high temperature. Subjects ate a controlled diet with no alcohol or nutritional supplements. For 7 d they consumed ground beef cooked at 100 degrees C for 20 min (low-temperature meat) followed by 7 d with meat fried at 250 degrees C for 22 min (high-temperature meat). Prior to the study, subjects consumed their normal free choice diet with moderate amounts of meat. The concentration of MDA in urine at baseline was 2.1 +/- 0.3 mu mol TBA-MDA equivalents/day (mean +/- SEM). After 7 d of low-temperature meat, urinary TBA-MDA equivalents increased to 23.1 +/- 1.4 mu mol/d. Urinary TBA-MDA equivalents were consistently lower (6.9-8.0 mu mol/d) 1, 2, 3, and 7 d after subjects changed to high-temperature meat. After 7 d of treatment, 97% of the MDA-equivalents in the meat was recovered in 24-h urine samples. The low temperature meat had 3-4 times more MDA than did the high-temperature meat. These data indicate that the amount of meat eaten and the cooking procedures used can dramatically alter urinary MDA. Dietary sources of MDA must be controlled if urinary MDA is to be used as an indicator of oxidative stress. C1 NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP BROWN, ED (reprint author), USDA ARS,BELTSVILLE AGR RES CTR,BELTSVILLE HUMAN NUTR RES CTR,BELTSVILLE,MD 20705, USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [Y01-CP-20521] NR 20 TC 28 Z9 28 U1 0 U2 3 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD NOV PY 1995 VL 30 IS 11 BP 1053 EP 1056 DI 10.1007/BF02536291 PG 4 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA TE229 UT WOS:A1995TE22900012 PM 8569434 ER PT J AU KOZAK, CA LEONARD, WJ AF KOZAK, CA LEONARD, WJ TI GENETIC-MAPPING OF THE INTERLEUKIN-2 RECEPTOR-ALPHA AND BETA-CHAIN GENES IN THE MOUSE SO MAMMALIAN GENOME LA English DT Note ID LOCALIZATION; EXPRESSION; CHROMOSOME-10; ASSIGNMENT; IL-2RB; CDNA C1 NHLBI,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. RP KOZAK, CA (reprint author), NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. NR 19 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD NOV PY 1995 VL 6 IS 11 BP 823 EP 824 DI 10.1007/BF00539014 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA TF651 UT WOS:A1995TF65100015 PM 8597644 ER PT J AU COLMAN, E KATZEL, LI ROGUS, E COON, P MULLER, D GOLDBERG, AP AF COLMAN, E KATZEL, LI ROGUS, E COON, P MULLER, D GOLDBERG, AP TI WEIGHT-LOSS REDUCES ABDOMINAL FAT AND IMPROVES INSULIN ACTION IN MIDDLE-AGED AND OLDER MEN WITH IMPAIRED GLUCOSE-TOLERANCE SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID ADIPOSE-TISSUE DISTRIBUTION; CORONARY-HEART-DISEASE; BODY-COMPOSITION; OBESITY; RESISTANCE; PARTICIPANTS; SENSITIVITY; FOLLOW; RISK; BORN AB Aging is associated with an increased accumulation of abdominal fat, glucose intolerance, and insulin resistance. We tested the hypothesis that diet-induced weight loss would reduce the abdominal distribution of fat and improve glucose tolerance and insulin action in a group of obese middle-aged and older men with normal or impaired glucose tolerance (IGT). Oral glucose tolerance tests (OGITs) were performed at baseline and after 9 months of diet-induced weight loss in 35 men (mean age, 60 +/- 8 years). Fifteen men of comparable age and degree of obesity who did not participate in the weight loss intervention served as controls. Subjects lost 9.0 +/- 2.0 kg (mean +/- SD) body weight (P <.001), resulting in a 19% reduction in percent body fat (30.0 +/- 4.0% to 24.0% +/- 4.0%, P <.001), an 8% reduction in waist circumference (104.0 +/- 7.0 to 96.0 +/- 7.0 cm, P <.001), and a 2% reduction in waist to hip ratio [WHR] (0.97 +/- 0.06 to 0.95 +/- 0.06, P <.01). Weight loss improved glucose tolerance: nine men with IGT at baseline reverted to normal glucose tolerance following the intervention. Glucose area during the OGTT was significantly reduced after weight loss (-22.0%, P <.001), while it increased in control subjects (+32%, P <.004). In multiple regression analysis, the improvement in glucose area following weight loss in these 35 men was attributed to the reduction in waist circumference (P <.01) and baseline glucose area (P <.05). Insulin response to glucose and tissue sensitivity to endogenous insulin were measured in a subset of eight men using the hyperglycemic clamp technique. Weight loss resulted in significant reductions in acute (P <.05) and second-phase (P <.01) insulin responses and a significant increase in the rate of glucose utilization {[M] P <.05), indicative of increased tissue sensitivity to insulin. Our results support the hypothesis that weight loss significantly improves glucose tolerance and insulin action in obese middle-aged and older men with normal glucose tolerance or IGT, in part by reducing the distribution of fat in upper-body sites. Copyright (C) 1995 by W.B. Saunders Company. C1 UNIV MARYLAND,SCH MED,DEPT MED,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,GIV GERONTOL,BALTIMORE,MD 21201. BALTIMORE VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,BALTIMORE,MD. NIA,CLIN PHYSIOL LAB,METAB SECT,BALTIMORE,MD 21224. FU NCRR NIH HHS [MO1-RR02719-03]; NIA NIH HHS [5-KO8-AG00497, P01AG004402-05] NR 35 TC 68 Z9 70 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 1995 VL 44 IS 11 BP 1502 EP 1508 DI 10.1016/0026-0495(95)90153-1 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TD891 UT WOS:A1995TD89100022 PM 7476341 ER PT J AU LANDSBERGER, N WOLFFE, AP AF LANDSBERGER, N WOLFFE, AP TI ROLE OF CHROMATIN AND XENOPUS-LAEVIS HEAT-SHOCK TRANSCRIPTION FACTOR IN REGULATION OF TRANSCRIPTION FROM THE X-LAEVIS HSP70 PROMOTER IN-VIVO SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA POLYMERASE-II; MINICHROMOSOMES ASSEMBLED INVITRO; DNA-BINDING; DROSOPHILA-MELANOGASTER; MOLECULAR-CLONING; MESSENGER-RNA; SOMATIC-CELLS; 5' END; OOCYTES; GENE AB Xenopus laevis oocytes activate transcription from the Xenopus hsp70 promoter within a chromatin template in response to heat shock. Expression of exogenous Xenopus heat shock transcription factor 1 (XHSF1) causes the activation of the wild-type hsp70 promoter within chromatin. XHSF1 activates transcription at normal growth temperatures (18 degrees C), but heat shock (34 degrees C) facilitates transcriptional activation. Titration of chromatin in vivo leads to constitutive transcription from the wild-type hsp70 promoter. The Y box elements within the hsp70 promoter facilitate transcription in the presence or absence of chromatin. The presence of the Y box elements prevents the assembly of canonical nucleosomal arrays over the promoter and facilitates transcription. In a mutant hsp70 promoter lacking Y boxes, exogenous XHSF1 activates transcription from a chromatin template much more efficiently under heat shack conditions. Activation of transcription from the mutant promoter by exogenous XHSF1 correlates with the disappearance of a canonical nucleosomal array over the promoter. Chromatin structure on a mutant hsp70 promoter lacking Y boxes can restrict XHSF1 access; however, on both mutant and wild-type promoters, chromatin assembly can also restrict the function of the basal transcriptional machinery. We suggest that chromatin assembly has a physiological role in establishing a transcriptionally repressed state on the Xenopus hsp70 promoter in vivo. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. OI Landsberger, Nicoletta/0000-0003-0820-3155 NR 74 TC 56 Z9 56 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 NOV PY 1995 VL 15 IS 11 BP 6013 EP 6024 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TA617 UT WOS:A1995TA61700018 PM 7565754 ER PT J AU BIRCHENALLROBERTS, MC RUSCETTI, FW KASPER, JJ BERTOLETTE, DC YOO, YD BANG, OS ROBERTS, MS TURLEY, JM FERRIS, DK KIM, SJ AF BIRCHENALLROBERTS, MC RUSCETTI, FW KASPER, JJ BERTOLETTE, DC YOO, YD BANG, OS ROBERTS, MS TURLEY, JM FERRIS, DK KIM, SJ TI NUCLEAR-LOCALIZATION OF V-ABL LEADS TO COMPLEX-FORMATION WITH CYCLIC-AMP RESPONSE ELEMENT (CRE)-BINDING PROTEIN AND TRANSACTIVATION THROUGH CRE MOTIFS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; CHRONIC MYELOGENOUS LEUKEMIA; RETINOBLASTOMA GENE-PRODUCT; TYROSINE KINASE; INDUCED TRANSCRIPTION; SIGNAL TRANSDUCTION; NUCLEOTIDE-SEQUENCE; SOMATOSTATIN GENE; MOLECULAR-CLONING; LEUCINE ZIPPER AB Deregulated expression of v-abl and BCR/abl genes has been associated with myeloproliferative syndromes and myelodysplasia, both of which can progress to acute leukemia. These studies identify the localization of the oncogenic form of the abl gene product encoded by the Abelson murine leukemia virus in the nuclei of myeloid cells and the association of the v-Abl protein with the transcriptional regulator cyclic AMP response element-binding protein (CREB). We have mapped the specific domains within each of the proteins responsible for this interaction. We have shown that complex formation is a prerequisite for transcriptional potentiation of CREB. Transient overexpression of the homologous cellular protein c-Abl also results in the activation of promoters containing an intact CRE. These observations identify a novel function for v-Abl, that of a transcriptional activator that physically interacts with a transcription factor. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. RP BIRCHENALLROBERTS, MC (reprint author), SCI APPLICAT INT CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD, USA. NR 57 TC 15 Z9 15 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1995 VL 15 IS 11 BP 6088 EP 6099 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TA617 UT WOS:A1995TA61700025 PM 7565761 ER PT J AU ROBERTSON, KD HAYWARD, SD LING, PD SAMID, D AMBINDER, RF AF ROBERTSON, KD HAYWARD, SD LING, PD SAMID, D AMBINDER, RF TI TRANSCRIPTIONAL ACTIVATION OF THE EPSTEIN-BARR-VIRUS LATENCY C PROMOTER AFTER 5-AZACYTIDINE TREATMENT - EVIDENCE THAT DEMETHYLATION AT A SINGLE CPG SITE IS CRUCIAL SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GENE-EXPRESSION; NUCLEAR ANTIGEN-2; MEMBRANE-PROTEIN; LYMPHOCYTES-B; HOST-CELL; DNA; EBNA-2; METHYLATION; ENHANCER; BINDING AB The Epstein-Barr Virus (EBV) latency C promoter (C-p) is the origin of transcripts for six viral proteins, The promoter is active in lymphoblastoid B-cell lines but silent in many EBV-associated tumors and tumor cell lines, In these latter cell lines, the viral episome is hypermethylated in the vicinity of this promoter, We show that in such a cell line (Rael, a Burkitt's lymphoma line), 5-azacytidine inhibits DNA methyltransferase, brings about demethylation of EBV genomes, activates C-p transcription, and induces the expression of EBNA-2, Investigation of the phenomenon demonstrates the importance of the methylation status of a particular CpG site for the regulation of the C-p: (i) genomic sequencing shows that this site is methylated when the C-p is inactive and is not methylated when the promoter is active; (ii) methylation or transition mutation at this site abolishes complex formation with a cellular binding activity (CBF2) as determined by electrophoretic mobility shift analyses, competition binding analyses, and DNase I footprinting; and (iii) a single C --> T transition mutation at this site is associated with a marked reduction (> 50-fold) of transcriptional activity in a reporter plasmid, Thus, the CBF2 binding activity is showm to be methylation sensitive and crucial to EBNA-2-mediated activation of the C-p. C1 JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,DEPT ONCOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL,BALTIMORE,MD 21205. NIH,PHARMACOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [R01 CA42245, R01 CA63532] NR 30 TC 100 Z9 101 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 NOV PY 1995 VL 15 IS 11 BP 6150 EP 6159 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TA617 UT WOS:A1995TA61700031 PM 7565767 ER PT J AU DEVER, TE YANG, WM ASTROM, S BYSTROM, AS HINNEBUSCH, AG AF DEVER, TE YANG, WM ASTROM, S BYSTROM, AS HINNEBUSCH, AG TI MODULATION OF TRNA(I)(MET), EIF-2, AND EIF-2B EXPRESSION SHOWS THAT GCN4 TRANSLATION IS INVERSELY COUPLED TO THE LEVEL OF EIF-2-CENTER-DOT-GTP-CENTER-DOT-MET-TRNA(I)(MET) TERNARY COMPLEXES SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INITIATION FACTOR-II; NUCLEOTIDE-EXCHANGE FACTOR; AMINO-ACID BIOSYNTHESIS; TRANSFER-RNA GENES; SACCHAROMYCES-CEREVISIAE; PROTEIN-SYNTHESIS; ALPHA-SUBUNIT; TRANSCRIPTIONAL ACTIVATOR; SHUTTLE VECTORS; MESSENGER-RNA AB To understand how phosphorylation of eukaryotic translation initiation factor (eIF)-2 alpha in Saccharomyces cerevisiae stimulates GCN4 mRNA translation while at the same time inhibiting general translation initiation, we examined the effects of altering the gene dosage of initiator tRNA(Met), eIF-2, and the guanine nucleotide exchange factor for eIF-2, eIF-2B. Overexpression of all three subunits of eIF-2 or all five subunits of eIF-2B suppressed the effects of eIF-2 alpha hyperphosphorylation on both GCN4-specific and general translation initiation. Consistent with eIF-2 functioning in translation as part of a ternary complex composed of eIF-2, GTP, and Met-tRNA(i)(Met), reduced gene dosage of initiator tRNA(Met) mimicked phosphorylation of eIF-2 alpha and stimulated GCN4 translation. In addition, overexpression of a combination of eIF-2 and tRNA(i)(Met) suppressed the growth-inhibitory effects of eIF-2 hyperphosphorylation more effectively than an increase in the level of either component of the ternary complex alone. These results provide in vivo evidence that phosphorylation of eIF-2 alpha reduces the activities of both eIF-2 and eIF-2B and that the eIF-2 . GTP . Met-tRNA(i)(Met) ternary complex is the principal component limiting translation in cells when eIF-2 alpha is phosphorylated on serine 51. Analysis of eIF-2 alpha phosphorylation in the eIF-2-overexpressing strain also provides in vivo evidence that phosphorylated eIF-2 acts as a competitive inhibitor of eIF-2B rather than forming an excessively stable inactive complex. Finally, our results demonstrate that the concentration of eIF-2 . GTP . Met-tRNA(i)(Met) ternary complexes is the cardinal parameter determining the site of reinitiation on GCN4 mRNA and support the idea that reinitiation at GCN4 is inversely related to the concentration of ternary complexes in the cell. C1 NICHHD, MOLEC GENET LAB, MOLEC GENET LOWER EUKARYOTES SECT, BETHESDA, MD 20892 USA. UMEA UNIV, DEPT MICROBIOL, S-90187 UMEA, SWEDEN. NR 52 TC 97 Z9 99 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1995 VL 15 IS 11 BP 6351 EP 6363 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TA617 UT WOS:A1995TA61700052 PM 7565788 ER PT J AU COLE, N TERASAKI, M SCIAKY, N LIPPINCOTTSCHWARTZ, J AF COLE, N TERASAKI, M SCIAKY, N LIPPINCOTTSCHWARTZ, J TI DYNAMICS OF A KDEL RECEPTOR GREEN FLUORESCENT PROTEIN CHIMERA VISUALIZED IN GOLGI MEMBRANES OF LIVING CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD. UNIV CONNECTICUT,CTR HLTH,FARMINGTON,CT. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 8 EP 8 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300009 ER PT J AU BOHEN, SP AF BOHEN, SP TI PHARMACOLOGICAL AND GENETIC-ANALYSIS OF THE ROLES OF HSF90 AND P23 IN SIGNALING PROTEIN FUNCTION SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 32 EP 32 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300031 ER PT J AU BENAV, P CROFFORD, LJ WILDER, RL HLA, T AF BENAV, P CROFFORD, LJ WILDER, RL HLA, T TI INDUCTION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR EXPRESSION BY PROSTAGLANDINS E(1), E(2) AND INTERLEUKIN-1-ALPHA IN SYNOVIAL FIBROBLASTS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 AMER RED CROSS,HOLLAND LAB,DEPT MOLEC BIOL,ROCKVILLE,MD. UNIV MICHIGAN,SCH MED,DEPT RHEUMATOL,ANN ARBOR,MI. NIAMS,BETHESDA,MD. RI Hla, Timothy/G-5873-2012; Crofford, Leslie/J-8010-2013 OI Hla, Timothy/0000-0001-8355-4065; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 53 EP 53 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300055 ER PT J AU CIOCE, V CSAKY, KG CHAN, AML BOTTARO, DP TAYLOR, WG JENSEN, R DIRSCH, O AARONSON, SA RUBIN, JS AF CIOCE, V CSAKY, KG CHAN, AML BOTTARO, DP TAYLOR, WG JENSEN, R DIRSCH, O AARONSON, SA RUBIN, JS TI HGF/NK1 IS A NATURALLY-OCCURRING HGF/SF VARIANT WITH PARTIAL AGONIST-ANTAGONIST ACTIVITY SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 64 EP 64 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300064 ER PT J AU RABINOVITZ, M AF RABINOVITZ, M TI THE AMINO-ACID RESTRICTION POINT AT THE G1 TO S-TRANSITION IS REGULATED VIA INHIBITION OF PHOSPHOFRUCTOKINASE BY UNCHARGED TRANSFER-RNA SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 77 EP 77 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300079 ER PT J AU MEEHAN, SC WU, AJ AMBUDKAR, IS AF MEEHAN, SC WU, AJ AMBUDKAR, IS TI THE ANTIPROLIFERATIVE EFFECT OF INTERFERON-GAMMA IS ASSOCIATED WITH A PERSISTENT DEPLETION OF INTERNAL CALCIUM STORES AND A DECREASE IN SERCA-2 PROTEIN IN A HUMAN SUBMANDIBULAR DUCTAL CELL-LINE SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR,CIPCB,SECRETORY PHYSIOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 82 EP 82 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300082 ER PT J AU BAKER, PD EVANS, CH AF BAKER, PD EVANS, CH TI CYTOKINE MODULATION OF CERVICAL-CARCINOMA CELL SIALYL-LEWIS EXPRESSION SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,BIOL LAB,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 94 EP 94 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300094 ER PT J AU CASTRO, M KARL, M BAMBERGER, C ELLIOT, S KINO, T WEBSTER, E CHROUSOS, GP AF CASTRO, M KARL, M BAMBERGER, C ELLIOT, S KINO, T WEBSTER, E CHROUSOS, GP TI THE NONLIGAND-BINDING ISOFORM OF THE HUMAN GLUCOCORTICOID RECEPTOR (HGR-BETA) TRANSLOCATES INTO THE NUCLEUS IN THE PRESENCE OF GLUCOCORTICOID - EVIDENCE FOR EARLY CYTOPLASMIC DIMERIZATION SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,DEB,PEDIAT ENDOCRINOL SECT,BETHESDA,MD 20892. RI Castro, Margaret/A-4918-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 104 EP 104 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300102 ER PT J AU ITOH, K ADELSTEIN, RS AF ITOH, K ADELSTEIN, RS TI EXPRESSION OF NEURON-SPECIFIC ISOFORMS OF HEAVY-MEROMYOSIN II-B (HMM) IN NONNEURONAL CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 147 EP 147 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300147 ER PT J AU SELLERS, JR PATO, MD PRESTON, YA HARVEY, EV ADELSTEIN, RS AF SELLERS, JR PATO, MD PRESTON, YA HARVEY, EV ADELSTEIN, RS TI BACULOVIRUS EXPRESSION OF ALTERNATIVELY SPLICED ISOFORMS OF MYOSIN HEAVY-CHAIN (MHC) II-B AND EVIDENCE FOR PHOSPHORYLATION BY PROLINE-DIRECTED KINASES SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 148 EP 148 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300148 ER PT J AU TAKENAKA, T PRESTON, YA ITOH, K WANG, F SELLERS, JR ADELSTEIN, RS AF TAKENAKA, T PRESTON, YA ITOH, K WANG, F SELLERS, JR ADELSTEIN, RS TI BACULOVIRAL EXPRESSION OF HUMAN NONMUSCLE HEAVY-MEROMYOSIN (HMM) II-B WITH AN INSERT OF 21 AMINO-ACIDS AT THE 50-20 KD BOUNDARY (LOOP-2) AND WITH INSERTS OF 10 AMINO-ACIDS AT THE 25-50 KD BOUNDARY (LOOP-1) AS WELL AS 21 AMINO-ACIDS IN LOOP-2 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 149 EP 149 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300151 ER PT J AU KELLEY, CA SELLERS, JR ADELSTEIN, RS BAINES, IC AF KELLEY, CA SELLERS, JR ADELSTEIN, RS BAINES, IC TI XENOPUS NONMUSCLE MYOSIN ISOFORMS HAVE DIFFERENT ENZYMATIC-ACTIVITIES AND SUBCELLULAR LOCALIZATIONS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 150 EP 150 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300149 ER PT J AU REDOWICZ, MJ KORN, ED RAU, DC AF REDOWICZ, MJ KORN, ED RAU, DC TI NUCLEOTIDE-BINDING INCREASES THE INTERNAL FLEXIBILITY OF ACANTHAMOEBA DEPHOSPHORYLATED MYOSIN-II MINIFILAMENTS AS PROBED BY ELECTRIC BIREFRINGENCE SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NIDDK,BIOCHEM & METAB LAB,BETHESDA,MD 20892. RI Redowicz, Maria Jolanta/R-4083-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 155 EP 155 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300157 ER PT J AU WANG, F CONTI, MA JIANG, H HARVEY, EV SELLERS, JR AF WANG, F CONTI, MA JIANG, H HARVEY, EV SELLERS, JR TI MOLECULAR-GENETIC EXPRESSION AND CHARACTERIZATION OF CHICKEN BRUSH-BORDER MYOSIN-I SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. NR 0 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 166 EP 166 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300166 ER PT J AU VAUGHNS, J GETAHUN, Z JOHNSON, R LIN, CM HAMEL, E AF VAUGHNS, J GETAHUN, Z JOHNSON, R LIN, CM HAMEL, E TI INTERACTIONS OF TUBULIN WITH GUANINE-NUCLEOTIDES THAT HAVE PACLITAXEL-LIKE EFFECTS ON TUBULIN ASSEMBLY SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 169 EP 169 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300170 ER PT J AU ANDREWS, KL NETTESHEIM, P ASAI, DJ OSTROWSKI, LE AF ANDREWS, KL NETTESHEIM, P ASAI, DJ OSTROWSKI, LE TI IDENTIFICATION OF 7 RAT AXONEMAL DYNEIN HEAVY-CHAIN GENES AND EXPRESSION DURING CILIATED CELL-DIFFERENTIATION SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. PURDUE UNIV,W LAFAYETTE,IN 47907. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 198 EP 198 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300197 ER PT J AU RAY, JM STETLERSTEVENSON, WG AF RAY, JM STETLERSTEVENSON, WG TI CHARACTERIZATION OF A CELL-SURFACE ASSOCIATED SUBSTRATE FOR GELATINASE-A FROM A2058 HUMAN-MELANOMA CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,PATHOL LAB,EXTRACELLULAR MATRIX PATHOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 276 EP 276 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300277 ER PT J AU HRYCYNA, CA LICHT, TL HUANG, M AHN, CH YIN, JJ PINE, PS ASZALOS, A AF HRYCYNA, CA LICHT, TL HUANG, M AHN, CH YIN, JJ PINE, PS ASZALOS, A TI EFFECTS OF COMBINATIONS OF SUBOPTIMAL DOSES OF P-GLYCOPROTEIN BLOCKERS ON MULTIDRUG-RESISTANT CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. US FDA,CTR DRUG EVALUAT & RES,LAUREL,MD 20708. US FDA,CTR FOOD SAFETY & APPL NUTR,LAUREL,MD 20708. RI Yin, Jun Jie /E-5619-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 317 EP 317 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300318 ER PT J AU AHUJA, SK MURPHY, PM AF AHUJA, SK MURPHY, PM TI STRUCTURE-FUNCTION-RELATIONSHIPS OF THE HUMAN IL-8 RECEPTORS .1. ROLE OF THE N-TERMINUS IN DETERMINING SUBTYPE SELECTIVITY .2. MAPPING OF DISTINCT HIGH AND LOW-AFFINITY BINDING-SITES THAT MEDIATE IL8RB ACTIVATION SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 323 EP 323 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300322 ER PT J AU HRYCYNA, CA RAMACHANDRA, M PASTAN, I GOTTESMAN, MM AF HRYCYNA, CA RAMACHANDRA, M PASTAN, I GOTTESMAN, MM TI FUNCTIONAL EXPRESSION AND MUTATIONAL ANALYSIS OF HUMAN P-GLYCOPROTEIN USING A VACCINIA VIRUS BACTERIOPHAGE-T7 RNA-POLYMERASE HYBRID EXPRESSION SYSTEM SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 335 EP 335 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300333 ER PT J AU MALIDE, D DWYER, NK BLANCHETTEMACKIE, EJ CUSHMAN, SW AF MALIDE, D DWYER, NK BLANCHETTEMACKIE, EJ CUSHMAN, SW TI INSULIN-STIMULATED GLUT4 SUBCELLULAR TRAFFIC IN RAT ADIPOSE-CELLS - A CONFOCAL MICROSCOPY APPROACH SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD 20892. NIDDK,LIPID CELL BIOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 341 EP 341 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300339 ER PT J AU SHI, S BOWERS, B LEAPMAN, R AF SHI, S BOWERS, B LEAPMAN, R TI ION CONCENTRATIONS IN THE CONTRACTILE VACUOLE OF ACANTHAMOEBA-CASTELLANII AS DETERMINED BY ANALYTICAL ELECTRON-MICROSCOPY SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 343 EP 343 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300343 ER PT J AU KASSESSINOFF, TA SCHWARTZ, MP BEAVEN, MA AF KASSESSINOFF, TA SCHWARTZ, MP BEAVEN, MA TI IDENTIFICATION OF SNARE-COMPLEX COMPONENTS EXPRESSED IN THE RBL-2H3 CELL SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 354 EP 354 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300354 ER PT J AU SENYSHYN, J BEAVEN, MA AF SENYSHYN, J BEAVEN, MA TI DIRECT ACTIVATION OF A G-PROTEIN REQUIRED FOR EXOCYTOSIS (G(E)) IN A RAT MAST-CELL LINE SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,MOLEC IMMUNOL LAB,BETHESDA,MD. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 357 EP 357 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300356 ER PT J AU WILLIAMSON, LC HALPERN, J DUNLAP, V NEALE, EA AF WILLIAMSON, LC HALPERN, J DUNLAP, V NEALE, EA TI BOTULINUM NEUROTOXIN-C ACTS ON SYNTAXIN AND SNAP-25 AND IS CYTOTOXIC TO NEURONS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 358 EP 358 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300359 ER PT J AU PETROPAVLOVSKAJA, M CHUNG, KN ELWOOD, PE ROBERTS, SJ AF PETROPAVLOVSKAJA, M CHUNG, KN ELWOOD, PE ROBERTS, SJ TI MUTATIONAL ANALYSIS OF THE N-LINKED GLYCOSYLATION SITES ON THE HUMAN FOLATE RECEPTOR SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,MED BRANCH,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 387 EP 387 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300388 ER PT J AU MEHTA, A LEE, J TILLY, K GAMBILL, D PALTER, K AF MEHTA, A LEE, J TILLY, K GAMBILL, D PALTER, K TI PURIFICATION AND CHARACTERIZATION OF DROE1, A DROSOPHILA HOMOLOG OF BACTERIAL GRPE SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 TEMPLE UNIV,DEPT BIOL,PHILADELPHIA,PA 19122. NIAID,ROCKY MT LAB,HAMILTON,MT 59840. SO METHODIST UNIV,DEPT BIOL SCI,DALLAS,TX 75275. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 390 EP 390 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300390 ER PT J AU KING, C EISENBERG, E GREENE, L AF KING, C EISENBERG, E GREENE, L TI POLYMERIZATION OF HSP70 BY DNAJ IN THE PRESENCE OF ATP SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 391 EP 391 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300393 ER PT J AU OHNO, H STEWART, J FOURNIER, MC BOSSHART, H RHEE, I MIYATAKE, S SAITO, T GALLUSSER, A KIRCHHAUSEN, T BONIFACINO, JS AF OHNO, H STEWART, J FOURNIER, MC BOSSHART, H RHEE, I MIYATAKE, S SAITO, T GALLUSSER, A KIRCHHAUSEN, T BONIFACINO, JS TI INTERACTION OF TYROSINE-BASED SORTING SIGNALS WITH THE MEDIUM CHAINS OF CLATHRIN-ASSOCIATED PROTEIN SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,CBMB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,BOSTON,MA 02115. CHIBA UNIV,SCH MED,CHIBA 260,JAPAN. RI Ohno, Hiroshi/L-7899-2014 OI Ohno, Hiroshi/0000-0001-8776-9661 NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 398 EP 398 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300397 ER PT J AU LEHEL, C OLAH, Z JAKAB, G ANDERSON, WB AF LEHEL, C OLAH, Z JAKAB, G ANDERSON, WB TI INFLUENCE OF VARIOUS DOMAINS OF PROTEIN-KINASE-C-EPSILON ON ITS PHORBOL ESTER-INDUCED TRANSLOCATION FROM THE TRANS-GOLGI NETWORK TO THE PLASMA-MEMBRANE SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NINCDS,EXPTL NEUROPATHOL LAB,BETHESDA,MD 20892. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 400 EP 400 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300398 ER PT J AU IVANOVA, VS BONNER, WM AF IVANOVA, VS BONNER, WM TI RECONSTITUTION OF NUCLEOSOMES WITH BACTERIALLY EXPRESSED HUMAN H2A HISTONE VARIANTS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 436 EP 436 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300436 ER PT J AU OLIVERO, OA CHANG, P LARRAZA, DML SEMINO, MC POIRIER, MC AF OLIVERO, OA CHANG, P LARRAZA, DML SEMINO, MC POIRIER, MC TI PREFERENTIAL BINDING AND LACK OF REMOVAL OF CISPLATIN IN MITOCHONDRIAL-DNA OF CHINESE-HAMSTER OVARY CELLS MEASURED BY DISSOCIATION ENHANCED LANTHANIDE FLUOROIMMUNOASSAY (DELFIA) AND ELECTRON-MICROSCOPY SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 441 EP 441 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300439 ER PT J AU RAMAYYA, MS DRIGGERS, PH PARKER, KL CHROUSOS, GP AF RAMAYYA, MS DRIGGERS, PH PARKER, KL CHROUSOS, GP TI CLONING AND SEQUENCING OF HUMAN STEROIDOGENIC FACTOR-I CDNA SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,DURHAM,NC 27710. NICHHD,DEB,PEDIAT ENDOCRINOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 446 EP 446 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300444 ER PT J AU SAITOH, H COOKE, CA BURGESS, WH EARNSHAW, WC DASSO, M AF SAITOH, H COOKE, CA BURGESS, WH EARNSHAW, WC DASSO, M TI A 340 KDA NUCLEAR-PORE PROTEIN INTERACTS WITH RCC1 AND RAN IN XENOPUS EGG EXTRACTS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 AMER RED CROSS,HOLLAND LAB,DEPT BIOL MOLEC,ROCKVILLE,MD 20855. JOHNS HOPKINS UNIV,SCH MED,DEPT ANAT & CELL BIOL,BALTIMORE,MD 21205. NICHHD,LME,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 477 EP 477 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300477 ER PT J AU PU, RT DASSO, MC AF PU, RT DASSO, MC TI STUDIES ON RANBP1 IN XENOPUS-LAEVIS EGG EXTRACTS - ITS ROLE IN NUCLEAR ASSEMBLY AND FUNCTION SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 478 EP 478 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300480 ER PT J AU KARAVANOV, AA KARAVANOV, I PERANTONI, A DAWID, IB AF KARAVANOV, AA KARAVANOV, I PERANTONI, A DAWID, IB TI EXPRESSION PATTERN OF RAT LHX-1/LTM-1 GENE DURING KIDNEY DIFFERENTIATION SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,GENET MOLEC LAB,BETHESDA,MD 20892. NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 491 EP 491 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300492 ER PT J AU ROBINSON, GW SMITH, GH FURTH, PA GALLAHAN, D HENNIGHAUSEN, L AF ROBINSON, GW SMITH, GH FURTH, PA GALLAHAN, D HENNIGHAUSEN, L TI MAMMARY SECRETORY DIFFERENTIATION REQUIRES REGULATED EXPRESSION OF TGF-ALPHA, TGF-BETA, WAP, INT3 AND THE ACTIVE FUNCTION OF P53 AND RB SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 512 EP 512 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300514 ER PT J AU GALLO, CJ JONES, TLZ BATTEY, JF ARAGAY, AM JAFFE, LA AF GALLO, CJ JONES, TLZ BATTEY, JF ARAGAY, AM JAFFE, LA TI EXPRESSION OF ALPHA-Q FAMILY G-PROTEINS DURING OOCYTE MATURATION AND EARLY DEVELOPMENT OF XENOPUS-LAEVIS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract ID PHOSPHOLIPASE-C; RECEPTOR C1 UNIV CONNECTICUT,CTR HLTH,DEPT PHYSIOL,FARMINGTON,CT. NIDDK,BETHESDA,MD. NIDCD,BETHESDA,MD. CALTECH,DIV BIOL,PASADENA,CA 91125. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 524 EP 524 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300523 ER PT J AU TSUTSU, T TANAKA, Y MATSUDO, Y HASEGAWA, H BARRETT, JC AF TSUTSU, T TANAKA, Y MATSUDO, Y HASEGAWA, H BARRETT, JC TI IMMORTALIZATION OF CULTURED HUMAN FIBROBLASTS INDUCED BY AFLATOXIN B-1 OR X-RAYS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIPPON DENT UNIV TOKYO,SCH DENT,DEPT PHARMACOL,TOKYO 102,JAPAN. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 540 EP 540 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300542 ER PT J AU DAVENPORT, RW THIES, E COHEN, ML NELSON, PG AF DAVENPORT, RW THIES, E COHEN, ML NELSON, PG TI REPULSIVE GUIDANCE CUES IN DISSOCIATED CELLS FROM EMBRYONIC MAMMALIAN SUPERIOR COLLICULUS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 596 EP 596 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300596 ER PT J AU PIMENTA, PF SACKS, DL AF PIMENTA, PF SACKS, DL TI LOCALIZATION OF THE LIPOPHOSPHOGLYCAN OF LEISHMANIA DURING THE FIRST STEPS OF MACROPHAGE INVASION BY THE PARASITE SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV ESTADUAL NORTE FLUMIMENSE,CTR BIOCIENCIAS & BIOTECNOL,BR-28015620 RIO JANEIRO,BRAZIL. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 624 EP 624 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300624 ER PT J AU CARROLL, J NUSSBAUM, J AF CARROLL, J NUSSBAUM, J TI DNA-SEQUENCING PARTNERSHIP - HIGH-SCHOOL-STUDENTS PARTICIPATE IN THE HUMAN GENOME PROJECT SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. SIDWEL FRIENDS SCH,WASHINGTON,DC 20016. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 640 EP 640 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300640 ER PT J AU WONG, JM WOLFFE, AP SHI, YB AF WONG, JM WOLFFE, AP SHI, YB TI A ROLE FOR NUCLEOSOME ASSEMBLY IN BOTH SILENCING AND ACTIVATION OF THE XENOPUS TRB GENE BY THE THYROID-HORMONE RECEPTOR SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 695 EP 695 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300696 ER PT J AU MOZES, M SHRIVASTAV, S FACTOR, V THORGEIRSSON, SS KOPP, JB AF MOZES, M SHRIVASTAV, S FACTOR, V THORGEIRSSON, SS KOPP, JB TI INCREASED INTERSTITIAL MATRIX AND TIMP-1 MESSENGER-RNA EXPRESSION IN TGF-BETA-1 TRANSGENIC MOUSE KIDNEY SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,METAB DIS BRANCH,KIDNEY DIS SECT,BETHESDA,MD. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 726 EP 726 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300726 ER PT J AU ARORA, JK DIKDAN, GS LYSZ, TW ZELENKA, PS AF ARORA, JK DIKDAN, GS LYSZ, TW ZELENKA, PS TI 12(S)HETE REGULATES MAP KINASE-ACTIVITY IN RABBIT LENS EPITHELIAL-CELLS STIMULATED BY EGF/INSULIN SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. UNIV MED & DENT NEW JERSEY,SCH MED,NEWARK,NJ 07103. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 735 EP 735 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300734 ER PT J AU TOPOL, LZ MARX, M CALOTHY, G BLAIR, DG AF TOPOL, LZ MARX, M CALOTHY, G BLAIR, DG TI ACTIVATION OF MKK-1 AND/OR MKK-2 IS NECESSARY AND SUFFICIENT FOR V-MOS TRANSFORMATION OF RAT FIBROBLASTS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. INST CURIE,F-91405 ORSAY,FRANCE. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 737 EP 737 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300735 ER PT J AU STEINMANN, KE DASSO, MC AF STEINMANN, KE DASSO, MC TI INVESTIGATING A ROLE FOR MESSENGER-RNA STABILITY IN MITOTIC CHECKPOINT CONTROL SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 770 EP 770 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300772 ER PT J AU NEKHAI, S ROTHBLUM, C SHUKLA, RR MITKOVITZ, J KUMAR, A AF NEKHAI, S ROTHBLUM, C SHUKLA, RR MITKOVITZ, J KUMAR, A TI ACTIVATED T-LYMPHOCYTE DERIVED TAT-TAR RNA ACTIVATED KINASE PROMOTES PHOSPHORYLATION OF RNA-POLYMERASE-II C-TERMINAL REPEATS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC. NCI,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 779 EP 779 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300777 ER PT J AU KAWASE, M ITOH, K KAJIGAYA, S YOUNG, NS AF KAWASE, M ITOH, K KAJIGAYA, S YOUNG, NS TI ERK3 IS A CANDIDATE ENZYME CATALYZING PHOSPHORYLATION OF B19 PARVOVIRUS NONSTRUCTURAL PROTEIN SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 781 EP 781 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300781 ER PT J AU TARDIEUX, IC MOSSAKOWSKA, M WARD, GE AF TARDIEUX, IC MOSSAKOWSKA, M WARD, GE TI A PROTEIN COMPLEX CONTAINING HSP70 FROM MALARIA PARASITES INHIBITS ACTIN POLYMERIZATION SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH,PARASIT DIS & CELL BIOL LABS,BETHESDA,MD. RI Tardieux, Isabelle/G-4733-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 805 EP 805 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300804 ER PT J AU AVRAHAM, KB HASSON, T STEEL, KP KINGSLEY, DM RUSSELL, LB MOOSEKER, MS COPELAND, NG JENKINS, NA AF AVRAHAM, KB HASSON, T STEEL, KP KINGSLEY, DM RUSSELL, LB MOOSEKER, MS COPELAND, NG JENKINS, NA TI THE MOUSE SNELLS WALTZER DEAFNESS GENE ENCODES A CLASS-VI UNCONVENTIONAL MYOSIN SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BRP,MAMMILIAN GENET LAB,FREDERICK,MD 21702. YALE UNIV,DEPT BIOL,NEW HAVEN,CT. UNIV NOTTINGHAM,MRC,INST HEARING RES,NOTTINGHAM NG7 2RD,ENGLAND. STANFORD UNIV,DEPT DEV BIOL,STANFORD,CA 94305. OAK RIDGE NATL LAB,DIV BIOL,OAK RIDGE,TN 37831. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 835 EP 835 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300834 ER PT J AU HAMMER, JA JUNG, G AF HAMMER, JA JUNG, G TI THE SEQUENCE OF THE DICTYOSTELIUM MYO-J HEAVY-CHAIN GENE PREDICTS A NOVEL, DIMERIC, UNCONVENTIONAL MYOSIN WITH A HEAVY-CHAIN MOLECULAR-WEIGHT OF 258 KDA SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,LCB,MCBS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 838 EP 838 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300838 ER PT J AU EVANS, LL HAMMER, J BRIDGMAN, PC AF EVANS, LL HAMMER, J BRIDGMAN, PC TI SUBCELLULAR-LOCALIZATION OF MYOSIN-V IN NERVE GROWTH CONES SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 WASHINGTON UNIV,DEPT ANAT & NEUROBIOL,ST LOUIS,MO 63110. NIH,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 844 EP 844 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300844 ER PT J AU SILVER, DL FORD, HL KACHAR, B SELLERS, JR ZAIN, SB AF SILVER, DL FORD, HL KACHAR, B SELLERS, JR ZAIN, SB TI IN-VITRO ANALYSIS OF THE INTERACTIONS OF MTS1 WITH NONMUSCLE MYOSIN-II AND F-ACTIN SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NIDCD,BETHESDA,MD 20892. UNIV ROCHESTER,SCH MED,DEPT BIOCHEM,ROCHESTER,NY 14642. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 857 EP 857 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300857 ER PT J AU SILVER, DL VOROTNIKOV, AV WATTERSON, DM SHIRINSKY, VP SELLERS, JR AF SILVER, DL VOROTNIKOV, AV WATTERSON, DM SHIRINSKY, VP SELLERS, JR TI BINDING OF KINASE-RELATED PROTEIN TO UNPHOSPHORYLATED SMOOTH-MUSCLE MYOSIN SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. RUSSIAN CARDIOL RES CTR,INST EXPTL CARDIOL,MOLEC ENDOCRINOL LAB,MOSCOW 121552,RUSSIA. NORTHWESTERN UNIV,DEPT MOLEC PHARMACOL,CHICAGO,IL 60611. RI Vorotnikov, Alexander/A-8392-2014 OI Vorotnikov, Alexander/0000-0002-1460-971X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 862 EP 862 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300862 ER PT J AU CRISWELL, PS OSTROWSKI, L ASAI, DJ AF CRISWELL, PS OSTROWSKI, L ASAI, DJ TI RAT DHC1B, A NOVEL CYTOPLASMIC DYNEIN SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 PURDUE UNIV,DEPT BIOL SCI,W LAFAYETTE,IN 47907. NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 890 EP 890 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300887 ER PT J AU VAUGHAN, KT MIKAMI, A PASCHAL, BM HOLZBAUR, ELF HUGHES, SM ECHEVERRI, CJ MOORE, KJ GILBERT, DJ COPELAND, NG JENKINS, NA VALLEE, RB AF VAUGHAN, KT MIKAMI, A PASCHAL, BM HOLZBAUR, ELF HUGHES, SM ECHEVERRI, CJ MOORE, KJ GILBERT, DJ COPELAND, NG JENKINS, NA VALLEE, RB TI IDENTIFICATION OF MULTIPLE GENOMIC LOCI INVOLVED IN DYNEIN-BASED MOTILITY SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 WORCESTER FDN BIOMED RES,CELL BIOL GRP,SHREWSBURY,MA 01545. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 892 EP 892 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300897 ER PT J AU RADHAKRISHNA, H FISCHER, M DONALDSON, JG AF RADHAKRISHNA, H FISCHER, M DONALDSON, JG TI ACTIVATORS AND INHIBITORS OF PSEUDOPODIA FORMATION IN CELLS TRANSFECTED WITH THE ARF6 GTPASE SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 924 EP 924 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300921 ER PT J AU RADHAKRISHNA, H VANDONSELAAR, E PETERS, PJ KLAUSNER, RD DONALDSON, JG AF RADHAKRISHNA, H VANDONSELAAR, E PETERS, PJ KLAUSNER, RD DONALDSON, JG TI ALUMINUM FLUORIDE STIMULATES THE FORMATION OF ACTIN-RICH PSEUDOPODIA IN ARF6 TRANSFECTED CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,CBMB,BETHESDA,MD 20892. UNIV UTRECHT,DEPT CELL BIOL,UTRECHT,NETHERLANDS. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 925 EP 925 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300924 ER PT J AU WARD, R ROBBINS, A AF WARD, R ROBBINS, A TI CHANGES IN CYTOSKELETAL ORGANIZATION IN A CHO CELL MUTANT EXPRESSING ALTERED GAPDH SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 929 EP 929 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300929 ER PT J AU ROMANOV, V MONTUORI, N SIMMONS, T CASTRONOVO, V DASILVA, PP SOBEL, ME AF ROMANOV, V MONTUORI, N SIMMONS, T CASTRONOVO, V DASILVA, PP SOBEL, ME TI INTRACELLULAR-LOCALIZATION OF THE 67 KD LAMININ RECEPTOR AND ITS 37 KD PRECURSOR IN HUMAN-MELANOMA A2058 CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Montuori, Nunzia/J-8542-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 966 EP 966 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300964 ER PT J AU POWELL, SK WILLIAMS, CC NOMIZU, M YAMADA, Y KLEINMAN, HK AF POWELL, SK WILLIAMS, CC NOMIZU, M YAMADA, Y KLEINMAN, HK TI LAMININ ALPHA-1 AND ALPHA-2 CHAIN PEPTIDES STIMULATE NERVE OUTGROWTH IN PRIMARY CEREBELLAR GRANULE NEURONS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 981 EP 981 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300983 ER PT J AU HOFFMAN, MP KIBBEY, MC NOMIZU, M KLEINMAN, HK AF HOFFMAN, MP KIBBEY, MC NOMIZU, M KLEINMAN, HK TI LAMININ PEPTIDES PROMOTE ACINAR-LIKE DEVELOPMENT OF A HUMAN SUBMANDIBULAR-GLAND CELL-LINE (HSG) IN-VITRO SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 983 EP 983 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300984 ER PT J AU WILDING, JC STAMP, GWH SOUTTER, WP MCCREA, PD VOUSDEN, K PIGNATELLI, MN AF WILDING, JC STAMP, GWH SOUTTER, WP MCCREA, PD VOUSDEN, K PIGNATELLI, MN TI INFLUENCE OF E6 AND E7 INDUCED IMMORTALIZATION AND TRANSFORMATION UPON E-CADHERIN/CATENIN COMPLEX SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 ROYAL POSTGRAD MED SCH,DEPT HISTOPATHOL,LONDON W12 0NN,ENGLAND. ROYAL POSTGRAD MED SCH,INST OBSTET & GYNAECOL,LONDON W12 0NN,ENGLAND. MD ANDERSON CANC CTR,DEPT BIOCHEM & MOLEC BIOL,HOUSTON,TX. NCI,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 999 EP 999 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51300998 ER PT J AU SALGALLER, ML POWDERLY, JW RIVOLTINI, L ROSENBERG, SA MARINCOLA, FM AF SALGALLER, ML POWDERLY, JW RIVOLTINI, L ROSENBERG, SA MARINCOLA, FM TI DIFFERENTIAL EXPRESSION AND CTL RECOGNITION OF THE MELANOCYTIC-LINEAGE-ASSOCIATED ANTIGENS MART-1 AND GP100 COMPLEXED WITH HLA-A2 IN MELANOCYTES COMPARED TO MELANOMA-CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1030 EP 1030 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301028 ER PT J AU GARCIA, MC WARD, G MA, YC SALEM, N KIM, HY AF GARCIA, MC WARD, G MA, YC SALEM, N KIM, HY TI MODULATION OF PHOSPHATIDYLSERINE SYNTHESIS BY LIPID-COMPOSITION SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAAA,LMBB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1038 EP 1038 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301040 ER PT J AU DIMITROV, DS BLUMENTHAL, R AF DIMITROV, DS BLUMENTHAL, R TI CONCERTED ACTION OF HIV-1 ENVELOPE GLYCOPROTEINS IN MEDIATING MEMBRANE-FUSION SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1048 EP 1048 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301048 ER PT J AU PURI, A MORRIS, SJ JONES, P RYAN, M BLUMENTHAL, R AF PURI, A MORRIS, SJ JONES, P RYAN, M BLUMENTHAL, R TI TRANSFER OF HUMAN ERYTHROCYTE-MEMBRANE COMPONENTS TO CD4(+) NONHUMAN CELLS CONFERS HIV-1 FUSION SUSCEPTIBILITY TO THOSE CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1050 EP 1050 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301049 ER PT J AU PLONSKY, I ZIMMERBERG, J AF PLONSKY, I ZIMMERBERG, J TI COMPARISON OF VIRUSES-INDUCED FUSION PORES SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract ID ENVELOPE GLYCOPROTEIN; MEMBRANE-FUSION; BACULOVIRUS C1 NICHHD,LTPB,BETHESDA,MD 20892. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1052 EP 1052 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301050 ER PT J AU BLUMENTHAL, R SARKAR, DP DURELL, S HOWARD, DE MORRIS, SJ AF BLUMENTHAL, R SARKAR, DP DURELL, S HOWARD, DE MORRIS, SJ TI INDIVIDUAL INFLUENZA HEMAGGLUTININ-MEDIATED MEMBRANE-FUSION EVENTS FROM FUSION PORE TO WIDE OPENING SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. UNIV DELHI,DELHI 110007,INDIA. UNIV MISSOURI,KANSAS CITY,MO 64110. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1054 EP 1054 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301054 ER PT J AU WARD, GE SUSSTOBY, E ZIMMERBERG, J AF WARD, GE SUSSTOBY, E ZIMMERBERG, J TI ELECTRICAL EVENTS ACCOMPANYING THE FORMATION AND PINCHING OFF OF THE PARASITOPHOROUS VACUOLE MEMBRANE DURING INVASION BY TOXOPLASMA-GONDII SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH,PARASIT DIS LAB,BETHESDA,MD 20892. NIH,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1060 EP 1060 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301060 ER PT J AU VERTINOBELL, A WILLIAMSON, LC ARORA, N LEPPLA, SH HALPERN, JL AF VERTINOBELL, A WILLIAMSON, LC ARORA, N LEPPLA, SH HALPERN, JL TI INHIBITION OF VESICULAR TRANSPORT BY TETANUS TOXIN IN NONNEURONAL CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH,US FDA,DIV BACTERIAL PROD,BETHESDA,MD 20892. NIH,DEV NEUROL LAB,BETHESDA,MD 20892. NIH,MICROBIAL ECOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1069 EP 1069 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301070 ER PT J AU REMALEY, AT HOEG, JM BREWER, HB AF REMALEY, AT HOEG, JM BREWER, HB TI DEFECTIVE APOLIPOPROTEIN-MEDIATED CHOLESTEROL AND PHOSPHOLIPID EFFLUX FROM TANGIER DISEASE FIBROBLASTS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1070 EP 1070 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301068 ER PT J AU MILLER, DS VILLALOBOS, AR PRITCHARD, JB AF MILLER, DS VILLALOBOS, AR PRITCHARD, JB TI ORGANIC-BASE TRANSPORT IN RAT CHOROID-PLEXUS CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS,CELL & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1071 EP 1071 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301071 ER PT J AU MEREZHINSKAYA, N KUIJPERS, GAJ POLLARD, HB RAVIV, Y AF MEREZHINSKAYA, N KUIJPERS, GAJ POLLARD, HB RAVIV, Y TI QUANTITATIVE SITE-DIRECTED PHOTOSENSITIZATION AS A NOVEL-APPROACH FOR STUDYING PROTEIN-MEMBRANE INTERACTIONS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1082 EP 1082 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301080 ER PT J AU STEINERT, PM TARCSA, E MAREKOV, LN AF STEINERT, PM TARCSA, E MAREKOV, LN TI EVIDENCE THAT THE ASSEMBLY OF THE CORNIFIED CELL, ENVELOPE OF HUMAN EPIDERMIS IS INITIATED AT THE SITE OF DESMOSOMES SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1110 EP 1110 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301109 ER PT J AU ROBERTS, GA PIDSLEY, SC MAGEE, AI BUXTON, RS AF ROBERTS, GA PIDSLEY, SC MAGEE, AI BUXTON, RS TI INHIBITION OF DESMOSOME FORMATION IN MDCK CELLS BY SYNTHESIS OF TYPE-2 DESMOCOLLIN ANTISENSE RNA SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1111 EP 1111 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301111 ER PT J AU SKALLI, O STEINERT, PM GOLDMAN, RD AF SKALLI, O STEINERT, PM GOLDMAN, RD TI MECHANISMS INVOLVED IN ANCHORING KERATIN INTERMEDIATE FILAMENTS (IF) TO DESMOSOMES SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV ILLINOIS,DEPT ANAT & CELL BIOL,CHICAGO,IL 60680. NIAMS,SKIN BIOL BRANCH,BETHESDA,MD 20892. NORTHWESTERN UNIV,DEPT CELL & MOLEC BIOL,EVANSTON,IL 60208. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1114 EP 1114 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301113 ER PT J AU PECULIS, BA AF PECULIS, BA TI U8 AND U14 SNORNAS ARE ESSENTIAL FOR PRE-RIBOSOMAL-RNA PROCESSING IN VERTEBRATES SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,GBB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1130 EP 1130 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301132 ER PT J AU KAWAMOTO, S AF KAWAMOTO, S TI A CIS-REGULATORY ELEMENT DIRECTING NEURON-SPECIFIC ALTERNATIVE SPLICING OF THE NONMUSCLE MYOSIN HEAVY CHAIN-B GENE TRANSCRIPT SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1149 EP 1149 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301148 ER PT J AU SAINTJEANNET, JP HE, X WOODGETT, JR VARMUS, HE DAWID, IB AF SAINTJEANNET, JP HE, X WOODGETT, JR VARMUS, HE DAWID, IB TI GLYCOGEN-SYNTHASE KINASE-3 AND DORSALISING SIGNALS IN XENOPUS EMBRYOS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NCI,VARMUS LAB,BETHESDA,MD 20892. ONTARIO CANC INST,TORONTO,ON M4X 1K9,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1190 EP 1190 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301192 ER PT J AU REBAGLIATI, MR DAWID, IB AF REBAGLIATI, MR DAWID, IB TI NODAL-RELATED FACTORS EXPRESSED IN EARLY ZEBRAFISH DEVELOPMENT SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,GENET MOLEC LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1217 EP 1217 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301217 ER PT J AU UHM, CS TANNER, V DANIELS, MP AF UHM, CS TANNER, V DANIELS, MP TI AXONS THAT INDUCE ACETYLCHOLINE-RECEPTOR AGGREGATION HAVE ADHESIVE INTERACTIONS WITH MUSCLE DIFFERENT FROM DENDRITES SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,BIOCHIM GENET LAB,BETHESDA,MD 20892. NINCDS,EM FACIL,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1223 EP 1223 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301223 ER PT J AU WALLACE, WC AKAR, CA LYONS, WE HAROUTUNIAN, V AF WALLACE, WC AKAR, CA LYONS, WE HAROUTUNIAN, V TI AMYLOID PRECURSOR PROTEIN ACTS AS A NEUROTROPHIC POTENTIATING FACTOR SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD 21224. VET ADM MED CTR,BRONX,NY 10468. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1243 EP 1243 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301244 ER PT J AU LANE, NJ RAPOPORT, SI BALBO, A GALDZICKI, Z AF LANE, NJ RAPOPORT, SI BALBO, A GALDZICKI, Z TI EFFECTS OF BETA-AMYLOID PEPTIDE OVER TIME ON THE FINE-STRUCTURE OF CULTURED PC-12 CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 DEPT ZOOL,CAMBRIDGE CB2 3EJ,ENGLAND. NIA,BETHESDA,MD 20892. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1258 EP 1258 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301260 ER PT J AU COMBADIERE, C AHUJA, SK MURPHY, PM AF COMBADIERE, C AHUJA, SK MURPHY, PM TI CLONING AND FUNCTIONAL EXPRESSION OF A HUMAN MONOCYTE CC-CHEMOKINE RECEPTOR SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID,LHD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1299 EP 1299 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301301 ER PT J AU MARGOLIS, LB BAIBAKOV, BA GLUSHAKOVA, SE ZIMMERBERG, J AF MARGOLIS, LB BAIBAKOV, BA GLUSHAKOVA, SE ZIMMERBERG, J TI APOPTOSIS DURING HIV-INFECTION OF HUMAN LYMPHOID-TISSUE IN-VITRO SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,LTPB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1312 EP 1312 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301311 ER PT J AU DYER, KD ROSENBERG, HF AF DYER, KD ROSENBERG, HF TI CHARACTERIZATION OF THE CARBOHYDRATE-BINDING PROPERTIES OF CHARCOT-LEYDEN CRYSTAL PROTEIN SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1317 EP 1317 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301319 ER PT J AU HACKSTADT, T ROCKEY, DD SCIDMORE, MA HEINZEN, RA AF HACKSTADT, T ROCKEY, DD SCIDMORE, MA HEINZEN, RA TI DIRECT TRAFFICKING OF ENDOGENOUSLY SYNTHESIZED SPHINGOMYELIN FROM THE GOLGI-APPARATUS TO THE CHLAMYDIA-TRACHOMATIS INCLUSION SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HOST PARASITE INTERACT SECT,HAMILTON,MT 59840. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1340 EP 1340 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301341 ER PT J AU DWYER, NK COXEY, RA PENTCHEV, PG BLANCHETTEMACKIE, EJ AF DWYER, NK COXEY, RA PENTCHEV, PG BLANCHETTEMACKIE, EJ TI LYSOSOMAL AND GOLGI MODULATION OF THE INTRACELLULAR-DISTRIBUTION OF CHOLESTEROL IN HUMAN FIBROBLASTS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,LCBB,LIPID CELL BIOL SECT,BETHESDA,MD 20892. NINCDS,DMNB,CELLULAR & MOLEC PATHOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1342 EP 1342 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301342 ER PT J AU HTUN, H BARSONY, J HAGER, GL AF HTUN, H BARSONY, J HAGER, GL TI GFP-GR - A MODEL SYSTEM FOR STUDYING CYTOPLASM-TO-NUCLEAR TRANSLOCATION AND NUCLEAR ARCHITECTURE IN CULTURED LIVING CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NIDDK,CELLULAR BIOCHEM & BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1345 EP 1345 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301344 ER PT J AU BARSONY, J RENYI, I MCKOY, W AF BARSONY, J RENYI, I MCKOY, W TI ROLE OF CYCLIC-GMP IN THE TRANSLOCATION OF VITAMIN-D RECEPTORS - STUDIES WITH A BODIPY-LABELED CALCITRIOL IN LIVE CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,CELLULAR BIOCHEM & BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1347 EP 1347 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301345 ER PT J AU TENG, CT SHIGETA, H YANG, NY AF TENG, CT SHIGETA, H YANG, NY TI ISOFORM OF ESTROGEN RELATED RECEPTOR-1 INVOLVED IN ESTROGEN-RECEPTOR MEDIATED ACTIVATION OF HUMAN LACTOFERRIN GENE SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS,LRDT,GENE REGULAT GRP,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1348 EP 1348 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301348 ER PT J AU DEMENDEZ, I ADAMS, AG LETO, TL AF DEMENDEZ, I ADAMS, AG LETO, TL TI SPECIFICITY OF P47-PHOX SH3 DOMAIN INTERACTION IN THE NADPH OXIDASE ASSEMBLY AND ACTIVATION SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1395 EP 1395 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301394 ER PT J AU LETO, TL ADAMS, AG DEMENDEZ, I AF LETO, TL ADAMS, AG DEMENDEZ, I TI ACTIVATION AND ASSEMBLY OF NADPH OXIDASE - ROLE OF THE TAIL-TAIL INTERACTION BETWEEN CYTOSOLIC COMPONENTS P47(PHOX) AND P67(PHOX) SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1396 EP 1396 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301395 ER PT J AU HE, HY GAO, CY ZELENKA, PS AF HE, HY GAO, CY ZELENKA, PS TI H1 KINASE-ACTIVITY IS ASSOCIATED WITH CYCLIN B/CDC2 COMPLEXES IN DIFFERENTIATING RAT LENS FIBER CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1405 EP 1405 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301403 ER PT J AU GAO, CY CHAUTHAIWALE, VM RAMPALLI, AM ZELENKA, PS AF GAO, CY CHAUTHAIWALE, VM RAMPALLI, AM ZELENKA, PS TI EXPRESSION OF ALTERNATIVELY SPLICED RAT PCTAIRE-1 MESSENGER-RNA IN PC12 CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1409 EP 1409 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301407 ER PT J AU KING, KL CIDLOWSKI, JA AF KING, KL CIDLOWSKI, JA TI 28S RIBOSOMAL-RNA DEGRADATION - A POSSIBLE MECHANISM FOR CESSATION OF PROTEIN-SYNTHESIS DURING APOPTOSIS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS,INTEGRAT BIOL LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1419 EP 1419 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301420 ER PT J AU LOVELACE, CIP SMITH, ML FORNACE, A VANEK, PG CHIRIKJIAN, JG COLLIER, GB AF LOVELACE, CIP SMITH, ML FORNACE, A VANEK, PG CHIRIKJIAN, JG COLLIER, GB TI COMPARISON OF ENZYMES USED IN THE IN-SITU TECHNIQUE FOR DETECTION OF APOPTOTIC CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 TREVIGEN INC,GAITHERSBURG,MD 20877. NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1422 EP 1422 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301419 ER PT J AU MURESAN, V REESE, TS SCHNAPP, BJ AF MURESAN, V REESE, TS SCHNAPP, BJ TI RECONSTITUTION OF PHYSIOLOGICALLY RELEVANT PLUS-END VESICLE MOTILITY FROM CYTOSOL AND PROTEASE-INACTIVATED SQUID AXONAL ORGANELLES SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NIH,NEUROBIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1479 EP 1479 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301477 ER PT J AU LEE, HY MURATA, J CLAIR, T POLYMEROPOULOS, MH TORRES, R MANROW, RE LIOTTA, LA STRACKE, ML AF LEE, HY MURATA, J CLAIR, T POLYMEROPOULOS, MH TORRES, R MANROW, RE LIOTTA, LA STRACKE, ML TI CDNA CLONING OF A HUMAN TERATOCARCINOMA AUTOTAXIN - ITS DIFFERENTIAL TISSUE EXPRESSION, AND ITS CHROMOSOME LOCALIZATION SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1537 EP 1537 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301535 ER PT J AU SONG, SY NOMIZU, M YAMADA, Y KLEINMAN, HK AF SONG, SY NOMIZU, M YAMADA, Y KLEINMAN, HK TI LAMININ ALPHA-1 CHAIN PEPTIDE LQVQLSIR PROMOTES TUMOR-GROWTH AND METASTASIS OF THE LIVER SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1995 VL 6 SU S BP 1622 EP 1622 PG 1 WC Cell Biology SC Cell Biology GA TF513 UT WOS:A1995TF51301622 ER EF