FN Thomson Reuters Web of Science™ VR 1.0 PT J AU ELENBERG, E SWINFORD, RD LEWIS, J KLEINMAN, RD HAMMOND, CH NORLING, LL DAOUK, GH INGELFINGER, JR AF ELENBERG, E SWINFORD, RD LEWIS, J KLEINMAN, RD HAMMOND, CH NORLING, LL DAOUK, GH INGELFINGER, JR TI FEEDING PROBLEMS IN YOUNG CYSTINOTIC CHILDREN SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 417 EP 417 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600458 ER PT J AU KROLEWSKI, M KROLEWSKI, AS WARRAM, JH AF KROLEWSKI, M KROLEWSKI, AS WARRAM, JH TI MAGNITUDE OF END-STAGE RENAL-DISEASE IN IDDM - 35 YEAR FOLLOW-UP-STUDY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 452 EP 452 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600597 ER PT J AU WARRAM, JH DONG, F KROLEWSKI, AS AF WARRAM, JH DONG, F KROLEWSKI, AS TI BIMODAL DISTRIBUTION OF THE INCIDENCE RATE OF MICROALBUMINURIA ACCORDING TO DURATION OF IDDM SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. BATTELLE MEM INST,SEATTLE,WA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 457 EP 457 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600619 ER PT J AU CHERTOW, GM LAZARUS, JM CHRISTIANSEN, CL COOK, EF HAMMERMEISTER, KE GROVER, F DALEY, J AF CHERTOW, GM LAZARUS, JM CHRISTIANSEN, CL COOK, EF HAMMERMEISTER, KE GROVER, F DALEY, J TI ACUTE-RENAL-FAILURE FOLLOWING CARDIAC-SURGERY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV RENAL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BROCKTON W ROXBURY VET AFFAIRS MED CTR,HSR&D,RENAL SECT,BOSTON,MA 02115. UNIV COLORADO,HLTH SCI CTR,DENVER VA MED CTR,DIV CARDIOL,DENVER,CO 80202. UNIV COLORADO,HLTH SCI CTR,DENVER VA MED CTR,DIV CARDIOTHORAC SURG,DENVER,CO 80202. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 460 EP 460 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600632 ER PT J AU RABITO, CA LOPEZ, IA MOORE, RH TOLKOFFRUBIN, AN WILLIAMS, WW COSIMI, B HAUG, CE AF RABITO, CA LOPEZ, IA MOORE, RH TOLKOFFRUBIN, AN WILLIAMS, WW COSIMI, B HAUG, CE TI FAST MEASUREMENTS OF RENAL-FUNCTION IN PATIENTS WITH DELAYED GRAFT FUNCTION (DGF) TREATED WITH AN ANTI-ICAM ANTIBODY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 473 EP 473 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600684 ER PT J AU BROSIUS, FC KIM, P PISONI, R DESHMUKH, G JACOB, H SIMON, J ALPER, SL AF BROSIUS, FC KIM, P PISONI, R DESHMUKH, G JACOB, H SIMON, J ALPER, SL TI ARE AE1 AND AE2 CANDIDATE GENES FOR GENETIC-HYPERTENSION - LINKAGE ANALYSIS AND EXPRESSION IN SPONTANEOUSLY HYPERTENSIVE RATS (SHR) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV MICHIGAN,SCH MED,ANN ARBOR,MI. VAMC,ANN ARBOR,MI 48105. BETH ISRAEL HOSP,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 619 EP 619 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601265 ER PT J AU NORLING, LL SMITH, TM INGELFINGER, JR AF NORLING, LL SMITH, TM INGELFINGER, JR TI CHARACTERIZATION OF RAT-KIDNEY RENIN ISOFORMS IN DEVELOPMENT SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PEDIAT NEPHROL UNIT,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 629 EP 629 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601305 ER PT J AU JUNG, FF PROVOOST, AP HAVERAN, L INGELFINGER, JR AF JUNG, FF PROVOOST, AP HAVERAN, L INGELFINGER, JR TI UP-REGULATION OF ANGIOTENSIN-II (AT(1)) RECEPTORS IN THE HYPERTENSIVE FAWN-HOODED RAT SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 ERASMUS UNIV ROTTERDAM,ROTTERDAM,NETHERLANDS. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 1 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 680 EP 680 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601511 ER PT J AU AZIZ, N NEARING, J BROWN, D AF AZIZ, N NEARING, J BROWN, D TI IMMUNOFLUORESCENT LOCALIZATION OF KE-6-PROTEIN IN NORMAL MOUSE AND CPK HOMOZYGOTE KIDNEYS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 CHILDRENS HOSP,DIV NEPHROL,BOSTON,MA. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 690 EP 690 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601551 ER PT J AU DRUMMOND, IA SUKHATME, VP AF DRUMMOND, IA SUKHATME, VP TI FGF2 EXPRESSION IN KIDNEY DEVELOPMENT - A URETERAL BUD DERIVED MESENCHYMAL CELL MITOGEN SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 BETH ISRAEL HOSP,DIV RENAL,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 693 EP 693 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601563 ER PT J AU FISCHER, E LELONGT, B VERPONT, MC DELAUCHE, M URENA, P SEGRE, GV RONCO, PM AF FISCHER, E LELONGT, B VERPONT, MC DELAUCHE, M URENA, P SEGRE, GV RONCO, PM TI ONTOGENY OF THE PTH/PHTRP RECEPTOR IN THE RAT-KIDNEY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 TENON HOSP,INSERM,U64,PARIS,FRANCE. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 694 EP 694 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601566 ER PT J AU IGARASHI, G WHYTE, DA NAGAMI, GT PAYNE, JA FORBUSH, B AF IGARASHI, G WHYTE, DA NAGAMI, GT PAYNE, JA FORBUSH, B TI KIDNEY-CELL-SPECIFIC ACTIVITY OF THE MURINE NA-K-CL COTRANSPORTER (NKCC2) PROMOTER SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 YALE UNIV,SCH MED,NEW HAVEN,CT. W LOS ANGELES DVAMC,LOS ANGELES,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 697 EP 697 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601580 ER PT J AU PALSSON, R MCLAUGHLIN, M SHARMA, CP BROWN, D ARNAOUT, MA AF PALSSON, R MCLAUGHLIN, M SHARMA, CP BROWN, D ARNAOUT, MA TI IMMUNOLOCALIZATION OF PKD1 IN NORMAL KIDNEYS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 705 EP 705 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601611 ER PT J AU GRANDALIANO, G ABBOUD, HE AF GRANDALIANO, G ABBOUD, HE TI THROMBIN-INDUCED DNA-SYNTHESIS IN HUMAN MESANGIAL CELLS (HMC) IS G-PROTEIN DEPENDENT AND PLATELET-DERIVED GROWTH-FACTOR (PDGF) INDEPENDENT SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV BARI,BARI,ITALY. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RI Grandaliano, Giuseppe/G-2963-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 736 EP 736 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601735 ER PT J AU TANG, SS DIAMANT, D RHOADS, DB INGELFINGER, JR AF TANG, SS DIAMANT, D RHOADS, DB INGELFINGER, JR TI ANGIOTENSIN-II (ANG-II) REGULATES GLUCOSE-UPTAKE IN IMMORTALIZED RAT PROXIMAL TUBULAR CELLS (IRPTC) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 748 EP 748 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601782 ER PT J AU SHERIDAN, AM FORCE, TA BONVENTRE, JV AF SHERIDAN, AM FORCE, TA BONVENTRE, JV TI IDENTIFICATION OF PROTEINS WHICH INTERACT WITH THE [CA2+] PHOSPHOLIPID-BINDING (CALB) DOMAIN OF CYTOSOLIC PHOSPHOLIPASE A(2) (CPLA(2)) BY 2-HYBRID CLONING SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 761 EP 761 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601832 ER PT J AU CHOUDHURY, GG MARRA, F KIYOMOTO, H ABBOUD, HE AF CHOUDHURY, GG MARRA, F KIYOMOTO, H ABBOUD, HE TI PLATELET-DERIVED GROWTH-FACTOR (PDGF) STIMULATES TYROSINE PHOSPHORYLATION OF JANUS-KINASE-1 (JAK-1) PROTEIN-TYROSINE KINASE IN HUMAN MESANGIAL CELLS (MC) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 765 EP 765 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601849 ER PT J AU SWINFORD, RD TANG, SS DIAMANT, D INGELFINGER, JR AF SWINFORD, RD TANG, SS DIAMANT, D INGELFINGER, JR TI BETA-ADRENERGIC REGULATION OF TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1) EXPRESSION IN IMMORTALIZED RAT PROXIMAL TUBULE CELLS (IRPTC) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 777 EP 777 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601898 ER PT J AU CHOUDHURY, GG MARRA, F ABBOUD, HE AF CHOUDHURY, GG MARRA, F ABBOUD, HE TI ASSOCIATION OF THE SH2-SH3 DOMAIN-CONTAINING ADAPTER PROTEIN NCK WITH FOCAL ADHESION KINASE IN THROMBIN-STIMULATED MESANGIAL CELLS (MC) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 786 EP 786 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601935 ER PT J AU DEMBER, LM KIM, ND LIU, KQ ANDERSON, PJ AF DEMBER, LM KIM, ND LIU, KQ ANDERSON, PJ TI SEQUENCE-SPECIFIC RNA-BINDING BY THE TIA-1 AND TIAR RRM-TYPE RNA-BINDING PROTEINS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA. BRIGHAM & WOMENS HOSP,DIV RENAL,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT RHEUMATOL,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 788 EP 788 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601940 ER PT J AU KINANE, TB KANG, I ERCOLANI, L AF KINANE, TB KANG, I ERCOLANI, L TI G-ALPHA-I-2 ACTIVATES MAPK AND ENHANCES RENAL-CELL GROWTH SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 796 EP 796 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601975 ER PT J AU LISTMAN, JA RIMM, IJ ROTHSTEIN, AM FINN, PW PERKINS, DL AF LISTMAN, JA RIMM, IJ ROTHSTEIN, AM FINN, PW PERKINS, DL TI AUTOIMMUNE INHIBITED BY RESTRICTED T-CELL RECEPTOR REPERTOIRE IN LPR TCR-TRANSGENIC MICE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. BOSTON UNIV,MED CTR,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 840 EP 840 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602147 ER PT J AU WENZEL, UO BHANDARI, B CHOUDHURY, GG VALENTE, AJ ABBOUD, HE AF WENZEL, UO BHANDARI, B CHOUDHURY, GG VALENTE, AJ ABBOUD, HE TI REPORTER MESANGIAL CELL-LINE TRANSFECTED WITH A MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1) PROMOTER - TRANSCRIPTIONAL ACTIVATION BY THROMBIN SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 858 EP 858 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602218 ER PT J AU BARNES, JL MITCHELL, RJ TORRES, ES AF BARNES, JL MITCHELL, RJ TORRES, ES TI EXPRESSION OF CELLULAR FIBRONECTIN (FN-EIIIA) AND THROMBOSPONDIN (TSP) DURING REMODELING IN HABU SNAKE-VENOM (HV)-INDUCED GLOMERULONEPHRITIS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. VET ADM MED CTR,SAN ANTONIO,TX. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 861 EP 861 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602232 ER PT J AU KAWACHI, B BROWN, D SHIA, MA SHIMIZU, F SALANT, DJ AF KAWACHI, B BROWN, D SHIA, MA SHIMIZU, F SALANT, DJ TI IMMUNOLOCALIZATION OF THE NEPHRITOGENIC ANTIGEN OF MONOCLONAL-ANTIBODY (MAB)-5-1-6 SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIIGATA UNIV,NIIGATA,JAPAN. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BOSTON UNIV,BOSTON,MA 02215. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 871 EP 871 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602270 ER PT J AU KIYOMOTO, H CHOUDHURY, GG ABBOUD, HE AF KIYOMOTO, H CHOUDHURY, GG ABBOUD, HE TI STIMULATION OF MITOGEN-ACTIVATED PROTEIN-KINASE (MAPK) AND SUPPRESSION OF PROTEIN-TYROSINE-PHOSPHATASE (PTPASE) IN EXPERIMENTAL PROLIFERATIVE GLOMERULONEPHRITIS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 872 EP 872 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602275 ER PT J AU RIEU, P SUGIMORI, T ARNAOUT, MA AF RIEU, P SUGIMORI, T ARNAOUT, MA TI THE STRUCTURAL BASIS OF LIGAND-BINDING TO INTEGRINS - A DIRECT ROLE OF A NOVEL METAL-ION-DEPENDENT SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 908 EP 908 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602419 ER PT J AU RICCARDI, D PLOTKIN, MD LEE, WS LEE, K SEGRE, GV BROWN, EM HEBERT, SC AF RICCARDI, D PLOTKIN, MD LEE, WS LEE, K SEGRE, GV BROWN, EM HEBERT, SC TI COLOCALIZATION OF THE CA2+-SENSING RECEPTOR AND PTH/PTHRP RECEPTOR IN RAT-KIDNEY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV RENAL & ENDOCRINE HYPERTENS,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 954 EP 954 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602603 ER PT J AU GOODMAN, WG BELIN, T GALES, B JUPPNER, H SEGRE, GV SALUSKY, IB AF GOODMAN, WG BELIN, T GALES, B JUPPNER, H SEGRE, GV SALUSKY, IB TI CALCIUM-REGULATED PARATHYROID-HORMONE RELEASE BEFORE AND AFTER SUCCESSFUL LONG-TERM CALCITRIOL THERAPY IN SECONDARY HYPERPARATHYROIDISM SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 962 EP 962 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602637 ER PT J AU GOODMAN, WG BELIN, T GALES, B JUPPNER, H SEGRE, GV SALUSKY, IB AF GOODMAN, WG BELIN, T GALES, B JUPPNER, H SEGRE, GV SALUSKY, IB TI CALCIUM-REGULATED PARATHYROID-HORMONE RELEASE IN MILD AND ADVANCED SECONDARY HYPERPARATHYROIDISM SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 962 EP 962 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602636 ER PT J AU JARA, A FELSENFELD, A FU, YS RODRIGUEZ, I KLEEMAN, CR AF JARA, A FELSENFELD, A FU, YS RODRIGUEZ, I KLEEMAN, CR TI PARATHYROID-GLAND PATHOLOGY IN AZOTEMIC RATS WITH MARKED SECONDARY HYPERPARATHYROIDISM SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,DEPT PATHOL,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 965 EP 965 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602646 ER PT J AU INGELFINGER, JR HAVERAN, L DIAMANT, D JUNG, FF TANG, SS AF INGELFINGER, JR HAVERAN, L DIAMANT, D JUNG, FF TANG, SS TI IGF-I MODULATES RESPONSE TO OXIDANT INJURY IN IMMORTALIZED RAT PROXIMAL TUBULE CELLS (IRPTC) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,PEDIAT NEPHROL UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 981 EP 981 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602710 ER PT J AU MANGE, KC STANTON, RC AF MANGE, KC STANTON, RC TI H2O2 INHIBITS RELEASE OF 6-PHOSPHOGLUCONATE DEHYDROGENASE (6PGD) FROM PERMEABILIZED CELLS BY PROTEIN-KINASE-C (PKC) DEPENDENT AND INDEPENDENT PATHWAYS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 DEACONESS HOSP,BOSTON,MA. JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 984 EP 984 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602724 ER PT J AU MOROOKA, H BONVENTRE, JV KYRIAKIS, J FORCE, T AF MOROOKA, H BONVENTRE, JV KYRIAKIS, J FORCE, T TI MODULATION OF ATF-2 DNA-BINDING BY AN ISCHEMIA REPERFUSION-ACTIVATED ATF-2 KINASE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 985 EP 985 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602726 ER PT J AU SAPIRSTEIN, A SPECH, R WITZGALL, R BONVENTRE, JV AF SAPIRSTEIN, A SPECH, R WITZGALL, R BONVENTRE, JV TI BCL-2 PREVENTS CYTOSOLIC PLA(2)-MEDIATED CELL INJURY IN RENAL EPITHELIAL-CELLS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 988 EP 988 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602741 ER PT J AU ISHII, H TAKAGI, C KOYA, D JIROUSEK, MR STRAMM, L BURSELL, SE KING, GL AF ISHII, H TAKAGI, C KOYA, D JIROUSEK, MR STRAMM, L BURSELL, SE KING, GL TI PREVENTION OF ABNORMAL RENAL AND RETINAL FUNCTIONS IN DIABETIC RATS BY AN ORALLY-ACTIVE ISOFORM-SPECIFIC INHIBITOR OF PROTEIN-KINASE-C (PKC) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 1041 EP 1041 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602951 ER PT J AU KASINATH, BS ABBOUD, HE MALDONADO, R TERHUNE, WC AF KASINATH, BS ABBOUD, HE MALDONADO, R TERHUNE, WC TI REGULATION OF GLOMERULAR ENDOTHELIAL-CELL (G-ENDO) SYNTHESIS OF GLOMERULAR-BASEMENT-MEMBRANE HEPARAN-SULFATE PROTEOGLYCAN (GBM HSPG) BY HIGH GLUCOSE MEDIUM SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 1042 EP 1042 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602955 ER PT J AU KOYA, D ISHII, H KING, GL AF KOYA, D ISHII, H KING, GL TI PREVENTION OF GLOMERULAR HYPERFILTRATION IN DIABETIC RATS THROUGH THE INHIBITION OF DAG-PKC SIGNALING BY VITAMIN-E SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 1042 EP 1042 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602957 ER PT J AU PARK, IS KIYOMOTO, H ABBOUD, HE AF PARK, IS KIYOMOTO, H ABBOUD, HE TI INCREASED EXPRESSION OF RENAL TGF-BETA(1) AND ALPHA-1-(IV) COLLAGEN MESSENGER-RNAS AND PROTEINS IN EARLY STREPTOZOTOCIN-INDUCED DIABETES SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV NEPHROL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 1046 EP 1046 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602970 ER PT J AU PARK, IS KIYOMOTO, H ABBOUD, SL ABBOUD, HE AF PARK, IS KIYOMOTO, H ABBOUD, SL ABBOUD, HE TI INCREASED EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1) AND INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS (IGFBPS) IN EARLY STREPTOZOTOCIN-INDUCED DIABETES SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 1046 EP 1046 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602971 ER PT J AU PASCUAL, M WEE, SL EASON, JD TOLKOFFRUBIN, N BLOSCH, C MOHLER, K COSIMI, AB AF PASCUAL, M WEE, SL EASON, JD TOLKOFFRUBIN, N BLOSCH, C MOHLER, K COSIMI, AB TI RECOMBINANT HUMAN DIMERIC TNF RECEPTOR ATTENUATES OKT3-INDUCED ACUTE SYNDROME SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT UNIT,BOSTON,MA. IMMUNEX RES CORP,SEATTLE,WA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 1110 EP 1110 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68603228 ER PT J AU HOLMAN, WL SPRUELL, RD FERGUSON, ER CLYMER, JJ VICENTE, WVA MURRAH, CP PACIFICO, AD AF HOLMAN, WL SPRUELL, RD FERGUSON, ER CLYMER, JJ VICENTE, WVA MURRAH, CP PACIFICO, AD TI TISSUE OXYGENATION WITH GRADED DISSOLVED-OXYGEN DELIVERY DURING CARDIOPULMONARY BYPASS SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID EXTREME HEMODILUTION; CONSUMPTION; METABOLISM; TRANSPORT; FLOW AB Background: Intravascular perfluorochemical emulsions together with a high oxygen tension may increase the delivery of dissolved oxygen to useful levels, The hypothesis of this study is that increasing the dissolved oxygen content of blood with incremental doses of a perfluorochemical emulsion improves tissue oxygenation during cardiopulmonary bypass in a dose-related fashion, Methods and Results: Oxygen utilization was studied in a profoundly anemic canine model of hypothermic cardiopulmonary bypass, Forty-two dogs underwent normovolemic hemodilution to a hematocrit of 15.8% +/- 0.6% (mean +/- standard error of the mean), Cardiopulmonary bypass was begun and resulted in a hematocrit of 9.4% +/- 0.6%. A standard priming solution was used in the control group (n = 12), and the test groups received 1.35 gm perfluorochemical . kg(-1) (n = 10 dogs), 2.7 gm perfluorochemical . kg(-1) (n = 10 dogs), or 5.4 gm perfluorochemical . kg(-1) (n = 10 dogs) through the venous return cannula, Each animal underwent a series of randomized pump flows (0.25, 0.5, 1.0, 1.5, 2.0, and 3.0 L . min(-1). m(-2)) at 32 degrees C, After the randomized flows were completed at 32 degrees C, the temperature was raised to 38 degrees C and cardiopulmonary bypass was discontinued, Mortality from cardiac failure on separation from cardiopulmonary bypass was 42% in the control group and 20% in perfluorochemical-treated groups. The mean perfluorochemical dose was higher in survivors than in nonsurvivors (2.9 +/- 0.4 versus 1.3 +/- 0.5 gm perfluorochemical . kg(-1); p < 0.05), No differences in oxygen consumption or transbody lactate gradient were found between groups during cardiopulmonary bypass, Analysis of mixed venous oxygen tension (a surrogate measure for tissue oxygenation) as a function of cardiopulmonary bypass flow normalized to body surface area showed that the control group had significantly lower mixed venous oxygen tension (p < 0.05) than the perfluorochemical emulsion-treated groups, Furthermore, the differences were related to the perfluorochemical emulsion dose, These differences in mixed venous oxygen tension continued after termination of cardiopulmonary bypass, The coronary sinus oxygen tension and cardiac arterial-venous oxygen content differences during and after cardiopulmonary bypass were similar among the control and perfluorochemical emulsion-treated animals, Dissolved oxygen consumption during and after cardiopulmonary bypass was calculated, Dissolved oxygen consumption increased in the perfluorochemical-treated animals in a perfluorochemical dose-related manner and was significantly higher in perfluoro-chemical-treated animals than in the control animals (p < 0.05). Conclusions: Graded increases in mixed venous oxygen tension during cardiopulmonary bypass were observed in response to graded increases in the dissolved oxygen delivery. These data suggest that enhancing oxygenation with perfluorochemical-dissolved oxygen is an effective temporary substitute for the use of hemoglobin-bound oxygen during cardiopulmonary bypass. Perfluorochemical-dissolved oxygen may be particularly beneficial in the setting of multiple hypoxic stresses. C1 BIRMINGHAM VET AFFAIRS MED CTR,BIRMINGHAM,AL. ALLIANCE PHARMACEUT CORP,SAN DIEGO,CA 92121. RP HOLMAN, WL (reprint author), UNIV ALABAMA,DEPT SURG,DIV CARDIOTHORAC SURG,UNIV STN,BIRMINGHAM,AL 35294, USA. NR 31 TC 26 Z9 26 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD SEP PY 1995 VL 110 IS 3 BP 774 EP 785 DI 10.1016/S0022-5223(95)70111-7 PG 12 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA RV197 UT WOS:A1995RV19700024 PM 7564446 ER PT J AU Shepard, JAO AF Shepard, JAO TI The bronchi: An imaging perspective SO JOURNAL OF THORACIC IMAGING LA English DT Article DE bronchi, diffuse lesions; focal lesions; helical CT scanning; HRCT; MRI AB Recent advances in high-resolution computed tomography (HRCT), inspiratory/expiratory CT staining of the lung, helical multiplanar reconstruction CT, and a broadened experience in magnetic resonance imaging of bronchial pathological conditions provide additional diagnostic information about the bronchi. This article reviews diffuse and focal lesions involving the large bronchi and small airways of the lung. C1 Harvard Univ, Sch Med, Boston, MA USA. RP Shepard, JAO (reprint author), Massachusetts Gen Hosp, Dept Radiol, ELL 234,32 Fruit St, Boston, MA 02114 USA. NR 98 TC 10 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD FAL PY 1995 VL 10 IS 4 BP 236 EP 254 DI 10.1097/00005382-199501040-00002 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V3019 UT WOS:000169110400002 PM 8523505 ER PT J AU SHIPP, TD BROMLEY, B BENACERRAF, B AF SHIPP, TD BROMLEY, B BENACERRAF, B TI THE ULTRASONOGRAPHIC APPEARANCE AND OUTCOME FOR FETUSES WITH MASSES DISTORTING THE FETAL FACE SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE FACE; MASS; FETUS; TUMOR ID INTRACRANIAL TERATOMA; PRENATAL-DIAGNOSIS; EPIGNATHUS; MANAGEMENT; TUMOR AB Our objective was to determine the appearance, cause, and outcome of fetal face masses diagnosed antenatally by ultrasonography. Over a 6 year period, 10 consecutive fetuses with facial masses were identified. Ultrasonographic findings, neonatal pathologic findings, and outcome data were correlated. Four (40%) of the 10 fetuses died, including one with a palatal teratoma associated with a Dandy-Walker malformation and three with intracranial teratomas-one of which was associated with hydrops fetalis. Among the survivors, one fetus had a dacryocystocele that was managed conservatively and one had drainage of a salivary gland cyst. The remaining four neonates had successful excision of their tumors in the neonatal period and survived; these infants had a nasal teratoma, a thyroid teratoma, a gingival granular cell tumor, and a scalp hemangioma. Four of the 10 pregnancies had associated polyhydramnios, three of which ended in stillbirth or neonatal death. In conclusion, 40% of the fetuses with antenatal diagnosis of fetal facial masses did not survive. If those with intracranial teratomas are removed from this group, one of seven (14%) fetuses with extracranial masses died. The intracranial teratomas were uniformly fatal. Polyhydramnios was associated with a poor outcome. C1 BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 19 TC 41 Z9 41 U1 1 U2 1 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 SEP PY 1995 VL 14 IS 9 BP 673 EP 678 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA RR007 UT WOS:A1995RR00700008 PM 7500433 ER PT J AU LOUGHLIN, KR AF LOUGHLIN, KR TI TESTIS CANCER - SHIBBOLETHS RECONSIDERED SO JOURNAL OF UROLOGY LA English DT Editorial Material RP LOUGHLIN, KR (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DANA FARBER CANC INST,DIV UROL,BOSTON,MA 02115, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 1995 VL 154 IS 3 BP 1050 EP 1051 DI 10.1016/S0022-5347(01)66973-8 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA RN531 UT WOS:A1995RN53100039 PM 7637052 ER PT J AU BARRY, MJ FOWLER, FJ CHANG, YC LISS, CL WILSON, H STEK, M AF BARRY, MJ FOWLER, FJ CHANG, YC LISS, CL WILSON, H STEK, M TI THE AMERICAN-UROLOGICAL-ASSOCIATION SYMPTOM INDEX - DOES MODE OF ADMINISTRATION AFFECT ITS PSYCHOMETRIC PROPERTIES SO JOURNAL OF UROLOGY LA English DT Article DE PROSTATE; PROSTATIC HYPERTROPHY; QUESTIONNAIRES; DATA INTERPRETATION, STATISTICAL ID CORRELATION-COEFFICIENTS AB Purpose: We determine whether self-administration and interviewer administration of the American Urological Association (AUA) symptom index are equivalent. Materials and Methods: The AUA symptom index was administered twice to 41 visually impaired or illiterate men, Men who were able were randomized to self-administration first and then interviewer administration (43) or the reverse (40), Results: The scores in each group were reliable. However, because we could not reject a differential carryover effect, the nonsignificant test of mode effect in the crossover design may have been invalid. At time 1 there was no significant difference between group mean scores for randomized patients (p = 0.13), Conclusions: Although the AUA symptom index should be self-administered when possible, interviewer administration appears to be acceptable. C1 UNIV MASSACHUSETTS,SURVEY RES CTR,BOSTON,MA 02125. MERCK SHARP & DOHME LTD,DIV HUMAN HLTH,W POINT,PA. RP BARRY, MJ (reprint author), MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,BOSTON,MA 02114, USA. FU AHRQ HHS [HS 08397, HS 06336] NR 13 TC 22 Z9 23 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 1995 VL 154 IS 3 BP 1056 EP 1059 DI 10.1016/S0022-5347(01)66975-1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA RN531 UT WOS:A1995RN53100041 PM 7543597 ER PT J AU RICE, SA LONG, MC LAM, V SCHAFFER, PA SPENCER, CA AF RICE, SA LONG, MC LAM, V SCHAFFER, PA SPENCER, CA TI HERPES-SIMPLEX VIRUS IMMEDIATE-EARLY PROTEIN ICP22 IS REQUIRED FOR VIRAL MODIFICATION OF HOST RNA-POLYMERASE-II AND ESTABLISHMENT OF THE NORMAL VIRAL TRANSCRIPTION PROGRAM SO JOURNAL OF VIROLOGY LA English DT Article ID CARBOXYL-TERMINAL DOMAIN; DNA-BINDING PROPERTIES; REGULATORY PROTEIN; RIBONUCLEOTIDE REDUCTASE; DELETION MUTANTS; LARGE SUBUNIT; NONPHOSPHORYLATED FORM; MONOCLONAL-ANTIBODY; GENE-EXPRESSION; MESSENGER-RNA AB Infection of cells with herpes simplex virus type 1 (HSV-1) results in a rapid alteration of phosphorylation on the large subunit of cellular RNA polymerase II (RNAP II), most likely on its C-terminal domain (S. A. Rice, M.C. Long, V. Lam, and C. A. Spencer, J. Virol. 68:98 and 1001, 1994). This phosphorylation modification generates a novel form of the large submit which we have designated IIi. In this study, we examine the roles that HSV-I gene products play in this process, An HSV-I mutant defective in the immediate-early transcriptional activator protein ICP4 is able to efficiently induce IIi. Viruses having mutations in the genes for the ICPO, ICP6, or ICP27 proteins are also competent for IIi formation. In contrast, 22/n199, an HSV-1 mutant which contains a nonsense mutation in the gene encoding the immediate-early protein ICP22, is significantly deficient in IIi induction, This effect is seen in Vero cells, where 22/n199 grows relatively efficiently, and in human embryonic lung (HEL) cells, where 22/n199 growth is more restricted, RNAP II is recruited into viral replication compartments in 22/n199-infected cells, indicating that altered phosphorylation of RNAP II is not a prerequisite for nuclear relocalization of RNAP II. In addition, we show by nuclear run-on transcription analysis that viral gene transcription is deficient in HEL cells infected with 22/n199, Viral late gene transcription does not occur efficiently, and antisense transcription throughout the genome is diminished compared with that of the wild-type HSV-1 infection, These transcriptional effects cannot be explained by differences in viral DNA replication, since 22/n199 replicates its DNA efficiently in HEL cells. Our results demonstrate that ICP22 is necessary for virus-induced aberrant phosphorylation of RNAP II and for normal patterns of viral gene transcription in certain cell lines. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MOLEC GENET,BOSTON,MA 02115. RP RICE, SA (reprint author), UNIV ALBERTA,DEPT BIOCHEM,474 MED SCI BLDG,EDMONTON,AB T6G 2H7,CANADA. NR 68 TC 112 Z9 116 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1995 VL 69 IS 9 BP 5550 EP 5559 PG 10 WC Virology SC Virology GA RN986 UT WOS:A1995RN98600043 PM 7637000 ER PT J AU WYATT, R MOORE, J ACCOLA, M DESJARDIN, E ROBINSON, J SODROSKI, J AF WYATT, R MOORE, J ACCOLA, M DESJARDIN, E ROBINSON, J SODROSKI, J TI INVOLVEMENT OF THE V1/V2 VARIABLE LOOP STRUCTURE IN THE EXPOSURE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120 EPITOPES INDUCED BY RECEPTOR-BINDING SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; AMINO-ACID CHANGES; GP41 ENVELOPE GLYCOPROTEIN; RECOMBINANT SOLUBLE CD4; SYNCYTIUM FORMATION; T-CELL; MEMBRANE-FUSION; HTLV-III; TRANSMEMBRANE GLYCOPROTEIN; NEUTRALIZING ANTIBODIES AB The binding of human immunodeficiency virus type 1 (HIV-1) to the cellular receptor CD4 has been suggested to induce conformational changes in the viral envelope glycoproteins that promote virus entry. Conserved, discontinuous epitopes on the HIV-1 gp120 glycoprotein recognized by the 17b, 48d, and A32 antibodies are preferentially exposed upon the binding of soluble CD4 (sCD4). The binding of the 17b and 48d antibodies to the gp120 glycoprotein can also be enhanced by the binding of the A32 antibody. Here we constructed HIV-1 gp120 mutants in which the variable segments of the V1/V2 and V3 structures were deleted, individually or in combination, while the 17b, 48d, and A32 epitopes were retained. The effects of the variable loop deletions on the function of the HIV-1 envelope glycoproteins ind on the exposure of epitopes induced by sCD4 or A32 binding to the monomeric gp120 glycoprotein were examined. The variable-loop-deleted envelope glycoproteins were able to mediate virus entry, albeit at lower efficiencies than those of the wild-type glyco; proteins. Thus, the V1/V2 and V3 variable sequences contribute to the efficiency of HIV-1 entry but are not absolutely required for the process. Neither the V1/V2 nor V3 loops were necessary for the increase in exposure of the 17b/48d epitopes induced by binding of the A32 monoclonal antibody. By contrast, induction of the 17b, 48d, and A32 epitopes by sCD4 binding apparently involves a movement of the V1/V2, loops, which in the absence of CD4 partially mask these epitopes on the native gp120 monomer. The results obtained with a mutant glycoprotein containing a deletion of the V1 loop alone indicated that the contribution of the V2 loop to these phenomena was more significant than that of the V1 sequences. These results suggest that the V1/V2 loops, which have been previously implicated in CD4-modulated, postattachment steps in HIV-1 entry, contribute to CD4-induced gp120 conformational changes detected by the 17b, 48d, and A32 antibodies. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. NYU,SCH MED,AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016. UNIV CONNECTICUT,CTR HLTH SCI,DEPT PEDIAT,FARMINGTON,CT 06030. FU NIAID NIH HHS [AI36082, AI 31783, AI24030] NR 91 TC 350 Z9 354 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1995 VL 69 IS 9 BP 5723 EP 5733 PG 11 WC Virology SC Virology GA RN986 UT WOS:A1995RN98600062 PM 7543586 ER PT J AU IVERSEN, AKN SHPAER, EG RODRIGO, AG HIRSCH, MS WALKER, BD SHEPPARD, HW MERIGAN, TC MULLINS, JI AF IVERSEN, AKN SHPAER, EG RODRIGO, AG HIRSCH, MS WALKER, BD SHEPPARD, HW MERIGAN, TC MULLINS, JI TI PERSISTENCE OF ATTENUATED REV GENES IN A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED ASYMPTOMATIC INDIVIDUAL SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTED INDIVIDUALS; HIV-1 INFECTION; LEUKEMIA-VIRUS; BIOLOGICAL PHENOTYPE; EXPRESSION REQUIRES; NUCLEOTIDE-SEQUENCE; SYNCYTIUM FORMATION; ACTIVATION DOMAIN; RESPONSE ELEMENT; MEMBRANE-FUSION AB With the goal of examining the functional diversity of human immunodeficiency virus type 1 (HIV-1) env genes within the peripheral blood mononuclear cells of an asymptomatic individual, we substituted four complete env genes into the replication-competent NL4-3 provirus, Despite encoding full-length open reading frames for gp120 and gp41 and the second coding exon of tat and rev, each chimera was replication defective. Site-directed mutagenesis of codon 78 in the Rev activation domain (from a hitherto unique Ile to the subtype B consensus Leu) partially restored infectivity for two of three chimeras tested. Similarly, mutagenesis of rev codon 78 of NL4-3 from Leu to Ile partially attenuated this virus. Ile-78 was found in all 13 clones examined from samples taken from this asymptomatic subject 4.5 years after infection, including 9 from peripheral blood mononuclear cells and 4 from a virus isolate, as well as 4 additional clones each from peripheral blood mononuclear cells sampled 37 and 51 months later. We next examined conservation of the Rev activation domain within and among long-term survivors (LTS) and patients with AIDS, as well as T-cell-line-adapted strains of HIV-1. Putative attenuating mutations were found in a minority of sequences from all five LTS and two of four patients with AIDS. Of the 11 T-cell-line-adapted viruses examined, none had these changes. Among and within LTS, virus populations had marginally higher levels of diversity in Rev than in Env; patients with AIDS had similar levels of diversity in the two reading frames; and T-cell-line-adapted viruses had higher levels of diversity in Env. These results are consistent with the hypothesis that asymptomatic individuals harbor attenuated variants of HIV-1 which correlate with and contribute to their lack of disease progression. C1 STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. STANFORD UNIV,SCH MED,CTR AIDS RES,DIV INFECT DIS & GEOG MED,STANFORD,CA 94305. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. STATE CALIF HLTH & WELF AGCY,DEPT HLTH SERV,BERKELEY,CA 94704. RI Rodrigo, Allen/E-8905-2015 OI Rodrigo, Allen/0000-0002-8327-7317 FU NIAID NIH HHS [AI82515, AI32885, AI34783] NR 67 TC 80 Z9 81 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1995 VL 69 IS 9 BP 5743 EP 5753 PG 11 WC Virology SC Virology GA RN986 UT WOS:A1995RN98600064 PM 7637019 ER PT J AU MILLER, DJ YOSHIKAWA, TT NORMAN, DC AF MILLER, DJ YOSHIKAWA, TT NORMAN, DC TI EFFECT OF AGE ON FEVER RESPONSE TO RECOMBINANT INTERLEUKIN-6 IN A MURINE MODEL SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID HYBRIDOMA GROWTH-FACTOR; BACTEREMIA; PATHOGENESIS; SURVIVAL; ADULTS; CDNA; RATS AB Background. A blunted or absent fever response to infection may occur in elderly people. Fever is mediated by endogenously produced molecules of leukocytes. The best studied of these molecules is interleukin-1 (IL-1). However, interleukin-6 (IL-6) is also known to possess the biological properties of pyrogenic cytokines. In this study, we assessed the influence of age on the febrile response to recombinant IL-6 (rIL-6) using a well-defined murine model. Methods. Balb/c male mice were injected intravenously and intraperitoneally with varying doses of rIL-6. Control mice received pyrogen-free phosphate buffered saline. Temperatures were measured rectally at baseline and at 10-minute intervals for 120 minutes post-injection using a thermistor probe. Stable baseline temperatures were first determined, and post-injection temperatures were recorded every 10 minutes for up to 120 minutes. Results. A dose-response correlation was found between the amount of the injected rIL-6 and the mean temperature changes in both young and old mice. The mean temperature changes for both young and old mice were higher following a 25 ng dose compared to a 12.5 ng dose of rIL-6 injected intravenously, and, likewise, following a 500 ng dose compared to a 250 ng dose of rIL-6 injected intraperitoneally. A significant delay in the peak temperature response was seen for both young and old mice when comparing intraperitoneal injections to intravenous injections. However, control mice showed no changes. Conclusions. Our findings confirm that IL-6 has a role in the pathogenesis of fever and that aging alters the febrile response to rIL-6. C1 W LOS ANGELES VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. DEPT VET AFFAIRS,OFF GERIATR & EXTENDED CARE,WASHINGTON,DC. NR 25 TC 9 Z9 9 U1 0 U2 0 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 SEP PY 1995 VL 50 IS 5 BP M276 EP M279 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RY605 UT WOS:A1995RY60500018 PM 7671030 ER PT J AU ROBBINS, J LEVINE, R WOOD, J ROECKER, EB LUSCHEI, E AF ROBBINS, J LEVINE, R WOOD, J ROECKER, EB LUSCHEI, E TI AGE EFFECTS ON LINGUAL PRESSURE GENERATION AS A RISK FACTOR FOR DYSPHAGIA SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID SWALLOWING DISORDERS; ORAL-PHASE; PERFORMANCE AB Background. Tongue activity plays a crucial role in both oral and pharyngeal phases of swallowing. In this study, maximum lingual isometric and swallowing pressures were quantified in two groups of healthy men to investigate possible age effects on performance. Magnetic resonance images of the brain were also obtained to examine the relationship between age-related anatomical changes and swallowing function. Methods. Pressures were recorded at three lingual sites (tip, blade, and dorsum) during a maximal isometric task and during saliva swallows. Task order was randomized, and subjects performed three trials per placement site. Additionally, t2-weighted MRIs were obtained on 9 of the 10 young subjects (mean age = 25 years) and all 15 older subjects (mean age = 75 years). Results. Maximal isometric pressures were significantly greater for younger subjects at the tongue blade site (p = .002), whereas peak swallowing pressures remained similar across both age groups. Within-subject comparisons of maximum isometric to swallowing pressures, a measure of reserve capacity, revealed reduced difference scores at the tongue blade in the older group (p = .02). Older subjects exhibited significantly more cerebral atrophy (p = .001) and greater incidence of periventricular white matter lesions (p = .0001) than did younger subjects. Conclusions. While swallowing pressures remain similar across the life span, overall pressure reserve declines with age. The implications are: (a) older people may be working harder to produce adequate swallowing pressures, and (b) age-related illness may put geriatric patients at higher risk for dysphagia, thus further complicating recovery. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI. UNIV WISCONSIN,DEPT NEUROL,MADISON,WI 53706. UNIV WISCONSIN,DEPT BIOSTAT,MADISON,WI 53706. UNIV IOWA,DEPT SPEECH PATHOL & AUDIOL,IOWA CITY,IA 52242. RP ROBBINS, J (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN 11G,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. FU FDA HHS [R01BS24427] NR 45 TC 123 Z9 125 U1 0 U2 10 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 SEP PY 1995 VL 50 IS 5 BP M257 EP M262 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RY605 UT WOS:A1995RY60500015 PM 7671027 ER PT J AU AMOAHAPRAKU, B CHANDLER, LJ HARRISON, JK TANG, SS INGELFINGER, JR GUZMAN, NJ AF AMOAHAPRAKU, B CHANDLER, LJ HARRISON, JK TANG, SS INGELFINGER, JR GUZMAN, NJ TI NF-KAPPA-B AND TRANSCRIPTIONAL CONTROL OF RENAL EPITHELIAL-INDUCIBLE NITRIC-OXIDE SYNTHASE SO KIDNEY INTERNATIONAL LA English DT Article ID BACTERIAL LIPOPOLYSACCHARIDE; MOUSE MACROPHAGES; PERITONEAL-MACROPHAGES; IFN-GAMMA; GENE; INDUCTION; EXPRESSION; PROMOTER; TUBULE AB Expression of the inducible isoform of nitric oxide synthase (iNOS) is subject to strict tissue specific transcriptional control. Recently, the NF-kappa B/Rel family of transcription factors, and particularly c-rel, was shown to mediate bacterial lipopolysaccharide (LPS) induction of iNOS in macrophages. Since LPS is only a weak inducer of iNOS in most nonimmune cells, we investigated the role of NF-kappa B in the regulation of iNOS expression in mouse renal epithelial cells. We report that LPS activates NF-kappa B in renal epithelium, but that this is not sufficient for induction of iNOS activity. The NF-kappa B complexes activated by LPS in renal epithelium differ from those in macrophages in that they lack c-rel, which may explain the absence of iNOS induction in renal epithelium. Conversely, LPS and interferon-gamma (IFN) synergize to induce renal epithelial iNOS. Functional iNOS promoter analysis indicate that this synergistic induction requires NF-kappa B. We conclude that NF-kappa B is necessary but not sufficient for the induction of renal epithelial iNOS expression, and that in contrast to macrophages, c-rel does not appear to play a major role in the regulation of renal epithelial iNOS. C1 UNIV FLORIDA,COLL MED,DEPT PHARMACOL,GAINESVILLE,FL 32610. UNIV FLORIDA,COLL MED,DIV NEPHROL HYPERTENS & TRANSPLANTAT,GAINESVILLE,FL 32610. MASSACHUSETTS GEN HOSP,DIV PEDIAT NEPHROL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. FU NHLBI NIH HHS [HL43131, HL48455]; NIAAA NIH HHS [AA09888] NR 33 TC 40 Z9 40 U1 1 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 SEP PY 1995 VL 48 IS 3 BP 674 EP 682 DI 10.1038/ki.1995.337 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA RQ658 UT WOS:A1995RQ65800003 PM 7474651 ER PT J AU SANCHEZ, CP GOODMAN, WG RAMIREZ, JA GALES, B BELIN, TR SEGRE, GV SALUSKY, IB AF SANCHEZ, CP GOODMAN, WG RAMIREZ, JA GALES, B BELIN, TR SEGRE, GV SALUSKY, IB TI CALCIUM-REGULATED PARATHYROID-HORMONE SECRETION IN ADYNAMIC RENAL OSTEODYSTROPHY SO KIDNEY INTERNATIONAL LA English DT Article ID HEMODIALYSIS-PATIENTS; BONE-DISEASE; GLAND FUNCTION; ASSAY; 1,25-DIHYDROXYVITAMIN-D; CALCITRIOL; DIALYSATE; FAILURE; CELLS AB Hypercalcemia and low serum parathyroid hormone (PTH) levels are features of the adynamic lesion (AD) of renal osteodystrophy, but there is little information about parathyroid gland function in this disorder. Therefore, the four parameter model was used to evaluate calcium-regulated PTH release in patients with either adynamic bone or secondary hyperparathyroidism (OF) as documented by bone biopsy and in normal volunteers (NL). Patients had undergone CCPD for 20 +/- 4.2 months, and all received calcium carbonate as the sole phosphate-binding agent During two hours infusions of sodium citrate, the rate of decline in serum ionized calcium levels did not differ among groups; serum PTH levels rose from 136 +/- 38 to 342 +/- 140 pg/ml in AD and from 691 +/- 99 to 869 +/- 121 pg/ml in OF. Maximum PTH levels were 322 +/- 42% of baseline values in AD but only 146 +/- 9.7% of baseline in OF (P < 0.001), and the increase above baseline levels in AD did not differ from that in NL (300 +/- 25%, NS). During calcium infusions, serum PTH levels fell from 164 +/- 75 to 39 +/- 11 pg/ml in AD and from 622 +/- 76 to 171 +/- 29 pg/ml in OF; minimum serum PTH levels, expressed as a percentage of pre-infusion values, were 25 +/- 2% in AD and 26 +/- 5% in OF (NS). The slope of the sigmoidal calcium-PTH curve was less in AD than in OF (54 +/- 27 versus 127 +/- 149 pg/ml/mmol, P < 0.05), suggesting a decrease in sensitivity of the parathyroids to changes in ionized calcium; however, set point values were 1.20 +/- 0.01, 1.22 +/- 0.01 and 1.21 +/- 0.01 mmol/liter in AD, OF and NL, respectively. The results indicate that abnormalities in the set point for calcium-regulated PTH release do not account for marked differences in serum PTH levels in patients with low-turnover and high-turnover skeletal lesions of renal osteodystrophy. C1 UNIV CALIF LOS ANGELES,MED CTR,SCH MED,DEPT PEDIAT,DIV PEDIAT NEPHROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED & BIOMATH,LOS ANGELES,CA 90024. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,ENDOCRINE UNIT,BOSTON,MA. FU NCRR NIH HHS [RR-00865]; NIDDK NIH HHS [DK-35423] NR 33 TC 43 Z9 43 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 SEP PY 1995 VL 48 IS 3 BP 838 EP 843 DI 10.1038/ki.1995.359 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA RQ658 UT WOS:A1995RQ65800025 PM 7474673 ER PT J AU KREISBERG, JI KREISBERG, SH AF KREISBERG, JI KREISBERG, SH TI HIGH GLUCOSE ACTIVATES PROTEIN-KINASE-C AND STIMULATES FIBRONECTIN GENE-EXPRESSION BY ENHANCING A CAMP RESPONSE ELEMENT SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 2nd Hyonam-Kidney-Laboratory International Symposium on Pathogenesis of Diabetic Nephropathy - Experimental Approaches CY JAN 21, 1995 CL SEOUL, SOUTH KOREA SP Hyonam Kidney Lab ID SIGNAL TRANSDUCTION PATHWAYS; MESANGIAL CELLS; TRANSCRIPTIONAL ACTIVATION; INDUCED BINDING; MESSENGER-RNA; CYCLIC-AMP; FAMILY; PHOSPHORYLATION; INCREASE; JUN/AP-1 C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP KREISBERG, JI (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIDDK NIH HHS [DK 29787] NR 39 TC 30 Z9 32 U1 0 U2 0 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 SEP PY 1995 VL 48 SU 51 BP S3 EP S11 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA RR159 UT WOS:A1995RR15900002 PM 7474685 ER PT J AU BLOCH, DB RABKINA, D BLOCH, KD AF BLOCH, DB RABKINA, D BLOCH, KD TI THE CELL PROLIFERATION-ASSOCIATED PROTEIN KI-67 IS A TARGET OF AUTOANTIBODIES IN THE SERUM OF MRL MICE SO LABORATORY INVESTIGATION LA English DT Article DE AUTOANTIGEN; CELL CYCLE ID SYSTEMIC LUPUS-ERYTHEMATOSUS; MONOCLONAL-ANTIBODY KI-67; NUCLEAR ANTIGEN; ESCHERICHIA-COLI; PURIFICATION; SEQUENCES; BIOLOGY; DISEASE; PROBES; MODELS AB BACKGROUND: Ab in the serum of patients with autoimmune diseases have been used to identify, characterize, and purify many autoantigens. EXPERIMENTAL DESIGN: Serum from a patient (Gel with Sjogren's syndrome was used to identify cDNA clones encoding novel autoantigens. This patient's serum was chosen for study because it contained antinuclear Ab that were different from those frequently detected in patients with autoimmune diseases. RESULTS: Ge serum identified a cDNA clone encoding part of protein Ki-67, a cell proliferation-associated protein. The Ki-67 protein (pKi-67) was not previously known to be a target of autoantibodies. To investigate the association between Ab directed against pKi-67 and autoimmune diseases, sera from autoimmune mice were tested for reactivity with a recombinant fragment of pKi-67. Ab were detected in serum from MRL/MpJ-+/+ and MRL/MpJ-lpr/lpr mice but not in serum from other autoimmune mice or control animals. CONCLUSIONS: Protein Ki-67 joins the proliferating cell nuclear Ag (PCNA) as an example of a cell proliferation-associated protein that is a target of autoantibodies. The presence of anti-pKi-67 Ab in MRL mice, but not other autoimmune mice, suggests that anti-pKi-67 Ab may be specific markers for the systemic lupus erythematosus-like illness that develops in these animals. Further characterization of the immune response directed against this Ag may provide clues to the etiology and pathogenesis of autoimmune disease in these animals. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,GEN MED SERV,ARTHRITIS UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02114. FU NHLBI NIH HHS [HL45895]; NIAMS NIH HHS [AR01866] NR 25 TC 7 Z9 7 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 SEP PY 1995 VL 73 IS 3 BP 366 EP 371 PG 6 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA RV087 UT WOS:A1995RV08700007 PM 7564269 ER PT J AU CHENEY, ML MCKENNA, MJ MEGERIAN, CA OJEMANN, RG AF CHENEY, ML MCKENNA, MJ MEGERIAN, CA OJEMANN, RG TI EARLY TEMPORALIS MUSCLE TRANSPOSITION FOR THE MANAGEMENT OF FACIAL PARALYSIS SO LARYNGOSCOPE LA English DT Article ID REANIMATION; REHABILITATION; FACE AB Temporalis muscle transposition is a reliable surgical technique for the reanimation of patients with long-standing facial paralysis. It is often employed when facial nerve reinnervation via crossover or cable grafting is not possible. Temporalis muscle transposition can also be used for the immediate treatment of complete facial paralysis due to insults leaving the facial nerve anatomically intact but requiring a prolonged recovery time (more than I year). Because temporalis muscle transposition does not interfere with neuronal regeneration, it may be employed early in the management of complete facial paralysis when recovery is predicted to be extended and incomplete. The authors report their experience with early temporalis muscle transposition in the management of facial paralysis in 56 patients with an anatomically intact facial nerve. More than 90% of these patients achieved improved symmetry at rest as well as purposeful movement at the corner of the mouth. In the last 30 patients, the temporoparietal fascial flap was simultaneously harvested and successfully used to obliterate the donor site defect. In conjunction with the immediate implantation of a gold weight in the ipsilateral upper eyelid, this approach to the early management of facial paralysis helps reduce the period of facial disability from years to weeks in a select group of patients. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,CTR FACIAL NERVE,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DIV OTOL & NEUROTOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROSURG,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA. RP CHENEY, ML (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114, USA. NR 15 TC 29 Z9 29 U1 0 U2 0 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 1995 VL 105 IS 9 BP 993 EP 1000 DI 10.1288/00005537-199509000-00021 PN 1 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA TK188 UT WOS:A1995TK18800021 PM 7666737 ER PT J AU CHENEY, ML MEGERIAN, CA BROWN, MT MCKENNA, MJ AF CHENEY, ML MEGERIAN, CA BROWN, MT MCKENNA, MJ TI MASTOID OBLITERATION AND LINING USING THE TEMPOROPARIETAL FASCIAL FLAP SO LARYNGOSCOPE LA English DT Article ID RECONSTRUCTION C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA. RP CHENEY, ML (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 6 TC 18 Z9 18 U1 0 U2 0 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 1995 VL 105 IS 9 BP 1010 EP 1013 DI 10.1288/00005537-199509000-00024 PN 1 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA TK188 UT WOS:A1995TK18800024 PM 7666712 ER PT J AU GRAY, ML BURSTEIN, D LESPERANCE, LM GEHRKE, L AF GRAY, ML BURSTEIN, D LESPERANCE, LM GEHRKE, L TI MAGNETIZATION-TRANSFER IN CARTILAGE AND ITS CONSTITUENT MACROMOLECULES SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note DE MAGNETIZATION TRANSFER; CARTILAGE; COLLAGEN; GLYCOSAMINOGLYCANS ID ARTICULAR-CARTILAGE; SPECTROSCOPY; RESONANCE; JOINT AB The goal of this work was to investigate magnetization transfer (MT) in cartilage by measuring water proton signals M(s)/M(o), as an indicator of MT, in (i) single-component systems of the tissue's constituent macromolecules and (ii) intact cartilage under control conditions and after two pathomimetic interventions, M(s)/M(o) was quantified with a 12-mu T saturation pulse applied 6 kHz off resonance, Both glycosaminoglycans (GAG) and collagen exhibited concentration dependent effects on M(s)/M(o), being approximately linear for GAG solutions (M(s)/M(o) = -0.0137[% GAG] + 1.02) and exponential for collagen suspensions (M(s)/M(o) = 0.80 x exp[-(%collagen)/6.66] + 0.20); the direct saturation of water could not account for the measured M(s)/M(o). Although the effect of collagen on M(s)/M(o) is much stronger than for a corresponding concentration of GAG, M(s)/M(o) is not very sensitive to changes in collagen concentration in the physiological range, Tissue degradation with 25 mg/ml trypsin led to an increase inM(s)/M(o) from the baseline value of 0.2 (final/initial values = 1.15 +/- 0.13, n = 11, P < 0.001), In contrast, a 10-day treatment of cartilage with 100 ng/ml of interieukin-1 beta (IL-1 beta) caused a 19% decrease in M(s)/M(o) (final/initial values = 0.81 +/- 0.08, n = 3, P = 0.085), The changes in hydration and macromolecular content for the two treatments were comparable, suggesting that M(s)/M(o) is sensitive to macromolecular structure as well as concentration, In conclusion, whereas the baseline M(s)/M(o) value in cartilage may be primarily due to the tissue collagen concentration, changes in M(s)/M(o) may be due to physiological or pathophysiological changes in GAG concentration and tissue structure, and the measured M(s)/M(o) may differentiate between various pathomimetic degradative procedures. C1 HARVARD MIT DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA. MIT,DEPT ELECT ENGN & COMP SCI,ELECTROMAGNET & ELECTR SYST LAB,CONTINUUM ELECTROMECH GRP,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,ARTHRIT UNIT,BOSTON,MA. BETH ISRAEL HOSP,CHARLES A DANA RES INST,DEPT RADIOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIAMS NIH HHS [AR41713] NR 22 TC 117 Z9 122 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD SEP PY 1995 VL 34 IS 3 BP 319 EP 325 DI 10.1002/mrm.1910340307 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RR687 UT WOS:A1995RR68700006 PM 7500869 ER PT J AU DONAHUE, KM WEISSKOFF, RM PARMELEE, DJ CALLAHAN, RJ WILKINSON, RA MANDEVILLE, JB ROSEN, BR AF DONAHUE, KM WEISSKOFF, RM PARMELEE, DJ CALLAHAN, RJ WILKINSON, RA MANDEVILLE, JB ROSEN, BR TI DYNAMIC GD-DTPA ENHANCED MRI MEASUREMENT OF TISSUE CELL-VOLUME FRACTION SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE CELL FRACTION; GD-DTPA; PROTON EXCHANGE ID BLOOD-FLOW; NEOPLASTIC TISSUES; RELAXATION-TIMES; SKELETAL-MUSCLE; WATER PROTONS; RAT; EXCHANGE; TUMORS; TRANSPORT; DIFFUSION AB A new technique for measuring tissue cellular volume fraction, based on an improved modeling of the dynamic distribution of Gd-DTPA and the effect of proton exchange, is described, This technique uses peak T-1 enhancement and blood Gd-DTPA concentration to compute tissue cellular volume fraction, The feasibility of this technique is demonstrated with computer simulations that explore the limits of the simplifying assumptions (small vascular space, slow vascular-extravascular proton exchange), and by direct comparison of MR and radionuclide cell fraction measurements made in muscle, liver, and tumor tissue in a rat model, The computer simulations demonstrate that with slow to intermediate vascular proton exchange and vascular fractions less than 10% the error in our cell fraction measurements typically remains less than 10%, Consistent with this prediction, a direct comparison between MR and radionuclide measurements of cell fraction demonstrates mean percent differences of less than 10%: 1.9% in muscle (n = 4); 9% in liver (n = 1) and 9.5% in tumor (n = 4), Similarly, for all rats studied, the MR-measured cell fractions (muscle (0.92 +/- 0.04, n = 20); liver (0.76 +/- 0.11, n = 9); whole tumor (0.69 +/- 0.15, n = 22)) agree with the cell fraction values reported in the literature, In general, the authors' results demonstrate the feasibility of a simple method for measuring tissue cell fraction that is robust across a broad range of vascular volume, flow, and exchange conditions, Consequently, this method may prove to be an important means for evaluating the response of tumors to therapy, Key words: Cell fraction; Gd-DTPA; proton exchange. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. METASYN INC,CAMBRIDGE,MA. RP DONAHUE, KM (reprint author), MASSACHUSETTS GEN HOSP,CTR NMR,2ND FLOOR,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 59 TC 78 Z9 79 U1 0 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD SEP PY 1995 VL 34 IS 3 BP 423 EP 432 DI 10.1002/mrm.1910340320 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RR687 UT WOS:A1995RR68700019 PM 7500882 ER PT J AU OTSEN, M DENBIEMAN, M WINER, ES JACOB, HJ SZPIRER, J SZPIRER, C BENDER, K VANZUTPHEN, LFM AF OTSEN, M DENBIEMAN, M WINER, ES JACOB, HJ SZPIRER, J SZPIRER, C BENDER, K VANZUTPHEN, LFM TI USE OF SIMPLE SEQUENCE LENGTH POLYMORPHISMS FOR GENETIC-CHARACTERIZATION OF RAT INBRED STRAINS SO MAMMALIAN GENOME LA English DT Article ID MARKERS; NORVEGICUS; EVOLUTION; LINKAGE; LOCI AB Genetic monitoring is an essential component of colony management and for the rat has been accomplished primarily by using immunological and biochemical markers. Here, we report that simple sequence length polymorphisms (SSLPs) are a faster and more economical way of monitoring inbred strains of rats. We characterized 61 inbred strains of rats, using primer pairs for 37 SSLPs. Each of these loci appeared to be highly polymorphic, with the number of alleles per locus ranging between 3 and 14 and, as a result, all the 61 inbred strains tested in this study could be provided with a unique strain profile. These strain profiles are also used for estimating the degree of similarity between strains. This information may provide the rationale in selecting strains for genetic crosses or for other specific purposes. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129. FREE UNIV BRUSSELS,DEPT MOLEC BIOL,B-1640 RHODE ST GENESE,BELGIUM. UNIV FREIBURG,INST HUMAN GENET & ANTROPOL,D-79106 FREIBURG,GERMANY. RP OTSEN, M (reprint author), UNIV UTRECHT,FAC VET MED,DEPT LAB ANIM SCI,3508 TD UTRECHT,NETHERLANDS. NR 32 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD SEP PY 1995 VL 6 IS 9 BP 595 EP 601 DI 10.1007/BF00352364 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RU971 UT WOS:A1995RU97100006 PM 8535065 ER PT J AU PAUL, SD EAGLE, KA AF PAUL, SD EAGLE, KA TI A STEPWISE STRATEGY FOR CORONARY RISK ASSESSMENT FOR NONCARDIAC SURGERY SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID PERIPHERAL VASCULAR-SURGERY; DOBUTAMINE STRESS ECHOCARDIOGRAPHY; ABDOMINAL AORTIC-ANEURYSM; PERIOPERATIVE MYOCARDIAL-INFARCTION; ARTERY BYPASS-SURGERY; DIPYRIDAMOLE-THALLIUM SCINTIGRAPHY; NON-CARDIAC SURGERY; ISCHEMIC-HEART-DISEASE; DEEP-VEIN THROMBOSIS; TL-201 SCINTIGRAPHY AB Patients undergoing noncardiac surgery are at high risk for early postoperative and late cardiac complications. A careful preoperative assessment and perioperative management may help to optimize the care of patients. The authors suggest a stepwise strategy for assessment of patients undergoing noncardiac surgery based on their previous work and that of others. C1 UNIV MICHIGAN,MED CTR,DEPT CARDIOL,ANN ARBOR,MI. RP PAUL, SD (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,ELLISON ROOM 908,BOSTON,MA 02114, USA. NR 119 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 1995 VL 79 IS 5 BP 1241 EP & PG 0 WC Medicine, General & Internal SC General & Internal Medicine GA RW547 UT WOS:A1995RW54700015 PM 7674693 ER PT J AU CARMICHAEL, KA CARMICHAEL, DH AF CARMICHAEL, KA CARMICHAEL, DH TI BONE METABOLISM AND OSTEOPENIA IN EATING DISORDERS SO MEDICINE LA English DT Review ID CORTICOSTEROID-INDUCED OSTEOPOROSIS; WEIGHT-BEARING EXERCISE; X-RAY ABSORPTIOMETRY; ANOREXIA-NERVOSA; MINERAL DENSITY; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; ADOLESCENT GIRLS; SERUM OSTEOCALCIN; LUMBAR SPINE C1 ST LOUIS UNIV,SCH MED,DEACONESS MED CTR,DEPT MED,ST LOUIS,MO. NR 132 TC 51 Z9 51 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD SEP PY 1995 VL 74 IS 5 BP 254 EP 267 DI 10.1097/00005792-199509000-00003 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA RX348 UT WOS:A1995RX34800003 PM 7565066 ER PT J AU BARSTOW, TJ SCREMIN, AME MUTTON, DL KUNKEL, CF CAGLE, TG WHIPP, BJ AF BARSTOW, TJ SCREMIN, AME MUTTON, DL KUNKEL, CF CAGLE, TG WHIPP, BJ TI GAS-EXCHANGE KINETICS DURING FUNCTIONAL ELECTRICAL-STIMULATION IN SUBJECTS WITH SPINAL-CORD INJURY SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE TIME CONSTANT; EXPONENTIAL; O-2 DEFICIT; EXCESS POSTEXERCISE OXYGEN CONSUMPTION; O-2 DEBT; SPINAL CORD INJURY ID OXYGEN-UPTAKE KINETICS; SUBMAXIMAL EXERCISE; QUADRICEPS MUSCLE; HEAVY EXERCISE; ONSET; DYNAMICS; CONSTANT; FIBERS; HUMANS; REST AB We examined the kinetics of VO2, VCO2, and V-E following the onset of unloaded leg cycling, and in recovery, in sis patients with spinal cord injury (SCI). Exercise was produced by functional electrical stimulation (FES) of the quadriceps, hamstrings, and gluteal muscles. End-exercise VO2 (1.03 +/- 0.16 l . min(-1)), VCO2 (1.20 +/- 0.22 l . min(-1)) and V-E (41 +/- 10 l . min(-1)) were elevated compared to values typically seen in healthy ambulatory subjects performing similar unloaded cycling Mean response times for the on transients (MRT(on)) were both long and Variable across subjects for VO2 (165 +/- 62 s), VCO2 (173 +/- 58 s), and V-E (202 +/- 61 s). Recovery kinetics showed much less intersubject variability, and for five of sis subjects were faster than the equivalent exercise MRT for all three variables (MRT(off) for VO2 of 103 +/- 28 s, VCO2 136 +/- 20 s, and V-E 144 +/- 34 s), but P > 0.05 for all three. Size of the O-2 deficit (1.96 +/- 0.90 l) and end-exercise lactate (7.05 +/- 1.65 mmol . l(-1)) were similar to Values reported for healthy sedentary subjects performing maximal voluntary exercise, but the end-exercise heart rate (102 +/- 16 bpm) was lower than expected for this intensity of exercise. Tn conclusion, FES-induced unloaded cycling leads to exaggerated responses of pulmonary gas exchange and long time constants in patients with SCI. The delayed kinetics may be due in part to a blunted increase in heart rate in addition to severe deconditioning. C1 W LOS ANGELES VET AFFAIRS MED CTR,PHYS MED & REHABIL SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. VET AFFAIRS MED CTR,PHYS MED & REHABIL SERV,ALBUQUERQUE,NM 87108. UNIV NEW MEXICO,DEPT ORTHOPED,ALBUQUERQUE,NM 87131. ST GEORGE HOSP,SCH MED,DEPT PHYSIOL,LONDON SW17 0RE,ENGLAND. RP BARSTOW, TJ (reprint author), UNIV CALIF LOS ANGELES,HARBOR MED CTR,ST JOHNS CARDIOVASC RES CTR,DEPT MED,TORRANCE,CA 90509, USA. NR 42 TC 25 Z9 25 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD SEP PY 1995 VL 27 IS 9 BP 1284 EP 1291 PG 8 WC Sport Sciences SC Sport Sciences GA RU235 UT WOS:A1995RU23500008 PM 8531627 ER PT J AU BOUCHER, Y LEE, I JAIN, RK AF BOUCHER, Y LEE, I JAIN, RK TI LACK OF GENERAL CORRELATION BETWEEN INTERSTITIAL FLUID PRESSURE AND OXYGEN PARTIAL-PRESSURE IN SOLID TUMORS SO MICROVASCULAR RESEARCH LA English DT Article ID RAT MAMMARY-TUMORS; BLOOD-FLOW; HUMAN-BREAST; HYPERTENSION; XENOGRAFTS; CARCINOMA; TISSUE; GROWTH; MICROENVIRONMENT; NICOTINAMIDE AB Several studies have shown a decrease in blood perfusion and oxygen partial pressure (pO(2)), and an increase in interstitial fluid pressure (IFP) with increasing tumor size. However, it is not evident if the elevated IFP is a key parameter responsible for the poor perfusion and oxygenation of solid tumors. To this end, IFP and pO(2) were measured in nine human tumor xenografts in immunodeficient mice at a fixed tumor size (similar to 250 mm(3)). IFP and pO(2) were also measured as a function of tumor volume in one human colon adenocarcinoma (LS174T) and in one human glioblastoma (HGL-9). In LS174T tumors IFP did not vary with size (P < 0.7); however, median pO(2) decreased from similar to 35 mm Hg in 100-mm(3) tumors to similar to 15 mm Hg in tumors of similar to 500 mm(3) (P < 0.001). In HGL-9 tumors an inverse correlation between IFP and pO(2) was found; IFP increased (P < 0.001) and pO(2) decreased (P < 0.001) with increasing tumor size. At a fixed tumor size of 250 mm(3) no correlation was found between mean IFP and median pO(2) (P < 0.5) or between the mean IFP and the hypoxic fraction PO2 < 2.5 mm Hg) (P < 0.7) in the nine tumors studied. The absence of a general relationship between IFP and pO(2) could result in part from differences in vascular resistance between tumors. For example, a high geometric resistance to blood flow on the arterial side will lead to a low IFP and blood flow, whereas an elevation of the venous resistance will reduce blood flow and increase IFP. In conclusion, our results show that there is no general relationship between IFP and oxygen levels in solid tumors. (C) 1995 Academic Press, Inc. RP BOUCHER, Y (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,RADIAT ONCOL BRANCH,EDWIN L STEELE LAB,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 56591] NR 29 TC 52 Z9 52 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 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD SEP PY 1995 VL 50 IS 2 BP 175 EP 182 DI 10.1006/mvre.1995.1051 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RX798 UT WOS:A1995RX79800004 PM 8538498 ER PT J AU OLIVA, E YOUNG, RH AF OLIVA, E YOUNG, RH TI NEPHROGENIC ADENOMA OF THE URINARY-TRACT - A REVIEW OF THE MICROSCOPIC APPEARANCE OF 80 CASES WITH EMPHASIS ON UNUSUAL FEATURES SO MODERN PATHOLOGY LA English DT Article DE NEPHROGENIC ADENOMA; BLADDER; URETHRA; URETER ID CLEAR CELL ADENOCARCINOMA; BLADDER; URETHRA; METAPLASIA; CARCINOMA; CYSTITIS AB A detailed review of the microscopic features of 80 nephrogenic adenomas of the urinary tract was undertaken. The lesions occurred in patients who ranged in age from 15 to 94 (average, 52) years. There was a 2:1 male/female ratio. Fifty-five percent of the lesions occurred in the urinary bladder, 41% in the urethra, and 4% in the ureter. The most common microscopic pattern, present in 96% of the cases, was tubular. The tubules were usually small, hollow, and round, but some were solid and occasionally elongated. Their arrangement varied from orderly, sometimes laminar, to pseudoinfiltrative. A basement membrane was appreciable around the tubules in 25% of the cases but was rarely prominent. In two prostatic urethral cases tubules involved the fibromuscular prostatic stroma. A cystic pattern was seen in 72% of the cases. The tubules and cysts most commonly contained eosinophilic secretion but in 25% of the cases the secretion was basophilic. In 12% of the cases some of the tubules were tiny and when they contained basophilic secretion occasionally mimicked signet-ring cells. The third most frequent pattern, seen in 65% of the cases, was papillary to polypoid. Edematous polyps were commonest but thin, delicate filiform papillae were present in 10% of the cases. A complex branching pattern with prominent budding of small papillae was seen in three cases. The papillary-polypoid pattern was usually associated with a tubular component but in three cases it was pure. The final pattern, present in 14% of the cases, was diffuse, but it was prominent in only one case. The usual cell type was cuboidal to low columnar but cells with bulbous apical nuclei (hobnail cells) were seen in 70% of the cases; however, they were numerous in only five cases. Fifteen percent of the cases contained cells with appreciable clear cytoplasm but they were conspicuous in only two cases. Nucleoli were typically absent or inconspicuous, but were focally prominent in 20% of the cases. Mitotic figures were not identified in 76 cases; single mitotic figures were present in four cases. The lack of significant cytologic atypicality, dearth of mitoses, frequent orderly growth, characteristic admired patterns, and lack of a transitional cell layer at the periphery of hollow tubules aid in distinction from adenocarcinoma and low-grade transitional cell carcinomas with small nests or hollow tubules which may mimic nephrogenic adenoma. Awareness of the spectrum of morphology of nephrogenic adenoma is crucial in enabling it to be diagnosed correctly and distinguished from its mimics. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114. NR 27 TC 68 Z9 71 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 1995 VL 8 IS 7 BP 722 EP 730 PG 9 WC Pathology SC Pathology GA RU831 UT WOS:A1995RU83100006 PM 8539229 ER PT J AU EICHHORN, JH SCULLY, RE AF EICHHORN, JH SCULLY, RE TI ADENOID CYSTIC AND BASALOID CARCINOMAS OF THE OVARY - EVIDENCE FOR A SURFACE EPITHELIAL LINEAGE - A REPORT OF 12 CASES SO MODERN PATHOLOGY LA English DT Article DE OVARY; ADENOID CYSTIC CARCINOMA; BASALOID CARCINOMA; AMELOBLASTOMA ID UTERINE CERVIX; ESOPHAGUS; TUMORS AB Twelve ovarian neoplasms resembling salivary gland carcinomas and cutaneous basal cell carcinomas were studied and assigned to two groups: six with an exclusive or conspicuous component resembling adenoid cystic carcinoma and six with an exclusive or predominant component resembling basal cell carcinoma. The patients whose tumors simulated an adenoid cystic carcinoma presented at 60 to 78 (mean, 67) years of age. The adenoid cystic-like pattern was present in the primary ovarian tumor in five cases and four of these tumors had an additional surface epithelial-stromal component (serous adenocarcinoma in two, endometrioid adenocarcinoma in one, and mixed clear cell/endometrioid adenocarcinoma in one). The one patient with a Stage Ia tumor was free of disease at 37 months. Of the four patients whose tumors were Stage IIIc, two died of tumor at 13 and 123 months, respectively; another was alive with tumor at 27 months; and one was lost to follow-up. In the sixth case, an adenoid cystic-like pattern was present in a recurrent tumor in a patient from whom an ovarian endometrioid adenocarcinoma had been excised 11 years earlier. The patients whose carcinomas were predominantly or entirely basaloid presented at 19 to 65 (mean, 49) years of age. Three of these tumors had prominent squamous differentiation and gland formation, suggesting a relation to endometrioid carcinoma; three other tumors had an ameloblastoma-like pattern, with focal squamous differentiation in one, and a minor component of endometrioid adenocarcinoma adjacent to another. The four patients in the basaloid carcinoma group with Stage Ia tumors were alive without tumor at 16 to 71 (mean, 35) months. Three of these patients had not received chemotherapy; it was not known if the fourth patient had received adjuvant therapy. The two other patients had Stage IIb and IIIb tumors, received chemotherapy, and were alive without disease at 59 and 39 months. The findings suggested that the carcinomas with adenoid cystic or basaloid patterns were of surface epithelial lineage. Those with an adenoid cystic appearance generally presented at a higher stage and behaved more aggressively than the basaloid carcinomas. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. RP EICHHORN, JH (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,WARREN 120,BOSTON,MA 02114, USA. NR 29 TC 9 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 1995 VL 8 IS 7 BP 731 EP 740 PG 10 WC Pathology SC Pathology GA RU831 UT WOS:A1995RU83100007 PM 8539230 ER PT J AU CHEN, DI VANHORN, DJ WHITE, MF BACKER, JM AF CHEN, DI VANHORN, DJ WHITE, MF BACKER, JM TI INSULIN-RECEPTOR SUBSTRATE-1 RESCUES INSULIN ACTION IN CHO CELLS EXPRESSING MUTANT INSULIN-RECEPTORS THAT LACK A JUXTAMEMBRANE NPXY MOTIF SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TYROSINE KINASE-ACTIVITY; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3'-KINASE; HEMATOPOIETIC-CELLS; IRS-1; PROTEIN; RAS; DOMAIN; SH2; PHOSPHORYLATION AB Insulin signals are mediated through tyrosine phosphorylation of specific proteins such as insulin receptor substrate 1 (IRS-1) and Shc by the activated insulin receptor (IR). Phosphorylation of both proteins is nearly abolished by an alanine substitution at Tyr-960 (A960) in the beta-subunit of the receptor. However, overexpression of IRS-1 in CHO cells expressing the mutant receptor (A960 cells) restored sufficient tyrosine phosphorylation of IRS-1 to rescue IRS-1/Grb-2 binding and phosphatidylinositol 3' kinase activation during insulin stimulation. Shc tyrosine phosphorylation and its binding to Grb-2 were impaired in the A960 cells and were unaffected by overexpression of IRS-1. Although overexpression of IRS-1 increased IRS-1 binding to Grb-2, ERK-1/ERK-2 activation was not rescued. These data suggest that signaling molecules other than IRS-1, perhaps including Shc, are critical for insulin stimulation of p21(ras). Interestingly, overexpression of IRS-1 in the A960 cells restored insulin-stimulated mitogenesis and partially restored insulin stimulation of glycogen synthesis. Thus, IRS-1 tyrosine phosphorylation is sufficient to increase the mitogenic response to insulin, whereas insulin stimulation of glycogen synthesis appears to involve other factors. Moreover, IRS-1 phosphorylation is either not sufficient or not involved in insulin stimulation of ERK. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MOLEC PHARMACOL,BRONX,NY 10461. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. FU NIDDK NIH HHS [DK-44541] NR 53 TC 23 Z9 23 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 SEP PY 1995 VL 15 IS 9 BP 4711 EP 4717 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RQ134 UT WOS:A1995RQ13400006 PM 7651388 ER PT J AU ZHANG, YJ ROLLINS, BJ AF ZHANG, YJ ROLLINS, BJ TI A DOMINANT-NEGATIVE INHIBITOR INDICATES THAT MONOCYTE CHEMOATTRACTANT PROTEIN-1 FUNCTIONS AS A DIMER SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID 3-DIMENSIONAL STRUCTURE; PLATELET FACTOR-4; ACTIVATING FACTOR; CYTOKINE FAMILY; INTERLEUKIN-8; PURIFICATION; EXPRESSION; CELLS AB Monocyte chemoattractant protein 1 (MCP-1) is a member of the chemokine family of proinflammatory cytokines, all of which share a high degree of amino acid sequence similarity, Aberrant expression of chemokines occurs in a variety of diseases that have an inflammatory component, such as atherosclerosis, Although structural analyses indicate that chemokines form homodimers, there is controversy about whether dimerization is necessary for activity. To address this question for MCP-1, we obtained evidence in four steps, First, coprecipitation experiments demonstrated that MCP-1 forms dimers at physiological concentrations, Second, chemically cross-linked MCP-1 dimers attract monocytes in vitro with a 50% effective concentration of 400 pM, identical to the activity of non-cross-linked MCP-1. Third, an N-terminal deletion variant of MCP-1 (called 7ND) that inhibits MCP-1-mediated monocyte chemotaxis specifically forms heterodimers with wild-type MCP-1, Finally, although 7ND inhibits wild-type MCP-1 activity, it has no effect on cross-linked MCP-1, These results indicate that 7ND is a dominant negative inhibitor, implying that MCP-1 activates its receptor as a dimer, In addition, chemical cross-linking restores activity to an inactive N-terminal insertional variant of MCP-1, further supporting the need for dimerization. Since the reported K-d for MCP-1 monomer dissociation is much higher than its 50% effective concentration or K-d for receptor binding, active dimer formation may require high local concentrations of MCP-1. Our data further suggest that the dimer interface can be a target for MCP-1 inhibitory drugs. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA53091] NR 29 TC 128 Z9 131 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1995 VL 15 IS 9 BP 4851 EP 4855 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RQ134 UT WOS:A1995RQ13400022 PM 7651403 ER PT J AU Geysen, HM Houghten, RA Kauffman, S Lebl, M Moos, MH Pavia, MR Szostak, JW AF Geysen, HM Houghten, RA Kauffman, S Lebl, M Moos, MH Pavia, MR Szostak, JW TI Molecular diversity comes of age! SO MOLECULAR DIVERSITY LA English DT Editorial Material C1 HOUGHTON PHARMACEUT INC,SAN DIEGO,CA 92121. SANTA FE INST,SANTA FE,NM 87501. CHIRON CORP,EMERYVILLE,CA 94608. SPHINX PHARMACEUT,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. SELECTIDE CORP,TUCSON,AZ 85737. RP Geysen, HM (reprint author), GLAXO WELLCOME INC,DIVERS SCI DEPT,5 MOORE DR,RES TRIANGLE PK,NC 27709, USA. OI Moos, Walter/0000-0001-7244-811X NR 0 TC 2 Z9 2 U1 0 U2 3 PU ESCOM SCI PUBL BV PI LEIDEN PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS SN 1381-1991 J9 MOL DIVERS JI Mol. Divers. PD SEP PY 1995 VL 1 IS 1 BP 1 EP 3 DI 10.1007/BF01715803 PG 3 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA VV712 UT WOS:A1995VV71200001 ER PT J AU WESTERHOF, GR SCHORNAGEL, JH KATHMANN, I JACKMAN, AL ROSOWSKY, A FORSCH, RA HYNES, JB BOYLE, FT PETERS, GJ PINEDO, HM JANSEN, G AF WESTERHOF, GR SCHORNAGEL, JH KATHMANN, I JACKMAN, AL ROSOWSKY, A FORSCH, RA HYNES, JB BOYLE, FT PETERS, GJ PINEDO, HM JANSEN, G TI CARRIER-MEDIATED AND RECEPTOR-MEDIATED TRANSPORT OF FOLATE ANTAGONISTS TARGETING FOLATE-DEPENDENT ENZYMES - CORRELATES OF MOLECULAR-STRUCTURE AND BIOLOGICAL-ACTIVITY SO MOLECULAR PHARMACOLOGY LA English DT Review ID THYMIDYLATE SYNTHASE INHIBITORS; BREAST-CANCER-CELLS; GLYCINAMIDE RIBONUCLEOTIDE FORMYLTRANSFERASE; MAMMALIAN FOLYLPOLYGLUTAMATE SYNTHETASE; DENOVO PURINE SYNTHESIS; L1210 LEUKEMIA-CELLS; BINDING-PROTEIN; METHOTREXATE TRANSPORT; CCRF-CEM; MEMBRANE-TRANSPORT AB The transport properties and growth-inhibitory potential of 37 classic and novel antifolate compounds have been tested in vitro against human and murine cell lines expressing different levels of the reduced folate carrier (RFC), the membrane-associated folate binding protein (mFBP), or both. The intracellular targets of these drugs were dihydrofolate reductase (DHFR), glycinamide ribonucleotide transformylase (GARTF), folylpolyglutamate synthetase (FPGS), and thymidylate synthase (TS). Parameters that were investigated included the affinity of both folate-transport systems for the antifolate drugs, their growth-inhibitory potential as a function of cellular RFC/mFBP expression, and the protective effect of either FA or leucovorin against growth inhibition. Methotrexate, aminopterin, N-10-propargyl-5,8-dideazafolic acid (CB3717), ZD1694, 5,8-dideazaisofolic acid (IAHQ), 5,10-dideazatetrahydrofolic acid (DDATHF), and 5-deazafolic acid (efficient substrate for FPGS) were used as the basic structures in the present study, from which modifications were introduced in the pteridine/quinazoline ring, the C-9-N-10 bridge, the benzoyl ring, and the glutamate side chain. It was observed that RFC exhibited an efficient substrate affinity for all analogues except CB3717, 2-NH2-ZD1694, and glutamate side-chain-modified FPGS inhibitors. Substitutions at the a-position (e.g., 2-CH3) improved the RFC substrate affinity for methotrexate and aminopterin. Other good substrates included PT523 (N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-orrithine), 10-ethyl-10-deazaaminopterin, and DDATHF. With respect to mFBP, modifications at the N-3 and 4-oxo positions resulted in a substantial loss of binding affinity. Modifications at other sites of the molecule were well tolerated. Growth-inhibition studies identified a series of drugs that were preferentially transported via RFC (2,4-diamino structures) or mFBP (CB3717, 2-NH2-ZD1694, or 5,8-dideazaisofolic acid), whereas other drugs were efficiently transported via both transport pathways (e.g., DDATHF, ZD1694, BW1843U89, or LY231514). Given the fact that for an increasing number of normal and neoplastic cells and tissues, different expression levels of RFC and mFBP are being recognized, this folate antagonist structure-activity relationship can be of value for predicting drug sensitivity and resistance of tumor cells or drug-related toxicity to normal cells and for the rational design and development of novel antifolates. C1 FREE UNIV AMSTERDAM HOSP, DEPT ONCOL, 1007 MB AMSTERDAM, NETHERLANDS. NETHERLANDS CANC INST, DEPT INTERNAL MED, 1066 CX AMSTERDAM, NETHERLANDS. INST CANC RES, DRUG DEV SECT, SUTTON 5N2 5NG, SURREY, ENGLAND. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02215 USA. MED UNIV S CAROLINA, DEPT PHARMACEUT SCI, CHARLESTON, SC 29425 USA. ZENECA PHARMACEUT, MACCLESFIELD SK10 4TG, CHESHIRE, ENGLAND. NR 115 TC 163 Z9 166 U1 0 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1995 VL 48 IS 3 BP 459 EP 471 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RX635 UT WOS:A1995RX63500011 PM 7565626 ER PT J AU SACHS, DH SYKES, M GREENSTEIN, JL COSIMI, AB AF SACHS, DH SYKES, M GREENSTEIN, JL COSIMI, AB TI TOLERANCE AND XENOGRAFT SURVIVAL SO NATURE MEDICINE LA English DT Editorial Material ID NONLETHAL PREPARATIVE REGIMEN C1 MASSACHUSETTS GEN HOSP EAST,BOSTON,MA 02129. BIOTRANSPLANT INC,BOSTON,MA 02129. RP SACHS, DH (reprint author), HARVARD UNIV,SCH MED,BLDG 149-9019,13TH ST,BOSTON,MA 02129, USA. NR 6 TC 37 Z9 37 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 1995 VL 1 IS 9 BP 969 EP 969 DI 10.1038/nm0995-969 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RT303 UT WOS:A1995RT30300056 PM 7585228 ER PT J AU FUJIMOTO, JG BREZINSKI, ME TEARNEY, GJ BOPPART, SA BOUMA, B HEE, MR SOUTHERN, JF SWANSON, EA AF FUJIMOTO, JG BREZINSKI, ME TEARNEY, GJ BOPPART, SA BOUMA, B HEE, MR SOUTHERN, JF SWANSON, EA TI OPTICAL BIOPSY AND IMAGING USING OPTICAL COHERENCE TOMOGRAPHY SO NATURE MEDICINE LA English DT Editorial Material ID BIOLOGICAL TISSUES; REFLECTOMETRY C1 MIT,COMP SCI RES LAB ELECTR,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MIT,LINCOLN LAB,LEXINGTON,MA 02173. RP FUJIMOTO, JG (reprint author), MIT,DEPT ELECT ENGN,30 VASSAR ST,CAMBRIDGE,MA 02139, USA. RI Boppart, Stephen/C-7338-2009 NR 21 TC 534 Z9 544 U1 3 U2 45 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 1995 VL 1 IS 9 BP 970 EP 972 DI 10.1038/nm0995-970 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RT303 UT WOS:A1995RT30300057 PM 7585229 ER PT J AU WAEBER, C MOSKOWITZ, MA AF WAEBER, C MOSKOWITZ, MA TI [H-3] SUMATRIPTAN LABELS BOTH 5-HT1D AND 5HT(1F) RECEPTOR-BINDING SITES IN THE GUINEA-PIG BRAIN - AN AUTORADIOGRAPHIC STUDY SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE [I-125] GTI; 5-CARBOXAMIDOTRYPTAMINE; CP-122,288; 5-HT RECEPTOR SUBTYPES ID SEROTONIN RECEPTOR; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; REGIONAL DISTRIBUTION; RADIOLIGAND BINDING; MESSENGER-RNA; RAT; SUBTYPE; SUMATRIPTAN; NEURONS AB We have used in vitro autoradiography to visualize [H-3]sumatriptan binding sites in sections of guinea-pig and rat brain. In saturation studies, this ligand recognized a single saturable population of high affinity binding sites in all regions examined (pK(D) = 8.3-9.3). While 5-HT and the sumatriptan derivative CP-122,288 (5-methyl-aminosulfonylmethyl-3-(N -methylpyrrolidin-2R-yl-methyl)-1H-indole) competed for [H-3]sumatriptan binding sites with a high affinity and monophasic profile, displacement experiments with 5-carboxamidotryptamine revealed the existence of 2 classes of binding sites. The high affinity component (pK(D) = 9.2-9.9) probably corresponded to 5-HT1B (rat) or 5-HT1D (guinea-pig) receptors. The intermediate affinity (pK(D) = 5.7-7.3) of the other component, taken together with their high affinity for [H-3]sumatriptan, was similar to that of the cloned 5-HT1F receptor. The regional distribution of the 5-HT1B/1D [H-3]sumatriptan binding sites was in agreement with previously published studies (striatonigral system, hypothalamus, central gray, superficial layer of the superior colliculus) and corresponded to the pattern of serotonin-5-O-carboxymethyl-glycyl [I-125]tyrosinamide labeling in consecutive sections. [H-3]sumatriptan binding sites with a low affinity for 5-CT predominated in the intermediate neocortical layers, the claustrum (in the guinea-pig only), the mammillary nuclei, most of the thalamic nuclei and the principal oculomotor nucleus (in the guinea-pig only). This distribution is very similar to that of 5-HT1F mRNA, indicating further the identity of these sites with 5-HT1F receptors. Very high densities of 5-HT1F sites were also found in the rat parafascicular nucleus. Some regions, such as the caudate/nucleus, the lateral geniculate nuclei and the spinal trigeminal nucleus appeared to contain both 5-HT1B/1D and 5-HT1F binding sites. Ketanserin had a low affinity for [H-3]sumatriptan binding sites in all guinea-pig brain regions, compatible with the presence of the 5-HT1D beta subtype. An exception was the substantia nigra, where a significant proportion of sites displayed an intermediate affinity for this compound, suggesting the presence of 5-HT1D alpha receptors. [H-3]5-HT labeled 5-HT1F sites in the claustrum and intermediate cortical layers in the guinea-pig. However these data show that [H-3]sumatriptan, in the presence of 10 nM 5-carboxamidotryptamine, is a more suitable radioligand to study the distribution of 5-HT1F binding sites. RP WAEBER, C (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,NEUROSURG SERV,149 13TH ST,BOSTON,MA 02129, USA. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 NR 56 TC 83 Z9 87 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD SEP PY 1995 VL 352 IS 3 BP 263 EP 275 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RT295 UT WOS:A1995RT29500003 PM 8584041 ER PT J AU GIORDANO, M DEFRONZO, RA AF GIORDANO, M DEFRONZO, RA TI ACUTE EFFECT OF HUMAN RECOMBINANT INSULIN-LIKE GROWTH-FACTOR-I ON RENAL-FUNCTION IN HUMANS SO NEPHRON LA English DT Article DE GLOMERULAR FILTRATION RATE; PHOSPHATE; POTASSIUM; RENAL PLASMA FLOW; SODIUM ID GLOMERULAR-FILTRATION RATE; COLLECTING DUCT; MESANGIAL CELLS; GENE-EXPRESSION; PLASMA-FLOW; HORMONE; SOMATOMEDIN; MEMBRANE; GLUCOSE; KIDNEY AB We examined the acute effects of insulin-like growth factor I (IGF-I) on renal function in 8 normal subjects who received a 3-hour intravenous infusion of IGF-I at a rate of 0.4 mu g/kg . min. After starting the IGF-I infusion, the plasma IGF-I concentration rose quickly and achieved a plateau after 90 min that was threefold above the basal value. During IGF-I infusion, progressive rises in glomerular filtration rate (from 93 +/- 4 to 121 +/- 6 ml/173 m(2) . min; p < 0.01) and renal plasma flow (from 529 +/- 31 to 703 +/- 55 ml/1.73 m(2) . min; p < 0.01) were observed, with no change in filtration fraction. The plasma levels of potassium and phosphate decreased significantly during the last 90 min of the study, while the plasma sodium concentration remained unchanged. A significant decrease in the fractional excretion of sodium, potassium, and phosphate was observed during the last 90 min of the IGF-I infusion period. The heart rate rose modestly with no change in mean arterial pressure. These findings show that, when administered acutely, IGF-I is a potent renal. vasodilator, but is antinatriuretic. IGF-I also enhances potassium and phosphate uptake by extrarenal tissues and reduces renal potassium and phosphate excretion. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV DIABET,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV NAPLES 2,INST INTERNAL MED & NEPHROL,NAPLES,ITALY. NR 30 TC 33 Z9 35 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-2766 J9 NEPHRON JI Nephron PD SEP PY 1995 VL 71 IS 1 BP 10 EP 15 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA RT600 UT WOS:A1995RT60000002 PM 8538827 ER PT J AU VANN, JM GOLDMAN, AJ SZUREK, PF BROOKS, BR AF VANN, JM GOLDMAN, AJ SZUREK, PF BROOKS, BR TI DEOXYGLUCOSE UPTAKE BY MOUSE ASTROCYTES - EFFECTS OF TEMPERATURE AND RETROVIRUS INFECTION SO NEUROCHEMICAL RESEARCH LA English DT Article DE FIBROBLAST; MURINE LEUKEMIA VIRUS; SARCOMA VIRUS; HIV-1; POSITRON EMISSION TOMOGRAPHY ID HUMAN-IMMUNODEFICIENCY-VIRUS; ROUS-SARCOMA VIRUS; CENTRAL-NERVOUS-SYSTEM; AIDS DEMENTIA COMPLEX; CHICK-EMBRYO FIBROBLASTS; MURINE LEUKEMIA-VIRUS; HUMAN GLIAL-CELLS; SUGAR-TRANSPORT; HEXOSE-TRANSPORT; GLUCOSE-UPTAKE AB Deoxyglucose uptake by FVB/N mouse astrocytes was studied before and after infection by ts1 retrovirus which causes a neurodegenerative disease in mice similar to HIV-1 encephalopathy in man. The Michaelis-Menten kinetic parameters, Km and Vmax, of 2-deoxy-D-glucose uptake by brain and cerebellar astrocytes were measured following culture al 34 degrees C where ts1 retrovirus replicates optimally, and at 37 degrees C. Compared to astrocytes cultured at 37 degrees C, astrocytes cultured at 34 degrees C had increased Km and decreased deoxyglucose uptake despite increased or unchanged Vmax. Following ts1 retrovirus infection, brain astrocyte deoxyglucose uptake doubled [132%] associated with decreased Km but unchanged Vmax, whereas cerebellar astrocyte deoxyglucose uptake doubled [102%] associated with increased Vmax but unchanged Km. These observations of altered deoxyglucose uptake kinetic parameters following retrovirus infection indicate different neurochemical mechanisms for the regional variation in deoxyglucose uptake observed following retrovirus infection of the CNS in vivo. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,NEUROL SERV,MADISON,WI 53705. WILLIAM S MIDDLETON MEM VET ADM MED CTR,RES SERV,MADISON,WI 53705. UNIV WISCONSIN,SCH MED,DEPT NEUROL MED MICROBIOL,MADISON,WI. UNIV WISCONSIN,SCH MED,DEPT IMMUNOL,MADISON,WI. NR 40 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD SEP PY 1995 VL 20 IS 9 BP 1013 EP 1020 DI 10.1007/BF00995554 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RX664 UT WOS:A1995RX66400006 PM 8570004 ER PT J AU MATTAMMAL, MB HARING, JH CHUNG, HD RAGHU, G STRONG, R AF MATTAMMAL, MB HARING, JH CHUNG, HD RAGHU, G STRONG, R TI AN ENDOGENOUS DOPAMINERGIC NEUROTOXIN - IMPLICATION FOR PARKINSONS-DISEASE SO NEURODEGENERATION LA English DT Article DE CELL DEATH; DOPAMINE; METABOLISM; NEUROTOXIN; PARKINSONISM ID NERVE GROWTH-FACTOR; PHEOCHROMOCYTOMA CELLS; BRAIN; GLUTATHIONE; NEURONS; 1-METHYL-4-PHENYLPYRIDINIUM; N-METHYL-4-PHENYLPYRIDINE; HYPOTHESIS; METABOLITE; ETIOLOGY AB Oxidation of dopamine by monoamine oxidase results in the endogenous metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). The toxicity of DOPAL for dopaminergic neurons was investigated using rat neostriatal synaptosomes, PC-12 cells and cultures of fetal rat dissociated mesencephalon. The Na+-dependent uptake of [H-3]DOPAL in synaptosomes was inhibited by mazindol. DOPAL selectively inhibited dopamine uptake but not [C-14]GABA uptake, induced membrane damage and liberation of dopamine into the medium. Incubation of PC-12 cells with 6.5 mu M of DOPAL for 24 h caused degeneration of the neuritic process, and the number of viable cells were reduced by 25% of control. There were practically no surviving cells after 24 h of incubation with 33 mu M of DOPAL. After 8 h of treatment with 33 mu M of DOPAL, dopamine and 3,4-dihydroxyphenylacetic acid content in the cells were reduced by 38% and 53% of control. DOPAL-induced cell damage released lactic acid dehydrogenase into the incubation media. This toxic effect of DOPAL was time- and concentration-dependent. In mesencephalic cultures, after exposure to 33 mu M of DOPAL, the surviving TH+ cells showed rounded cell body, and fibre network was highly reduced. These results indicate DOPAL is a neurotoxin and may be involved in the degeneration of dopaminergic neurons. (C) 1995 Academic Press Limited C1 VET ADM MED CTR, CLIN LAB SERV, ST LOUIS, MO 63125 USA. ST LOUIS UNIV, HLTH SCI CTR, DEPT INTERNAL MED, ST LOUIS, MO 63104 USA. ST LOUIS UNIV, HLTH SCI CTR, DEPT PATHOL, ST LOUIS, MO 63104 USA. ST LOUIS UNIV, HLTH SCI CTR, DEPT ANAT & NEUROBIOL, ST LOUIS, MO 63104 USA. AUDIE L MURPHY MEM VET ADM MED CTR, CTR GERIATR RES EDUC & CLIN, SAN ANTONIO, TX 78284 USA. UNIV TEXAS, HLTH SCI CTR, DEPT CELL & STRUCT BIOL, SAN ANTONIO, TX 78284 USA. UNIV TEXAS, HLTH SCI CTR, DEPT PHARMACOL, SAN ANTONIO, TX 78284 USA. RP VET ADM MED CTR, CTR GERIATR RES EDUC & CLIN 11G JB, ST LOUIS, MO 63125 USA. NR 37 TC 66 Z9 66 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1055-8330 J9 NEURODEGENERATION JI Neurodegeneration PD SEP PY 1995 VL 4 IS 3 BP 271 EP 281 DI 10.1016/1055-8330(95)90016-0 PG 11 WC Neurosciences SC Neurosciences & Neurology GA RX774 UT WOS:A1995RX77400004 PM 8581559 ER PT J AU SAPP, PC ROSEN, DR HOSLER, BA ESTEBAN, J MCKENNAYASEK, D OREGAN, JP HORVITZ, HR BROWN, RH AF SAPP, PC ROSEN, DR HOSLER, BA ESTEBAN, J MCKENNAYASEK, D OREGAN, JP HORVITZ, HR BROWN, RH TI IDENTIFICATION OF 3 NOVEL MUTATIONS IN THE GENE FOR CU/ZN SUPEROXIDE-DISMUTASE IN PATIENTS WITH FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS SO NEUROMUSCULAR DISORDERS LA English DT Article DE ALS; SOD1; MOTOR NEURON DISEASE; GENES AB About 10% of cases of amyotrophic lateral sclerosis (ALS), a paralytic disorder characterized by death of motor neurons in the brain and spinal cord, exhibit autosomal dominant inheritance. A subgroup of these familial cases are caused by mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). We report here three additional mutations occurring in the SOD1 gene in three families with ALS. Two of these changes are missense mutations in exon 5 of the SOD1 gene, resulting in leucine 144 to serine and alanine 145 to threonine substitutions. The third, a single base pair change in intron 4 immediately upstream of exon 5, results in an alternatively spliced mRNA. The alternate transcript conserves the open reading frame of exon 5, producing an SOD1 protein with three amino acids inserted between exons 4 and 5 (following residue 118). These three mutations bring to 29 the total number of distinct SOD1 mutations associated with familial ALS. C1 MASSACHUSETTS GEN HOSP EAST,CECIL B DAY LAB NEUROMUSCULAR RES,NEUROL SERV,BOSTON,MA 02129. MIT,HOWARD HUGHES MED INST,DEPT BIOL,CAMBRIDGE,MA 02139. INST SALUD CARLOS 3,CTR INVEST CLIN,SERV NEUROL,E-28019 MADRID,SPAIN. FU NINDS NIH HHS [1F32NSO9263-01A1, 1PO1NS31248-01] NR 20 TC 38 Z9 39 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD SEP PY 1995 VL 5 IS 5 BP 353 EP 357 DI 10.1016/0960-8966(95)00007-A PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RR939 UT WOS:A1995RR93900001 PM 7496169 ER PT J AU PODURI, A BEASONHELD, LL MOSS, MB ROSENE, DL HYMAN, BT AF PODURI, A BEASONHELD, LL MOSS, MB ROSENE, DL HYMAN, BT TI CA3 NEURONAL DEGENERATION FOLLOWS CHRONIC ENTORHINAL CORTEX LESIONS SO NEUROSCIENCE LETTERS LA English DT Article DE NEURODEGENERATION; ENTORHINAL CORTEX LESIONS; HIPPOCAMPUS; STEREOLOGY AB Entorhinal cortex lesions are a common experimental paradigm to study memory function and neural plasticity after hippocampal deafferentation, The long term consequences of such lesions are of particular interest both in the context of these models and because pathological changes of Alzheimer's disease destroy entorhinal cortex projection neurons. We used stereological counting techniques to assess the structural integrity of the hippocampal formation 0.5-28 months after entorhinal lesion in the rhesus monkey. Surprisingly, 18-28 months after lesion the number of CA3 neurons was decreased by 57%, while neuron numbers in other subfields did not change. These results suggest that delayed transsynaptic neural degeneration can occur long after brain injury. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. BOSTON UNIV,SCH MED,DEPT ANAT & NEUROBIOL,BOSTON,MA 02118. NIA,NEUROSCI LAB,BETHESDA,MD 20892. RI Rosene, Douglas/G-1973-2015 FU NIA NIH HHS [AG08487, AG00001] NR 15 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 1 PY 1995 VL 197 IS 1 BP 1 EP 4 DI 10.1016/0304-3940(95)11879-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA RV602 UT WOS:A1995RV60200001 PM 8545043 ER PT J AU UCHIYAMA, CM ZHU, JG CARROLL, RS LEON, SP BLACK, PM AF UCHIYAMA, CM ZHU, JG CARROLL, RS LEON, SP BLACK, PM TI DIFFERENTIAL DISPLAY OF MESSENGER-RIBONUCLEIC-ACID - A USEFUL TECHNIQUE FOR ANALYZING DIFFERENTIAL GENE-EXPRESSION IN HUMAN BRAIN-TUMORS SO NEUROSURGERY LA English DT Article DE BRAIN NEOPLASMS; DIFFERENTIAL DISPLAY; GENE EXPRESSION; KINESIN HEAVY CHAIN; POLYMERASE CHAIN REACTION ID HUMAN-MALIGNANT ASTROCYTOMA; SUPPRESSOR GENE; SHORT ARM; CHROMOSOME-17; HETEROZYGOSITY; IDENTIFICATION; PROGRESSION; INVOLVEMENT; SEQUENCE; DISTINCT AB IN THIS STUDY, a differential display method for messenger ribonucleic acid was successfully used to identify genes differentially expressed between normal human brain and malignant glioma tissues. A total of 60 differentially expressed sequences were initially identified, of which 21 were cloned and sequenced. Twenty of the cloned sequences represented novel genes, and one sequence represented a kinesin heavy chain (KHC) gene isoform. The KHC isoform was selected for further characterization. Northern blots of total ribonucleic acid isolated from normal brain and a glioblastoma were probed with our KHC probe and confirmed the differential expression of this gene. Expression analysis of a variety of normal human tissues demonstrated that this KHC isoform is expressed only in brain tissues, with no detectable expression in placenta, spleen, kidney, lung, liver, or skeletal muscle. Our results confirm the rapid and sensitive nature of the differential display technique in identifying differential gene expression. This method offers a means to identify new genes of biological interest in human brain tumors such as oncogenes, tumor suppressor genes, and tumor-specific markers. C1 BRIGHAM & WOMENS HOSP,NEUROSURG LABS,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,CTR BRAIN TUMOR,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV UTAH,MED CTR,DEPT NEUROSURG,SALT LAKE CITY,UT 84112. NR 25 TC 17 Z9 18 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD SEP PY 1995 VL 37 IS 3 BP 464 EP 469 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA RU161 UT WOS:A1995RU16100041 PM 7501111 ER PT J AU CARROLL, RS ZHANG, JP DASHNER, K SAR, M BLACK, PM AF CARROLL, RS ZHANG, JP DASHNER, K SAR, M BLACK, PM TI STEROID-HORMONE RECEPTORS IN ASTROCYTIC NEOPLASMS SO NEUROSURGERY LA English DT Article DE ANDROGEN RECEPTOR; GLUCOCORTICOID RECEPTOR; IMMUNOHISTOCHEMISTRY; NEOPLASMS; NORTHERN BLOT ANALYSIS; POLYMERASE CHAIN REACTION; PROGESTERONE RECEPTOR ID HUMAN GLUCOCORTICOID RECEPTOR; HUMAN ANDROGEN RECEPTOR; HUMAN-BREAST-CANCER; ANTIPEPTIDE ANTIBODIES; PROGESTERONE RECEPTORS; INTRACRANIAL TUMORS; HUMAN LEUKEMIA; DEXAMETHASONE; MENINGIOMAS; DNA AB THE PRESENCE OF specific steroid hormone-binding receptors has been correlated with the clinical response to hormonal therapy in a number of different neoplasias, including breast and prostate cancer. In this article, we investigated the expression of the androgen, estrogen, glucocorticoid, and progesterone receptor messenger ribonucleic acid (mRNA) and protein in a number of astrocytic neoplasms of various histological grades. Androgen and glucocorticoid receptor mRNA were detected in all astrocytic neoplasms examined, regardless of histological subtype. In contrast, progesterone receptor mRNA was observed more frequently in high-grade tumors than in low-grade tumors. Estrogen receptor mRNA was undetectable in all astrocytic tumors examined. These studies suggest a possible adjunct clinical use of hormonal therapy for the treatment of astrocytomas. Specific antagonists and agonists may allow the modulation of the growth of these tumors. Development of this body of knowledge may lead to the development of better treatment for these aggressive tumors. C1 BRIGHAM & WOMENS HOSP,CTR BRAIN TUMOR,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT SURG,BOSTON,MA 02115. UNIV N CAROLINA,SCH MED,DEPT CELL BIOL & ANAT,CHAPEL HILL,NC 27599. UNIV N CAROLINA,SCH MED,REPROD BIOL LABS,CHAPEL HILL,NC. RP CARROLL, RS (reprint author), BRIGHAM & WOMENS HOSP,NEUROSURG LABS,221 LONGWOOD AVE,ROOM 121,BOSTON,MA 02115, USA. NR 54 TC 57 Z9 61 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD SEP PY 1995 VL 37 IS 3 BP 496 EP 503 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA RU161 UT WOS:A1995RU16100057 PM 7501116 ER PT J AU RICE, LW MARK, SD BERKOWITZ, RS GOFF, BA LAGE, JM AF RICE, LW MARK, SD BERKOWITZ, RS GOFF, BA LAGE, JM TI CLINICOPATHOLOGICAL VARIABLES, OPERATIVE CHARACTERISTICS, AND DNA-PLOIDY IN PREDICTING OUTCOME IN OVARIAN EPITHELIAL CARCINOMA SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID FLOW CYTOMETRIC ANALYSIS; PROGNOSTIC FACTORS; CANCER; TUMORS; SURVIVAL; STAGE; PARAMETERS AB Objective: To test the hypothesis that DNA content can predict operative morbidity and survival in patients with ovarian carcinoma. Methods: Subjects included patients diagnosed with invasive epithelial ovarian carcinoma at Brigham and Women's Hospital between July 1987 and November 1989. Fifty-nine patients were included in this analysis, In all cases, now cytometry was performed on fresh tissue to evaluate DNA content. The medical records were reviewed in all patients for estimated blood loss, hospitalization days, intensive care unit days, operating room time, presence and size of residual disease, grade and type of tumor, stage, size of primary tumor, lymph node status, disease status, date of last examination, and number of months of follow-up. Results: Predictors for death included increasing age (P = .01), advanced stage (P = .007), the presence of malignant ascites (P = .03), residual tumor at completion of operation (P < .001), increased estimated blood loss (P < .001), increased hospitalization days (P < .001), and increased operating room hours (P < .001). When we controlled for age and stage, only estimated blood loss and residual tumor predicted poor outcome. Deoxyribonucleic acid ploidy, whether stratified as diploid or aneuploid or with DNA index cutoffs, did not predict tumor recurrence or survival rates. Conclusion: Deoxyribonucleic acid ploidy has not yet been proven to be of independent prognostic importance for identifying groups of patients at high risk of dying from invasive epithelial ovarian carcinoma. C1 BRIGHAM & WOMENS HOSP,DEPT OBSTET,DIV GYNECOL ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT GYNECOL,DIV GYNECOL ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT REPROD BIOL & PATHOL,DIV GYNECOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NCI,DIV CANC ETIOL,BIOSTAT BRANCH,ROCKVILLE,MD. GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC. NR 21 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 1995 VL 86 IS 3 BP 379 EP 385 DI 10.1016/0029-7844(95)00163-L PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RQ637 UT WOS:A1995RQ63700012 PM 7651646 ER PT J AU REMULLA, HD RUBIN, PAD SHORE, JW CUNNINGHAM, MJ AF REMULLA, HD RUBIN, PAD SHORE, JW CUNNINGHAM, MJ TI PSEUDODACRYOCYSTITIS ARISING FROM ANTERIOR ETHMOIDITIS SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article DE DACRYOCYSTITIS; ETHMOIDITIS; DACRYOCYSTORHINOSTOMY; ETHMOIDECTOMY AB The contiguous spread of inflammation from infected ethmoid sinuses to the surrounding tissues of the lacrimal drainage system can produce symptoms easily confused with acute dacryocystitis. We report the cases of two patients with presumed dacryocystitis whose patency of the lacrimal apparatus was established by probing, irrigation, and dacryocystography. Computerized tomography and magnetic resonance imaging demonstrated opacification of anterior ethmoid air cells adjacent to the region of the lacrimal sac. A greater awareness of this diagnostic possibility of pseudodacryocystitis arising from anterior ethmoiditis, together with improved noninvasive imaging techniques, will likely increase the observed incidence of this disease. This distinction is important since anterior ethmoidectomy, rather than dacryocystorhinostomy, is the treatment of choice when such pseudodacryocystitis proves unresponsive to antibiotic therapy. In misdiagnosed patients who undergo dacryocystorhinostomy, it is the coincidental limited anterior ethmoidectomy and not the lacrimal-nasal fistula that provides the cure. C1 MASSACHUSETTS EYE & EAR INFIRM,CTR EYE PLAST & ORBIT,DEPT OPHTHALMOL,BOSTON,MA 02114. NR 0 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0740-9303 J9 OPHTHALMIC PLAST REC JI Ophthalmic Plast. Reconstr. Surg. PD SEP PY 1995 VL 11 IS 3 BP 165 EP 168 DI 10.1097/00002341-199509000-00002 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA RQ920 UT WOS:A1995RQ92000002 PM 8541257 ER PT J AU DAMATO, RJ ADAMS, AP AF DAMATO, RJ ADAMS, AP TI ANGIOGENESIS INHIBITION IN AGE-RELATED MACULAR DEGENERATION SO OPHTHALMOLOGY LA English DT Editorial Material C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,SURG RES LAB,BOSTON,MA 02115. RP DAMATO, RJ (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114, USA. NR 9 TC 25 Z9 27 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 1995 VL 102 IS 9 BP 1261 EP 1262 PG 2 WC Ophthalmology SC Ophthalmology GA RX355 UT WOS:A1995RX35500010 PM 9097761 ER PT J AU SIEGNER, SW NETLAND, PA URBAN, RC WILLIAMS, AS RICHARDS, DW LATINA, MA BRANDT, JD AF SIEGNER, SW NETLAND, PA URBAN, RC WILLIAMS, AS RICHARDS, DW LATINA, MA BRANDT, JD TI CLINICAL-EXPERIENCE WITH THE BAERVELDT GLAUCOMA DRAINAGE IMPLANT SO OPHTHALMOLOGY LA English DT Article ID CHAMBER TUBE SHUNT; NEOVASCULAR GLAUCOMA; MOLTENO IMPLANT; REFRACTORY GLAUCOMA; ENCIRCLING BAND; LONG-TERM; FILTERING SURGERY; VALVE IMPLANTS; PATCH GRAFTS; SINGLE-PLATE AB Purpose: To assess clinical outcomes in patients who were treated with the Baerveldt glaucoma drainage implant. Methods: The authors performed a retrospective multicenter study of 100 patients (103 eyes) with medically uncontrollable glaucomas who underwent a one-stage implantation with either the 200-, 250-, 350-, or 500-mm(2) Baerveldt implant. The authors defined surgical success as 5 mmHg less than intraocular pressure less than 22 mmHg without additional glaucoma surgery and without loss of light perception. Results: With a mean follow-up of 13.6 +/- 0.9 months (range, 4-37 months), 74 eyes (71.8%) had successful outcomes. Cumulative life-table success rates were 90.3% at 3 months (n = 103), 72.6% at 6 months (n = 84), and 60.3% at 24 months (n = 34). Intraocular pressure (IOP) was reduced from a mean of 38.5 +/- 1.4 mmHg with 2.2 +/- 0.1 antiglaucoma medications to 15.1 +/- 0.8 mmHg (P < 0.0005) with 0.5 +/- 0.1 antiglaucoma medications (P < 0.0005). Visual acuity was improved or remained within one line of the preoperative visual acuity in 90 eyes (87.4%). Complications occurred in 74 eyes (71.8%). A significant portion of these complications (45%) was transient, resolving without any intervention. Only 8% were serious sight-threatening complications. The most common complications included shallow anterior chamber or hypotony (32%), choroidal effusion or hemorrhage (20.4%), corneal decompensation or edema (17.5%), hyphema (14.1%), and tube obstruction (12.6%). Conclusion: The Baerveldt implant is effective in lowering the IOP in patients with intractable glaucomas. Hypotony and other complications are common, which also have been reported in other nonvalved glaucoma drainage implants. However, the majority of these complications did not affect surgical outcome. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. UNIV S FLORIDA,DEPT OPHTHALMOL,TAMPA,FL. UNIV CALIF SAN FRANCISCO,DEPT OPHTHALMOL,SAN FRANCISCO,CA 94143. UNIV CALIF DAVIS,DEPT OPHTHALMOL,SACRAMENTO,CA 95817. NR 49 TC 106 Z9 109 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 1995 VL 102 IS 9 BP 1298 EP 1307 PG 10 WC Ophthalmology SC Ophthalmology GA RX355 UT WOS:A1995RX35500015 PM 9097766 ER PT J AU CHYNN, EW LOPEZ, MA PAVANLANGSTON, D TALAMO, JH AF CHYNN, EW LOPEZ, MA PAVANLANGSTON, D TALAMO, JH TI ACANTHAMOEBA-KERATITIS - CONTACT-LENS AND NONCONTACT LENS CHARACTERISTICS SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 30-NOV 03, 1994 CL SAN FRANCISCO, CA SP Amer Acad Ophthalmol AB Purpose: To identify potential differences in time to diagnosis and final visual outcome between contact lens and noncontact lens users with Acanthamoeba keratitis. Background: Prior studies have shown early diagnosis and therapy to be related to outcome but have not analyzed differences among patients with and without contact lenses. Methods: A retrospective analysis of II consecutive cases (involving 13 eyes) of Acanthamoeba keratitis diagnosed at one institution over a 3-year period. Results: Mean time to diagnosis was significantly longer in noncontact lens users versus those who wore contact lenses (mean, 5.8 versus 3.3 weeks). Fifty percent of patients who did not wear contact lenses had a poor outcome (visual acuity worse than 20/40 or penetrating keratoplasty) versus 14% of patients who wore contact lenses. Conclusion: Diagnoses were made later in patients without contact lenses, and these patients had a worse visual outcome than those with Acanthamoeba keratitis who wore contact lenses. All patients with unresponsive microbial keratitis, even those without contact lens use, should be evaluated for Acanthamoeba. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,CORNEA SERV,BOSTON,MA 02114. UNIV PEDRO HENRIQUEZ URENA,ELIAS SANTANA HOSP,DEPT OPHTHALMOL,SANTO DOMINGO,DOMINICAN REP. NR 16 TC 26 Z9 28 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 1995 VL 102 IS 9 BP 1369 EP 1373 PG 5 WC Ophthalmology SC Ophthalmology GA RX355 UT WOS:A1995RX35500024 PM 9097775 ER PT J AU HARRIS, WH AF HARRIS, WH TI THE LESSONS OF ACETABULAR COMPONENT FIXATION SO ORTHOPEDICS LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD SEP PY 1995 VL 18 IS 9 BP 811 EP 812 PG 2 WC Orthopedics SC Orthopedics GA RV956 UT WOS:A1995RV95600008 PM 8570478 ER PT J AU HARRIS, WH AF HARRIS, WH TI CEMENTED REVISION FOR FEMORAL FAILURE SO ORTHOPEDICS LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD SEP PY 1995 VL 18 IS 9 BP 854 EP 855 PG 2 WC Orthopedics SC Orthopedics GA RV956 UT WOS:A1995RV95600020 PM 8570490 ER PT J AU BUSABA, NY RAUCH, SD AF BUSABA, NY RAUCH, SD TI SIGNIFICANCE OF AUDITORY BRAIN-STEM RESPONSE AND GADOLINIUM-ENHANCED MAGNETIC-RESONANCE-IMAGING FOR IDIOPATHIC SUDDEN SENSORINEURAL HEARING-LOSS SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 18-21, 1994 CL SAN DIEGO, CA SP Amer Acad Otolaryngol Head & Neck Surg ID BELLS-PALSY; POTENTIALS; RECOVERY AB Previous studies tried to correlate prognosis and response to oral corticosteroids in patients with idiopathic sudden sensorineural hearing loss to such factors as the age of the patient, presence of vertigo, shape of the audiogram, or severity of the hearing loss. However, temporal bone histopathologic evidence shows that idiopathic sudden sensorineural hearing loss may be caused by cochleitis or cochlear nerve neuritis. Herein we report results of a retrospective study of 96 consecutive patients with idiopathic sudden sensorineural hearing loss who were evaluated with auditory brain stem responses and gadolinium-enhanced magnetic resonance imaging. Results of the auditory brain stem response and magnetic resonance imaging were correlated with hearing outcome. Follow-up was available for 65 patients: 14 with abnormal and 51 with normal auditory brain stem responses. The overall rate of hearing recovery or improvement was 65% in the normal auditory brain stem response group compared with 43% in the abnormal auditory brain stem response group (p = 0.07). Among the 38 patients treated with a tapering course of oral corticosteroids, the recovery or improvement rate was 83% for those with normal auditory brain stem responses and 56% for those with abnormal auditory brain stem responses (p < 0.05). Of the 27 patients who did not receive steroid therapy, the improvement rate was 41% in those with normal auditory brain stem responses and 20% in those with abnormal auditory brain stem responses (p = 0.09). Magnetic resonance imaging with gadolinium was obtained on all 14 patients with abnormal auditory brain stem responses but on none with normal auditory brain stem responses. Only 1 magnetic resonance image of 14 demonstrated an abnormality, showing a high signal intensity in the distal internal auditory canal; this resolved 6 weeks later on a follow-up magnetic resonance image. We conclude that idiopathic sudden sensorineural hearing loss patients with abnormal auditory brain stem responses have poorer hearing prognoses compared with those patients with normal auditory brain stem responses, irrespective of treatment. Idiopathic sudden sensorineural hearing loss patients with abnormal auditory brain stem responses may have cochlear neuritis causing their hearing loss or may have a more extensive involvement of their auditory system, and this ''lesion'' may have a lower spontaneous recovery rate and less response to therapy. Magnetic resonance imaging with gadolinium may show abnormal signal intensities along the course of the eighth nerve in patients with idiopathic sudden sensorineural hearing loss, but this is infrequent, and its prognostic implications are not clear. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP BUSABA, NY (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL HEAD & NECK SURG,243 CHARLES ST,BOSTON,MA 02114, USA. NR 15 TC 8 Z9 9 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 1995 VL 113 IS 3 BP 271 EP 275 DI 10.1016/S0194-5998(95)70117-6 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA RU335 UT WOS:A1995RU33500019 PM 7675489 ER PT J AU KRALL, LP AF KRALL, LP TI THE HISTORY OF DIABETES LAY ASSOCIATIONS SO PATIENT EDUCATION AND COUNSELING LA English DT Article; Proceedings Paper CT Patient Education 2000 Congress CY JUN 01-04, 1994 CL GENEVA, SWITZERLAND DE EDUCATION; TEACHING NURSES; INDIVIDUAL TEACHING; GROUP TEACHING; EMPOWERMENT AB With much of the developed world having the increasing sociologic and economic problems of an aging population, there is an increased awareness of educating patients to not only understand and follow the instructions of their medical teams but to have increased responsibility for their own care. Of all the chronic conditions? diabetes, for which there is no cure, is among the most expensive and education-intensive. The lifelong Type I insulin-dependent diabetics need to know how to adjust their life-style and activities but also how to take and adjust several times daily insulin injections, diet and exercise and how to keep a wary eye to avoid complications that might be life-threatening. Since individual instruction is not possible for the 100 million diabetics in the known world, this can be best accomplished by educating in groups. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP KRALL, LP (reprint author), JOSLIN DIABET CTR,BOSTON,MA 02215, USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD SEP PY 1995 VL 26 IS 1-3 BP 285 EP 291 DI 10.1016/0738-3991(95)00735-I PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA RW195 UT WOS:A1995RW19500045 PM 7494740 ER PT J AU CHAPMAN, PH BUCHBINDER, BR COSGROVE, GR JIANG, HJ AF CHAPMAN, PH BUCHBINDER, BR COSGROVE, GR JIANG, HJ TI FUNCTIONAL MAGNETIC-RESONANCE-IMAGING FOR CORTICAL MAPPING IN PEDIATRIC NEUROSURGERY SO PEDIATRIC NEUROSURGERY LA English DT Article DE CORTICAL MAPPING; EPILEPSY; FUNCTIONAL MAGNETIC RESONANCE IMAGING; NEUROIMAGING ID VISUAL-CORTEX; STIMULATION; LOCALIZATION; SURGERY AB Currently there is considerable interest in applying functional imaging modalities to the problem of cortical localization. We present the case of a 15-year-old boy with a seizure disorder related to a tumor in the dominant supplementary motor area. This case illustrates the usefulness of functional magnetic resonance imaging as a new imaging tool for localization of cortical function in younger patients. The functional magnetic resonance imaging provided an anatomically accurate topographic map of operative site and subcortical structures along with relevant functional cortex. This information was useful for both presurgical planning and intraoperative localization, Validation of the technique in this instance was confirmed with intraoperative cortical motor mapping and the postoperative result. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP CHAPMAN, PH (reprint author), MASSACHUSETTS GEN HOSP,DIV NEUROSURG,FRUIT ST,GRB 502,BOSTON,MA 02114, USA. NR 17 TC 19 Z9 20 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1016-2291 J9 PEDIATR NEUROSURG JI Pediatr. Neurosurg. PD SEP PY 1995 VL 23 IS 3 BP 122 EP 126 DI 10.1159/000120948 PG 5 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA TK034 UT WOS:A1995TK03400003 PM 8751292 ER PT J AU HAYES, G FORGO, J BRINGHURST, FR SEGRE, G MURER, H AF HAYES, G FORGO, J BRINGHURST, FR SEGRE, G MURER, H TI EXPRESSION OF PARATHYROID-HORMONE RECEPTORS IN MDCK AND LLC-PK1 CELLS SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE TISSUE CULTURE; ADENYLATE CYCLASE; PROXIMAL TUBULE; TRANSFECTION; PARATHYROID HORMONE ID OPOSSUM KIDNEY-CELLS; NA+/H+ EXCHANGER ISOFORM; PHOSPHATE-TRANSPORT; OK CELLS; CELLULAR MECHANISMS; EPITHELIAL-CELLS; COMMON RECEPTOR; PEPTIDE; CLONING; PTH AB Parathyroid hormone (PTH) inhibits renal proximal tubular phosphate (P-i) and bicarbonate reabsorption by regulating the activity of apical Na/P-i cotransport and Na/H exchange. Two renal epithelial cell lines [''proximal tubular'', LLC-PKi; ''distal tubular'', Madin-Darby canine kidney, (MDCK) cells] were stably transfected with complementary deoxyribonucleic acids (cDNAs) encoding a cloned PTH receptor in order to examine the polarity of transfected receptor function and whether or not intrinsic P-i transport is regulated by the transfected PTH receptor. The receptors are functionally coupled to the stimulation of adenosine 3':5' cyclic monophosphate (cAMP) production at both cell surfaces in LLC-PK1 cells, whereas this response is primarily limited to the basolateral surface in MDCK cells. Immunocytochemistry suggests an apical and basolateral localization of the transfected PTH receptor in LLC-PK, cells and only a basolateral localization in MDCK cells. PTH activation of the transfected receptors is not coupled to the regulation of intrinsic P-i transport in either LLC-PK1 or MDCK cells. C1 UNIV ZURICH,INST PHYSIOL,CH-8057 ZURICH,SWITZERLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE UNIT,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 11794, DK 47034] NR 35 TC 8 Z9 8 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD SEP PY 1995 VL 430 IS 5 BP 636 EP 644 DI 10.1007/BF00386157 PG 9 WC Physiology SC Physiology GA RZ138 UT WOS:A1995RZ13800006 PM 7478914 ER PT J AU YAO, ZH ELLIOTT, GT GROSS, GJ AF YAO, ZH ELLIOTT, GT GROSS, GJ TI MONOPHOSPHORYL LIPID-A PRESERVES MYOCARDIAL CONTRACTILE FUNCTION FOLLOWING MULTIPLE, BRIEF PERIODS OF CORONARY-OCCLUSION IN DOGS SO PHARMACOLOGY LA English DT Article DE MULTIPLE CORONARY OCCLUSIONS; MONOPHOSPHORYL LIPID A; MYOCARDIAL STUNNING; ISCHEMIA-REPERFUSION INJURY ID ISCHEMIA REPERFUSION INJURY; SUPEROXIDE-DISMUTASE; PROTECTION; CATALASE AB The effects of a 1- or 24-hour pretreatment regimen with monophosphoryl lipid A (MLA, 35 mu g/kg i.v.) on myocardial stunning produced by repetitive coronary occlusions were studied in barbital-anesthetized dogs. Regional segment function (% SS) and myocardial blood flow were measured by sonomicrometry and the radioactive microsphere technique, respectively. In controls, six 5-min periods of coronary occlusion interpersed with IO-min periods of reperfusion and ultimately followed by 2 h of reperfusion produced regional segment dysfunction. Pretreatment with MLA for Ih prior to the first occlusion period had no effect on % SS, however, pretreatment with MLA 24 h prior to the first occlusion period resulted in a significant (p < 0.05) improvement in the recovery of % SS at all reperfusion periods as compared to the control group, In addition, segment dysfunction during each occlusion period was significantly less severe in animals receiving a 24-hour pretreatment with MLA as compared to the controls, These results are the first to demonstrate that MLA, a lipid A derivative of endotoxin, preserves contractile function of ischemic myocardium in an in vivo canine model and that its cardio-protection is time dependent. C1 MED COLL WISCONSIN,DEPT PHARMACOL & TOXICOL,MILWAUKEE,WI 53226. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA. RIBI IMMUNOCHEM RES INC,HAMILTON,MT 59840. FU NHLBI NIH HHS [HL 08311] NR 14 TC 20 Z9 20 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0031-7012 J9 PHARMACOLOGY JI Pharmacology PD SEP PY 1995 VL 51 IS 3 BP 152 EP 159 DI 10.1159/000139329 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RV547 UT WOS:A1995RV54700003 PM 7501700 ER PT J AU NETSCHER, DT WIGODA, P THORNBY, J YIP, B RAPPAPORT, NH AF NETSCHER, DT WIGODA, P THORNBY, J YIP, B RAPPAPORT, NH TI THE HEMODYNAMIC AND HEMATOLOGIC EFFECTS OF CIGARETTE-SMOKING VERSUS A NICOTINE PATCH SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID BLOOD-FLOW; BREAST RECONSTRUCTION; TOBACCO SMOKING; FACE LIFT; SKIN; COMPLICATIONS; FIBRINOLYSIS; FIBRINOGEN; PATIENT; SMOKERS AB Patients who smoke have higher complication rates than nonsmokers in the postoperative period. The authors designed an experimental protocol for habitual smokers (n = 30) to determine the specific hemodynamic and hematologic adverse effects possibly caused by nicotine and whether the method of nicotine delivery and systemic nicotine levels achieved might influence these adverse effects. During the 5-day study, subjects were asked to refrain from smoking, and testing sessions were conducted as follows: on day 1, the subjects smoked two cigarettes immediately before testing; on day 3 (control day), testing was done after not smoking for 48 hours and then the subjects were instructed to wear a transdermal nicotine patch (PROSTEP 22 mg/day) for 24 hours and replace it with another so that, on day 5, testing took place after the subjects had worn the patch for approximately 34 hours. At each testing session, digital artery pulse amplitude and a number of clinical and serum blood level parameters were measured. Relative digital blood flow after smoking (69.2 +/- 5.8%) and with the patch (80.4 +/- 7.6%) was lower than on the control day (100.0 +/- 0.0%). The nicotine patch, unlike smoking, had no effect on vasopressin or fibrinogen concentrations, hematocrit, or white cell or platelet counts; both smoking and the patch resulted in elevated norepinephrine levels. C1 BAYLOR COLL MED,DIV PLAST SURG,HOUSTON,TX 77030. DEPT VET AFFAIRS MED CTR,HOUSTON,TX. UNIV TEXAS,SW MED CTR,DALLAS,TX. NR 37 TC 28 Z9 28 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD SEP PY 1995 VL 96 IS 3 BP 681 EP 688 DI 10.1097/00006534-199509000-00022 PG 8 WC Surgery SC Surgery GA RP607 UT WOS:A1995RP60700022 PM 7638293 ER PT J AU ODDOUX, C REICH, E AXELROD, F BLUMENFELD, A MAAYAN, C SLAUGENHAUPT, S GUSELLA, J OSTRER, H AF ODDOUX, C REICH, E AXELROD, F BLUMENFELD, A MAAYAN, C SLAUGENHAUPT, S GUSELLA, J OSTRER, H TI PRENATAL DIAGNOSTIC TESTING FOR FAMILIAL DYSAUTONOMIA USING LINKED GENETIC-MARKERS SO PRENATAL DIAGNOSIS LA English DT Article DE FAMILIAL DYSAUTONOMIA; PRENATAL DIAGNOSIS; LINKAGE ANALYSIS; LINKAGE DISEQUILIBRIUM ID LINKAGE MAP; CHROMOSOME-9 AB Familial dysautonomia (FD), a recessively inherited disease, has been mapped to chromosome 9q31. Highly polymorphic dinucleotide repeat markers flanking the genetic locus and at the same genetic location have been identified. We describe the prenatal diagnosis of FD using linkage and linkage disequilibrium analyses with these markers. Twelve families were analysed for informativeness and of these, seven went on to have prenatal testing (a total of eight fetuses tested). All of these fetuses were predicted to be heterozygous unaffected (FD carriers). Seven fetuses have come to term and are normal. In the absence of a recombinant proband, a panel of three proximal and three distal markers is sufficient to provide informative flanking markers and an 87-96 per cent likelihood of a highly predictive test. In an additional family at 1:4 risk for FD, no DNA was available from the propositus. This family was analysed using linkage disequilibrium to the #18 allele of the tightly linked marker D9S58 in conjunction with linkage analysis using data from two unaffected children. Prenatal diagnosis in this family indicated an affected fetus. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT GENET,CHARLESTON MOLEC NEUROGENET UNIT,CHARLESTON,MA 02129. HADASSAH UNIV HOSP,IL-91240 JERUSALEM,ISRAEL. RP ODDOUX, C (reprint author), NYU,MED CTR,DEPT PEDIAT,HUMAN GENET PROGRAM,MSB 136,550 1ST AVE,NEW YORK,NY 10016, USA. NR 13 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD SEP PY 1995 VL 15 IS 9 BP 817 EP 826 DI 10.1002/pd.1970150905 PG 10 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA RX991 UT WOS:A1995RX99100004 PM 8559751 ER PT J AU BLOCK, SD BILLINGS, JA AF BLOCK, SD BILLINGS, JA TI PATIENT REQUESTS FOR EUTHANASIA AND ASSISTED SUICIDE IN TERMINAL ILLNESS - THE ROLE OF THE PSYCHIATRIST SO PSYCHOSOMATICS LA English DT Review ID CANCER PAIN RELIEF; MEDICAL ILLNESS; ILL PATIENTS; PSYCHOLOGICAL FUNCTION; MENTAL-DISORDERS; MANAGEMENT; DEPRESSION; AIDS; DECISIONS; DEATH AB Psychosocial assessment and treatment are critical elements of care for terminally ill patients who desire hastened death. Most patients, in saying that they want to die, are asked for assistance in living-for help in dealing with depression, anxiety about the future , grief, lack of control, dependence, physical suffering, and spiritual despair. In this article, the authors review current understandings of the psychiatric aspects of request by terminally ill patients for assisted suicide and euthanasia; describe an approach to the common problems of physical, psychological, social, and spiritual suffering encountered in managing dying patients; and elaborate the functions of the psychiatrist in addressing these problems. C1 BRIGHAM & WOMENS HOSP,DIV PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT AMBULATORY CARE & PREVENT,TEACHING PROGRAM,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHELSEA MEM HLTH CTR,ADULT MED UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. OLSTEN KIMBERLY QUAL CARE HOSPICE,BOSTON,MA. TRINITY HOSPICE GREATER BOSTON,BOSTON,MA. RP BLOCK, SD (reprint author), HARVARD UNIV,COMMUNITY HLTH PLAN,DEPT AMBULATORY CARE & PREVENT,TEACHING PROGRAM,BOSTON,MA 02215, USA. NR 77 TC 78 Z9 78 U1 3 U2 7 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 1995 VL 36 IS 5 BP 445 EP 457 PG 13 WC Psychiatry; Psychology SC Psychiatry; Psychology GA RR104 UT WOS:A1995RR10400003 PM 7568652 ER PT J AU GREENBERG, DB AF GREENBERG, DB TI OXFORD TEXTBOOK OF PALLIATIVE MEDICINE - DOYLE,D, HANKS,GWC, MACDONALD,N SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP GREENBERG, DB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 1995 VL 36 IS 5 BP 505 EP 505 PG 1 WC Psychiatry; Psychology SC Psychiatry; Psychology GA RR104 UT WOS:A1995RR10400012 ER PT J AU RODRIGUEZDEVELASQUEZ, A YODER, IC VELASQUEZ, P PAPANICOLAOU, N AF RODRIGUEZDEVELASQUEZ, A YODER, IC VELASQUEZ, P PAPANICOLAOU, N TI IMAGING THE EFFECTS OF DIABETES ON THE GENITOURINARY SYSTEM SO RADIOGRAPHICS LA English DT Article ID URINARY-TRACT INFECTION; RENAL-ARTERY STENOSIS; EMPHYSEMATOUS PYELONEPHRITIS; TUBOOVARIAN ABSCESS; CYSTITIS; MELLITUS; SPECTRUM; DISEASE; WOMEN AB Diabetes mellitus is a common multisystemic disease with serious effects on the genitourinary system, In the radiology Literature, Little attention has been paid to developing an integral approach to imaging of the genitourinary tract in diabetes, The long-term effects of diabetes on the genitourinary system include diabetic nephropathy, papillary necrosis, renal artery stenosis, diabetic cystopathy, and vas deferens calcification, Diabetes-associated urinary tract infections include renal and perirenal abscesses, gas-forming infections such as emphysematous pyelonephritis and emphysematous cystitis, fungal infections, and xanthogranulomatous pyelonephritis, Diabetes-associated genital infections include Fournier gangrene and postmenopausal tube-ovarian abscess, In a diabetic with fever of unknown origin or in the event of a persistent infection in a diabetic with clinical deterioration despite use of antibiotics, radiologic studies can demonstrate the presence of genitourinary complications, Finally, radiologists should be aware of the risk of contrast material-induced nephropathy in diabetics. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 30 TC 34 Z9 34 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP PY 1995 VL 15 IS 5 BP 1051 EP 1068 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RV156 UT WOS:A1995RV15600005 PM 7501850 ER PT J AU PALMER, WE ROSENTHAL, DI SCHOENBERG, OI FISCHMAN, AJ SIMON, LS RUBIN, RH POLISSON, RP AF PALMER, WE ROSENTHAL, DI SCHOENBERG, OI FISCHMAN, AJ SIMON, LS RUBIN, RH POLISSON, RP TI QUANTIFICATION OF INFLAMMATION IN THE WRIST WITH GADOLINIUM-ENHANCED MR-IMAGING AND PET WITH 2-[F-18]-FLUORO-2-DEOXY-D-GLUCOSE SO RADIOLOGY LA English DT Article; Proceedings Paper CT 1994 Radiological-Society-of-North-America Scientific Assembly CY NOV 27-DEC 02, 1994 CL CHICAGO, IL SP Radiol Soc N Amer DE WRIST, ARTHRITIS; WRIST, CT; WRIST, MR; WRIST, RADIONUCLIDE STUDIES ID RHEUMATOID-ARTHRITIS; GADOPENTETATE DIMEGLUMINE; F-18 FLUORODEOXYGLUCOSE; DISEASE; THERAPY; KNEE; ABNORMALITIES; RADIOGRAPHS; SYNOVITIS; SYSTEM AB PURPOSE: To quantify the activity of joint inflammation with magnetic resonance (MR) imaging and positron emission tomography (PET). MATERIALS AND METHODS: Gadolinium-enhanced MR imaging and 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) PET of the wrist were performed prospectively in 12 patients receiving antiinflammatory therapy. Patients were studied three times: off medications for 2 weeks, after 2 weeks of treatment with prednisone or nonsteroid antiinflammatory drugs, and after 12 weeks of treatment with methotrexate. Volume of enhancing pannus (VEP) was determined from fat-suppressed MR images (12 patients). FDG uptake was calculated from PET images (11 patients). RESULTS: VEP and FDG uptake were closely correlated (r > .86, P < .0001), as were changes in VEP and standardized uptake volume (r > .91, P < .0002). VEP and FDG uptake were strongly associated with clinical findings in wrists (P < .002) but not with treatment outcomes (P > .05). CONCLUSION: Contrast material-enhanced MR imaging and PET allow quantification of volumetric and metabolic changes in joint inflammation and comparison of efficacies of antiinflammatory drugs. C1 MASSACHUSETTS GEN HOSP,DIV NUCL MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,ARTHRITIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NEW ENGLAND DEACONESS HOSP,DEPT MED,RHEUMATOL SECT,BOSTON,MA 02215. HARVARD UNIV,CTR EXPTL PHARMACOL & THERAPEUT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02138. MIT,CAMBRIDGE,MA 02139. RP PALMER, WE (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV BONE & JOINT,BOSTON,MA 02114, USA. NR 45 TC 145 Z9 147 U1 1 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1995 VL 196 IS 3 BP 647 EP 655 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RQ243 UT WOS:A1995RQ24300013 PM 7644624 ER PT J AU SHIOTA, G KAWASAKI, H NAKAMURA, T SCHMIDT, EV AF SHIOTA, G KAWASAKI, H NAKAMURA, T SCHMIDT, EV TI DOWN-REGULATION OF C-MYC MESSENGER-RNA AFTER COMPLETION OF LIVER-REGENERATION IN TRANSGENIC MICE EXPRESSING HEPATOCYTE GROWTH-FACTOR IN LIVER SO RESEARCH COMMUNICATIONS IN MOLECULAR PATHOLOGY AND PHARMACOLOGY LA English DT Article ID CELL-CYCLE; TRANSCRIPTION; GENE; PURIFICATION; INHIBITION; SEQUENCE; PROTEINS; CLONING; DNA; RNA AB Hepatocyte growth factor (HGF) is the potent mitogen for liver parenchymal cells. It has been demonstrated that HGF enhances liver regeneration in transgenic mice which express HGF highly and exclusively in hepatocytes. In HGF transgenic mice where DNA synthesis of hepatocytes is active, c-myc is induced through an increased transcription rate by HGF. Therefore, expression of c-myc is up-regulated by HGF in this condition. However, relations between c-myc, HGF and cell growth still remain unclear. To clarify regulatory mechanisms of c-myc, we measured c-myc mRNA, HGF mRNA, proliferating nuclear antigen (PCNA) mRNA, PCNA protein and labeling index after a two thirds partial hepatectomy in livers from transgenic mice which express HGF in liver. We found that expression of c-myc mRNA was high on day 1 and day 3, and decreased drastically on day 5 when liver regeneration had completed in HGF: transgenic mice (Shiota, et aE., 1994). Levels of PCNA protein and labeling index on day 1 after liver regeneration were higher in HGF: transgenic mice than those of normal siblings, but no differences were observed between HGF transgenic and wild type mice on day 3. Endogenous expression of HGF was observed only on day I, although transgene expression was almost constant during liver regeneration. These data suggest that cell-to-cell contact is more important for regulation of c-myc than levels of HGF mRNA. C1 OSAKA UNIV,BIOMED RES CTR,DIV BIOCHEM,SUITA,OSAKA 565,JAPAN. MASSACHUSETTS GEN HOSP,CTR CANC,DIV TUMOR BIOL,BOSTON,MA 02129. RP SHIOTA, G (reprint author), TOTTORI UNIV,SCH MED,DEPT INTERNAL MED 2,YONAGO,TOTTORI 683,JAPAN. NR 21 TC 3 Z9 3 U1 0 U2 0 PU P J D PUBLICATIONS LTD PI WESTBURY PA PO BOX 966, WESTBURY, NY 11590 SN 1078-0297 J9 RES COMMUN MOL PATH JI Res. Commun. Mol. Pathol. Pharmacol. PD SEP PY 1995 VL 89 IS 3 BP 259 EP 268 PG 10 WC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy GA RX914 UT WOS:A1995RX91400001 PM 8680795 ER PT J AU WITTE, T HARTUNG, K BODE, FM SCHMIDT, RE DEICHER, H AF WITTE, T HARTUNG, K BODE, FM SCHMIDT, RE DEICHER, H TI CHARACTERIZATION OF B-CELL LINES FROM SLE PATIENTS AND THEIR RELATIVES SO RHEUMATOLOGY INTERNATIONAL LA English DT Article DE SLE; LUPUS; EBV TRANSFORMATION; GENETICS ID SYSTEMIC LUPUS-ERYTHEMATOSUS; NATURAL-KILLER CELLS; EPSTEIN-BARR VIRUS; FC-GAMMA-RII; LYMPHOCYTES-B; HETEROGENEITY; HAPLOTYPES; EXPRESSION; RECEPTORS; RELEASE AB Epstein-Barr-virus (EBV)-transformed lymphoblastoid B-cell lines were generated from peripheral blood lymphocytes of 55 patients with systemic lupus erythematosus (SLE) and 44 healthy relatives. All donors have previously been extensively characterized with regard to clinical, serologic, and genetic parameters. Here, peripheral blood lymphocytes and lines were characterized for cell surface antigens. Furthermore, autoantibody production and proliferation rate of the cell lines were monitored. A significant difference between patients and relatives was the lower proliferation rate of EBV-transformed cell lines of the SLE patients. All SLE cell lines are available for interested researches and can be obtained from the European Cell Bank, Salisbury, UK. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV IMMUNOL,BOSTON,MA 02115. ZENT KRANKENHAUS REINKENHEIDE,ZENT LAB,W-2850 BREMERHAVEN,GERMANY. RP WITTE, T (reprint author), HANNOVER MED SCH,ZENTRUM INNERE MED & DERMATOL,KLIN IMMUNOL ABT,HANNOVER,GERMANY. RI Witte, Torsten/B-5783-2016 NR 29 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0172-8172 J9 RHEUMATOL INT JI Rheumatol. Int. PD SEP PY 1995 VL 15 IS 3 BP 89 EP 93 DI 10.1007/BF00302123 PG 5 WC Rheumatology SC Rheumatology GA RY276 UT WOS:A1995RY27600001 PM 8588125 ER PT J AU STONE, ME AF STONE, ME TI HANDBOOK OF CURRENT HEALTH AND MEDICINE - BUNCH,B SO RQ LA English DT Book Review RP STONE, ME (reprint author), MASSACHUSETTS GEN HOSP,TREADWELL LAB,REFERENCE SERV,BOSTON,MA 02114, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER LIBRARY ASSN PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 SN 0033-7072 J9 RQ JI RQ PD FAL PY 1995 VL 35 IS 1 BP 119 EP 120 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA TD108 UT WOS:A1995TD10800029 ER PT J AU ARRUNATEGUICORREA, VR DUTT, JE FOSTER, CS AF ARRUNATEGUICORREA, VR DUTT, JE FOSTER, CS TI VARIABLE REGION USAGE IN B-CELL DEFICIENT MICE IN A MODEL OF EXPERIMENTAL HERPES-SIMPLEX VIRUS RETINITIS SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN; ACTIVATION; GENES AB By using PCR, we have found previously that differences in T cell receptor alpha/beta chain variable region (TCR alpha/beta) gene expression in lymph nodes (LN) existed between susceptible and resistant mice following anterior chamber (AC) inoculation with herpes simplex virus (HSV). We now report and compare the immunoglobulin gene variable region (Ig V-H) and the TCR V beta mRNA expression in normal congenic mice (BALB/c and C.B-17) and also in B cell modulated C.B-17 mice (B-). RNA prepared from spleen and LN of these mice before and after HSV-AC inoculation was analysed by PCR using oligoprimers specific for 11 V-H gene families and 19 V beta gene families. Densitometry analysis revealed that V-H family mRNA expression levels in spleen and lymph nodes did not correlate with HSV susceptibility or resistance patterns in B-, BALB/c and C.B-17 mice. Analysis of TCR V beta chain genes showed that spleen of resistant C.B-17 and B- Ab transferred mice showed a preference for V beta 11 gene expression not seen in susceptible mice. In contrast, LN of BALB/c and B-, both susceptible mice, made TCR V beta transcripts that were indistinguishable from those generated by resistant C.B-17 mice, following HSV-AC inoculation. Finally, TCR V beta gene family repertoire appears to be severely diminished in uninfected B- mice (50% in LN and 45% in spleen) by anti-mu treatment. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HILLES IMMUNOL LABS,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,RHOADS MOLEC IMMUNOL LABS,BOSTON,MA 02114. FU NEI NIH HHS [EY-06008] NR 21 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD SEP PY 1995 VL 42 IS 3 BP 387 EP 395 DI 10.1111/j.1365-3083.1995.tb03672.x PG 9 WC Immunology SC Immunology GA RR540 UT WOS:A1995RR54000015 PM 7660070 ER PT J AU WYSS, DF CHOI, JS LI, J KNOPPERS, MH WILLIS, KJ ARULANANDAM, ARN SMOLYAR, A REINHERZ, EL WAGNER, G AF WYSS, DF CHOI, JS LI, J KNOPPERS, MH WILLIS, KJ ARULANANDAM, ARN SMOLYAR, A REINHERZ, EL WAGNER, G TI CONFORMATION AND FUNCTION OF THE N-LINKED GLYCAN IN THE ADHESION DOMAIN OF HUMAN CD2 SO SCIENCE LA English DT Article ID CELL-SURFACE LIGAND; LYMPHOCYTE-T; ALTERNATIVE PATHWAY; COUPLING-CONSTANTS; MAGNETIC-RESONANCE; BINDING-SITE; PROTEIN; ACTIVATION; RESOLUTION; GLYCOSYLATION AB The adhesion domain of human CD2 bears a single N-linked carbohydrate. The solution structure of a fragment of CD2 containing the covalently bound high-mannose N-glycan [-(N-acetylglucosamine)(2)-(mannose)5-8] was solved by nuclear magnetic resonance. The stem and two of three branches of the carbohydrate structure are well defined and the mobility of proximal glycan residues is restricted. Mutagenesis of all residues in the vicinity of the glycan suggests that the glycan is not a component of the CD2-CD58 interface; rather, the carbohydrate stabilizes the protein fold by counterbalancing an unfavorable clustering of five positive charges centered about lysine-61 of CD2. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. PROCEPT INC,CAMBRIDGE,MA 02139. DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 50 TC 274 Z9 283 U1 0 U2 12 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 1 PY 1995 VL 269 IS 5228 BP 1273 EP 1278 DI 10.1126/science.7544493 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RR842 UT WOS:A1995RR84200037 PM 7544493 ER PT J AU ABBOTT, WM AF ABBOTT, WM TI TRAINING VASCULAR SURGEONS IN ENDOVASCULAR PROCEDURES - ONE SURGEONS VIEW SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article RP ABBOTT, WM (reprint author), MASSACHUSETTS GEN HOSP,DEPT VASC SURG,FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD SEP PY 1995 VL 12 IS 3 BP 236 EP 241 DI 10.1055/s-2008-1061331 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RV998 UT WOS:A1995RV99800005 ER PT J AU KAUFMAN, JA AF KAUFMAN, JA TI MEDICAL DEVICE REGULATION IN THE UNITED-STATES - PROTECTING THE PUBLIC OR IMPEDING PROGRESS SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article RP KAUFMAN, JA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV VASC RADIOL,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD SEP PY 1995 VL 12 IS 3 BP 277 EP 283 DI 10.1055/s-2008-1061338 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RV998 UT WOS:A1995RV99800012 ER PT J AU DRUCKER, EA BRENNAN, TA AF DRUCKER, EA BRENNAN, TA TI LEGAL IMPLICATIONS OF PRACTICE GUIDELINES FOR PHYSICIANS AND PROFESSIONAL SOCIETIES SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article RP DRUCKER, EA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD SEP PY 1995 VL 12 IS 3 BP 310 EP 317 DI 10.1055/s-2008-1061344 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RV998 UT WOS:A1995RV99800018 ER PT J AU KAUFMAN, JA WALTMAN, AC AF KAUFMAN, JA WALTMAN, AC TI POLITICAL AND ECONOMIC-ISSUES IN INTERVENTIONAL RADIOLOGY - PREFACE SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Editorial Material RP KAUFMAN, JA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV VASC RADIOL,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD SEP PY 1995 VL 12 IS 3 BP U7 EP U8 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RV998 UT WOS:A1995RV99800002 ER PT J AU MUELLER, PR AF MUELLER, PR TI POLITICAL AND ECONOMIC-ISSUES IN INTERVENTIONAL RADIOLOGY SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Editorial Material RP MUELLER, PR (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD SEP PY 1995 VL 12 IS 3 BP U5 EP U5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RV998 UT WOS:A1995RV99800001 ER PT J AU PATRICK, DL DEYO, RA ATLAS, SJ SINGER, DE CHAPIN, A KELLER, RB AF PATRICK, DL DEYO, RA ATLAS, SJ SINGER, DE CHAPIN, A KELLER, RB TI ASSESSING HEALTH-RELATED QUALITY-OF-LIFE IN PATIENTS WITH SCIATICA SO SPINE LA English DT Article DE DISABILITY EVALUATION; HEALTH STATUS INDEXES; LOW BACK PAIN; QUALITY OF LIFE; SCIATICA AB Study Design. This study analyzed health-related quality-of-life measures and other clinical and questionnaire data obtained from the Maine Lumbar Spine Study, a prospective cohort study of persons with low back problems. Objective. For persons with sciatica, back pain-specific and general measures of health-related quality-of-life were compared with regard to internal consistency, construct validity, reproducibility, and responsiveness in detecting small changes over a 3-month period. Summary of Background Data. Data were collected from 427 participants with sciatica. Baseline in-person interviews were conducted with surgical and medical patients before treatment and by mail at 3 months. Methods. Health-related quality-of-life measures included symptoms (frequency and bothersomeness of pain and sciatica) functional status and well-being (modified back pain-specific Roland scale and Medical Outcomes Study 36-item Short Form Health Survey (SF-36), and disability (bed rest, work loss, and restricted activity days). Results. Internal consistency of measures was high. Reproducibility was moderate, as expected after a 3-month interval. The SF-36 bodily pain item and the modified Roland measure demonstrated the greatest amount of change and were the most highly associated with self-rated improvement. The specific and generic measures changed in the expected direction, except for general health perceptions, which declined slightly. A high correlation between clinical findings or symptoms and the modified Roland measure, SF-36, and disability days indicated a high degree of construct validity. Conclusions. These measures performed well in measuring the health-related quality-of-life of patients with sciatica, The modified Roland and the physical dimension of the SF-36 were the measures most responsive to change over time, suggesting their use in prospective evaluation. Disability day measures, although valuable for assessing the societal impact of dysfunction, were less responsive to changes over this short-term follow-up of 3 months. C1 UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. VET AFFAIRS MED CTR,HLTH SERV RES & DEV PROGRAM,SEATTLE,WA 98108. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MAINE HLTH INFORMAT CTR,AUGUSTA,ME. MAINE MED ASSESSMENT FDN,AUGUSTA,ME. RP PATRICK, DL (reprint author), UNIV WASHINGTON,SCH PUBL HLTH & COMMUNITY MED,DEPT HLTH SERV,SC-37,SEATTLE,WA 98195, USA. FU AHRQ HHS [HS-06344] NR 0 TC 488 Z9 503 U1 1 U2 13 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0362-2436 J9 SPINE JI SPINE PD SEP 1 PY 1995 VL 20 IS 17 BP 1899 EP 1908 DI 10.1097/00007632-199509000-00011 PG 10 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA RR718 UT WOS:A1995RR71800011 PM 8560339 ER PT J AU SHAMBERGER, RC HOLZMAN, RS GRISCOM, NT TARBELL, NJ WEINSTEIN, HJ WOHL, ME AF SHAMBERGER, RC HOLZMAN, RS GRISCOM, NT TARBELL, NJ WEINSTEIN, HJ WOHL, ME TI PROSPECTIVE EVALUATION BY COMPUTED-TOMOGRAPHY AND PULMONARY-FUNCTION TESTS OF CHILDREN WITH MEDIASTINAL MASSES SO SURGERY LA English DT Article ID THREATENING AIRWAY-OBSTRUCTION; FLOW-VOLUME LOOPS; ANESTHETIC MANAGEMENT; HODGKINS-DISEASE; TRACHEA AB Background. Our ability to predict respiratory compromise during general anesthesia in a child with an anterior mediastinal mass is limited. Two prior reports have found a correlation between adequacy of ventilation during general anesthesia and the tracheal cross-sectional area obtained from computed tomograms (computed tomography [CT] scans). These and other reports have suggested that pulmonary function tests may provide additional information regarding anesthetic risks, but no studies have evaluated the extent of respiratory compromise in children with an anterior mediastinal mass. Methods. We prospectively evaluated 31 children with mediastinal masses before 34 surgical procedures. At each evaluation the tracheal area (as a percent of the predicted area on the basis of age and gender) was determined by CT. Pulmonary function tests were performed in the sitting and supine positions. The eleven children with either a tracheal area or peak expiratory flow rate (PEFR) of less than 50% of predicted received only a local anesthetic; the majority of children above these levels (17 of 22) received a general anesthetic. Results. Eleven of 31 patients had significant pulmonary restriction as defined by total lung capacity of less than 75% of predicted. Eight patients had a PEFR in the supine position of less than 50% of predicted. PEFR was lower in the supine than the upright position in all patients (median value of decrease, 12%). In 28 of 34 evaluations the child had a tracheal area greater than 50% of predicted, a criterion proposed for safe uttilization of general anesthesia. This latter guideline, however, did not identify all patients with significant impairment of pulmonary function; five patients had a PEFR of less than 50% of predicted but tracheal areas of greater than 50% of predicted. All children were administered anesthetics uneventfully with these guidelines. Conclusions. Although the tracheal area can be accurately measured with the CT scan, this does not identify all children with mediastinal masses and abnormal pulmonary function. A large mass may produce significant restrictive impairment and hence reduction in PEFR by the intrathoracic volume it occupies and yet not cause tracheal compression. It may also reduce the PEFR by narrowing the bronchi distal to the carina. Currently no CT standards exist for measuring bronchial areas in children. Our study did not evaluate whether impaired pulmonary function as measured by PEFR would be predictive of respiratory collapse during general anesthesia because all were excluded and operated on under local anesthesia. General anesthesia was well tolerated in children with tracheal area and PEFR greater than 50% of predicted. Pulmonary function tests in children with anterior mediastinal masses may add valuable information to the anatomic evaluation obtained by CT scan. C1 CHILDRENS HOSP,DANA FARBER CANC INST,DEPT ANESTHESIA,BOSTON,MA. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT RADIOL,BOSTON,MA. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT RADIAT ONCOL,BOSTON,MA. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA. CHILDRENS HOSP,DANA FARBER CANC INST,DIV PULM MED,BOSTON,MA. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP SHAMBERGER, RC (reprint author), CHILDRENS HOSP,DANA FARBER CANC INST,DEPT SURG,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 15 TC 33 Z9 33 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 1995 VL 118 IS 3 BP 468 EP 471 DI 10.1016/S0039-6060(05)80360-5 PG 4 WC Surgery SC Surgery GA RT059 UT WOS:A1995RT05900002 PM 7652680 ER PT J AU AWDEH, ZL ALPER, CA FICI, DA RONCO, P YUNIS, EJ AF AWDEH, ZL ALPER, CA FICI, DA RONCO, P YUNIS, EJ TI PREDICTABILITY OF ALLOREACTIVITY AMONG UNRELATED INDIVIDUALS - ROLE FOR HLA-DPB1 SO TISSUE ANTIGENS LA English DT Article DE CLASS II; MLR-I; UNRELATED INDIVIDUAL; HLA-OPB1; SSOPH; PCR-ONV ID MIXED-LYMPHOCYTE CULTURE; INHERITED STRUCTURAL POLYMORPHISM; EXTENDED HAPLOTYPES; DNA; POLYMERASE; RESPONSES; ANTIGENS; LINKAGE; CELLS; MLC AB compared the mixed lymphocyte culture reaction (MLR-I) among unrelated individuals who are carriers of the extended haplotype [HLA-B8,SC01,DR3,DRB1*0301,DQB1*0201] on one chromosome and the generic specificity HLA-DR4 on the second chromosome. Genomic DNA samples from the same individuals were also analyzed for HLA-DRB1, DQB1 and DPB1 alleles by PCR and SSOPH typing and for DOB polymorphism by RFLP. HLA-DRB1 alleles, in paired MLR responses between unrelated individuals indicated that matching of HLA-DRB1 was a better predictor of non-reactivity than identity in HLA-DR generic types, (43% vs 22%). Moreover, 90% of the DRB1 matched pairs had nonreactive and weakly reactive MLR, whereas only 37% of DRB1 mismatched unrelated individuals gave weak or no reactions. Matching for HLA-DRB1 and HLA-DPB1 alleles eliminates a significant number of cell mixtures with MLR-I reactivity. Furthermore, some DPB1 mismatches, but not all, do not seem to elicit MLR-I reactivity. C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP AWDEH, ZL (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL29583, HL48675]; NIAID NIH HHS [AI14157] NR 36 TC 7 Z9 7 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD SEP PY 1995 VL 46 IS 3-1 SI SI BP 180 EP 186 DI 10.1111/j.1399-0039.1995.tb03117.x PG 7 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA RU718 UT WOS:A1995RU71800005 PM 8525477 ER PT J AU LEWIS, CB AF LEWIS, CB TI TREATMENT STRATEGIES AND RESEARCH IDEAS FOR THE OLDER PERSON - FROM THE EDITOR SO TOPICS IN GERIATRIC REHABILITATION LA English DT Editorial Material C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,WASHINGTON,DC 20052. MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. RP LEWIS, CB (reprint author), PHYS THERAPY SERV WASHINGTON DC INC,WASHINGTON,DC, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21701 SN 0882-7524 J9 TOP GERIATR REHABIL JI Top. Geriatr. Rehabil. PD SEP PY 1995 VL 11 IS 1 BP R6 EP R6 PG 1 WC Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA RQ879 UT WOS:A1995RQ87900001 ER PT J AU DAWSON, R BEAL, MF BONDY, SC DIMONTE, DA ISOM, GE AF DAWSON, R BEAL, MF BONDY, SC DIMONTE, DA ISOM, GE TI EXCITOTOXINS, AGING, AND ENVIRONMENTAL NEUROTOXINS - IMPLICATIONS FOR UNDERSTANDING HUMAN NEURODEGENERATIVE DISEASES SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Review ID CYANIDE-INDUCED NEUROTOXICITY; D-ASPARTATE RECEPTOR; TOXIN 3-NITROPROPIONIC ACID; EXCITATORY AMINO-ACIDS; DOPAMINE UPTAKE SITES; RAT CEREBRAL-CORTEX; PARKINSONS-DISEASE; AGED RATS; LIPID-PEROXIDATION; STRIATAL DOPAMINE AB We are an aging society and current demographic trends point to a likely increase in age-related neurodegenerative diseases. The aged population may have a number of unique risk factors that result in a predisposition to neuronal damage from environmental neurotoxins. This symposium addressed the involvement of excitatory amino acids as final common mediators of neuronal death associated with various types of neurotoxic insult. The roles of oxidative stress, mitochondrial energy metabolism, and disruption of calcium homeostasis were discussed in relation to excitoxicity and several experimental models of human neurodegenerative diseases. The neurotoxic actions of kainic acid, 3-nitropropionic acid, cyanide, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and methamphetamine were examined for their relevance as models of human neurodegenerative disorders. The mechanisms of action of excitotoxins in experimental models of Huntingtons's disease and Parkinson's disease were explored in light of the enhanced susceptibility and potential vulnerability of the aged nervous system to neurotoxins that perturb cellular metabolism and homeostatic processes. Bioenergetic defects and oxidative stress were found to be critical links in a neurotoxic cascade of events that trigger the sustained release of excitotoxic amino acids. The interrelationships among the aging process, the pathophysiology of neurodegenerative diseases, and the mechanism of action of various neurotoxins were addressed from the unifying perspective of the excitotoxic hypothesis of neuronal death. (C) 1995 Academic Press. Inc. C1 MASSACHUSETTS GEN HOSP, NEUROCHEM LAB, BOSTON, MA 02114 USA. UNIV CALIF IRVINE, DEPT COMMUNITY & ENVIRONM MED, IRVINE, CA 92717 USA. PARKINSONS INST, SUNNYVALE, CA 94086 USA. PURDUE UNIV, DEPT PHARMACOL & TOXICOL, W LAFAYETTE, IN 47907 USA. RP UNIV FLORIDA, DEPT PHARMACODYNAM, GAINESVILLE, FL 32610 USA. FU NIEHS NIH HHS [ES04140] NR 156 TC 75 Z9 77 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD SEP PY 1995 VL 134 IS 1 BP 1 EP 17 DI 10.1006/taap.1995.1163 PG 17 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA RU763 UT WOS:A1995RU76300001 PM 7676443 ER PT J AU VAMVAKAS, EC AF VAMVAKAS, EC TI PERIOPERATIVE BLOOD-TRANSFUSION AND CANCER RECURRENCE - METAANALYSIS FOR EXPLANATION SO TRANSFUSION LA English DT Article ID DESIGN AFFECTS OUTCOMES; COLORECTAL-CANCER; BREAST-CANCER; LUNG-CANCER; GASTRIC-CANCER; CURATIVE RESECTION; PROMOTE RECURRENCE; RANDOMIZED TRIALS; TUMOR RECURRENCE; LARYNGEAL-CANCER AB Background: Meta-analysis was used to explain disagreements across observational studies in regard to the association between perioperative transfusion and cancer recurrence. Study Design and Methods: Observational studies published in English from 1982 through 1994 were retrieved. Five or more articles published in complete form were identified for each of six cancer sites: colorectum, breast, head and neck, lung, prostate, and stomach. Necessary information for building a 2 x 2 contingency table could be extracted from 60 studies. Summary relative risks (RR) reflecting the ''average'' adverse transfusion effect were computed for each cancer site by the random-effects method. Seven study characteristics were examined as potential explanations for the disagreements among the published studies. Results: Before any adjustment for the effect of confounding, computed crude summary RRs suggested a significant (p < 0.05) deleterious transfusion effect in all cancer sites, except for breast. The RR of an adverse outcome was 1.49 in colorectal cancer (95% Cl, 1.23-1.79) and ranged from 1.06 in breast cancers to 3.62 in head and neck cancers. The disagreements among published studies were most marked in the case of colorectal and gastric cancers. These discrepancies could be explained, in part, by study design, because prospective investigations had not produced a significant unadjusted transfusion effect (RR = 1.18; 95% Cl, 0.93-1.51 in the case of colorectal cancer). Conclusion: A reduction in the size of the computed unadjusted transfusion effect (of an appropriate magnitude to adjust for the effect of confounding) might eliminate the significance of the average adverse effect in most studied cancer sites. Whether the entire unadjusted transfusion effect should be ascribed to the effect of confounding or whether a true, deleterious transfusion effect also exists can be resolved only by randomized controlled trials. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BLOOD TRANSFUS SERV,BOSTON,MA 02114. RP VAMVAKAS, EC (reprint author), HARVARD UNIV,SCH MED,GRJ-224,GRAY BLDG,BOSTON,MA 02114, USA. NR 99 TC 98 Z9 100 U1 0 U2 2 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1995 VL 35 IS 9 BP 760 EP 768 DI 10.1046/j.1537-2995.1995.35996029162.x PG 9 WC Hematology SC Hematology GA RW513 UT WOS:A1995RW51300011 PM 7570938 ER PT J AU ANDERSON, KC AF ANDERSON, KC TI CURRENT TRENDS - EVOLVING CONCEPTS IN TRANSFUSION MEDICINE - LEUKODEPLETED CELLULAR BLOOD COMPONENTS FOR PREVENTION OF TRANSFUSION-ASSOCIATED GRAFT-VERSUS-HOST DISEASE SO TRANSFUSION SCIENCE LA English DT Article RP ANDERSON, KC (reprint author), BOSTON UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BLOOD COMPONENT LAB,BOSTON,MA 02115, USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0955-3886 J9 TRANSFUS SCI JI Transfus. Sci. PD SEP PY 1995 VL 16 IS 3 BP 265 EP 268 DI 10.1016/0955-3886(95)90066-7 PG 4 WC Hematology SC Hematology GA TB455 UT WOS:A1995TB45500015 PM 10159884 ER PT J AU CAVINESS, VS TAKAHASHI, T NOWAKOWSKI, RS AF CAVINESS, VS TAKAHASHI, T NOWAKOWSKI, RS TI NUMBERS, TIME AND NEOCORTICAL NEURONOGENESIS - A GENERAL DEVELOPMENTAL AND EVOLUTIONARY MODEL SO TRENDS IN NEUROSCIENCES LA English DT Review ID CEREBRAL-CORTEX; VISUAL-CORTEX; STEM-CELLS; MAMMALS; NEURONS; BRAIN; MOUSE AB The number of neurons in the neocortex is the product of the size of the preneuronogenetic founder population, that is, the number of proliferative cells that are present at the onset of neuronogenesis, and neuronogenetic amplification occurring as neurons are being produced. The amount of neuronogenetic amplification is determined by changes in the output fraction, Q, from 0 to 1, over a fixed number of cell cycles, Greater neuronogenetic amplification would occur across species if the number of cell cycles during which Q < 0.5 increased. Since neither the length of the cell cycle nor the length of the neuronogenetic interval, that is, time per se, influence neuron number directly it is speculated that changes in these parameters are essential to neuronal diversity. C1 KEIO UNIV, SCH MED, DEPT PEDIAT, TOKYO 160, JAPAN. UNIV MED & DENT NEW JERSEY, ROBERT WOOD JOHNSON MED SCH, DEPT NEUROSCI & CELL BIOL, PISCATAWAY, NJ 08854 USA. RP CAVINESS, VS (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT NEUROL, BOSTON, MA 02114 USA. RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NINDS NIH HHS [NS12005, NS28061] NR 23 TC 411 Z9 418 U1 0 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD SEP PY 1995 VL 18 IS 9 BP 379 EP 383 DI 10.1016/0166-2236(95)93933-O PG 5 WC Neurosciences SC Neurosciences & Neurology GA RQ361 UT WOS:A1995RQ36100003 PM 7482802 ER PT J AU DICKERSIN, GR YOUNG, RH SCULLY, RE AF DICKERSIN, GR YOUNG, RH SCULLY, RE TI SIGNET-RING STROMAL AND RELATED TUMORS OF THE OVARY SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article; Proceedings Paper CT 7th Biennial Meeting of the Society-for-Ultrastructural-Pathology CY AUG, 1994 CL STEAMBOAT SPRINGS, CO SP Soc Ultrastruct Pathol DE NEOPLASM; OVARY; SIGNET-RING CELLS; STROMAL TUMOR; ULTRASTRUCTURE AB The signet-ring stromal tumor of the ovary, described only twice previously, is an enigmatic lesion in respect to its cell lineage and the nature of the cytoplasmic vacuoles that cause the signet-ring cell appearance. The vacuoles were shown in the initial report to contain no lipid, mucoprotein, or glycogen, and the ovarian stromal cell was assumed to be the cell of origin. The present study describes three ovarian neoplasms in which the immunohistochemical and ultrastructural findings support a stromal origin for the cells, and a fourth tumor that simulated the other three closely on light microscopic examination but had several features supporting a sex-cord rather than stromal origin: immunohistochemical staining for keratin and alpha smooth muscle actin, and globular keratin staining, similar to that seen in granulosa cell tumors; and numerous prominent junctions including desmosomes on electron microscopy. In only one of the four tumors were the vacuoles similar ultrastructurally to those in the first reported case, appearing to result from generalized edema of the cytoplasmic matrix. In a second tumor, the vacuoles resulted from hydropic swelling of numerous mitochondria, which filled the cytoplasm of the cells. In the other two tumors, the vacuoles were not cytoplasmic, but cytoplasmic pseudoinclusions of edematous extracellular matrix. An additional interesting finding in one of the four tumors was the presence of hyaline globules within and adjacent to the signet-ring cells. Ultrastructural examination revealed the globules to be degenerating erythrocytes, many of which had been phagocytosed by the tumor cells. C1 MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. RP DICKERSIN, GR (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,100 BLOSSOM ST,COX 5,BOSTON,MA 02114, USA. NR 9 TC 39 Z9 42 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD SEP-OCT PY 1995 VL 19 IS 5 BP 401 EP 419 PG 19 WC Microscopy; Pathology SC Microscopy; Pathology GA RT745 UT WOS:A1995RT74500009 PM 7483017 ER PT J AU DICKERSIN, GR OLIVA, E YOUNG, RH AF DICKERSIN, GR OLIVA, E YOUNG, RH TI ENDOMETRIOID-LIKE VARIANT OF OVARIAN YOLK-SAC TUMOR WITH FOCI OF CARCINOID - AN ULTRASTRUCTURAL-STUDY SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article; Proceedings Paper CT 7th Biennial Meeting of the Society-for-Ultrastructural-Pathology CY AUG, 1994 CL STEAMBOAT SPRINGS, CO SP Soc Ultrastruct Pathol DE GLANDULAR VARIANT; NEUROENDOCRINE DIFFERENTIATION; OVARY; ULTRASTRUCTURE; YOLK-SAC TUMOR ID ENDODERMAL SINUS TUMOR; INTESTINAL DIFFERENTIATION AB The endometrioid-like variant of ovarian yolk sac tumor is a rare neoplasm composed partially or completely of glandular tissue resembling endometrioid carcinoma, but identifiable histologically and immunohistochemically as an extraembryonic endodermally differentiated germ cell tumor. Only nine examples of this neoplasm have been published previously, and none was studied by electron microscopy. One of these rare neoplasms, the first documented to have foci of carcinoid, has recently been observed and studied ultrastructurally. Electron microscopic observations showed that the main component of the neoplasm had glandular epithelial cells with nuclear and cytoplasmic features difficult to distinguish from the cells of Mullerian endometrioid and endometrial adenocarcinoma, but a minor component of mucinous adenocarcinoma was confirmed as intestinal by the epithelial cells having characteristic microvilli with filamentous cores and rootlets. In addition, neuroendocrine cells present in the glands and in nests were readily identified ultrastructurally by their dense-core granules. Electron microscopy may be useful in supplementing light microscopic and immunohistochemical examination of this variant of yolk sac tumor. C1 MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. RP DICKERSIN, GR (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,100 BLOSSOM ST,COX 5,BOSTON,MA 02114, USA. NR 12 TC 6 Z9 6 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD SEP-OCT PY 1995 VL 19 IS 5 BP 421 EP 429 PG 9 WC Microscopy; Pathology SC Microscopy; Pathology GA RT745 UT WOS:A1995RT74500010 PM 7483018 ER PT J AU BARRY, MJ FLEMING, C COLEY, CM WASSON, JH FAHS, MC OESTERLING, JE AF BARRY, MJ FLEMING, C COLEY, CM WASSON, JH FAHS, MC OESTERLING, JE TI SHOULD MEDICARE PROVIDE REIMBURSEMENT FOR PROSTATE-SPECIFIC ANTIGEN TESTING FOR EARLY DETECTION OF PROSTATE-CANCER .3. MANAGEMENT STRATEGIES AND OUTCOMES SO UROLOGY LA English DT Review ID PREDICT PATHOLOGICAL STAGE; RADICAL RETROPUBIC PROSTATECTOMY; LYMPH-NODE DISSECTION; RADIATION-THERAPY; FOLLOW-UP; CONSERVATIVE MANAGEMENT; TRANSRECTAL ULTRASOUND; CLINICAL STAGE; GLEASON SCORE; PELVIC LYMPHADENECTOMY C1 HLTH OUTCOMES ASSOCIATES,VANCOUVER,WA. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,CTR EVALUAT CLIN SCI,HANOVER,NH 03756. MT SINAI SCH MED,INT LONGEV CTR,NEW YORK,NY. UNIV MICHIGAN,DEPT SURG,DIV UROL,ANN ARBOR,MI. RP BARRY, MJ (reprint author), MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,BOSTON,MA 02114, USA. FU AHRQ HHS [HS 08397, HS 06336] NR 141 TC 18 Z9 18 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD SEP PY 1995 VL 46 IS 3 BP 277 EP 289 DI 10.1016/S0090-4295(99)80208-8 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA RT469 UT WOS:A1995RT46900001 PM 7544931 ER PT J AU KHARBANDA, S REN, RB PANDEY, P SHAFMAN, TD FELLER, SM WEICHSELBAUM, RR KUFE, DW AF KHARBANDA, S REN, RB PANDEY, P SHAFMAN, TD FELLER, SM WEICHSELBAUM, RR KUFE, DW TI ACTIVATION OF THE C-ABL TYROSINE KINASE IN THE STRESS-RESPONSE TO DNA-DAMAGING AGENTS SO NATURE LA English DT Article ID CELL-CYCLE; PHOSPHORYLATION; BINDING AB THE product of the c-abl gene is a non-receptor tyrosine kinase that is localized to the nucleus and cytoplasm. The precise function of c-Abl is unknown. Here we show that ionizing radiation activates c-Abl. Similar results were obtained with the alkylating agents cis-platinum and mitomycin C. We also demonstrate that cells deficient in c-Abl fail to activate Jun kinase (JNK/SAP kinase) after ionizing radiation or alkylating agent exposure and that reconstitution of c-Abl in these cells restores that response. In contrast, the stress response to tumour-necrosis factor is stimulated by a c-Abl-independent mechanism. These findings indicate that c-abl is involved in the stress response to DNA-damaging agents. C1 BRANDEIS UNIV,ROSENSTIEL BASIC MED SCI RES CTR,DEPT BIOL,WALTHAM,MA 02254. UNIV WURZBURG,INST RADIOBIOL & CELL BIOL,MOLEC ONCOL LAB,D-97078 WURZBURG,GERMANY. UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP KHARBANDA, S (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CAN PHARMACOL,BOSTON,MA 02115, USA. NR 19 TC 428 Z9 436 U1 0 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD AUG 31 PY 1995 VL 376 IS 6543 BP 785 EP 788 DI 10.1038/376785a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RR836 UT WOS:A1995RR83600043 PM 7651539 ER PT J AU DEFRONZO, RA GOODMAN, AM ABELOVE, W REID, E PITA, J CALLAHAN, M JOHNSON, D PELAYO, E PUGH, J SHANK, M GARZA, P HAAG, B KORFF, J ANGELO, A IZENSTEIN, B VANDERLEEDEN, M CATHCART, H TIERNEY, M BIGGS, D KARAM, J NOLTE, M GAVIN, L ELDER, MA CORBOY, J THWAITE, D WONG, S DAVIDSON, M PETERS, A DUNCAN, T KERCHER, S FISCHER, J KIPNES, M RADNICK, BJ ROURA, M ROQUE, J MONTGOMERY, C COLLUM, P RUST, M POHL, S PFEIFER, M ALLWEISS, P LEICHTER, S LEACH, P GALLINA, D MUSEY, V BERKOWITZ, K EASTMAN, R TAYLOR, T DELAPENA, MS ZAWADSKI, J GRIMES, P TANENBERG, R VIGERSKY, R PHILLIPS, G BROWNING, S FLOOD, T FLOOD, J SELTZER, H DAVIDSON, J ROSENSTOCK, J ROBERTS, V FLANDERS, D CLARK, C ALEXANDER, C STEINKELER, S FISHER, C FINEBERG, S BRIDGES, J BLEVINS, V SAUDEK, C GEORGOPOULOS, K MONAKIL, M COOPPAN, R BEASER, R GANDA, O ROSENZWEIG, J WOLFSDORF, J WRAY, M KILO, C DUDLEY, J OJILE, J WHITSETT, M PALUMBO, PJ KENNEDY, F KUBLY, M GARBER, A HUFFMAN, D GANDY, S KELLY, L TUCKER, W MILLER, E HINSHAW, H KLEINMANN, R BECK, J BLONDE, L ZIMMERMAN, R MURRAY, J REDDY, S MIRANDA, E MURRAY, J FAESSLER, V FALKO, J RAO, M JEFFERS, L BROWN, J LARSON, L FLOYD, J KNOPF, R VANAPPLEDORN, S GERICH, J JOHNSTON, J SALATA, R CONSOLI, A EVRON, W KORYTKOWSKI, M MOKAN, M DERISO, L VIGNATI, L GOLDSTEIN, H HUDSON, M SHEEHAN, R GRUNBERGER, G VANDENBERG, M AF DEFRONZO, RA GOODMAN, AM ABELOVE, W REID, E PITA, J CALLAHAN, M JOHNSON, D PELAYO, E PUGH, J SHANK, M GARZA, P HAAG, B KORFF, J ANGELO, A IZENSTEIN, B VANDERLEEDEN, M CATHCART, H TIERNEY, M BIGGS, D KARAM, J NOLTE, M GAVIN, L ELDER, MA CORBOY, J THWAITE, D WONG, S DAVIDSON, M PETERS, A DUNCAN, T KERCHER, S FISCHER, J KIPNES, M RADNICK, BJ ROURA, M ROQUE, J MONTGOMERY, C COLLUM, P RUST, M POHL, S PFEIFER, M ALLWEISS, P LEICHTER, S LEACH, P GALLINA, D MUSEY, V BERKOWITZ, K EASTMAN, R TAYLOR, T DELAPENA, MS ZAWADSKI, J GRIMES, P TANENBERG, R VIGERSKY, R PHILLIPS, G BROWNING, S FLOOD, T FLOOD, J SELTZER, H DAVIDSON, J ROSENSTOCK, J ROBERTS, V FLANDERS, D CLARK, C ALEXANDER, C STEINKELER, S FISHER, C FINEBERG, S BRIDGES, J BLEVINS, V SAUDEK, C GEORGOPOULOS, K MONAKIL, M COOPPAN, R BEASER, R GANDA, O ROSENZWEIG, J WOLFSDORF, J WRAY, M KILO, C DUDLEY, J OJILE, J WHITSETT, M PALUMBO, PJ KENNEDY, F KUBLY, M GARBER, A HUFFMAN, D GANDY, S KELLY, L TUCKER, W MILLER, E HINSHAW, H KLEINMANN, R BECK, J BLONDE, L ZIMMERMAN, R MURRAY, J REDDY, S MIRANDA, E MURRAY, J FAESSLER, V FALKO, J RAO, M JEFFERS, L BROWN, J LARSON, L FLOYD, J KNOPF, R VANAPPLEDORN, S GERICH, J JOHNSTON, J SALATA, R CONSOLI, A EVRON, W KORYTKOWSKI, M MOKAN, M DERISO, L VIGNATI, L GOLDSTEIN, H HUDSON, M SHEEHAN, R GRUNBERGER, G VANDENBERG, M TI EFFICACY OF METFORMIN IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RISK-FACTORS; NIDDM; SULFONYLUREAS; BIGUANIDES; THERAPY; RETINOPATHY; PREVALENCE; RESISTANCE; MECHANISM; PLASMA AB Background. Sulfonylurea drugs have been the only oral therapy available for patients with non-insulin-dependent diabetes mellitus (NIDDM) in the United States, Recently, however, metformin has been approved for the treatment of NIDDM. Methods. We performed two large, randomized, parallel-group, double-blind, controlled studies in which metformin or another treatment was given for 29 weeks to moderately obese patients with NIDDM whose diabetes was inadequately controlled by diet (protocol 1: metformin vs. placebo; 289 patients), or diet plus glyburide (protocol 2: metformin and glyburide vs, metformin vs. glyburide; 632 patients). To determine efficacy we measured plasma glucose (while the patients were fasting and after the oral administration of glucose), lactate, lipids, insulin, and glycosylated hemoglobin before, during, and at the end of the study. Results. In protocol 1, at the end of the study the 143 patients in the metformin group, as compared with the 146 patients in the placebo group, had lower mean (+/-SE) fasting plasma glucose concentrations (189+/-5 vs. 244+/-6 mg per deciliter [10.6+/-0.3 vs. 13.7+/-0.3 mmol per liter], P<0.001) and glycosylated hemoglobin values (7.1+/-0.1 percent vs. 8.6+/-0.2 percent, P<0.001). In protocol 2, the 213 patients given metformin and glyburide, as compared with the 209 patients treated with glyburide alone, had lower mean fasting plasma glucose concentrations (187+/-4 vs. 261+/-4 mg per deciliter [10.5+/-0.2 vs. 14.6+/-0.2 mmol per liter], P<0.001) and glycosylated hemoglobin values (7.1+/-0.1 percent vs. 8.7+/-0.1 percent, P<0.001). The effect of metformin alone was similar to that of glyburide alone. Eighteen percent of the patients given metformin and glyburide had symptoms compatible with hypoglycemia, as compared with 3 percent in the glyburide group and 2 percent in the metformin group. In both protocols the patients given metformin had statistically significant decreases in plasma total and low-density lipoprotein cholesterol and triglyceride concentrations, whereas the values in the respective control groups did not change. There were no significant changes in fasting plasma lactate concentrations in any of the groups. Conclusions. Metformin monotherapy and combination therapy with metformin and sulfonylurea are well tolerated and improve glycemic control and lipid concentrations in patients with NIDDM whose diabetes is poorly controlled with diet or sulfonylurea therapy alone. C1 LIPHA PHARMACEUT,NEW YORK,NY. ARIZONA HLTH SCI CTR,TUCSON,AZ. AUDIE L MURPHY VET AFFAIRS HOSP,SAN ANTONIO,TX. BAYSTATE MED CTR,SPRINGFIELD,MA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA. CEDARS SINAI MED CTR,LOS ANGELES,CA. DIABET EDUC & RES CTR,PHILADELPHIA,PA. DIABET & GLANDULAR DIS CLIN,SAN ANTONIO,TX. MEM HOSP,CTR DIABET & THYROID,JACKSONVILLE,FL. DIABET RES & ANAL ASSOC,LEXINGTON,KY. EMORY UNIV,SCH MED,ATLANTA,GA. GEORGETOWN UNIV HOSP,WASHINGTON,DC. GEORGIA CTR DIABET,ATLANTA,GA. HUMANA MED CITY DALLAS HOSP,DALLAS,TX. INDIANA UNIV,SCH MED,INDIANAPOLIS,IN. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. JOSLIN DIABET CTR,BOSTON,MA. KILO DIABET & VASC RES FDN,ST LOUIS,MO. MAYO CLIN,ROCHESTER,MN. METHODIST HOSP,HOUSTON,TX. NALLE CLIN,CHARLOTTE,NC. OCHSNER CLIN & ALTON OCHSNER MED FDN,NEW ORLEANS,LA. OHIO STATE UNIV,COLL MED,COLUMBUS,MS. UNIV IOWA,IOWA CITY,IA. UNIV MICHIGAN HOSP,CLIN RES CTR,ANN ARBOR,MI. UNIV PITTSBURGH,PRESBYTERIAN UNIV HOSP,PITTSBURGH,PA. WALTHAM WESTERN HOSP & MED CTR,WALTHAM,MA. WAYNE STATE UNIV,SCH MED,DETROIT,MI. RP DEFRONZO, RA (reprint author), UNIV TEXAS,HLTH SCI CTR,DIV DIABET,7703 FLOYD CURL DR,SAN ANTONIO,TX 78229, USA. NR 32 TC 777 Z9 801 U1 3 U2 25 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 31 PY 1995 VL 333 IS 9 BP 541 EP 549 DI 10.1056/NEJM199508313330902 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA RQ751 UT WOS:A1995RQ75100002 PM 7623902 ER PT J AU VALLEJO, M MILLER, CP BEEKMAN, W HABENER, JF AF VALLEJO, M MILLER, CP BEEKMAN, W HABENER, JF TI REPRESSION OF SOMATOSTATIN GENE-TRANSCRIPTION MEDIATED BY 2 PROMOTER SILENCER ELEMENTS SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE TRANSCRIPTION; SILENCER; SOMATOSTATIN; PANCREATIC ISLET ID NEURON-SPECIFIC EXPRESSION; PANCREATIC-ISLET CELLS; CAMP-RESPONSE ELEMENT; DNA-BINDING PROTEINS; SODIUM-CHANNEL GENE; RAT SOMATOSTATIN; NEGATIVE REGULATION; SCG10 GENE; ENHANCER; SEQUENCE AB We report that expression of the somatostatin gene in pancreatic islet and in non-islet cells is negatively regulated by two proximal silencer elements, PS1 and PS2. Transient transfection assays showed that PS1 decreases somatostatin gene promoter activity stimulated by an upstream enhancer in the islet D-cell line RIN-1027-B2, but not in the islet B-cell line RIN-1046-38, whereas PS2 inhibits gene transcription in both B- and D-cell lines. In BHK fibroblasts, both PS1 and PS2 independently inhibit somatostatin gene promoter activity, suggesting that both elements are involved in preventing the expression of the somatostatin gene in non-islet cells. DNA-binding studies revealed that both PS1 and PS2 bind similar nuclear protein complexes in islet and non-islet cells (120 and 130 kDa). PS1 also binds a 100-kDa protein present in islet Band D-cell lines. In addition, both PS1 and PS2 bind three D-cell-specific proteins (40, 43 and 45 kDa). These observations support a direct involvement of both positive and negative transcriptional control mechanisms in the regulation of the islet cell-specific expression of the somatostatin gene. RP VALLEJO, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,REPROD ENDOCRINE UNIT,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK30834, DK30457] NR 42 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD AUG 30 PY 1995 VL 113 IS 1 BP 61 EP 72 DI 10.1016/0303-7207(95)03615-E PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA RW774 UT WOS:A1995RW77400007 PM 8674814 ER PT J AU COLE, BF GELBER, RD GOLDHIRSCH, A AF COLE, BF GELBER, RD GOLDHIRSCH, A TI A QUALITY-ADJUSTED SURVIVAL METAANALYSIS OF ADJUVANT CHEMOTHERAPY FOR PREMENOPAUSAL BREAST-CANCER SO STATISTICS IN MEDICINE LA English DT Article ID CONTROLLED TRIAL; CMF PROGRAM; CYCLOPHOSPHAMIDE; METHOTREXATE; FLUOROURACIL; THERAPIES; DISEASE AB The purpose of this paper is to develop and apply a meta-analysis methodology, that does not require patient-level data, for comparing treatments in terms of quality-of-life-adjusted survival. As a motivating example, we considered adjuvant chemotherapy for breast cancer. This therapy has been shown to offer an improvement in recurrence-free and overall survival, especially for younger women, but its acute toxic effects discourage some physicians from prescribing it. To determine whether the benefit of adjuvant chemotherapy treatment outweighs its costs in terms of toxic effects, we performed a meta-analysis of quality-adjusted survival based on data from 1229 patients, 49 years of age or younger, randomized in eight clinical trials that compared chemotherapy versus no adjuvant systemic therapy. We conducted the meta-analysis by performing a quality-adjusted survival analysis known as a Q-TWiST analysis on each trial. A Q-TWiST analysis allows one to make treatment comparisons that incorporate differences in quality of life associated with various health states. In this analysis, we define as health states the periods of time patients spend: (i) with subjective toxic effects of chemotherapy; (ii) without symptoms of recurrence and toxicity, and (iii) following disease recurrence. We assigned weights to each health state which reflect their relative value in terms of quality of life and allowed them to vary in a sensitivity analysis. We then combined the individual trial results in a meta-analysis, using a multivariate regression model, in such a way that we could easily perform an overall sensitivity analysis. Individual patient-level data are not required to perform this meta-analysis methodology if the individual Q-TWiST analysis results for each trial are available. C1 BROWN UNIV,DIV APPL MATH,PROVIDENCE,RI 02912. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. OSPED CIVICO,DEPT ONCOL,CH-6900 LUGANO,SWITZERLAND. RP COLE, BF (reprint author), BROWN UNIV,DEPT COMMUNITY HLTH,BOX F,PROVIDENCE,RI 02912, USA. FU NCI NIH HHS [CA-06516] NR 27 TC 17 Z9 17 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD AUG 30 PY 1995 VL 14 IS 16 BP 1771 EP 1784 DI 10.1002/sim.4780141606 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA RQ642 UT WOS:A1995RQ64200005 PM 7481209 ER PT J AU KOBAYASHI, T GRABAREK, Z GERGELY, J COLLINS, JH AF KOBAYASHI, T GRABAREK, Z GERGELY, J COLLINS, JH TI EXTENSIVE INTERACTIONS BETWEEN TROPONIN-C AND TROPONIN-I - ZERO-LENGTH CROSS-LINKING OF TROPONIN-I AND ACETYLATED TROPONIN-C SO BIOCHEMISTRY LA English DT Article ID SKELETAL-MUSCLE TROPONIN; AMINO-ACID-SEQUENCE; PROTON-MAGNETIC-RESONANCE; BIOLOGICAL-ACTIVITY; INHIBITORY REGION; BINDING-SITES; PROTEOLYTIC FRAGMENTS; SYNTHETIC PEPTIDES; REGULATORY DOMAIN; DISULFIDE BOND AB Interactions between troponin C (TnC) and troponin I (TnI) play an important role in the Ca2+-dependent regulation of vertebrate striated muscle contraction. Earlier studies have led to the proposal that the ''inhibitory region'' (residues 96-116) of TnI binds to an alpha-helical segment of TnC comprising residues 89-100 in the nonregulatory, C-terminal domain. Subsequently, on the basis of the results of zero-length cross-linking, we suggested that the inhibitory region of TnI also interacts with the N-terminal, regulatory domain of TnC [Leszyk, J., Grabarek, Z., Gergely, J., and Collins, J. H. (1990) Biochemistry 29, 299-304]. In the present study, we acetylated the epsilon-NH2 groups of the nine lysines of TnC in order to avoid complications which may arise from intramolecular cross-linking between NH2 and COOH groups of TnC. We then activated the COOH groups of acetylated TnC (AcTnC) with 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide and N-hydroxysuccinimide. The activated AcTnC was combined with TnI, and zero-length cross-links were formed between COOH groups in AcTnC and lysine epsilon-NH2 groups in TnI. The cross-linked heterodimer (AcCxI) was cleaved with CNBr and proteases, and the resulting cross-linked peptides were separated by HPLC and then sequenced. Our results show extensive cross-linking between AcTnC and TnI, involving both the N-terminal and C-terminal domains of TnC, as well as the N-terminal, C-terminal, and inhibitory regions of TnI. C1 UNIV MARYLAND,SCH MED,INST BIOTECHNOL,DEPT BIOL CHEM,BALTIMORE,MD 21201. UNIV MARYLAND,INST BIOTECHNOL,CTR MED BIOTECHNOL,BALTIMORE,MD 21201. BOSTON BIOMED RES INST,MUSCLE RES GRP,BOSTON,MA. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NHLBI NIH HHS [R-37-HL-05949]; NIAMS NIH HHS [AR-41156] NR 56 TC 18 Z9 18 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 29 PY 1995 VL 34 IS 34 BP 10946 EP 10952 DI 10.1021/bi00034a029 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RT655 UT WOS:A1995RT65500029 PM 7662676 ER PT J AU MALACH, R REPPAS, JB BENSON, RR KWONG, KK JIANG, H KENNEDY, WA LEDDEN, PJ BRADY, TJ ROSEN, BR TOOTELL, RBH AF MALACH, R REPPAS, JB BENSON, RR KWONG, KK JIANG, H KENNEDY, WA LEDDEN, PJ BRADY, TJ ROSEN, BR TOOTELL, RBH TI OBJECT-RELATED ACTIVITY REVEALED BY FUNCTIONAL MAGNETIC-RESONANCE-IMAGING IN HUMAN OCCIPITAL CORTEX SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; HUMAN BRAIN; SENSORY STIMULATION; RECOGNITION AB The stages of integration leading from local feature analysis to object recognition were explored in human visual cortex by using the technique of functional magnetic resonance imaging. Here we report evidence for object-related activation. Such activation was located at the lateral-posterior aspect of the occipital lobe, just abutting the posterior aspect of the motion-sensitive area MT/V5, in a region termed the lateral occipital complex (LO), LO showed preferential activation to images of objects, compared to a wide range of texture patterns, This activation was not caused by a global difference in the Fourier spatial frequency content of objects versus texture images, since object images produced enhanced LO activation compared to textures matched in power spectra but randomized in phase, The preferential activation to objects also could not be explained by different patterns of eye movements: similar levels of activation were observed when subjects fixated on the objects and when they scanned the objects with their eyes, Additional manipulations such as spatial frequency filtering and a 4-fold change in visual size did not affect LO activation, These results suggest that the enhanced responses to objects were not a manifestation of low-level visual processing, A striking demonstration that activity in LO is uniquely correlated to object detectability was produced by the ''Lincoln'' illusion, in which blurring of objects digitized into large blocks paradoxically increases their recognizability. Such blurring led to significant enhancement of LO activation, Despite the preferential activation to objects, LO did not seem to be involved in the final, ''semantic,'' stages of the recognition process, Thus, objects varying widely in their recognizability (e.g., famous faces, common objects, and unfamiliar three-dimensional abstract sculptures) activated it to a similar degree. These results are thus evidence for an intermediate link in the chain of processing stages leading to object recognition in human visual cortex. C1 MASSACHUSETTS GEN HOSP,CTR NUCL MAGNET RESONANCE,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NCI NIH HHS [P01CA48729]; NEI NIH HHS [EY07980]; NIMH NIH HHS [R01MH50054] NR 17 TC 1100 Z9 1105 U1 1 U2 50 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 29 PY 1995 VL 92 IS 18 BP 8135 EP 8139 DI 10.1073/pnas.92.18.8135 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RR844 UT WOS:A1995RR84400010 PM 7667258 ER PT J AU SCHULTZE, JL CARDOSO, AA FREEMAN, GJ SEAMON, MJ DALEY, J PINKUS, GS GRIBBEN, JG NADLER, LM AF SCHULTZE, JL CARDOSO, AA FREEMAN, GJ SEAMON, MJ DALEY, J PINKUS, GS GRIBBEN, JG NADLER, LM TI FOLLICULAR LYMPHOMAS CAN BE INDUCED TO PRESENT ALLOANTIGEN EFFICIENTLY - A CONCEPTUAL-MODEL TO IMPROVE THEIR TUMOR IMMUNOGENICITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID T-CELL PROLIFERATION; ANTITUMOR IMMUNITY; B-CELLS; COSTIMULATION; ACTIVATION; CTLA-4; EXPRESSION; RECEPTOR; SIGNAL; CD28 AB In the tumor-bearing host, T cells invariably fail to induce a clinically significant antitumor immune response, Although model systems support the existence of tumor peptide antigens, the molecular interactions critical for antigen presentation by the tumor cell remain unresolved, Here, we demonstrate that human follicular lymphoma cells are highly inefficient at presenting alloantigen despite their strong expression of major histocompatibility complex and low-to-intermediate expression of some adhesion and B7 costimulatory molecules, Activation of follicular lymphoma cells via CD40 induces or up-regulates both adhesion and B7 costimulatory molecules essential to repair this defect, More importantly, once primed, alloreactive T cells efficiently recognize unstimulated follicular lymphoma cells. Thus, correction of defective tumor immunity requires not only expression of major histocompatibility complex but also sufficient expression of multiple adhesion and costimulatory molecules. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP SCHULTZE, JL (reprint author), DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [CA40216, CA34183]; NIAID NIH HHS [AI 35225] NR 28 TC 170 Z9 174 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 29 PY 1995 VL 92 IS 18 BP 8200 EP 8204 DI 10.1073/pnas.92.18.8200 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RR844 UT WOS:A1995RR84400024 PM 7545296 ER PT J AU UBERLA, K STAHLHENNIG, C BOTTIGER, D MATZRENSING, K KAUP, FJ LI, J HASELTINE, WA FLECKENSTEIN, B HUNSMANN, G OBERG, B SODROSKI, J AF UBERLA, K STAHLHENNIG, C BOTTIGER, D MATZRENSING, K KAUP, FJ LI, J HASELTINE, WA FLECKENSTEIN, B HUNSMANN, G OBERG, B SODROSKI, J TI ANIMAL-MODEL FOR THE THERAPY OF ACQUIRED-IMMUNODEFICIENCY-SYNDROME WITH REVERSE-TRANSCRIPTASE INHIBITORS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SCID-HU MOUSE; RHESUS-MONKEYS; EXPERIMENTAL-INFECTION; CYNOMOLGUS MONKEYS; ZIDOVUDINE AZT; HTLV-III; VIRUS; HIV-1; SIV; MACAQUES AB The reverse transcriptase (RT) of the human immunodeficiency virus type 1 (HIV-1) is the major target for antiretroviral therapy of the acquired immunodeficiency syndrome (AIDS), While some inhibitors exhibit activity against most retroviral RTs, others are specific for the HIV-1 enzyme. To develop an animal model for the therapy of the HIV-1 infection with RT inhibitors, the RT of the simian immuno-deficiency virus (SIV) was replaced by the RT of HIV-1. Macaques infected with this SIV/HIV-1 hybrid virus developed AIDS-like symptoms and pathology, The HIV-1-specific RT inhibitor LY300046 . HCl, but not zidovudine [3'-azido-3'deoxythymidine (AZT)] delayed the appearance of plasma antigenemia in macaques infected with a high dose of the chimeric virus, Infection of macaques with the chimeric virus seems to be a valuable model to study the in vivo efficacy of new RT inhibitors, the emergence and reversal of drug resistance, the therapy of infections with drug-resistant viruses, and the efficacy of combination therapy. C1 GERMAN PRIMATE CTR,D-37077 GOTTINGEN,GERMANY. KAROLINSKA INST,CTR MICROBIOL & TUMORBIOL,S-17177 STOCKHOLM,SWEDEN. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HUMAN GENOME SCI INC,ROCKVILLE,MD 20850. MEDIVIR,S-14144 HUDDINGE,SWEDEN. RP UBERLA, K (reprint author), UNIV ERLANGEN NURNBERG,INST VIROL,D-91054 ERLANGEN,GERMANY. RI Uberla, Klaus/C-5676-2008 NR 38 TC 104 Z9 106 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 29 PY 1995 VL 92 IS 18 BP 8210 EP 8214 DI 10.1073/pnas.92.18.8210 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RR844 UT WOS:A1995RR84400026 PM 7545297 ER PT J AU MIURA, M FRIEDLANDER, RM YUAN, JY AF MIURA, M FRIEDLANDER, RM YUAN, JY TI TUMOR NECROSIS FACTOR-INDUCED APOPTOSIS IS MEDIATED BY A CRMA-SENSITIVE CELL-DEATH PATHWAY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PROGRAMMED CELL DEATH; TUMOR NECROSIS FACTOR ALPHA; INTERLEUKIN 1-BETA-CONVERTING ENZYME ID C-ELEGANS; FACTOR-ALPHA; GENE CED-3; RECEPTOR; ENZYME; INTERLEUKIN-1-BETA; INFLAMMATION; ANTIBODIES; GENERATION; ENCODES AB We report here that the activation of the interleukin 1 beta (IL-1 beta)-converting enzyme (ICE) family is likely to be one of the crucial events of tumor necrosis factor (TNF) cytotoxicity, The cowpox virus CrmA protein, a member of the serpin superfamily, inhibits the enzymatic activity of ICE and ICE-mediated apoptosis, HeLa cells overexpressing crmA are resistant to apoptosis induced by Ice but not by Ich-1, another member of the Ice/ced-3 family of genes, We found that the CrmA-expressing HeLa cells are resistant to TNF-alpha/cycloheximide (CHX)-induced apoptosis, Induction of apoptosis in HeLa cells by TNF-alpha/CHX is associated with secretion of mature IL-1 beta, suggesting that an IL-1 beta-processing enzyme, most likely ICE itself, is activated by TNF-alpha/CHX stimulation. These results suggest that one or more members of the ICE family sensitive to CrmA inhibition are activated and play a critical role in apoptosis induced by TNF. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG,BOSTON,MA 02114. RP MIURA, M (reprint author), MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,149 13TH ST,BOSTON,MA 02129, USA. RI Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 NR 35 TC 220 Z9 223 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 29 PY 1995 VL 92 IS 18 BP 8318 EP 8322 DI 10.1073/pnas.92.18.8318 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RR844 UT WOS:A1995RR84400048 PM 7667287 ER PT J AU ASAHINA, A MORO, O HOSOI, J LERNER, EA XU, S TAKASHIMA, A GRANSTEIN, RD AF ASAHINA, A MORO, O HOSOI, J LERNER, EA XU, S TAKASHIMA, A GRANSTEIN, RD TI SPECIFIC INDUCTION OF CAMP IN LANGERHANS CELLS BY CALCITONIN-GENE-RELATED PEPTIDE - RELEVANCE TO FUNCTIONAL-EFFECTS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CULTURED HUMAN KERATINOCYTES; IA-ANTIGEN EXPRESSION; PROTEIN-KINASE-C; CYCLASE ACTIVITY; RECEPTORS; MACROPHAGES; DIFFERENTIATION; PROSTAGLANDINS; NEUROPEPTIDES; PROLIFERATION AB Epidermal Langerhans cells (LC) are associated anatomically with epidermal nerves, and a product of these nerves, calcitonin gene-related peptide (CGRP), inhibits the antigen-presenting capacity of LC and macrophages. As the CGRP receptor appears to be coupled to G(s) a protein, which in turn activates adenylate cyclase, the ability of CGRP to induce cAMP in LC was examined and correlated with functional effects. LC were isolated from murine epidermal cells using antibodies on magnetic microspheres, Exposure to CGRP induced a significant increase in cAMP content, which could be inhibited by coculture with a truncated form of CGRP [CGRP-(8-37)] that is a specific competitive inhibitor of CGRP, Substance P and calcitonin failed to induce cAMP in LC, Although culture in CGRP reduced the ability of murine epidermal cells enriched for LC content to present pigeon cytochrome c to a responsive clone or to present antigen for elicitation of delayed-type hypersensitivity in immune mice, culture in forskolin had little or no effect on antigen presentation despite increased cAMP content of LC as much or more than that induced by CGRP, The effect of CGRP on antigen presentation in these systems could be blocked with CGRP-(8-37). CGRP inhibited the induction of B7-2 by lipopolysaccharide on peritoneal macrophages and a LC Line, whereas calcitonin did not, CGRP induces specific accumulation of cAMP in LC and inhibits LC antigen-presenting function by a receptor-mediated event, However, the induction of cAMP by itself does not account for inhibition of antigen presentation, Suppression of the expression of B7-2 may be one mechanism by which CGRP inhibits antigen presentation. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV TEXAS,SW MED CTR,DEPT DERMATOL,DALLAS,TX 75235. FU NIAMS NIH HHS [AR 42429] NR 38 TC 90 Z9 93 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 29 PY 1995 VL 92 IS 18 BP 8323 EP 8327 DI 10.1073/pnas.92.18.8323 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RR844 UT WOS:A1995RR84400049 PM 7667288 ER PT J AU REINECKER, HC PODOLSKY, DK AF REINECKER, HC PODOLSKY, DK TI HUMAN INTESTINAL EPITHELIAL-CELLS EXPRESS FUNCTIONAL CYTOKINE RECEPTORS SHARING THE COMMON GAMMA-C CHAIN OF THE INTERLEUKIN-2 RECEPTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TYROSINE PHOSPHORYLATION; IL-2 RECEPTOR; BETA-CHAIN; ASSOCIATION; BINDING; INVIVO; LINE AB Interleukin (IL) 2 signaling requires the dimerization of the IL-2 receptor beta (IL-2R beta) and common gamma (gamma c) chains, The gamma c is also a component of the receptors for IL-4, IL-7, and IL-9, To assess the extent and role of the receptor signal transducing system utilizing the gamma c chain on human intestinal epithelial cells, the expression of gamma c, IL-2R beta, and receptor chains specific for IL-4, IL-7, and IL-9 was assessed by reverse transcription-coupled PCR on human intestinal epithelial cell lines and on isolated primary human intestinal epithelial cells, Caco-2, HT-29, and T-84 cells were found to express transcripts for the gamma c and IL-4R chains constitutively, IL-2R beta chain expression was demonstrated in Caco-2 and HT-29 but not in T-84 cells, None of the cell lines expressed mRNA for the IL-2R alpha chain, After stimulation with epidermal growth factor for 24 h Caco-2, HT-29, and T-84 cells expressed transcripts for IL-7R, In addition, Caco-2 and HT-29 cells expressed mRNA for the IL-9R. Receptors for IL-2, IL-4, IL-7, and IL-9 on intestinal epithelial cells lines appeared to be functional; stimulation with these cytokines caused rapid tyrosine phosphorylation of proteins, The relevance of the observations in intestinal epithelial cell lines for intestinal epithelial function in vivo was supported by the demonstration of transcripts for gamma c, IL-2R beta, IL-4R, IL-7R, and IL-9R in primary human intestinal epithelial cells. C1 LAHEY CLIN FDN,BURLINGTON,MA 01805. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP REINECKER, HC (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,CTR STUDY INFLAMATORY BOWEL DIS,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK 41557, DK 43351] NR 23 TC 137 Z9 141 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 29 PY 1995 VL 92 IS 18 BP 8353 EP 8357 DI 10.1073/pnas.92.18.8353 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RR844 UT WOS:A1995RR84400055 PM 7667294 ER PT J AU SICINSKI, P DONAHER, JL PARKER, SB LI, TS GARDNER, H HASLAM, SZ BRONSON, RT ELLEDGE, SJ WEINBERG, RA AF SICINSKI, P DONAHER, JL PARKER, SB LI, TS GARDNER, H HASLAM, SZ BRONSON, RT ELLEDGE, SJ WEINBERG, RA TI CYCLIN D1 PROVIDES A LINK BETWEEN DEVELOPMENT AND ONCOGENESIS IN THE RETINA AND BREAST SO CELL LA English DT Article ID MOUSE MAMMARY-GLAND; GENOMIC ORGANIZATION; CELL-CYCLE; GENES; AMPLIFICATION; EXPRESSION; ONTOGENY; CANCER; PROTOONCOGENE; PIGMENTOSA AB Mice lacking cyclin D1 have been generated by gene targeting in embryonic stem cells. Cyclin D1-deficient animals develop to term but show reduced body size, reduced viability, and symptoms of neurological impairment. Their retinas display a striking reduction in cell number due to proliferative failure during embryonic development. In situ hybridization studies of normal mouse embryos revealed an extremely high level of cyclin al in the retina, suggesting a special dependence of this tissue on cyclin D1. In adult mutant females, the breast epithelial compartment fails to undergo the massive proliferative changes associated with pregnancy despite normal levels of ovarian steroid hormones, thus, steroid-induced proliferation of mammary epithelium during pregnancy may be driven through cyclin D1. C1 MIT,DEPT BIOL,CAMBRIDGE,MA 02142. BAYLOR COLL MED,VERNA & MARRS MCLEAN DEPT BIOCHEM,HOWARD HUGHES MED INST,HOUSTON,TX 77030. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. MICHIGAN STATE UNIV,DEPT PHYSIOL,E LANSING,MI 48824. TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. TUFTS UNIV,SCH VET MED,BOSTON,MA 02111. RP SICINSKI, P (reprint author), MIT,WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142, USA. FU NCI NIH HHS [R35CA39826]; NIA NIH HHS [AG11085] NR 51 TC 817 Z9 825 U1 0 U2 16 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD AUG 25 PY 1995 VL 82 IS 4 BP 621 EP 630 DI 10.1016/0092-8674(95)90034-9 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RR734 UT WOS:A1995RR73400013 PM 7664341 ER PT J AU FUKAZAWA, T REEDQUIST, KA PANCHAMOORTHY, G SOLTOFF, S TRUB, T DRUKER, B CANTLEY, L SHOELSON, SE BAND, H AF FUKAZAWA, T REEDQUIST, KA PANCHAMOORTHY, G SOLTOFF, S TRUB, T DRUKER, B CANTLEY, L SHOELSON, SE BAND, H TI T-CELL ACTIVATION-DEPENDENT ASSOCIATION BETWEEN THE P85 SUBUNIT OF THE PHOSPHATIDYLINOSITOL 3-KINASE AND GRB2/PHOSPHOLIPASE C-GAMMA-1-BINDING PHOSPHOTYROSYL PROTEIN PP36/38 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE; ANTIGEN RECEPTOR; SH2 DOMAINS; ZETA-CHAIN; GROWTH; CLONING; P59FYN; BIND; CD4 AB Tyrosine phosphorylation of cellular proteins is an early and an essential step in T cell receptor-mediated lymphocyte activation, Tyrosine phosphorylation of transmembrane receptor chains (such as zeta and CD3 chains) and membrane-associated proteins provides docking sites for SH2 domains of adaptor proteins and signaling enzymes, resulting in their recruitment in the vicinity of activated receptors, pp36/38 is a prominent substrate of early tyrosine phosphorylation upon stimulation through the T cell receptor, The tyrosine-phosphorylated form of pp36/38 is membrane-associated and directly interacts with phospholipase C-gamma l and Grb2, providing one mechanism to recruit downstream effecters to the cell membrane, Here, we demonstrate that in Jurkat T cells, pp36/38 associates with the p85 subunit of phosphatidylinositol 3-kinase (PI-S-K p85) in an activation-dependent manner, Association of pp36/38 with PI-3-K p85 was confirmed by transfection of a hemagglutinin-tagged p85 alpha cDNA into Jurkat cells followed by anti-hemagglutinin immunoprecipitation, In vitro binding experiments with glutathione S-transferase fusion proteins of PI-S-K p85 demonstrated that the SH2 domains, but not the SH3 domain, mediated binding to pp36/38, This binding was selectively abrogated by phosphopeptides that bind to p85 SH2 domains with high affinity, Filter binding assays demonstrated that association between pp36/38 and PI-3-K p85 SH2 domains was due to direct binding. These results strongly suggest the role of pp36/38 in recruiting PI-3-K to the cell membrane and further support the idea that pp36/38 is a multifunctional docking protein for SH2 domain-containing signaling proteins in T cells. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT IMMUNOL & RHEUMATOL,LYMPHOCYTE BIOL SECT,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DEPT MED,DIV RES,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV SIGNAL TRANSDUCT,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIAID NIH HHS [R29-AI28508]; NIAMS NIH HHS [AR36308]; NIGMS NIH HHS [R01 GM041890] NR 45 TC 68 Z9 70 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 25 PY 1995 VL 270 IS 34 BP 20177 EP 20182 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RQ991 UT WOS:A1995RQ99100074 PM 7544353 ER PT J AU MOLNAR, G OLEARY, N PARDEE, AB BRADLEY, DW AF MOLNAR, G OLEARY, N PARDEE, AB BRADLEY, DW TI QUANTIFICATION OF DNA-PROTEIN INTERACTION BY UV CROSS-LINKING SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CLEAVABLE BIOTINYLATED NUCLEOTIDE; THYMIDINE KINASE PROMOTER; LAC REPRESSOR PROTEIN; SINGLE-STRANDED-DNA; RNA-POLYMERASE; CROSS-LINKING; AFFINITY-CHROMATOGRAPHY; TRANSCRIPTION FACTOR; NUCLEAR-PROTEIN; BINDING PROTEIN AB Measurement of the affinity of a protein for a promoter sequence is critical when assessing its potential to regulate transcription, Here we report that the DNA protein crosslinking (DPC) assay can be used to measure affinity, amount and molecular weight of DNA binding proteins to specific and non-specific DNA sequences, By applying a theoretical analysis to evaluate the binding data, it was shown that the affinity constants of two proteins (named DPC80 and DPC107) to the MT3 region of the mouse thymidine kinase promoter were 2 x 10(-9) M, which is 10(4) times higher than to non-specific DNA, Similar affinity constants were found when the purified proteins corresponding to DPC80 and DPC107 instead of nuclear extracts were used to assess the reliability of the DPC assay, A value for crosslinking efficiency was determined as 0.07, however, it is not needed for computation of the DNA-protein affinity, but with it the abundance of a binding protein can be estimated, In summary, the DPC assay is useful for quantifying DNA binding proteins and thereby judging their influence on transcription. C1 BIOMOLEC ASSAYS INC, WOBURN, MA 01801 USA. DANA FARBER CANC INST, DIV CELL GROWTH & REGULAT, BOSTON, MA 02115 USA. FU NIGMS NIH HHS [GM24571] NR 41 TC 12 Z9 12 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 25 PY 1995 VL 23 IS 16 BP 3318 EP 3326 DI 10.1093/nar/23.16.3318 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU269 UT WOS:A1995RU26900031 PM 7667109 ER PT J AU KOZAK, JJ MANDEVILLE, JB AF KOZAK, JJ MANDEVILLE, JB TI INFLUENCE OF SWELLING ON REACTION EFFICIENCY IN INTERCALATED CLAY-MINERALS .3. ION-DIPOLE REACTANT PAIRS SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article AB We continue our study of the influence of swelling on reaction efficiency in intercalated clay minerals. We consider ion-dipole reactant pairs and recognize that when a smectite-type clay begins to swell, there will be a critical interlamellar spacing for which a dipolar molecule, previously constrained owing to the geometry of the host lattice, can begin to ''tumble''. The range of the potential function governing the interaction of an ion-dipole reactant pair then switches from a 1/r(2) dependence, where an orientation angle theta must be specified, to a 1/r(4) dependence, where the angular dependence is washed out. We examine the consequences of this ''crossover'' by formulating a lattice-statistical model and studying in detail three cases where the effects of angular orientation on the reaction efficiency can be thoroughly documented. Our principal conclusion is that the regions of theta-space where, statistically, the tumbling dipole spends the most time are the regions characterized by the maximal (theta-specific) attractive interactions between the ion-dipole reactant pair. C1 MASSACHUSETTS GEN HOSP,CTR NUCL MAGNET RESONANCE,BOSTON,MA 02129. RP KOZAK, JJ (reprint author), IOWA STATE UNIV SCI & TECHNOL,DEPT CHEM,AMES,IA 50011, USA. NR 4 TC 1 Z9 1 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD AUG 24 PY 1995 VL 99 IS 34 BP 12933 EP 12940 DI 10.1021/j100034a036 PG 8 WC Chemistry, Physical SC Chemistry GA RR250 UT WOS:A1995RR25000036 ER PT J AU SLAVC, I MACCOLLIN, MM DUNN, M JONES, S SUTTON, L GUSELLA, JF BIEGEL, JA AF SLAVC, I MACCOLLIN, MM DUNN, M JONES, S SUTTON, L GUSELLA, JF BIEGEL, JA TI EXON SCANNING FOR MUTATIONS OF THE NF2 GENE IN PEDIATRIC EPENDYMOMAS, RHABDOID TUMORS AND MENINGIOMAS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID NEUROFIBROMATOSIS-2; CHROMOSOME-22; SUPPRESSOR; CHILDHOOD; BRAIN AB Deletions of chromosome 22 have been identified in 3 types of childhood primary brain tumor: meningiomas, rhabdoid or atypical teratoid tumors (ATT) and ependymomas. This implicates the involvement of tumor suppressor genes on chromosome 22 in the genesis of these rare tumors. One such candidate tumor suppressor gene is the recently cloned neurofibromatosis 2 (NF2) locus. The purpose of our study was to determine the frequency of germ-line and somatic NF2 mutations in a selected group of brain tumors in children. Using single-strand conformation polymorphism (SSCP) assays we screened 17 exons of the NF2 gene in 13 pediatric brain tumors and 9 matched normal blood DNA samples. Tumors included 3 meningiomas, 2 rhabdoid or ATTs, 7 ependymomas and 1 malignant tumor of glial lineage. In addition, lymphoblastoid cell lines from 3 patients with rhabdoid/ATT in whom no tumor tissue was available were analyzed for germ-line mutations. Migration shifts were not detected in any of the normal DNA samples analyzed. Of the 13 tumors screened by SSCP, 1 meningioma with monosomy 22 produced a migration shift in exon 13. DNA sequencing of exon 13 revealed a deletion of a single guanine nucleotide (base 1397) in codon 466, causing a frame shift. While not all mutations might have been picked up by this technique, the data suggest that, similar to adult sporadic meningiomas, some pediatric meningiomas may result from somatic mutations in the NF2 gene. For rhabdoid tumors and ependymomas it appears that a locus distinct from NF2 might be responsible for tumorigenesis. (C) 1995 Wiley-Liss, Inc. C1 CHILDRENS HOSP PHILADELPHIA,DIV HUMAN GENET & MOLEC BIOL,PHILADELPHIA,PA 19104. CHILDRENS HOSP PHILADELPHIA,DIV NEUROSURG,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104. FU NCI NIH HHS [CA 46274]; NHGRI NIH HHS [HG00425]; NINDS NIH HHS [NS 24279] NR 33 TC 43 Z9 43 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD AUG 22 PY 1995 VL 64 IS 4 BP 243 EP 247 DI 10.1002/ijc.2910640406 PG 5 WC Oncology SC Oncology GA RT350 UT WOS:A1995RT35000005 PM 7657387 ER PT J AU AWERBUCH, TE SANDBERG, S AF AWERBUCH, TE SANDBERG, S TI TRENDS AND OSCILLATIONS IN TICK POPULATION-DYNAMICS SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article ID LYME-DISEASE; SURVIVAL; IXODIDAE; ACARI AB The life cycle of ticks is complex, proceeding through four developmental stages: egg, larva, nymph and adult. In temperate zones it is punctuated by seasonality, as in the case of the deer tick, which is the vector of the agent of Lyme disease in the northeastern parts of the United States. A model of 12 monthly stage-structured matrices were constructed and their product was used to follow the annual changes in the tick population. A judicious choice of the cut-off date for the yearly cycle enabled us to gain insight into the algebraic structure of the 11 x 11 annual transition matrix, and discover that it possesses only three non-zero eigenvalues: a dominant one that determines the main trend and two minor ones that add a riding oscillatory behavior, demonstrating the inherent nature of population swings even under constant external conditions. In addition, we find oscillations due to fluctuating environments that are strongly affected by the magnitude of the eigenvalues. Thus, both inherent and environmental oscillations determine patterns of tick population growth. In a non-fluctuating environment, tick population structure ultimately converges to a stable stage distribution, regardless of whether the population thrives or declines. (C) 1995 Academic Press Limited C1 FRAMINGHAM STATE COLL,DEPT MATH,FRAMINGHAM,MA 01701. HARVARD UNIV,SCH PUBL HLTH,DEPT POPULAT & INT HLTH,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. NR 15 TC 12 Z9 12 U1 2 U2 8 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD AUG 21 PY 1995 VL 175 IS 4 BP 511 EP 516 DI 10.1006/jtbi.1995.0158 PG 6 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA RT168 UT WOS:A1995RT16800008 ER PT J AU KOTANIDES, H MOCZYGEMBA, M WHITE, MF REICH, NC AF KOTANIDES, H MOCZYGEMBA, M WHITE, MF REICH, NC TI CHARACTERIZATION OF THE INTERLEUKIN-4 NUCLEAR ACTIVATED FACTOR/STAT AND ITS ACTIVATION INDEPENDENT OF THE INSULIN-RECEPTOR SUBSTRATE PROTEINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE PHOSPHORYLATION; HEMATOPOIETIC-CELLS; GAMMA-CHAIN; MAP KINASE; IL-4; EXPRESSION; DISTINCT; IDENTIFICATION; LYMPHOKINE; ELEMENTS AB The activation of a latent DNA binding factor by interleukin-4 (IL-4), the IL-4 nuclear activated factor (IL-4 NAF), occurs within minutes of IL-4 binding to its receptor. Molecular characterization of IL-4 NAF by ultraviolet light cross-linking experiments revealed a single protein of 120-130 kDa in contact with the DNA target site. Glycerol gradient sedimentation analysis indicated a molecular mass of IL-4 NAF consistent with a monomer that is capable of binding DNA. The IL-4 NAF target site is a palindromic sequence that is also recognized by the interferon-induced transcription factor, p91/STAT1 alpha. However, IL-4 NAF and p91/STAT1 alpha display distinguishable DNA binding specificities that may generate one level of specificity in the expression of target genes. Previous studies suggested the involvement of the insulin receptor substrate-1 (IRS-1) in the IL-4 signal transduction pathway. Although IRS-1 is involved in the stimulation of mitogenesis, our results demonstrate that activation of IL-4 NAF is independent of IRS-signaling proteins. The results of this study indicate that IL-4 stimulates bifurcating signal pathways that can direct mitogenesis via the IRS-signaling proteins and specific gene expression via the IL-4 NAF. C1 SUNY STONY BROOK,GRAD PROGRAM MOLEC & CELLULAR BIOL,STONY BROOK,NY 11794. SUNY STONY BROOK,DEPT PATHOL,STONY BROOK,NY 11794. HARVARD UNIV,SCH MED,BOSTON,MA 02215. JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. NR 39 TC 40 Z9 40 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 18 PY 1995 VL 270 IS 33 BP 19481 EP 19486 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RP703 UT WOS:A1995RP70300046 PM 7642632 ER PT J AU LEVYLAHAD, E WASCO, W POORKAJ, P ROMANO, DM OSHIMA, J PETTINGELL, WH YU, CE JONDRO, PD SCHMIDT, SD WANG, K CROWLEY, AC FU, YH GUENETTE, SY GALAS, D NEMENS, E WIJSMAN, EM BIRD, TD SCHELLENBERG, GD TANZI, RE AF LEVYLAHAD, E WASCO, W POORKAJ, P ROMANO, DM OSHIMA, J PETTINGELL, WH YU, CE JONDRO, PD SCHMIDT, SD WANG, K CROWLEY, AC FU, YH GUENETTE, SY GALAS, D NEMENS, E WIJSMAN, EM BIRD, TD SCHELLENBERG, GD TANZI, RE TI CANDIDATE GENE FOR THE CHROMOSOME-1 FAMILIAL ALZHEIMERS-DISEASE LOCUS SO SCIENCE LA English DT Article ID PRECURSOR PROTEIN GENE; CATHEPSIN-E; LINKAGE; MUTATION; KINDREDS; MARKERS AB A candidate gene for the chromosome 1 Alzheimer's disease (AD) locus was identified (STM2). The predicted amino acid sequence for STM2 is homologous to that of the recently cloned chromosome 14 AD gene (S182). A point mutation in STM2, resulting in the substitution of an isoleucine for an asparagine (N141I), was identified in affected people from Volga German AD kindreds. This N141I mutation occurs at an amino acid residue that is conserved in human S182 and in the mouse S182 homolog. The presence of missense mutations in AD subjects in two highly similar genes strongly supports the hypothesis that mutations in both are pathogenic. C1 VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,SEATTLE,WA 98108. MASSACHUSETTS GEN HOSP,GENET & AGING UNIT,BOSTON,MA 02129. DARWIN MOLEC,BOTHELL,WA 98021. UNIV WASHINGTON,DEPT MED,DIV MED GENET,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. VET AFFAIRS MED CTR,DIV NEUROL,SEATTLE,WA 98108. RI Schmidt, Stephen/B-5398-2012 FU NIA NIH HHS [AG0513C, R01-AG11762, R01-AG11899] NR 30 TC 1715 Z9 1743 U1 5 U2 57 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 18 PY 1995 VL 269 IS 5226 BP 973 EP 977 DI 10.1126/science.7638622 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP738 UT WOS:A1995RP73800035 PM 7638622 ER PT J AU LUO, XN REDDY, JC YEYATI, PL IDRIS, AH HOSONO, S HABER, DA LICHT, JD ATWEH, GF AF LUO, XN REDDY, JC YEYATI, PL IDRIS, AH HOSONO, S HABER, DA LICHT, JD ATWEH, GF TI THE TUMOR-SUPPRESSOR GENE WT1 INHIBITS RAS-MEDIATED TRANSFORMATION SO ONCOGENE LA English DT Article DE WT1; TUMOR SUPPRESSORS; RAS-TRANSFORMATION ID WILMS-TUMOR; HUMAN CHROMOSOME-11; PROMOTER ACTIVITY; NUDE MICE; CELL-LINE; GROWTH; PRODUCT; EXPRESSION; ONCOGENE; KIDNEY AB Wilms' tumor belongs to a small group of pediatric neoplasms that have served as paradigms of human cancers in which recessive mutations play a primary role in tumorigenesis. WT1 is a candidate tumor suppressor gene that is mutationally inactivated in a proportion of both familial and sporadic Wilms' tumors. Recent studies demonstrated that WT1 can partially suppress growth of a Wilms' tumor cell line in vitro and in vivo. We investigated the ability of WT1 to inhibit the expression of the transformed phenotype in non-Wilms' tumor cells. The expression of WT1 cDNA in ras-transformed NIH3T3 cells yielded large, flat cells that exhibited complete contact-inhibition. These morphologic changes were associated with decreased proliferation, suppression of clonogenicity in soft agar and inhibition of tumor growth in nude mice. Moreover, expression of WT1 in non-transformed NIH3T3 cells resulted in similar morphologic changes and profound resistance to transformation by an activated uas oncogene. These studies suggest that tumor inhibition by WT1 in these cells may be achieved by interference with the ras-mediated signalling pathway. C1 CUNY MT SINAI SCH MED,DEPT MED,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,BROOKDALE CTR MOLEC BIOL,NEW YORK,NY 10029. MASSACHUSETTS GEN HOSP,CTR CANC,GENET MOLEC LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NCI NIH HHS [CA37887, CA59998]; NHLBI NIH HHS [HL42919] NR 44 TC 54 Z9 56 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 17 PY 1995 VL 11 IS 4 BP 743 EP 750 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RQ469 UT WOS:A1995RQ46900016 PM 7651738 ER PT J AU ELLEDGE, RM GRAY, R MANSOUR, E YU, YY CLARK, GM RAVDIN, P OSBORNE, CK GILCHRIST, K DAVIDSON, NE ROBERT, N TORMEY, DC ALLRED, DC AF ELLEDGE, RM GRAY, R MANSOUR, E YU, YY CLARK, GM RAVDIN, P OSBORNE, CK GILCHRIST, K DAVIDSON, NE ROBERT, N TORMEY, DC ALLRED, DC TI ACCUMULATION OF P53 PROTEIN AS A POSSIBLE PREDICTOR OF RESPONSE TO ADJUVANT COMBINATION CHEMOTHERAPY WITH CYCLOPHOSPHAMIDE, METHOTREXATE, FLUOROURACIL, AND PREDNISONE FOR BREAST-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID APOPTOSIS; EXPRESSION; INDUCTION; LEUKEMIA; CELLS C1 UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DIV MED ONCOL,SAN ANTONIO,TX 78284. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. WISCONSIN COMPREHENS CANC CTR,MADISON,WI. CASE WESTERN RESERVE UNIV,DEPT SURG,CLEVELAND,OH 44106. JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21205. FAIRFAX HOSP,HEMATOL ONCOL SECT,FALLS CHURCH,VA 22046. AMC,CANC RES CTR,DENVER,CO. FU NCI NIH HHS [CA30195, P30CA54174, P50CA5818302] NR 10 TC 100 Z9 100 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 16 PY 1995 VL 87 IS 16 BP 1254 EP 1256 DI 10.1093/jnci/87.16.1254 PG 3 WC Oncology SC Oncology GA RN297 UT WOS:A1995RN29700017 PM 7563172 ER PT J AU AXELROD, L AF AXELROD, L TI INSULINOMA - COST-EFFECTIVE CARE IN PATIENTS WITH A RARE DISEASE SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID LOCALIZATION; ULTRASONOGRAPHY RP AXELROD, L (reprint author), MASSACHUSETTS GEN HOSP,DIABET UNIT,BULFINCH 408,32 FRUIT ST,BOSTON,MA 02114, USA. NR 14 TC 12 Z9 12 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 15 PY 1995 VL 123 IS 4 BP 311 EP 312 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RN665 UT WOS:A1995RN66500011 PM 7611598 ER PT J AU KIM, DK RORDORF, G NEMENOFF, RA KOROSHETZ, WJ BONVENTRE, JV AF KIM, DK RORDORF, G NEMENOFF, RA KOROSHETZ, WJ BONVENTRE, JV TI GLUTAMATE STABLY ENHANCES THE ACTIVITY OF 2 CYTOSOLIC FORMS OF PHOSPHOLIPASE A(2) IN BRAIN CORTICAL CULTURES SO BIOCHEMICAL JOURNAL LA English DT Article ID PROTEIN-KINASE-C; ARACHIDONIC-ACID RELEASE; LONG-TERM POTENTIATION; CALCIUM-CONCENTRATION; SIGNAL TRANSDUCTION; ENZYMATIC-ACTIVITY; MESANGIAL CELLS; DENTATE GYRUS; GERBIL BRAIN; RAT-KIDNEY AB The mechanisms by which glutamatergic neurotransmitters modulate neuronal lipid metabolism are not well established. We have directly measured phospholipase A(2) (PLA(2)) enzymic activity in cell-free extracts from cortical neuronal cultures from rat brain and have found that the PLA(2) activity is up-regulated after cells are exposed to glutamate. Brief exposure to a calcium ionophore or phorbol 12-myristate 13-acetate (PMA) stably enhanced PLA(2) activity. Down-regulation of protein kinase C activity partially blocked glutamate's effects. Two Ca2+- and pH-dependent forms of PLA(2) were identified in cytosolic extracts. Activation of both forms of PLA(2) was enhanced by prior exposure of the cultures to glutamate. One of the two forms had chromatographic characteristics on heparin-Sepharose, Mono Q and Superose 12 columns similar to the 100 kDa cytosolic PLA(2) (cPLA(2)), and was recognized by an antibody raised to pig spleen cPLA(2). The second form was similar in size to Group-I and -II PLA(2)s but differed in chromatographic characteristics. It was not inhibited by dithiothreitol, and did not react with antibodies to pancreatic Group-I PLA(2), features that distinguish it from Group-I and -II PLA(2). In extracts from cells pretreated with glutamate, the activity-Ca2+ concentration dose-response relationship of the 13.5 kDa form of PLA(2) was shifted to the left with activation at lower Ca2+ concentration as the result of stable modification of the enzyme induced by glutamate. Thus glutamate-induced stable enhancement of PLA(2) activity, by processes involving calcium and protein kinase C activation, is a potential molecular switch probably mediating changes in synaptic function and contributing to excitotoxicity. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 39773]; NINDS NIH HHS [NS10828, NS01276] NR 54 TC 56 Z9 59 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 AUG 15 PY 1995 VL 310 BP 83 EP 90 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN733 UT WOS:A1995RN73300012 PM 7646475 ER PT J AU XU, YY BHAVANI, K WANDS, JR DELAMONTE, SM AF XU, YY BHAVANI, K WANDS, JR DELAMONTE, SM TI ETHANOL INHIBITS INSULIN-RECEPTOR SUBSTRATE-1 TYROSINE PHOSPHORYLATION AND INSULIN-STIMULATED NEURONAL THREAD PROTEIN GENE-EXPRESSION SO BIOCHEMICAL JOURNAL LA English DT Article ID GROWTH FACTOR-I; HEPATOCYTE DNA-SYNTHESIS; CULTURED FETAL NEURONS; CENTRAL-NERVOUS-SYSTEM; C-FOS TRANSCRIPTION; ALZHEIMERS-DISEASE; NEURITE FORMATION; LIVER-REGENERATION; SIGNAL TRANSDUCTION; SECRETORY PROTEIN AB Neuronal thread proteins (NTPs) are molecules that accumulate in the brains of patients with Alzheimer's disease, and may play a key role in both normal and neurodegenerative neuritic sprouting. In this investigation we determined whether NTP expression is up-regulated by insulin, an important neurotrophic factor that stimulates differentiation-associated neurite outgrowth, and studied the effects of ethanol, a known inhibitor of growth factor receptor tyrosine phosphorylation, on NTP expression and insulin-mediated signal transduction cascade in neuronal [primitive neuroectodermal tumour cell line 2; (PNET2)] cells. PNET2 cells were treated with 50 m-units/ml insulin in the presence or absence of 100 mM ethanol for 0.2-96 h, and cell proliferation and expression of NTP molecules were investigated by metabolic labelling, immunoprecipitation and immunohistochemical staining. Insulin stimulation resulted in an immediate increase in the levels of three (38, 18 and 15 kDa) of five NTP species (the others were of 26 and 21 kDa), followed by a decline in expression within 120 min; however, studies performed up to 96 h of culture demonstrated up-regulation by insulin of all five NTP species. Ethanol either abolished or severely muted the short- and long-term insulin-mediated upregulation of NTP expression, and substantially reduced insulin-mediated neuronal differentiation. The effects of ethanol on NTP gene expression were associated with impaired insulin-mediated tyrosine phoshorylation of both the insulin receptor beta subunit and the insulin receptor substrate-1 (IRS-1), resulting in decreased association of phosphatidylinositol 3-kinase with IRS-1. The findings suggest that ethanol may inhibit NTP expression associated with central nervous system neuronal differentiation by uncoupling the IRS-1-mediated insulin signal transduction pathway. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV NEUROPATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MGH CANC CTR,BOSTON,MA 02114. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666]; NINDS NIH HHS [NS-29793] NR 90 TC 50 Z9 50 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 AUG 15 PY 1995 VL 310 BP 125 EP 132 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN733 UT WOS:A1995RN73300018 PM 7646434 ER PT J AU REED, GL LIN, LF PARHAMISEREN, B KUSSIE, P AF REED, GL LIN, LF PARHAMISEREN, B KUSSIE, P TI IDENTIFICATION OF A PLASMINOGEN BINDING REGION IN STREPTOKINASE THAT IS NECESSARY FOR THE CREATION OF A FUNCTIONAL STREPTOKINASE-PLASMINOGEN ACTIVATOR COMPLEX SO BIOCHEMISTRY LA English DT Article ID MECHANISM; PROTEINS; GENE; SEQUENCE; CLEAVAGE; FUSION; DNA AB Streptokinase is a plasminogen activator widely used to treat patients with myocardial infarction. However, streptokinase is not a protease, and must first bind and interact with plasminogen to form an enzymatic complex. By measuring the binding of recombinant streptokinase fragments to plasminogen, we have sought, first, to identify a plasminogen binding region in streptokinase and, second, to explore the relation between binding (via this region) and the generation of a functional streptokinase-plasminogen activator complex. Recombinant streptokinase bound in a saturable and specific manner to human Glu-plasminogen with a dissociation constant of 4.2 x 10(-10) M, Recombinant streptokinase fragments spanning amino acids 1-127 and 1-253 could not be shown to bind to Glu-plasminogen, whereas fragments spanning amino acids 1-352, 120-352, and 244-414 bound tightly to plasminogen and each fragment completely inhibited the binding of full-length streptokinase to plasminogen. Although these latter streptokinase fragments formed a complex with plasminogen, enzymatic assays indicated that none of them was capable of generating an active site. When the streptokinase region shared by these three fragments, spanning residues 244-352, was expressed, it also bound plasminogen and competitively inhibited the formation of a functional plasminogen activator complex by full-length streptokinase, Taken together, these data indicate that streptokinase binds to plasminogen with high affinity, that a primary binding region for plasminogen is located within amino acids 244-352, and that binding via this region is necessary for the generation of a functional plasminogen activator complex. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP REED, GL (reprint author), HARVARD UNIV,SCH PUBL HLTH,CARDIOVASC BIOL LAB,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 24432]; NHLBI NIH HHS [HL-02348] NR 32 TC 58 Z9 61 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 15 PY 1995 VL 34 IS 32 BP 10266 EP 10271 DI 10.1021/bi00032a021 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RP771 UT WOS:A1995RP77100021 PM 7640282 ER PT J AU GALLAGHER, RE LI, YP RAO, S PAIETTA, E ANDERSEN, J ETKIND, P BENNETT, JM TALLMAN, MS WIERNIK, PH AF GALLAGHER, RE LI, YP RAO, S PAIETTA, E ANDERSEN, J ETKIND, P BENNETT, JM TALLMAN, MS WIERNIK, PH TI CHARACTERIZATION OF ACUTE PROMYELOCYTIC LEUKEMIA CASES WITH PML-RAR-ALPHA BREAK FUSION SITES IN PML EXON-6 - IDENTIFICATION OF A SUBGROUP WITH DECREASED IN-VITRO RESPONSIVENESS TO ALL-TRANS-RETINOIC ACID SO BLOOD LA English DT Article ID POLYMERASE CHAIN-REACTION; MINIMAL RESIDUAL DISEASE; MESSENGER-RNA; ISOFORMS; TRANSCRIPTION; BINDING; CELLS; DIFFERENTIATION; TRANSLOCATION; EXPRESSION AB Of 113 acute promyelocytic leukemia cases documented to have diagnostic PML-RAR alpha hybrid mRNA. 10 cases (8.8%) had fusion sites in PML gene exon 6 (V-forms) rather than in the two common hybrid mRNA configurations resulting from breaksites in either PML gene intron 6 (L-forms) or intron 3 (S-forms). In 4 V-form cases, a common break/fusion site was discovered at PML gene nucleotide (nt) 1685, abutting a 3' cryptic splice donor sequence. The fusion site was proximal to the common site in 1 case and more distal in 5 cases. The open reading frame encoding a PML-RAR alpha gene was consistently preserved, either by an in-frame fusion site or by the insertion of 3 to 127 unidentified nts. In 2 V-form cases, hybridization analysis of the reverse transcriptase-polymerase chain reaction products with a PML-RAR alpha juction probe was required for discrimination from L-form cases. Two V-form subgroups were defined by in vitro sensitivity to all-trans retinoic acid (tRA)-induced differentiation: 4 of 4 cases tested with fusion sites at or 5' to nt 1685 (subgroup E6S) had reduced sensitivity (EC(50) greater than or equal to 10(-7) mol/L), whereas 4 of 4 cases with fusion sites at or 3' to nt 1709 (subgroup E6L) had high sensitivity (EC(50) < 10(-8) mol/L) indistinguishable from that of L-form and S-form cases. These results provide the first link between PML-RAR alpha configuration and tRA sensitivity in vitro and support the importance of subclassifying APL cases according to PML-RAR alpha transcript type. (C) 1995 by The American Society of Hematology. C1 DANA FARBER CANC INST,BOSTON,MA 02115. UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. RP GALLAGHER, RE (reprint author), MONTEFIORE MED CTR,ALBERT EINSTEIN CANC CTR,DEPT ONCOL,111 E 210TH ST,BRONX,NY 10467, USA. FU NCI NIH HHS [CA56771, CA17145, CA14985] NR 35 TC 90 Z9 92 U1 0 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 AUG 15 PY 1995 VL 86 IS 4 BP 1540 EP 1547 PG 8 WC Hematology SC Hematology GA RN467 UT WOS:A1995RN46700040 PM 7632962 ER PT J AU NAKAGAWA, H ZUKERBERG, L TOGAWA, K MELTZER, SJ NISHIHARA, T RUSTGI, AK AF NAKAGAWA, H ZUKERBERG, L TOGAWA, K MELTZER, SJ NISHIHARA, T RUSTGI, AK TI HUMAN CYCLIN D1 ONCOGENE AND ESOPHAGEAL SQUAMOUS-CELL CARCINOMA SO CANCER LA English DT Article DE CYCLIN D1; ONCOGENE; ESOPHAGEAL SQUAMOUS CELL CARCINOMA; POLYMERASE CHAIN REACTION; GENE AMPLIFICATION ID RETINOBLASTOMA PROTEIN; RAS MUTATIONS; GENE; AMPLIFICATION; EXPRESSION; CANCER; OVEREXPRESSION; HETEROZYGOSITY; PROGRESSION; FIBROBLASTS AB Background. Oncogene activation and tumor suppressor gene inactivation have been implicated in the genetic basis of esophageal squamous cell carcinoma (ESCC). Cyclin D1, an oncogene that has a critical role in G1 progression of the cell cycle, has been observed to be amplified in carcinomas of the breast and head and neck, and translocated in parathyroid adenomas and centrocytic lymphomas. Methods. Established ESCC cell lines were assayed for cyclin D1 amplification and overexpression by Southern, Northern, and Western blot analyses. In addition, cyclin D1 overexpression was determined in primary tumors and adjacent normal mucosa by differential polymerase chain reaction (PCR) and immunohistochemical staining. Results. The authors observed that approximately 50% of ESCC cell lines with cyclin D1 DNA amplification also had RNA and protein overexpression. Related genes, cyclin D2 and D3, were not amplified or overexpressed in these cell lines with rare exception. The cyclin D1 protein was able to associate with the cell-cycle-dependent kinases, cdk4 and cdk6, but not always with proliferating cell nuclear antigen in selected cell lines tested, representing a novel finding. In addition, approximately 50% of primary tumors had cyclin D1 overexpression that was not present in adjacent normal mucosa. Cyclin D1 overexpression based on PCR correlated with enhanced cyclin D1 protein nuclear staining in malignant cells. Conclusion. Cyclin D1 is amplified and overexpressed in ESCC and may be important in its molecular pathogenesis. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. UNIV MARYLAND,DIV GASTROENTEROL,BALTIMORE,MD 21201. TOHOKU UNIV,DEPT SURG,SENDAI,MIYAGI 980,JAPAN. NR 44 TC 86 Z9 91 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 1995 VL 76 IS 4 BP 541 EP 549 DI 10.1002/1097-0142(19950815)76:4<541::AID-CNCR2820760402>3.0.CO;2-I PG 9 WC Oncology SC Oncology GA RN418 UT WOS:A1995RN41800001 PM 8625145 ER PT J AU INOUE, Y BODE, BP COPELAND, EM SOUBA, WW AF INOUE, Y BODE, BP COPELAND, EM SOUBA, WW TI ENHANCED HEPATIC AMINO-ACID-TRANSPORT IN TUMOR-BEARING RATS IS PARTIALLY BLOCKED BY ANTIBODY TO TUMOR-NECROSIS-FACTOR SO CANCER RESEARCH LA English DT Article ID PLASMA-MEMBRANE VESICLES; PROTEIN-SYNTHESIS; CANCER CACHEXIA; GLUTAMINE; LIVER; SYSTEM; GROWTH; METABOLISM; HEPATOCYTE; NUTRITION AB The liver of the host with cancer exhibits an enhanced requirement for amino acids to support tumor-induced increases in hepatic protein synthesis and gluconeogenesis. To address the mechanism by which the liver ensures adequate delivery of these substrates for intracellular utilization during cancer, we studied the activities of several amino acid transporters in hepatic plasma membrane vesicles prepared from rats implanted with a rapidly growing s.c. fibrosarcoma. The presence of the tumor resulted in a generalized stimulation of concentrative (Na+-dependent) glucogenic (small neutral) amino acid uptake via System A (3.4-fold), System N (2.3-fold), and System ASC (1.7-fold), as well as in the facilitative (Na+-independent) uptake of arginine via System y(+) (1.7-fold). Kinetic analysis revealed that the tumor-induced enhancement of transport activity was due to increases in the maximum transport velocity (V-max), whereas transporter substrate affinities (K-m) did not change significantly. Administration of antibody to tumor necrosis factor-alpha to tumor-bearing rats attenuated the increase in hepatic amino acid transport activity by 60-100%, Treatment of nontumor-bearing control rats with tumor necrosis factor-alpha mAb did not alter basal transport activity. The results from these studies suggest that the tumor elicits a generalized increase in hepatic plasma membrane amino acid transport activity via a pathway that involves the cytokine tumor necrosis factor. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,DIV SURG ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV FLORIDA,COLL MED,DEPT SURG,GAINESVILLE,FL 32610. FU NCI NIH HHS [R01 CA57690] NR 39 TC 25 Z9 26 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1995 VL 55 IS 16 BP 3525 EP 3530 PG 6 WC Oncology SC Oncology GA RN654 UT WOS:A1995RN65400014 PM 7627959 ER PT J AU CHEN, CG LI, L CHEN, LL PRADA, JV CHEN, MH FALLON, JT WEYMAN, AE WATERS, D GILLAM, L AF CHEN, CG LI, L CHEN, LL PRADA, JV CHEN, MH FALLON, JT WEYMAN, AE WATERS, D GILLAM, L TI INCREMENTAL DOSES OF DOBUTAMINE INDUCE A BIPHASIC RESPONSE IN DYSFUNCTIONAL LEFT-VENTRICULAR REGIONS SUBTENDING CORONARY STENOSES SO CIRCULATION LA English DT Article DE DOBUTAMINE; ECHOCARDIOGRAPHY; MYOCARDIUM; ISCHEMIA ID MYOCARDIAL BLOOD-FLOW; COLLATERAL-DEPENDENT MYOCARDIUM; HIBERNATING MYOCARDIUM; INOTROPIC STIMULATION; STUNNED MYOCARDIUM; ARTERY DISEASE; STRESS ECHOCARDIOGRAPHY; CONSCIOUS DOGS; ISCHEMIC MYOCARDIUM; INFARCTION AB Background Dobutamine stress echocardiography has been proposed as a diagnostic tool to identify viable myocardium. How regional wall thickening responds to dobutamine in the ischemic or short-term hibernating myocardium has not been adequately defined. We hypothesized that regional wall thickening would improve initially and subsequently deteriorate with incremental doses of dobutamine in viable myocardial regions supplied by a stenotic coronary artery. This study was undertaken to determine whether this biphasic pattern of regional function characterizes the response of ischemic or hibernating myocardium to dobutamine and to explore the factors and mechanisms that determine this response. Methods and Results Twenty-six pigs in four groups were studied: a control group (n=5) to assess the response of myocardium perfused by nonstenotic coronary artery to incremental doses of dobutamine, and three experimental groups with a left anterior descending coronary artery stenosis producing acute myocardial ischemia (n=7), short-term myocardial hibernation for 90 minutes (n=7), and short-term hibernation for 24 hours (n=7) to determine the functional and metabolic response to dobutamine under these conditions. Regional coronary flow was reduced to 40% to 60% of baseline, with significant reductions of regional wall thickening as measured by two-dimensional echocardiography and sonomicrometers. An incremental dobutamine infusion from 2.5 to 25 mu g . kg(-1). min(-1) increased wall thickening and coronary flow without lactate production in the control group. In the other three groups, during the incremental dobutamine infusion, regional wall thickening improved initially, from 11.4 +/- 7.5% to 19.8 +/- 11.4%, P<.01, at dobutamine doses of 2.5 to 10 (4.5+/-2.2) mu g . min(-1). kg(-1) but deteriorated subsequently to 5.0+/-5.8% at the maximal dose of dobutamine of 12.6+/-4.1 mu g . min(-1). kg(-1). The initial improvement of regional wall thickening was associated with a small increase in regional coronary flow (from 0.53+/-0.18 to 0.68+/-0.25 mL . min(-1). g(-1) myocardium, P<.05) and with regional lactate production. High doses of dobutamine did not further increase regional coronary flow but markedly increased lactate production and induced regional myocardial acidosis (pH 7.26+/-0.07). The biphasic pattern of response to dobutamine was observed in each of the three experimental groups. Both peak improvement and peak deterioration occurred earlier and at lower dobutamine dose levels in the group with acute ischemia compared with the group with short-term hibernation for 24 hours (P<.05). Conclusions A biphasic response of wall thickening to incremental dobutamine with initial improvement and subsequent deterioration is characteristic of ischemic or short-term hibernating myocardium. The initial low-dose dobutamine infusion improved wall thickening in the ischemic or hibernating myocardial region to a modest level. This initial modest improvement was transient and at the expense of metabolic deterioration of myocardial ischemia, so that at higher doses during prolonged dobutamine infusion, wall thickening deteriorated, lactate accumulated, and myocardial acidosis developed. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,BOSTON,MA. RP CHEN, CG (reprint author), UNIV CONNECTICUT,HARTFORD HOSP,DIV CARDIOL,HARTFORD,CT 06102, USA. NR 46 TC 115 Z9 127 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 15 PY 1995 VL 92 IS 4 BP 756 EP 766 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RN852 UT WOS:A1995RN85200012 PM 7641353 ER PT J AU ALLAN, JS RAY, P BROUSSARD, S WHITEHEAD, E HUBBARD, G BUTLER, T BRASKY, K LUCIW, P CHENGMAYER, C LEVY, JA STEIMER, K LI, J SODROSKI, J GARCIAMOLL, M AF ALLAN, JS RAY, P BROUSSARD, S WHITEHEAD, E HUBBARD, G BUTLER, T BRASKY, K LUCIW, P CHENGMAYER, C LEVY, JA STEIMER, K LI, J SODROSKI, J GARCIAMOLL, M TI INFECTION OF BABOONS WITH SIMIAN HUMAN IMMUNODEFICIENCY VIRUSES SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE SIMIAN/HUMAN IMMUNODEFICIENCY VIRUS (SHIV); BABOON; HIV-1; SIVMAC; AIDS VACCINE; ANIMAL MODEL ID T-LYMPHOTROPIC RETROVIRUS; HTLV-III/LAV ENVELOPE; RHESUS-MONKEYS; PERSISTENT INFECTION; MACAQUE MONKEYS; MACACA-NEMESTRINA; CHIMERIC HUMAN; SIV VACCINE; AIDS VIRUS; III LAV AB Baboons were evaluated for their utility to serve as a model for testing envelope-based vaccines against human immunodeficiency virus type 1 (HIV-1). The ability of HIV-1 strains IIIB, RF, and SF2 to infect baboons was compared with that of simian/human immunodeficiency virus (SHIV) recombinant viruses comprised of either HXB2 or SF2 env, tat, rev, and vpu genes inserted into the SIVmac239 backbone. Both SHIV recombinants replicated in baboon PBMC in vitro, while no evidence of replication was noted for HIV-1 strains (MN, IIIB, SF2). Infection of baboons in vivo correlated with the restriction of infection in vitro. Virus was recovered by cocultivation methods early after SHIV(HXBc2) infection of two baboons with seroconversion profiles that parallel those observed in simian immunodeficiency virus (SIV)mac-infected rhesus monkeys. One of two baboons inoculated with SHIV(SF2) also seroconverted within 4 weeks; however, the kinetics of infection in a second animal appeared much later, with seroconversion to gp120 not evident until 20 weeks and no virus recovery during 32 weeks following infection. Viral DNA was detected in the lymph nodes of the SHIV-inoculated animals by nested polymerase chain reaction (PCR) amplification. Histopathologic changes were evident in lymph nodes, yet no overt clinical disease was observed. When HIV-1 strains (IIIB, RF, and SF2) were inoculated into baboons, virus was not recovered and no seroconversion to the major HIV-1 antigens was observed. However, viral DNA from the lymph nodes of four animals inoculated with HIV-1 strains could be detected by nested PCR, indicating a persistent but diminutive infection of HIV-1. The baboon thus represents a new animal model for testing HIV-1 envelope-based vaccines including the evaluation of new immunogens, dosages, routes, and adjuvants that act in eliciting protective responses. C1 SW FDN BIOMED RES,DEPT LAB ANIM MED,SAN ANTONIO,TX 78228. DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV CALIF DAVIS,SCH MED,DEPT PATHOL,DAVIS,CA. UNIV CALIF SAN FRANCISCO,SCH MED,CANC RES INST,SAN FRANCISCO,CA 94143. CHIRON CORP,EMERYVILLE,CA 94608. BIOMOLEC TECHNOL INC,FREDERICK,MD. RP ALLAN, JS (reprint author), SW FDN BIOMED RES,DEPT VIROL & IMMUNOL,7620 NW LOOP 410 MIL DR,SAN ANTONIO,TX 78228, USA. FU NIAID NIH HHS [AI33832, AI28696, N01-AI05084SI] NR 61 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD AUG 15 PY 1995 VL 9 IS 5 BP 429 EP 441 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RM668 UT WOS:A1995RM66800001 PM 7627620 ER PT J AU KIM, J MODLIN, RL MOY, RL DUBINETT, SM MCHUGH, T NICKOLOFF, BJ UYEMURA, K AF KIM, J MODLIN, RL MOY, RL DUBINETT, SM MCHUGH, T NICKOLOFF, BJ UYEMURA, K TI IL-10 PRODUCTION IN CUTANEOUS BASAL AND SQUAMOUS-CELL CARCINOMAS - A MECHANISM FOR EVADING THE LOCAL T-CELL IMMUNE-RESPONSE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR INFILTRATING LYMPHOCYTES; INHIBITS CYTOKINE PRODUCTION; EXPRESSION; INTERFERON; CANCER; PROFILES; CLONES; TH1; INTERLEUKIN-10; IMMUNOTHERAPY AB Cytokines play a vital role in the host immune response by regulating the development and function of immunocompetent cells. To explore the possibility that tumors may alter the host response via release of immuno-modulatory cytokines, we studied two different skin cancers, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) as models. By RT-PCR, we found that the type 2 cytokines, IL-4 and IL-10, were strongly expressed in BCC compared with matched PBMC. Furthermore, IL-10 was more strongly expressed in SCC compared with benign growths. To identify the cell types responsible for production of these cytokines, tumor and tumorinfiltrating lymphocyte (TIL) cell lines were derived from BCC and SCC biopsy specimens. IL-2 and IFN-gamma mRNAs were expressed in TIL, while IL-10 mRNA were strongly expressed in BCC lines. In addition, IL-10 was detected in culture supernatants from BCC and SCC cell lines by ELISA and in tissue sections by immunohistology. TIL lines derived from these tumors demonstrated proliferative activity to autologous tumor cells in the presence of APCs, dependent on the addition of low concentrations of rIL-2 or neutralizing anti-IL-10 mAb in the culture medium. Furthermore, treatment of BCC with intralesional IFN-alpha induced tumor regression with concomitant up-regulation of IL-2 and down-regulation of IL-10 mRNA expression in lesions. These data suggest that tumor production of the cytokine, IL-10, may provide a mechanism for evading the local T cell-mediated immune response. C1 UNIV CALIF LOS ANGELES,SCH MED,DIV DERMATOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90024. UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109. OI Modlin, Robert/0000-0003-4720-031X FU NCI NIH HHS [CA56860]; NIAID NIH HHS [AI22553]; NIAMS NIH HHS [AR31957] NR 29 TC 239 Z9 252 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1995 VL 155 IS 4 BP 2240 EP 2247 PG 8 WC Immunology SC Immunology GA RN464 UT WOS:A1995RN46400062 PM 7636270 ER PT J AU LOEB, JDJ SCHLENSTEDT, G PELLMAN, D KORNITZER, D SILVER, PA FINK, GR AF LOEB, JDJ SCHLENSTEDT, G PELLMAN, D KORNITZER, D SILVER, PA FINK, GR TI THE YEAST NUCLEAR IMPORT RECEPTOR IS REQUIRED FOR MITOSIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NUCLEOCYTOPLASMIC TRANSPORT; IMPORTIN ID SACCHAROMYCES-CEREVISIAE; LOCALIZATION SEQUENCES; BINDING-PROTEINS; BUDDING YEAST; 2 STEPS; TRANSLOCATION; PORE; IDENTIFICATION; MUTATIONS; ENVELOPE AB The nuclear import system is highly conserved among eukaryotes. Here we report the effects of a conditional mutation in SRP1, which encodes a Saccharomyces cerevisiae homolog of the vertebrate nuclear import receptor importin. Importin was isolated as a factor required for the initial targeting step of a nuclear import substrate to the nuclear envelope in a mammalian in vitro assay. We show that yeast Srp1 is similarly required for protein import. In addition, Srp1 is also required for the execution of mitosis: we demonstrate that cells containing a conditional mutation of SRP1 arrest with a G(2)/M phenotype in a manner analogous to classic cdc mutants. This defect may be due to the failure of the mutant to degrade the mitotic cyclin Clb2 and other proteins required for mitosis. The requirement of a nuclear import receptor for cell cycle-regulated proteolysis implies that import of cell cycle regulators into the nucleus is critical for cell cycle progression. C1 MIT,DEPT BIOL,CAMBRIDGE,MA 02142. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. RP LOEB, JDJ (reprint author), MIT,WHITEHEAD INST BIOMED RES,9 CAMBRIDGE CTR,CAMBRIDGE,MA 02142, USA. FU NIGMS NIH HHS [GM-40266, GM-36373] NR 35 TC 138 Z9 138 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 15 PY 1995 VL 92 IS 17 BP 7647 EP 7651 DI 10.1073/pnas.92.17.7647 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP748 UT WOS:A1995RP74800010 PM 7644471 ER PT J AU LAZAR, G SCHAAL, T MANIATIS, T GOODMAN, HM AF LAZAR, G SCHAAL, T MANIATIS, T GOODMAN, HM TI IDENTIFICATION OF A PLANT SERINE-ARGININE-RICH PROTEIN SIMILAR TO THE MAMMALIAN SPLICING FACTOR SF2/ASF SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PRE-MESSENGER-RNA; CELL NUCLEAR EXTRACT; SITE SELECTION; PREMESSENGER RNA; SR PROTEINS; INVITRO; SEQUENCES; INTRONS; DNA; EXPRESSION AB We show that the higher plant Arabidopsis thaliana has a serine-arginine-rich (SR) protein family whose members contain a phosphoepitope shared by the animal SR family of splicing factors, In addition, we report the cloning and characterization of a cDNA encoding a higher-plant SR protein from Arabidopsis, SR1, which has striking sequence and structural homology to the human splicing factor SF2/ASF, Similar to SF2/ASF, the plant SR1 protein promotes splice site switching in mammalian nuclear extracts, A novel feature of the Arabidopsis SR protein is a C-terminal domain containing a high concentration of proline, serine, and lysine residues (PSK domain), a composition reminiscent of histones, This domain includes a putative phosphorylation site for the mitotic kinase cyclin/p34(cdc2). C1 MASSACHUSETTS GEN HOSP,DEPT BIOL MOLEC,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,DEPT MOLEC & CELLULAR BIOL,CAMBRIDGE,MA 02138. NR 45 TC 74 Z9 76 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 15 PY 1995 VL 92 IS 17 BP 7672 EP 7676 DI 10.1073/pnas.92.17.7672 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP748 UT WOS:A1995RP74800015 PM 7644475 ER PT J AU LI, TS DAVIDSON, BL AF LI, TS DAVIDSON, BL TI PHENOTYPE CORRECTION IN RETINAL-PIGMENT EPITHELIUM IN MURINE MUCOPOLYSACCHARIDOSIS-VII BY ADENOVIRUS-MEDIATED GENE-TRANSFER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BETA-GLUCURONIDASE DEFICIENCY; BONE-MARROW TRANSPLANTATION; LYSOSOMAL-ENZYME; MPS-VII; MOUSE; DEGENERATION; FIBROBLASTS; THERAPY; VECTORS; MODEL AB We have studied the use of adenovirus-mediated gene transfer to reverse the pathologic changes of lysosomal storage disease caused by beta-glucuronidase deficiency in the eyes of mice with mucopolysaccharidosis VII. A recombinant adenovirus carrying the human beta-glucuronidase cDNA coding region under the control of a non-tissue-specific promoter was injected intravitreally or subretinally into the eyes of mice with mucopolysaccharidosis VII. At 1-3 weeks after injection, the treated and control eyes were examined histochemically for beta-glucuronidase expression and histologically for phenotypic correction of the lysosomal storage defect. Enzymatic expression was detected 1-3 weeks after injection. Storage vacuoles in the retinal pigment epithelium (RPE) were still present 1 week after gene transfer but were reduced to undetectable levels by 3 weeks in both intravitreally and subretinally injected eyes. There was minimal evidence of ocular pathology associated with the viral injection. These data indicate that adenovirus-mediated gene transfer to the eye may provide for adjunctive therapy for lysosomal storage diseases affecting the RPE in conjunction with enzyme replacement and/or gene therapies for correction of systemic disease manifestations. The data also support the view that recombinant adenovirus may be useful as a gene therapy vector for retinal degenerations that result from a primary genetic defect in the RPE cells. C1 UNIV IOWA,COLL MED,IOWA CITY,IA 52242. RP LI, TS (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY10581]; NICHD NIH HHS [HD33531] NR 30 TC 76 Z9 83 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 AUG 15 PY 1995 VL 92 IS 17 BP 7700 EP 7704 DI 10.1073/pnas.92.17.7700 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP748 UT WOS:A1995RP74800021 PM 7644479 ER PT J AU FRANK, DA ROBERTSON, MJ BONNI, A RITZ, J GREENBERG, ME AF FRANK, DA ROBERTSON, MJ BONNI, A RITZ, J GREENBERG, ME TI INTERLEUKIN-2 SIGNALING INVOLVES THE PHOSPHORYLATION OF STAT PROTEINS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TYROSINE PHOSPHORYLATION; CYTOKINE; LYMPHOCYTE; NATURAL KILLER CELL ID TYROSINE PHOSPHORYLATION; TRANSDUCTION PATHWAYS; TRANSCRIPTION FACTOR; BINDING PROTEIN; LYMPHOCYTE-T; S6 KINASE; CELL LINE; C-MYC; ACTIVATION; GAMMA AB One of the most important cytokines involved in immune response regulation is interleukin 2 (IL-2), a potent activator of the proliferation and function of T lymphocytes and natural killer cells, The mechanisms by which the effects of IL-2 are propagated within cells are not understood, While the binding of IL-2 to its receptor was recently shown to lead to the activation of two kinases, Jak-1 and Jak-3, subsequent steps in the signaling pathway to the nucleus that lead to the activation of specific genes had not been characterized, Since many cytokines that activate Jak kinases also lead to the tyrosine phosphorylation and activation of members of the Stat family of transcription factors, the ability of IL-2 to trigger Stat phosphorylation was examined. Exposure of activated human T lymphocytes or of a natural killer cell line (NKL) to IL-2 leads to the phosphorylation of Stat1 alpha, Stat1 beta, and Stat3, as well as of two Stat-related proteins, p94 and p95. p94 and p95 share homology with Stat1 at the phosphorylation site and in the Src homology 2 (SH2) domain, but otherwise are immunologically distinct from Stat1, These Stat proteins were found to translocate to the nucleus and to bind to a specific DNA sequence. These findings suggest a mechanism by which IL-2 binding to its receptor may activate specific genes involved in immune cell function. C1 HARVARD UNIV,SCH MED,DEPT MOLEC GENET & MICROBIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA43855, CA41619] NR 37 TC 91 Z9 92 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 15 PY 1995 VL 92 IS 17 BP 7779 EP 7783 DI 10.1073/pnas.92.17.7779 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP748 UT WOS:A1995RP74800037 PM 7544001 ER PT J AU ZHOU, MM MEADOWS, RP LOGAN, TM YOON, HS WADE, WS RAVICHANDRAN, KS BURAKOFF, SJ FESIK, SW AF ZHOU, MM MEADOWS, RP LOGAN, TM YOON, HS WADE, WS RAVICHANDRAN, KS BURAKOFF, SJ FESIK, SW TI SOLUTION STRUCTURE OF THE SHC SH2 DOMAIN COMPLEXED WITH A TYROSINE-PHOSPHORYLATED PEPTIDE FROM THE T-CELL RECEPTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NMR; SIGNAL TRANSDUCTION ID AFFINITY PHOSPHOTYROSYL PEPTIDE; NUCLEAR MAGNETIC-RESONANCE; LARGER PROTEINS; SIDE-CHAIN; SIGNAL-TRANSDUCTION; COUPLING-CONSTANTS; NMR-SPECTROSCOPY; C-13; ASSIGNMENTS; CALMODULIN AB Shc is a widely expressed adapter protein that plays an important role in signaling via a variety of cell surface receptors and has been implicated in coupling the stimulation of growth factor, cytokine, and antigen receptors to the Ras signaling pathway. Shc interacts with several tyrosine-phosphorylated receptors through its C-terminaI SH2 domain, and one of the mechanisms of T-cell receptor-mediated Ras activation involves the interaction of the Shc SH2 domain with the tyrosine-phosphorylated zeta chain of the T-cell receptor. Here we describe a high-resolution NMR structure of the Shc SH2 domain complexed to a phosphopeptide (GHDGLpYQGLSTATK) corresponding to a portion of the zeta chain of the T-cell receptor. Although the overall architecture of the protein is similar to other SH2 domains, distinct structural differences were observed in the smaller beta-sheet, BG loop, (pY + 3) phosphopeptide-binding site, and relative position of the bound phosphopeptide. C1 ABBOTT LABS,DIV PHARMACEUT DISCOVERY,ABBOTT PK,IL 60064. DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RI Yoon, Ho Sup/A-2193-2011 NR 40 TC 57 Z9 59 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 AUG 15 PY 1995 VL 92 IS 17 BP 7784 EP 7788 DI 10.1073/pnas.92.17.7784 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP748 UT WOS:A1995RP74800038 PM 7544002 ER PT J AU XU, C MEIKRANTZ, W SCHLEGEL, R SAGER, R AF XU, C MEIKRANTZ, W SCHLEGEL, R SAGER, R TI THE HUMAN PAPILLOMA-VIRUS 16E6 GENE SENSITIZES HUMAN MAMMARY EPITHELIAL-CELLS TO APOPTOSIS INDUCED BY DNA-DAMAGE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE P53; P21; MITOMYCIN C; STAUROSPORINE; UBIQUITINYLATION ID POTENT INHIBITOR; MITOMYCIN-C; P53; PROTEIN; CYTOTOXICITY; TYPE-16; CANCER; E1A AB Programmed cell death (apoptosis) is a normal physiological process, which could in principle be manipulated to play an important role in cancer therapy. The key importance of p53 expression in the apoptotic response to DNA-damaging agents has been stressed because mutant or deleted p53 is so common in most kinds of cancer. An important strategy, therefore, is to find ways to induce apoptosis in the absence of wild-type p53. In this paper, we compare apoptosis in normal human mammary epithelial cells, in cells immortalized with human papilloma virus (HPV), and in mammary carcinoma cell lines expressing wild-type p53, mutant p53, or no p53 protein. Apoptosis was induced with mitomycin C (MMC), a DNA cross-linking and damaging agent, or with staurosporine (SSP), a protein kinase inhibitor, The normal and HPV-transfected cells responded more strongly to SSP than did the tumor cells. After exposure to MMC, cells expressing wild-type p53 underwent extensive apoptosis, whereas cells carrying mutated p53 responded weakly. Primary breast cancer cell lines null for p53 protein were resistant to MMC. In contrast, two HPV immortalized cell lines in which p53 protein was destroyed by E6-modulated ubiquitinylation were highly sensitive to apoptosis induced by MMC. Neither p53 mRNA nor protein was induced in the HPV immortalized cells after MMC treatment, although p53 protein was elevated by MMC in cells with wild-type p53. Importantly, MMC induced p21 mRNA but not p21 protein expression in the HPV immortalized cells. Thus, HPV 16E6 can sensitize mammary epithelial cells to MMC-induced apoptosis via a p53- and p21-independent pathway. We propose that the HPV 16E6 protein modulates ubiquitin-mediated degradation not only of p53 but also of p21 and perhaps other proteins involved in apoptosis. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL ADM,DEPT MOLEC & CELLULAR TOXICOL,BOSTON,MA 02115. FU NCI NIH HHS [CA57517] NR 35 TC 76 Z9 78 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 15 PY 1995 VL 92 IS 17 BP 7829 EP 7833 DI 10.1073/pnas.92.17.7829 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP748 UT WOS:A1995RP74800047 PM 7644500 ER PT J AU SAHIN, M SLAUGENHAUPT, SA GUSELLA, JF HOCKFIELD, S AF SAHIN, M SLAUGENHAUPT, SA GUSELLA, JF HOCKFIELD, S TI EXPRESSION OF PTPH1, A RAT PROTEIN-TYROSINE-PHOSPHATASE, IS RESTRICTED TO THE DERIVATIVES OF A SPECIFIC DIENCEPHALIC SEGMENT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NERVOUS-SYSTEM AXONS; PHOSPHOTYROSINE PHOSPHATASE; MOUSE FOREBRAIN; CLONING; HOMOLOGY; NEURONS; GENES; DIFFERENTIATION; IDENTIFICATION; DEFINES AB Studies to date have identified only a few proteins that are expressed in a segment-specific manner within the mammalian brain. Here we report that a nonreceptor protein tyrosine phosphatase, PTPH1, is selectively expressed in the adult thalamus. Expression of PTPH1 mRNA is detected in most, but not all, thalamic nuclei, Nuclei that are derived embryonically from the dorsal thalamus and project to the neocortex express this gene, whereas those derived from the ventral thalamus do not. PTPH1 mRNA expression is also restricted to the dorsal thalamus during development and, thus, can serve as a specific marker for the dorsal thalamic nuclei. Since the subcellular localization of PTPH1 protein is not known, its functional role is not clear. However, the restriction of its expression to the thalamic nuclei that have thalamocortical connections suggests that PTPH1 may play a role in the maintenance of these connections or in determining the physiological properties of thalamic relay nuclei. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. RP SAHIN, M (reprint author), YALE UNIV,SCH MED,NEUROBIOL SECT,NEW HAVEN,CT 06510, USA. FU NHGRI NIH HHS [HG00169]; NINDS NIH HHS [NS22807, NS24279] NR 40 TC 11 Z9 11 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 AUG 15 PY 1995 VL 92 IS 17 BP 7859 EP 7863 DI 10.1073/pnas.92.17.7859 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP748 UT WOS:A1995RP74800053 PM 7644504 ER PT J AU KHARBANDA, S SALEEM, A SHAFMAN, T EMOTO, Y TANEJA, N RUBIN, E WEICHSELBAUM, R WOODGETT, J AVRUCH, J KYRIAKIS, J KUFE, D AF KHARBANDA, S SALEEM, A SHAFMAN, T EMOTO, Y TANEJA, N RUBIN, E WEICHSELBAUM, R WOODGETT, J AVRUCH, J KYRIAKIS, J KUFE, D TI IONIZING-RADIATION STIMULATES A GRB2-MEDIATED ASSOCIATION OF THE STRESS-ACTIVATED PROTEIN-KINASE WITH PHOSPHATIDYLINOSITOL 3-KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR TYROSINE KINASES; MYELOID-LEUKEMIA CELLS; C-JUN GENE; SH3 DOMAINS; GRB2; BINDS; PHOSPHORYLATION; EXPRESSION AB The stress-activated protein (SAP) kinases are induced by tumor necrosis factor, oncoproteins, and UV light. The present studies demonstrate that ionizing radiation (IR) activates p54 SAP kinase. IR-induced activation of SAP kinase is associated with binding to the SH2/SH3-containing adaptor protein Grb2, This interaction is mediated by the SH3 domains of Grb2 and the proline-rich sequence PPPKIP in the carboxyl terminal region of SAP kinase, We also demonstrate that SAP kinase and the p85 alpha-subunit of phosphatidylinositol (PI) 3-kinase form a complex in irradiated cells, The results indicate that this complex involves binding of the p85 alpha subunit of PI 3-kinase to the SH2 domain of Grb2. The functional role of linking SAP kinase to PI 3-kinase is further supported by the finding that wortmannin, an inhibitor of PI 3-kinase, stimulates SAP kinase activity. These results suggest that the cellular response to IR may include regulation of SAP kinase by a PI 3-kinase-dependent signaling pathway. C1 HARVARD UNIV,DANA FARBER CANC INST,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP EAST,DIABET RES LAB,MED SRV,BOSTON,MA 02129. UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. UNIV TORONTO,ONTARIO CANC INST,TORONTO,ON M4X 1K9,CANADA. RP KHARBANDA, S (reprint author), HARVARD UNIV,DANA FARBER CANC INST,DIV CANC PHARMACOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Woodgett, Jim/F-1087-2010 OI Woodgett, Jim/0000-0003-3731-5797 FU NCI NIH HHS [CA55241] NR 33 TC 73 Z9 74 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 11 PY 1995 VL 270 IS 32 BP 18871 EP 18874 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN954 UT WOS:A1995RN95400029 PM 7642542 ER PT J AU HUANG, CC SPRINGER, TA AF HUANG, CC SPRINGER, TA TI A BINDING INTERFACE ON THE I-DOMAIN OF LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 (LFA-1) REQUIRED FOR SPECIFIC INTERACTION WITH INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-SUBUNIT; BETA-SUBUNIT; MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; MEDIATED CYTOLYSIS; COUNTER-RECEPTOR; DISTINCT; INTEGRIN; CLONING; EXPRESSION AB Previous studies have shown that lymphocyte function-associated antigen-1 (LFA-1) molecules containing the human alpha (CD11a) and human beta (CD18) subunits but not the murine a and human beta subunits can bind to human intercellular adhesion molecule 1 (ICAM-1). Using human/mouse LFA-1 alpha subunit chimeras, we mapped regions required for binding to ICAM-1 N-terminal to amino acid (aa) residue 359. Ligand binding sites were mapped in greater detail by scanning this region with murine sequences from 56 down to 17 aa in length and finally by introducing single or few murine aa residue replacements into the human sequence. Replacement of two non-contiguous regions of aa residues 119-153 and 218-248 in the I domain with the corresponding mouse sequences abolished most binding to human ICAM-1, without affecting alpha beta subunit association or expression on the surface of transfected COS cells. Specific residues within the I domain found to be important were Met-140, Glu-146, Thr-243, and Ser-245. Using the recently solved structure of the Mac-1 (CD11b) I domain as a model (Lee, J.-O., Rieu, P., Aznaout, M. A., and Liddington, R. (1995) Cell 80, 631-638), these residues are shown to be located on the surface of the I domain surrounding the site to which Mg2+ is chelated, and define a ligand binding interface. Mapping of the epitopes of a panel of mouse anti-human and rat anti-mouse monoclonal antibodies gave concordant results. Epitopes were mapped to two different regions in the N-terminal domain, four regions within the I domain, and two regions between the I domain and the EF handlike repeats. Monoclonal antibodies to epitopes within the mid- to C-terminal portion of the I domain and the N-terminal portion of the region between the I domain and the EF hand-like repeats gave good inhibition of LFA-1-dependent homotypic aggregation with cells that express either ICAM-1 or ICAM-3 as the major LFA-1 ligand. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 31798] NR 53 TC 151 Z9 152 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 11 PY 1995 VL 270 IS 32 BP 19008 EP 19016 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN954 UT WOS:A1995RN95400049 PM 7642561 ER PT J AU TAKAHASHI, K YONEZAWA, K NISHIMOTO, I AF TAKAHASHI, K YONEZAWA, K NISHIMOTO, I TI INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR-ACTIVATED BY A TRANSMEMBRANE MUTATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE; ANTIBODY ALPHA-IR-3; PROTEIN-KINASES; POINT MUTATION; SIGNAL; DOMAIN; SUBSTITUTION; SPECIFICITY; ONCOPROTEIN; EXPRESSION AB We constructed mutant receptors by mutating transmembrane Val(922) of the human insulin-like growth factor I receptor (IGF-IR). Assays of receptor kinase and autophosphorylation revealed constitutively augmented tyrosine kinase activity of V922E IGF-IR in both transient and stable expression. The constitutively active tyrosine kinase of this mutant was verified by promoted tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in the absence of IGF-I. In CHO cells stably expressing V922E IGF-IR, both IRS-1 phosphorylation and the IRS-1-associated phosphoinositide 3-kinase activity were stimulated in the absence of IGF-I to the level attained by 1 nM IGF-I stimulation of wild type IGF-IR, whereas the Ras-mitogen-activated protein kinase pathway was not activated under the same condition. In these CHO cells, V922E IGF-IR significantly stimulated glucose uptake but did not promote mitogenesis in the absence of IGF-I. We thus conclude that the V922E mutation of IGF-IR switches on the intrinsic tyrosine kinase and differentially activates the downstream pathways. This mutant is extremely useful in clarifying the turning on mechanism of IGF-IR as well as the differential roles of individual downstream pathways of receptor tyrosine kinases. C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02129. NR 41 TC 21 Z9 21 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 11 PY 1995 VL 270 IS 32 BP 19041 EP 19045 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN954 UT WOS:A1995RN95400054 PM 7642566 ER PT J AU FUKAZAWA, T REEDQUIST, KA TRUB, T SOLTOFF, S PANCHAMOORTHY, G DRUKER, B CANTLEY, L SHOELSON, SE BAND, H AF FUKAZAWA, T REEDQUIST, KA TRUB, T SOLTOFF, S PANCHAMOORTHY, G DRUKER, B CANTLEY, L SHOELSON, SE BAND, H TI THE SH3 DOMAIN-BINDING T-CELL TYROSYL PHOSPHOPROTEIN P120 - DEMONSTRATION OF ITS IDENTITY WITH THE C-CBL PROTOONCOGENE PRODUCT AND IN-VIVO COMPLEXES WITH FYN, GRB2, AND PHOSPHATIDYLINOSITOL 3-KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID V-CBL; SIGNAL TRANSDUCTION; ANTIGEN RECEPTOR; PROTO-ONCOGENE; TRANSFORMATION; KINASES; CLONING; GENE; RAS; LYMPHOCYTES AB Previously, we have identified p120 as a Fyn/Lck SH3 and SH2 domain-binding protein that is tyrosine phosphorylated rapidly after T cell receptor triggering. Here, we used direct protein purification, amino acid sequence analysis, reactivity with antibodies, and two-dimensional gel analyses to identify p120 as the human c-cbl protooncogene product. We demonstrate in, vivo complexes of p120(cbl) with Fyn tyrosine kinase, the adaptor protein Grb2, and the p85 subunit of phosphatidylinositol (PI) 3-kinase, The association of p120(cbl) with Fyn and the p85 subunit of PI 3-kinase (together with PI 3-kinase activity) was markedly increased by T cell activation, consistent with in vitro binding of p120(cbl) to their SH2 as well as SH3 domains, In contrast, a large fraction of p120(cbl) was associated with Grb2 prior to activation, and this association did not change upon T cell activation. In vitro, p120(cbl) interacted with Grb2 exclusively through its SH3 domains, These results demonstrate a novel Grb2-p120(cbl) signaling complex in T cells, distinct from the previously analyzed Grb2-Sos complex. The association of p120(cbl) with ubiquitous signaling proteins strongly suggests a general signal transducing function for this enigmatic protooncogene with established leukemogenic potential but unknown physiological function. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RHEUMATOL & IMMUNOL,LYMPHOCYTE BIOL SECT,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,JOSLIN DIABET CTR,RES DIV,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV SIGNAL TRANSDUCT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIAID NIH HHS [R29-AI28508]; NIAMS NIH HHS [AR36308]; NIGMS NIH HHS [R01 GM041890] NR 61 TC 189 Z9 191 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 11 PY 1995 VL 270 IS 32 BP 19141 EP 19150 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN954 UT WOS:A1995RN95400069 PM 7642581 ER PT J AU LORSCH, JR BARTEL, DP SZOSTAK, JW AF LORSCH, JR BARTEL, DP SZOSTAK, JW TI REVERSE-TRANSCRIPTASE READS THROUGH A 2'-5'-LINKAGE AND A 2'-THIOPHOSPHATE IN A TEMPLATE SO NUCLEIC ACIDS RESEARCH LA Russian DT Article ID PRE-MESSENGER RNA; EXTENSION; KINETICS AB Avian myeloblastosis virus and Maloney murine leukemia Virus RNase H- reverse transcriptases pause when they encounter a 2'-5' linkage or a 2'-thiophosphate in their template RNAs, but eventually read through these backbone modifications, Both reverse transcriptases pause after the 2'-5' linkage but before the 2'-thiophosphate, These results suggest that in the absence of precise information concerning the behavior of a given reverse transcriptase with respect to a particular lesion or modification, caution should be exercised in the interpretation of primer extension data that is being used to determine the existence of, or map the position of, a crosslink, site of chemical modification or non-standard linkage in an RNA template. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. OI Lorsch, Jon/0000-0002-4521-4999 NR 12 TC 41 Z9 41 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 AUG 11 PY 1995 VL 23 IS 15 BP 2811 EP 2814 DI 10.1093/nar/23.15.2811 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR361 UT WOS:A1995RR36100002 PM 7544885 ER PT J AU ZHAO, N LO, LC BEROVA, N NAKANISHI, K TYMIAK, AA LUDENS, JH HAUPERT, GT AF ZHAO, N LO, LC BEROVA, N NAKANISHI, K TYMIAK, AA LUDENS, JH HAUPERT, GT TI NA,K-ATPASE INHIBITORS FROM BOVINE HYPOTHALAMUS AND HUMAN PLASMA ARE DIFFERENT FROM OUABAIN - NANOGRAM SCALE CD STRUCTURAL-ANALYSIS SO BIOCHEMISTRY LA English DT Article ID DIGITALIS-LIKE-FACTOR; ENDOGENOUS OUABAIN; COMPOUND AB The specific, high affinity binding of plant-derived digitalis glycosides by the mammalian sodium and potassium transporting adenosine triphosphatase (Na,K-ATPase, or sodium pump), a plasma membrane enzyme with critical physiological importance in mammalian tissues, has raised the possibility that a mammalian analog of digitalis might exist.: We previously isolated and structurally characterized from bovine hypothalamus a novel isomer of the plant glycoside, ouabain, which differs structurally only in the attachment site and/or the stereochemistry of the steroid moiety [Tymiak et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 8189-8193]. Hamlyn and co-workers reported a molecule purified from human plasma which by mass spectrometry could not be distinguished from plant ouabain [Hamlyn et al. (1991) PI-oc. Natl. Acad. Sci. U.S.A. 88, 6259-6263]. Since rhamnoside cardiotonic steroids are not known as natural products from mammalian sources, it became important to compare these two pure isolates to determine if the same or structurally distinct compounds had been found. Our results indicate that the human and bovine Na,K-ATPase-inhibitors are identical, but different from plant ouabain. This supports the notion that the human sodium pump may be under specific physiological regulation by a mammalian analog of the digitalis glycosides. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MED SERV,RENAL UNIT,BOSTON,MA 02129. COLUMBIA UNIV,DEPT CHEM,NEW YORK,NY 10027. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543. UPJOHN CO,UPJOHN LABS,KALAMAZOO,MI 49001. FU NHLBI NIH HHS [HL52282] NR 20 TC 114 Z9 115 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 8 PY 1995 VL 34 IS 31 BP 9893 EP 9896 DI 10.1021/bi00031a010 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN732 UT WOS:A1995RN73200010 PM 7632688 ER PT J AU STERNINI, C SU, D GAMP, PD BUNNETT, NW AF STERNINI, C SU, D GAMP, PD BUNNETT, NW TI CELLULAR SITES OF EXPRESSION OF THE NEUROKININ-1 RECEPTOR IN THE RAT GASTROINTESTINAL-TRACT SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE EXCITATORY MOTOR-NEURONS; INTERNEURONS; SENSORY NEURONS; TACHYKININS; NEUROKININ RECEPTORS ID GUINEA-PIG ILEUM; ENTERIC NERVOUS-SYSTEM; VASOACTIVE INTESTINAL POLYPEPTIDE; SUBSTANCE-P; CIRCULAR MUSCLE; BINDING-SITES; PEPTIDE IMMUNOREACTIVITY; AUTORADIOGRAPHIC LOCALIZATION; MOLECULAR CHARACTERIZATION; TACHYKININ RECEPTORS AB In the digestive system, substance P is an excitatory transmitter to muscle, a putative excitatory neuro-neuronal transmitter, a vasodilator, and a mediator in inflammatory processes. Many of the biological effects of substance P are mediated by a high-affinity interaction with the tachykinin receptor neurokinin-1. The aim of the present study was to identify the sites of expression of this receptor in the rat stomach and intestine by immunohistochemistry with a polyclonal antiserum raised to the intracellular C-terminal portion of the rat neurokinin-1 receptor. Neurokinin-1 receptor immunoreactivity is present in a large population of enteric neurons. The relative density of these neurons along the gut is colon > ileum >> stomach. In the intestine, stained neurons have a smooth cell body with processes that can be followed within and between plexuses, and make close approaches to other neuronal cells, but do not appear to project outside the plexuses, suggesting that they are interneurons. In the stomach, neurokinin-1 receptor-immunoreactive neurons are infrequent and have a poorly defined and irregular shape. Neurokinin-1 receptor immunoreactivity is also localized to numerous non-neuronal cells in the inner portion of the circular muscle layer of the small intestine, which have the appearance of small dark smooth muscle cells or interstitial cells of Cajal. These cells are postulated to form a ''stretch-sensitive'' system with the deep muscular plexus and thus constitute an important site of regulation of muscle activity. Double labeling immunofluorescence was used to simultaneously localize neurokinin-1 receptor and substance P/tachykinin immunoreactivities. These experiments demonstrate that in the enteric plexuses, substance P/tachykinin-immunoreactive varicose fibers encircle the cell bodies of most neurokinin-1 receptor-containing neurons, and in the inner portion of the circular muscle layer of the small intestine they lie close to neurokinin-1 receptor-immunoreactive non-neuronal cells. In addition, some enteric neurons express both neurokinin-1 receptor and substance P/tachykinin immunoreactivities. The present study provides strong evidence that the neurokinin-1 receptor is the tachykinin receptor mediating the actions of substance P on enteric neurons and smooth muscle. (C) 1995 Wiley-Liss, Inc. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,BRAIN RES INST,LOS ANGELES,CA 90024. UNIV CALIF SAN FRANCISCO,DEPT SURG,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. RP STERNINI, C (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CURE VA UCLA GASTROENTEROL BIOL CTR,BLDG 115,ROOM 224,LOS ANGELES,CA 90073, USA. FU NIDDK NIH HHS [DK 43207, DK 38752, DK 41301] NR 57 TC 134 Z9 135 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD AUG 7 PY 1995 VL 358 IS 4 BP 531 EP 540 DI 10.1002/cne.903580406 PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA RL458 UT WOS:A1995RL45800005 PM 7593747 ER PT J AU NUNES, SL CALDERWOOD, SK AF NUNES, SL CALDERWOOD, SK TI HEAT-SHOCK FACTOR-I AND THE HEAT-SHOCK COGNATE-70 PROTEIN ASSOCIATE IN HIGH-MOLECULAR-WEIGHT COMPLEXES IN THE CYTOPLASM OF NIH-3T3 CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ACTIVATION; TRANSCRIPTION; BINDING AB Interaction of heat shock transcription factor-1 (HSF-1) with the seventy kilodalton heat shock cognate protein (HSC70) was examined in NIH 3T3 cells. HSF-1 was found in the cytoplasm of non-stressed cells associated with HSC70 in large (Mr 400-500,000) complexes. After heat shock, HSF-1 became concentrated in the nucleus in smaller, more stable complexes that did not contain HSC70, an indication of significant rearrangement within the complexes. These experiments show a profound effect of heat shock on the structure and stability of HSF-1 complexes during nuclear localization and support the hypothesis that HSC70 binding may control HSF-1 function. (C) 1995 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. FU NCI NIH HHS [CA31303, CA506421] NR 10 TC 31 Z9 31 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 AUG 4 PY 1995 VL 213 IS 1 BP 1 EP 6 DI 10.1006/bbrc.1995.2090 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RN594 UT WOS:A1995RN59400001 PM 7639722 ER PT J AU TRUB, T CHOI, WE WOLF, G OTTINGER, E CHEN, YJ WEISS, M SHOELSON, SE AF TRUB, T CHOI, WE WOLF, G OTTINGER, E CHEN, YJ WEISS, M SHOELSON, SE TI SPECIFICITY OF THE PTB DOMAIN OF SHC FOR BETA-TURN-FORMING PENTAPEPTIDE MOTIFS AMINOTERMINAL TO PHOSPHOTYROSINE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID INTERNALIZATION SIGNAL; TYROSINE KINASES; RECEPTOR; PROTEIN; GRB2; RAS; ASSOCIATION; BINDING; PHOSPHORYLATION; TRANSDUCTION AB She phosphorylation in cells following growth factor, insulin, cytokine, and lymphocyte receptor activation leads to its association with Grb2 and activation of Ras, In addition to being a cytoplasmic substrate of tyrosine kinases, She contains an SH2 domain and a non-SH2 phosphotyrosine binding (PTB) domain, Here we show that the She PTB domain, but not the SH2 domain, binds with high affinity (ID50 congruent to 1 mu M) to phosphopeptides corresponding to the sequence surrounding Tyr(250) Of the polyoma virus middle T (mT) antigen (LLSNPTpYS-VMRSK), Truncation studies show that five residues amino terminal to tyrosine are required for high affinity binding, whereas all residues carboxyl-terminal to tyrosine can be deleted without loss of affinity, Substitution studies show that tyrosine phosphorylation is required and residues at -5, -3, -2, and -1 positions relative to pTyr are important for this interaction, H-1 NMR studies demonstrate that the phosphorylated mT antigen-derived sequence forms a stable beta turn in solution, and correlations between structure and function indicate that the beta turn is important for PTB domain recognition. These results show that PTB domains are functionally distinct from SH2 domains, Whereas SH2 domain binding specificity derives from peptide sequences carboxyl-terminal to phosphotyrosine, the She PTB domain gains specificity by interacting with beta turn-forming sequences amino-terminal to phosphotyrosine. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. UNIV CHICAGO,DEPT MOLEC ONCOL,CHICAGO,IL 60637. FU NIDDK NIH HHS [DK36836, DK09146, DK07260] NR 28 TC 86 Z9 86 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 4 PY 1995 VL 270 IS 31 BP 18205 EP 18208 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RM642 UT WOS:A1995RM64200009 PM 7543098 ER PT J AU CHEN, XR RAAB, G DEUTSCH, U ZHANG, JC EZZELL, RM KLAGSBRUN, M AF CHEN, XR RAAB, G DEUTSCH, U ZHANG, JC EZZELL, RM KLAGSBRUN, M TI INDUCTION OF HEPARIN-BINDING EGF-LIKE GROWTH-FACTOR EXPRESSION DURING MYOGENESIS - ACTIVATION OF THE GENE BY MYOD AND LOCALIZATION OF THE TRANSMEMBRANE FORM OF THE PROTEIN ON THE MYOTUBE SURFACE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE CELLS; DIPHTHERIA-TOXIN RECEPTOR; DNA-BINDING; FIBROBLAST GROWTH; SKELETAL-MUSCLE; MESSENGER-RNA; MYC HOMOLOGY; DIFFERENTIATION; SULFATE; MEMBER AB Heparin binding epidermal growth factor-like growth factor (HB-EGF) gene expression and protein localization were analyzed during the process of myogenic differentiation, The mouse HB-EGF gene was isolated, and a 1.8-kilobase genomic fragment flanking the 5' end of the cDNA was cloned, This fragment contains two sequences which match the consensus CANNTG sequence for E-boxes, binding sites for the MyoD family of DNA-binding transcription factors that regulate myogenesis. Accordingly, HB-EGF synthesis was analyzed in 10T1/2 cells and C2C12 cells which are used commonly for the study of myogenesis, HB-EGF gene expression was upregulated in both cell types during myogenesis. In 10T1/2 cells, direct activation of HB-EGF gene expression by MyoD was shown in that: i) transient transfection of these cells with a plasmid expressing MyoD resulted in a 10-20-fold increase in endogenous HB-EGF mRNA levels; ii) co-transfection of MyoD and an HE EGF promoter-reporter plasmid resulted in a 5-10-fold increase in reporter activity, an increase that was abrogated by deletion of a putative HB-EGF proximal E-box sequence; and iii) incubation of MyoD protein with a 25-base pair double stranded oligonucleotide corresponding to the HB-EGF proximal E-box sequence resulted in retarded electrophoretic mobility of the oligonucleotide. In C2C12 cells, differentiation of myoblasts into myotubes resulted in a 40-50 fold increase in HB-EGF promoter activity, In addition, immunostaining and laser confocal microscopy detected HB-EGF protein in C2C12 myotubes but not in myoblasts, The HB-EGF produced was in its transmembrane form and localized to the myotube surface, Taken together, it was concluded that during skeletal muscle cell differentiation, MyoD plays a direct role in activating HB-EGF gene expression and that HB-EGF protein is expressed preferentially in myotubes and in its membrane-anchored form. C1 CHILDRENS HOSP,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,SURG RES LAB,BOSTON,MA 02129. FU NCI NIH HHS [CA37392]; NIGMS NIH HHS [GM47397] NR 53 TC 51 Z9 51 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 4 PY 1995 VL 270 IS 31 BP 18285 EP 18294 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RM642 UT WOS:A1995RM64200023 PM 7629148 ER PT J AU AVERY, AC ZHAO, ZS RODRIGUEZ, A BIKOFF, EK SOHEILIAN, M FOSTER, CS CANTOR, H AF AVERY, AC ZHAO, ZS RODRIGUEZ, A BIKOFF, EK SOHEILIAN, M FOSTER, CS CANTOR, H TI RESISTANCE TO HERPES STROMAL KERATITIS CONFERRED BY AN IGG2A-DERIVED PEPTIDE SO NATURE LA English DT Article ID T-CELL CLONES; SIMPLEX KERATITIS; ANTIGEN; MICE; MHC; UNRESPONSIVENESS; SUSCEPTIBILITY; DETERMINANTS; LYMPHOCYTES; ALLOTYPE AB NOT all peripheral tissue antigens enter the thymus and it is unclear how the immune system remains tolerant to this class of self antigen. As tolerance to self peptides can generate gaps in the T-cell repertoire for cross-reactive foreign antigens(1,2), we investigated whether this mechanism might also diminish autoimmune reactions to similar peptides expressed by peripheral tissues. Herpes stromal keratitis (HSK) is a virally induced autoimmune reaction against corneal tissues mediated by T cells(3-5), and is a leading cause of human blindness(6). Resistance to HSK in mice is associated with allotypic variation in immunoglobulin genes(7,8), possibly because circulating immunoglobin-derived peptides can cross-tolerize T cells specific for corneal tissue autoantigens. Here we show that HSK is mediated by T-cell clones specific for corneal self antigens which also recognize an allotype-bearing peptide derived from IgG2a, and that exposure of HSK-susceptible mice to a soluble form of this peptide confers resistance to HSK. Shared expression of peptide subsequences between sequestered tissue proteins and circulating proteins may be important for maintenance of self-tolerance and prevention of autoimmunity. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,HILLES IMMUNOL LAB,BOSTON,MA 02114. HARVARD UNIV,DEPT MOLEC & CELLULAR BIOL,CAMBRIDGE,MA 02138. RP AVERY, AC (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,IMMUNOPATHOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. OI Rodriguez-Garcia, Alejandro/0000-0002-1419-2109 NR 28 TC 99 Z9 101 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 AUG 3 PY 1995 VL 376 IS 6539 BP 431 EP 434 DI 10.1038/376431a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RM639 UT WOS:A1995RM63900053 PM 7630419 ER PT J AU AGARWAL, S CORBLEY, MJ ROBERTS, TM AF AGARWAL, S CORBLEY, MJ ROBERTS, TM TI RECONSTITUTION OF SIGNAL-TRANSDUCTION FROM THE MEMBRANE TO THE NUCLEUS IN A BACULOVIRUS EXPRESSION SYSTEM - ACTIVATION OF RAF-1 LEADS TO HYPERMODIFICATION OF C-JUN AND C-FOS VIA MULTIPLE PATHWAYS SO ONCOGENE LA English DT Article DE SIGNALING PATHWAYS; KINASES; RAF-1; ERK-1; NUCLEAR ONCOGENES; C-FOS; C-JUN; POSTTRANSLATIONAL MODIFICATIONS ID GLYCOGEN-SYNTHASE KINASE-3; DEPENDENT PROTEIN-KINASE; DNA-BINDING ACTIVITY; MAP KINASE; HA-RAS; COMPLEX-FORMATION; GROWTH-FACTORS; INSECT CELLS; S6 KINASE; 3T3 CELLS AB We have attempted to dissect signaling pathways involved in transmitting activating signals from the cell surface to the nucleus by reconstituting them in the baculovirus/Sf9 cell system. We have used this system to coexpress different combinations of the critical signaling proteins pp60(v-src), p21(v-ras), Raf-1 and ERK-1 and assayed the effects of resulting signaling cascades on the modifications of coexpressed transcription factors c-jun or c-fos. We observe that activation of ERK-1 via Raf-1 and p21(ras) dependent signals can result in the hyperphosphorylation of c-jun. In contrast, c-fos appears to be the target of two Raf-1 activated modifying signals: one independent of ERK-1 and the other dependent on ERK-1 stimulation. Thus, coexpression of c-fos with pp60(v-src), p21(v-ras) or constitutively active forms of Raf-1 results in a dramatic reduction of its electrophoretic mobility in the absence of coexpressed ERK-1. Activation of this ERK-1-independent pathway together with the ERK-1 dependent pathway that modifies c-jun results in additional modification of c-fos. Our observation of a Raf-1 activated, ERK-independent signaling pathway is consistent with previous reports that constitutively active Raf-1 can, in some cell types, result in transformation or differentiation without activation of ERKs. Our data indicate the presence of multiple Raf-1 activated pathways that lead to modification of transcription factors. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. FU NCI NIH HHS [CA43803]; NICHD NIH HHS [HD24926] NR 92 TC 22 Z9 22 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD AUG 3 PY 1995 VL 11 IS 3 BP 427 EP 438 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RN530 UT WOS:A1995RN53000002 PM 7543194 ER PT J AU GOLDBERG, SN GAZELLE, GS DAWSON, SL RITTMAN, WJ MUELLER, PR ROSENTHAL, DI AF GOLDBERG, SN GAZELLE, GS DAWSON, SL RITTMAN, WJ MUELLER, PR ROSENTHAL, DI TI TISSUE ABLATION WITH RADIOFREQUENCY USING MULTIPROBE ARRAYS SO ACADEMIC RADIOLOGY LA English DT Article DE RADIOFREQUENCY; TISSUE ABLATION; MULTIPROBE ARRAYS; TISSUE COAGULATION ID ELECTRODE AB Rationale and Objectives. We studied the feasibility of increasing the volume of tissue destroyed by radiofrequency tissue coagulation using multiprobe arrays and defined parameters that determine lesion size and shape. Methods. Radiofrequency was applied to ex vivo calf liver using arrays of two to five 18-gauge probes for 6 min at 70-90 degrees C. Probe spacing (1-3 cm) and arrangement, as well as the method of radiofrequency application (simultaneous or sequential), were varied. The resulting areas of tissue coagulation were measured and compared. Results. Uniform tissue necrosis was observed with simultaneous radiofrequency application for probes 1.5 cm or less apart. At 1.5 cm, arrays of three equidistant probes produced spheroid lesions approximately 3.0 +/- 0.2 cm in diameter. Arrays of four equidistant probes produced cuboid lesions of 3.2 +/- 0.1 cm per side. However, probes placed 2 cm or more apart produced independent lesions 1.4 cm in diameter, with incomplete necrosis between probes. In the trials using five-probe arrays, a central region 4mm in diameter showed no visible evidence of tissue necrosis. With each array, lesion size varied less than 3 mm in any direction. Greater necrosis was accomplished when radiofrequency was applied simultaneously rather than sequentially. Conclusion. Multiprobe radiofrequency arrays permit the destruction of more tissue in a single treatment session than is possible with multiple individual probes operating alone. Probes spaced 1.5 cm or less apart act synergistically, producing a total volume of coagulated tissue that is greater than when the individual probes are operated sequentially. C1 RADION INC,BURLINGTON,MA. RP GOLDBERG, SN (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 10 TC 164 Z9 171 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1995 VL 2 IS 8 BP 670 EP 674 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RL338 UT WOS:A1995RL33800004 PM 9419623 ER PT J AU GAZELLE, GS WOLF, GL MCINTIRE, GL BACON, ER NA, G HALPERN, EF TONER, JL AF GAZELLE, GS WOLF, GL MCINTIRE, GL BACON, ER NA, G HALPERN, EF TONER, JL TI HEPATIC IMAGING WITH IODINATED NANOPARTICLES - A COMPARISON WITH IOHEXOL IN RABBITS SO ACADEMIC RADIOLOGY LA English DT Article DE ETHYL ESTER OF DIATRIZOIC ACID; IOHEXOL; LIVER ABSCESS; LIVER COMPUTED TOMOGRAPHY; NANOPARTICLES ID IODIPAMIDE ETHYL-ESTER; COMPUTED-TOMOGRAPHY; CONTRAST AGENT; LIVER; CT; PERFLUOROOCTYLBROMIDE; SPLEEN; LIPOSOMES; RAT AB Rationale and Objectives. We evaluated the efficacy of a particulate computed tomography (CT) contrast agent in an animal model of focal liver disease. Methods. Ethyl ester of diatrizoic acid (EEDA) is an iodinated (89 mg I/ ml) nanoparticulate (200 nm) contrast agent intended for intravenous use that is currently undergoing preclinical testing in our laboratory. Focal liver abscesses were created in 11 New Zealand White rabbits. Iohexol and EEDA were administered to each animal on different days. CT scanning was performed at intervals following contrast agent administration, Liver and abscess enhancement were measured and compared. Dynamic imaging experiments in normal animals were also performed using both agents. Results. EEDA resulted in significantly greater enhancement of the liver and liver-to-abscess contrast than did iohexol at all time points beyond 5 min at approximately 25% of the total iodine load. During dynamic imaging, liver and aortic enhancement were greater with EEDA than with iohexol, except during a 20- to 40-sec period immediately following contrast agent administration. Conclusion. EEDA is superior to iohexol for imaging liver abscesses. Our results suggest that liver-directed agents such as EEDA may prove to be more efficacious than currently available extracellular agents designed for Liver CT scanning. C1 NYCOMED RES & DEV INC,COLLEGEVILLE,PA. RP GAZELLE, GS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,CTR IMAGING & PHARMACEUT RES,32 FRUIT ST,BOSTON,MA 02114, USA. NR 19 TC 12 Z9 13 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1995 VL 2 IS 8 BP 700 EP 704 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RL338 UT WOS:A1995RL33800008 PM 9419627 ER PT J AU IGARASHI, H KOJIMA, M IGARASHI, S YOSHIDA, A CHENG, HM AF IGARASHI, H KOJIMA, M IGARASHI, S YOSHIDA, A CHENG, HM TI A SIMPLE AND EFFECTIVE VIDEO KERATOMETRIC SYSTEM SO ACTA OPHTHALMOLOGICA SCANDINAVICA LA English DT Article DE CORNEA; ASTIGMATISM; RADIUS OF CURVATURE; PLACIDO RINGS; KERATOMETRY AB We tested a personal computer-based video keratometric system used to analyze projected placido disk rings. The system consists of a Maloney surgical keratometer that projects the rings and a video camera attached to an operating microscope. Images of the rings were transmitted to a video image processing board and analyzed on a personal computer using an anlaysis program we developed. System precision was evaluated in 18 eyes. The values were compared with those obtained using a commercial photokeratometer (control). In all eyes, the principal meridian values differed from the controls by < 0.04 mm. In 15 eyes (83%), the measurements were within 0.03 mm of the controls. The corneal astigmatism values and cylindrical axes were within 0.12 diopters in 17 eyes (94%) and within 5 degrees in all cases, respectively. Our system, which can analyze placido disc rings projected from other systems, is sufficiently precise to measure the corneal radius of curvature and astigmatism. C1 SAPPORO MED COLL,DEPT STAT,SAPPORO,HOKKAIDO 060,JAPAN. SIMMONS & SMITH EYE ASSOCIATES,BOSTON,MA. ASAHIKAWA MED COLL,DEPT OPHTHALMOL,ASAHIKAWA,HOKKAIDO,JAPAN. RP IGARASHI, H (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HOWE LAB OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 4 TC 6 Z9 8 U1 0 U2 0 PU SCRIPTOR PUBLISHER PI HVIDOVRE PA SOVANGSVEJ 1-5, DK-2650 HVIDOVRE, DENMARK SN 1395-3907 J9 ACTA OPHTHALMOL SCAN JI Acta Ophthalmol. Scand. PD AUG PY 1995 VL 73 IS 4 BP 336 EP 339 PG 4 WC Ophthalmology SC Ophthalmology GA RZ826 UT WOS:A1995RZ82600012 PM 8646580 ER PT J AU DHANDA, R MULROW, CD GERETY, MB LEE, S CORNELL, JE AF DHANDA, R MULROW, CD GERETY, MB LEE, S CORNELL, JE TI CLASSIFYING CHANGE WITH THE SICKNESS IMPACT PROFILE - FOR NURSING-HOMES (SIP-NH) SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE FRAIL ELDERLY; FUNCTIONAL STATUS; HEALTH STATUS MEASURES; NURSING HOMES; QUESTIONNAIRES AB The aim of this cohort study was to evaluate the concordance of the Sickness Impact Profile for Nursing Homes (SIP-NH) and Sickness Impact Profile (SIP) in classifying change. Subjects consisted of 194 consecutive long-stay nursing home residents at one academic department of the V.A. and in 8 community proprietary nursing homes in San Antonio, Texas. They were to have more than 3 months residency; to be greater than or equal to 61 years; and to be dependent in at least 2 ADLs with an MMSE score of greater than or equal to 15. Subjects were administered a 128-item SIP and a reduced 66-item SIP-NH at baseline and 4, 8, and 12-month follow-up. At each follow-up, subjects were classified into 3 mutually exclusive change categories using a change score of greater than or equal to 5 points. Concordance of the classification of subjects by the SIP-NH an SIP was evaluated. The misclassification rate as well as its direction was also assessed. Both instruments classified a little over one-quarter of the subjects as better, over a third as being unchanged, and another third as being worse at the four-month follow-up. More subjects were classified as worse by both in struments at 8 and 12 months. All kappas ranged from 0.52 to 0.78, indicating good to excellent agreement. Overall, the SIP-NH characterized persons as changed more often than the SIP with no systematic directional bias. In conclusion, the SIP-NH was concordant with the SIP in classifying change in subjects. However, Lye cannot say which of the two is better for detecting change. Future research must focus on defining a change score which has clinical meaning, and evaluate responsiveness to change. C1 UNIV TEXAS,HLTH SCI CTR,DIV GEN MED,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,DIV GERIATR & GERONTOL,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,CTR AGING RES & EDUC,SAN ANTONIO,TX. RP DHANDA, R (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. FU NIA NIH HHS [U01AG09117] NR 0 TC 2 Z9 2 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD AUG PY 1995 VL 7 IS 4 BP 228 EP 233 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA RY072 UT WOS:A1995RY07200011 PM 8541376 ER PT J AU AYEHUNIE, S GROVES, RW BRUZZESE, AM RUPRECHT, RM KUPPER, TS LANGHOFF, E AF AYEHUNIE, S GROVES, RW BRUZZESE, AM RUPRECHT, RM KUPPER, TS LANGHOFF, E TI ACUTELY INFECTED LANGERHANS CELLS ARE MORE EFFICIENT THAN T-CELLS IN DISSEMINATING HIV TYPE-1 TO ACTIVATED T-CELLS FOLLOWING A SHORT CELL-CELL CONTACT SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GENITAL MUCOSAL TRANSMISSION; DENDRITIC CELLS; REPLICATION; INDIVIDUALS; MACROPHAGES; EXPRESSION; EPIDERMIS; MODEL; PCR AB Most human immunodeficiency virus type 1 (HIV-1) infections involve sexual contact and virus passage across mucosal surfaces, While Langerhans cells (LCs) and dendritic cells (DCs) have been implicated in mucosal infection, their role is undefined. Here we demonstrate that acutely HIV-1-infected LCs and DCs effectively transmit virus to uninfected, activated T cells. Cocultivation of these cells results in massive virus production that requires a short cell-cell contact; as little as 30 min contact time is sufficient for HIV-1-pulsed DCs to infect their target T cells, Furthermore, surface-bound virus inactivation by trypsin does not significantly decrease the efficiency of virus transmission by LC/DCs, suggesting rapid internalization of virus. This effective virus transfer by infected LCs and blood-derived DCs requires prior activation of T cells, Surprisingly, cocultivation of acutely infected T cells with uninfected, activated target T cells results only in low virus production, even with T cell-tropic virus. We conclude that LCs and DCs are not only important targets of HIV-1 infection, but may also play a key role in the early dissemination of virus to T cells they encounter in skin or lymphoid tissue. C1 DANA FARBER CANC INST,VIRAL PATHOGENESIS LAB,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,HARVARD SKIN DIS RES CTR,DIV DERMATOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. FU NIAID NIH HHS [AI32330]; PHS HHS [A128734, 2U01-A124845] NR 41 TC 43 Z9 43 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 AUG PY 1995 VL 11 IS 8 BP 877 EP 884 DI 10.1089/aid.1995.11.877 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RN993 UT WOS:A1995RN99300001 PM 7492434 ER PT J AU WEISSMAN, NJ LEVANGIE, MW NEWELL, JB GUERRERO, JL WEYMAN, AE PICARD, MH AF WEISSMAN, NJ LEVANGIE, MW NEWELL, JB GUERRERO, JL WEYMAN, AE PICARD, MH TI EFFECT OF BETA-ADRENERGIC-RECEPTOR BLOCKADE ON THE PHYSIOLOGICAL-RESPONSE TO DOBUTAMINE STRESS ECHOCARDIOGRAPHY SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY DISEASE; PRESSURE-VOLUME; PERICARDIUM; PERFORMANCE; TOMOGRAPHY; INFUSION AB Dobutamine is an effective pharmacologic stress agent because of its beta-adrenergic receptor agonist properties. Theoretically, concurrent beta-adrenergic receptor blockade might alter this effectiveness, but clinical experience has been variable. Before assessing the relative effectiveness and implications of dobutamine stress echocardiography (DSE) to detect myocardial ischemia in the presence of beta-blockade the physiologic and hemodynamic effects of dobutamine with simultaneous beta-blockade must be understood in a controlled setting. Therefore the purpose of this study was to determine if beta-blocking agents alter the timing and magnitude of the physiologic response to graded doses of dobutamine during a standard DSE. Paired DSEs were performed in seven instrumented open-chest dogs with and without beta-blockade (esmolol 500 mu g/kg initial bolus and 100 mu g/kg/min infusion). Heart rate, systolic pressure, proximal left anterior descending coronary artery flow, myocardial thickening, and percentage left ventricular area change (%AC) were monitored. The data for each parameter were fit to linear or exponential functions. With graded doses of dobutamine, the rate of increase in coronary flow was greater than that in %AC, which in turn was greater than that in heart rate (p < 0.05). With the addition of beta-blockade, (1) despite attainment of a higher peak dobutamine dosage (14.6 +/- 8.2 vs 38.6 +/- 3.8 mu g/kg/min; p < 0.005), the peak heart rate, coronary flow, and %AC were lower (p < 0.01); (2) the rates of increase in heart rate, flow, and %AC were blunted compared with pre-beta-blockade responses (p < 0.05); and (3) the rates of increase in heart rate and Row were less than that in %AC (p = 0.03). Regardless of beta-blockade, mean systolic blood pressure remained relatively unchanged from pre-dobutamine levels. beta-Blocking agents alter the magnitude and timing of the physiologic response during DSE in this canine model. By lowering the peak cardiac workload and inotropic response during DSE, beta-blockade has the potential to influence the sensitivity of this test. z C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CARDIAC ULTRASOUND LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Guerrero, Jorge/I-3666-2015 OI Guerrero, Jorge/0000-0003-4315-7318 NR 14 TC 11 Z9 12 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD AUG PY 1995 VL 130 IS 2 BP 248 EP 253 DI 10.1016/0002-8703(95)90436-0 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RM718 UT WOS:A1995RM71800008 PM 7631603 ER PT J AU DEPRADA, JAV JIANG, L CHEN, MH PADIAL, LR GUERRERO, JL SCHWAMMENTHAL, E KING, ME WEYMAN, AE CHEN, CG LEVINE, RA AF DEPRADA, JAV JIANG, L CHEN, MH PADIAL, LR GUERRERO, JL SCHWAMMENTHAL, E KING, ME WEYMAN, AE CHEN, CG LEVINE, RA TI INTRACARDIAC ULTRASONOGRAPHIC ASSESSMENT OF ATRIAL SEPTAL-DEFECT AREA - IN-VITRO VALIDATION AND TECHNICAL CONSIDERATIONS SO AMERICAN HEART JOURNAL LA English DT Article ID TRANSCATHETER CLOSURE; CATHETER; DEVICE; SIZE AB Assessment of atrial septal defect (ASD) size and shape is important for planning and guiding its transcatheter occlusion and can potentially be achieved by intracardiac ultrasonography (ICUS). ICUS accuracy, however, must first be established against stable standards and technical imaging requirements defined. We therefore used 10, 20, and 30 MHz ICUS catheters to examine 17 ASDs that were 0.16 to 6.7 cm(2) in area and were surgically created in excised ovine hearts with 10, 20, and 30 MHz ICUS catheters. ASD shape and area by ICUS were compared with direct video images of the actual ASD. In all instances minimal area by ICUS pullback agreed well with actual values (y = 1.04x + 0.2, SEE = 0.23 cm(2), r = 0.99) and corresponded well with defect shapes. The maximum angle between ultrasonography beam and septal plane allowing for complete ASD visualization was 20 degrees. The angle depended on transducer frequency and septal thickness. This new technique has potential value for the accurate assessment of ASD shape and size and may be especially useful in the setting of transcatheter occlusion. C1 HARTFORD HOSP, DIV CARDIOL, HARTFORD, CT USA. RP DEPRADA, JAV (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED, CARDIAC ULTRASOUND LAB, VINCENT BURNHAM 5, BOSTON, MA 02114 USA. NR 14 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD AUG PY 1995 VL 130 IS 2 BP 302 EP 306 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RM718 UT WOS:A1995RM71800016 ER PT J AU JOHNS, JP ABRAHAM, SA EAGLE, KA AF JOHNS, JP ABRAHAM, SA EAGLE, KA TI DIPYRIDAMOLE-THALLIUM VERSUS DOBUTAMINE ECHOCARDIOGRAPHIC STRESS-TESTING - A CLINICIAN VIEWPOINT SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY DISEASE; ACUTE MYOCARDIAL-INFARCTION; EMISSION COMPUTED-TOMOGRAPHY; PERIPHERAL VASCULAR-DISEASE; CARDIAC RISK; PROGNOSTIC VALUE; EXERCISE ELECTROCARDIOGRAPHY; NONCARDIAC SURGERY; VIABLE MYOCARDIUM; PREOPERATIVE EVALUATION C1 VET AFFAIRS MED CTR,RENO,NV. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV MICHIGAN,MED CTR,ANN ARBOR,MI. RP JOHNS, JP (reprint author), UNIV NEVADA,SCH MED,1000 LOCUST ST,RENO,NV 89520, USA. NR 77 TC 7 Z9 7 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD AUG PY 1995 VL 130 IS 2 BP 373 EP 385 DI 10.1016/0002-8703(95)90456-5 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RM718 UT WOS:A1995RM71800028 PM 7631623 ER PT J AU MORRISON, D CROWLEY, ST BIES, R BARBIERE, CC AF MORRISON, D CROWLEY, ST BIES, R BARBIERE, CC TI SYSTOLIC BLOOD-PRESSURE RESPONSE TO PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY FOR CARDIOGENIC-SHOCK SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION AB This study reports that an improvement in systolic blood pressure of >10 mm Hg after percutaneous transluminal coronary angioplasty in patients with cardiogenic shock was associated with in-hospital survival (8 of 8 patients), Failure to achieve infarct artery patency (6 of 6 patients) or technically successful percutaneous transluminal coronary angioplasty unaccompanied by improved systolic blood pressure in the laboratory were both accompanied by in-hospital mortality in this series. C1 UNIV COLORADO,HLTH SCI CTR,DENVER,CO 80220. RP MORRISON, D (reprint author), DENVER VET AFFAIRS MED CTR,CARDIOL SECT,1055 CLERMONT ST,DENVER,CO 80220, USA. NR 6 TC 5 Z9 5 U1 0 U2 0 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 AUG 1 PY 1995 VL 76 IS 4 BP 313 EP 314 DI 10.1016/S0002-9149(99)80090-3 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RL359 UT WOS:A1995RL35900023 PM 7618633 ER PT J AU CLARK, JL KUCUK, O NEUBERG, DS BENSON, AB TAYLOR, SG PANDYA, KJ MANSOUR, EG DOUGLASS, HO HALLER, DG AF CLARK, JL KUCUK, O NEUBERG, DS BENSON, AB TAYLOR, SG PANDYA, KJ MANSOUR, EG DOUGLASS, HO HALLER, DG TI PHASE-II TRIAL OF ETOPOSIDE, DOXORUBICIN, AND CISPLATIN COMBINATION IN ADVANCED MEASURABLE GASTRIC-CANCER - AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP STUDY SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE ADVANCED GASTRIC CANCER; COMBINATION CHEMOTHERAPY; ETOPOSIDE; DOXORUBICIN; CISPLATIN ID MITOMYCIN-C FAM; 5-FLUOROURACIL; ADRIAMYCIN; CHEMOTHERAPY; CARCINOMA; ADENOCARCINOMAS; BCNU AB A phase II study was performed to determine the efficacy and toxicity of the etoposide, doxorubicin, cisplatin (EAP) regimen in the treatment of patients with advanced measurable gastric cancer in a multi-institutional cooperative group setting. Thirty-one evaluable patients with advanced measurable gastric adenocarcinoma were treated with etoposide 120 mg/m(2) on days 3, 4, and 5, doxorubicin 20 mg/m(2) on days 1 and 8, and cisplatin 40 mg/m(2) on days 2 and 9. The treatment was repeated every 28 days. Objective responses were seen in 7 (23%) patients, all achieving partial remissions. Median survival was 9 months for the entire group. Toxicity was mostly hematologic, with grade 3 leukopenia in 26% and grade 4 leukopenia in 55% of the patients. There were 4 treatment-related deaths that were attributable to severe leukopenia and sepsis. Because of the high toxicity and moderate response rate, this regimen is not superior to other less toxic regimens and cannot be recommended for the treatment of advanced gastric cancer outside of an investigational protocol. C1 UNIV HLTH SCI CHICAGO MED SCH,N CHICAGO,IL 60064. VET AFFAIRS MED CTR,N CHICAGO,IL. NORTHWESTERN UNIV,CHICAGO,IL 60611. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV ROCHESTER,ROCHESTER,NY 14627. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. ROSWELL PK CANC INST,BUFFALO,NY. UNIV PENN,PHILADELPHIA,PA 19104. FU NCI NIH HHS [CA21115] NR 25 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD AUG PY 1995 VL 18 IS 4 BP 318 EP 324 DI 10.1097/00000421-199508000-00010 PG 7 WC Oncology SC Oncology GA RM009 UT WOS:A1995RM00900010 PM 7625373 ER PT J AU LAPOSATA, M AF LAPOSATA, M TI FATTY-ACIDS - BIOCHEMISTRY TO CLINICAL-SIGNIFICANCE SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Review DE FATTY ACIDS; LIPIDS; ATHEROSCLEROSIS; DIETARY FAT ID GAMMA-LINOLENIC ACID; THIOESTER LINKAGES; MAMMALIAN-CELLS; HUMAN-PLATELETS; PALMITIC ACID; CHOLESTEROL; METABOLISM; DENSITY; LIPOPROTEINS; ARACHIDONATE AB Fatty acids are a major source of lipids in the diet. Dietary fatty acids are able to significantly influence the concentration of serum cholesterol and thereby influence the risk of atherosclerosis. This brief review on fatty acids will present information on the structure and nomenclature of fatty acids, the metabolic pathways for fatty acids in cells, and the influence of dietary fatty acids on serum cholesterol levels. RP LAPOSATA, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,DIV CLIN LABS,BOSTON,MA 02114, USA. NR 44 TC 8 Z9 9 U1 0 U2 2 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 AUG PY 1995 VL 104 IS 2 BP 172 EP 179 PG 8 WC Pathology SC Pathology GA RN608 UT WOS:A1995RN60800011 PM 7639192 ER PT J AU LIU, AW DELGADOESCUETA, AV SERRATOSA, JM ALONSO, ME MEDINA, MT GEE, MN CORDOVA, S ZHAO, HZ SPELLMAN, JM PEEK, JRR DONNADIEU, FR SPARKES, RS AF LIU, AW DELGADOESCUETA, AV SERRATOSA, JM ALONSO, ME MEDINA, MT GEE, MN CORDOVA, S ZHAO, HZ SPELLMAN, JM PEEK, JRR DONNADIEU, FR SPARKES, RS TI JUVENILE MYOCLONIC EPILEPSY LOCUS IN CHROMOSOME 6P21.2-P11 - LINKAGE TO CONVULSIONS AND ELECTROENCEPHALOGRAPHY TRAIT SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID IDIOPATHIC GENERALIZED EPILEPSY; NORMAL-CHILDREN; HLA REGION; FAMILIES AB Despite affecting 4 million Americans and 100-200 million persons worldwide, the precise molecular mechanisms of human epilepsies remain unknown. Juvenile myoclonic epilepsy (JME) is the most frequent and, hence, most important form of hereditary grand mal epilepsy. In this epilepsy, electroencephalographic (EEG) 15-30-Hz multispikes produce myoclonic and tonic-clonic convulsions beginning at 8-20 years of age. Moreover, EEG 3.5-6-Hz multispike wave complexes appear in clinically asymptomatic family members. We first studied 38 members of a four-generation LA-Belize family with classical JME but with no pyknoleptic absences. Five living members had JME; four clinically asymptomatic members had EEG multispike wave complexes. Pairwise analysis tightly linked microsatellites centromeric to HLA, namely D6S272 (peak lod score [Z(max)] = 3.564-3.560 at male-female recombination [theta(m=f)] = 0.001) and D6S257 (Z(max) = 3.672-3.6667 at theta(m=f) = 0.001), spanning 7 cM, to convulsive seizures and EEG multispike wave complexes. A recombination between D6S276 and D6S273 in one affected member placed the JME locus within or below HLA. Pairwise, multipoint, and recombination analyses in this large family independently proved that a JME gene is located in chromosome 6p, centromeric to HLA. We next screened, with the same chromosome 6p21.2-p11 short tandem-repeat polymorphic markers, seven multiplex pedigrees with classic JME, When led scores for small multiplex families are added to led scores of the LA-Belize pedigree, Z(max) values for D6S294 and D6S257 are >7 (theta(m=f) = .000). Our results prove that in chromosome 6p21.2-p11 an epilepsy locus exists whose phenotype consists of classic JME with convulsions and/or EEG rapid multispike wave complexes. C1 W LOS ANGELES VET AFFAIRS MED CTR,VET AFFAIRS SW REG EPILEPSY CTR,NEUROL SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,VET AFFAIRS SW REG EPILEPSY CTR,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,CALIF COMPREHENS EPILEPSY PROGRAM,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA. NATL AUTONOMOUS UNIV,TEGUCIGALPA,HONDURAS. NATL INST NEUROL & NEUROSURG,MEXICO CITY,DF,MEXICO. FU NINDS NIH HHS [5P01 NS21908] NR 31 TC 115 Z9 116 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 AUG PY 1995 VL 57 IS 2 BP 368 EP 381 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA RL771 UT WOS:A1995RL77100020 PM 7668263 ER PT J AU WEINRAUCH, LA DELIA, JA GLEASON, RE KEOUGH, J MANN, D KENNEDY, FP AF WEINRAUCH, LA DELIA, JA GLEASON, RE KEOUGH, J MANN, D KENNEDY, FP TI AUTONOMIC FUNCTION IN TYPE-I DIABETES-MELLITUS COMPLICATED BY NEPHROPATHY - A CROSS-SECTIONAL ANALYSIS IN THE PRESYMPTOMATIC PHASE SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE TYPE I DIABETES; AUTONOMIC DYSFUNCTION; HEART RATE VARIATION; CROSS-SECTIONAL ANALYSIS AB The purpose of this study was to determine the prevalence of parasympathetic and sympathetic autonomic dysfunction in long-standing type I diabetics with established nephropathy and to correlate autonomic function with cardiac risk factors. We used prospective analysis of heart rate variations to standardized testing and 24-hour blood pressure control prior to enrollment in a study utilizing various methods of intense diabetic control to prevent deterioration of kidney function. The settings were outpatient clinical research units. The patients were 42 type I diabetics with proteinuria (total urinary protein greater than or equal to 300 mg/day or urinary albumin greater than or equal to 100 mg/day) and creatinine clearance greater than or equal to 30 mL/min. Heart rate variation during respiratory cycles with change in posture from supine to upright, and during the Valsalva maneuver was recorded by a computerized method. Mean arterial blood pressure was recorded for 24 h by a computerized method. Heart rate variations in this group were abnormal during timed respiratory cycles in 26 of 40 patients (56%), during changes in posture in 15 of 40 patients (38%), and during Valsalva maneuver in 13 of 34 patients (38%) whose retinal disease permitted Valsalva testing. Blunted day/night mean arterial pressure ratios occurred in 18 of 41 (44%) patients and were more severe in men than in women (1.00 v 1.06, P less than or equal to .05). Absence of deep tendon reflexes was associated with an increased incidence of both parasympathetic (respiratory rate variation) and sympathetic (postural rate variation) abnormalities (both P less than or equal to .05). Loss of vibration sensation was not associated with autonomic functional abnormalities. Patients in whom heart rate variations during respiratory cycles were decreased had significantly lower mean serum albumin and higher incidence of the need for laser treatment for retinal microvascular disease. Individuals with an HDL cholesterol less than or equal to 40 mg/dL had a significantly higher incidence of blunted day/night mean arterial pressure ratios. Gender differences occurred in mean levels of HDL cholesterol (women, 54 v men, 45 mg/dL, P < .05). The results of autonomic nerve testing were not predictable from history, physical examination, or blood testing. The levels of blood pressure, serum, total cholesterol, triglyceride, creatinine, urinary protein excretion, and creatinine clearance did not correlate with either prevalence or severity of autonomic nerve testing. Follow-up to determine the relevance of autonomic nerve testing as an independent cardiac risk factor in this high-risk population is ongoing. C1 JOSLIN DIABET CTR,JOHN E COOK RENAL UNIT,BOSTON,MA 02215. OI Weinrauch, Larry/0000-0003-1357-9528 NR 0 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD AUG PY 1995 VL 8 IS 8 BP 782 EP 789 DI 10.1016/0895-7061(95)00148-I PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RM142 UT WOS:A1995RM14200002 PM 7576394 ER PT J AU UY, HL REASNER, CA SAMUELS, MH AF UY, HL REASNER, CA SAMUELS, MH TI PATTERN OF RECOVERY OF THE HYPOTHALAMIC-PITUITARY-THYROID AXIS FOLLOWING RADIOACTIVE IODINE THERAPY IN PATIENTS WITH GRAVES-DISEASE SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID THYROTROPIN-RELEASING-HORMONE; LONG-TERM FOLLOW; FEEDBACK-REGULATION; I-131 THERAPY; HYPERTHYROIDISM; SECRETION; TSH; THYROTOXICOSIS; HYPOTHYROIDISM; SUPPRESSION AB PURPOSE: To characterize the time course of recovery of the hypothalamic-pituitary-thyroid (HPT) axis by determining the frequency, onset, duration, and clinical attributes of the central hypothyroid phase following I-131 therapy for Graves' disease and to examine whether the central hypothyroid phase is due to direct pituitary thyrotroph suppression or to hypothalamic thyrotropin-releasing hormone (TRH) deficiency. PATIENTS AND METHODS: Twenty-one hyperthyroid patients with Graves' disease evaluated at a university endocrine clinic and treated with radioactive iodine were prospectively studied. Serial thyroid function levels (sevum thyroxine [T-4], free thyroxine [free T-4], triiodothyronine [T-3], and thyroid-stimulating hormone [TSH]) were measured and TRH stimulation tests were performed at 2 to 4 week intervals for all subjects following I-131 treatment. None of the patients was treated with thionamides after receiving I-131 therapy. RESULTS: Nineteen (90%) of the patients with Graves' disease experienced a transient central hypothyroid phase defined as the presence of a suppressed or inappropriately normal TSH level despite a low free T-4 level following I-131 treatment. This phase occurred a mean of 62.8 +/- 5.1 days following I-131 treatment, persisted for an average of 24.7 +/- 2.4 days, and was not predictive of eventual treatment outcome. All patients had concordantly low T-4 and T-3 levels during this period and exhibited a blunted TSH response to TRH compared to 29 euthyroid control subjects, suggesting primary feedback suppression at the level of the pituitary thyrotrophs. The suppressed thyrotrophs required a minimum of 2 weeks to recover once patients became hypothyroid. The length of preexisting hyperthyroidism, basal free T-4 elevation, and administered dose of I-131 failed to predict the duration of the central hypothyroid phase, although a higher dose of I-131 was associated with an earlier onset of central hypothyroidism (r = -.51, P <0.05). CONCLUSIONS: Clinicians should be aware of the delay in the recovery of the HPT axis that occurs in the majority of patients with Graves' disease treated with I-131 and is manifested by a transient central hypothyroid phase. The blunted TSH response to TRH stimulation during this period suggests that suppression occurs primarily at the level of the pituitary thyrotrophs. The use of sensitive TSH measurements alone to monitor these patients during this period is not helpful and may be misleading. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP UY, HL (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV ENDOCRINOL & METAB,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NCRR NIH HHS [MO1-RR-01345] NR 30 TC 39 Z9 42 U1 0 U2 1 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 1995 VL 99 IS 2 BP 173 EP 179 DI 10.1016/S0002-9343(99)80137-5 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA RN319 UT WOS:A1995RN31900010 PM 7625422 ER PT J AU GORDON, S GRADY, EM AF GORDON, S GRADY, EM TI WHATS IN A NAME SO AMERICAN JOURNAL OF NURSING LA English DT Article C1 MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. NR 2 TC 2 Z9 2 U1 0 U2 0 PU AMER J NURSING CO PI NEW YORK PA 555 W 57TH ST, NEW YORK, NY 10019-2961 SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD AUG PY 1995 VL 95 IS 8 BP 31 EP 33 PG 3 WC Nursing SC Nursing GA RP009 UT WOS:A1995RP00900034 PM 7631654 ER PT J AU WANG, DH BALKOVETZ, DF WARNOCK, DG AF WANG, DH BALKOVETZ, DF WARNOCK, DG TI MUTATIONAL ANALYSIS OF TRANSMEMBRANE HISTIDINES IN THE AMILORIDE-SENSITIVE NA+/H+ EXCHANGER SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE SODIUM HYDROGEN EXCHANGER; CIMETIDINE; DIETHYL PYROCARBONATE; ETHYL ISOPROPYL AMILORIDE ID RAT NA/H EXCHANGER; BRUSH-BORDER MEMBRANE; H+ EXCHANGER; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; CHEMICAL MODIFICATION; ESCHERICHIA-COLI; CYTOSOLIC PH; ANTIPORTER; NHE-1 AB The histidine-reactive reagent, diethyl pyrocarbonate (DEPC) inhibits the human amiloride-sensitive Na+/H+ exchanger (NHE1) in stably transfected fibroblasts. NHE1 was protected by cimetidine and amiloride from DEPC, and DEPC inhibition was reversed with hydroxylamine, suggesting a role for critical histidine groups in NHE activity. We replaced the histidines CH) in putative transmembrane domains (H35, H120, H349) with glycine (G) using site-directed mutagenesis. There was no significant change in NHE activity of the H120G; H349G; H120,349G; and H35,120,349G mutants compared with wild type. The 50% inhibition concentration values for amiloride, ethyl isopropyl amiloride (EIPA), and cimetidine of the H349G mutant were significantly increased compared with the wildtype NHE1. We also examined the DEPC effect on the transport activity of the triple histidine mutant (H35,120,349G) and found that NHE1 activity was still inhibited by DEPC with reversal by hydroxylamine and protected by amiloride and cimetidine. Kinetic analysis of DEPC inhibition indicated that two ''critical'' histidine residues are required for NHE transport activity. Substitutions of H349 with asparagine (N), glutamine (Q), serine (S), tyrosine (Y), valine (V), leucine (L), and phenylalanine (F) were also examined. There were no changes in NHE activity of these mutants compared with wild type. The H349G and H349L mutants became more resistant to amiloride, whereas the H349Y and H349F mutants became more sensitive to amiloride. The H349S (mimics NHE3) and H349Y (mimics NHE4) mutations had only modest effects on amiloride sensitivity. These results indicate that H349 affects the interaction of NHE1 with its inhibitors, even though substitutions at this site, per se, do not appear to explain the differences in amiloride sensitivity between different NHE isoforms. Despite clear-cut effects of the H349G mutation on the competitive interaction of NHE1 with cimetidine and EIPA, this mutation did not affect the affinity of NHE1 for its cationic substrates (Na+, Li+). C1 UNIV ALABAMA, DEPT MED, DIV NEPHROL, BIRMINGHAM, AL 35294 USA. UNIV ALABAMA, VASC BIOL & HYPERTENS PROGRAM, CTR NEPHROL RES & TRAINING, DEPT PHYSIOL & BIOPHYS, BIRMINGHAM, AL 35294 USA. UNIV ALABAMA, BIRMINGHAM VET AFFAIRS MED CTR, DEPT VET AFFAIRS, BIRMINGHAM, AL 35294 USA. FU NHLBI NIH HHS [5T32-HL-07457]; NIDDK NIH HHS [P50-DK-39258, R01-DK-19407] NR 47 TC 53 Z9 53 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD AUG PY 1995 VL 269 IS 2 BP C392 EP C402 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA RP469 UT WOS:A1995RP46900012 PM 7653521 ER PT J AU AJIE, HO CONNOR, MJ LEE, WNP BASSILIAN, S BERGNER, EA BYERLEY, LO AF AJIE, HO CONNOR, MJ LEE, WNP BASSILIAN, S BERGNER, EA BYERLEY, LO TI IN-VIVO STUDY OF THE BIOSYNTHESIS OF LONG-CHAIN FATTY-ACIDS USING DEUTERATED WATER SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE LONG-CHAIN FATTY ACID TURNOVER AND RECYCLING; CHAIN ELONGATION; PRIMERS OF FATTY ACID SYNTHESIS ID STEROL SYNTHESIS; STABLE ISOTOPES; TRITIATED-WATER; INVIVO AB To determine the contributions of preexisting fatty acid, de novo synthesis, and chain elongation in long-chain fatty acid (LCFA) synthesis, the synthesis of LCFAs, palmitate (16:0), stearate (18:0), arachidate (20:0), behenate (22:0), and lignocerate (24:0), in the epidermis, liver, and spinal cord was determined using deuterated water and mass isotopomer distribution analysis in hairless mice and Sprague-Dawley rats. Animals were given 4% deuterated water for 5 days or 8 wk in their drinking water. Blood was withdrawn at the end of these times for the determination of deuterium enrichment, and the animals were killed to isolate the various tissues for lipid extraction for the determination of the mass isotopomer distributions. The mass isotopomer distributions in LCFA were incompatible with synthesis from a single pool of primer. The synthesis of palmitate, stearate, arachidate, behenate, and lignocerate followed the expected biochemical pathways for the synthesis of LCFAs. On average, three deuterium atoms were incorporated for every addition of an acetyl unit. The isotopomer distribution resulting from chain elongation and de novo synthesis can be described by the linear combination of two binomial distributions. The proportions of preexisting, chain elongation, and de novo-synthesized fatty acids as a percentage of the total fatty acids were determined using multiple linear regression analysis. Fractional synthesis was found to vary, depending on the tissue type and the fatty acid, from 47 to 87%. A substantial fraction (24-40%) of the newly synthesized molecules was derived from chain elongation of unlabeled (recycled) palmitate. C1 UNIV CALIF LOS ANGELES, LOS ANGELES CTY HARBOR MED CTR, INST RES & EDUC, TORRANCE, CA 90502 USA. UNIV CALIF LOS ANGELES, SCH MED, CTR HLTH SCI, DIV DERMATOL, LOS ANGELES, CA 90024 USA. W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA 90073 USA. UNIV TEXAS, DEPT HUMAN ECOL, AUSTIN, TX 78712 USA. FU NCRR NIH HHS [M01-RR-00425]; NIDDK NIH HHS [R01-DK-46353]; NIEHS NIH HHS [R01-ES-03597] NR 19 TC 22 Z9 22 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD AUG PY 1995 VL 269 IS 2 BP E247 EP E252 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA RP468 UT WOS:A1995RP46800007 PM 7653542 ER PT J AU KUNISAKI, M BURSELL, SE CLERMONT, AC ISHII, H BALLAS, LM JIROUSEK, MR UMEDA, F NAWATA, H KING, GL AF KUNISAKI, M BURSELL, SE CLERMONT, AC ISHII, H BALLAS, LM JIROUSEK, MR UMEDA, F NAWATA, H KING, GL TI VITAMIN-E PREVENTS DIABETES-INDUCED ABNORMAL RETINAL BLOOD-FLOW VIA THE DIACYLGLYCEROL-PROTEIN KINASE-C PATHWAY SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE HYPERGLYCEMIA; RETINAL HEMODYNAMICS; RETINAL ENDOTHELIAL CELLS ID VASCULAR SMOOTH-MUSCLE; ALPHA-TOCOPHEROL; GLYCEMIC CONTROL; RATS; COMPLICATIONS; CIRCULATION; GLUCOSE; PATHOGENESIS; ACTIVATION; MEDIATION AB We have characterized effects of d-alpha-tocopherol (vitamin E) on activation of protein kinase C (PKC) and diacylglycerol (DAG) levels in retinal tissues of diabetic rats and correlated its effects to diabetes-induced changes in retinal hemodynamics. Membrane PKC specific activities were increased by 71% in streptozocin-induced diabetic rats compared with controls (P < 0.05). Western blot analysis showed that membrane PKC-P-II was increased by 133 +/- 5% (P < 0.05). Injection of d-alpha-tocopherol (40 mg/kg ip) every other day prevented the increases in membrane PKC specific activity and PKC-beta(II) protein by immunoblots. Diabetes-induced increases in DAG levels were also normalized by d-alpha-tocopherol treatment of 2 wk duration. Physiologically, angiographic abnormalities of retinal hemodynamics based on computerized video-based fluorescein angiography and associated with increases of DAG and membranous PKC levels were also prevented by d-alpha-tocopherol treatment in diabetic rats. The effect of d-alpha-tocopherol on retinal vascular cells was also studied. Exposure of retinal endothelial cells to 22 mM glucose for 3 days increased total DAG and [H-3]palmitate-labeled DAG levels by 35 +/- 8 and 50 +/- 8% (P < 0.05), respectively, compared with exposure to 5.5 mM glucose. The presence of d-alpha-tocopherol (50 mu g/ml) prevented the increases in total DAG and [H-3]palmitate-labeled DAG levels in cells exposed to 22 mM glucose. These findings suggested that treatment with d-alpha-tocopherol can prevent diabetes-induced abnormalities in rat retinal blood flow. The mechanism of d-alpha-tocopherol's effect appears to be mediated by normalization of hyperglycemia-induced activation of the DAG-PKC pathway in the retina of diabetic rats. C1 JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02215 USA. BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02215 USA. KYUSHU UNIV, FAC MED, DEPT INTERNAL MED 3, FUKUOKA 812, JAPAN. SPHINX PHARMACEUT CORP, DURHAM, NC 27717 USA. LILLY RES LABS INC, INDIANAPOLIS, IN 46285 USA. FU NEI NIH HHS [EY-05110]; NIDDK NIH HHS [DK-36836] NR 41 TC 129 Z9 134 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD AUG PY 1995 VL 269 IS 2 BP E239 EP E246 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA RP468 UT WOS:A1995RP46800006 PM 7653541 ER PT J AU MORROW, NS QUINONEZ, G WEINER, H TACHE, Y GARRICK, T AF MORROW, NS QUINONEZ, G WEINER, H TACHE, Y GARRICK, T TI INTERLEUKIN-1-BETA IN THE DORSAL VAGAL COMPLEX INHIBITS TRH ANALOG-INDUCED STIMULATION OF GASTRIC CONTRACTILITY SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE VAGUS; INTERLEUKIN-1 RECEPTOR ANTAGONIST; HYPOGLOSSAL NUCLEUS ID THYROTROPIN-RELEASING-HORMONE; NERVOUS-SYSTEM ACTION; RECEPTOR ANTAGONIST; ACID-SECRETION; INTESTINAL MOTILITY; BRAIN; RATS; EXPRESSION; LOCALIZATION; MECHANISMS AB The effect of murine interleukin-1 beta (mIL-1 beta) microinjected into the dorsal vagal complex (DVC) on thyrotropin-releasing hormone (TRH) analogue (RX-77368)-induced stimulation of gastric contractility was examined in fasted, urethan-anesthetized rats. Gastric corpus contractions were measured with extraluminal force transducers and analyzed by computer. Microinjection of RX-17368 (30 ng) into the right DVC with mIL-1 beta microinjected either into the right (100, 250 pg) or into the left (100, 500 pg) DVC inhibited gastric contractility for 30-120 min postinjection. Peak suppression of gastric contractility (64-78%) occurred at 50-60 min postinjection. Microinjedion of mIL-1 beta into the DVC at a lower dose (10 pg) or into sites adjacent to the DVC (100-500 pg) did not suppress the stimulated gastric contractility pattern. Injection of mIL-1 beta (250 pg) or 0.1% bovine serum albumin into the DVC alone did not alter basal gastric contractlity. Intracisternal injection of the IL-1 receptor antagonist (250 ng/10 mu l) abofished the inhibitory effect of mIL-1 beta (250 pg) on gastric contractility. These results demonstrate that mIL-1 beta acts in the DVC to inhibit vagally stimulated gastric contractility, and its action is mediated by IL-1 receptors. C1 W LOS ANGELES VET AFFAIRS MED CTR, DEPT PSYCHIAT, CTR GASTROENTER BIOL, CTR ULCER RES & EDUC, LOS ANGELES, CA USA. W LOS ANGELES VET AFFAIRS MED CTR, DEPT MED, LOS ANGELES, CA USA. W LOS ANGELES VET AFFAIRS MED CTR, RES DEPT, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, DEPT PSYCHIAT & BIOBEHAV SCI, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, DEPT MED, LOS ANGELES, CA 90024 USA. FU NIADDK NIH HHS [AM-33061]; NIDDK NIH HHS [DK-41301]; NIMH NIH HHS [MH-00663] NR 40 TC 8 Z9 8 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD AUG PY 1995 VL 269 IS 2 BP G196 EP G202 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA RP346 UT WOS:A1995RP34600003 PM 7653558 ER PT J AU RUSSELL, WJ HO, YS PARISH, G JACKSON, RM AF RUSSELL, WJ HO, YS PARISH, G JACKSON, RM TI EFFECTS OF HYPOXIA ON MNSOD EXPRESSION IN MOUSE LUNG SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE SUPEROXIDE DISMUTASE; GENE REGULATION; OXYGEN TOXICITY ID CONTAINING SUPEROXIDE-DISMUTASE; ANTIOXIDANT ENZYMES; RAT LUNGS; ESCHERICHIA-COLI; MAMMALIAN-CELLS; OXYGEN; SEQUENCE; PREEXPOSURE; TOXICITY; OXIDANTS AB Mitochondrial manganese-containing SOD (MnSOD) is located at the primary site of O-2 metabolism, and its expression may be regulated by changes in O-2 level. We hypothesized that lung MnSOD expression and promoter activity would decrease in response to hypoxia. We tested effects of hypoxia (10% O-2 at sea level for 7 days) on chloramphenicol acetyltransferase (CAT) reporter and MnSOD gene expression in transgenic mice. The transgene consisted of a 3.3-kb portion of the rat MnSOD gene 5' flanking region coupled to a CAT reporter gene. Lung MnSOD activity in male (but not female) mice decreased significantly after hypoxia exposure. The decrease in MnSOD enzymatic activity in male mice was specific. Neither total SOD nor glucose-6-phosphate dehydrogenase (G-6-PDH) activity decreased significantly in hypoxia. CAT protein expression decreased in transgenic males exposed to hypoxia, while CAT protein expression in hypoxic transgenic females remained comparable with controls. The mRNA for both the native MnSOD and the MnSOD-CAT reporter genes remained constant after hypoxia, as did CuZnSOD and G-6-PDH mRNAs. C1 UNIV ALABAMA, DIV PULM & CRIT CARE MED, BIRMINGHAM, AL 35294 USA. BIRMINGHAM VET AFFAIRS MED CTR, BIRMINGHAM, AL 35294 USA. WAYNE STATE UNIV, DETROIT, MI 48202 USA. FU NHLBI NIH HHS [HL-39585, HL-39147]; NIDDK NIH HHS [1T32-DK-07545] NR 39 TC 20 Z9 20 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD AUG PY 1995 VL 269 IS 2 BP L221 EP L226 PG 6 WC Physiology; Respiratory System SC Physiology; Respiratory System GA RP719 UT WOS:A1995RP71900013 PM 7653584 ER PT J AU GOFF, DC TSAI, GC MANOACH, DS COYLE, JT AF GOFF, DC TSAI, GC MANOACH, DS COYLE, JT TI DOSE-FINDING TRIAL OF D-CYCLOSERINE ADDED TO NEUROLEPTICS FOR NEGATIVE SYMPTOMS IN SCHIZOPHRENIA SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Note CT 33rd Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 12-16, 1994 CL SAN JUAN, PR SP Amer Coll Neuropsychopharm ID MODULATION; STRATEGY; BRAIN AB Objective: The authors conducted a dose-finding study of D-cycloserine, a partial agonist at the glycine site of the N-methyl-D-aspartate subtype of the glutamate receptor, added to conventional neuroleptics for schizophrenic patients with prominent negative symptoms. Method: Nine patients with schizophrenia completed consecutive 2-week trials of placebo and four doses of o-cycloserine. Clinical assessments were videotaped and were scored by a rater who was blind to temporal sequence. Results: D-Cycloserine at a dose of 50 mg/day produced a significant reduction (mean=21%, SD=28%) in negative symptoms and significantly improved reaction time as measured by Sternberg's Item Recognition Paradigm, a test mediated in part by prefrontal cortex. Conclusions: This preliminary evidence suggests that o-cycloserine may improve negative symptoms and cognitive deficits over a narrow dose range when added to conventional antipsychotic agents. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP GOFF, DC (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,ERICH LINDEMANN MENTAL HLTH CTR,FREEDOM TRAIL CLIN,BOSTON,MA 02114, USA. NR 16 TC 188 Z9 189 U1 0 U2 2 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 AUG PY 1995 VL 152 IS 8 BP 1213 EP 1215 PG 3 WC Psychiatry SC Psychiatry GA RL642 UT WOS:A1995RL64200021 PM 7625475 ER PT J AU BUCKLEY, KM WHITMAN, GJ CHEW, FS AF BUCKLEY, KM WHITMAN, GJ CHEW, FS TI DIAPHRAGMATIC PHEOCHROMOCYTOMA SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note ID EXTRAADRENAL PHEOCHROMOCYTOMA C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP BUCKLEY, KM (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 4 TC 7 Z9 7 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 1995 VL 165 IS 2 BP 260 EP 260 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RJ959 UT WOS:A1995RJ95900003 PM 7618536 ER PT J AU DRUCKER, EA BROOKS, R GARAN, H SWEENEY, MO RUSHKIN, JM MCGOVERN, BA MILLER, SW AF DRUCKER, EA BROOKS, R GARAN, H SWEENEY, MO RUSHKIN, JM MCGOVERN, BA MILLER, SW TI MALFUNCTION OF IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS PLACED BY A NONTHORACOTOMY APPROACH - FREQUENCY OF MALFUNCTION AND VALUE OF CHEST RADIOGRAPHY IN DETERMINING CAUSE SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article AB OBJECTIVE. The purpose of this study was to determine the frequency of system malfunction in patients with nonthoracotomy implantable cardioverter defibrillators and to assess the role of chest radiography in detecting and determining the cause of malfunction. MATERIALS AND METHODS. The study population consisted of 300 consecutive patients in whom implantable cardioverter defibrillators were implanted using an initial nonthoracotomy approach between September 1990 and October 1994. Transvenous electrodes were placed via the subclavian or cephalic vein under local anesthetic. Intraoperative testing, pulse generator implantation, and, if necessary, subcutaneous patch or extrapericardial patch placement via thoracotomy were done in the operating room under general anesthetic, follow-up consisted of routine device interrogation every 2-3 months and annual chest radiography. Chest radiographs were obtained more often if patients were symptomatic or if results of device interrogation were abnormal. RESULTS. Patients were followed up for a mean +/- SD of 19 +/- 14 months following implantation. Implantable cardioverter-defibrillator malfunction occurred in 17 patients (6%) during the follow-up period. Of these, 12 (71%) had component abnormalities on chest radiographs. Patients with radiographically apparent implantable cardioverter-defibrillator abnormalities presented in two discrete ti me periods after device implantation, early (mean, 35 +/- 14 days) and late (mean, 18 +/- 5 months). CONCLUSION. Malfunction of nonthoracotomy implantable cardioverter-defibrillator systems develops infrequently after device implantation. In most cases, the cause can be identified on chest radiographs. C1 MASSACHUSETTS GEN HOSP,CARDIAC ARRHYTHMIA SERV,CARDIAC UNIT,BOSTON,MA 02114. RP DRUCKER, EA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114, USA. NR 10 TC 10 Z9 10 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 1995 VL 165 IS 2 BP 275 EP 279 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RJ959 UT WOS:A1995RJ95900006 PM 7618539 ER PT J AU CHUNG, KY MAYOSMITH, WW SAINI, S RAHMOUNI, A GOLLI, M MATHIEU, D AF CHUNG, KY MAYOSMITH, WW SAINI, S RAHMOUNI, A GOLLI, M MATHIEU, D TI HEPATOCELLULAR ADENOMA - MR-IMAGING FEATURES WITH PATHOLOGICAL CORRELATION SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID FOCAL NODULAR HYPERPLASIA; LIVER-CELL ADENOMA; HEPATIC ADENOMA; CT; TUMORS; APPEARANCE; DISEASE AB OBJECTIVE. The purpose of this study was to describe the MR imaging characteristics of hepatic adenomas and to correlate these features with pathologic findings. MATERIALS AND METHODS. Sixteen patients from four institutions who had 31 hepatocellular adenomas underwent MR imaging with T1- and T2-weighted pulse sequences at 1.5 T. Dynamic gadolinium-chelate-enhanced gradient-recalled-echo (GRE) MR imaging was done in eight patients with 15 lesions. Twenty-three lesions in 15 patients were confirmed by surgical excision. MR images were retrospectively reviewed by three experienced radiologists for signal intensity of lesions relative to liver, heterogeneity, contrast enhancement, and presence of signs of histopathologic correlates. These imaging findings were then compared with histopathologic findings. RESULTS. Nearly all (29 of 31 lesions) hepatocellular adenomas showed heterogeneous signal intensity on MR images. Most (19/31) were predominantly hyperintense on proton density- or T2-weighted images; the predominant signal intensity on T1-weighted images varied. Thirteen of 15 lesions showed early arterial enhancement relative to liver on dynamic GRE MR images. MR imaging was most successful in showing intratumoral hemorrhage (10 of 12 histopathologically proven lesions), large intratumoral vessels (five of five), fatty change (three of six), and peliosis (three of three cases). In two lesions, capsules (one of five) and central scars (one of three) were detected. CONCLUSION. Hepatocellular adenomas have a highly variable appearance on MR images because of their varied histologic appearances. Although no definitive MR imaging signal or structural characteristics can be identified, tumor heterogeneity, particularly when related to hemorrhage, and early arterial enhancement can suggest a diagnosis of hepatocellular adenoma in the proper patient population. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HOP HENRI MONDOR,F-94010 CRETEIL,FRANCE. NR 21 TC 75 Z9 80 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 1995 VL 165 IS 2 BP 303 EP 308 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RJ959 UT WOS:A1995RJ95900012 PM 7618545 ER PT J AU MCNICHOLAS, MMJ MUELLER, PR LEE, MJ ECHEVERRI, J GAZELLE, GS BOLAND, GW DAWSON, SL AF MCNICHOLAS, MMJ MUELLER, PR LEE, MJ ECHEVERRI, J GAZELLE, GS BOLAND, GW DAWSON, SL TI PERCUTANEOUS DRAINAGE OF SUBPHRENIC FLUID COLLECTIONS THAT OCCUR AFTER SPLENECTOMY - EFFICACY AND SAFETY OF TRANSPLEURAL VERSUS EXTRAPLEURAL APPROACH SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ABSCESSES; COMPLICATIONS AB OBJECTIVE. The purpose of this study was to compare the safety and efficacy of transpleural and extrapleural approaches for draining left subphrenic abscesses in patients who have had splenectomy. MATERIALS AND METHODS. Twenty-five patients who had percutaneous catheter drainage (28 drainages) of postsplenectomy fluid collections were studied. Twenty drainages were transpleural and eight were extrapleural. In eight of the 20 transpleural drainages, it was elected to place the catheter transpleurally. In the remaining 12 patients, catheter drainage was judged to be transpleural on review, despite efforts to use an extrapleural approach. RESULTS. Sixteen of 18 patients who had transpleural percutaneous drainage and six of seven patients who had true extrapleural (subcostal) percutaneous drainage were cured by catheter drainage requiring no further intervention. The mean number of days of drainage was not significantly different (p > .05) for the group drained transpleurally (mean, 18 days; range, 1-90 days) versus the group drained extrapleurally (mean, 20 days; range, 6-43 days). Complications (pneumothorax) requiring treatment were seen in two patients in whom a transpleural approach was used and in none of the patients in whom an extrapleural approach was used. Complications that did not require treatment were seen in four further patients drained transpleurally, These were inadvertent placement of catheter into pleural space (two patients) and pneumothorax not requiring treatment (two patients). No patient had an empyema. CONCLUSION. Transpleural drainage of left subphrenic collections occurring after splenectomy is associated with a slightly increased complication rate but has a success rate similar to that of extrapleural drainage. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. BEAUMONT HOSP,DEPT RADIOL,DUBLIN 9,IRELAND. NR 7 TC 16 Z9 16 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 1995 VL 165 IS 2 BP 355 EP 359 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RJ959 UT WOS:A1995RJ95900024 PM 7618556 ER PT J AU FERRARI, LR GOUDSOUZIAN, NG AF FERRARI, LR GOUDSOUZIAN, NG TI THE USE OF THE LARYNGEAL MASK AIRWAY IN CHILDREN WITH BRONCHOPULMONARY DYSPLASIA SO ANESTHESIA AND ANALGESIA LA English DT Article ID INTRAOCULAR-PRESSURE; ENDOTRACHEAL-TUBE; TERM INFANTS; ANESTHESIA; SURGERY; INSERTION AB Airway maintenance with the laryngeal mask airway (LMA) was evaluated and compared to the endotracheal (ET) tube in 27 former premature infants and children with bronchopulmonary dysplasia (BPD) during second stage open-sky vitrectomy. The children were randomly assigned to a study group and anesthetized with halothane in N2O:O-2. The airway was maintained with the LMA (n = 13) or the ET tube (n = 14). Respiratory and hemodynamic variables were recorded. Intraoperative and postoperative complications were noted. The respiratory rate and the end-tidal CO2 were significantly higher in the LMA group as compared with the ET tube group (P < 0.01); however, the pulse rate and both systolic and diastolic blood pressures throughout the surgical procedure were lower in the LMA group (P < 0.05). The incidence of coughing, with and without desaturation, wheezing, and hoarseness in the postoperative period was higher in the ET tube group. Awakening, after discontinuation of the anesthetic (P < 0.01) was more rapid, and home discharge time (P < 0.002) was shorter in the LMA group (P < 0.0025), although our study design could not isolate the use of the LMA as the factor responsible for this. This study in patients with mild chronic lung disease demonstrated that the LMA can maintain a satisfactory airway during minor surgical procedures in children with bronchopulmonary dysplasia and result in fewer respiratory adverse effects than with the ET tube. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. RP FERRARI, LR (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT ANESTHESIA,243 CHARLES ST,BOSTON,MA 02114, USA. NR 22 TC 17 Z9 17 U1 2 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD AUG PY 1995 VL 81 IS 2 BP 310 EP 313 DI 10.1097/00000539-199508000-00018 PG 4 WC Anesthesiology SC Anesthesiology GA RL645 UT WOS:A1995RL64500018 PM 7618721 ER PT J AU KIM, C HIROSE, M MARTYN, JAJ AF KIM, C HIROSE, M MARTYN, JAJ TI D-TUBOCURARINE ACCENTUATES THE BURN-INDUCED UP-REGULATION OF NICOTINIC ACETYLCHOLINE-RECEPTORS AT THE MUSCLE MEMBRANE SO ANESTHESIOLOGY LA English DT Article DE BURNS, DRUG INTERACTION; NEUROMUSCULAR RELAXANTS, D-TUBOCURARINE; RECEPTORS, ACETYLCHOLINE, NICOTINIC ID LONG-TERM; SKELETAL-MUSCLE; UP-REGULATION; HEART-FAILURE; INJURY; SENSITIVITY; RESISTANCE; MYOGENIN; THERAPY; PROTEIN AB Background: Increases in acetylcholine receptors (AChRs) the muscle membrane, induced by burn injury, have been associated with a hyperkalemic response to succinylcholine and resistance to d-tubocurarine-like drugs, Muscle relaxants often are administered to burn-injured patients in the intensive care unit to facilitate mechanical ventilation. This study in rats tested whether continuous administration of d-tubocurarine in subparalytic doses exaggerates the upregulation of AChRs induced by burn trauma. Subparalytic doses were used to avoid the confounding effects of immobilization. Methods: Three days after an approximate 50% body surface area burn or sham injury, the animals received an infusion of 3.03 +/- 0.05 mu g/h of d-tubocurarine or equal volume of saline directly to the left gastrocnemius muscle via a catheter connected to a subcutaneously implanted osmotic pump. After 7 days of d-tubocurarine or saline infusion, the AChRs were quantitated using I-125-alpha-bungarotoxin. The AChRs on the d-tubocurarine or saline-infused left gastrocnemius were compared to the contralateral gastrocnemius in the same group. The right or left gastrocnemius AChRs were compared to the ipsilateral muscles between groups. These intra- and inter-group comparisons allowed the delineation of the effects of catheter irritation, burns, or d-tubocurarine on AChRs. Results: Daily examination of the withdrawal response to toe-pinch revealed no evidence of paralysis. Weight loss in the burn-injury animals receiving d-tubocurarine or saline was similar, confirming that the infusion of d-tubocurarine did not impair the mobility of the animals to move and feed. The plasma d-tubocurarine concentration after 7 days of infusion was 26.0 +/- 12 ng/ml (mean +/- SE). Regardless of burn or sham injury or of d-tubocurarine or saline infusion, the concentration of AChRs on the left was consistently greater than in the contralateral right gastrocnemius muscles within the same group, indicating that manipulation of the area alone can result in upregulation of AChRs. The AChRs in the right gastrocnemius of burn-injured animals were greater than those in the same muscle of sham-injured animals, regardless of saline (7.24 +/- 0.9 vs. 5.7 +/- 0.5 fmoles/mg protein, P = 0.06) or d-tubocurarine (7.3 +/- 0.4 vs. 5.7 +/- 0.5, P < 0.05) infusion to the burn-injury groups. AChRs in the left gastrocnemius of burn-injury animals receiving d-tubocurarine were significantly greater than those in burn- or sham-injury animals receiving saline (13.9 +/- 1.1 vs. 9.8 +/- 1.2 and 7.1 +/- 0.5 fmoles/mg protein, respectively, P < 0.05). Conclusions: Burn-induced upregulation of AChRs is accentuated by infusion of subparaltic doses of d-tubocurarine, Concomitant administration of d-tubocurarine to burn-injured patients may result in further exaggeration of the aberrant responses to neuromuscular relaxants. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,CLIN & BIOCHEM PHARMACOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANAESTHESIOL,BOSTON,MA. SHRINERS BURNS INST,BOSTON,MA. FU NIGMS NIH HHS [R01 GM31569-12] NR 40 TC 14 Z9 16 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD AUG PY 1995 VL 83 IS 2 BP 309 EP 315 DI 10.1097/00000542-199508000-00011 PG 7 WC Anesthesiology SC Anesthesiology GA RM711 UT WOS:A1995RM71100012 PM 7631953 ER PT J AU LI, FQ LINAN, MJ STEIN, MC FAUSTMAN, DL AF LI, FQ LINAN, MJ STEIN, MC FAUSTMAN, DL TI REDUCED EXPRESSION OF PEPTIDE-LOADED HLA CLASS-I MOLECULES ON MULTIPLE-SCLEROSIS LYMPHOCYTES SO ANNALS OF NEUROLOGY LA English DT Article ID COMPLEX CLASS-I; TRANSPORTER; CELLS; GENES; SUSCEPTIBILITY; AUTOIMMUNITY; POLYMORPHISM; ANTIGENS; LINKAGE; DISEASE AB Lymphocytes from patients with HLA class II-linked autoimmune diseases such as type I diabetes, systemic lupus erythematosus, rheumatoid arthritis, and Graves' have recently been shown to have a decrease in the expression of self-peptide-filled HLA class I antigens on the surface of peripheral lymphocytes. The human demyelinating diseases of multiple sclerosis in some cases are also associated with the presence of certain HLA class II genes, which may in turn be linked to genes in the class II region that control class I expression. Hence, we studied fresh peripheral blood mononuclear cells (PBMCs) and newly produced Epstein-Barr virus (EBV)-transformed cell lines from multiple sclerosis patients for the class I defect. Unseparated PBMCs, as well as T cells, B cells, and macrophages from multiple sclerosis patients had a decrease in the amount of conformationally correct peptide-filled HLA class I molecules on the cell surface compared with matched controls detectable by flow cytometry. To demonstrate the independence of this defect from exogenous serum factors, newly produced EBV-transformed cell lines from B cells of patients with multiple sclerosis maintained the defect. In addition, DR2 +/+, +/-, and -/- EBV-transformed B cells from these patients similarly demonstrated the self-antigen presentation defect. Analysis of a set of discordant multiple sclerosis twins revealed the class I defect was exclusively found on the affected twin lymphocytes, suggesting a role of this class I complex in disease expression. These data indicate that multiple sclerosis patients have abnormal presentation of self-antigens. This phenomenon, common to a number of HLA-linked autoimmune disorders, may be associated with failed self-tolerance and improper T-cell education secondary to faulty HLA class I assembly controlled by HLA class II linked genes. C1 MASSACHUSETTS GEN HOSP,IMMUNOBIOL LABS,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,NEUROIMMUNOL UNIT,BOSTON,MA 02114. NR 41 TC 20 Z9 20 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 1995 VL 38 IS 2 BP 147 EP 154 DI 10.1002/ana.410380205 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RN985 UT WOS:A1995RN98500004 PM 7654061 ER PT J AU GREENBERG, SM REBECK, GW VONSATTEL, JPG GOMEZISLA, T HYMAN, BT AF GREENBERG, SM REBECK, GW VONSATTEL, JPG GOMEZISLA, T HYMAN, BT TI APOLIPOPROTEIN-E EPSILON-4 AND CEREBRAL-HEMORRHAGE ASSOCIATED WITH AMYLOID ANGIOPATHY SO ANNALS OF NEUROLOGY LA English DT Article ID SPORADIC ALZHEIMERS-DISEASE; PRECURSOR PROTEIN GENE; BETA-PROTEIN; MUTATION; ALLELE; PEPTIDE; COMPLICATIONS; DIAGNOSIS; BINDING; BRAIN AB Cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular deposition of the amyloid beta-peptide, leading to intracerebral hemorrhage in severe cases. Other than rare familial cases, the only identified risks for CAA are advancing age and accompanying Alzheimer's disease. We tested whether the apolipoprotein E epsilon 4 (apoE epsilon 4) allele was associated with CAA and hemorrhage and whether this association was independent of Alzheimer's disease. The apoE epsilon 4 genotype was determined without knowledge of the pathology for 93 postmortem cases systematically graded for severity of CAA and for 15 patients with CAA-associated intracerebral hemorrhage. We found a significant and independent effect of the apoE genotype in both cohorts. Among the postmortem cases, the presence of apoE epsilon 4 increased the odds ratio for moderate or severe CAA by 2.9-fold, relative to cases without epsilon 4; two copies of epsilon 4 increased the odds ratio 13.1-fold. In the cohort of CAA-associated cerebral hemorrhages, the apoE epsilon 4 allele frequency was 0.40, significantly greater than the control frequency of 0.14. The increase in CAA remained even after controlling for the presence of Alzheimer's disease, suggesting that apoE epsilon 4 is a risk factor for CAA and CAA-related hemorrhage, independent of its association with Alzheimer's disease. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CS KUBIK LAB NEUROPATHOL,BOSTON,MA 02114. MCLEAN HOSP,CTR BRAIN TISSUE RESOURCE,BELMONT,MA 02178. RP GREENBERG, SM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,VINCENT BURHAM 801,FRUIT ST,BOSTON,MA 02114, USA. FU NIA NIH HHS [AG05134, AG08487, AG12406] NR 44 TC 369 Z9 374 U1 0 U2 6 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 1995 VL 38 IS 2 BP 254 EP 259 DI 10.1002/ana.410380219 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RN985 UT WOS:A1995RN98500018 PM 7654074 ER PT J AU RYAN, CM SHERIDAN, RL SCHOENFELD, DA WARSHAW, AL TOMPKINS, RG AF RYAN, CM SHERIDAN, RL SCHOENFELD, DA WARSHAW, AL TOMPKINS, RG TI POSTBURN PANCREATITIS SO ANNALS OF SURGERY LA English DT Article ID CARDIOPULMONARY BYPASS; AMYLASE; ISCHEMIA; LIPASE; ENZYME; SERUM; LUNG AB Objective The authors examined the prevalence and complications of pancreatitis in severely burned patients. Factors predictive for the development of pancreatitis after burns are considered. Summary Background Data Pancreatitis has been documented at necropsy after burns; however, it is not clinically recognized as a common complication of burn injury. Recent improvements in survival rates could yield previously unrecognized complications, such as pancreatitis, particularly in those patients who previously would have not survived. The hypothesis is that pancreatitis is a frequent complication after major burn injury and causes significant morbidity for patients with large burns. Methods This retrospective review of adult patients with large burns examines postburn pancreatitis using stepwise logistic regression analysis. Results Forty-nine of 121 (40%) patients developed hyperamylasemia or hyperlipasemia well after the admission period (23 +/- 3 days), and all enzyme abnormalities were temporally associated with emerging infections. Most of these patients (40/49, 82%) had symptoms of pancreatitis. Three patients (6%) had pancreatic pseudocysts or abscesses. Inhalation injury (p = 0.0001), associated trauma (p = 0.0311), and escharotomy (p = 0.0415) were risk factors for pancreatitis. Using Fischer's exact test, patients with pancreatitis had increased mortality and length of stay. Patients with high enzyme elevations and greater than or equal to 50% body surface area burned were at severe risk of pancreatic pseudocyst or abscess development (43%; 90% confidence interval of 23-77%). Conclusions Pancreatitis is a frequent complication after large burn injuries. Patients at high risk for pancreatitis complications should receive surveillance examinations during their acute hospitalization. C1 MASSACHUSETTS GEN HOSP,SURG SERV,SUMMER REDSTONE BURN CTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR BIOSTAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. SHRINERS BURNS INST,BOSTON,MA. FU NIGMS NIH HHS [GM T32-07035, GM P50-21700] NR 23 TC 14 Z9 17 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD AUG PY 1995 VL 222 IS 2 BP 163 EP 170 DI 10.1097/00000658-199508000-00008 PG 8 WC Surgery SC Surgery GA RM734 UT WOS:A1995RM73400008 PM 7543741 ER PT J AU FOITZIK, T DELCASTILLO, CF FERRARO, MJ MITHOFER, K RATTNER, DW WARSHAW, AL AF FOITZIK, T DELCASTILLO, CF FERRARO, MJ MITHOFER, K RATTNER, DW WARSHAW, AL TI PATHOGENESIS AND PREVENTION OF EARLY PANCREATIC INFECTION IN EXPERIMENTAL ACUTE NECROTIZING PANCREATITIS SO ANNALS OF SURGERY LA English DT Article ID SELECTIVE DECONTAMINATION; BACTERIAL-INFECTION; DIGESTIVE-TRACT; TRANSLOCATION; ANTIBIOTICS; MICE; COLONIZATION; CLINDAMYCIN; IMIPENEM; SEPSIS AB Objective The authors test antibiotic strategies aimed at either mitigating bacterial translocation from the gut or delivering antibiotics specifically concentrated by the pancreas for prevention of early secondary infection after acute necrotizing pancreatitis. Background Infection currently is the principal cause of death after severe pancreatitis. The authors have shown that the risk of bacterial infection correlates directly with the degree of tissue injury in a rodent model of pancreatitis. Bacteria most likely arrive by translocation from the colon. Methods Severe acute necrotizing pancreatitis was induced in rats by a combination of low-dose controlled intraductal infusion of glycodeoxycholic acid superimposed on intravenous cerulein hyperstimulation. At 6 hours, animals were randomly allocated to five treatment groups: controls, selective gut decontamination (oral antibiotics and cefotaxime), oral antibiotics alone, cefotaxime alone, or imipenem. At 96 hours, surviving animals were killed for quantitative bacterial study of the cecum, pancreas, and kidney. Results The 95-hour mortality (35%) was unaffected by any treatment regimen. Cecal gram-negative bacteria were significantly reduced only by the oral antibiotics. Pancreatic infection was significantly reduced by full-gut decontamination and by imipenem, but not by oral antibiotics or by cefotaxime alone. Renal infection was reduced by both intravenous antibiotics. Conclusions Early pancreatic infection after acute necrotizing pancreatitis can be reduced with a full-gut decontamination regimen or with an antibiotic concentrated by the pancreas (imipenem) but not by unconcentrated antibiotics of similar spectrum (cefotaxime) or by oral antibiotics alone. These findings suggest that 1) both direct bacterial translocation from the out and hematogenous seeding interplay in pancreatic infection while hematogenous seeding is dominant at extrapancreatic sites and 2) imipenem may be useful in clinical pancreatitis. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 46 TC 81 Z9 84 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD AUG PY 1995 VL 222 IS 2 BP 179 EP 185 DI 10.1097/00000658-199508000-00010 PG 7 WC Surgery SC Surgery GA RM734 UT WOS:A1995RM73400010 PM 7639584 ER PT J AU WRIGHT, CD MATHISEN, DJ WAIN, JC MONCURE, AC HILGENBERG, AD GRILLO, HC AF WRIGHT, CD MATHISEN, DJ WAIN, JC MONCURE, AC HILGENBERG, AD GRILLO, HC TI REINFORCED PRIMARY REPAIR OF THORACIC ESOPHAGEAL-PERFORATION SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 30-FEB 02, 1995 CL PALM SPRINGS, CA SP Soc Thorac Surgeons ID MANAGEMENT; EXPERIENCE AB Background. Treatment of esophageal perforation, especially when diagnosed late, remains controversial. Methods. Twenty-eight patients were treated for thoracic esophageal perforation with reinforced primary repair regardless of time of presentation. Results. Fifteen patients were treated early (<24 hours) with no deaths. Two had contained postoperative leaks, which healed. Thirteen were treated late (mean, 5.5 days) with four deaths (3 with healed repairs). Postoperative leaks occurred in 7 patients; of the leaks, 4 healed, 2 became a controlled fistula, and 1 required reoperation. Primary healing with preservation of the native esophagus was achieved in 25 patients (89%). Among the 18 patients without evidence of sepsis preoperatively, postoperative leaks developed in 2 (11%). Ten patients had evidence of sepsis preoperatively, and postoperative leaks developed in 7 (70%). Conclusions. Patients who present with sepsis have an increased risk of postoperative leak and therefore should have the repair buttressed. Overall mortality was 14% and no deaths were due to persistent leaks or mediastinal sepsis. Reinforced primary repair retains the native esophagus and avoids the need for later reconstructive operations. In the absence of a nondilatable stricture or cancer, reinforced primary repair should be performed for most thoracic esophageal perforations, early or late. C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP WRIGHT, CD (reprint author), MASSACHUSETTS GEN HOSP,GEN THORAC SURG UNIT,BOSTON,MA 02114, USA. NR 14 TC 94 Z9 102 U1 0 U2 2 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 1995 VL 60 IS 2 BP 245 EP 249 DI 10.1016/0003-4975(95)00377-W PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA RQ583 UT WOS:A1995RQ58300004 PM 7646082 ER PT J AU AKINS, CW MONCURE, AC DAGGETT, WM CAMBRIA, RP HILGENBERG, AD TORCHIANA, DF VLAHAKES, GJ AF AKINS, CW MONCURE, AC DAGGETT, WM CAMBRIA, RP HILGENBERG, AD TORCHIANA, DF VLAHAKES, GJ TI SAFETY AND EFFICACY OF CONCOMITANT CAROTID AND CORONARY-ARTERY OPERATIONS SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 30-FEB 02, 1995 CL PALM SPRINGS, CA SP Soc Thorac Surgeons ID CEREBROVASCULAR-DISEASE; INTRAVENOUS ANGIOGRAPHY; NONOPERATIVE TREATMENT; BYPASS-SURGERY; FOLLOW-UP; ENDARTERECTOMY; STENOSIS; STROKE; REVASCULARIZATION; SURVIVAL AB Background. Controversy exists concerning the best management for patients with concurrent severe carotid and coronary artery disease. Methods. The records of 200 consecutive patients having concurrent carotid endarterectomy and coronary artery bypass grafting from 1979 to 1993 were reviewed, and follow-up was obtained (99% complete). Of the group (77% male; mean age, 67 years), 134 (67%) had unstable angina, 130 (65%) had triple-vessel disease, and 86 (43%) had left main coronary stenosis. Preoperative investigation revealed asymptomatic bruits in 116 (58%), transient ischemia in 65 (32%), strokes in 31 (16%), and bilateral carotid disease in 44 patients (22%). Nonelective operations were required in 66 patients (33%). Results. Hospital death occurred in 7 patients (3.5%), myocardial infarction in 5 (2.5%), and permanent stroke in 6 (3%). Ten-year actuarial event-free rates were as follows: death, 58%; myocardial infarction, 81%; stroke, 92%; percutaneous angioplasty, 98%; redo coronary artery grafting, 94%; and all morbidity and mortality, 56%. Significant multivariate predictors of hospital death were postoperative stroke, failure to use an internal mammary artery graft, intraoperative intraaortic balloon, and nonelective operation. Significant predictors of postoperative stroke were peripheral vascular disease and unstable angina. Significant predictors of prolonged hospital stay were postoperative stroke, advanced age, and nonelective operation. Conclusions. Concomitant carotid endarterectomy and coronary bypass grafting can be performed with acceptably low operative risk and good long-term freedom from coronary and neurologic events. C1 MASSACHUSETTS GEN HOSP,CARDIAC SURG UNIT,BOSTON,MA 02114. NR 30 TC 92 Z9 93 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 1995 VL 60 IS 2 BP 311 EP 318 DI 10.1016/0003-4975(95)00397-4 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA RQ583 UT WOS:A1995RQ58300014 PM 7646091 ER PT J AU OUABDESSELAM, S HOOPER, DC TANKOVIC, J SOUSSY, CJ AF OUABDESSELAM, S HOOPER, DC TANKOVIC, J SOUSSY, CJ TI DETECTION OF GYRA AND GYRB MUTATIONS IN QUINOLONE-RESISTANT CLINICAL ISOLATES OF ESCHERICHIA-COLI BY SINGLE-STRAND CONFORMATIONAL POLYMORPHISM ANALYSIS AND DETERMINATION OF LEVELS OF RESISTANCE CONFERRED BY 2 DIFFERENT SINGLE GYRA MUTATIONS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID POLYMERASE CHAIN-REACTION; DNA GYRASE; GENE; FLUOROQUINOLONES; ACCUMULATION; MECHANISMS; CLONING; PROTEIN; STRAINS; NFXB AB Twelve quinolone-resistant clinical isolates of Escherichia coli (nalidixic acid MICs, 64 to 512 mu g/ml; norfloxacin MICs; 0.25 to 8 mu g/ml) were transformed with plasmid pJSW101 carrying the gyrA(+) gene and with plasmid pJB11 carrying the gyrB(+) gene to examine the proportion of gyrA and gyrB mutations. Transformation with pJSW101 resulted in complementation (nalidixic acid MICs, 4 to 32 mu g/ml; norfloxacin MICs, 0.06 to 0.25 mu g/ml). In contrast, no change in MICs were observed after transformation with pJB11, A 418-bp fragment of gyrA from the 12 strains was amplified by PCR. Direct DNA sequencing of that fragment identified the causes of quinolone resistance in eight strains as a single point mutation leading to a substitution of the serine at position 83 (Ser-83) to Leu and in four strains as a single point mutation leading to a substitution of Asp-87 to Gly. Exchange of the fragment from one of these strains with that of gyrA(+) and transformation of resistance with the hybrid gyrA plasmid indicated the contribution of Gly-87 to resistance and the stabilities of mutants containing GyrA (Gly-87), Thus, gyrA gene mutations are probably encountered more often than gyrB gene mutations in clinical isolates off. coli, In addition, the Substitution of Asp-87 to Gly can be encountered in such strains, On the basis of the level of resistance found in the fragment exchange experiment, the quinolone resistance attributable to Gly-87 appears to be comparable to that attributable to Leu-83, The levels of resistance found in the clinical isolates shown to have a Gly-87 mutation (nalidixic acid MICs, 64 to 512 mu g/ml; norfloxacin MICs, 0.5 to 4 mu g/ml) suggest that the Gly-87 mutation causes resistance at the lei el of the nalidixic acid MIC (64 mu g/ml) or the norfloxacin MIC (0.5 mu g/ml or less) and that the additional increments in resistance seen in the other strains with higher levels of resistance may be attributable to additional mutations, The single-strand conformational polymorphism analysis with PCR products readily detected the Leu 83 and Gly-87 mutations. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP OUABDESSELAM, S (reprint author), CHU HENRI MONDOR,F-94010 CRETEIL,FRANCE. NR 26 TC 49 Z9 53 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 1995 VL 39 IS 8 BP 1667 EP 1670 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA RM378 UT WOS:A1995RM37800004 PM 7486897 ER PT J AU NGUYEN, MH BARCHIESI, F MCGOUGH, DA YU, VL RINALDI, MG AF NGUYEN, MH BARCHIESI, F MCGOUGH, DA YU, VL RINALDI, MG TI IN-VITRO EVALUATION OF COMBINATION OF FLUCONAZOLE AND FLUCYTOSINE AGAINST CRYPTOCOCCUS-NEOFORMANS VAR NEOFORMANS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMPHOTERICIN-B; MENINGITIS; THERAPY; SYNERGY; AIDS AB Amphotericin B and fluconazole are current acceptable therapies for cryptococcal meningitis; however, their effect remains suboptimal. The combination of fluconazole and flucytosine has yielded encouraging clinical results in human immunodeficiency virus patients,vith cryptococcal meningitis, To investigate the biological basis of this finding, we performed in vitro combination testing of fluconazole and flucytosine against 50 clinical strains of Cryptococcus neoformans var, neoformans, Synergy (fractional inhibitory concentration index of <1.0) was observed in 62% of cases, while antagonism (fractional inhibitory concentration index of >2.0) was not observed, For cases in which synergy was not achieved (autonomous or additive effects), the beneficial effect of the combination was still seen (i.e,, there was still a decrease, although not as dramatic, in the MIC of one or both drugs when used in combination), The in vitro inhibitory action of flucytosine was greatly enhanced by the addition of fluconazole; the flucytosine MICs for Cryptococcus isolates were markedly decreased to concentrations which were severalfold lower than the achievable cerebrospinal fluid flucytosine concentration, On the other hand, the addition of flucytosine did not greatly enhance the in vitro activity of fluconazole if the initial fluconazole MIC for the isolate was greater than or equal to 8 mu g/ml. Controlled clinical studies are warranted to further elucidate the potential utility of fluconazole-flucytosine combination therapy. C1 UNIV PITTSBURGH,MED CTR,DEPT MED,DIV INFECT DIS,PITTSBURGH,PA 15213. VET AFFAIRS MED CTR,PITTSBURGH,PA. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,FUNGUS TESTING LAB,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV ANCONA,IST MALATTIE INFECT & MED PUBBL,ANCONA,ITALY. NR 14 TC 60 Z9 65 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 1995 VL 39 IS 8 BP 1691 EP 1695 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA RM378 UT WOS:A1995RM37800009 PM 7486902 ER PT J AU GRAYBILL, JR BOCANEGRA, R AF GRAYBILL, JR BOCANEGRA, R TI LIPOSOMAL AMPHOTERICIN-B THERAPY OF MURINE HISTOPLASMOSIS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ITRACONAZOLE; IMMUNITY; INVITRO; MICE AB Liposomal amphotericin B (AmBisome) was compared with amphotericin B deoxycholate for the treatment of disseminated murine histoplasmosis. Liposomal amphotericin B was well tolerated and, milligram for milligram, was as potent as amphotericin B deoxycholate. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. RP GRAYBILL, JR (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,DIV INFECT DIS,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. FU PHS HHS [N0I-A1-25141] NR 19 TC 22 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 1995 VL 39 IS 8 BP 1885 EP 1887 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA RM378 UT WOS:A1995RM37800048 PM 7486941 ER PT J AU SHEN, GQ KRESBACH, G SPIRO, MJ SPIRO, RG AF SHEN, GQ KRESBACH, G SPIRO, MJ SPIRO, RG TI EVALUATION OF THE CELL-SPECIFICITY AND SULFATE DEPENDENCE OF GLOMERULAR EXTRACELLULAR-MATRIX PROTEOGLYCAN SYNTHESIS SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE PROTEOGLYCANS; HEPARAN SULFATE; CHONDROITIN SULFATE; DERMATAN SULFATE; GLOMERULUS; EXTRACELLULAR MATRIX; MESANGIUM; BASEMENT MEMBRANE; EPITHELIAL CELL; ENDOTHELIAL CELL, MESANGIAL CELL; SULFATE ID BASEMENT-MEMBRANE PROTEOGLYCANS; HEPARAN-SULFATE; MESANGIAL CELLS; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; LENS CAPSULE; GLYCOSAMINOGLYCANS; CULTURE; COLLAGEN; IDENTIFICATION AB Homogeneous cultures of epithelial, endothelial, and mesangial cells from calf glomeruli were radiolabeled with [S-35]sulfate in order to evaluate their capacity for the biosynthesis of the proteoglycan (PG) components present in the glomerular extracellular matrix. Although each cell type was observed to incorporate into its matrix predominantly immunologically related heparan sulfate (HS) PGs (M(r) similar to 500 kDa), endothelial and mesangial cells also deposited substantial amounts of PGs with chondroitin sulfate (CS) and dermatan sulfate (DS) chains. The limited capacity of epithelial cells to synthesize PGs other than those containing HS was also evident from the immunologically distinct components (M(r) similar to 300 kDa) shed into the medium which in contrast to those from the endothelial and mesangial cells contained no CS and only small amounts of DS glycosaminoglycans. While the matrix proteoglycan HS chains differed in length depending on cell type, they were similar in containing the six mono- and disulfated disaccharide species previously found in bovine glomerular basement membrane, including the distinctive iduronic-GlcNSO(3) (3-SO4) sequences, While the addition of sulfate to medium free of this ion brought about no change in HS PG production by any of the three cell types and the formation of CS and DS chains by epithelial and mesangial cells was unaffected, the formation of CS/DS PGs by endothelial cells was altered to a pronounced extent through the conversion of an undersulfated PG to a more polyanionic molecule. Our findings are consistent with the concept that the glomerular extracellular matrix is made up of two biosynthetically distinct regions (mesangium and basement membrane) and are relevant to an understanding of various diseases affecting the renal filter. (C) 1995 Academic Press, Inc. C1 JOSLIN DIABET CTR, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. FU NHLBI NIH HHS [HL31315]; NIDDK NIH HHS [DK17325] NR 45 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD AUG 1 PY 1995 VL 321 IS 1 BP 83 EP 93 DI 10.1006/abbi.1995.1371 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RN517 UT WOS:A1995RN51700012 PM 7639540 ER PT J AU SCHWARTZ, CE COLE, BF GELBER, RD AF SCHWARTZ, CE COLE, BF GELBER, RD TI MEASURING PATIENT-CENTERED OUTCOMES IN NEUROLOGIC DISEASE - EXTENDING THE Q-TWIST METHOD SO ARCHIVES OF NEUROLOGY LA English DT Article ID PROGRESSIVE MULTIPLE-SCLEROSIS; ADJUSTED SURVIVAL ANALYSIS; STATUS SCALE EDSS; COGNITIVE DYSFUNCTION; THERAPEUTIC TRIALS; FUNCTIONAL-SYSTEMS; ADJUVANT THERAPY; CLINICAL-TRIAL; BREAST-CANCER; DOUBLE-BLIND AB Background: Current clinical research and outcomes assessment on multiple sclerosis rely on an approach to disability measurement that is heavily influenced by ambulation. Not only is this strategy often insensitive to the clinical changes affected by pharmacotherapeutic or rehabilitative interventions but it also disregards the symptoms that patients seem to consider most enervating. We propose a new method for evaluating clinical interventions in terms of their impact on the symptoms of multiple sclerosis, side effects, parameters of exacerbation, and disease progression, while considering the patient's perspective. Methods: The extended Q-TWiST method yields an estimation of treatment trade-offs in terms of Quality-adjusted Time Without Symptoms and Toxicities (Q-TWiST). An illustration of this method is presented by using a hypothetical clinical trial of two treatments. The trade-offs between the two treatments are highlighted to facilitate treatment decision making by using individual patient importance weights. Conclusion: We discuss applications to other clinical research and other chronic diseases. C1 ROCKY MT MULTIPLE SCLEROSIS CTR,ENGLEWOOD,CO. BROWN UNIV,DEPT COMMUNITY HLTH,DIV APPL MATH,PROVIDENCE,RI 02912. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP SCHWARTZ, CE (reprint author), FRONTIER SCI & TECHNOL RES FDN INC,303 BOYLSTON ST,BROOKLINE,MA 02146, USA. NR 60 TC 29 Z9 29 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 1995 VL 52 IS 8 BP 754 EP 762 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA RN516 UT WOS:A1995RN51600005 PM 7639627 ER PT J AU SULTZER, DL MAHLER, ME CUMMINGS, JL VANGORP, WG HINKIN, CH BROWN, C AF SULTZER, DL MAHLER, ME CUMMINGS, JL VANGORP, WG HINKIN, CH BROWN, C TI CORTICAL ABNORMALITIES ASSOCIATED WITH SUBCORTICAL LESIONS IN VASCULAR DEMENTIA - CLINICAL AND POSITRON EMISSION TOMOGRAPHIC FINDINGS SO ARCHIVES OF NEUROLOGY LA English DT Article ID MULTI-INFARCT DEMENTIA; CEREBRAL BLOOD-FLOW; ALZHEIMERS-DISEASE; ENERGY-METABOLISM; THALAMIC STROKE; RATING-SCALE; DIASCHISIS; CORTEX; SEVERITY; HUMANS AB Objective: To examine the effects of subcortical lesions on cortical metabolic rate and clinical symptoms in patients with vascular dementia. Method: Eleven elderly patients with vascular dementia who demonstrated no lesion involving the cerebral cortex on magnetic resonance imaging underwent F-18-fluorodeoxyglucose positron emission tomography to assess global cortical metabolism and metabolic activity in each cortical lobe. Subcortical lesions on magnetic resonance imaging (periventricular hyperintensities, deep white matter hyperintensities, and subcortical lacunar infarcts) were measured using a graded scale of severity. Cognitive and noncognitive symptoms were assessed with the Neurobehavioral Rating Scale. Results: Reduced cortical metabolism was generally associated with the severity of subcortical pathologic changes, but there was substantial heterogeneity in the relationship between subcortical lesions and cortical metabolic activity. Mean global cortical metabolism was lower in patients with periventricular hyperintensities in anterior subcortical regions than in those without such lesions. The metabolic rate in the frontal cortex was lower in patients with a lacunar infarct of the basal ganglia or thalamus than in those without. Neurobehavioral Rating Scale total score, the Verbal Output Disturbance factor score, and the Anxiety/Depression factor score were correlated with the severity of white matter lesions. Conclusions: Cortical metabolic dysfunction is related to ischemic subcortical lesions in patients with vascular dementia. Metabolism in the frontal cortex may be particularly dependent on pathologic alterations of subcortical nuclei. Anxiety, depression, and the overall severity of neuropsychiatric symptoms in vascular dementia are associated with the extent of white matter ischemia. C1 W LOS ANGELES VET AFFAIRS MED CTR,NUCL MED SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BEHAV SCI,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHOL SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV 116AF,BEHAV NEUROSCI SECT,LOS ANGELES,CA 90073. FU NIA NIH HHS [AG10123]; NIMH NIH HHS [MH00910] NR 39 TC 112 Z9 112 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 1995 VL 52 IS 8 BP 773 EP 780 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA RN516 UT WOS:A1995RN51600007 PM 7639629 ER PT J AU KREMER, JM LAWRENCE, DA PETRILLO, GF LITTS, LL MULLALY, PM RYNES, RI STOCKER, RP PARHAMI, N GREENSTEIN, NS FUCHS, BR MATHUR, A ROBINSON, DR SPERLING, RI BIGAOUETTE, J AF KREMER, JM LAWRENCE, DA PETRILLO, GF LITTS, LL MULLALY, PM RYNES, RI STOCKER, RP PARHAMI, N GREENSTEIN, NS FUCHS, BR MATHUR, A ROBINSON, DR SPERLING, RI BIGAOUETTE, J TI EFFECTS OF HIGH-DOSE FISH-OIL ON RHEUMATOID-ARTHRITIS AFTER STOPPING NONSTEROIDAL ANTIINFLAMMATORY DRUGS - CLINICAL AND IMMUNE CORRELATES SO ARTHRITIS AND RHEUMATISM LA English DT Article ID FATTY-ACIDS; DOUBLE-BLIND; DIETARY SUPPLEMENTATION; EICOSAPENTAENOIC ACID; ENRICHMENT; PLACEBO; GENERATION; DISEASE AB Objective. To determine the following: 1) whether dietary supplementation with fish oil will allow the discontinuation of nonsteroidal antiinflammatory drugs (NSAlDs) in patients with rheumatoid arthritis (RA); 2) the clinical efficacy of high-dose dietary omega 3 fatty acid fish oil supplementation in RA patients; and 3) the effect of fish oil supplements on the production of multiple cytokines in this population, Methods, Sixty-six RA patients entered a double-blind, placebo-controlled, prospective study of fish oil supplementation while taking diclofenac (75 mg twice a day), Patients took either 130 mg/kg/day of omega 3 fatty acids or 9 capsules/day of corn oil, Placebo diclofenac was substituted at week 18 or 22, and fish oil supplements were continued for 8 weeks (to week 26 or 30), Serum levels of interleukin-1 beta (IL-1 beta), 1L-2, 1L-6, and IL-8 and tumor necrosis factor alpha were measured by enzyme-linked immunosorbent assay at baseline and during the study. Results, In the group taking fish oil, there were significant decreases from baseline in the mean ( +/- SEM) number of tender joints (5.3 +/- 0.835; P < 0.0001), duration of morning stiffness (-67.7 +/- 23.3 minutes; P = 0.008), physician's and patient's evaluation of global arthritis activity (-0.33 +/- 0.13; P = 0.017 and -0.38 +/- 0.17; P = 0.036, respectively), and physician's evaluation of pain (-0.38 +/- 0.12; P = 0.004), In patients taking corn oil, no clinical parameters improved from baseline, The decrease in the number of tender joints remained significant 8 weeks after discontinuing diclofenac in patients taking fish oil (-7.8 +/- 2.6; P = 0.011) and the decrease in the number of tender joints at this time was significant compared with that in patients receiving corn oil (P = 0.043), IL-1 beta decreased significantly from baseline through weeks 18 and 22 in patients consuming fish oil (-7.7 +/- 3.1; P = 0.026). Conclusion, Patients taking dietary supplements of fish oil exhibit improvements in clinical parameters of disease activity from baseline, including the number of tender joints, and these improvements are associated with significant decreases in levels of IL-1 beta from baseline. Some patients who take fish oil are able to discontinue NSAIDs without experiencing a disease hare. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. RP KREMER, JM (reprint author), ALBANY MED COLL,DIV RHEUMATOL,ALBANY,NY 12208, USA. NR 32 TC 126 Z9 133 U1 1 U2 15 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 1995 VL 38 IS 8 BP 1107 EP 1114 DI 10.1002/art.1780380813 PG 8 WC Rheumatology SC Rheumatology GA RP620 UT WOS:A1995RP62000012 PM 7639807 ER PT J AU SCHUTT, W THOMANECK, U GRUMMER, G KRAEFT, SK REINHOLZ, F WALDSCHLAGER, U AF SCHUTT, W THOMANECK, U GRUMMER, G KRAEFT, SK REINHOLZ, F WALDSCHLAGER, U TI NEW METHODS FOR THE INVESTIGATION OF BLOOD-BIOMATERIAL INTERACTION SO ARTIFICIAL ORGANS LA English DT Article DE CELL ELECTROPHORESIS; IMAGE PROCESSING; LASER SCANNING MICROSCOPY; STAINING; LYMPHOID CELLS; CYTOKINE; CHEMOTAXIS; DIALYSIS; MEMBRANES ID MEMBRANES; CELLS AB Quantitative microscopy with integrated image processing is a useful tool for investigation of the interaction of blood components with biomaterials. We have developed new automated measuring devices suitable for simultaneously characterizing biological cells (size, shape, localization, migration, electrophoresis), synthetic particles (electrophoretic fingerprinting), and dialysis membranes (morphology, electric charge). These techniques are useful for the investigation of cell adherence on biomaterials, localization of cells in membrane filters (Chemotaxis), characterization of the protein adsorption on model systems, detection of cytokines (produced after lymphocyte-biomaterial contact), and estimation of morphological properties and charge distribution in dialysis membranes. C1 PROMONTA LUNDBECK,HAMBURG,GERMANY. HASOTEC,ROSTOCK,GERMANY. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV AUCKLAND,DEPT ENGN SCI,AUCKLAND,NEW ZEALAND. INST UMWELTTECHNOL,BERLIN,GERMANY. RP SCHUTT, W (reprint author), CORNELL UNIV,COLL MED,DEPT PHYSIOL & BIOPHYS,1300 YORK AVE,NEW YORK,NY 10021, USA. NR 32 TC 1 Z9 1 U1 1 U2 2 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD AUG PY 1995 VL 19 IS 8 BP 847 EP 851 DI 10.1111/j.1525-1594.1995.tb02439.x PG 5 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA RV388 UT WOS:A1995RV38800012 PM 8573007 ER PT J AU RAINES, DE WU, G DALTON, LA MILLER, KW AF RAINES, DE WU, G DALTON, LA MILLER, KW TI ELECTRON-SPIN-RESONANCE STUDIES OF ACYL-CHAIN MOTION IN RECONSTITUTED NICOTINIC ACETYLCHOLINE-RECEPTOR MEMBRANES SO BIOPHYSICAL JOURNAL LA English DT Article ID LIPID-PROTEIN INTERACTIONS; SEGMENT DISK MEMBRANES; ROTATIONAL-DYNAMICS; SATURATION; LABELS; MODEL AB The electron spin resonance spectra of spin-label positional isomers of stearic acid (n-SASL) incorporated into nicotinic acetylcholine receptors (nAcChoR) reconstituted into dioleoylphosphatidylcholine (DOPC) were deconvoluted into bilayer- and protein-associated components by subtraction under conditions of slow exchange. The selectivity of n-SASL (n = 6, 9, 12, and 14) for the lipid-protein interface of the nAcChoR was threefold greater than that: of DOPC and independent of the spin label position. The temperature at which exchange became apparent as judged from lineshape broadening of the mobile lipid component spectrum was dependent upon the position of the spin-label moiety; near the bilayer center, exchange broadening occurred at lower temperatures than it did closer to the lipid headgroup. This suggests thai the lipid headgroup region of boundary lipids is relatively fixed, whereas its acyl chain whips on and off the protein with increasing frequency near the bilayer center. Motions on the microsecond time scale were examined by microwave power saturation, Each n-SASL saturated more readily when incorporated into vesicles containing the nAcChoR than when in pure DOPC liposomes. Therefore, lipid mobility is perturbed by the nAcChoR on the microsecond time scale with an apparent magnitude that is relatively modest, probably due to exchange on this time scale. C1 MASSACHUSETTS GEN HOSP,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP RAINES, DE (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. FU NIAAA NIH HHS [AA-07040]; NIGMS NIH HHS [GM07592] NR 25 TC 2 Z9 2 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 1995 VL 69 IS 2 BP 498 EP 505 PG 8 WC Biophysics SC Biophysics GA RX251 UT WOS:A1995RX25100022 PM 8527664 ER PT J AU DOLAN, M ALLY, A PURZYCKI, MS GILBERT, W GILLEVET, PM AF DOLAN, M ALLY, A PURZYCKI, MS GILBERT, W GILLEVET, PM TI LARGE-SCALE GENOMIC SEQUENCING - OPTIMIZATION OF GENOMIC CHEMICAL SEQUENCING REACTIONS SO BIOTECHNIQUES LA English DT Article ID DNA AB We have developed a streamlined reproducible method for performing genomic chemical sequencing reactions on the genomic DNA of Mycoplasma capricolum, which has a genome size of about 750000 base pairs and whose composition is 75% AT The general modifications that ensure reproducibility and allow the processing of multiple samples can be widely adopted to other large-scale sequencing projects, while the specific modifications to the chemical reactions are applicable to the sequencing of other DNAs with a high AT content. C1 LIFE TECHNOL,ROCKVILLE,MD. HARVARD UNIV,CAMBRIDGE,MA 02138. NIH,CAMBRIDGE,MD. RP DOLAN, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. FU NHGRI NIH HHS [R01 HGD0124] NR 10 TC 4 Z9 4 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD AUG PY 1995 VL 19 IS 2 BP 264 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN024 UT WOS:A1995RN02400025 PM 8527148 ER PT J AU JOHNSON, RC MAYADAS, TN FRENETTE, PS MEBIUS, RE SUBRAMANIAM, M LACASCE, A HYNES, RO WAGNER, DD AF JOHNSON, RC MAYADAS, TN FRENETTE, PS MEBIUS, RE SUBRAMANIAM, M LACASCE, A HYNES, RO WAGNER, DD TI BLOOD-CELL DYNAMICS IN P-SELECTIN-DEFICIENT MICE SO BLOOD LA English DT Article ID GRANULE MEMBRANE-PROTEIN; INTERCELLULAR-ADHESION MOLECULE-1; HIGH-ENDOTHELIAL VENULES; WEIBEL-PALADE BODIES; MONOCLONAL-ANTIBODY; ACTIVATED PLATELETS; PLASMA-MEMBRANE; HOMING RECEPTOR; GMP-140; NEUTROPHILS AB P-selectin is expressed on the surfaces of activated platelets and endothelium where it mediates binding to leukocytes. P-selectin-deficient mice were shown to exhibit peripheral neutrophilia (Mayadas et al: Cell 74:541, 1993). We now show that this is not caused by changes in bone marrow precursors nor by a lack of neutrophil margination. Both P-selectin-positive and -negative animals displayed similar increases in peripheral blood neutrophil numbers after injection of epinephrine. However, clearance of (51)Chromium-labeled neutrophils is delayed in mice deficient for P-selectin, indicating that the neutrophilia is at least in part the result of delayed removal. We detected no obvious alterations in lymphocyte differentiation, distribution, or adhesion to high endothelial venules in peripheral lymph nodes. Through intravital microscopy, we examined the impact of P-selectin deficiency on leukocyte/endothelial interaction beyond the initial stages of inflammation. Four hours after the administration of an inflammatory irritant, leukocyte rolling was observed even in the absence of P-selectin. There were significantly fewer rolling cells relative to wild-type mice, and their velocity was reduced. Moreover, in the peritonitis model, the number of peritoneal macrophages in wild-type mice increased threefold at 48 hours, whereas the macrophages in the mutant mice remained near baseline levels. Thus, whereas P-selectin is known to be involved in early stages of an inflammatory response, our results indicate that it is additionally responsible for leukocyte rolling and macrophage recruitment in more prolonged tissue injury. (C) 1995 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MIT,CTR CANC RES,HOWARD HUGHES MED INST,DEPT BIOL,CAMBRIDGE,MA. STANFORD UNIV,MED CTR,BECKMAN CTR,STANFORD,CA. RI Frenette, Paul/J-8272-2012 FU NHLBI NIH HHS [HL08908, P01 HL41484, P01-HL42443] NR 39 TC 95 Z9 96 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 AUG 1 PY 1995 VL 86 IS 3 BP 1106 EP 1114 PG 9 WC Hematology SC Hematology GA RM450 UT WOS:A1995RM45000032 PM 7542495 ER PT J AU YUNIS, JJ CORZO, D SALAZAR, M LIEBERMAN, JA HOWARD, A YUNIS, EJ AF YUNIS, JJ CORZO, D SALAZAR, M LIEBERMAN, JA HOWARD, A YUNIS, EJ TI HLA ASSOCIATIONS IN CLOZAPINE-INDUCED AGRANULOCYTOSIS SO BLOOD LA English DT Article ID PEMPHIGUS-VULGARIS PATIENTS; JEWISH PATIENTS; RHEUMATOID-ARTHRITIS; EXTENDED HAPLOTYPES; ALLELES; REGION; CHLORPROMAZINE; SUSCEPTIBILITY; POLYMORPHISM; HLA-DRW4 AB We previously reported preliminary results of association of clozapine-induced agranulocytosis (CA) with HLA-B38, DR4, DQ3 in five Ashkenazi Jewish patients and with HLA-DR2, DQ1 in four non-Jewish patients. In the present study, 31 additional patients with CA, 10 Ashkenazi Jewish, and 21 of non-Jewish ancestry, were studied. HLA alleles and haplotypes were compared among 52 patients (33 Ashkenazi Jewish, 19 non-Jewish) matched for ethnic background and clinical status. Our results show two associations and define the HLA allele markers for the Ashkenazi Jewish and non-Jewish haplotypes associated with CA. The most important markers for susceptibility for CA in Ashkenazi Jewish patients were DRB1*0402, DQB1*0302, and DQA1*0301, and in non-Jewish patients, HLA-DR*02, DQB1*0502, and DQA1*0102. HLA-DRB1*011 and DQB1*0301 were underrepresented in Ashkenazi Jewish patients when compared with controls. We hypothesize that genes of the major histocompatability complex, other than class I and class II, are responsible for CA; among them are the variants of the heat-shock proteins 70 or the tumor necrosis factor loci. (C) 1995 by The American Society of Hematology. C1 HARVARD UNIV,DANA FARBER CANC INST,DIV IMMUNOGENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. AMER RED CROSS,DEDHAM,MA. LONG ISL JEWISH MED CTR,HILLSIDE HOSP,GLEN OAKS,NY 11004. MONTEFIORE MED CTR,ALBERT EINSTEIN COLL MED,DEPT PSYCHIAT,BRONX,NY. FU NIMH NIH HHS [MH-00537, MH-41960, MH-47029] NR 40 TC 65 Z9 66 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 AUG 1 PY 1995 VL 86 IS 3 BP 1177 EP 1183 PG 7 WC Hematology SC Hematology GA RM450 UT WOS:A1995RM45000041 PM 7620171 ER PT J AU JUPPNER, H AF JUPPNER, H TI FUNCTIONAL-PROPERTIES OF THE PTH/PTHRP RECEPTOR SO BONE LA English DT Article; Proceedings Paper CT XII International Conference on Calcium Regulating Hormones CY FEB 14-19, 1995 CL MELBOURNE, AUSTRALIA DE PTH/PTHRP RECEPTOR; G-PROTEIN-COUPLED RECEPTOR; PSEUDOHYPOPARATHYROIDISM; JANSEN-TYPE METAPHYSEAL CHONDRODYSPLASIA ID HUMAN PARATHYROID-HORMONE; PEPTIDE RECEPTOR; PSEUDOHYPOPARATHYROIDISM; FIBROBLASTS; EXPRESSION; RESISTANCE; CLONING; CALCIUM; ACIDS; IB AB The PTH/PTHrP receptor belongs to a novel family of G-protein-coupled receptors which also includes an insect receptor for a diuretic hormone and the protein encoded by a genomic DNA clone from Caenorhabditis elegans. Despite significant structural conservation, rat, opossum, and human PTH/PTHrP receptor homologs display distinct functional characteristics when tested with either [Arg(2), Tyr(34)]hPTH(1-34)amide or [Nle(8,18), Tyr(34)]bPTH(7-34)amide, These PTH analogs, and chimeras between rat/opossum and between rat/human PTH/PTHrP receptors, led to the identification of receptor residues that appear to be involved in ligand/receptor interaction and receptor activation, respectively, The search for mutations in the PTH/PTHrP receptor gene in genomic DNA of patients with pseudohypoparathyroidism type Ib (PHP-Ib) revealed several silent polymorphisms and a missense mutation in the receptor's tail region which did not affect receptor function, Mutations in the PTH/PTHrP receptor are therefore rarely, if at all, responsible for PHP-Ib. A mutation in the PTH/PTHrP receptor is, however, the most likely cause of Jansen-type metaphyseal chondrodysplasia, a rare form of short-limbed dwarfism which is associated with severe hypercalcemia despite normal or low levels of circulating PTH and PTHrP, A missense mutation was identified which causes constitutive, ligand-independent receptor activation, and thus explains the laboratory and the growth-plate abnormalities in affected individuals. C1 MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP JUPPNER, H (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114, USA. NR 28 TC 9 Z9 9 U1 1 U2 1 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 AUG PY 1995 VL 17 IS 2 SU S BP S39 EP S42 DI 10.1016/8756-3282(95)00206-S PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RU724 UT WOS:A1995RU72400011 PM 8579896 ER PT J AU KRONENBERG, H FISCHER, I AF KRONENBERG, H FISCHER, I TI CALCIOTROPIC HORMONES - RECEPTORS AND ACTION - SESSION-3 SO BONE LA English DT Editorial Material C1 UNIV ZURICH,KLIN BALGRIST,ZURICH,SWITZERLAND. RP KRONENBERG, H (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE UNIT,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 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 AUG PY 1995 VL 17 IS 2 SU S BP S31 EP S32 DI 10.1016/8756-3282(95)00204-Q PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RU724 UT WOS:A1995RU72400009 ER PT J AU ROODMAN, GD AF ROODMAN, GD TI OSTEOCLAST FUNCTION IN PAGETS-DISEASE AND MULTIPLE-MYELOMA SO BONE LA English DT Article; Proceedings Paper CT XII International Conference on Calcium Regulating Hormones CY FEB 14-19, 1995 CL MELBOURNE, AUSTRALIA DE PAGETS DISEASE; OSTEOCLASTS; MULTIPLE MYELOMA; INTERLEUKIN-6; BONE RESORPTION; OSTEOCLAST ULTRASTRUCTURE ID B-CELL MALIGNANCIES; NUCLEAR INCLUSIONS; BONE; MARROW; INTERLEUKIN-6; RESORPTION; CYTOKINE AB Paget's disease of bone and multiple myeloma are characterized by increased numbers of osteoclasts and markedly increased bone resorption at the sites of the disease, In Paget's disease the osteoclasts are abnormal morphologically and contain viral-like nuclear inclusions, but in multiple myeloma the osteoclasts are normal, The bone lesions in both Paget's disease and multiple myeloma appear to be due to local stimulation of osteoclast formation and bone resorption, In situ hybridization techniques, bone marrow cultures, and cytokine assays have been used to examine osteoclast function in Paget's disease and multiple myeloma, Interleukin-6 (IL-6) has been implicated as a potential mediator for the increased osteoclast activity in both diseases, In Paget's disease, IL-6 is produced by the osteoclasts, the osteoclasts express IL-6 receptors and IL-6 mRNA, and increased levels of IL-6 are present in the marrow plasma and serum of these patients, Similarly, increased levels of IL-6 have been detected in sera from some patients with multiple myeloma, Multiple myeloma cells do not produce IL-6 in vivo but marrow stromal cells or the osteoclasts may be the source of IL-6 in multiple myeloma, IL-6 is a growth factor for multiple myeloma cells, and treating patients with anti-IL-6 decreases the tumor burden in some patients, Thus, IL-6 may be an autocrine/paracrine factor in both Paget's disease and in multiple myeloma, Multiple myeloma cells also produce osteoclast activating factors (OAFs) that can stimulate osteoclast formation and activity, In vitro studies have suggested IL-1, TNF-alpha, and lymphotoxin as potential OAFs, but the identity of the OAF produced by multiple myeloma cells in vivo remains uncertain, Thus, osteoclast function is markedly enhanced in Paget's disease and multiple myeloma, but the basis for the increased osteoclast activity remains to be clearly defined. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED HEMATOL,SAN ANTONIO,TX. VET ADM MED CTR,SAN ANTONIO,TX. NR 30 TC 28 Z9 28 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 AUG PY 1995 VL 17 IS 2 SU S BP S57 EP S61 DI 10.1016/8756-3282(95)00179-H PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RU724 UT WOS:A1995RU72400016 PM 8579899 ER PT J AU FILLEY, CM AF FILLEY, CM TI NEUROPSYCHIATRIC FEATURES OF LEWY BODY DISEASE SO BRAIN AND COGNITION LA English DT Article ID PARKINSONS-DISEASE; PROGRESSIVE DEMENTIA; ALZHEIMERS-DISEASE; BODIES; PATHOLOGY; TANGLES AB Although traditionally associated with Parkinson's disease, the eosinophilic intracytoplasmic neuronal inclusion known as the Lewy body has recently been regarded as the primary neuropathologic finding in a variety of conditions affecting the aging brain. The term Lewy Body Disease (LBD) will be used in this review to refer to a spectrum of clinical states varying from those due to incidental or mildly symptomatic histopathologic changes to progressive dementia and psychosis. Many unanswered questions remain about the neurobehavioral and neuropathological implications of Lewy bodies, but it is useful to consider the LED spectrum in terms of the variable effects on neuropsychiatric function that can be observed clinically. (C) 1995 Academic Press, Inc. C1 UNIV COLORADO,SCH MED,DEPT PSYCHIAT,DENVER,CO 80262. DENVER VET AFFAIRS MED CTR,DENVER,CO. RP FILLEY, CM (reprint author), UNIV COLORADO,SCH MED,HLTH SCI CTR,DEPT NEUROL,BEHAV NEUROL SECT,B-183,4200 E 9TH AVE,DENVER,CO 80262, USA. NR 31 TC 13 Z9 13 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 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD AUG PY 1995 VL 28 IS 3 BP 229 EP 239 DI 10.1006/brcg.1995.1254 PG 11 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA RT796 UT WOS:A1995RT79600003 PM 8546851 ER PT J AU CUMMINGS, JL AF CUMMINGS, JL TI LEWY BODY DISEASES WITH DEMENTIA - PATHOPHYSIOLOGY AND TREATMENT SO BRAIN AND COGNITION LA English DT Article ID ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; CONTROLLED TRIAL; SENILE DEMENTIA; PROTEIN; PHYSOSTIGMINE; ANTAGONISTS; HYPOTHESIS; GLUTAMATE; TACRINE AB There are four major Lewy body disorders with dementia: Parkinson's disease (PD), PD with Alzheimer's disease (AD), cortical Lewy bodies and neuritic plaques, and cortical Lewy bodies and no concomitant AD-type pathology. A variety of pathogenetic processes may underly this panoply of diseases including oxidative stress, excitatory amino acid toxicity, amyloidogenesis, neurofibrillary tangle formation, inflammation, apoptotic cell death, and neurotransmitter deficiency. Treatment strategies include transmitter replacement, neuroprotection, agents to limit AD-type pathology, iron chelation, and anti-inflammatory drugs. Patients with Lewy body disorders exhibit cognitive decline resulting from a variety of disease processes and treatment must address the disease-specific pathogenesis. (C) 1995 Academic Press, Inc. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,BEHAV NEUROSCI SECT,LOS ANGELES,CA 90073. RP CUMMINGS, JL (reprint author), UNIV CALIF LOS ANGELES,SCH MED,REED NEUROL RES CTR,DEPT NEUROL,710 WESTWOOD PLAZA,LOS ANGELES,CA 90024, USA. FU NIA NIH HHS [AG10123] NR 69 TC 14 Z9 14 U1 1 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD AUG PY 1995 VL 28 IS 3 BP 266 EP 280 DI 10.1006/brcg.1995.1257 PG 15 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA RT796 UT WOS:A1995RT79600006 PM 8546854 ER PT J AU AKINS, CW AF AKINS, CW TI THE CASE FOR CONCOMITANT CAROTID AND CORONARY-ARTERY SURGERY SO BRITISH HEART JOURNAL LA English DT Editorial Material ID INTRAVENOUS ANGIOGRAPHY; NONOPERATIVE TREATMENT; BYPASS-SURGERY; ENDARTERECTOMY; STENOSIS; DISEASE; STROKE; OPERATIONS RP AKINS, CW (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC SURG UNIT,BOSTON,MA 02114, USA. NR 21 TC 9 Z9 9 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-0769 J9 BRIT HEART J JI Br. Heart J. PD AUG PY 1995 VL 74 IS 2 BP 97 EP 98 PG 2 WC Cardiac & Cardiovascular Systems; History & Philosophy Of Science SC Cardiovascular System & Cardiology; History & Philosophy of Science GA RN944 UT WOS:A1995RN94400001 PM 7547007 ER PT J AU FERNANDEZDELCASTILLO, C RATTNER, DW WARSHAW, AL AF FERNANDEZDELCASTILLO, C RATTNER, DW WARSHAW, AL TI FURTHER EXPERIENCE WITH LAPAROSCOPY AND PERITONEAL CYTOLOGY IN THE STAGING OF PANCREATIC-CANCER SO BRITISH JOURNAL OF SURGERY LA English DT Article ID SURVIVAL; MANAGEMENT; DIAGNOSIS; CARCINOMA; MORTALITY AB A total of 114 patients with pancreatic cancer and no evidence of metastatic disease by computed tomography underwent laparoscopy. Intra-abdominal spread was present in 27 patients (24 per cent). Metastases were 2.4 times more common in tumours of the distal pancreas (11 of 25, 44 per cent) than in pancreatic head tumours (16 of 89, 18 per cent) (P<0.05). None of the 27 patients with metastases underwent further surgery. Of the 87 patients without metastatic spread, 42 were found to have vascular invasion by angiography and were offered radiation therapy. Thirty of 40 patients explored surgically were resected; two of the remaining ten had peritoneal spread that had been missed at laparoscopy (false-negative rate of 7 per cent). Cytological examination of peritoneal washings was performed in 94 patients at the time of laparoscopy; cytology was positive in 16 (17 per cent). There was a significant correlation between positive cytology and presence of visible liver or peritoneal metastases (ten of 22 with metastases versus six of 72 without, P<0.001). Positive cytology was present in six patients (8 per cent) without visible metastases, but none had resectable disease. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP FERNANDEZDELCASTILLO, C (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,WAC 464,BOSTON,MA 02114, USA. NR 19 TC 113 Z9 114 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD AUG PY 1995 VL 82 IS 8 BP 1127 EP 1129 PG 3 WC Surgery SC Surgery GA RM118 UT WOS:A1995RM11800035 PM 7648172 ER PT J AU REMENSNYDER, JP ASTROZJNIKOVA, S BELL, L BUDKEVICH, L BULETOVA, AA DICARLO, J FEATHERSTON, D JOHNSON, L KOLOTUKIN, A KRASSOVSKY, V KTSOEV, R LEBEDEV, D LYBARGER, P MORRIS, W OKATYEV, V PRODEUS, P VASILOVA, L VOZDVIDZENSKY, S YANKINA, N AF REMENSNYDER, JP ASTROZJNIKOVA, S BELL, L BUDKEVICH, L BULETOVA, AA DICARLO, J FEATHERSTON, D JOHNSON, L KOLOTUKIN, A KRASSOVSKY, V KTSOEV, R LEBEDEV, D LYBARGER, P MORRIS, W OKATYEV, V PRODEUS, P VASILOVA, L VOZDVIDZENSKY, S YANKINA, N TI PROGRESS IN A MOSCOW CHILDRENS BURN UNIT - A JOINT RUSSIAN-AMERICAN COLLABORATION SO BURNS LA English DT Article AB A joint Russian-American paediatric burn programme involving Chiidrens Hospital No. 9 in Moscow and Project HOPE in Millwood, Virginia emerged from the efforts of burn professionais from both countries in caring for a group of children seriously burned as a result of the train-pipeline catastrophe that occurred in June 1989 in the Ural Mountains. This paper describes the burn unit and its activities during the years 1985-93 and includes: (1) a general description of the physical and administrative structure of the unit; (2) the demography of burn admissions; (3) clinical activities; (4) a comparison of the clinical results of the years before the institution of the combined programme (1985-89) with those achieved during the first 4 years of the combined collaboration (1990-93). Among the important changes that have occurred since the onset of the combined programme are: (1) overall reduction in the crude burn mortality rate; (2) decrease in burn deaths in all burn size groups; (3) dramatic reduction in the length of stay of children with the deepest burns; (4) marked improvement in the take of skin grafts applied to burn wounds and an almost total elimination of complete skin graft failures. RP REMENSNYDER, JP (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,WHITE 504,BOSTON,MA 02114, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA LINACRE HOUSE JORDAN HILL, OXFORD, OXON, ENGLAND OX2 8DP SN 0305-4179 J9 BURNS JI Burns PD AUG PY 1995 VL 21 IS 5 BP 323 EP 335 DI 10.1016/0305-4179(95)00015-1 PG 13 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA RJ938 UT WOS:A1995RJ93800001 PM 7546252 ER PT J AU SHORTEN, GD MERK, H SIEBER, T AF SHORTEN, GD MERK, H SIEBER, T TI PERIOPERATIVE TRAIN-OF-4 MONITORING AND RESIDUAL CURARIZATION SO CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Article DE MONITORING, NEUROMUSCULAR RELAXANTS, PANCURONIUM ID NEUROMUSCULAR BLOCKADE; NERVE-STIMULATION; ATRACURIUM; RECOVERY; PANCURONIUM; VECURONIUM; ALCURONIUM; RESPONSES; TACTILE; HUMANS AB It has been suggested that perioperative train-of-four (TOF) monitoring does not reduce the incidence of postoperative residual curarization (PORC). The purpose of this study was to examine whether the use of tactile assessment of the response of the adductor pollicis to supramaximal TOF stimulation of the ulnar nerve at the wrist during anaesthesia affected the incidence of PORC. Thirty-nine ASA I or II surgical patients were studied during thiopentone/fentanyl N2O/enflurane anaesthesia. Pancuronium (70-100 mu g . kg(-1) was used to facilitate tracheal intubation and additional pancuronium increments used to maintain surgical relaxation. The requirement for incremental doses of pancuronium and adequacy of recovery following reversal were assessed according to random allocation, either with (Group A; n = 20) or without (Group B; n = 19) access to TOF monitoring. Patients in the two groups received neostigmine in similar doses (Group A: 53 mu g . kg(-1) (5.9); Group B: 55 mu g . kg(-1) (5.4)). On arrival of the patient to the recovery area, neuromuscular function was assessed electromyographically (using the Datex NMT 221 to measure TOF ratio) and clinically. The incidence of PORC (TOF ratio < 70%) war;greater in Group B (47%) than in Group A (15%) (P = 0.029). We conclude that the use of perioperative TOF monitoring decreases the incidence of pancuronium-induced PORC. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 21 TC 33 Z9 35 U1 0 U2 0 PU CANADIAN ANAESTHETISTS SOC INC PI TORONTO PA 1 EGLINTON AVE EAST, SUITE 208, TORONTO ON M4P 3A1, CANADA SN 0832-610X J9 CAN J ANAESTH JI Can. J. Anaesth.-J. Can. Anesth. PD AUG PY 1995 VL 42 IS 8 BP 711 EP 715 PG 5 WC Anesthesiology SC Anesthesiology GA RL947 UT WOS:A1995RL94700010 PM 7586111 ER PT J AU FOLLIS, F MILLER, K SCREMIN, OU PETT, S KESSLER, R TEMES, T WERNLY, JA AF FOLLIS, F MILLER, K SCREMIN, OU PETT, S KESSLER, R TEMES, T WERNLY, JA TI EXPERIMENTAL DELAYED POSTISCHEMIC SPINAL-CORD HYPOPERFUSION AFTER AORTIC CROSS-CLAMPING SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article ID BLOOD-FLOW; DETERIORATING STROKE; ISCHEMIA; MODEL; PARAPLEGIA; DAMAGE; RABBIT; REPERFUSION; OCCLUSION; INJURY AB Background: As in the brain, recent evidence has suggested a defect in the microcirculation during the reperfusion period after spinal cord ischemia. This investigation was undertaken in order to delineate blood flow dynamics in the postischemic spinal cord of the rat. Methods: Male Sprague-Dawley rats underwent cross-clamping of the aorta and subclavian arteries (XC) for 11 minutes. Spinal cord blood flow (SCBF) was measured by autoradiography in the gray and white matter of cervical (Ce), thoracic (Th) and lumbar (Lu) regions during XC, 1 h, 6 h and 24 h (XC n = 8, 1 h n = 9, 6 h n = 9, and 24 h n = 11, groups) after XC. Control groups underwent surgical manipulations and SCBF measurement but no XC (Sham 1, n = 8), or clamping of the subclavian arteries only (Sham 2, n = 8). Results: In Ce cord, there was no difference between SCBF of 1 h, 6 h, 24 h and Sham 1. In Th cord, SCBF was reduced during XC (P < 0.003 vs. Sham 2), 1 h, 6 h (P < 0.04 and P < 0.01 vs. Sham 1). In Lu cord, SCBF was not detectable in XC, and depressed in 1 h (P < 0.003) and 6 h (P < 0.003). There was no difference between 24 h and Sham 1 in Ce, Th, and Lu cords. Conclusions: The study demonstrated a period of delayed postischemic hypoperfusion in the white and gray matter of Th and Lu cord segments lasting 6 h after XC. The phenomenon may play an important role in the ultimate fate of neural elements with borderline viability after ischemic injury. C1 UNIV CALIF LOS ANGELES, SCH MED, W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT PHYSIOL, LOS ANGELES, CA USA. RP UNIV NEW MEXICO, DEPT CARDIOVASC & THORAC SURG, 2211 LOMAS BLVD, ALBUQUERQUE, NM 87131 USA. NR 28 TC 5 Z9 6 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0317-1671 EI 2057-0155 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD AUG PY 1995 VL 22 IS 3 BP 202 EP 207 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA RQ318 UT WOS:A1995RQ31800005 PM 8529172 ER PT J AU WRIGHT, JE ELIAS, A TRETYAKOV, O HOLDEN, S ANDERSEN, J WHEELER, C SCHWARTZ, G ANTMAN, K ROSOWSKY, A FREL, E AYASH, LJ AF WRIGHT, JE ELIAS, A TRETYAKOV, O HOLDEN, S ANDERSEN, J WHEELER, C SCHWARTZ, G ANTMAN, K ROSOWSKY, A FREL, E AYASH, LJ TI HIGH-DOSE IFOSFAMIDE, CARBOPLATIN, AND ETOPOSIDE PHARMACOKINETICS - CORRELATION OF PLASMA DRUG LEVELS WITH RENAL TOXICITY SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE PHARMACOKINETICS; CHEMOTHERAPY; BONE MARROW TRANSPLANTATION ID BONE-MARROW SUPPORT; PHASE-I; SOLID TUMORS; CISPLATIN AB An autologous bone marrow transplant regimen of ifosfamide, carboplatin, and etoposide (ICE) has been developed as treatment for certain malignancies. At maximum tolerated doses renal insufficiency precludes dose escalation, The objective was to examine whether measurement of plasma drug levels early during treatment would provide warning of renal failure. Nine patients received a 96-h continuous infusion of ifosfamide 16000 mg/m(2), carboplatin 1600 mg/m(2), and etoposide 1200 mg/m(2). Pharmacokinetics, including drug levels and plasma concentration-time curves, of ifosfamide, ultrafiltrable platinum (uPt) and etoposide were analyzed and correlated with renal function. One of the nine patients developed anuric renal failure requiring hemodialysis. By 17 h from the start of infusion, this patient showed substantially higher drug levels of ifosfamide (200 vs mean 217 mu M) and uPt (19 vs mean 10 mu M) than those patients with preserved renal function. The 95% confidence intervals suggested that a 16-22 h ifosfamide level > 153 mu M and an uPt level > mu M predict the development of significant renal dysfunction. Although drug levels were substantially higher at 56 h, the serum creatinine did not yet reflect kidney injury. This study suggests that high plasma ifosfamide and uPt levels, analyzed early in the course of a 96-h infusion of high-dose ICE, provide warning of severe and potentially fatal renal injury. Since ICE has substantial activity in a number of malignancies, but significant renal morbidity, real-time pharmacokinetic-guided dosing may reduce treatment-related toxicity. C1 DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA-06516, P01-CA-38493] NR 20 TC 20 Z9 21 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD AUG PY 1995 VL 36 IS 4 BP 345 EP 351 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA RJ661 UT WOS:A1995RJ66100012 PM 7628055 ER PT J AU SHAFMAN, TD SALEEM, A KYRIAKIS, J WEICHSELBAUM, R KHARBANDA, S KUFE, DW AF SHAFMAN, TD SALEEM, A KYRIAKIS, J WEICHSELBAUM, R KHARBANDA, S KUFE, DW TI DEFECTIVE INDUCTION OF STRESS-ACTIVATED PROTEIN-KINASE ACTIVITY IN ATAXIA-TELANGIECTASIA CELLS EXPOSED TO IONIZING-RADIATION SO CANCER RESEARCH LA English DT Note ID SENSITIVITY; P53 AB The activity of stress-activated protein (SAP) kinase is stimulated by diverse agents such as tumor necrosis factor, UV Light, and protein synthesis inhibitors. The present study demonstrates that ionizing radiation (IR) exposure is also associated with the induction of SAP kinase activity. Cells derived from patients with ataxia-telangiectasia (A-T) are characterized by hypersensitivity to IR. In this study, we demonstrate that IR-induced activation of SAP kinase is defective in A-T cells. In contrast, exposure of A-T cells to UV light or anisomycin results in the induction of SAP kinase activity. These findings indicate that IR-induced signals involved in SAP kinase activation are defective in A-T cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP EAST,MED SERV,DIABET RES LABS,BOSTON,MA 02114. UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. RP SHAFMAN, TD (reprint author), HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,50 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA55241] NR 16 TC 71 Z9 73 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 1995 VL 55 IS 15 BP 3242 EP 3245 PG 4 WC Oncology SC Oncology GA RL493 UT WOS:A1995RL49300005 PM 7614455 ER PT J AU GWATHMEY, JK LIAO, RL HELM, PA THAIYANANTHAN, G HAJJAR, RJ AF GWATHMEY, JK LIAO, RL HELM, PA THAIYANANTHAN, G HAJJAR, RJ TI IS CONTRACTILITY DEPRESSED IN THE FAILING HUMAN HEART SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Article DE FAILING HEART; MYOCARDIUM; END STAGE HEART FAILURE; AND CONTRACTILITY ID CARDIAC SARCOPLASMIC-RETICULUM; FORCE-FREQUENCY RELATIONSHIP; HUMAN VENTRICULAR MYOCARDIUM; CORONARY-ARTERY DISEASE; DILATED CARDIOMYOPATHY; ISOFORM EXPRESSION; GENE-EXPRESSION; SKELETAL-MUSCLE; CA-2+ UPTAKE; FAILURE AB Is contractility depressed in the failing human heart? The question must be approached in a stringent manner. Myocardium from failing human hearts has been shown to generate normal physiological force under the ideal conditions of low stimulation and an adequate energy supply. Nevertheless, even when subjected to physiologically conducive conditions, failing myocardium experiences a slowed relaxation, adversely affecting the diastolic properties of the heart. In addition, experiments have shown that increasing the contraction rates of failing hearts clearly results in lowered force and pressure evolution. This information indicates a decrease in contractile reserve in both a systolic and diastolic sense. Not surprisingly, the term end-stage heart failure becomes questionable when applied to myocardium obtained from patients undergoing cardiac transplantation. A number of studies involve such myocardium from feasible regions of the heart perfused within ideal physiological conditions yielding, at times, nonfailing performance. Therefore, it becomes imperative to bear in mind the role of such myocardium within the framework of the entire diseased heart. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD THORNDIKE LABS,BOSTON,MA 02114. BETH ISRAEL HOSP,DIV CARDIOVASC DIS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02115. RP GWATHMEY, JK (reprint author), HARVARD UNIV,SCH MED,CARDIOVASC DIS & MUSCLE RES LABS,220 LONGWOOD AVE,BLDG B1-ROOM 146,BOSTON,MA 02115, USA. NR 40 TC 2 Z9 2 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD AUG PY 1995 VL 9 IS 4 BP 581 EP 587 DI 10.1007/BF00878090 PG 7 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA RZ998 UT WOS:A1995RZ99800005 PM 8547208 ER PT J AU BUZZI, MG BONAMINI, M MOSKOWITZ, MA AF BUZZI, MG BONAMINI, M MOSKOWITZ, MA TI NEUROGENIC MODEL OF MIGRAINE SO CEPHALALGIA LA English DT Article; Proceedings Paper CT 2nd EHF Workshop on Investigations of Neurotransmitters and Receptors in the Headache Patient CY JUN 18, 1994 CL LIEGE, BELGIUM SP EHF ID RAT DURA-MATER; TRIGEMINAL NUCLEUS CAUDALIS; GENE-RELATED PEPTIDE; VASCULAR HEAD PAIN; PLASMA EXTRAVASATION; BLOOD-VESSELS; ULTRASTRUCTURAL EVIDENCE; ANTIMIGRAINE DRUG; NERVE-FIBERS; MAST-CELLS AB Activation of peripheral trigeminal fibers induces neurogenic inflammation in rat dura mater, as well as vascular and mast cell changes. These changes parallel an increase of vasodilating and permeability promoting peptides in venous effluent of the cephalic circulation. The experimental model of electrical trigeminal ganglion stimulation or systemic capsaicin administration has proven effective in detecting cellular activation in brainstem trigeminal nuclei. Animal experimental models of trigeminovascular activation and the effects of antimigraine drugs on functional and morphological consequences of such activation provide the background for further models and for developing pharmacological strategies in this field. C1 MASSACHUSETTS GEN HOSP,STROKE RES LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP BUZZI, MG (reprint author), IRCCS SANATRIX,VIA ATINENSE 18,I-86077 POZZILLI,ITALY. RI Moskowitz, Michael/D-9916-2011 NR 33 TC 89 Z9 90 U1 0 U2 2 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD AUG PY 1995 VL 15 IS 4 BP 277 EP 280 DI 10.1046/j.1468-2982.1995.1504277.x PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RP279 UT WOS:A1995RP27900005 PM 7585923 ER PT J AU CAHALIN, L PAPPAGIANOPOULOS, P PREVOST, S WAIN, J GINNS, L AF CAHALIN, L PAPPAGIANOPOULOS, P PREVOST, S WAIN, J GINNS, L TI THE RELATIONSHIP OF THE 6-MIN WALK TEST TO MAXIMAL OXYGEN-CONSUMPTION IN TRANSPLANT CANDIDATES WITH END-STAGE LUNG-DISEASE SO CHEST LA English DT Article DE EXERCISE TEST; EXERCISE TOLERANCE; LUNG DISEASE; OXYGEN CONSUMPTION; TRANSPLANTATION; WALKING ID OBSTRUCTIVE PULMONARY-DISEASE; DIFFUSING-CAPACITY; CHRONIC HEART; EXERCISE; HEMODYNAMICS; PERFORMANCE; VALUES; PREDICTION AB Study objective : To assess the relationship of distance ambulated during the 6-min walk test (6'WT) to maximal oxygen consumption (Vo(2) max). Design: Multivariate analysis of patient characteristics to Vo(2) max. Setting: Pre-lung transplant evaluation. Patients: 60 patients (22 men, 38 women; mean age, 44 years) with end-stage lung disease (mean FEV(1) and forced vital capacity of 0.97 and 1.93, respectively). Measurements and results: The 6'WT was performed on a level hallway surface, and Vo(2) max was obtained during maximal cycle ergometry exercise testing with respiratory gas analysis. Multivariate analysis of patient characteristics (age, sex, weight, FEV(1), FVC, diffusing capacity for carbon monoxide (Dco), 6'WT distance ambulated, number of rests per 6'WT, and the maximal heart rate, blood pressure, rate-pressure product, respiratory rate, oxygen saturation, rating of perceived exertion, and amount of supplemental oxygen used during the 6'WT) was performed on two groups of 30 patients each (group A or B) who were randomly assigned to either group by a process of random selection using a computer-generated random numbers program. Distance ambulated was the strongest independent predictor of Vo(2) max (r=0.73; p<0.0001) in both groups, and adding age, weight, and pulmonary function test results (FVC, FEV(1), and Dco) to the regression equation increased the correlation coefficient to 0.83, Because of the significant correlation of distance ambulated during the 6'WT to Vo(2); max, the prediction equation obtained from the multivariate analysis of group A, Vo(2) max=0.006xdistance (feet) +3.38, was used to estimate the Vo(2) max of the group B patients. No significant difference was observed between the estimated (x+/-SD=8.9+/-2.4 mL/kg/min) and observed (x+/-SD=9.4+/-3.8 ml/kg/min) Vo(2) max (mean difference, 0.5 ml/kg/min; SD of the difference=2.88). Conclusions: The distance ambulated during a 6'WT can predict Vo(2) max in patients with end-stage lung disease. The addition of several patient characteristics can increase the ability to predict Vo(2) max and account for more of the variability. Such information is valuable when assessing patient response to therapeutic intervention if respiratory gas analysis is unavailable or impractical. C1 MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,THORAC SURG UNIT,BOSTON,MA 02114. RP CAHALIN, L (reprint author), MASSACHUSETTS GEN HOSP,PHYS THERAPY SERV,LUNG TRANSPLANT PROGRAM,BIGELOW 858,32 FRUIT ST,BOSTON,MA 02114, USA. NR 34 TC 121 Z9 130 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD AUG PY 1995 VL 108 IS 2 BP 452 EP 459 DI 10.1378/chest.108.2.452 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RN842 UT WOS:A1995RN84200032 PM 7634883 ER PT J AU RUSSELL, ME WALLACE, AF WYNER, LR NEWELL, JB KARNOVSKY, MJ AF RUSSELL, ME WALLACE, AF WYNER, LR NEWELL, JB KARNOVSKY, MJ TI UP-REGULATION AND MODULATION OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN RAT CARDIAC ALLOGRAFTS WITH CHRONIC REJECTION AND TRANSPLANT ARTERIOSCLEROSIS SO CIRCULATION LA English DT Article DE ARTERIOSCLEROSIS; MACROPHAGES; REJECTION; TRANSPLANT ID FATTY-ACID DEFICIENCY; EXPERIMENTAL GRAFT ARTERIOSCLEROSIS; L-ARGININE; MONOCYTE CHEMOATTRACTANT; MOUSE MACROPHAGES; INTERFERON-GAMMA; HEART; EXPRESSION; CELLS; MECHANISMS AB Background The Lewis-F344 rat cardiac transplantation model produces cardiac allografts with chronic rejection characterized by arteriosclerotic lesions composed of macrophages and smooth muscle cells. Modulation of the inflammatory response with a diet deficient in essential fatty acids protects against the development of intimal thickening. Little is known about the components of the inflammatory response mediating this process. The cytokine-inducible isoform of nitric oxide synthase (iNOS) regulates the high-output nitric oxide pathway that confers activation properties to macrophages and regulates vasomotion, monocyte adherence, and smooth muscle cell proliferation in the vasculature. The purpose of the present study was to determine whether the iNOS pathway was upregulated during the course of chronic cardiac rejection. Methods and Results We studied iNOS mRNA and protein expression patterns in a series of Lewis-F344 cardiac allografts with early and late chronic rejection and after modulation of the inflammatory response (in an effort to attenuate arteriosclerosis). Relative gene transcript levels were measured with a P-32-dCTP reverse-transcriptase polymerase chain reaction assay designed to amplify iNOS mRNA. The distribution of the iNOS gene product was examined by immunocytochemistry with a polyclonal antibody against iNOS. NOS transcript levels increased significantly in cardiac allografts (days 7, 14, 28, and 75) compared with paired host hearts (exposed to the same circulation) and syngrafts (P<.003). Immunostaining localized the iNOS antigen within subpopulations of mononuclear inflammatory cells in cardiac allografts-presumably, activated macrophages. The number of iNOS-positive mononuclear cells was 25-fold higher in cardiac allografts compared with paired host hearts and syngrafts (P<.009). In cardiac allografts of 75 days or older, there also was striking iNOS staining within some medial and intimal smooth muscle cells in various vessels. Modulation of the inflammatory response (with a diet deficient in essential fatty acids) produced significant decreases in the intimal thickening score and in the percentage of diseased vessels in 28-day cardiac allografts compared with allografts from rats fed a control diet. There was a correlate decrease in iNOS transcript levels and in the number of iNOS-positive mononuclear cells in the 28-day cardiac allografts from rats fed the essential fatty acid-deficient diet. Conclusions The early and persistent upregulation of iNOS in chronic cardiac rejection and the coincident reduction in arteriosclerosis and downregulation of iNOS suggest that this inducible regulator may contribute to the inflammatory response mediating transplant arteriosclerosis. C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DIV CARDIOVASC,BOSTON,MA 02115. RP RUSSELL, ME (reprint author), HARVARD UNIV,SCH PUBL HLTH,CARDIOVASC BIOL LAB,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL-17747, HL-43318] NR 39 TC 113 Z9 115 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 AUG 1 PY 1995 VL 92 IS 3 BP 457 EP 464 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RL562 UT WOS:A1995RL56200030 PM 7543380 ER PT J AU NARULA, J PETROV, A BIANCHI, C DITLOW, CC LISTER, BC DILLEY, J PIESLAK, I CHEN, FW TORCHILIN, VP KHAW, BA AF NARULA, J PETROV, A BIANCHI, C DITLOW, CC LISTER, BC DILLEY, J PIESLAK, I CHEN, FW TORCHILIN, VP KHAW, BA TI NONINVASIVE LOCALIZATION OF EXPERIMENTAL ATHEROSCLEROTIC LESIONS WITH MOUSE-HUMAN CHIMERIC Z2D3 F(AB')(2) SPECIFIC FOR THE PROLIFERATING SMOOTH-MUSCLE CELLS OF HUMAN ATHEROMA - IMAGING WITH CONVENTIONAL AND NEGATIVE CHARGE-MODIFIED ANTIBODY FRAGMENTS SO CIRCULATION LA English DT Article DE ATHEROSCLEROSIS; IMAGING; ANGIOPLASTY; ANTIBODIES; SMOOTH MUSCLE CELLS ID LOW-DENSITY LIPOPROTEINS; CAROTID ATHEROSCLEROSIS; SCINTIGRAPHIC DETECTION; AUTOLOGOUS PLATELETS; PATHOGENESIS; ANGIOPLASTY; EXPRESSION; EVOLUTION; THROMBI AB Background A murine monoclonal antibody designated Z2D3 (IgM) generated against homogenized human atherosclerotic plaques was demonstrated to be highly specific for proliferating smooth muscle cells. The primary clone subsequently was genetically engineered to provide a mouse/human chimeric antibody with human IgG(1) constant region expressed in a rat myeloma cell line. The resulting Z2D3-73.30 chimeric retained the immunoreactivity relative to the parent Z2D3-IgM and was pepsin-digested to yield F(ab')(2). In-111-labeled chimeric Z2D3 F(ab')(2) was then used for noninvasive imaging of experimental atherosclerotic lesions. To improve the imaging characteristics, we modified chimeric Z2D3 F(ab')(2) fragments to carry a high negative charge. Improved visualization of targets with In-111-labeled, negatively charged, polymer-modified antibodies most probably is the result of faster blood clearance and a decrease in nontarget background activity. Methods and Results Experimental atherosclerotic lesions were induced in rabbits by deendothelialization of the infradiaphragmatic aorta followed by a 6% peanut oil-2% cholesterol diet. After 12 weeks, localization of the conventionally labeled In-111-Z2D3 F(ab')(2) (24 Mbq [650 mu Ci]/500 to 750 mu g) (n=4) was compared with In-111-labeled, negatively charged, polymer-modified Z2D3 F(ab')(2) (24 Mbq [650 mu Ci]/25 to 50 mu g) in eight atherosclerotic rabbits. Three control rabbits also received radiolabeled polymer-modified Z2D3. Ten rabbits with atherosclerotic lesions received In-111-labeled nonspecific human IgG(1) F(ab')(2) with (n=6) or without (n=4) negative charge modification. Atherosclerotic lesions were visualized in all rabbits with the conventional Z2D3 F(ab')(2) at 48 hours. However, unequivocal lesion visualization was possible at 24 hours only with negatively charged, polymer-modified Z2D3 F(ab')(2). Quantitative uptake of F(ab')(2) fragments was essentially determined by the presence of atherosclerotic lesions (F-1.37=69.8; P<.0001) and the specificity of the antibody (F-1.37-36.6; P<.0001). Uptake of the conventional Z2D3 in atherosclerotic lesions (mean+/-SEM percent injected dose per gram, 0.112+/-0.024%) was six times higher than background activity in the normal aortic segments (nondenuded thoracic aorta; mean percent injected dose per gram, 0.019+/-0.003%). Uptake of the conventional Z2D3 was also significantly higher than that of nonspecific human IgG(1) F(ab')(2) (0.027+/-0.004%). Specific uptake of the conventional Z2D3 in the lesions was comparable to the charge-modified Z2D3 uptake (0.084+/-0.017; P=.20). Uptake of negative charge-modified Z2D3 in the lesions was significantly higher than in the corresponding background activity in normal thoracic aorta (0.021+/-0.002). Uptake of negative charge-modified Z2D3 F(ab')(2) in the lesions was higher than the uptake of negative charge-modified nonspecific IgG(1) F(ab')(2) (0.020+/-0.002) in the lesions. Uptake of charge-modified Z2D3 in the atherosclerotic lesions was also significantly higher than the corresponding regions of the aorta of the control rabbits (0.017+/-0.002; F-1.18=27.9; P=.0001). There was, however, no difference in the specific lesion uptake of negative charge-modified Z2D3 at 24 hours (0.079+/-0.014) and 48 hours (0.084+/-0.0017; P=.99) after intravenous administration. Nontarget organ activities were lower with negative charge-modified In-111-labeled Z2D3 F(ab')(2) than with the conventional Z2D3 F(ab')(2). Mean kidney activity was fourfold less with the modified (0.45+/-0.06) than with the conventionally radiolabeled (1.67+/-0.264; P=.001) Z2D3 F(ab')(2). Conclusions The present study demonstrates the feasibility of noninvasive visualization of experimental atherosclerotic lesions with a mouse/human chimeric antibody Z2D3 F(ab')(2) directed against the proliferating smooth muscle cells. Furthermore, negative charge modification of the chimeric Z2D3 F(ab')(2) enabled (1) earlier visualization of the atherosclerotic lesions, (2) use of 10- to 15-fold less antibody than with conventional Z2D3 F(ab')(2), and (3) reduction of the radiation burden to nontarget organs. C1 NORTHEASTERN UNIV,BOUVE COLL PHARM,CTR DRUG TARGETING & ANAL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. SCOTGEN BIOPHARMACEUT INC,MENLO PK,CA. RI bianchi, cesario/H-6238-2012 NR 43 TC 62 Z9 63 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 1 PY 1995 VL 92 IS 3 BP 474 EP 484 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RL562 UT WOS:A1995RL56200032 PM 7634463 ER PT J AU NATHAN, DM AF NATHAN, DM TI PREVENTION OF LONG-TERM COMPLICATIONS OF NON-INSULIN-DEPENDENT DIABETES-MELLITUS SO CLINICAL AND INVESTIGATIVE MEDICINE-MEDECINE CLINIQUE ET EXPERIMENTALE LA English DT Article; Proceedings Paper CT Symposium on Diabetes Update - New Developments in Pathophysiology and Treatment of NIDDM CY OCT 15-16, 1994 CL VANCOUVER, CANADA SP Bayer Inc DE LONG-TERM COMPLICATIONS; PATHOGENESIS; NONINSULIN-DEPENDENT DIABETES MELLITUS; GLYCATION END-PRODUCTS; SORBITOL ID ALDOSE-REDUCTASE INHIBITOR; ANTIHYPERTENSIVE TREATMENT; CARDIOVASCULAR-DISEASE; PERIPHERAL NEUROPATHY; GLUCOSE-TOLERANCE; RETINOPATHY; PROGRESSION; NEPHROPATHY; POPULATION; ONSET AB Non-insulin-dependent diabetes mellitus (NIDDM) may be the most rapidly-growing chronic disease in the world. Its long-term complications, including retinopathy, nephropathy, neuropathy, and accelerated macrovascular disease cause major morbidity and mortality. Although therapy that normalizes glycemia may prevent the development and delay the progression of long-term complications in NIDDM, as has been demonstrated in insulin-dependent diabetes mellitus (IDDM), no direct data exist to support the efficacy of ''intensive therapy'' in NIDDM. An alternative approach to preventing the development of long-term complications may be to intervene more distally, i.e., inhibit the mechanism(s) by which elevated glucose levels cause complications. Potential pathogenic mechanisms include the accumulation of sorbitol and other biochemical changes in tissues with aldose reductase, and the modfication of proteins by glycation. Pharmacologic probes, including aldose reductase inhibitors and glycation inhibitors such as aminoguanidine, are currently under study and may provide an efficient means of preventing complications, independent of the ambient glycemic level. C1 MASSACHUSETTS GEN HOSP,DIABET RES CTR,BOSTON,MA 02114. RP NATHAN, DM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIABET UNIT,32 FRUIT ST,BOSTON,MA 02114, USA. NR 44 TC 18 Z9 18 U1 0 U2 1 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA ON K1G 3Y6, CANADA SN 0147-958X J9 CLIN INVEST MED JI Clin. Invest. Med.-Med. Clin. Exp. PD AUG PY 1995 VL 18 IS 4 BP 332 EP 339 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RQ224 UT WOS:A1995RQ22400016 PM 8549021 ER PT J AU Shapiro, CL Dezube, BJ Tretyakov, O Wright, J Cap, B Henderson, IC Hayes, DF AF Shapiro, CL Dezube, BJ Tretyakov, O Wright, J Cap, B Henderson, IC Hayes, DF TI Dose escalation of N,N',N''-triethylenethiophosphoramide combined with pentoxifylline for advanced breast cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-I; ALKYLATING-AGENTS; HUMAN-TUMORS; THIOTEPA; CAFFEINE; CELLS; PHARMACOKINETICS; INVIVO; RADIOSENSITIVITY; OXYGENATION AB Pentoxifylline potentiates the cytotoxicity of alkylating agents in preclinical models, In this study we sought to define the maximum tolerated dose (MTD) of N,N',N ''-triethylenethiophosphoramide (thioTEPA) with pentoxifylline, and to estimate the antitumor response to this combination in previously treated breast cancer patients, Thirty-five previously treated advanced breast cancer patients received 70 cycles (median, 2 cycles/patient; range, 1-6) of 1600 mg of oral sustained release pentoxifylline every 8 h for 4 doses in combination with escalating doses of i,v, bolus thioTEPA 40-65 mg/m(2) administered 3 h after the second dose of pentoxifylline. Thrombocytopenia was dose limiting at 65 mg/m(2) of thioTEPA, and the MTD was defined as 60 mg/m(2), Among 25 patients treated at the MTD, leukopenia was grade 2 in 9 patients (36%), grade 3 in 4 patients (16%), and grade 4 in 2 patients (8%); thrombocytopenia was grade 2 in 3 patients (12%), grade 3 in 4 patients (16%), and grade 4 in 3 patients (12%), No other thioTEPA-related toxicity was observed, Plasma concentrations of thioTEPA, TEPA, and pentoxifylline were measured in 6 patients, The median (range) area under the plasma concentration versus time curve for thioTEPA was 29.4 mu M/h (26.2-40.5) and for TEPA was 16.3 mu M/h (9.2-21.7 uM-h), The median (range) maximal plasma concentration of pentoxifylline and major metabolites I, IV, and V were 1.2 mu g/ml (0.2-7.8), 4.0 mu g/ml (0.5-16.4), 0.4 (range 0.1-0.8), and 2.9 (1.1-5.5), respectively, No objective responses were observed among 21 evaluable patients treated at the MTD (95% confidence interval, 0-15%), The combination of pentoxifylline and thioTEPA is well tolerated hut not active in previously treated advanced breast cancer patients, Further clinical trials using commercially available oral sustained release pentoxifylline as a modulator of alkylating agents are not warranted. C1 DANA FARBER CANC INST,DEPT CELL GROWTH & REGULAT,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. RP Shapiro, CL (reprint author), DANA FARBER CANC INST,CTR BREAST EVALUAT,ROOM 1508,BOSTON,MA 02115, USA. FU NCI NIH HHS [P01-CA 19589] NR 33 TC 3 Z9 3 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 AUG PY 1995 VL 1 IS 8 BP 791 EP 796 PG 6 WC Oncology SC Oncology GA TL083 UT WOS:A1995TL08300002 PM 9816047 ER PT J AU GROSSBARD, ML FIDIAS, P AF GROSSBARD, ML FIDIAS, P TI PROSPECTS FOR IMMUNOTOXIN THERAPY OF NON-HODGKINS-LYMPHOMA SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Review ID B-CELL LYMPHOMA; BONE-MARROW TRANSPLANTATION; PHASE-I TRIAL; RICIN-A-CHAIN; MONOCLONAL-ANTIBODY; ANTI-B4-BLOCKED RICIN; CONTINUOUS INFUSION; ANTITUMOR-ACTIVITY; RECEPTOR; CANCER AB The use of unconjugated monoclonal antibodies to treat patients with non-Hodgkin's lymphoma by targeting specific antigenic determinants on malignant cells has been an area of intense laboratory and clinical research, Although occasional clinical successes have been seen, many limitations of such therapy have been identified, including the low endogenous cytotoxicity of most of the antibodies. More recently, investigators have attempted to employ monoclonal antibody-toxin conjugates (immunotoxins) to deliver specific cytotoxins to the lymphoma cell surface. This article describes the preclinical development of immunotoxin therapy as well as the initial results from selected Phase I and II clinical trials in patients with NHL. In addition, future directions are suggested for the use of these agents as adjuvant therapy and as treatment for patients with human immunodeficiency virus-related NHL. (C) 1995 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP GROSSBARD, ML (reprint author), MASSACHUSETTS GEN HOSP,HEMATOL ONCOL UNIT,BOSTON,MA 02114, USA. NR 51 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 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD AUG PY 1995 VL 76 IS 2 BP 107 EP 114 DI 10.1006/clin.1995.1103 PG 8 WC Immunology; Pathology SC Immunology; Pathology GA RJ459 UT WOS:A1995RJ45900001 PM 7614729 ER PT J AU LEWANDROWSKI, KU TOMFORD, WW YEADON, A DEUTSCH, TF MANKIN, HJ UHTHOFF, HK AF LEWANDROWSKI, KU TOMFORD, WW YEADON, A DEUTSCH, TF MANKIN, HJ UHTHOFF, HK TI FLEXURAL RIGIDITY IN PARTIALLY DEMINERALIZED DIAPHYSEAL BONE-GRAFTS SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID MORPHOGENETIC PROTEIN; ALLOGRAFTS AB Control of biomechanical properties of demineralized diaphyseal bone allografts is required for their clinical application, Therefore, the changes in flexural rigidity in human fibulae were investigated as a function of the demineralization depth using a nondestructive bending test, Starting at the facies medialis, the flexural rigidity was determined in 24 planes at 15 degrees sequential angular increments, which allowed data collection around the circumference of the bone, Test bones included 4 pairs of left and right human fibulae and 15 single fibulae, The elliptical distribution of the flexural rigidity of left and right fibulae and single fibulae before and after demineralization was compared, The stiffness index and the area ratio were defined as parameters to describe the mechanical status of the test bones, Results show that the rigidity of diaphyseal bones is strongly dependent on the reduction of their cortical thickness by demineralization, A mathematical model allowing prediction of the reduction of the rigidity of diaphyseal bone grafts as a function of the demineralization depth is presented. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED RES LABS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. FU NIAMS NIH HHS [AR-21896] NR 28 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD AUG PY 1995 IS 317 BP 254 EP 262 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA RP273 UT WOS:A1995RP27300038 PM 7671488 ER PT J AU TEICHER, BA AF TEICHER, BA TI ANGIOGENESIS AND CANCER METASTASES - THERAPEUTIC APPROACHES SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review ID LEWIS LUNG-CARCINOMA; FIBROBLAST GROWTH-FACTOR; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ENDOTHELIAL-CELL MITOGEN; TUMOR-NECROSIS-FACTOR; VASCULAR-PERMEABILITY FACTOR; BASEMENT-MEMBRANE COLLAGEN; SUBENDOTHELIAL EXTRACELLULAR-MATRIX; PLASMINOGEN-ACTIVATOR PRODUCTION; INVASIVE BREAST-CARCINOMA RP TEICHER, BA (reprint author), DANA FARBER CANC INST, 44 BINNEY ST, BOSTON, MA 02115 USA. NR 407 TC 31 Z9 33 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD AUG PY 1995 VL 20 IS 1-2 BP 9 EP 39 DI 10.1016/1040-8428(94)00142-G PG 31 WC Oncology; Hematology SC Oncology; Hematology GA RG593 UT WOS:A1995RG59300002 PM 7576200 ER PT J AU STEFANOVICH, P EZZELL, RM SHEEHAN, SJ TOMPKINS, RG YARMUSH, ML TONER, M AF STEFANOVICH, P EZZELL, RM SHEEHAN, SJ TOMPKINS, RG YARMUSH, ML TONER, M TI EFFECTS OF HYPOTHERMIA ON THE FUNCTION, MEMBRANE INTEGRITY, AND CYTOSKELETAL STRUCTURE OF HEPATOCYTES SO CRYOBIOLOGY LA English DT Article ID OF-WISCONSIN SOLUTION; STORED RAT HEPATOCYTES; UW SOLUTION; COLD-STORAGE; PHOSPHOLIPID-VESICLES; POLYETHYLENE-GLYCOL; PRIMARY CULTURE; EURO-COLLINS; PRESERVATION; LIVER AB To increase the storage time of livers for transplantation, a better understanding of hypothermia-induced hepatocyte damage is necessary. To this end, we have characterized the effects of hypothermia on long-term function and cytoskeletal organization of hepatocytes cultured in the collagen sandwich configuration, which maintains the expression of liver-specific functions for several weeks. In these studies, cultured hepatocytes (maintained at 37 degrees C for 7 days) were exposed to 4 degrees C in Leibovitz-15 (L15), University of Wisconsin (UW) solution, or L15 supplemented with 2.5 g% polyethylene glycol (PEG) for various time periods followed by a return to normothermia. When L15 medium was used, the long-term albumin secretion rate of cultured hepatocytes was decreased by 50% after 4 h, and by 95% after 24 h of exposure to 4 degrees C. Amorphous precipitates of F-actin and fragmented short microtubules were also observed after 4 and 12 h of hypothermia, respectively. Similar results were obtained when hepatocytes were stored in UW solution. However, in L15 supplemented with PEG, no significant reduction in long-term albumin secretion rates and intact actin and microtubule morphology was observed even after 24 h of exposure to 4 degrees C. The membrane integrity and long-term albumin secretion of hepatocytes stored in the presence of PEG were decreased to similar to 50% only after 48 h of exposure to 4 degrees C. Thus, PEG may be a useful additive in preservation solutions for hepatocytes in hepatocyte-based liver support systems and for intact tissue as well. (C) 1995 Academic Press,Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,SURG SERV,BOSTON,MA 02114. SHRINERS BURNS INST,BOSTON,MA 02114. RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. NR 39 TC 64 Z9 69 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 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD AUG PY 1995 VL 32 IS 4 BP 389 EP 403 DI 10.1006/cryo.1995.1039 PG 15 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA RL366 UT WOS:A1995RL36600011 PM 7656572 ER PT J AU CHEN, L OAKLEY, MG GLOVER, JNM JAIN, JN DERVAN, PB HOGAN, PG RAO, A VERDINE, GL AF CHEN, L OAKLEY, MG GLOVER, JNM JAIN, JN DERVAN, PB HOGAN, PG RAO, A VERDINE, GL TI ONLY ONE OF THE 2 DNA-BOUND ORIENTATIONS OF AP-1 FOUND IN SOLUTION COOPERATES WITH NFATP SO CURRENT BIOLOGY LA English DT Article ID ACTIVATED T-CELLS; CYCLOSPORINE-A; BINDING DOMAIN; NUCLEAR FACTOR; LYMPHOCYTES-T; C-FOS; TRANSCRIPTION FACTORS; RESPONSE ELEMENTS; HIN RECOMBINASE; LEUCINE ZIPPER AB Background: The transcription factor AP-1 activates the expression of numerous genes in response to mitogenic stimuli. AP-1 regulates gene expression both through solitary binding to independent recognition sites and, in cooperation with various heterologous transcription factors, through targeting to composite response elements. The two subunits that make up the AP-1 heterodimer, Fos and Jun, possess identical residues at positions that make sequence-specific contacts to DNA. This degeneracy leaves the protein with no apparent way of orienting itself uniquely on DNA by differentially recognizing its two non-identical half-sites. Here, we have analyzed the orientation of the AP-1 basic-leucine-zipper (bZip) domain on a cognate site, both alone and in the cooperative complex formed together with the 'nuclear factor of activated T cells' (NFATp). Results: The results of affinity cleaving experiments demonstrate that, in solution, the AP-1 bZip binds DNA as a mixture of two orientational isomers. However, in the cooperative complex formed with NFATp on a composite response element, the AP-1 bZip adopts a single orientation, with Jun and Fos bound to the NFATp-proximal and NFATp-distal half-sites, respectively. Protein cross-linking experiments demonstrate that protein-protein contacts are responsible for this 'orientational locking'. Conclusions: Our results demonstrate that, through protein-protein interactions, one protein can force another to adopt a single DNA-bound orientation. Thus, cooperative interactions between adjacent regulatory proteins can influence not only the energetics of their interactions with DNA, but also their precise geometric and stereochemical arrangement. Because orientational isomers present markedly different structures to the transcriptional apparatus, it seems likely that orientation will exert an effect on the ability to activate transcription. C1 HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138. CALTECH,DEPT CHEM,PASADENA,CA 91125. HARVARD UNIV,DEPT MOLEC & CELLULAR BIOL,CAMBRIDGE,MA 02138. DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. RI Chen, Lin/A-3392-2008 FU NIGMS NIH HHS [GM 27681] NR 39 TC 51 Z9 51 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 1 PY 1995 VL 5 IS 8 BP 882 EP 889 DI 10.1016/S0960-9822(95)00178-3 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RN569 UT WOS:A1995RN56900017 PM 7583146 ER PT J AU AGRE, P BROWN, D NIELSEN, S AF AGRE, P BROWN, D NIELSEN, S TI AQUAPORIN WATER CHANNELS - UNANSWERED QUESTIONS AND UNRESOLVED CONTROVERSIES SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID MAJOR INTRINSIC PROTEIN; INTEGRAL MEMBRANE-PROTEIN; LENS FIBER MEMBRANES; RAT-KIDNEY; XENOPUS-OOCYTES; EXPRESSION; CLONING; CDNA; CYSTEINE-189; LOCALIZATION AB The long-standing biophysical question of how water crosses plasma membranes has been answered by the recent discovery of the aquaporins. Identification of this large family of membrane water-transport proteins has generated new questions about the physiological functions, tissue distributions, and regulatory mechanisms of individual aquaporins. The fast pace of developments in this field has also resulted in major discrepancies in published reports which warrant resolution. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02129. AARHUS UNIV,INST ANAT,DEPT CELL BIOL,DK-8000 AARHUS C,DENMARK. RP AGRE, P (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM,PHYSIOL BLDG,ROOM 420,725 N WOLFE ST,BALTIMORE,MD 21205, USA. FU NHLBI NIH HHS [HL33991, HL48268]; NIDDK NIH HHS [DK38452] NR 85 TC 187 Z9 198 U1 0 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD AUG PY 1995 VL 7 IS 4 BP 472 EP 483 DI 10.1016/0955-0674(95)80003-4 PG 12 WC Cell Biology SC Cell Biology GA RM815 UT WOS:A1995RM81500003 PM 7495566 ER PT J AU HA, I WIGHTMAN, B RUVKUN, G AF HA, I WIGHTMAN, B RUVKUN, G TI TEMPORAL PATTERN-FORMATION BY THE LIN-14 TEMPORAL GRADIENT SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 737 EP 737 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400046 ER PT J AU ROSENTHAL, N AF ROSENTHAL, N TI CONTROL OF GENE ACCESSIBILITY IN MUSCLE DEVELOPMENT SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,BOSTON,MA 02129. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 738 EP 738 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400047 ER PT J AU CRAWFORD, K WEISSIG, H BINETTE, F MILLAN, JL GOETINCK, PF AF CRAWFORD, K WEISSIG, H BINETTE, F MILLAN, JL GOETINCK, PF TI TISSUE-NONSPECIFIC ALKALINE-PHOSPHATASE PARTICIPATES IN THE ESTABLISHMENT AND GROWTH OF FEATHER GERMS IN EMBRYONIC CHICK SKIN CULTURES SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 ST MARYS COLL MARYLAND,DEPT BIOL,ST MARYS CITY,MD 20686. LA JOLLA CANC RES FDN,LA JOLLA,CA 92037. GENZYME TISSUE REPAIR,CAMBRIDGE,MA 02142. MASSACHUSETTS GEN HOSP EAST,CBRC,BOSTON,MA 02129. RI Millan, Jose Luis/B-6580-2008 NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 749 EP 749 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400116 ER PT J AU NEVILLE, C ROSENTHAL, N AF NEVILLE, C ROSENTHAL, N TI TRANSGENIC ANALYSIS OF RAT MYOSIN LIGHT-CHAIN-1 EXPRESSION UTILIZING A NOVEL REPORTER GENE SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129. RI Rosenthal, Nadia/O-7009-2015 NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 756 EP 756 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400159 ER PT J AU BOGDANOVA, N NEVILLE, C KAUSHAL, S CECCARELLI, E GONG, X ROSENTHAL, N AF BOGDANOVA, N NEVILLE, C KAUSHAL, S CECCARELLI, E GONG, X ROSENTHAL, N TI DEVELOPMENTAL EXPRESSION PATTERN OF ZBU1, A NOVEL SW12/SNF2 HOMOLOG WITH DNA-BINDING ACTIVITY AND CELL-CYCLE REGULATION SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,BOSTON,MA 02129. RI Rosenthal, Nadia/O-7009-2015 NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 757 EP 757 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400161 ER PT J AU MOSS, JB PRICE, AL RAZ, E ROSENTHAL, N AF MOSS, JB PRICE, AL RAZ, E ROSENTHAL, N TI THE GREEN FLUORESCENT PROTEIN MARKS MUSCLE IN MURINE CELL-LINES AND ZEBRAFISH SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,BOSTON,MA 02129. RI Rosenthal, Nadia/O-7009-2015 NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 762 EP 762 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400194 ER PT J AU REICHMANFRIED, M TAHAOGLU, E WHITE, K AF REICHMANFRIED, M TAHAOGLU, E WHITE, K TI IDENTIFICATION OF CELL-DEATH GENES IN DROSOPHILA SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. RI White, Kristin/D-7936-2013 NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 767 EP 767 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400225 ER PT J AU HOUGHTON, LA ROSENTHAL, N AF HOUGHTON, LA ROSENTHAL, N TI COMPARATIVE-ANALYSIS OF HOMEOBOX GENE-EXPRESSION IN MURINE MUSCLE - NORMAL DENERVATED AND REGENERATING TISSUE SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 BOSTON UNIV,DEPT BIOL,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,BOSTON,MA. RI Rosenthal, Nadia/O-7009-2015 NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 770 EP 770 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400239 ER PT J AU JOKI, R KLEIN, RL LOPESVIRELLA, MF COLWELL, JA AF JOKI, R KLEIN, RL LOPESVIRELLA, MF COLWELL, JA TI RELEASE OF PLATELET PLASMINOGEN-ACTIVATOR INHIBITOR-1 IN WHOLE-BLOOD IS INCREASED IN PATIENTS WITH TYPE-II DIABETES SO DIABETES CARE LA English DT Article ID THROMBOLYSIS; AGGREGATION; THROMBOSIS; MELLITUS; DISEASE AB OBJECTIVE - To compare platelet plasminogen activator inhibitor 1 (PAI-1) release in type II diabetic patients and healthy control subjects. RESEARCH DESIGN AND METHODS - We studied a group of 27 diabetic patients and a group of 16 nondiabetic control subjects. Whole-blood platelet aggregation, defined as a decrease in platelet count during shaking (180 rpm) of blood samples al 37 degrees C, and plasma PAI-1 antigen concentrations were measured in parallel at time 0, 7.5, 15, 30, 60, 120, and 180 min. RESULTS - Platelet aggregation did not differ significantly between the two groups at any time period. However, the increase in plasma PAI-1 antigen concentration over basal levels at time 0 was higher for the group of diabetic patients when compared with their matched control subjects. The increment of PAI-1 antigen was 61.8 +/- 29.4 vs. 35.9 +/- 13.4 ng/ml (P < 0.005, means +/- SD) after 180 min for the diabetic and control subjects, respectively. Platelet PAI-1 release was correlated to very-low-density lipoprotein cholesterol and triglyceride plasma levels, but not to HbA(1c) levels. CONCLUSIONS - Platelets of patients with type II diabetes release significantly more PAI-1 than platelets of healthy subjects al the same level of platelet aggregation. This may contribute to enhanced thrombosis in diabetes. C1 MED UNIV S CAROLINA,DIV ENDOCRINOL DIABET & METAB,CHARLESTON,SC 29425. RP JOKI, R (reprint author), RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,109 BEE ST,CHARLESTON,SC 29401, USA. NR 21 TC 4 Z9 4 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 1995 VL 18 IS 8 BP 1150 EP 1155 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RM113 UT WOS:A1995RM11300009 ER PT J AU HORTON, ES AF HORTON, ES TI NIDDM - THE DEVASTATING DISEASE SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article; Proceedings Paper CT Hoechst Satellite Symposium on New Oral Antidiabetic Agents - From Today to Tomorrow, at the 15th International-Diabetes-Federation Congress CY NOV 04-05, 1994 CL KOBE, JAPAN SP Int Diabetes Federat DE NON-INSULIN-DEPENDENT DIABETES; HETEROGENEOUS DISORDER; ATHEROSCLEROSIS; HYPOGLYCEMIA ID IMPAIRED GLUCOSE-TOLERANCE; DEPENDENT DIABETES-MELLITUS; BODY-FAT DISTRIBUTION; UNITED-STATES POPULATION; JAPANESE-AMERICAN MEN; ALL-CAUSE MORTALITY; 10-YEAR FOLLOW-UP; RISK-FACTORS; WEIGHT-LOSS; PHYSICAL-ACTIVITY AB Of the various types of diabetes mellitus, non-insulin-dependent diabetes (NIDDM) is by far the most common and is increasing rapidly in many populations around the world. It is a heterogeneous disorder, characterized by a genetic predisposition and interaction between insulin resistance and decreased pancreatic beta-cell function. There is a strong association between the presence of obesity and low levels of physical exercise and the development of NIDDM. However, NIDDM may also develop in lean individuals and the incidence increases significantly with increasing age. A diagnosis of impaired glucose tolerance or gestational diabetes is a strong predictor for future development of NIDDM and should signal appropriate interventions to prevent or delay the progression to NIDDM. NIDDM is frequently associated with other conditions such as hypertension, hypertriglyceridemia and decreased high-density lipoprotein which are additional risk factors for atherosclerosis and cardiovascular disease. The 'insulin resistance syndrome', which includes obesity, NIDDM, hypertension, hyperinsulinemia and dyslipidemia is a major and increasing cause of morbidity and mortaility in many populations. In addition, people with NIDDM and poor glycemic control may develop severe microvascular complications of diabetes, including retinopathy, nephropathy and neuropathy. Appropriate diet, weight control and increased physical activity will increase insulin sensitivity in insulin resistant patients and are effective treatments for patients with NIDDM or may prevent the development of NIDDM in susceptible individuals. If these measures are unsuccessful, then oral hypoglycemic agents or insulin therapy may be required. Maintaining near normal blood glucose levels will decrease the development or progression of long-term complications of diabetes and should be a major goal of therapy, balancing intensive treatment with the increased risk of severe hypoglycemia. Because of the increasing prevalence of NIDDM in many populations, increased awareness of the disease, surveillance of high-risk populations and early diagnosis and treatment are all important in reducing the morbidity associated with this disease. RP HORTON, ES (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 89 TC 8 Z9 9 U1 0 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD AUG PY 1995 VL 28 SU S BP S3 EP S11 DI 10.1016/0168-8227(95)01087-T PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RV476 UT WOS:A1995RV47600002 PM 8529517 ER PT J AU DAVALLI, AM BOSCHETTI, E RHODES, C SKELLY, R WEIR, GC LIPES, MA AF DAVALLI, AM BOSCHETTI, E RHODES, C SKELLY, R WEIR, GC LIPES, MA TI TRANSGENIC ENGINEERING OF NON-ISLET CELLS FOR THE TREATMENT OF IDDM SO DIABETOLOGIA LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A55 EP A55 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18400210 ER PT J AU DONAGHUE, VM FIELDING, RA GIURINI, JM MULLOOLY, CA KISTLER, JA HORTON, ES VEVES, A AF DONAGHUE, VM FIELDING, RA GIURINI, JM MULLOOLY, CA KISTLER, JA HORTON, ES VEVES, A TI THE EFFECT OF DIABETES AND NEUROPATHY IN THE EXERCISING CAPACITY OF ATHLETICALLY-TRAINED SUBJECTS SO DIABETOLOGIA LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEACONESS JOSLIN FOOT CTR,BOSTON,MA 02115. BOSTON UNIV,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A52 EP A52 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18400199 ER PT J AU GIORGINO, F LAVIOLA, L MONTRONE, C SMITH, RJ AF GIORGINO, F LAVIOLA, L MONTRONE, C SMITH, RJ TI CLONING OF A NOVEL UBIQUITIN-CONJUGATING ENZYME THAT ASSOCIATES WITH THE GLUT-4 GLUCOSE-TRANSPORTER SO DIABETOLOGIA LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA. IST CLIN MED ENDOCRINOL & MALATTIE METAB,BARI,ITALY. RI Giorgino, Francesco/K-7262-2016 OI Giorgino, Francesco/0000-0001-7372-2678 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A9 EP A9 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18400025 ER PT J AU GIURINI, JM SARNOW, MR DONAGHUE, VM ROSENBLUM, BI CHRZAN, JS HABERSHAW, GM VEVES, A AF GIURINI, JM SARNOW, MR DONAGHUE, VM ROSENBLUM, BI CHRZAN, JS HABERSHAW, GM VEVES, A TI IN-SHOE FOOT PRESSURE RELIEF ACHIEVED BY SPECIALLY DESIGNED FOOTWEAR IN HIGH-RISK DIABETIC-PATIENTS SO DIABETOLOGIA LA English DT Meeting Abstract C1 DEACONESS JOSLIN FOOT CTR,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A273 EP A273 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18401053 ER PT J AU KING, GL BURSELL, SE ISHII, H TAKAGI, C KUNISAKI, M JIROUSEK, MR KOYA, D AF KING, GL BURSELL, SE ISHII, H TAKAGI, C KUNISAKI, M JIROUSEK, MR KOYA, D TI NORMALIZATION OF VASCULAR CELL GENE-EXPRESSION AND BLOOD-FLOW BY SPECIFIC INHIBITORS OF DIACYLGLYCEROL-PROTEIN KINASE-C SO DIABETOLOGIA LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A261 EP A261 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18400987 ER PT J AU LOGOLUSO, F DAVALLI, A NAPOLI, R SMITH, RJ GIROGINO, R WEIR, GC GIORGINO, F AF LOGOLUSO, F DAVALLI, A NAPOLI, R SMITH, RJ GIROGINO, R WEIR, GC GIORGINO, F TI ISLET TRANSPLANTATION RESTORES ALTERED INSULIN SIGNALING IN SKELETAL-MUSCLE AND HEART OF STREPTOZOTOCIN-DIABETIC RATS SO DIABETOLOGIA LA English DT Meeting Abstract C1 IST CLIN MED ENDOCRINOL & MALATTIE METAB,BARI,ITALY. JOSLIN DIABET CTR,BOSTON,MA. RI Giorgino, Francesco/K-7262-2016 OI Giorgino, Francesco/0000-0001-7372-2678 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A86 EP A86 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18400331 ER PT J AU NOMA, Y BONENRWEIR, S LATIMER, JB DAVALLI, AM WEIR, GC AF NOMA, Y BONENRWEIR, S LATIMER, JB DAVALLI, AM WEIR, GC TI BETA-CELL GLUCOKINASE IS TRANSLOCATED BY ACUTE GLUCOSE STIMULATION SO DIABETOLOGIA LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A107 EP A107 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18400412 ER PT J AU PATTI, ME BRAYBRAMBILLA, F KAHN, CR LUZI, L AF PATTI, ME BRAYBRAMBILLA, F KAHN, CR LUZI, L TI RESISTANCE TO INSULIN EFFECTS ON BOTH PROTEIN AND GLUCOSE-METABOLISM IN THE OBESE ZUCKER RAT SO DIABETOLOGIA LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A138 EP A138 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18400534 ER PT J AU VEVES, A DONAGHUE, VM SARNOW, MR GIURINI, JM CAMPBELL, DR LOGERFO, FW AF VEVES, A DONAGHUE, VM SARNOW, MR GIURINI, JM CAMPBELL, DR LOGERFO, FW TI REVERSAL OF HYPOXIA BY REVASCULARIZATION IN DIABETIC-PATIENTS - ANY EFFECT IN THE PERIPHERAL-NERVE FUNCTION SO DIABETOLOGIA LA English DT Meeting Abstract C1 HARVARD UNIV,DEACONESS JOSLIN FOOT CTR,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A231 EP A231 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18400892 ER PT J AU ZANGEN, DH MILLER, CP SMITH, FE LISSAUER, ME WEIR, GC HABENER, JF BONNERWEIR, S AF ZANGEN, DH MILLER, CP SMITH, FE LISSAUER, ME WEIR, GC HABENER, JF BONNERWEIR, S TI INCREASED ISLET AND DUCTAL INSULIN PROMOTER FACTOR-1/IDX-1 EXPRESSION IN PANCREATIC REGENERATION SO DIABETOLOGIA LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A45 EP A45 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18400172 ER PT J AU LANG, J NISHIMOTO, I OKAMOTO, T REGAZZI, R KIRALY, C WELLER, U WOLLHEIM, CB AF LANG, J NISHIMOTO, I OKAMOTO, T REGAZZI, R KIRALY, C WELLER, U WOLLHEIM, CB TI DIRECT CONTROL OF EXOCYTOSIS BY RECEPTOR-MEDIATED ACTIVATION OF THE HETEROTRIMERIC GTPASES G(I) AND G(O) OR BY THE EXPRESSION OF THEIR ACTIVE G-ALPHA SUBUNITS SO EMBO JOURNAL LA English DT Article DE CALCIUM; EPINEPHRINE; EXOCYTOSIS; G-PROTEINS; INSULIN ID PERMEABILIZED HIT-T15 CELLS; GTP-BINDING PROTEIN-G(O); INSULIN-SECRETION; REGULATED SECRETION; HORMONAL INHIBITION; PANCREATIC-ISLETS; CHROMAFFIN CELLS; GOLGI MEMBRANES; CYCLIC-AMP; FREE CA-2+ AB The exocytotic release of potent hormones is a tightly controlled process. Its direct regulation without the involvement of second messengers would ensure rapid signal processing. In streptolysin O-permeabilized insulin-secreting cells, a preparation allowing dialysis of cytosolic macromolecules, activation of alpha(2)-adrenergic receptors caused pertussis toxin-sensitive inhibition of calcium-induced exocytosis. This inhibition was mimicked very efficiently by the use of specific receptor-mimetic peptides, indicating the involvement of G(i) and, to a lesser extent, of G(o). The regulation was exerted beyond the ATP-dependent step of exocytosis. In addition, low nanomolar amounts of pre-activated G(i)/G(o) directly inhibited exocytosis. As transient overexpression of constitutively active mutants of G alpha(i)1, G alpha(i)2, G alpha(i)3 and G alpha(o)2 but not of G alpha(o)1 reproduced this regulation, the G alpha subunit alone is sufficient to induce inhibition. These results define exocytosis as an effector for heterotrimeric G-proteins and delineate the properties of the transduction pathway. C1 MASSACHUSETTS GEN HOSP EAST, DEPT MED, BOSTON, MA USA. UNIV MAINZ, INST MED MIKROBIOL, W-6500 MAINZ, GERMANY. RP UNIV GENEVA, DIV BIOCHEM CLIN, CH-1211 GENEVA 4, SWITZERLAND. RI Lang, Jochen/B-1215-2010; Lang, Jochen/F-5782-2014 OI Lang, Jochen/0000-0001-6847-5641; Lang, Jochen/0000-0001-6847-5641 NR 56 TC 116 Z9 116 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD AUG 1 PY 1995 VL 14 IS 15 BP 3635 EP 3644 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RN943 UT WOS:A1995RN94300005 PM 7641683 ER PT J AU IKEDA, H BEAUCHAMP, RL YOSHIMOTO, T YANDELL, DW AF IKEDA, H BEAUCHAMP, RL YOSHIMOTO, T YANDELL, DW TI DETECTION OF HETEROZYGOUS MUTATION IN THE RETINOBLASTOMA GENE IN A HUMAN PITUITARY-ADENOMA USING PCR-SSCP ANALYSIS AND DIRECT SEQUENCING SO ENDOCRINE PATHOLOGY LA English DT Article DE RETINOBLASTOMA GENE; MUTATION; HUMAN; PITUITARY ADENOMA; SSCP ID OSTEO-SARCOMA; DNA-SEQUENCE; C-MYC; TUMORS; PROTEIN; EXPRESSION; ORIGIN AB Genomic deoxyribonucleic acid from surgical specimens of 25 pituitary adenomas was screened for the presence of mutations in the tumor suppressor gene, retinoblastoma gene, using polymerase chain reaction and single-strand conformation polymorphism analysis, followed by direct deoxyribonucleic acid sequencing. Mutation causing an amino acid change was found in one of the 25 pituitary adenomas. The mutation site was in exon 19 (codon 621) of the retinoblastoma gene. In addition, there were three types of silent mutations in introns of the gene. The patient in whom the retinoblastoma mutation was identified had a tumor with high clinical malignancy, a high percentage of c-myc protein-labeled cells, and a diagnosis of plurihormonal pituitary adenoma based on the presence of cells immunoreactive for five pituitary hormones. This article suggests that point mutation of retinoblastoma gene is rare in human pituitary adenomas but may provide a marker for aggressive pituitary adenoma. C1 HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RP IKEDA, H (reprint author), TOHOKU UNIV,SCH MED,DEPT NEUROSURG,1-1 SEIRYO MACHI,SENDAI,MIYAGI 980,JAPAN. NR 24 TC 10 Z9 11 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 1046-3976 J9 ENDOCR PATHOL JI Endocr. Pathol. PD AUG PY 1995 VL 6 IS 3 BP 189 EP 196 DI 10.1007/BF02739882 PG 8 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA RP114 UT WOS:A1995RP11400003 ER PT J AU UY, HL GUISE, TA DELAMATA, J TAYLOR, SD STORY, BM DALLAS, MR BOYCE, BF MUNDY, GR ROODMAN, GD AF UY, HL GUISE, TA DELAMATA, J TAYLOR, SD STORY, BM DALLAS, MR BOYCE, BF MUNDY, GR ROODMAN, GD TI EFFECTS OF PARATHYROID-HORMONE (PTH)-RELATED PROTEIN AND PTH ON OSTEOCLASTS AND OSTEOCLAST PRECURSORS IN-VIVO SO ENDOCRINOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; BONE-MARROW CULTURES; HUMORAL HYPERCALCEMIA; IMMUNORADIOMETRIC ASSAY; OSTEOTROPIC HORMONES; SYNTHETIC PEPTIDE; CELL-FORMATION; ORGAN-CULTURE; RESORPTION; MALIGNANCY AB Increased production of PTH-related protein (PTHrP) and PTH is frequently responsible for hypercalcemia and its associated morbidity. However, it is unclear whether these peptides produce identical effects on cells in the osteoclast lineage in vivo. To examine the effects of continuous in vivo exposure to these factors on both the osteoclast precursors and mature osteoclasts, we inoculated Chinese hamster ovarian cells expressing PTH-(1-84), PTHrP-(1-141), or nontransfected Chinese hamster ovarian cells into nude mice. The effects of these tumors on blood ionized calcium, plasma PTH and PTHrP concentrations, and osteoclast formation were then determined. PTH and PTHrP tumor-bearing mice became hypercalcemic (1.90 +/- 0.04 and 1.97 +/- 0.16 mmol/liter, respectively) compared with control mice (1.29 +/- 0.015 mmol/liter). After 4 days of hypercalcemia, mice were killed, and bone marrow cells were harvested to examine cells at three discrete stages of osteoclast development: multipotent osteoclast precursors, the granulocyte/macrophage colony-forming unit; more committed marrow mononuclear osteoclast precursors; and mature osteoclasts. Neither PTH nor PTHrP had an effect on granulocyte/macrophage colony-forming unit, but similarly increased the number of more committed mononuclear osteoclast progenitors as well as mature osteoclasts in the calvaria. No differences were detected between the effects of PTH and PTHrP on cells in the osteoclast lineage in vivo. Thus, PTH and PTHrP appear to affect only more differentiated cells in the osteoclast lineage, and the differences in osteoclastic bone resorption between primary hyperparathyroidism and humoral hypercalcemia of malignancy are probably due to mechanisms other than effects on osteoclast precursor cells in vivo. C1 AUDIE L MURPHY MEM VET ADM MED CTR,RES SERV 151,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV ENDOCRINOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV HEMATOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. FU NCI NIH HHS [CA-40035]; NIADDK NIH HHS [AM-35188]; NIAMS NIH HHS [AR-39529] NR 37 TC 30 Z9 30 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1995 VL 136 IS 8 BP 3207 EP 3212 DI 10.1210/en.136.8.3207 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RL632 UT WOS:A1995RL63200006 PM 7628353 ER PT J AU JONGEN, JWJM WILLEMSTEINVANHOVE, EC VANDERMEER, JM BOS, MP JUPPNER, H SEGRE, GV ABOUSAMRA, AB FEYEN, JHM HERRMANNERLEE, MPM AF JONGEN, JWJM WILLEMSTEINVANHOVE, EC VANDERMEER, JM BOS, MP JUPPNER, H SEGRE, GV ABOUSAMRA, AB FEYEN, JHM HERRMANNERLEE, MPM TI DOWN-REGULATION OF THE RECEPTOR FOR PARATHYROID-HORMONE (PTH) AND PTH-RELATED PEPTIDE BY TRANSFORMING GROWTH-FACTOR-BETA IN PRIMARY FETAL-RAT OSTEOBLASTS SO ENDOCRINOLOGY LA English DT Article ID CYCLIC-AMP; CELLS; BINDING; BONE; EXPRESSION; CULTURES; INVITRO; CALCIUM; CAMP AB We studied the effects of transforming growth factor-beta 2 (TGF beta 2) on the level of PTH/PTH-related peptide (PTHrP) receptor messenger RNA (mRNA), PTHrP binding, and PTH-stimulated cAMP accumulation in cultured osteoblasts derived from fetal rat calvariae (ROB). When ROB were pretreated with TGF beta 2 at concentrations ranging from 1-100 pM for 24 h, dose-dependent decreases in the level of PTH/PTHrP receptor mRNA, PTHrP binding, and PTH-stimulated cAMP accumulation were observed. For the PTH/PTHrP receptor mRNA level and PTH-stimulated cAMP accumulation, the half-maximal effective concentration was approximately 4 pM. For the inhibition of PTHrP binding, the half-maximal effective concentration was much higher. A 50% decrease in both PTH/PTHrP receptor mRNA level and PTH-stimulated cAMP accumulation was obtained when ROB were treated with 100 pM TGF beta 2 for 4 h. A comparable decrease in PTHrP binding was only observed after 24 h of incubation with 100 pM TGF beta 2. Actinomycin D induced a rapid decrease in the PTH/PTHrP receptor mRNA level (70% after 4 h), indicating a half-life for the receptor mRNA of 2-3 h. Under the same conditions, PTHrP binding and PTH-stimulated cAMP accumulation did not change. When ROB were treated with cycloheximide for the same period, only a small decrease in PTHrP binding (20%) was observed, suggesting that PTH/PTHrP receptors do not have a rapid turnover. Cycloheximide also reduced PTH-stimulated cAMP production; after coincubation of cycloheximide with TGF beta 2, this inhibition was smaller than that in ROB cultures treated with TGF beta 2 exclusively. From these observations we conclude that TGF beta 2 induces a decrease in steady state levels of PTH/PTHrP receptor mRNA that results in decreased PTHrP receptor binding. The PTH-stimulated cAMP accumulation is at least to some extent independent of the PTH/PTHrP receptor availability. Furthermore, there is a high turnover of PTH/PTHrP receptor mRNA, whereas turnover of the receptor protein is much slower. Finally, protein synthesis is required for TGF beta 2-induced desensitization of cAMP responsiveness to PTH. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. SANDOZ PHARMA AG,PRECLIN UNIT,BASEL,SWITZERLAND. RP JONGEN, JWJM (reprint author), LEIDEN UNIV,CELL BIOL & HISTOL LAB,RIJNSBURGERWEG 10,BLDG 55,2333 AA LEIDEN,NETHERLANDS. NR 30 TC 23 Z9 24 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1995 VL 136 IS 8 BP 3260 EP 3266 DI 10.1210/en.136.8.3260 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RL632 UT WOS:A1995RL63200013 PM 7628359 ER PT J AU WALKER, WH FUCCI, L HABENER, JF AF WALKER, WH FUCCI, L HABENER, JF TI EXPRESSION OF THE GENE ENCODING TRANSCRIPTION FACTOR CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE (CAMP) RESPONSE ELEMENT-BINDING PROTEIN (CREB) - REGULATION BY FOLLICLE-STIMULATING HORMONE-INDUCED CAMP SIGNALING IN PRIMARY RAT SERTOLI CELLS SO ENDOCRINOLOGY LA English DT Article ID RECEPTOR MESSENGER-RNA; RIBONUCLEIC-ACID; C-FOS; PROMOTER; MONOPHOSPHATE; CONTAINS; CLONING; DOMAINS; EXON; SPERMATOGENESIS AB The somatic Sertoli cells of the testis are major targets for FSH and are important for the regulation of spermatogenesis. The binding of FSH to Sertoli cells activates the cAMP-dependent protein kinase A signaling pathway, resulting in phosphorylation of the cAMP response element-binding protein (CREB), which is required to transactivate genes containing cAMP response elements (CREs). Here we show that the addition of forskolin to cultured primary Sertoli cells results in the phosphorylation of CREB within 2-5 min. Phospho-CREB levels remain elevated with continued forskolin stimulation, but fall by 60% within 5 min after the removal of forskolin. In addition, we found that 8-bromo-cAMP induces CREB RNA accumulation in the Sertoli cells. Transient transfections of primary Sertoli cells with CREB promoter-chloramphenicol acetyltransferase reporter plasmids define a conserved 300-base pair region of the CREB promoter surrounding the transcription start site that is required for both basal and cAMP-inducible expression of the CREB gene. This region of the promoter contains three Sp1-binding sites flanking the transcription initiation site and two CREs located 65 and 85 base pairs downstream of the transcription initiation site. We show that the Sp1 motifs bind Sp1 in Sertoli extracts and contribute to basal promoter activity, and that the CREs bind CREB and are essential for cAMP induction of CREB gene transcription. These findings support the model of FSH- and cAMP-mediated CREB autoregulation of its own promoter and may explain the dramatic stage-specific oscillations in Sertoli cells of CREB messenger RNA levels during the 12-day cycles of spermatogenesis in rat seminiferous tubules. C1 MASSACHUSETTS GEN HOSP, HOWARD HUGHES MED INST, MOLEC ENDOCRINOL LAB, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-25532] NR 62 TC 88 Z9 89 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1995 VL 136 IS 8 BP 3534 EP 3545 DI 10.1210/en.136.8.3534 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RL632 UT WOS:A1995RL63200047 PM 7628390 ER PT J AU MORRIS, MB LUX, SE AF MORRIS, MB LUX, SE TI CHARACTERIZATION OF THE BINARY INTERACTION BETWEEN HUMAN ERYTHROCYTE PROTEIN-4.1 AND ACTIN SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE ACTIN, COOPERATIVITY; ERYTHROCYTE; PROTEIN 4.1; SPECTRIN ID RABBIT SKELETAL-MUSCLE; BETA-SPECTRIN; HEREDITARY SPHEROCYTOSIS; SELF-ASSOCIATION; MEMBRANE SKELETON; CELL MEMBRANE; BANDS 2.1; F-ACTIN; BINDING; PHALLOIDIN AB The binary interaction between human erythrocyte protein 4.1 and rabbit skeletal muscle F-actin was examined by rapid pelleting of the binary complexes. The binding curves show that the reaction was saturable at approximately one protein 4.1 molecule/actin monomer. The reaction was highly co-operative, displaying a Hill coefficient close to 2. Using a fixed concentration of radiolabelled protein 4.1, and varying the concentration of F-actin, the apparent molar association constant, K-a, was observed to range from 5X10(4) M(-1) to > 10(6) M(-1). The binary interaction between erythrocyte spectrin and actin was also observed to be co-operative under the same conditions. The rate of reaction between protein 4.1 and actin was temperature sensitive in a manner consistent with a high energy of activation. The pelleting assay also showed that the concentration of actin was reduced in the supernatant in the presence of protein 4.1 compared with actin alone, indicating that the critical concentration of actin was lowered in the presence of protein 4.1. Polyvalent anions disrupted the binary interaction between F-actin and protein 4.1, the disruption being consistent with the number of negative charges on these anions at pH 7.5. We postulate that the co-operativity of the binding of protein 4.1 to actin results from a protein 4.1 molecule binding to a single monomer within the filament structure which then promotes conformational changes allowing further protein 4.1 binding. The demonstration of a specific binary association between protein 4.1 and actin suggests that this interaction contributes significantly to the stabilization of the spectrin-actin-protein-4.1 ternary complex. C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA 02115. NR 43 TC 15 Z9 15 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 AUG PY 1995 VL 231 IS 3 BP 644 EP 650 DI 10.1111/j.1432-1033.1995.0644d.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN395 UT WOS:A1995RN39500017 PM 7649164 ER PT J AU GRAYBILL, JR BOCANEGRA, R LUTHER, M AF GRAYBILL, JR BOCANEGRA, R LUTHER, M TI ANTIFUNGAL COMBINATION THERAPY WITH GRANULOCYTE-COLONY-STIMULATING FACTOR AND FLUCONAZOLE IN EXPERIMENTAL DISSEMINATED CANDIDIASIS SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Note ID RISK-FACTORS; CSF; CANDIDEMIA; INFECTION AB The present studies were performed to determine whether any beneficial interaction results from combination therapy with recombinant human granulocyte colony-stimulating factor (GCSF) and fluconazole in disseminated candidiasis in mice. Fluconazole extended survival and reduced tissue counts. GCSF had no direct benefit, but GCSF combined with fluconazole extended survival beyond that for fluconazole alone and reduced renal tissue counts below those for fluconazole alone. Thus, GCSF and fluconazole may be a useful combined therapy for disseminated candidiasis. C1 AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,DIV INFECT DIS,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,RES DEPT,SAN ANTONIO,TX 78284. RP GRAYBILL, JR (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV INFECT DIS,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIAID NIH HHS [N01-AI-25141] NR 15 TC 27 Z9 27 U1 0 U2 0 PU FRIEDR VIEWEG SOHN VERLAG GMBH PI WIESBADEN 1 PA PO BOX 5829, W-6200 WIESBADEN 1, GERMANY SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD AUG PY 1995 VL 14 IS 8 BP 700 EP 703 DI 10.1007/BF01690878 PG 4 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA RV705 UT WOS:A1995RV70500007 PM 8565989 ER PT J AU DANDREA, AD CARROLL, M ZHU, Y MERCHAV, S BARBER, D AF DANDREA, AD CARROLL, M ZHU, Y MERCHAV, S BARBER, D TI THE ERYTHROPOIETIN RECEPTOR IN NORMAL ERYTHROPOIESIS AND DISEASE SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL COLTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1995 VL 23 IS 8 BP 839 EP 839 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA RP116 UT WOS:A1995RP11600337 ER PT J AU DRANOFF, G MULLIGAN, RC AF DRANOFF, G MULLIGAN, RC TI COLONY-STIMULATING FACTOR KNOCKOUTS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. WHITEHEAD INST,CAMBRIDGE,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL COLTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1995 VL 23 IS 8 BP 841 EP 841 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA RP116 UT WOS:A1995RP11600343 ER PT J AU KUFE, DW WEICHSELBAUM, RR AF KUFE, DW WEICHSELBAUM, RR TI EFFECTS OF IRRADIATION ON THE CELL SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. UNIV CHICAGO,CHICAGO,IL 60637. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL COLTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1995 VL 23 IS 8 BP 894 EP 894 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA RP116 UT WOS:A1995RP11600535 ER PT J AU GRIFFIN, JD OKUDA, K SATTLER, M UEMARA, N SALGIA, R AF GRIFFIN, JD OKUDA, K SATTLER, M UEMARA, N SALGIA, R TI MECHANISMS OF TRANSFORMATION BY BCR/ABL IN PRIMARY CML CELLS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CARDEN JENNINGS PUBL COLTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1995 VL 23 IS 8 BP 895 EP 895 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA RP116 UT WOS:A1995RP11600539 ER PT J AU YONEMURA, Y KU, H HIRAYAMA, F OGAWA, M AF YONEMURA, Y KU, H HIRAYAMA, F OGAWA, M TI IL-3 OR IL-1 ABROGATES THE RECONSTITUTING ABILITY OF HEMATOPOIETIC STEM-CELLS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. NR 0 TC 5 Z9 5 U1 0 U2 0 PU CARDEN JENNINGS PUBL COLTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1995 VL 23 IS 8 BP 899 EP 899 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA RP116 UT WOS:A1995RP11600549 ER PT J AU SATTLER, M DURSTIN, MA FRANK, DA OKUDA, K KAUSHANSKY, K SALGIA, R GRIFFIN, JD AF SATTLER, M DURSTIN, MA FRANK, DA OKUDA, K KAUSHANSKY, K SALGIA, R GRIFFIN, JD TI THE THROMBOPOIETIN RECEPTOR C-MPL ACTIVATES JAK2 AND TYK2 TYROSINE KINASES SO EXPERIMENTAL HEMATOLOGY LA English DT Note DE THROMBOPOIETIN; C-MPL; JANUS KINASE; STAT ID VAV PROTOONCOGENE PRODUCT; MOLECULAR-CLONING; INTERFERON-ALPHA; PHOSPHORYLATION; GROWTH; CELLS; TRANSCRIPTION; PROTEINS; MEMBER; FAMILY AB Thrombopoietin (TPO) is a growth and differentiation factor for megakaryocyte-lineage cells. The receptor for TPO, c-MPL, is a member of the hematopoietic cytokine receptor family and has previously been shown to rapidly activate one or more cytoplasmic tyrosine kinases after ligand binding. In this study, we found that activation of the TPO receptor rapidly induced tyrosine phosphorylation of two members of the Jak tyrosine kinase family, JAK2 and TYK2, but not JAK1 or JAK3, in two different factor-dependent hematopoietic cell lines. The activation of both JAK2 and TYK2 was dose- and time-dependent and was associated with rapid tyrosine phosphorylation of a series of STAT proteins including STAT1, STAT3, and STAT5. Gel-shift assays indicated that one or more of these STATs is likely to participate in the formation of specific DNA-binding complexes. The activation of tyrosine kinases and signal propagation through tyrosine phosphorylation are likely to represent important initial steps in mediating the activities of TPO in myeloid cells. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT NEUROL,DIV NEUROSCI,BOSTON,MA 02115. UNIV WASHINGTON,DIV HEMATOL RM10,SEATTLE,WA 98195. FU NCI NIH HHS [CA 36167, CA 60821] NR 63 TC 146 Z9 148 U1 0 U2 2 PU CARDEN JENNINGS PUBL COLTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1995 VL 23 IS 9 BP 1040 EP 1048 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA RP118 UT WOS:A1995RP11800014 PM 7543416 ER PT J AU KINDON, H POTHOULAKIS, C THIM, L LYNCHDEVANEY, G PODOLSKY, DK AF KINDON, H POTHOULAKIS, C THIM, L LYNCHDEVANEY, G PODOLSKY, DK TI TREFOIL PEPTIDE PROTECTION OF INTESTINAL EPITHELIAL BARRIER FUNCTION - COOPERATIVE INTERACTION WITH MUCIN GLYCOPROTEIN SO GASTROENTEROLOGY LA English DT Article ID RAT SMALL-INTESTINE; BEAN PHASEOLUS-VULGARIS; DIFFICILE TOXIN-A; SPASMOLYTIC POLYPEPTIDE PSP; INFLAMMATORY BOWEL-DISEASE; LECTIN-INDUCED LESIONS; GROWTH-FACTOR-BETA; ELECTROLYTE TRANSPORT; MUCOSAL INJURY; RESTITUTION AB Background and Aims: Goblet cells secrete a combination of trefoil peptides and mucin glycoproteins to form a continuous gel on the mucosal surface. The functional effects of these products remain uncertain. Methods: Trefoil peptides and/or mucin glycoproteins were added to Transwell monolayers of the human colonic cancer-derived T84 cell line. Intact monolayers permitted penetration of <4% of the inert marker [H-3]mannitol at 4 hours. Exposure to the toxic lectin phytohemagglutinin (1 mg/mL), oleic acid (8 mmol/L) and taurocholic acid (12 mmol/L), or Clostridium difficile toxin A (0.7 mu g/mL) resulted in loss of barrier function with 36%, 62%, and 45% of [H-3]mannitol penetration, respectively. Results: Addition of recombinant human intestinal trefoil factor in physiological concentrations (1-5 mu g/mu L) resulted in attenuation of the damage to monolayer integrity by up to 52%. Protection was enhanced (up to 95%) by the copresence of human colonic mucin glycoproteins. Similar effects were observed when rat intestinal trefoil factor or human spasmolysin, another human trefoil peptide, were added alone or in the presence of human mucin glycoproteins. Conversely, mucin glycoproteins isolated from the rat colon or stomach facilitated protection when added with human spasmolysin or human intestinal trefoil factor. Conclusions: Trefoil peptides and mucin glycoproteins protect gastrointestinal mucosa from a variety of insults. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. BOSTON UNIV,UNIV HOSP,SCH MED,GASTROENTEROL SECT,BOSTON,MA. NOVO NORDISK AS,COPENHAGEN,DENMARK. FU NIDDK NIH HHS [DK 34503, DK 41557, DK 43351] NR 37 TC 275 Z9 287 U1 5 U2 15 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 1995 VL 109 IS 2 BP 516 EP 523 DI 10.1016/0016-5085(95)90340-2 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RM508 UT WOS:A1995RM50800022 PM 7615201 ER PT J AU HENSKE, EP NEUMANN, HPH SCHEITHAUER, BW HERBST, EW SHORT, MP KWIATKOWSKI, DJ AF HENSKE, EP NEUMANN, HPH SCHEITHAUER, BW HERBST, EW SHORT, MP KWIATKOWSKI, DJ TI LOSS OF HETEROZYGOSITY IN THE TUBEROUS SCLEROSIS (TSC2) REGION OF CHROMOSOME BAND 16P13 OCCURS IN SPORADIC AS WELL AS TSC-ASSOCIATED RENAL ANGIOMYOLIPOMAS SO GENES CHROMOSOMES & CANCER LA English DT Note AB Angiomyolipomas (AMLs) are renal tumors that occur both sporadically and in association with tuberous sclerosis (TSC). TSC is an autosomal dominant disorder characterized by hamartomatous lesions in multiple organs. Two TSC loci are recognized: TSC1 on 9q34 and TSC2 on 16p13. Loss of heterozygosity (LOH) at the TSC1 and TSC2 loci in lesions from TSC patients has recently been reported. Lesions that are not associated with TSC have not been previously examined for LOH at the TSC loci. We analyzed 29 renal angiomyolipomas; from patients without a history of TSC. Three tumors demonstrated LOH on 16p13. This is the first report indicating that mutations in TSC2 occur in tumors of patients who do not have TSC. We also found LOH on 1 bp 13 in 5 of 8 TSC-associated AMLs. Two of these tumors were from a single patient and demonstrated different regions of LOH. These findings support the hypothesis that the TSC2 gene functions as a tumor suppressor. C1 BRIGHAM & WOMENS HOSP, DIV HEMATOL ONCOL, BOSTON, MA 02115 USA. UNIV FREIBURG, DEPT HYPERTENS & NEPHROL, FREIBURG, GERMANY. UNIV FREIBURG, DEPT PATHOL, FREIBURG, GERMANY. MAYO CLIN, DIV ANAT PATHOL, ROCHESTER, MN USA. MASSACHUSETTS GEN HOSP, DEPT NEPHROL, BOSTON, MA 02114 USA. RP HENSKE, EP (reprint author), BRIGHAM & WOMENS HOSP, DIV EXPTL MED, 221 LONGWOOD AVE, LMRC 301, BOSTON, MA 02115 USA. FU NINDS NIH HHS [NS01571, NS31535] NR 15 TC 172 Z9 176 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-2257 EI 1098-2264 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD AUG PY 1995 VL 13 IS 4 BP 295 EP 298 DI 10.1002/gcc.2870130411 PG 4 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA RL890 UT WOS:A1995RL89000010 PM 7547639 ER PT J AU CANNISTRA, SA OTTENSMEIER, C NILOFF, J ORTA, B DICARLO, J AF CANNISTRA, SA OTTENSMEIER, C NILOFF, J ORTA, B DICARLO, J TI EXPRESSION AND FUNCTION OF BETA-1 AND ALPHA-V-BETA-3 INTEGRINS IN OVARIAN-CANCER SO GYNECOLOGIC ONCOLOGY LA English DT Article ID MURINE MELANOMA-CELLS; EXPERIMENTAL METASTASIS; EXTRACELLULAR-MATRIX; SYNTHETIC PEPTIDE; ADHESION; RECEPTOR; ALPHA-6-BETA-4; FIBRONECTIN; CARCINOMA; ANTIBODY AB Ovarian cancer cells disseminate by implanting onto the peritoneal mesothelial cell surface of the abdominal cavity. A common feature of these peritoneal implants is the presence of tumor cell. invasion into the submesothelial extracellular matrix (ECM). In view of the important role of integrins in ECM recognition and cell migration, we were interested in defining the pattern of integrin expression and function in ovarian cancer cell lines and primary tissue samples. The beta 1 integrin chain was expressed by CAOV-3, SKOV-3, OVCAR-3, and SW626 ovarian cancer cell lines, associated with expression of alpha 1, -2, -3, -5, and -6 chains. The alpha 4 chain was also expressed by two of the four Lines. In addition to beta 1 integrins, the alpha v beta 3 integrin was also expressed, although there was no expression of beta 2, -4, and -7 chains. Immunoprecipitation of surface-labeled CAOV-3 cells with an anti-beta 1 antibody revealed a band at approximate to 110-130 kDa consistent with the known molecular mass of the beta 1 chain, as well as several associated bands consistent with noncovalently linked integrin cr chains. A similar pattern of beta 1 and alpha v beta 3 integrin expression was observed for primary ovarian cancer tissue samples. Ovarian cancer cell lines exhibited significant binding to collagen type I and laminin which was primarily mediated by beta 1 integrins. In contrast, ovarian cancer cell binding to fibronectin was mediated by both alpha 5 beta 1 and alpha v beta 3 integrins. Even though mesothelial cells were observed to express fibronectin mRNA and protein, binding of ovarian cancer cells to peritoneal mesothelium was not blocked by neutralizing antibodies to beta 1 or alpha v beta 3 integrins. These data suggest that functional integrins are commonly expressed by ovarian cancer cells, although they do not appear to mediate ovarian cancer cell implantation onto peritoneal mesothelium. The role that integrins play in the invasion of ovarian cancer cells into the submesothelial ECM deserves further investigation. (C) 1995 Academic Press, Inc. RP CANNISTRA, SA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115, USA. RI Ottensmeier, Christian/E-8131-2012 OI Ottensmeier, Christian/0000-0003-3619-1657 FU NCI NIH HHS [CA 60670] NR 33 TC 101 Z9 104 U1 1 U2 4 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 AUG PY 1995 VL 58 IS 2 BP 216 EP 225 DI 10.1006/gyno.1995.1214 PG 10 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA RM506 UT WOS:A1995RM50600014 PM 7542622 ER PT J AU SUIT, H SPIRO, I AF SUIT, H SPIRO, I TI RADIATION AS A THERAPEUTIC MODALITY IN SARCOMAS OF THE SOFT-TISSUE SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID POSTOPERATIVE RADIOTHERAPY; RADIOBIOLOGICAL CHARACTERIZATION; PREOPERATIVE RADIATION; SURGICAL MARGINS; LOCAL-CONTROL; IRRADIATION; SURGERY; EXTREMITY; BRACHYTHERAPY; MANAGEMENT AB Management of the primary lesion in patients with soft tissue sarcomas is combined modality in the majority of instances. Themodalities are surgery and irradiation. Radical surgery as currently practiced in major oncology centers does not achieve local control in an important proportion of patients. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP SUIT, H (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,100 BLOSSOM ST,COX 302,BOSTON,MA 02114, USA. NR 45 TC 17 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 1995 VL 9 IS 4 BP 733 EP 746 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA RP163 UT WOS:A1995RP16300004 PM 7490238 ER PT J AU OBERLEY, TD SEMPF, JM OBERLEY, LW AF OBERLEY, TD SEMPF, JM OBERLEY, LW TI IMMUNOHISTOCHEMICAL LOCALIZATION OF ANTIOXIDANT ENZYMES DURING HAMSTER-KIDNEY DEVELOPMENT SO HISTOCHEMICAL JOURNAL LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; SYRIAN-HAMSTER; SUPEROXIDE DISMUTASES; RAT; TISSUES; DIFFERENTIATION; ISOENZYMES; EPITHELIUM; SUBSTRATE; MICE AB Immunolocalization studies of hamster kidney development were performed using polyclonal antibodies to antioxidant enzymes, including antibodies to copper, zinc and manganese superoxide dismutases, catalase, glutathione peroxidase and glutathione S-transferases and their subunits. Antibodies to extracellular matrix proteins were also studied to determine the temporal sequence between expression of immunoreactive protein for basement membrane proteins, which serve as markers of embryonic induction of nephron development, and antioxidant enzyme expression in kidney development. Immunoreactive proteins for antioxidant enzymes were not detectable in the developing kidney until after extracellular matrix proteins had been deposited. However, immunoreactive proteins for the antioxidant enzymes copper, zinc and manganese superoxide dismutases, catalase, and cw class glutathione S-transferase Ya subunit were detected in renal tubules before birth. mu, class glutathione S-transferase subunits Yb-1 and Yb-2 stained transitional epithelium at high levels before birth. Our results indicate: (1) each type of kidney cell has a unique antioxidant enzyme profile, (2) antioxidant enzymes are expressed in different types of cell at different times during development, but antioxidant enzyme immunoreactive protein was not present until after immunoreactive proteins for extracellular matrix molecules were detected, and (3) certain antioxidant enzymes are present before birth, indicating that high oxygen tension present at birth is not crucial for induction of immunoreactive protein. C1 UNIV WISCONSIN,SCH MED,DEPT PATHOL,MADISON,WI 53705. UNIV IOWA,COLL MED,RADIAT RES LAB,IOWA CITY,IA 52242. RP OBERLEY, TD (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,PATHOL SERV,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. FU PHS HHS [41267] NR 27 TC 8 Z9 8 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0018-2214 J9 HISTOCHEM J JI Histochem.J. PD AUG PY 1995 VL 27 IS 8 BP 575 EP 586 PG 12 WC Cell Biology SC Cell Biology GA RP232 UT WOS:A1995RP23200002 PM 8550376 ER PT J AU WANG, F LI, XP ANNIS, B FAUSTMAN, DL AF WANG, F LI, XP ANNIS, B FAUSTMAN, DL TI TAP-1 AND TAP-2 GENE-THERAPY SELECTIVELY RESTORES CONFORMATIONALLY DEPENDENT HLA CLASS-I EXPRESSION IN TYPE-I DIABETIC CELLS SO HUMAN GENE THERAPY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; PUTATIVE PEPTIDE TRANSPORTER; RMA-S CELLS; ANTIGEN PRESENTATION; LYMPHOID-CELLS; VIRAL-ANTIGEN; T-CELLS; MHC; MOLECULES; REGION AB Genetic susceptibility to many autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM) is statistically linked to the HLA class II region of chromosome 6. However, a distinguishing feature of patients with HLA class II-linked autoimmune disease is an abnormally low density of conformationally correct, self-peptide filled HLA class I molecules on the lymphocyte cell surface. The transporters associated with antigen processing (Tap-1 and Tap-2) are essential for normal class I expression and presentation of intracellular peptides, and these genes are located within the HLA class II region. The aims of this project were to determine if Tap genes could be implicated in the defective class I expression associated with IDDM by using a novel Epstein-Barr virus (EBV)-mediated gene transfer system to introduce a cloned, normal Tap-2 or Tap-1 gene into B cell lines from normal and IDDM patients and analyzing the effect on conformationally dependent class I expression. The results show that Tap-2 gene transfer in B cells from 40% of randomly selected IDDM patients increased expression of conformationally correct, cell-surface class I molecules to levels comparable with similarly treated B cells from normal control individuals. B cells from another 40% of IDDM patients responded to Tap-1 gene transfer. These effects were specific because B cells from normal individuals did not respond to Tap-1 or Tap-2 gene transfer with increased class I expression, and B cells from IDDM patients responding to Tap-2 gene transfer did not respond to Tap-1 gene transfer and vice versa. Thus, these complementation studies identify distinct, non-overlapping subsets of IDDM patients whose class I defect in B cells can be reversed by Tap-1 or Tap-2 gene transfer. The increase in class I expression induced by Tap gene transfer is associated with a reduction in the number of peptide-empty class I molecules as demonstrated by the response to exogenous peptide loading. Furthermore, the increase in self-peptide filled class I molecules induced by Tap gene transfer into B cells from IDDM patients is associated with restored antigen presentation to autologous T cells. These studies conclude that Tap gene dysfunctions may contribute to the defect in class I phenotype and antigen presentation demonstrated by IDDM patients. Defective presentation of self-peptides by antigen presenting cells can lead to the failed T cell education and tolerance to self antigens evident in IDDM. These studies functionally identify HLA class II region genes that contribute to an immunologic defect in IDDM. C1 BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,DIABET UNIT,IMMUNOBIOL LAB,BOSTON,MA 02129. FU NCI NIH HHS [CA52244] NR 46 TC 23 Z9 23 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 AUG PY 1995 VL 6 IS 8 BP 1005 EP 1017 DI 10.1089/hum.1995.6.8-1005 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA RP882 UT WOS:A1995RP88200004 PM 7578413 ER PT J AU LUCENTE, D CHEN, HM SHEA, D SAMEC, SN RUTTER, M CHRAST, R ROSSIER, C BUCKLER, A ANTONARAKIS, SE MCCORMICK, MK AF LUCENTE, D CHEN, HM SHEA, D SAMEC, SN RUTTER, M CHRAST, R ROSSIER, C BUCKLER, A ANTONARAKIS, SE MCCORMICK, MK TI LOCALIZATION OF 102 EXONS TO A 2.5-MB REGION INVOLVED IN DOWN-SYNDROME SO HUMAN MOLECULAR GENETICS LA English DT Article ID HUMAN GENOME; CHROMOSOME-21; MIDLINE; GENES AB Exon amplification has been applied to a 2.5 Mb region of chromosome 21 that has been associated with some features of Down syndrome (DS). Identification of the majority of genes from this region will facilitate the correlation of the over-expression of particular genes with specific phenotypes of DS, Over 100 gene fragments have been isolated from this 2.5 Mb segment. The exons have been characterized by sequence analysis, comparison with public databases and expansion to cDNA clones, Localization of the exons to chromosome 21 has been determined by hybridization to genomic Southern blots and to YAC and cosmid clones representing the region. This has resulted in a higher resolution physical map with a marker approximately every 25 kb. This integrated physical and transcript map will be valuable for fine mapping of DNA from individuals with partial aneuploidy of chromosome 21 as well as for assessing and ultimately generating a complete gene map of this segment of the genome. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,MOLEC NEUROGENET UNIT,BOSTON,MA 02140. HARVARD UNIV,SCH MED,BOSTON,MA 02140. UNIV GENEVA,SCH MED,DEPT GENET & MICROBIOL,GENES R US LAB HUMAN MOLEC GENET,GENEVA,SWITZERLAND. UNIV GENEVA,CANTONAL HOSP,DIV MED GENET,GENEVA,SWITZERLAND. RI Antonarakis, Stylianos/N-8866-2014 OI Antonarakis, Stylianos/0000-0001-8907-5823 FU NINDS NIH HHS [NS32675] NR 26 TC 47 Z9 47 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 AUG PY 1995 VL 4 IS 8 BP 1305 EP 1311 DI 10.1093/hmg/4.8.1305 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RM340 UT WOS:A1995RM34000008 PM 7581367 ER PT J AU ATTIE, T PELET, A EDERY, P ENG, C MULLIGAN, LM AMIEL, J BOUTRAND, L BELDJORD, C NIHOULFEKETE, C MUNNICH, A PONDER, BAJ LYONNET, S AF ATTIE, T PELET, A EDERY, P ENG, C MULLIGAN, LM AMIEL, J BOUTRAND, L BELDJORD, C NIHOULFEKETE, C MUNNICH, A PONDER, BAJ LYONNET, S TI DIVERSITY OF RET PROTOONCOGENE MUTATIONS IN FAMILIAL AND SPORADIC HIRSCHSPRUNG DISEASE SO HUMAN MOLECULAR GENETICS LA English DT Article ID TYROSINE KINASES; PROTOONCOGENE; GENE; CHROMOSOME-10; CADHERIN; CLONING; DOMAINS; FUSION; LINE AB Hirschsprung disease (HSCR) is a common congenital malformation (1 in 5 000 live births) due to the absence of autonomic ganglia in the terminal hindgut, and resulting in intestinal obstruction in neonates, Recently, a dominant gene for familial HSCR has been mapped to chromosome sub-band 10q11.2 and the disease has been ascribed to mutations in a tyrosine kinase receptor gene mapping to this region, the RET proto-oncogene, Studying the 20 exons of the RET gene by a combination of denaturating gradient gel electrophoresis and single strand conformation polymorphism in a large series of HSCR patients (45 sporadic cases and 35 familial forms), we found mutations of the RET gene in 50% of familial HSCR, regardless of the length of the aganglionic segment, The mean penetrance of the mutant allele in familial HSCR was significantly higher in males (72%) than in females (51%), Most interestingly, mutations at the RET locus accounted for at least 1/3 of sporadic HSCR in our series, These mutations were scattered along the length of the gene, Finally, among the mutations identified in sporadic cases (16/45), seven proved to be de novo mutations suggesting that new mutations at the RET locus significantly contribute to sporadic HSCR, Taken together, the low penetrance of the mutant gene, the lack of genotype-phenotype correlation, the sex-dependent effect of RET mutations and the variable clinical expression of the disease support the existence of one or more modifier genes in familial HSCR. C1 HOP NECKER ENFANTS MALAD,INST NECKER,SERV GENET MED,CHIRURG INFANTILE CLIN,F-75743 PARIS,FRANCE. HOP NECKER ENFANTS MALAD,INST NECKER,INSERM,U393,UNITE RECH HANDICAPS GENET ENFANT,F-75743 PARIS,FRANCE. UNIV CAMBRIDGE,DEPT PATHOL,CANC RES CAMPAIGN,HUMAN CANC GENET RES GRP,CAMBRIDGE,ENGLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV MED ONCOL,BOSTON,MA 02115. QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. QUEENS UNIV,DEPT PAEDIAT,KINGSTON,ON K7L 3N6,CANADA. HOP COCHIN,SERV BIOCHIM GENET,F-75014 PARIS,FRANCE. OI Eng, Charis/0000-0002-3693-5145 NR 51 TC 255 Z9 261 U1 3 U2 5 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 AUG PY 1995 VL 4 IS 8 BP 1381 EP 1386 DI 10.1093/hmg/4.8.1381 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RM340 UT WOS:A1995RM34000018 PM 7581377 ER PT J AU MOLRINE, DC POLK, DB CIAMARRA, A PHILLIPS, N AMBROSINO, DM AF MOLRINE, DC POLK, DB CIAMARRA, A PHILLIPS, N AMBROSINO, DM TI IMPAIRED HUMAN RESPONSES TO TETANUS TOXOID IN VITAMIN-A-DEFICIENT SCID MICE RECONSTITUTED WITH HUMAN PERIPHERAL-BLOOD LYMPHOCYTES SO INFECTION AND IMMUNITY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; ANTIBODY-RESPONSE; IGG RESPONSES; DEPLETED RATS; NK CELLS; HU MOUSE; MORTALITY; CHILDREN; SUPPLEMENTATION; POLYSACCHARIDE AB Vitamin A deficiency is associated with increased childhood morbidity and mortality from respiratory and diarrheal diseases, In order to evaluate the effect of vitamin A on human antibody responses, we developed a vitamin A-deficient severe combined immunodeficient (SCID) mouse model. Vitamin A-deficient mice were produced by depriving them of vitamin A at day 7 of gestation. Mice were reconstituted with human peripheral blood lymphocytes (huPBL) from tetanus toroid immune donors at 6 weeks of age and immunized with tetanus toroid at 6 and 8 weeks of age. Secondary human antibody responses were determined 10 days later, The geometric mean human anti-tetanus toroid immunoglobulin G concentrations were 3.75 mu g/ml for the deficient mice and 148 mu g/ml for controls (P = 0.0005), Vitamin A-deficient mice had only a 2.9-fold increase in human anti-tetanus toroid antibody compared with a 74-fold increase in controls (P < 0.01), Supplementation with vitamin A prior to reconstitution restored human antibody responses to normal, These data suggest that vitamin A deficiency impairs human antibody responses, We speculate that impaired responses could increase susceptibility to certain infections, Furthermore, we propose that effects of other nutritional deficiencies on the human immune system could be evaluated in the SCID-huPBL model. C1 VANDERBILT UNIV,SCH MED,DEPT PEDIAT,DIV PEDIAT GASTROENTEROL & NUTR,NASHVILLE,TN 37232. RP MOLRINE, DC (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CAO1730]; NIDDK NIH HHS [DK26657]; PHS HHS [A129623] NR 46 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1995 VL 63 IS 8 BP 2867 EP 2872 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RK640 UT WOS:A1995RK64000010 PM 7622207 ER PT J AU TAUBMAN, MA HOLMBERG, CJ SMITH, DJ AF TAUBMAN, MA HOLMBERG, CJ SMITH, DJ TI IMMUNIZATION OF RATS WITH SYNTHETIC PEPTIDE CONSTRUCTS FROM THE GLUCAN-BINDING OR CATALYTIC REGION OF MUTANS STREPTOCOCCAL GLUCOSYLTRANSFERASE PROTECTS AGAINST DENTAL-CARIES SO INFECTION AND IMMUNITY LA English DT Article ID SOBRINUS GLUCOSYLTRANSFERASE; NUCLEOTIDE-SEQUENCE; LOCAL IMMUNIZATION; GENE; ANTIBODY; SUCROSE; DOMAIN; SITE; IMMUNOGENICITY; INHIBITION AB Previously, we have described peptide constructs from two regions of glucosyltransferase (GTF) of mutans streptococci. A putative catalytic site in the amino-terminal half of the molecule and a repeated glucan-binding site in the carboxyl-terminal half of GTF were the regions upon which sequences were based. The present study explored the effects of immunization with these peptide constructs (called CAT or GLU) and with streptococcal GTFs from Streptococcus sobrinus and S. mutans on immunological, microbiological, and disease parameters, Groups of immunized Sprague-Dawley rats were infected with either 10(8) S. sobrinus 6715 or 10(8) S. mutans SJ32 organisms. Serum immunoglobulin G antibody levels, determined by enzyme-linked immunosorbent assay, to the respective peptide constructs and to the appropriate streptococcal GTP were significantly increased (after immunization) prior to infection and at the end of the experiment. Also, serum antibody from CAT-, GLU-, and S. sobrinus GTF-immunized rats inhibited S. sobrinus GTF-mediated insoluble glucan synthesis (all) and S. mutans GTF-mediated soluble glucan synthesis (all except anti-GLU) from sucrose. Immunization with the CAT or GLU peptide construct resulted in significantly reduced smooth surface and sulcal caries after infection with S. sobrinus. Sulcal dental caries after infection with S. mutans SJ32 were also significantly reduced in CAT- and GLU-immunized rats. Thus, immunization with peptides whose sequences are based on putative functional domains of mutans streptococcal GTF are protective toward a cariogenic S. sobrinus or S. mutans infection. RP TAUBMAN, MA (reprint author), FORSYTH DENT CTR,DEPT IMMUNOL,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-04733] NR 39 TC 50 Z9 54 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 AUG PY 1995 VL 63 IS 8 BP 3088 EP 3093 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RK640 UT WOS:A1995RK64000042 PM 7622235 ER PT J AU INGALLS, RR RICE, PA QURESHI, N TAKAYAMA, K LIN, JS GOLENBOCK, DT AF INGALLS, RR RICE, PA QURESHI, N TAKAYAMA, K LIN, JS GOLENBOCK, DT TI THE INFLAMMATORY CYTOKINE RESPONSE TO CHLAMYDIA-TRACHOMATIS INFECTION IS ENDOTOXIN MEDIATED SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; DIPHOSPHORYL-LIPID-A; PROTECTIVE MONOCLONAL-ANTIBODIES; HUMAN-IMMUNODEFICIENCY-VIRUS; RHODOPSEUDOMONAS-SPHAEROIDES; LIPOPOLYSACCHARIDE EPITOPE; ESCHERICHIA-COLI; HUMAN-MONOCYTES; EXPRESSION; CELLS AB Chlamydia trachomatis is a major etiologic agent of sexually transmitted diseases. Although C. trachomatis is a gram-negative pathogen, chlamydial infections are not generally thought of as endotoxin-mediated diseases. A molecular characterization of the acute immune response to chlamydia, especially with regard to the role of its lipopolysaccharide (LPS), remains to be undertaken. We extracted 15 mg of LPS from 5 x 10(12) C. trachomatis elementary bodies (EB) for analysis of structure and biological activity. When methylated lipid A was subjected to high-pressure liquid chromatography followed by mass spectrometry, the majority of the lipid A was found to be pentaacyl. The endotoxin activities of whole C. trachomatis EB and purified LPS were characterized in comparison with whole Salmonella minnesota R595 and with S. minnesota R595 LPS and lipooligosaccharide from Neisseria gonorrhoeae. Both C. trachomatis LPS and whole EB induced the release of tumor necrosis factor alpha from whole blood ex vivo, and C. trachomatis LPS was capable of inducing the translocation of nuclear factor kappa B in a Chinese hamster ovary fibroblast cell line transfected with the LPS receptor CD14. In both assays, however, C. trachomatis was similar to 100-fold less potent than S. minnesota and N. gonorrhoeae. The observation that C. trachomatis is a weak inducer of the inflammatory cytokine response correlates with the clinical observation that, unlike N. gonorrhoeae infection, genital tract infection with C. trachomatis is often asymptomatic. The ability of specific LPS antagonists to completely inhibit the tumor necrosis factor alpha-inducing activity of whole C. trachomatis EB suggests that the inflammatory cytokine response to chlamydia infection may be mediated primarily through LPS. This implies that the role of other surface protein antigens, at least in terms of eliciting the proinflammatory cytokine response, is likely to be minor. C1 BOSTON CITY HOSP,MAXWELL FINLAND LAB INFECT DIS,BOSTON,MA 02118. BOSTON UNIV,SCH MED,BOSTON,MA 02118. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. FU NIAID NIH HHS [AI33087]; NIGMS NIH HHS [GM47127]; PHS HHS [GN50870] NR 53 TC 132 Z9 135 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 AUG PY 1995 VL 63 IS 8 BP 3125 EP 3130 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RK640 UT WOS:A1995RK64000047 PM 7542638 ER PT J AU SHANG, ES EXNER, MM SUMMERS, TA MARTINICH, C CHAMPION, CI HANCOCK, REW HAAKE, DA AF SHANG, ES EXNER, MM SUMMERS, TA MARTINICH, C CHAMPION, CI HANCOCK, REW HAAKE, DA TI THE RARE OUTER-MEMBRANE PROTEIN, OMPL1, OF PATHOGENIC LEPTOSPIRA SPECIES IS A HEAT-MODIFIABLE PORIN SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; NONTYPEABLE HEMOPHILUS-INFLUENZAE; VIRULENT TREPONEMA-PALLIDUM; HARDJO-BOVIS INFECTION; ESCHERICHIA-COLI K-12; PSEUDOMONAS-AERUGINOSA; MOLECULAR-CLONING; NEISSERIA-GONORRHOEAE; MONOCLONAL-ANTIBODIES; RECOMBINANT PORIN AB The outer membranes of invasive spirochetes contain unusually small amounts of transmembrane proteins. Pathogenic Leptospira species produce a rare 31-kDa surface protein, OmpL1, which has a deduced amino acid sequence predictive of multiple transmembrane beta-strands. Studies were conducted to characterize the structure and function of this protein. Alkali, high-salt, and urea fractionation of leptospiral membranes demonstrated that OmpL1 is an integral membrane protein. The electrophoretic mobility of monomeric OmpL1 was modifiable by heat and reduction; complete denaturation of OmpL1 required prolonged boiling in sodium dodecyl sulfate (SDS), 8 M urea, and 2-mercaptoethanol. When solubilized in SDS at low temperature, a small proportion of OmpL1 exhibited an apparent molecular mass of approximately 90 kDa, indicating the existence of an SDS-unstable oligomer. OmpL1 dimers and trimers were demonstrated by nearest neighbor chemical cross-linking. In order to generate purified protein for functional studies, the ompL1 gene was ligated into the pMMB66 expression plasmid under control of the tac promoter. Although expression in Escherichia call was toxic, most of the OmpL1 produced was found in the outer membrane, as determined by subcellular fractionation. Purified recombinant OmpL1 was reconstituted into planar lipid bilayers, demonstrating an average single channel conductance of 1.1 nS, similar to the major porin activity of native leptospiral membranes. These findings indicate that OmpL1 spans the leptospiral outer membrane and functions as a porin. C1 W LOS ANGELES VET AFFAIRS MED CTR,DIV INFECT DIS 111F,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. UNIV BRITISH COLUMBIA,DEPT MICROBIOL,VANCOUVER,BC V6T 1Z3,CANADA. RI Hancock, Robert/E-1145-2013 FU NIAID NIH HHS [2-T32-AI07323-06] NR 58 TC 66 Z9 78 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1995 VL 63 IS 8 BP 3174 EP 3181 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RK640 UT WOS:A1995RK64000054 PM 7622245 ER PT J AU VONWEIZSACKER, F MAEDA, E BROWN, N POYNARD, T GALUN, E LABEIT, S CAPUT, JC ARIMA, T BLUM, H WANDS, JR AF VONWEIZSACKER, F MAEDA, E BROWN, N POYNARD, T GALUN, E LABEIT, S CAPUT, JC ARIMA, T BLUM, H WANDS, JR TI HEPATITIS-B AND HEPATITIS-C VIRUS-INFECTION IN HBSAG-NEGATIVE ALCOHOLICS WITHOUT IV DRUG-ABUSE OR PREVIOUS BLOOD-TRANSFUSIONS SO INTERNATIONAL HEPATOLOGY COMMUNICATIONS LA English DT Article DE ALCOHOLIC LIVER DISEASE; LATENT HBV INFECTION; LATENT HCV INFECTION; SYNTHETIC OLIGOPEPTIDE ID LIVER-DISEASE; HEPATOCELLULAR-CARCINOMA; ANTIBODIES; DNA; PREVALENCE; ANTIGEN; RNA AB The presence of low level hepatitis B virus (HBV) and hepatitis C virus (HCV) infections was assessed in serum from 67 hepatitis B surface antigen (HBsAg) negative alcoholics from France without previous blood transfusions and/or i.v. drug abuse. It was found that 19/67 (28%) of this alcoholic population had past exposure to HBV as shown by the presence of antibodies to the surface (anti-HBs), core (anti-HBc) and e (anti-HBe) antigens. Two patients (3%) had low level circulating encapsidated HBV as determined by the highly sensitive capture PCR technique. Previous exposure to HCV was assessed by three serological tests: the first generation ELISA (C-100-3), a second generation recombinant immunoblot assay (RIBA II) and a radioimmunoassay based on highly conserved HCV core peptide sequences; 7/67 (10.5%) were found to be reactive in at least two serological tests. Among 64 serum samples available for RNA PCR testing, 6 were found to be HCV RNA positive (9.4%). Taken together, 8/67 (13%) of this alcoholic population were positive for HCV by RNA PCR and/or at least two serological tests. We conclude, that even in the absence of known risk factors and HBsAg negativity, patients with alcoholic liver disease have a significantly higher prevalence of markers of past or ongoing HBV or HCV infection than healthy individuals. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. KAGOSHIMA UNIV,FAC MED,DEPT INTERNAL MED 2,KAGOSHIMA 890,JAPAN. HOP ANTOINE BECLERE,SERV HEPATOGASTROENTEROL,F-92141 CLAMART,FRANCE. HOP ANTOINE BECLERE,SERV MICROBIOL & IMMUNOL,CLAMART,FRANCE. HOP ANTOINE BECLERE,INSERM,U131,CLAMART,FRANCE. HADASSAH UNIV HOSP,DEPT MED,LIVER UNIT,IL-91120 JERUSALEM,ISRAEL. EUROPEAN MOLEC BIOL LAB,W-6900 HEIDELBERG,GERMANY. MASSACHUSETTS GEN HOSP,MGH CANC CTR,MOLEC HEPATOL LAB,BOSTON,MA 02114. NR 22 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0928-4346 J9 INT HEPATOL COMMUN JI Int. Hepatol. Commun. PD AUG PY 1995 VL 4 IS 2 BP 80 EP 87 DI 10.1016/0928-4346(95)00218-8 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RQ890 UT WOS:A1995RQ89000004 ER PT J AU NABOZNY, GH RIMM, IJ GRIFFITHS, MM LUTHRA, HS DAVID, CS AF NABOZNY, GH RIMM, IJ GRIFFITHS, MM LUTHRA, HS DAVID, CS TI EXPRESSION OF AN OVALBUMIN-SPECIFIC V(BETA)8.2 TCR TRANSGENE INHIBITS COLLAGEN ARTHRITIS IN B1O.Q MICE SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE AUTOIMMUNE ARTHRITIS; T CELL REPERTOIRE; TYPE II COLLAGEN ID T-CELL RECEPTORS; MAJOR HISTOCOMPATIBILITY COMPLEX; BETA-SPECIFIC ANTIBODIES; II COLLAGEN; AUTOIMMUNE ENCEPHALOMYELITIS; IMMUNE INTERVENTION; MOUSE THYROGLOBULIN; ANTIGEN RECEPTOR; GENES; SUSCEPTIBILITY AB Previous studies have illustrated the importance of T cells bearing alpha beta TCRs in the induction and development of collagen induced arthritis (CIA) in mice. However, the scope of TCR usage in CIA has yet to be clearly defined, Given the inherent diversity of the TCR repertoire, the relative flexibility of the arthritogenic TCR repertoire specific for type II collagen (CII) is not clear. Therefore, we chose to examine the influence of a highly skewed TCR repertoire on CIA. Arthritis susceptible B10.Q (H-2(q)) mice were mated with C57L (H-2(b)) animals expressing an ovalbumin-specific V beta 8,2 TCR transgene (Tg) and Tg(+) offspring were further backcrossed to B10.Q. Homozygous H-2(q/q), V beta 8.2 Tg(+) mice displayed a high level of V(beta)8.2(+) T cells in peripheral blood. However, expression of some endogenous V-beta TCR, such as V(beta)14, was still detected. Upon immunization with bovine CII in adjuvant, V(beta)8.2 Tg(+) mice were highly resistant to CIA when compared with Tg(-) littermates, Analysis of sera demonstrated a marked reduction in antibody specific for homologous mouse CII as well as heterologous bovine CII in Tg(+) animals. Interestingly, V beta 8.2 Tg(+) mice still mounted good antibody responses following immunization with human thyroglobulin, indicating that the skewed TCR repertoire affected anti-CII but not antithyroglobulin responses. Thus, our findings show that constraints placed on the TCR repertoire inhibit pathogenic responses against CII and suggest that in H-2(q) mice the arthritogenic TCR repertoire bears only limited flexibility. C1 MAYO CLIN & MAYO GRAD SCH MED,DEPT IMMUNOL,ROCHESTER,MN 55905. MAYO CLIN & MAYO GRAD SCH MED,DEPT RHEUMATOL,ROCHESTER,MN 55905. DANA FARBER CANC INST,DEPT PEDIAT,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. UNIV UTAH,VET ADM MED CTR,RES SERV,SALT LAKE CITY,UT 84132. UNIV UTAH,DEPT MED,DIV RHEUMATOL,SALT LAKE CITY,UT 84132. FU NIAMS NIH HHS [AR30752] NR 45 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD AUG PY 1995 VL 7 IS 8 BP 1279 EP 1286 DI 10.1093/intimm/7.8.1279 PG 8 WC Immunology SC Immunology GA RP590 UT WOS:A1995RP59000012 PM 7495734 ER PT J AU BERGMAN, S MEDEIROS, LJ RADR, T MANGHAM, DC LEWANDROWSKI, KB AF BERGMAN, S MEDEIROS, LJ RADR, T MANGHAM, DC LEWANDROWSKI, KB TI GIANT-CELL TUMOR OF THE PANCREAS ARISING IN THE OVARIAN-LIKE STROMA OF A MUCINOUS CYSTADENOCARCINOMA SO INTERNATIONAL JOURNAL OF PANCREATOLOGY LA English DT Note DE GIANT CELL TUMOR; PANCREAS; MUCINOUS CYSTIC NEOPLASM; CYSTIC TUMOR; MUCINOUS CYSTADENOCARCINOMA AB We describe a malignant mucinous cystic neoplasm of the pancreas with ovarian-like stroma within which an osteoclast-like giant cell rich tumor arose. This rare tumor had a unique immunohistochemical profile with the giant cells staining for vimentin, leukocyte common antigen, and the monocyte/macrophage marker CD68, whereas the mucinous epithelium stained for epithelial membrane antigen and cytokeratin. The immunohistochemical findings are consistent with two lines of differentiation, one epithelial and the other suggesting mesenchymal differentiation of the giant cell tumor with an immunophenotype similar to giant cell tumor of bone. The coexistence of these two rare tumors suggests that they are histogenetically related. The finding of a giant cell tumor arising in the ovarian stroma indicates that the stroma of mucinous tumors is not always an innocuous component of the tumor. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RHODE ISL HOSP,DEPT PATHOL,PROVIDENCE,RI 02902. BROWN UNIV,SCH MED,PROVIDENCE,RI 02912. NR 14 TC 14 Z9 15 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 0169-4197 J9 INT J PANCREATOL JI Int. J. Pancreatol. PD AUG PY 1995 VL 18 IS 1 BP 71 EP 75 PG 5 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA RR342 UT WOS:A1995RR34200010 PM 7594774 ER PT J AU NATHANSON, JA MCKEE, M AF NATHANSON, JA MCKEE, M TI IDENTIFICATION OF AN EXTENSIVE SYSTEM OF NITRIC OXIDE-PRODUCING CELLS IN THE CILIARY MUSCLE AND OUTFLOW PATHWAY OF THE HUMAN EYE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE CILIARY MUSCLE; NADPH-DIAPHORASE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; OUTFLOW RESISTANCE; TRABECULAR MESHWORK ID LOWERS INTRAOCULAR-PRESSURE; NADPH DIAPHORASE; SYNTHASE; LOCALIZATION; CYCLASE; TISSUES; BRAIN AB Purpose. Nitric oxide (NO) is an important intracellular and intercellular regulator in nerve tissue as well as in vascular endothelium, smooth muscle, and certain other cell types. In the ocular anterior segment, studies in rat have revealed a comparatively restricted distribution of the NO synthetic enzyme, NO synthase (NOS-1). Recent physiological studies, however, have shown that NO-mimicking nitrovasodilators can alter intraocular pressure in monkeys through an action (at least in part) on outflow resistance. The current studies, which determine the sites of NO synthesis in the human outflow pathway, were performed to provide an anatomic and biochemical explanation for these observations. Methods. The occurrence and distribution of sites of ocular NO production in postmortem human eyes were determined using the isozyme-independent NO-indicator marker, NADPH-diaphorase (NADPH-d), together with direct biochemical assay and immunocytochemical localization of specific NO synthase (NOS) isoforms. Results. The ciliary muscle (CM) and outflow pathway of normal human eyes were found to be substantially enriched in NADPH-d, the majority of which, by immunological analysis, consisted not of NOS-1 (brain or bNOS) but rather of NOS type 3 (endothelial cell or ecNOS). Biochemical analysis confirmed the NADPH-dependent production of NO and, unlike the primarily soluble distribution of bNOS, activity was found in both particulate and soluble fractions. NO reactivity was enriched in major sites of outflow resistance (trabecular meshwork and Schlemm's canal) as well as in collecting channels and was particularly prominent in the CM, especially in the anatomically distinct longitudinal subgroup of CM fibers that insert near (and may normally play a role in regulating resistance in) the trabecular meshwork. Conclusion. The human outflow pathway and CM are enriched sites of NO synthesis. These sites are anatomically distributed in such a manner as to suggest that one possible role for NO in the anterior segment may be to modulate outflow resistance either directly at the level of the trabecular meshwork, Schlemm's canal and collecting channels, or indirectly through alteration in the tone of the longitudinal CM. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA. RP NATHANSON, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROPHARMACOL RES LAB,CNY-6,149 13TH ST,BOSTON,MA 02129, USA. NR 36 TC 132 Z9 134 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 AUG PY 1995 VL 36 IS 9 BP 1765 EP 1773 PG 9 WC Ophthalmology SC Ophthalmology GA RN213 UT WOS:A1995RN21300005 PM 7543462 ER PT J AU NATHANSON, JA MCKEE, M AF NATHANSON, JA MCKEE, M TI ALTERATIONS OF OCULAR NITRIC-OXIDE SYNTHASE IN HUMAN GLAUCOMA SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE CILIARY MUSCLE; GLAUCOMA; NADPH-DIAPHORASE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; TRABECULAR MESHWORK ID AGE-RELATED LOSS; CILIARY MUSCLE; TRABECULAR MESHWORK; NADPH DIAPHORASE; RHESUS-MONKEY; LOCALIZATION; PILOCARPINE; BRAIN AB Purpose. The authors recently reported that sites of outflow resistance and regulation in the human eye are highly enriched in the endothelial isoform of nitric oxide (NO) synthase (ecNOS). In vasculature, ecNOS activation is associated with altered vascular resistance and, in the stomach, defects in NO are associated with pathologic gastric hypertension. Because human glaucoma sometimes is associated with an increase in intraocular pressure and resistance changes in the aqueous outflow pathway (OP), the authors have investigated the possibility that alterations in NO or defects in NO-synthesizing tissues might exist in glaucomatous eyes. Methods. Occurrence, distribution, and extent of sites of ocular NO production in the anterior segments of 16 normal eyes (10 patients) and 17 eyes (12 patients) with a history of primary open-angle glaucoma (POAG) were determined using the NO-indicator marker, NADPH-diaphorase (NADPH-d), which is known to colocalize with ecNOS immunoreactivity. Analysis of NADPH-d reactivity in tissues was combined with examination of overall cell distribution and use of neuron-specific markers. Results. The ciliary muscle (CM) and OP of glaucomatous eyes showed marked differences in the amount and distribution of NADPH-d and alterations in gross structure. NADPH-d reactivity was decreased in trabecular meshwork (TM) and Schlemm's canal, and there was a marked reduction of anterior longitudinal CM fibers that insert near (and may normally regulate resistance in) the TM. Conclusion. Abnormalities in NO or NO-containing cells occur in POAG. These abnormalities may be causally related to glaucoma or may be a manifestation of the disease or its treatment In either case, such alterations, together with recent pharmacologic studies showing that NO-mimicking nitrovasodilators alter IOP, indicate that NO has relevance to the course, treatment, or both, of some forms of this disease. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA. RP NATHANSON, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROPHARMACOL RES LAB,149 13TH ST,BOSTON,MA 02129, USA. NR 43 TC 96 Z9 97 U1 0 U2 2 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 AUG PY 1995 VL 36 IS 9 BP 1774 EP 1784 PG 11 WC Ophthalmology SC Ophthalmology GA RN213 UT WOS:A1995RN21300006 PM 7543463 ER PT J AU SANDBERG, MA WEIGELDIFRANCO, C DRYJA, TP BERSON, EL AF SANDBERG, MA WEIGELDIFRANCO, C DRYJA, TP BERSON, EL TI CLINICAL EXPRESSION CORRELATES WITH LOCATION OF RHODOPSIN MUTATION IN DOMINANT RETINITIS-PIGMENTOSA SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE ELECTRORETINOGRAPHY; MUTATION; RETINITIS PIGMENTOSA; RHODOPSIN; SENSITIVITY; VISUAL ACUITY; VISUAL FIELD ID OCULAR FINDINGS; CYSTEINE RESIDUE-110; RETINAL FUNCTION; GENE; IDENTIFICATION AB Purpose. To determine whether severity of retinitis pigmentosa caused by dominant rhodopsin mutations depends on the location altered by the mutation. Methods. Data from 128 patients (age range, 7 to 73 years), each with 1 of 27 rhodopsin mutations, were analyzed. To approximate normal distributions, visual acuities were converted to ranks and then to the normal form, kinetic visual fields to a V4e test light were converted to equivalent diameters, and dark-adapted sensitivities to an 11 degrees diameter stimulus and electroretinogram (ERG) amplitudes to full-field 0.5-Hz and 30-Hz flashes were converted to common logarithms. Each of these measures was then regressed on age, refractive error (for the ERG), and domain (intradiscal, transmembrane, or cytoplasmic) or codon number of the opsin molecule altered by the mutation. Results. All five measures of function varied significantly with the domain (P less than or equal to 0.0007) or codon number (P < 0.0001) altered by a mutation; visual acuity, visual field diameter, dark-adapted sensitivity, and ERG amplitudes were highest for mutations altering the intradiscal domain or low-numbered codons and lowest for mutations altering the cytoplasmic domain or high-numbered codons. Conclusions. These data indicate that severity of disease correlates with the location of the amino acid residue altered by a rhodopsin mutation in dominant retinitis pigmentosa. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,TAYLOR SMITH LAB,BOSTON,MA 02114. RP SANDBERG, MA (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY08683, EY00169] NR 34 TC 55 Z9 55 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 AUG PY 1995 VL 36 IS 9 BP 1934 EP 1942 PG 9 WC Ophthalmology SC Ophthalmology GA RN213 UT WOS:A1995RN21300022 PM 7635666 ER PT J AU RUBENSTEIN, LV FINK, A YANO, EM SIMON, B CHERNOF, B ROBBINS, AS AF RUBENSTEIN, LV FINK, A YANO, EM SIMON, B CHERNOF, B ROBBINS, AS TI PERFORMANCE IMPROVEMENT IN HEALTH-CARE ORGANIZATIONS - INCREASING THE IMPACT OF QUALITY IMPROVEMENT ON HEALTH - AN EXPERT PANEL METHOD FOR SETTING INSTITUTIONAL PRIORITIES SO JOINT COMMISSION JOURNAL ON QUALITY IMPROVEMENT LA English DT Article ID CONSENSUS AB Background: Successful implementation of modern ongoing quality improvement (QI) methods requires investment of institutional resources, but can produce significant improvements in medical care. A health care organization's goals and objectives for improving care are expressed in strategic plan documents, which could provide a framework for planning quality improvement initiatives. However, institutional strategic planning processes are often not well linked to QI staff and resources. We developed the Quality Action Program (QAP) to connect QI to strategic planning. History: In 1991, Sepulveda VHAMC implemented a major primary care initiative, documented in a comprehensive strategic plan. The QAP was developed to enable the initiative to be evaluated within a QI context. Three-round expert panel process: To carry out the QAP, members of an institution's quality council engage in a structured consensus process. The first round involves reading educational materials and filling out a quality action survey the second round includes participation in an expert panel meeting, and the third round involves making final priority rankings. Eight-step QAP implementation plan: QI staff carry out activities to prepare for and carry out the three-round expert panel process. Results: QAP induced significant institutional QI activity directed toward achieving the top-ranked QI criterion-ensuring continuity of care. Continuity of care improved significantly over time between the pre- and post-QAP periods. Conclusions: Expert panel methods can be used to link strategic plan goals and objectives to QI efforts. C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA. RAND CORP,SANTA MONICA,CA. OLIVE VIEW UCLA MED CTR,SYLMAR,CA 91342. RALPH H JOHNSON VET AFFAIRS MED CTR,CHARLESTON,SC 29403. MED UNIV S CAROLINA,CHARLESTON,SC 29425. RP RUBENSTEIN, LV (reprint author), VET AFFAIRS MED CTR,CTR STUDY HEALTHCARE PROVIDER BEHAV,SEPULVEDA,CA 91343, USA. NR 29 TC 21 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1070-3241 J9 JOINT COMM J QUAL IM JI Jt. Comm. J. Qual. Improv. PD AUG PY 1995 VL 21 IS 8 BP 420 EP 432 PG 13 WC Health Policy & Services SC Health Care Sciences & Services GA RR469 UT WOS:A1995RR46900005 PM 7496455 ER PT J AU SMITH, E HARRIS, WH AF SMITH, E HARRIS, WH TI INCREASING PREVALENCE OF FEMORAL LYSIS IN CEMENTLESS TOTAL HIP-ARTHROPLASTY SO JOURNAL OF ARTHROPLASTY LA English DT Article DE FEMORAL LYSIS; INCREASING RATE; CEMENTLESS TOTAL HIP ARTHROPLASTY AB A follow-up study was made of 94 primary total hip arthroplasties in 86 patients with a Harris-Galante (Zimmer, Warsaw, IN) porous-coated femoral component implant to determine the change in prevalence of femoral lysis and its clinical significance. At a mean follow-up period of 53 months (range, 16-86 months), femoral lysis was present in 31% of the femurs. In the first report of this condition, the incidence was 3%. The mean patient age was 54 years (range, 30-69 years). The most common diagnosis was osteoarthritis (62 hips). Of the 29 hips with femoral lysis, Ii were graded as extensive. Of the 14 hips in which the femoral component was defined as loose, 12 had femoral osteolysis; however, the mean Harris hip score among those with lysis was not reduced in those with femoral osteolysis (88 compared with 90 the entire group). Pelvic osteolysis, in contrast, was present in only one hip, around a screw. In this series, femoral lysis was a major complication, whether the femoral component was stable or not, and the prevalence of lysis increased sharply over time. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. NR 0 TC 51 Z9 51 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD AUG PY 1995 VL 10 IS 4 BP 407 EP 412 DI 10.1016/S0883-5403(05)80138-X PG 6 WC Orthopedics SC Orthopedics GA RT199 UT WOS:A1995RT19900001 PM 8522996 ER PT J AU LI, YP ALEXANDER, M WUCHERPFENNIG, AL YELICK, P CHEN, W STASHENKO, P AF LI, YP ALEXANDER, M WUCHERPFENNIG, AL YELICK, P CHEN, W STASHENKO, P TI CLONING AND COMPLETE CODING SEQUENCE OF A NOVEL HUMAN CATHEPSIN EXPRESSED IN GIANT-CELLS OF OSTEOCLASTOMAS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID BONE-RESORPTION; CYSTEINE-PROTEINASES; LOCALIZATION; COLLAGENASE; INHIBITORS; FIBROBLASTS; LACUNAE; CULTURE; ENZYME; TISSUE AB A gene encoding a possible novel human cathepsin, a cysteine proteinase that is distinct from previously characterized enzymes, has been identified by differential screening of a human osteoclastoma cDNA library, This molecule, termed cathepsin X, appears to represent the human homolog of the osteoclast-expressed rabbit cathepsin OC-2, Cathepsin X (GenBank accession number U20280) is 93.9% identical to OC-2 at the amino acid level, and is 92% identical at the nucleotide level within the coding region, Cathepsin X is 52.2 and 46.9% identical to cathepsins S and L, respectively, and is therefore clearly distinct from these enzymes, Cathepsin X mRNA was localized to multinucleated giant cells within the osteoclastoma tumor by in situ hybridization. These data strongly support the hypothesis that cathepsin X represents a novel cysteine proteinase which is expressed at high levels in osteoclasts. C1 FORSYTH DENT CTR,DEPT CYTOKINE BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH DENT MED,DEPT PERIODONTOL,BOSTON,MA 02115. FU NIDCR NIH HHS [DE-07378]; PHS HHS [1K16-0027501] NR 28 TC 101 Z9 107 U1 0 U2 3 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 IS 8 BP 1197 EP 1202 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RL318 UT WOS:A1995RL31800008 PM 8585423 ER PT J AU ABBOUD, SL ALSINA, M MUNDY, GR ROODMAN, GD AF ABBOUD, SL ALSINA, M MUNDY, GR ROODMAN, GD TI POTENTIAL ROLE OF INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS (IGFBPS) IN THE UNCOUPLING OF BONE TURNOVER IN MULTIPLE MYELMOMA (MM) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S315 EP S315 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400706 ER PT J AU ALSINA, M DEVLIN, R ROODMAN, GD AF ALSINA, M DEVLIN, R ROODMAN, GD TI MECHANISMS OF OSTEOLYTIC BONE DESTRUCTION IN MULTIPLE-MYELOMA IN-VIVO SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78284 USA. AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S503 EP S503 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401455 ER PT J AU BERGWITZ, C GARDELLA, TJ FLANNERY, MR GOLDRING, SR JUPPNER, H AF BERGWITZ, C GARDELLA, TJ FLANNERY, MR GOLDRING, SR JUPPNER, H TI HYBRIDS BETWEEN THE RECEPTORS FOR PARATHYROID-HORMONE (PTH) PTH-RELATED PEPTIDE (PTHRP) AND CALCITONIN (CT) ARE ACTIVATED BY CORRESPONDING HYBRID LIGANDS - EVIDENCE FOR A COMMON FUNCTIONAL ARCHITECTURE OF LIGAND-RECEPTOR INTERACTION SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S141 EP S141 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400010 ER PT J AU DAKLEIN, AI DRAKE, MT TAKEMURA, M ABOUSAMRA, AB SEGRE, GV AF DAKLEIN, AI DRAKE, MT TAKEMURA, M ABOUSAMRA, AB SEGRE, GV TI SOME POSITIVELY CHARGED RESIDUES OF THE PTH/PTHRP RECEPTORS CYTOPLASMIC LOOPS ARE CRITICAL FOR SIGNAL-TRANSDUCTION SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S385 EP S385 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400983 ER PT J AU DERASKA, DJ NEER, RM AF DERASKA, DJ NEER, RM TI PARATHYROID-HORMONE (PTH) EFFECTS ON OSTEOBLAST AND OSTEOCLAST ACTIVITY IN POSTMENOPAUSAL OSTEOPOROSIS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S456 EP S456 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401270 ER PT J AU DEVLIN, RD REDDY, SV ROODMAN, GD AF DEVLIN, RD REDDY, SV ROODMAN, GD TI ANNEXIN-II INCREASES OSTEOCLAST (OCL) FORMATION BY STIMULATING THE PROLIFERATION OF OSTEOCLAST PRECURSORS IN HUMAN MARROW CULTURES SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S323 EP S323 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400737 ER PT J AU DIVIETI, P LANSKE, BM KRONENBERG, HM BRINGHURST, FR AF DIVIETI, P LANSKE, BM KRONENBERG, HM BRINGHURST, FR TI PTH ACTION IN CONDITIONALLY IMMORTALIZED PRIMARY MURINE CALVARIAL OSTEOBLASTS HETEROZYGOUS FOR ABLATION OF THE PTH/PTHRP RECEPTOR SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S311 EP S311 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400689 ER PT J AU FINKELSTEIN, J KLIBANSKI, A NEER, R AF FINKELSTEIN, J KLIBANSKI, A NEER, R TI PREVENTION OF BONE LOSS FROM THE HIP AND SPINE WITH PARATHYROID-HORMONE IN ESTROGEN-DEFICIENT WOMEN SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S460 EP S460 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401284 ER PT J AU GARDELLA, TJ LUCK, MD FAN, MH LEE, CW AF GARDELLA, TJ LUCK, MD FAN, MH LEE, CW TI MUTATIONS IN THE TRANSMEMBRANE DOMAINS OF THE PTH RECEPTOR IMPAIR BINDING OF PTH-(1-34) BUT NOT PTH-(3-34) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S386 EP S386 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400987 ER PT J AU GOODMAN, WG BELIN, TR GALES, B JUPPNER, H SEGRE, GV SALUSKY, IB AF GOODMAN, WG BELIN, TR GALES, B JUPPNER, H SEGRE, GV SALUSKY, IB TI CALCIUM-REGULATED PARATHYROID-HORMONE RELEASE IN PATIENTS WITH MILD OR ADVANCED SECONDARY HYPERPARATHYROIDISM SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S512 EP S512 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401491 ER PT J AU GORN, AH RUDOLPH, SM FISHMAN, MC AF GORN, AH RUDOLPH, SM FISHMAN, MC TI PROCALCITONIN MAY ENCODE A DEVELOPMENTAL SIGNAL FOR EARLY AXIAL PATTERNING IN ZEBRAFISH EMBRYOS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ARTHRITIS UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIOVASC RES CTR,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S156 EP S156 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400069 ER PT J AU GRIMANIS, GA GUO, J LANSKE, B REINHART, AL REICHEL, H GLOWACKI, J BRINGHURST, FR AF GRIMANIS, GA GUO, J LANSKE, B REINHART, AL REICHEL, H GLOWACKI, J BRINGHURST, FR TI THE PARATHYROID-HORMONE RESPONSIVENESS OF BONE-MARROW STROMAL CELLS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH DENT MED,ENDOCRINE UNIT,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S481 EP S481 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401369 ER PT J AU GUO, J LANSKE, B LIU, B DIVIETI, P KRONENBERG, HM BRINGHURST, FR AF GUO, J LANSKE, B LIU, B DIVIETI, P KRONENBERG, HM BRINGHURST, FR TI ABLATION OF PTH/PTHRP RECEPTORS IN CONDITIONALLY IMMORTALIZED, PTH-RESPONSIVE CHONDROCYTE CELL-LINES SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S172 EP S172 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400136 ER PT J AU HOSOKAWA, Y POLLAK, MR BROWN, EM ARNOLD, A AF HOSOKAWA, Y POLLAK, MR BROWN, EM ARNOLD, A TI THE EXTRACELLULAR CALCIUM SENSING RECEPTOR GENE IN HUMAN PARATHYROID TUMORS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S383 EP S383 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400976 ER PT J AU HSI, E ZUKERBERG, LR YANG, WI ARNOLD, A AF HSI, E ZUKERBERG, LR YANG, WI ARNOLD, A TI CYCLIN-D1 (PRAD1) EXPRESSION IN PARATHYROID ADENOMAS - AN IMMUNOHISTOCHEMICAL STUDY SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ENDOCRINE ONCOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV MICHIGAN,MED CTR,DEPT PATHOL,ANN ARBOR,MI 48109. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S383 EP S383 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400978 ER PT J AU JOUN, H LANSKE, B ABOUSAMRA, AB AF JOUN, H LANSKE, B ABOUSAMRA, AB TI TISSUE-SPECIFIC TRANSCRIPTION-START SITE AND 5' ALTERNATIVE SPLICING OF THE PTH/PTHRP RECEPTOR (PPR) GENE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S488 EP S488 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401396 ER PT J AU KATZ, MS SONG, M HYMER, TK ELANGO, N AF KATZ, MS SONG, M HYMER, TK ELANGO, N TI CYTOKINES REGULATE THE EXPRESSION OF PARATHYROID-HORMONE PARATHYROID HORMONE-RELATED PROTEIN-RECEPTOR MESSENGER-RNA IN OSTEOBLAST-LIKE CELLS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. VET ADM MED CTR,GRECC,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S482 EP S482 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401372 ER PT J AU KOVACS, CS LANSKE, B KARAPLIS, A KRONENBERG, HM AF KOVACS, CS LANSKE, B KARAPLIS, A KRONENBERG, HM TI PTHRP-KNOCKOUT MICE HAVE REDUCED IONIZED CALCIUM, FETAL-MATERNAL CALCIUM GRADIENT AND 45-CALCIUM TRANSPORT SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S157 EP S157 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400073 ER PT J AU KRANE, SM BYRNE, MH WITTER, JP EECKHOUT, Y HENRIET, P LEMAITRE, V JEFFREY, JJ LIU, X WU, H JAENISCH, R AF KRANE, SM BYRNE, MH WITTER, JP EECKHOUT, Y HENRIET, P LEMAITRE, V JEFFREY, JJ LIU, X WU, H JAENISCH, R TI DIFFERENT COLLAGENASE (COLLASE) GENE-PRODUCTS HAVE DIFFERENT ROLES IN REMODELING OF TYPE-I COLLAGEN MATRICES SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. UNIV CATHOLIQUE LOUVAIN,SCH MED,ICP,B-1200 BRUSSELS,BELGIUM. ALBANY MED COLL,ALBANY,NY 12208. MIT,WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S165 EP S165 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400106 ER PT J AU LEE, K DEEDS, JD KOHNO, H TAKESHIGE, K LANSKE, B KOVACS, CS KARAPLIS, AC KRONENBERG, HM SEGRE, GV AF LEE, K DEEDS, JD KOHNO, H TAKESHIGE, K LANSKE, B KOVACS, CS KARAPLIS, AC KRONENBERG, HM SEGRE, GV TI ACTIVATION OF PTH/PTHRP RECEPTORS DELAYS CHONDROCYTIC DIFFERENTIATION DURING ENDOCHONDRAL BONE-FORMATION SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. MCGILL UNIV,SIR MORTIMER B DAVIS JEWISH HOSP,DEPT MED,MONTREAL,PQ H3A 2T5,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S384 EP S384 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400979 ER PT J AU LEUNG, AT ABOUSAMRA, AB AF LEUNG, AT ABOUSAMRA, AB TI THE PTH/PTHRP RECEPTOR DOES NOT UNDERGO AGONIST-INDUCED DESENSITIZATION IN ROS17/2.8 CELLS AND COS-7 CELLS EXPRESSING THE RAT PTH/PTHRP RECEPTOR SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. RI Leung, Albert/H-6030-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S488 EP S488 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401398 ER PT J AU NEER, R RAYNIKAR, V CRAWFORD, S SCHIFF, I MCKINLAY, S AF NEER, R RAYNIKAR, V CRAWFORD, S SCHIFF, I MCKINLAY, S TI POSTMENOPAUSAL RATES OF BONE LOSS ANTEDATE MENOPAUSE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NEW ENGLAND RES INST,WATERTOWN,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S348 EP S348 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400838 ER PT J AU REDDY, SV DEVLIN, R ROODMAN, GD AF REDDY, SV DEVLIN, R ROODMAN, GD TI CLONING AND CHARACTERIZATION OF A NOVEL AUTOCRINE OSTEOCLAST (OCL) STIMULATING FACTOR (OSF) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S325 EP S325 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400747 ER PT J AU REDDY, SV SINGER, FR MALLETTE, L ROODMAN, GD AF REDDY, SV SINGER, FR MALLETTE, L ROODMAN, GD TI DETECTION OF MEASLES-VIRUS (MV) TRANSCRIPTS IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS AND MARROW MONONUCLEAR-CELLS FROM PATIENTS WITH PAGETS-DISEASE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. JOHN WAYNE CANC INST, SANTA MONICA, CA 90404 USA. ST JOHNS HOSP, SANTA MONICA, CA 90404 USA. VET ADM MED CTR, HOUSTON, TX 77030 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S154 EP S154 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400061 ER PT J AU SCHIPANI, E JENSEN, G PARFITT, AM JUPPNER, H AF SCHIPANI, E JENSEN, G PARFITT, AM JUPPNER, H TI CONSTITUTIVELY ACTIVE PTH/PTHRP RECEPTORS IN JANSEN METAPHYSEAL CHONDRODYSPLASIA (JMC) - IDENTIFICATION OF A NOVEL T410P MUTATION AND FURTHER CHARACTERIZATION OF POSITION-223 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HENRY FORD HOSP,BONE & MINERAL RES LAB,DETROIT,MI 48202. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S173 EP S173 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400137 ER PT J AU SNEDDON, WB BOGADO, CE KIERNAN, MS DEMAY, MB AF SNEDDON, WB BOGADO, CE KIERNAN, MS DEMAY, MB TI DNA-SEQUENCES DOWNSTREAM FROM THE VITAMIN-D RESPONSE ELEMENT OF THE RAT OSTEOCALCIN GENE CONFER ENHANCED RESPONSIVENESS TO 1,25-DIHYDROXY-VITAMIN-D3 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S287 EP S287 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400595 ER PT J AU TAHARA, H CRYNS, VL GAZ, RD ARNOLD, A AF TAHARA, H CRYNS, VL GAZ, RD ARNOLD, A TI CHROMOSOMAL LOCATIONS OF NEW PARATHYROID TUMOR SUPRESSOR GENES SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE ONCOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S383 EP S383 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400977 ER PT J AU TAHARA, H CRYNS, VL GAZ, RD ARNOLD, A AF TAHARA, H CRYNS, VL GAZ, RD ARNOLD, A TI ANALYSIS OF THE P16 CYCLIN-DEPENDENT KINASE INHIBITOR AND LOSS OF CHROMOSOME ARM-9P DNA IN HUMAN PARATHYROID ADENOMAS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ENDOCRINE ONCOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S155 EP S155 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400065 ER PT J AU TETI, A PANICCIA, R GOLDRING, SR AF TETI, A PANICCIA, R GOLDRING, SR TI CALCINTONIN INCREASES CYSTOLIC FREE CALCIUM-CONCENTRATION VIA CAPACITATIVE CALCIUM-ENTRY PATHWAY SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV LAQUILA,DEPT EXPTL MED,I-67100 LAQUILA,ITALY. IDI,ROME,ITALY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ARTHRITIS UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S485 EP S485 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401385 ER PT J AU UY, HL MUNDY, GR DELAMATA, J BOYCE, BF GUISE, TA ROODMAN, GD AF UY, HL MUNDY, GR DELAMATA, J BOYCE, BF GUISE, TA ROODMAN, GD TI TUMOR-NECROSIS-FACTOR (TNF) ENHANCES INTERLEUKIN-6 (IL-6) MEDIATED HYPERCALCEMIA IN-VIVO SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S325 EP S325 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400744 ER PT J AU WITTER, JP BYRNE, MH AOUNWATHNE, M SUEN, LF KRANE, SM GOLDRING, MB AF WITTER, JP BYRNE, MH AOUNWATHNE, M SUEN, LF KRANE, SM GOLDRING, MB TI HUMAN MATRIX METALLOPROTEINASE-13 (MMP-13 OR COLLAGENASE-3) THE HOMOLOG OF MURINE INTERSTITIAL COLLAGENASE, IS EXPRESSED IN SKELETAL CELLS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 4 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S439 EP S439 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401199 ER PT J AU WU, Y ACKERMAN, JL CHESLER, DA NEER, R WANG, J GLIMCHER, MJ AF WU, Y ACKERMAN, JL CHESLER, DA NEER, R WANG, J GLIMCHER, MJ TI 3-DIMENSIONAL BONE-MINERAL DENSITY-MEASUREMENT BY SOLID-STATE P-31 MAGNETIC-RESONANCE-IMAGING SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 CHILDRENS HOSP MED CTR,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S477 EP S477 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401354 ER PT J AU WYATT, LE YAMAGUCHI, DT LIU, Y MA, D RUDKIN, GH ISHIDA, K MILLER, TA AF WYATT, LE YAMAGUCHI, DT LIU, Y MA, D RUDKIN, GH ISHIDA, K MILLER, TA TI EXPRESSION OF THE GAP JUNCTION STRUCTURAL PROTEIN CONNEXIN-40 AND MESSENGER-RNA IN MC3T3-E1 CELLS TREATED WITH TRANSFORMING GROWTH-FACTOR-BETA AND BONE MORPHOGENETIC PROTEIN-2 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 W LOS ANGELES VAMC,PLAST SURG SECT,LOS ANGELES,CA. W LOS ANGELES VAMC,GRECC,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S314 EP S314 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400701 ER PT J AU ABBOUD, SL AF ABBOUD, SL TI REGULATION OF PLATELET-DERIVED GROWTH-FACTOR-A AND GROWTH-FACTOR-B CHAIN GENE-EXPRESSION IN BONE-MARROW STROMAL CELLS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PROTEIN-KINASE-C; COLONY-STIMULATING FACTOR; MICROVASCULAR ENDOTHELIAL-CELLS; TUMOR NECROSIS FACTOR; FACTOR-BETA; TGF-BETA; TRANSCRIPTIONAL REGULATION; HEMATOPOIETIC PROGENITORS; SIGNAL TRANSDUCTION; LEUKEMIC-CELLS AB MBA-2, bone marrow-derived endothelial stromal cells, express platelet-derived growth factor (PDGF) A and and chain mRNAs and secrete PDGF activity that is induced by TGF-beta. Either chain of the PDGF molecule could modulate hematopoiesis and stromal cell growth. Intracellular pathways that regulate PDGF expression in the marrow microenvironment are unknown. in the present study, we examined the mechanisms that mediate PDGF A and B chain mRNA induction by TGF-beta and the role of protein kinase C (PKC) and cyclic AMP in PDGF regulation. TGF-beta was tested in parallel with PMA, an activator of phorbol ester-dependent PKC isoforms. Both PMA (10(-7) M) and TGF-beta (2.5 ng/ml) increased PDGF A and B chain mRNA levels. The serine/threonine protein kinase inhibitor, H7, blocked PDGF A and B chain mRNA induction in response to TGF-beta. However, down-regulation of PKC by prolonged incubation with PMA failed to abolish TGF-beta induction of PDGF A and B chain mRNAs. These findings indicate that induction of PDGF A and B chain mRNAs can be mediated via phorbol ester-dependent PKC pathway. In contrast, H7-sensitive protein kinase(s) other than phorbol ester-sensitive protein kinase C mediate the effect of TGF-beta. Agents that increase cAMP were also tested for their effect on PDGF gene expression. TGF-beta-mediated induction of PDGF A and B chain mRNAs was markedly inhibited by cAMP. cAMP also blocked stimulation of PDGF A chain mRNA by PMA. The positive and negative signaling mechanisms involved in modulating PDGF in the microenvironment may be important for determining hematopoietic and stromal cell responses in vivo. (C) 1995 Wiley-Liss, Inc. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP ABBOUD, SL (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIAMS NIH HHS [AR42306] NR 41 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD AUG PY 1995 VL 164 IS 2 BP 434 EP 440 DI 10.1002/jcp.1041640224 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA RK702 UT WOS:A1995RK70200023 PM 7622589 ER PT J AU WRIGHT, NM RENAULT, J WILLI, S VELDHUIS, JD PANDEY, JP GORDON, L KEY, LL BELL, NH AF WRIGHT, NM RENAULT, J WILLI, S VELDHUIS, JD PANDEY, JP GORDON, L KEY, LL BELL, NH TI GREATER SECRETION OF GROWTH-HORMONE IN BLACK THAN IN WHITE MEN - POSSIBLE FACTOR IN GREATER BONE-MINERAL DENSITY - A CLINICAL RESEARCH-CENTER STUDY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID OSTEOBLAST-LIKE CELLS; FACTOR-I; PREPUBERTAL GIRLS; TURNERS SYNDROME; BINDING PROTEIN; BODY HABITUS; SHORT-TERM; IGF-I; ESTRADIOL; WOMEN AB To determine why blacks have a higher bone mineral density (BMD) and lower incidence of osteoporosis and fractures than whites, we investigated whether the secretion of GH is higher in black than in white men. Measurements of GH were obtained at 20-min intervals over 24 h and analyzed by deconvolution. BMD was determined by dual energy x-ray absorptiometry in 16 normal black and 17 normal white men, aged 20-40 yr. The 24-h integrated GH concentration (942 +/- 174 us. 602 +/- 104 mu g/L; P = 0.0495) and GH secretory burst amplitude (0.499 +/- 0.163 vs. 0.169 +/- 0.027 mu g/L . min; P = 0.0482) were higher in black than in white men. GH burst frequency, half-duration, mass, and half-life were not different in the 2 groups. The serum 17 beta-estradiol level (162 +/- 12 vs. 108 +/- 11 pmol/L; P = 0.0011) was higher, and the serum insulin-like growth factor-binding protein 3 level (2.2 +/- 0.1 vs. 2.8 +/- 0.1 mu g/mL; P = 0.0001) was lower in black than in white men. BMD values for total body (1.22 +/- 0.02 us. 1.14 +/- 0.02 g/cm(2); P = 0.0041), forearm (0.69 +/- 0.01 vs. 0.66 +/- 0.01 g/cm(2); P = 0.0211), trochanter(0.91 +/- 0.03 vs. 0.77 +/- 0.03 g/cm(2); P = 0.0003), and femoral neck (1.08 +/- 0.03 os. 0.93 +/- 0.03 g/cm(2); P = 0.0007) were higher in black than in white men. Thus, serum 17 beta-estradiol level, GH secretion, and BMD values for the total body, forearm, trochanter, and femoral neck are greater in black than in white men. As estrogen is known to increase GH secretion and GH to increase bone mass, increases in circulating 17 beta-estradiol may contribute to the higher GH secretion and bone mass in black men. C1 MED UNIV S CAROLINA, DEPT MICROBIOL & IMMUNOL, CHARLESTON, SC 29425 USA. MED UNIV S CAROLINA, DEPT RADIOL, CHARLESTON, SC 29425 USA. MED UNIV S CAROLINA, DEPT MED & PHARMACOL, CHARLESTON, SC 29425 USA. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR, CHARLESTON, SC 29425 USA. UNIV VIRGINIA, SCH MED, DEPT INTERNAL MED, CHARLOTTESVILLE, VA 22908 USA. RP WRIGHT, NM (reprint author), MED UNIV S CAROLINA, DEPT PEDIAT, 171 ASHLEY AVE, CHARLESTON, SC 29425 USA. FU NCRR NIH HHS [MO1-RR-01070]; NIAMS NIH HHS [R01-AR-36066] NR 52 TC 78 Z9 79 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 AUG PY 1995 VL 80 IS 8 BP 2291 EP 2297 DI 10.1210/jc.80.8.2291 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN312 UT WOS:A1995RN31200005 PM 7543111 ER PT J AU HARDIN, DS AZZARELLI, B EDWARDS, J WIGGLESWORTH, J MAIANU, L BRECHTEL, G JOHNSON, A BARON, A GARVEY, WT AF HARDIN, DS AZZARELLI, B EDWARDS, J WIGGLESWORTH, J MAIANU, L BRECHTEL, G JOHNSON, A BARON, A GARVEY, WT TI MECHANISMS OF ENHANCED INSULIN SENSITIVITY IN ENDURANCE-TRAINED ATHLETES - EFFECTS ON BLOOD-FLOW AND DIFFERENTIAL EXPRESSION OF GLUT-4 IN SKELETAL-MUSCLES SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GLUCOSE-UPTAKE; FIBER TYPES; RAT; EXERCISE; RESISTANCE; INVIVO; RESPONSIVENESS; TRANSPORTERS; SECRETION; DISPOSAL AB Exercise is associated with increased insulin sensitivity. To better understand mechanisms that could be responsible for this association, we studied seven controls and seven endurance-trained athletes. A 600 mu/m(2)-min hyperinsulinemic euglycemic glucose clamp with the limb balance technique assessed insulin sensitivity as whole body glucose uptake (WBGU) and leg glucose uptake (LGU). Indirect calorimetry and hemodynamic measurements, such as leg blood flow (LBF) and cardiac output, were performed at baseline and maximal insulin stimulation. The content of the glucose transporter GLUT 4 and muscle fiber type were evaluated in three muscle groups: vastus lateralis, gastrocnemius, and biceps. Athletes exhibited 35% higher WBGU and 30% higher LGU than controls. Basal LBF (liters per min) was higher in athletes, but the difference was not statistically significant. After insulin stimulation, LBF was 31% higher in athletes than controls (P = 0.05). Indirect calorimetry revealed that athletes had a 44% higher rate of nonoxidative glucose metabolism than controls (P = 0.01). GLUT 4 levels in vastus were 90% (P < 0.05) greater in athletes, whereas smaller differences were noted between athletes and controls in biceps and gastrocnemius. Importantly, the vastus lateralis GLUT 4 content was correlated with WBGU (r = 0.60; P < 0.05) and LGU (r = 0.62; P < 0.05). Relative numbers of oxidative fibers were increased in vastus from athletes and were positively correlated with maximal oxygen consumption (VO2 max), but GLUT 4 content could not be correlated with oxidative fiber content in individual controls or athletes. We conclude that in humans 1) endurance training enhances insulin's ability to increase LBF; 2) GLUT 4 is differentially expressed as a function of muscle group and is up-regulated by exercise in a muscle-specific manner; 3) in vastus lateralis, GLUT 4 levels are well correlated with insulin-stimulated rates of both WBGU and LGU; and 4) GLUT 4 content and in vivo insulin sensitivity do not vary as a function of fiber type composition. Thus, blood flow and GLUT 4 expression in muscle are important mechanisms that mediate greater insulin sensitivity in athletes. C1 INDIANA UNIV, SCH MED, DEPT MED, INDIANAPOLIS, IN 46202 USA. INDIANA UNIV, SCH MED, DEPT PATHOL, INDIANAPOLIS, IN 46202 USA. INDIANA UNIV, SCH MED, DEPT KINESIOL, INDIANAPOLIS, IN 46202 USA. INDIANA UNIV, SCH MED, NATL INST FITNESS & SPORT, INDIANAPOLIS, IN 46202 USA. RICHARD L ROUDEBUSH VET AFFAIRS MED CTR, INDIANAPOLIS, IN 46202 USA. MED UNIV S CAROLINA, DEPT MED, CHARLESTON, SC 29425 USA. RALPH H JOHNSON VET AFFAIRS MED CTR, CHARLESTON, SC 29425 USA. RP HARDIN, DS (reprint author), UNIV TEXAS, SCH MED, DEPT PEDIAT, 6431 FANNIN MED SCI BLDG 3122, HOUSTON, TX 77030 USA. FU NCRR NIH HHS [M01-RR-750]; NIDDK NIH HHS [DK-38765, DK-42469] NR 50 TC 80 Z9 85 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1995 VL 80 IS 8 BP 2437 EP 2446 DI 10.1210/jc.80.8.2437 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN312 UT WOS:A1995RN31200026 PM 7629239 ER PT J AU XIA, P KRAMER, RM KING, GL AF XIA, P KRAMER, RM KING, GL TI IDENTIFICATION OF THE MECHANISM FOR THE INHIBITION OF NA+,K+-ADENOSINE TRIPHOSPHATASE BY HYPERGLYCEMIA INVOLVING ACTIVATION OF PROTEIN-KINASE-C AND CYTOSOLIC PHOSPHOLIPASE A(2) SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE DIABETES; VASCULAR CELLS; PROTEIN KINASE C; PHOSPHOLIPASE A(2); NA+,K+-ATPASE ID SODIUM-POTASSIUM-ATPASE; SMOOTH-MUSCLE CELLS; NA-K-ATPASE; PROSTAGLANDIN SYNTHESIS; DIABETIC COMPLICATIONS; SIGNAL TRANSDUCTION; ENDOTHELIAL-CELLS; MESANGIAL CELLS; HUMAN PLATELETS; BINDING AB Inhibition of Na+,K+ -ATPase activity by hyperglycemia could be an important etiological factor of chronic complications in diabetic patients, The biochemical mechanism underlying hyperglycemia's inhibitory effects has been thought to involve the alteration of the protein kinase C (PKC) pathway since agonists of PKC can normalize hyperglycemia-induced inhibition of Na+,K+-ATPase activity, Paradoxically, elevated glucose levels and diabetes have been shown to increase PKC activities in vascular cells, The present study tested the hypothesis that the inhibition of Na+,K+-ATPase activity is mediated by the sequential activation of PKC and cystolic phospholipase A(2) (cPLA(2)). In cultured rat vascular smooth muscle cells (VSMC),increasing glucose levels in the medium from 5.5 to 22 mM elevated cPLA(2) activity and increased [H-3]arachidonic acid release and PGE(2) production by 2.3-, 1.7- and 2-fold, respectively, Similar increases in cPLA(2) activity were also induced by elevated glucose levels in human VSMC and rat capillary endothelial cells, The activation of cPLA(2) was mediated by PKC since the increases in cPLA(2) phosphorylation and enzymatic activity were inhibited by the PKC inhibitor GFX. In contrast, elevation of glucose levels decreased Na+,K+-ATPase activity as measured by ouabain-sensitive Rb-86 uptake by twofold in rat VSMC, Surprisingly, both PMA, a PKC agonist, and GFX, a PKC inhibitor, were able to prevent glucose-induced decreases in Rb-86 uptake, Further, the PLA(2) inhibitor AACOCF(3) abolished both glucose-induced activation of cPLA(2), and the decrease in Rb-86 uptake, These data indicated that hyperglycemia is inhibiting Na+,K+-ATPase activity by the sequential activation of PKC and cPLA(2), resulting in the liberation of arachidonic acid and increased the production of PGE(2), which are known inhibitors of Na+, K+- ATPase. C1 JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02215 USA. LILLY RES LABS, INDIANAPOLIS, IN 46285 USA. RI Xia, Pu/G-3090-2010 OI Xia, Pu/0000-0003-4705-8878 FU NEI NIH HHS [EY 05110]; NIDDK NIH HHS [DK 36836] NR 47 TC 122 Z9 133 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1995 VL 96 IS 2 BP 733 EP 740 DI 10.1172/JCI118117 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RM466 UT WOS:A1995RM46600011 PM 7635966 ER PT J AU MEREDITH, M RABAGLIA, ME METZ, SA AF MEREDITH, M RABAGLIA, ME METZ, SA TI EVIDENCE OF A ROLE FOR GTP IN THE POTENTIATION OF CA2+-INDUCED INSULIN-SECRETION BY GLUCOSE IN INTACT RAT ISLETS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE GUANINE NUCLEOTIDES; ADENINE NUCLEOTIDES; STIMULUS-SECRETION COUPLING; DIAZOXIDE; SUCCINIC ACID ID PANCREATIC BETA-CELLS; SENSITIVE K+ CHANNELS; MOUSE B-CELLS; RELEASE; DIAZOXIDE; MECHANISMS; INHIBITION; ACID; DEHYDROGENASE; MITOCHONDRIA AB Glucose initiates insulin secretion by closing K+-ATP channels, leading to Ca2+ influx (E(1)); it also potentiates Ca2+-induced secretion (E(2)) when the K+-ATP channel is kept open using diazoxide and depolarizing concentrations of K+ are provided, To examine the roles of purine nucleotides in E(2), we compared the effects of glucose to those of the mitochondrial fuel monomethylsuccinate. Either agonist could induce E(2) accompanied by significant increases in ATP, ATP/ADP ratio, and GTP/GDP ratio; GTP increased significantly only with glucose, Mycophenolic acid (MPA), an inhibitor of cytosolic GTP synthesis, markedly inhibited glucose-induced E(2) (either in perifusions or in static incubations) and decreased GTP and the GTP/GDP ratio, but did not alter the ATP/ADP ratio, Provision of guanine (but not adenine) reversed these changes pari passu, In contrast, MPA had no effect on succinate-induced E(2), despite generally similar changes in nucleotides, A similar lack of effect of MPA on E(2) was Seen with a second mitochondrial fuel, alpha-ketoisocaproic acid (KIC), However, in the absence of diazoxide and K+, MPA blunted the secretory effects of either glucose, succinate, or KIC, These studies suggest that GTP plays a role in both glucose and succinate or KIC-induced insulin secretion at a step dependent on mitochondrial metabolism and the K+-ATP channel, In addition to mitochondrial effects, glucose appears to have extramitochondrial effects important to its potentiation of Ca2+-induced insulin secretion that are also dependent on GTP. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53792. UNIV WISCONSIN,DIV ENDOCRINOL,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM HOSP,MADISON,WI 53792. FU NIDDK NIH HHS [DK 37312] NR 41 TC 43 Z9 43 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1995 VL 96 IS 2 BP 811 EP 821 DI 10.1172/JCI118127 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RM466 UT WOS:A1995RM46600021 PM 7635976 ER PT J AU GRINSPOON, SK BAUM, HBA PETERSON, S KLIBANSKI, A AF GRINSPOON, SK BAUM, HBA PETERSON, S KLIBANSKI, A TI EFFECTS OF RHIGF-I ADMINISTRATION ON BONE TURNOVER DURING SHORT-TERM FASTING SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE INSULIN-LIKE GROWTH FACTOR I; BONE TURNOVER; FASTING; NUTRITION; OSTEOCALCIN ID GROWTH-FACTOR-I; MESSENGER RIBONUCLEIC-ACID; IGF-BINDING PROTEIN-3; PARATHYROID-HORMONE; ANOREXIA-NERVOSA; OSTEOBLASTIC CELLS; GUINEA-PIGS; COLLAGEN-SYNTHESIS; ORGAN-CULTURE; SOMATOMEDIN-C AB Insulin-like growth factor-I (IGF-I) is a nutritionally dependent bone trophic hormone which stimulates osteoblast function and collagen synthesis in vivo and in vitro, We hypothesized that in the fasting state, IGF-I levels would decline significantly and would establish a model in which we could investigate the effects of IGF-I administration on bone turnover, We therefore studied 14 normal women ages 19-33 (mean, 24+/-4 [SD] years) during a complete 10-d fast, After 4 d of fasting, subjects were randomized to receive rhIGF-I or placebo subcutaneously twice a day for 6 d, Bone turnover was assessed using specie markers of formation (osteocalcin and type I procollagen carboxyl-terminal propeptide [PICP]) and resorption (pyridinoline, deoxypyridinoline, type I collagen crosslinked N-telopeptide [N-telopeptide] and hydroxyproline), Serum levels of PICP and osteocalcin decreased from 143+/-52 to 60+/-28 ng/ml (P = 0.001) and from 7.6+/-5.4 to 4.2+/-3.1 ng/ml (P = 0.001) respectively with 4 d of fasting, Urinary excretion of pyridinoline and deoxypyridinoline decreased from 96+/-63 to 47+/-38 nmol/mmol creatinine (P < 0.05) and from 28+/-17 to 14+/-11 nmol/mmol creatinine (P ( 0.05) respectively, Mean IGF-I levels decreased from 310+/-81 to 186+/-78 ng/ml (P = 0.001), In the second part of the experimental protocol, serum osteocalcin and PICP levels increased 5- and 3-fold, respectively with rhIGF-I administration and were significantly elevated compared with the placebo group at the end of treatment (20.9+/-17.3 vs, 5.9+/-6.4 ng/ml for osteocalcin [P < 0.05] and 188+/-45 vs, 110+/-37 ng/ml for PICP [P < 0.05]), In contrast, all four markers of bone resorption, including urinary pyridinoline, deoxypyridinoline, N-telopeptide and hydroxyproline were unchanged with rhIGF-I administration. This report is the first to demonstrate that bone turnover falls rapidly with acute caloric deprivation in normal women, RhIGF-I administration uncouples bone formation in this setting by significantly increasing bone formation, but not resorption, These data suggest a novel use of rhIGF-I to selectively stimulate bone formation in states of undernutrition and low bone turnover. C1 MASSACHUSETTS GEN HOSP,NEUROENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NCRR NIH HHS [M01-RR01066]; NIDDK NIH HHS [P32-DK07028, F32-DK08783] NR 54 TC 82 Z9 82 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1995 VL 96 IS 2 BP 900 EP 906 DI 10.1172/JCI118137 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RM466 UT WOS:A1995RM46600031 PM 7543494 ER PT J AU CARMELI, Y RUOFF, KL AF CARMELI, Y RUOFF, KL TI REPORT OF CASES OF AND TAXONOMIC CONSIDERATIONS FOR LARGE-COLONY-FORMING LANCEFIELD GROUP-C STREPTOCOCCAL BACTEREMIA SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID BETA-HEMOLYTIC STREPTOCOCCI; INFECTIVE ENDOCARDITIS; MYOCARDIAL-INFARCTION; ENDEMIC PHARYNGITIS AB Traditionally, group C streptococci include four species: Streptococcus equisimilis, S. zooepidemicus, S. equi, and S. dysgalactiae, the first three of which are group C beta-hemolytic streptococci (GCBHS), However, many of the beta-hemolytic streptococci carrying Lancefield group C antigen isolated from clinical specimens are S. mulleri, These organisms can be differentiated by colony size, We retrospectively collected data concerning large-colony-forming GCBHS bacteremia that occurred during a period of 8 years at the Massachusetts General Hospital. A total of 222 cases of beta-hemolytic streptococcal bacteremia were identified; data on the Lancefield grouping were available in 192 cases: 45 cases (23.6%) were group A, 96 cases (50%) were group B, 7 cases (3.6%) were group C (large colony forming), and 44 cases (22.9) were group G. The medical records for cases of large-colony-forming GCBHS bacteremia were reviewed, In one case, the isolate was thought to be a contaminant; the other six cases are reported (five males and one female; mean age, 55 years). All patients had severe underlying conditions, and none had a history of exposure to animals, The clinical syndromes included two cases of cellulitis and one case each of endocarditis, myocardial infarction complicated by infection, pneumonia, and myofasciitis, The diagnoses for two patients with endovascular infections were delayed, Three of the six patients had fatal outcomes, and other two, after prolonged hospitalization, were transferred to a long-term rehabilitation center, We concluded that the severe outcomes reflect delay in diagnosis and treatment as well as the severity of the underlying diseases, The taxonomy of GCBHS is discussed, More reports differentiating large- and small-colony-forming GCBHS are needed. C1 MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MICROBIOL LABS,BOSTON,MA 02114. NR 24 TC 21 Z9 22 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 AUG PY 1995 VL 33 IS 8 BP 2114 EP 2117 PG 4 WC Microbiology SC Microbiology GA RJ052 UT WOS:A1995RJ05200027 PM 7559958 ER PT J AU CANNISTRA, SA ABUJAWDEH, G NILOFF, J STROBEL, T SWANSON, L ANDERSEN, J OTTENSMEIER, C AF CANNISTRA, SA ABUJAWDEH, G NILOFF, J STROBEL, T SWANSON, L ANDERSEN, J OTTENSMEIER, C TI CD44 VARIANT EXPRESSION IS A COMMON FEATURE OF EPITHELIAL OVARIAN-CANCER - LACK OF ASSOCIATION WITH STANDARD PROGNOSTIC FACTORS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID METASTASIS-ASSOCIATED VARIANT; COLONY-STIMULATING FACTOR; MONOCLONAL-ANTIBODIES; DEPENDENT MECHANISM; RECEPTOR; CELLS; HYALURONATE; CARCINOMAS; TRIGGERS; BINDING AB Purpose: CD44 is a hyaluronic acid receptor that exists as a standard 90-kd form (CD44S) as well as several CD44 variant isoforms produced through alternative splicing. Expression of CD44 variants is associated with clinically aggressive behavior in some human tumors. The purpose of the present study is to define the expression of CD44 variant isoforms in ovarian cancer and to investigate whether the expression of these molecules is associated with adverse prognosis. Materials and Methods Six specimens of normal ovarian surface epithelium (NOSE) and 31 separate cases of newly diagnosed ovarian cancer were studied by a combination of reverse-transcription polymerase chain reaction (RT-PCR) and immunoperoxidase staining. Clinical correlation wets made between CD44 variant expression and stage (I/II v III/IV), residual disease (less than or equal to 2.0- v > 2.0-cm mass), age (less than or equal to 65 v > 65 years), histology (papillary serous v other), grade, and survival. Results: RT-PCR analysis revealed that NOSE predominantly expressed transcripts for CD44S, as well as a restricted pattern of transcripts characteristic of CD44 splice variants. CD44S and CD44 variant exon nine sequences (CD44-9v) were focally expressed in one of two NOSE specimens examined by immunoperoxidase staining. In comparison, the majority (71%) of ovarian cancer specimens expressed a complex pattern of CD44 splice variants by RT-PCR analysis. Immunoperoxidase studies revealed that the majority of ovarian cancer specimens expressed both CD44S and CD44-9v, whereas expression of sequences from variant exons 3, 4, and 6 was uncommon. There was no association between CD44 variant expression (transcript or protein) and stage, residual disease, age, histology, grade, or survival. Conclusion: Expression of CD44S and CD44-9v is a common feature of epithelial ovarian cancer cells. The lack of a significant association between CD44 variant expression and prognosis suggests that other factors may be more important in determining the clinical behavior of this disease. J Clin Oncol 13:1912-1921. (C) 1995 by American Society of Clinical Oncology. RP CANNISTRA, SA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Ottensmeier, Christian/E-8131-2012 OI Ottensmeier, Christian/0000-0003-3619-1657 FU NCI NIH HHS [CA 06516, CA 60670] NR 35 TC 82 Z9 82 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1995 VL 13 IS 8 BP 1912 EP 1921 PG 10 WC Oncology SC Oncology GA RM473 UT WOS:A1995RM47300011 PM 7543560 ER PT J AU CANELLOS, GP PETRONI, GR BARCOS, M DUGGAN, DB PETERSON, BA AF CANELLOS, GP PETRONI, GR BARCOS, M DUGGAN, DB PETERSON, BA TI ETOPOSIDE, VINBLASTINE, AND DOXORUBICIN - AN ACTIVE REGIMEN FOR THE TREATMENT OF HODGKINS-DISEASE IN RELAPSE FOLLOWING MOPP SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; GERM-CELL TUMORS; COMBINATION CHEMOTHERAPY; SALVAGE CHEMOTHERAPY; DACARBAZINE ABVD; 1ST RELAPSE; BLEOMYCIN AB Purpose: To evaluate the activity and toxicity of combined etoposide, vinblastine, and doxorubicin (EVA) in advanced Hodgkin's disease (HD) in relapse from or refractory to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). Patients and Methods: Eligible patients were more than 15 years of age and had received only one prior course of MOPP and were in relapse with measurable disease. The EVA regimen (etoposide 100 mg/m(2) intravenously [1V] on days 1, 2, and 3; vinblastine 6 mg/m(2) IV on day 1; and doxorubicin 50 mg/m(2) IV on day 1) was administered every 28 days for a minimum of four and a maximum of six cycles, Patients were restaged at 3 and 6 months. Results: forty-five eligible patients were treated, with an overall response rate of 73%, There were 40% camplete responses (CRs) and 33% partial responses (PRs), The median follow-up time is 42 months, The median time to treatment failure (TTF) is 10 months, with 31% continuing progression-free. Eighteen patients achieved a second CR, with only seven recurrences in that group, Failure-free survival and overall survival were significantly better in patients whose first MOPP-induced remission was longer than 12 months and who were free of B symptoms at relapse. Toxicity was primarily myelosuppression, which resulted in two toxic deaths, Pulmonary toxicity was not observed. Conclusion: EVA is an effective second-line regimen for the treatment of HD in relapse following MOPP chemotherapy. J Clin Oncol 13:2005-2011. (C) 1995 by American Society of Clinical Oncology. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. DUKE UNIV,CTR BIOSTAT,CANC & LEUKEMIA GRP B,DURHAM,NC. ROSWELL PK CANC INST,DEPT PATHOL,BUFFALO,NY. SUNY HLTH SCI CTR,DEPT MED,SYRACUSE,NY 13210. UNIV MINNESOTA,DEPT MED,MINNEAPOLIS,MN 55455. RP CANELLOS, GP (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA47559, CA45808, CA03927] NR 33 TC 31 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1995 VL 13 IS 8 BP 2005 EP 2011 PG 7 WC Oncology SC Oncology GA RM473 UT WOS:A1995RM47300021 PM 7636541 ER PT J AU AYASH, LJ WHEELER, C FAIRCLOUGH, D SCHWARTZ, G REICH, E WARREN, D SCHNIPPER, L ANTMAN, K FREI, E ELIAS, A AF AYASH, LJ WHEELER, C FAIRCLOUGH, D SCHWARTZ, G REICH, E WARREN, D SCHNIPPER, L ANTMAN, K FREI, E ELIAS, A TI PROGNOSTIC FACTORS FOR PROLONGED PROGRESSION-FREE SURVIVAL WITH HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM-CELL SUPPORT FOR ADVANCED BREAST-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW SUPPORT; CONSOLIDATION THERAPY; STAGE; INTENSIFICATION; RESCUE; WOMEN AB Purpose: With a median observation time of 50 months from transplant, 13 (22%) of 62 women with metastatic breast cancer treated with high-dose chemotherapy at the Dana-Farber Cancer Institute (DFCl)/Beth Israel Hospital (BIH) remain progression-free. This study determined factors prognostic for prolonged progression-free survival (PFS). Methods: From June 1988 to January 1992, women who responded to standard chemotherapy received high-dose cyclophosphamide, thiotepo, and carboplatin with autotransplantation. Date encompassing initial breast cancer diagnosis, metastatic presentation, and response to induction treatment were examined for correlations with improved PFS. Results: The 5-year PFS rate for the entire group is estimated to be 21% (95% confidence interval [Cl], 10% to 32%). For those patients who attained a complete response (CR) to induction therapy, the 5-year PFS rate is estimated to be 31% (95% Cl, 0% to 63%). In univariate analyses, a single metastatic site, CR to induction therapy, prolonged interval from primary diagnosis to first metastases, estrogen receptor (ER)-negative tumors, and older age (greater than or equal to 40 years) were associated with prolonged PFS. In multivariate analyses, single metastatic site (P = .002) and attainment of a CR to induction chemotherapy (P = .04) were the most significant predictors for PFS, with a strong trend observed for an interval from primary diagnosis to onset of metastatic disease of 24+ months (P = .066). Conclusion: We and others have shown that 10% to 25% of women with metastatic breast cancer are progression-free after high-dose chemotherapy with autotransplantation. Those with chemosensitive disease, minimal tumor bulk, and a prolonged disease-free interval appear to benefit most. Emphasis should continue to focus on the development of more effective cytotoxic regimens and biologic approaches to increase the percentage of patients who may benefit from this approach. (C) 1995 by American Society of Clinical Oncology. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA. FU NCI NIH HHS [CA-06516, P01-CA-38493] NR 29 TC 116 Z9 116 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1995 VL 13 IS 8 BP 2043 EP 2049 PG 7 WC Oncology SC Oncology GA RM473 UT WOS:A1995RM47300027 PM 7636547 ER PT J AU HAFFAJEE, AD DIBART, S KENT, RL SOCRANSKY, SS AF HAFFAJEE, AD DIBART, S KENT, RL SOCRANSKY, SS TI CLINICAL AND MICROBIOLOGICAL CHANGES ASSOCIATED WITH THE USE OF 4 ADJUNCTIVE SYSTEMICALLY ADMINISTERED AGENTS IN THE TREATMENT OF PERIODONTAL INFECTIONS SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE PERIODONTAL DISEASES; PERIODONTITIS; TREATMENT; SURGERY; ANTIBODIES ID LOCALIZED JUVENILE PERIODONTITIS; HIGH-RISK PATIENTS; ACTINOMYCETEMCOMITANS-ASSOCIATED PERIODONTITIS; ALVEOLAR BONE LOSS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; REFRACTORY PERIODONTITIS; RECURRENT PERIODONTITIS; TETRACYCLINE THERAPY; PROGRESSIVE PERIODONTITIS; IMMUNOLOGICAL FEATURES AB The purpose of the present investigation was to assess the effects of periodontal surgery and 4 systemically administered agents, Augmentin, tetracycline, ibuprofen or a placebo on clinical and microbiological parameters of periodontal disease, 98 subjects were monitored at 2-month intervals at 6 sites per tooth for clinical parameters. Subgingival plaque samples were taken from the mesial surface of each tooth at each visit and evaluated for their content of 14 subgingival species using DNA probes and a colony lift method, 40 subjects who exhibited loss of attachment >2.5 mm at I or more sites during longitudinal monitoring were treated using modified Widman flap surgery at sites with probing pocket depth >4 mm, subgingival scaling at all other sites and were randomly assigned I of the 4 agents. Treatment was completed within 30 days during which time the subject took the assigned agent, Overall, subjects exhibited a mean attachment level ''gain'' of 0.34 +/- 0.10 mm (SEM) and a mean pocket depth reduction of 0.62 +/- 0.09 mm 10 +/- 4 months post-therapy. However, certain subjects in each treatment group showed a poor response. Subjects receiving antibiotics exhibited significantly more attachment level ''gain'' (0.57 +/- 0.15 mm, SEM) than subjects receiving either ibuprofen or a placebo (0.02 +/- 0.10). The differences between Augmentin and tetracycline groups were not significant, nor were the differences between ibuprofen and placebo. 10 months post-therapy, there was a reduction in the number of sites colonized in any subject group by detectable levels (10(3)) of P. gingivalis. Species showing similar reductions were B. forsythus; P. inter media and P. micros. Subjects receiving systemically administered antibiotics had a significant increase in the proportion of sites colonized by C. ochracea coupled with a greater decrease in the number of sites colonized by P. gingivalis, B. forsythus, P. intermedia and P. micros post-therapy than subjects not receiving antibiotics. The results of this investigation indicate that adjunctive systemic antibiotics increase periodontal attachment ''gain'' and decrease the levels of some suspected periodontal pathogens in subjects with evidence of current disease progression. C1 FORSYTH DENT CTR,DEPT BIOSTAT,BOSTON,MA 02115. RP HAFFAJEE, AD (reprint author), FORSYTH DENT CTR,DEPT PERIODONTOL,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-04881] NR 59 TC 73 Z9 73 U1 1 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD AUG PY 1995 VL 22 IS 8 BP 618 EP 627 DI 10.1111/j.1600-051X.1995.tb00815.x PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RM861 UT WOS:A1995RM86100007 PM 8583019 ER PT J AU HAFFAJEE, AD DIBART, S KENT, RL SOCRANSKY, SS AF HAFFAJEE, AD DIBART, S KENT, RL SOCRANSKY, SS TI FACTORS ASSOCIATED WITH DIFFERENT RESPONSES TO PERIODONTAL THERAPY SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE PERIODONTAL DISEASE; TREATMENT RESPONSE; SUBGINGIVAL PLAQUE ID ATTACHMENT LEVEL AB In a study of the efficacy of modified Widman flap surgery and scaling and root planing accompanied by I of 4 systemic adjunctive agents, Augmentin, tetracyline, ibuprofen or placebo, it was observed that subjects differed in their response to therapy. The difference was only partially accounted for by the adjunctive agent employed. The purpose of the present investigation was to examine clinical and microbiological features in subjects who showed different levels of attachment change post-therapy. 40 subjects were subset into 3 groups based on mean attachment level change post-therapy. 10 poor response subjects showed mean attachment loss; 19 moderate response subjects showed mean attachment gain between 0.02-0.5 mm and 1I good response subjects showed a mean gain of attachment >0.5 mm. Clinical parameters were measured at 6 sites per tooth both pre- and post-therapy. Microbiological samples were taken from the mesial aspect of each tooth and evaluated individually for their content of 14 subgingival taxa using a colony lift method and DNA probes. % of sites colonized by each species was computed for each subject both pre- and post-therapy. Significant differences were observed among treatment response groups for mean probing pocket depth, attachment level and % of sites with plaque pre-therapy. The poor response subjects had the lowest mean probing pocket depth and attachment level, but the highest plaque levels. Post-therapy, the poor response group exhibited the greatest degree of gingival inflammation as assessed by gingival redness and bleeding on probing. Subjects in the good response group showed decreases in the % of sites colonized for 9 of 14 test species, while subjects in the poor response group showed an increase in % of sites colonized for 12 species. The differences in change in % of sites colonized among groups were significant for B. forsythus and P. gingivalis. The majority of attachment loss in poor response subjects occurred at sites with pre-therapy probing pocket depths <4 mm. Subjects with moderate or good treatment responses had fewer shallow or moderate sites showing attachment loss and a large proportion of sites in all probing pocket depth categories showing attachment gain. Sites that lost attachment greater than or equal to 2 mm post-therapy showed a significant increase in counts of P. intermediate, B, forsythus and A. actinomycetemcomitans b, while sites that gained attachment showed a decrease in these species. The data indicated that subjects who showed a good treatment response exhibited a decrease in the level of gingival inflammation and a marked reduction in the % of sites colonized by suspected periodontal pathogens. In subjects showing a poor treatment response, the level of gingival inflammation was not decreased and levels of periodontal pathogens increased. C1 FORSYTH DENT CTR,DEPT BIOSTAT,BOSTON,MA 02115. RP HAFFAJEE, AD (reprint author), FORSYTH DENT CTR,DEPT PERIODONTOL,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-04881] NR 10 TC 29 Z9 30 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD AUG PY 1995 VL 22 IS 8 BP 628 EP 636 DI 10.1111/j.1600-051X.1995.tb00816.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RM861 UT WOS:A1995RM86100008 PM 8583020 ER PT J AU WEILBURG, JB SCHACHTER, S WORTH, J POLLACK, MH SACHS, GS IVES, JR SCHOMER, DL AF WEILBURG, JB SCHACHTER, S WORTH, J POLLACK, MH SACHS, GS IVES, JR SCHOMER, DL TI EEG ABNORMALITIES IN PATIENTS WITH ATYPICAL PANIC ATTACKS SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DISORDER; SEIZURES; ANXIETY AB Background: Panic attacks and certain partial seizures have phenomenologic similarities which suggest that they may somehow be related. No evidence of such a relationship, however, was found when the routine EEGs of patients with panic attacks were examined. Method: Fifteen subjects with atypical panic attacks who met DSM-III-R criteria for panic disorder agreed to have routine followed by prolonged ambulatory EEG monitoring with sphenoidal electrodes. Fourteen subjects actually underwent monitoring; 1 had a panic attack during premonitoring routine EEG. Results: Focal paroxysmal EEG changes consistent with partial seizure activity occurred during panic attacks in 33% (N = 5) of the 15 subjects; 2 (40%) of the 5 subjects with panic-related EEG changes had normal routine EEGs. Multiple attacks were recorded before panic-related EEG changes were demonstrated in several subjects. Conclusion: It may be necessary to monitor the EEG during multiple panic attacks to reveal an association between atypical panic attacks and epileptiform EEG changes. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. BETH ISRAEL HOSP,DEPT NEUROL,BOSTON,MA 02215. NR 24 TC 26 Z9 27 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 1995 VL 56 IS 8 BP 358 EP 362 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA RQ003 UT WOS:A1995RQ00300005 PM 7635852 ER PT J AU ROSENBAUM, JF AF ROSENBAUM, JF TI TREATMENT OF SOCIAL PHOBIA AND COMORBID DISORDERS SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP ROSENBAUM, JF (reprint author), MASSACHUSETTS GEN HOSP,DIV OUTPATIENT PSYCHIAT,BOSTON,MA 02114, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 1995 VL 56 IS 8 BP 380 EP 380 PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA RQ003 UT WOS:A1995RQ00300017 ER PT J AU WILENS, TE BIEDERMAN, J SPENCER, TJ PRINCE, J AF WILENS, TE BIEDERMAN, J SPENCER, TJ PRINCE, J TI PHARMACOTHERAPY OF ADULT ATTENTION-DEFICIT HYPERACTIVITY DISORDER - A REVIEW SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Review ID MINIMAL BRAIN-DYSFUNCTION; RESIDUAL TYPE; PSYCHIATRIC STATUS; OPEN TRIAL; STIMULANT MEDICATION; METHYLPHENIDATE; CHILDREN; BOYS; COMORBIDITY; PREVALENCE AB Adult attention deficit/hyperactivity disorder (ADHD) is an increasingly recognized disorder with associated psychiatric comorbidity and impairment. Although pharmacotherapy serves an important role in treating ADHD and other concurrent psychiatric disorders in children and adolescents, the use of pharmacotherapeutics for adults with ADHD remains less established. In this report, the effectiveness and dosing parameters of the various agents investigated for adult ADHD are reviewed. A systematic review of the available literature identified 7 studies (N = 193 subjects) of psychostimulants and 10 studies of nonstimulant medications (N = 167 subjects) including antidepressants, antihypertensives, and amino acids for the treatment of ADHD in adults. The majority of double-blind investigations were with the psychostimulants, with the nonstimulant agents, generally antidepressants, studied under open conditions. There was considerable variability in diagnostic criteria, dosing parameters, and response rates between the various studies. Under controlled conditions, the aggregate literature shows that the stimulants had a clinically and statistically significant effect on reducing ADHD symptoms. Open studies on the nonserotonergic antidepressants (tricyclics, bupropion, and monoamine oxidase inhibitors) also show a moderate anti-ADHD effect. The literature appears to support the use of robust doses of both stimulants and antidepressants for ADHD in adults. Further controlled studies applying stringent diagnostic criteria and outcome methodology are necessary to define the range of pharmacotherapeutic options for adults with ADHD. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP WILENS, TE (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,WACC 725,BOSTON,MA 02114, USA. NR 80 TC 97 Z9 98 U1 3 U2 8 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 1995 VL 15 IS 4 BP 270 EP 279 DI 10.1097/00004714-199508000-00006 PG 10 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA RM826 UT WOS:A1995RM82600006 PM 7593710 ER PT J AU KACHINSKY, AM DOMINOV, JA MILLER, JB AF KACHINSKY, AM DOMINOV, JA MILLER, JB TI INTERMEDIATE FILAMENTS IN CARDIAC MYOGENESIS - NESTIN IN THE DEVELOPING MOUSE HEART SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Note DE NESTIN; INTERMEDIATE FILAMENT; HEART DEVELOPMENT; CARDIOMYOCYTE; MOUSE; REVERSE TRANSCRIPTASE PCR; IMMUNOHISTOCHEMISTRY ID CELLS; EXPRESSION; PROTEIN; SYSTEM; DESMIN; RAT AB By using immunohistology combined with immunoblotting, cell. culture, and RT-PCR, we show that the intermediate filament protein nestin is transiently expressed in the midembryonic mouse heart. Monoclonal antibody (MAb) Rat-401, known to react with nestin in neural and skeletal muscle cells, was also found to react with ventricular and atrial cells throughout the mouse heart from embryonic day 9 (E9) through E10.5. Both before (E8.5) and after (E11-adult) this brief period, staining with Rat-401 was absent from atrial. and ventricular myocytes. To evaluate the specificity of staining with MAb Rat-401 in the heart, we used immunoblotting, cell culture, and RT-PCR to verify that the authentic nestin protein and mRNA were expressed in cardiomyocytes of the E10 mouse. Nestin expression is the first molecular marker for this distinct midembryonic period of heart development. C1 MASSACHUSETTS GEN HOSP,NEUROMUSCULAR LAB,BOSTON,MA 02129. NR 24 TC 100 Z9 105 U1 0 U2 2 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD AUG PY 1995 VL 43 IS 8 BP 843 EP 847 PG 5 WC Cell Biology SC Cell Biology GA RL823 UT WOS:A1995RL82300011 PM 7542682 ER PT J AU BEISSERT, S ULLRICH, SE HOSOI, J GRANSTEIN, RD AF BEISSERT, S ULLRICH, SE HOSOI, J GRANSTEIN, RD TI SUPERNATANTS FROM UVB RADIATION-EXPOSED KERATINOCYTES INHIBIT LANGERHANS CELL PRESENTATION OF TUMOR-ASSOCIATED ANTIGENS VIA IL-10 CONTENT SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE LANGERHANS CELLS; UVR; IL-10; TUMOR ANTIGEN PRESENTATION ID DELAYED-TYPE HYPERSENSITIVITY; NECROSIS-FACTOR-ALPHA; ULTRAVIOLET-RADIATION; HISTOCOMPATIBILITY ANTIGENS; SINGLE EXPOSURE; MICE; SUPPRESSION; LIGHT; INDUCTION AB Exposure of mice to midrange UV radiation (UVB) (280-320 mm) in vivo leads to suppression of the ability to induce delayed-type hypersensitivity (DTH), Systemic administration of supernatants from UVB exposed keratinocytes (KC) similarly inhibits the ability to induce DTH and the presence of interleukin-10 (IL-10) in the supernatants has been shown to be responsible for this effect. It has been hypothesized that release of IL-10 by KC after exposure to UVB radiation in vivo may be responsible for UVB-induced inhibition of DTH and also for the inability of chronically UVB-irradiated mice to immunologically reject immunogenic UVB-induced skin tumors, To test directly whether supernatants from UVB-irradiated KC can inhibit presentation of tumor-associated antigens (TAA) by epidermal Langerhans cells (LC), cultures of the transformed murine KC line PAM 212 were exposed to 200 J/m(2) of UVB radiation and 24 h supernatants obtained, CAF(1) (H-2(a/d)) epidermal cells (EC) enriched for LC content were exposed to supernatants from irradiated (UV-SN) or mock-irradiated (MI-SN) PAM 212 cells for 3 h followed by culture for 16 h in granulocyte-macrophage colony-stimulating factor and then were pulsed with soluble TAA derived from the murine spindle cell tumor S1509a (H-2(a)). ECs were then washed and injected subcutaneously into naive CAF(1) mice three times at weekly intervals for priming, One week after the final immunization these mice were challenged subcutaneously with live S1509(a) cells and tumor growth scored over time, Pretreatment of EC with UV-SN but not MI-SN inhibited the induction of effective immunity by this immunization scheme, ECs were also treated with UV-SN or MI-SN for 3 h then pulsed with TAA and injected into a hind footpad of previously immunized mice for elicitation of a DTH response, Pretreatment of EC with UV-SN but not MI-SN inhibited the ability of EC to elicit DTH. Neutralization studies with specific neutralizing antibodies to IL-10 demonstrated that the presence of IL-10 in UV-SN was responsible for the inhibition of antigen presentation both for induction and elicitation of immunity, UV-SN inhibits tumor antigen presentation by epidermal LC through the action of IL-10. C1 HARVARD UNIV,SCH MED,BOSTON,MA. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT IMMUNOL,HOUSTON,TX 77030. RP BEISSERT, S (reprint author), MASSACHUSETTS GEN HOSP,HARVARD CUTANEOUS BIOL RES CTR,DEPT DERMATOL,BLDG 149,13TH ST,3RD FLOOR,BOSTON,MA 02129, USA. FU NIAMS NIH HHS [AR40667] NR 26 TC 26 Z9 29 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD AUG PY 1995 VL 58 IS 2 BP 234 EP 240 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA RP559 UT WOS:A1995RP55900015 PM 7643016 ER PT J AU BERSOHN, MM AF BERSOHN, MM TI SODIUM-PUMP INHIBITION IN SARCOLEMMA FROM ISCHEMIC HEARTS SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE RABBIT HEART; SARCOLEMMAL VESICLES; SODIUM POTASSIUM ATPASE; OUABAIN; SODIUM CALCIUM EXCHANGE; PERMEABILITY ID NA+-K+-ATPASE; CALCIUM EXCHANGE; REPERFUSION; HYPOXIA; FAILURE AB Ischemic myocardial cells lose K+ and accumulate Na+. The role of the Na+/K+-pump in these changes was investigated by measuring both Na+/K+-ATPase activity and Na+ pumping in highly purified sarcolemmal vesicles from rabbit hearts made globally ischaemic for 1 h compared to non-ischemic controls, Purification of the sarcolemma was similar for control, 31 +/- 8-fold, and ischemia, 38 +/- 10-fold. The fraction of intact inside-out vesicles, in which Na+ pumping could be measured, was also the same for control, 60 +/- 16%, and ischemic, 56 +/- 8% as measured by H-3-ouabain binding in the presence and absence of detergent, Scatchard analysis of ouabain binding revealed a 26% increase in binding sites in ischemia compared to control. The Na+/K+-ATPase in the inside-out vesicles, measured as monensin-stimulated activity, was not affected by ischemia: 22 +/- 9 v 21 +/- 9 mu mol P-1 mg(-1) h(-1) for control and ischemic respectively, However, the initial velocity of ATP-dependent Na+ pumping into inside-out vesicles, assayed by subsequent exchange of Na-i(+) for Ca-45(2+) by the Na+-Ca2+ exchanger present in the vesicles, was inhibited in ischemia. At 18 mM Na-0(+) the velocity for control vesicles was 2.4 +/- 0.2 nmol mg(-1) s(-1) compared to 1.1 +/- 0.1 for ischemia vesicles, Passive sarcolemmal Na+ permeability was unchanged after 1 h of ischemia. The large reduction in Na+ pumping with unchanged Na+/K+-ATPase suggests uncoupling of the Na+/K+-pump in ischemia and a decreased ability to extrude Na+ despite the increase in number of pump sites in the sarcolemma. (C) 1995 academic Press Limited C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90073 USA. RP BERSOHN, MM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR, CARDIOL SECT 111E, 11301 WILSHIRE BLVD, LOS ANGELES, CA 90073 USA. NR 22 TC 19 Z9 19 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD AUG PY 1995 VL 27 IS 8 BP 1483 EP 1489 DI 10.1016/S0022-2828(95)90161-2 PG 7 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA RR075 UT WOS:A1995RR07500003 PM 8523412 ER PT J AU SCHWARTZ, PJ BERGER, UV COYLE, JT AF SCHWARTZ, PJ BERGER, UV COYLE, JT TI MICE TRANSGENIC FOR COPPER/ZINC SUPEROXIDE-DISMUTASE EXHIBIT INCREASED MARKERS OF BIOGENIC-AMINE FUNCTION SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE SUPEROXIDE DISMUTASE; TRISOMY 21; DOWNS SYNDROME; NEUROCHEMISTRY; OXIDATIVE STRESS ID NERVE GROWTH-FACTOR; GLUTATHIONE-PEROXIDASE ACTIVITIES; LIPID-PEROXIDATION; DOWNS-SYNDROME; MESSENGER-RNA; NEURONS; DEATH; CELLS; GENE; NEUROTOXICITY AB Mice that are transgenic for and overexpress human copper/zinc superoxide dismutase were used to investigate the role of this enzyme in the pathophysiology of Down's syndrome (DS; trisomy 21). Previous studies have indicated that overexpression of copper/zinc superoxide dismutase leads to deficits in peripheral markers of neurochemical function, which are consistent with the hypothesis that this enzyme plays a role in the pathophysiology of DS. We have measured concentrations of amino acids and biogenic amines (catecholamines, serotonin, and their metabolites), uptake of biogenic amines into crude synaptosomes, and activities of synthetic enzymes in both control mice and mice transgenic for human copper/zinc superoxide dismutase that overexpress it by two- to fivefold above control values. We find that these transgenic mice exhibit higher concentrations of the biogenic amines in specific brain regions, with little or no change in amino acid concentration. Furthermore, tyrosine hydroxylase activity is increased in the striatum of the transgenics, whereas glutamic acid decarboxylase and choline acetyltransferase activities are unchanged in all but one brain region. These findings indicate that overexpression of copper/zinc superoxide dismutase, by itself, is not sufficient to cause the synaptic neurochemical deficits reported in DS. C1 MASSACHUSETTS GEN HOSP,MOLEC & DEV NEUROSCI LAB,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. FU NIMH NIH HHS [P01-MH46529-02]; NINDS NIH HHS [R01-NS13584-15, R01-NS18414-10] NR 42 TC 4 Z9 4 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 AUG PY 1995 VL 65 IS 2 BP 660 EP 669 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RJ657 UT WOS:A1995RJ65700023 PM 7616222 ER PT J AU BEAL, MF FERRANTE, RJ HENSHAW, R MATTHEWS, RT CHAN, PH KOWALL, NW EPSTEIN, CJ SCHULZ, JB AF BEAL, MF FERRANTE, RJ HENSHAW, R MATTHEWS, RT CHAN, PH KOWALL, NW EPSTEIN, CJ SCHULZ, JB TI 3-NITROPROPIONIC ACID NEUROTOXICITY IS ATTENUATED IN COPPER/ZINC SUPEROXIDE-DISMUTASE TRANSGENIC MICE SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE 3-NITROPROPIONIC ACID; MITOCHONDRIAL TOXIN; EXCITOTOXICITY; TRANSGENIC MICE; HUMAN COPPER ZINC SUPEROXIDE DISMUTASE GENE; NEUROTOXICITY; OXYGEN FREE RADICAL; PEROXYNITRITE ID TOXIN; STRIATUM; LESIONS AB The mitochondrial toxin 3-nitropropionic acid (3-NP) produces selective striatal lesions in both experimental animals and humans. The pathogenesis of the lesions involves secondary excitotoxicity that may then lead to free radical generation. To test this further we examined the effects of 3-NP in both transgenic (Tg) mice that carry the complete sequence for the human copper/zinc superoxide dismutase (SOD) gene as well as non-Tg littermate controls. The Tg-SOD mice showed a pronounced attenuation of Nissl-stained striatal lesions compared with non-Tg mice. Systemic administration of 3-NP resulted in production of hydroxyl free radicals as assessed by the conversion of salicylate to 2,3- and 2,5-dihydroxybenzoic acid. This production was attenuated significantly in Tg-SOD mice. In a similar way, 3-NP produced significant increases in 3-nitrotyrosine/tyrosine, a marker for peroxynitrite-mediated damage, which were significantly attenuated in Tg-SOD mice. These results support that oxygen free radicals and peroxynitrite play an important role in the pathogenesis of 3-NP neurotoxicity. C1 HARVARD UNIV,SCH MED,BOSTON,MA. UNIV CALIF SAN FRANCISCO,DEPT NEUROL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT NEUROSURG,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. BOSTON UNIV,BEDFORD VA MED CTR,SCH MED,DEPT NEUROL,CTR GERIATR RES EDUC & CLIN,BOSTON,MA 02215. BOSTON UNIV,BEDFORD VA MED CTR,SCH MED,DEPT PATHOL,CTR GERIATR RES EDUC & CLIN,BOSTON,MA 02215. RP BEAL, MF (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,WARREN 408,BOSTON,MA 02114, USA. RI Schulz, Jorg/D-9786-2012; Kowall, Neil/G-6364-2012 OI Schulz, Jorg/0000-0002-8903-0593; Kowall, Neil/0000-0002-6624-0213 FU NINDS NIH HHS [NS 10828, NS 16367, NS 31579] NR 24 TC 124 Z9 124 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 AUG PY 1995 VL 65 IS 2 BP 919 EP 922 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RJ657 UT WOS:A1995RJ65700058 PM 7616254 ER PT J AU IGARASHI, M LI, WW SUDO, Y FISHMAN, MC AF IGARASHI, M LI, WW SUDO, Y FISHMAN, MC TI LIGAND-INDUCED GROWTH CONE COLLAPSE - AMPLIFICATION AND BLOCKADE BY VARIANT GAP-43 PEPTIDES SO JOURNAL OF NEUROSCIENCE LA English DT Article DE REGENERATION; NERVE GROWTH; MYELIN; G PROTEINS; GAP-43; GROWTH CONE ID CENTRAL-NERVOUS-SYSTEM; PROTEIN GAP-43; BINDING-PROTEIN; RAT-BRAIN; MEMBRANE; G0; NEURONS; TRANSDUCTION; FILOPODIA; MECHANISM AB Growth cones are powerful amplifiers for signals from the microenvironment. Their collapse can be triggered by cell surface components of myelin and brain membranes, as well as by soluble ligands, including neurotransmitters. GAP-43 is a protein concentrated on the inner surface of the growth cone membrane. Assayed in isolation, it interacts with the heterotrimeric protein, G(o), and in oocytes it amplifies the effects of ligand-triggered G protein activation. We wished to examine whether GAP-43 serves to amplify signals at the growth cone. The G(o), stimulating region of GAP-43 is encoded in the 10 amino acids (MLCCMRRTKQ) of the first exon. We examined the effect of this peptide upon chick dorsal root ganglion growth cone collapse and neurite retraction triggered by brain membranes or myelin, as well as by serotonin. We find that application of the GAP-43 1-10 peptide amplifies the effects of all three ligands. The amplification is greater when GAP-43 1-10 is injected intracellularly. Peptides with amino acid substitutions for the two cysteine residues manifest parallel changes in growth cone collapse and G(o) stimulation. In particular, tyrosine or methionine substitutions cause the peptide to inhibit G(o) and to block induced growth cone collapse. The GAP-43 peptides therefore regulate the sensitivity of growth cones to extrinsic signals. The modified peptides serve as a starting point for the design of reagents to enhance CNS regeneration. C1 MASSACHUSETTS GEN HOSP EAST,DEV BIOL LAB,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 51 TC 36 Z9 38 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG PY 1995 VL 15 IS 8 BP 5660 EP 5667 PG 8 WC Neurosciences SC Neurosciences & Neurology GA RP560 UT WOS:A1995RP56000019 PM 7643208 ER PT J AU HUANG, PG ALLAM, A TAGHIAN, A FREEMAN, J DUFFY, M SUIT, HD AF HUANG, PG ALLAM, A TAGHIAN, A FREEMAN, J DUFFY, M SUIT, HD TI GROWTH AND METASTATIC BEHAVIOR OF 5 HUMAN GLIOBLASTOMAS COMPARED WITH 9 OTHER HISTOLOGICAL TYPES OF HUMAN TUMOR XENOGRAFTS IN SCID MICE SO JOURNAL OF NEUROSURGERY LA English DT Article DE HUMAN GLIOBLASTOMA MULTIFORME; XENOGRAFT; GROWTH BEHAVIOR; METASTASIS; SCID MICE ID SEVERE COMBINED IMMUNODEFICIENCY; NCR/SED NUDE-MICE; EXTRANEURAL METASTASES; SUPRATENTORIAL GLIOBLASTOMA; CEREBRAL GLIOBLASTOMA; CELL-LINES; MULTIFORME; GLIOMAS; BRAIN; TRANSPLANTABILITY AB The growth and metastatic behavior of five human glioblastoma multiforme xenografts and nine human xenografts of various histological types were compared in severe combined immunodeficient (SCID) mice. The results demonstrate that the metastatic behavior of the human glioblastoma multiforme xenografts did not differ significantly from a variety of other histological xenografts when evaluated at the same transplantation site in the SCID model. These results are consistent with the hypothesis that the site of glioblastoma multiforme growth influences the extraneural metastatic spread of this disease and lead the authors to suggest that the clinical rarity of distant metastasis is not a fundamental property of these cells. A total of 340 male 7- to 8-week-old SCID mice received subcutaneous transplantation of tumor fragments (21-25 mice per tumor type). The tumor-bearing leg was amputated when the tumor reached a volume of 500 mm(3): mice were observed for up to 5 months. There was a trend for a lower take rate, longer latent period, longer volume doubling time (VDT) and growth time (GT) in glioblastoma multiforme as opposed to carcinoma and soft tissue sarcoma xenografts. The highest local recurrence rates (75% and 68%) were observed in two glioblastomas multiforme. Both the glioblastoma multiforme and the other histological xenografts exhibited a widely varying metastatic rate: no correlation was demonstrated between VDT, GT, local control/recurrence, and distant metastasis. These findings show SCID mice to be an attractive model for further biological and preclinical studies of human glioblastoma multiforme. RP HUANG, PG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB RADIAT BIOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA13311] NR 34 TC 49 Z9 50 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 1995 VL 83 IS 2 BP 308 EP 315 DI 10.3171/jns.1995.83.2.0308 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA RL110 UT WOS:A1995RL11000019 PM 7616277 ER PT J AU LI, KK MEARA, JG RUBIN, PAD AF LI, KK MEARA, JG RUBIN, PAD TI ORBITAL COMPARTMENT SYNDROME FOLLOWING ORTHOGNATHIC SURGERY SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Note ID BLINDNESS FOLLOWING BLEPHAROPLASTY C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,EYE PLAST & ORBIT SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL & OPHTHALMOL,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL HEAD & NECK SURG,BOSTON,MA. NR 15 TC 25 Z9 29 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD AUG PY 1995 VL 53 IS 8 BP 964 EP 968 DI 10.1016/0278-2391(95)90294-5 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RN300 UT WOS:A1995RN30000025 PM 7629632 ER PT J AU HURWITZ, CA MOUNCE, KG GRIER, HE AF HURWITZ, CA MOUNCE, KG GRIER, HE TI TREATMENT OF PATIENTS WITH ACUTE MYELOGENOUS LEUKEMIA - REVIEW OF CLINICAL-TRIALS OF THE PAST DECADE SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Review DE ACUTE MYELOGENOUS LEUKEMIA; PEDIATRICS; CLINICAL TRIALS ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE NONLYMPHOBLASTIC LEUKEMIA; ACUTE MYELOBLASTIC-LEUKEMIA; TRANS-RETINOIC ACID; ACUTE MYELOCYTIC-LEUKEMIA; COLONY-STIMULATING FACTOR; NON-LYMPHOCYTIC LEUKEMIA AB We discuss the history and progress of treatment for acute myelogenous leukemia (AML) in children as it has evolved over the past decade. We review the results of clinical trails for children with AML and examine the major strategies that have contributed to progresss in the treatment of this disease. Prior to the 1970's, nearly every child with AML died. Modern intensive chemotherapy, bone marrow transplantation, and advanced supportive care of critically ill patients have improved the outlook for children with this fatal disease. Conclusion: Although it represents only 15-20% of all childhood acute leukemias, >30% of deaths from leukemia are still a consequence of AML, and only 30-40% of children with newly diagnosed AML are expected to achieve a long-term remission. Greater advances in treatment are expected as headway is made in understanding the complex biology of this heterogenous disease. C1 ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN USA. CHILDRENS HOSP, BOSTON, MA USA. DANA FARBER CANC INST, BOSTON, MA USA. RP HURWITZ, CA (reprint author), MAINE MED CTR, DEPT PEDIAT, MAINE CHILDRENS CANC PROGRAM, 295 FOREST AVE, 2ND FLOOR, PORTLAND, ME 04101 USA. NR 127 TC 33 Z9 35 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD AUG PY 1995 VL 17 IS 3 BP 185 EP 197 DI 10.1097/00043426-199508000-00001 PG 13 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA RM090 UT WOS:A1995RM09000001 PM 7620918 ER PT J AU KUNG, FH DESAI, SJ DICKERMAN, JD GOORIN, AM HARRIS, MB INOUE, S KRISCHER, JP MURPHY, SB PRATT, CB TOLEDANO, S WILEY, JM YU, AL AF KUNG, FH DESAI, SJ DICKERMAN, JD GOORIN, AM HARRIS, MB INOUE, S KRISCHER, JP MURPHY, SB PRATT, CB TOLEDANO, S WILEY, JM YU, AL TI IFOSFAMIDE CARBOPLATIN ETOPOSIDE (ICE) FOR RECURRENT MALIGNANT SOLID TUMORS OF CHILDHOOD - A PEDIATRIC-ONCOLOGY-GROUP PHASE I/II STUDY SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE ICE; IFOSFAMIDE (I); CARBOPLATIN (C); ETOPOSIDE (E); RECURRENT CHILDHOOD MALIGNANT SOLID TUMORS ID II TRIAL; CHILDREN; COMBINATION AB Purpose: The combination of ifosfamide (I) and etoposide (E) was useful in salvaging patients with recurrent/resistant malignant solid tumors of childhood. Carboplatin (C), active against a number of pediatric cancers, was added to I and E to form a three-drug combination called ICE to improve the response rate. Patients and Methods: ICE, consisting of I 1.5 g/m(2) plus E 100 mg/m(2) i.v.q.d. X 3 plus C i.v. on day 3 only, was given in 21-28-day intervals. C was started at 300 mg/m(2), and the dose was escalated in 25% increments, with three evaluable patients treated at each level. Results: Ninety-two patients were enrolled in this phase I/II study between July 1990 and April 1993. A total of 331 courses of ICE was administered. Median courses of ICE received were three (range, 1-16). The maximum tolerated dose (MTD) for C when used in combination was found to be 635 mg/m(2). The response rate for ICE at the MTD for C was complete response (CR) 26% and CR + partial response (PR) 53%. The response was even better in those who received C at the MTD: 32% achieving a CR and 63% a CR + PR. Pancytopenia was the dose-limiting toxicity. Thirteen episodes of bacterial infection were reported, none fatal. Only one patient developed a Fanconi-like syndrome. Conclusion: The MTD of C when used with I and E was found to be 635 mg/m(2). The overall CR + PR rate for all patients treated at all C dose levels was 53%. Best responses were seen in non-Hodgkin's lymphoma, neuroblastoma, soft tissue sarcomas, and Wilms' tumor. Myelosuppression was the predominant toxicity and was dose limiting. C1 UNIV CALIF SAN DIEGO, SCH MED, LA JOLLA, CA USA. UNIV ALBERTA, CROSS CANC INST, EDMONTON, AB, CANADA. UNIV VERMONT, COLL MED, BURLINGTON, VT USA. DANA FARBER CANC INST, BOSTON, MA USA. TOMORROWS CHILDRENS INST, HACKENSACK, NJ USA. HURLEY MED CTR, FLINT, MI USA. UNIV S FLORIDA, TAMPA, FL USA. CHILDRENS MEM HOSP, CHICAGO, IL USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN USA. UNIV MIAMI, SCH MED, MIAMI, FL USA. JOHNS HOPKINS UNIV HOSP, BALTIMORE, MD USA. FU NCI NIH HHS [CA-20549, CA-11233, CA-28439] NR 12 TC 37 Z9 37 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD AUG PY 1995 VL 17 IS 3 BP 265 EP 269 DI 10.1097/00043426-199508000-00009 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA RM090 UT WOS:A1995RM09000009 PM 7620926 ER PT J AU GLASGOW, RE ANDERSON, BJ AF GLASGOW, RE ANDERSON, BJ TI FUTURE-DIRECTIONS FOR RESEARCH ON PEDIATRIC CHRONIC DISEASE MANAGEMENT - LESSONS FROM DIABETES SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE RESEARCH DESIGN; CHRONIC DISEASE MANAGEMENT; GENERALIZABILITY ID SELF-MANAGEMENT; HEALTH-STATUS; ADHERENCE; FAMILY; MELLITUS; ADOLESCENTS; OUTCOMES; CHILDREN; ISSUES; IDDM AB Discussed conceptual and methodological issues related to research on the management of pediatric chronic disease, focusing on diabetes. The quality of studies in this area has improved, but several problems remain. Recommendations include greater use of theory in planning studies; population-based samples; more sophisticated definitions of adherence; longitudinal designs; and analyses that control for demographic, developmental, and medical variables. Most needed are prevention and intervention studies that modify (rather than simply describe) contextual, behavioral, and psychological variables hypothesized to facilitate or impede adherence and adjustment. The questions asked and designs employed should match the state of knowledge regarding the conceptual issue(s) being studied. It is often not possible for a given study to incorporate all of the recommendations above, but it is hoped that more research studies will move toward these goals, and thereby enhance the contribution of pediatric psychology to chronic disease management. C1 HARVARD UNIV,JOSLIN DIABET CTR,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP GLASGOW, RE (reprint author), OREGON RES INST,1715 FRANKLIN BLVD,EUGENE,OR 97403, USA. FU NIDDK NIH HHS [DK35524, DK46887] NR 59 TC 51 Z9 51 U1 20 U2 23 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD AUG PY 1995 VL 20 IS 4 BP 389 EP 402 DI 10.1093/jpepsy/20.4.389 PG 14 WC Psychology, Developmental SC Psychology GA RL842 UT WOS:A1995RL84200002 PM 7666280 ER PT J AU DRISKO, CL COBB, CM KILLOY, WJ MICHALOWICZ, BS PIHLSTROM, BL LOWENGUTH, RA CATON, JG ENCARNACION, M KNOWLES, M GOODSON, JM AF DRISKO, CL COBB, CM KILLOY, WJ MICHALOWICZ, BS PIHLSTROM, BL LOWENGUTH, RA CATON, JG ENCARNACION, M KNOWLES, M GOODSON, JM TI EVALUATION OF PERIODONTAL TREATMENTS USING CONTROLLED-RELEASE TETRACYCLINE FIBERS - CLINICAL-RESPONSE SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE PERIODONTITIS DRUG THERAPY CLINICAL TRIALS; TETRACYCLINE THERAPEUTIC USE ID CREVICULAR FLUID; THERAPY; DISEASE; IRRIGATION; GINGIVAL; DENTIN; TISSUE; REGENERATION; ANTIBIOTICS; COLLAGENASE AB THE PURPOSE OF THIS INVESTIGATION was to evaluate the clinical efficacy of controlled-release tetracycline fiber therapy in adult periodontitis patients, One hundred-twenty-two (122) adult patients from 3 dental centers were enrolled at baseline for this study. Each patient provided at least one site in each of four quadrants that was greater than or equal to 5 mm and bled on probing. One or two such sites were selected as test sites and were randomly assigned to receive one of four treatments: scaling and root planing (S), scaling and root planing plus tetracycline fiber for 10 days (SF), fiber therapy alone for 10 days (F), or two 10-day serial fiber applications (FF). After treatment, no periodontal maintenance or supportive care was provided until the end of this 12-month study. Probing depth (PD), clinical attachment level (CAL), plaque, and bleeding on probing (BOP) were measured at baseline and at 1, 3, 6, 9, and 12 months following treatment. Repeated PD and CAL measurements were taken at three locations within each site and averaged for each site. One hundred-sixteen (116) subjects completed the study. All treatments resulted in similar improvements in clinical parameters compared to baseline and were equally effective in the treatment of periodontitis as measured by probing depth reduction, clinical attachment level gain, and reduction of bleeding on probing. The clinical response, established primarily by 3 months following therapy, was generally sustained in all treatment groups for 12 months without the benefit of supportive maintenance therapy. C1 UNIV MISSOURI,SCH DENT,KANSAS CITY,MO. UNIV MINNESOTA,CLIN DENT RES CTR,MINNEAPOLIS,MN 55455. EASTMAN DENT CTR,DEPT PERIODONTOL,ROCHESTER,NY. ALZA CORP,PALO ALTO,CA. FORSYTH DENT CTR,BOSTON,MA 02115. NR 40 TC 80 Z9 82 U1 0 U2 2 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD AUG PY 1995 VL 66 IS 8 BP 692 EP 699 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RQ815 UT WOS:A1995RQ81500006 PM 7473012 ER PT J AU LOWENGUTH, RA CHIN, I CATON, JG COBB, CM DRISKO, CL KILLOY, WJ MICHALOWICZ, BS PIHLSTROM, BL GOODSON, JM AF LOWENGUTH, RA CHIN, I CATON, JG COBB, CM DRISKO, CL KILLOY, WJ MICHALOWICZ, BS PIHLSTROM, BL GOODSON, JM TI EVALUATION OF PERIODONTAL TREATMENTS USING CONTROLLED-RELEASE TETRACYCLINE FIBERS - MICROBIOLOGICAL RESPONSE SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE CLINICAL TRIALS PERIODONTITIS DRUG THERAPY; PERIODONTAL DISEASES MICROBIOLOGY; TETRACYCLINE THERAPEUTIC USE ID SUBGINGIVAL MICROBIOTA; MULTICENTER EVALUATION; THERAPY; BACTERIA; POCKETS AB IN A 12-MONTH MULTI-CENTER STUDY OF 116 adult periodontitis subjects, six putative periodontal pathogens were monitored by DNA probe methods in a subset of 31 subjects. Monitored species included Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn), Eikenella corrodens (Ec), Campylobacter rectus (Cr), and Actinobacillus actinomycetemcomitans (A alpha) with an average detection limit of 1.8 x 10(4) bacterial colony forming units/sample, The microbiological response to four periodontal treatments was studied, one treatment in each quadrant: scaling and root planing (S), scaling and root planing with tetracycline (TC) fiber (SF), a single application of TC fiber (F) and two serial applications of TC fiber (FF). Generally two sites were sampled in each quadrant, however, in some quadrants only one site was selected. These treatments were evaluated at baseline; immediately following therapy; and post-treatment at 1, 3, 6, and 12 months. The study was conducted with a split-mouth design with no maintenance therapy over a 12-month period. At baseline, 70.8% of sites had detectable Fn; 42.9% Pg; 63.5% Pi; 29.7% Ec; 28.3% Cr; and 5.5% A alpha. No significant differences were seen in baseline proportions of these species between centers. Numbers and proportions of detectable pathogens (with the exception of Pg) exhibited a triphasic temporal response: a precipitous initial decrease immediately following therapy; a rise in proportions in the 1- to 3-month post-therapy period; and a spontaneous decline in the absence of therapy over the 3- to 12-month period, This response was particularly prominent with Ec, where numbers of sites with detected organisms at 1 month were approximately equal to or greater than numbers of positive sites at baseline, suggesting an opportunistic characteristic. The immediate post-treatment levels of Pi were substantially greater than other species, suggesting the relative difficulty in eliminating this species. Detected numbers of sites with A alpha were too low to provide data for meaningful analysis, In general all treatments reduced the numbers of sites positive for each of the species tested throughout the 1-year monitoring period, although exceptions were observed. At 12 months, however, differences in microbiological presence related to initial therapy of each of the pathogens were small and statistically insignificant, Numerically elevated post-therapy levels of Cr were associated with sites that lost greater than or equal to 1 mm between the 3- to 12-month post-treatment period, However, statistically this increase was not significant. Certain differences in detectable microbial presence between treatments were noted. Sites treated by TC fiber (F, FF,SF) exhibited lower post-therapy percentages of detectable Fn, Pg, Pi, and Cr in 56 out of 60 comparisons with scaling and root planing (S) over the monitoring period. Though each individual comparison was not generally statistically significant, the probability of this repeated observation occurring by chance alone is extremely low. Similarly, when compared with scaling and root planing (S) alone, the adjunctive use of TC fiber (SF) consistently resulted in a lower percentage of sites with detectable levels of Fn, Pg, Pi, and Cr. C1 ALZA CORP,PALO ALTO,CA. UNIV MISSOURI,SCH DENT,KANSAS CITY,MO. UNIV MINNESOTA,CLIN DENT RES CTR,MINNEAPOLIS,MN 55455. FORSYTH DENT CTR,BOSTON,MA 02115. RP LOWENGUTH, RA (reprint author), EASTMAN DENT CTR,DEPT PERIODONTOL,625 ELMWOOD AVE,ROCHESTER,NY 14620, USA. NR 24 TC 38 Z9 41 U1 1 U2 2 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD AUG PY 1995 VL 66 IS 8 BP 700 EP 707 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RQ815 UT WOS:A1995RQ81500007 PM 7473013 ER PT J AU MICHALOWICZ, BS PIHLSTROM, BL DRISKO, CL COBB, CM KILLOY, WJ CATON, JG LOWENGUTH, RA QUINONES, C ENCARNACION, M KNOWLES, M GOODSON, JM AF MICHALOWICZ, BS PIHLSTROM, BL DRISKO, CL COBB, CM KILLOY, WJ CATON, JG LOWENGUTH, RA QUINONES, C ENCARNACION, M KNOWLES, M GOODSON, JM TI EVALUATION OF PERIODONTAL TREATMENTS USING CONTROLLED-RELEASE TETRACYCLINE FIBERS - MAINTENANCE RESPONSE SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE PERIODONTITIS THERAPY; TETRACYCLINE THERAPEUTIC USE; PLANING; SCALING; CLINICAL TRIALS ID PROBING ATTACHMENT LOSS; THERAPY; DISEASE; SUPPURATION; DENTIN; DEPTH; METRONIDAZOLE; ANTIBIOTICS; COLLAGENASE; PLACEMENT AB THE PURPOSE OF THIS INVESTIGATION was to examine periodontal disease recurrence from 3 to 12 months following various treatments with scaling and root planing and controlled-release tetracycline fibers. One-hundred-twenty-two (122) adult volunteers with at least one bleeding pocket greater than or equal to 5 mm in each of four quadrants were enrolled in this study. One or two such sites in each quadrant were selected as test sites. Quadrants were randomly assigned to receive one of four treatments: scaling and root planing (S); scaling and root planing plus tetracycline fiber for 10 days (SF); fiber therapy alone for 10 days (F); or fiber therapy alone for 20 days (FF). After treatment, no supportive care was provided during the 12-month study period. Probing depth (PD), attachment loss (AL), plaque, and bleeding on probing were measured at baseline, and at 1, 3, 6, 9, and 12 months after treatment. PD and AL measures were taken at three locations within each site and averaged for each site. Disease recurrence was defined as greater than or equal to 1 mm mean attachment loss at a site during the 3- to 12-month period. One-hundred-sixteen (116) subjects completed the study. Sites treated with SF experienced significantly (P < 0.05) less disease recurrence (4%) than S, F, or FF (9%, 10%, and 12%, respectively). Results of this study suggest that, compared to S, F, or FF; scaling and root planing in conjunction with tetracycline fiber therapy for 10 days can significantly reduce disease recurrence 3 to 12 months following treatment in the absence of supportive care. C1 UNIV MINNESOTA,CLIN DENT RES CTR,MINNEAPOLIS,MN 55455. UNIV MISSOURI,SCH DENT,KANSAS CITY,MO. EASTMAN DENT CTR,DEPT PERIODONTOL,ROCHESTER,NY. ALZA CORP,PALO ALTO,CA. FORSYTH DENT CTR,BOSTON,MA 02115. NR 31 TC 51 Z9 54 U1 0 U2 0 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD AUG PY 1995 VL 66 IS 8 BP 708 EP 715 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RQ815 UT WOS:A1995RQ81500008 PM 7473014 ER PT J AU FARAONE, SV BIEDERMAN, J MILBERGER, S AF FARAONE, SV BIEDERMAN, J MILBERGER, S TI HOW RELIABLE ARE MATERNAL REPORTS OF THEIR CHILDRENS PSYCHOPATHOLOGY - ONE-YEAR RECALL OF PSYCHIATRIC DIAGNOSES OF ADHD CHILDREN SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE RELIABILITY, MATERNAL REPORTS; PSYCHOMETRICS; ATTENTION-DEFICIT HYPERACTIVITY DISORDER ID DEFICIT HYPERACTIVITY DISORDER; ANXIETY DISORDERS; STRUCTURED INTERVIEW; COMORBIDITY; CHILDHOOD; PARENT; PREVALENCE; STABILITY; AGREEMENT; ADOLESCENTS AB Objective: Although childhood psychiatric diagnoses often rely on maternal reports, little is known about their long-term reliability and diagnostic accuracy. Thus, the authors sought to examine these psychometric features in a cohort of ADHD and control children. Method: The sample consisted of 140 referred children with ADHD and 120 normal controls. The authors compared childhood diagnoses based on maternal reports of their children's psychopathology at this baseline assessment with those collected 1 year later. Results: Both reliability and accuracy were excellent for ADHD. Reliability and specificity were also excellent for conduct disorder, oppositional defiant disorder, major depression, bipolar disorder, separation anxiety, and multiple anxiety disorders. Reliability and sensitivity were relatively low for simple phobia, social phobia, agoraphobia, and overanxious disorder. Conclusions: With some exceptions, maternal reports of their children's psychopathology provided a reliable and accurate means of assessment. Generally, maternally derived diagnoses were less accurate for internalizing compared with externalizing disorders. However, specificity was high for all diagnoses, suggesting that mothers were not biased to report symptoms that had not occurred. C1 MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT ACC725,CHILD PSYCHIAT SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,MASSACHUSETTS MENTAL HLTH CTR,DEPT PSYCHIAT,BOSTON,MA 02115. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-41314-01A2] NR 40 TC 123 Z9 123 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 AUG PY 1995 VL 34 IS 8 BP 1001 EP 1008 DI 10.1097/00004583-199508000-00009 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA RL320 UT WOS:A1995RL32000009 PM 7665438 ER PT J AU SEIDMAN, LJ BIEDERMAN, J FARAONE, SV MILBERGER, S NORMAN, D SEIVERD, K BENEDICT, K GUITE, J MICK, E KIELY, K AF SEIDMAN, LJ BIEDERMAN, J FARAONE, SV MILBERGER, S NORMAN, D SEIVERD, K BENEDICT, K GUITE, J MICK, E KIELY, K TI EFFECTS OF FAMILY HISTORY AND COMORBIDITY ON THE NEUROPSYCHOLOGICAL PERFORMANCE OF CHILDREN WITH ADHD - PRELIMINARY FINDINGS SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ATTENTION-DEFICIT HYPERACTIVITY DISORDER; NEUROPSYCHOLOGY; BOYS ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT; LEARNING-DISABILITIES; PSYCHIATRIC STATUS; BOYS; CHILDHOOD; BEHAVIOR; ADULTS AB Objective: Because ADHD is heterogeneous with respect to psychiatric comorbidity, familiality, and learning disabilities, it was hypothesized that such features might influence the severity and pattern of neuropsychological function in ADHD. Method: Subjects were 9- to 20-year-old males with DSM-III-R ADHD (n = 65) and normal controls (n = 45). Information on neuropsychological performance was obtained in a standardized manner, blind to the proband's clinical status. Results: ADHD probands were significantly impaired on neuropsychological functions compared with controls irrespective of composite psychiatric comorbidity status, and those with a family history of ADHD were most impaired. ADHD probands with learning disabilities showed a pattern suggestive of reduced motor dominance and extremely slow reading speed. Conclusions: These results indicate that neuropsychological performance in ADHD is significantly affected by familial status and presence of learning disabilities. The similarity of findings between ADHD children with and without comorbid psychiatric disorders suggests that the neuropsychological impairments in our sample were associated with ADHD. These findings raise the possibility of alterations of cerebral dominance and of frontal networks in ADHD. Further research is needed to replicate these findings in larger samples, to clarify the role of specific comorbid psychiatric disorders, and to assess directly cerebral functioning in subjects with ADHD. C1 MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT ACC725,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-41314-01A2] NR 47 TC 95 Z9 102 U1 2 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 1995 VL 34 IS 8 BP 1015 EP 1024 DI 10.1097/00004583-199508000-00011 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA RL320 UT WOS:A1995RL32000011 PM 7665440 ER PT J AU STEVENSON, WG SAGER, PT NATTERSON, PD SAXON, LA MIDDLEKAUFF, HR WIENER, I AF STEVENSON, WG SAGER, PT NATTERSON, PD SAXON, LA MIDDLEKAUFF, HR WIENER, I TI RELATION OF PACE MAPPING QRS CONFIGURATION AND CONDUCTION DELAY TO VENTRICULAR-TACHYCARDIA REENTRY CIRCUITS IN HUMAN INFARCT SCARS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID RADIOFREQUENCY CATHETER ABLATION; PRIOR MYOCARDIAL-INFARCTION; SLOW CONDUCTION; HEART-DISEASE; ENTRAINMENT; ACTIVATION; ORIGIN; SITE; LOCALIZATION; MECHANISMS AB Objectives. This study sought to determine the relation of the paced QRS configuration and conduction delay during pace mapping to reentry circuit sites in patients,vith ventricular tachycardia late after myocardial infarction. Background. The QRS configuration produced by ventricular pacing during sinus rhythm (pace mapping) can locate focal idiopathic ventricular tachycardias during catheter mapping, but postinfarction reentry circuits may be relatively large and contain regions of slow conduction. We hypothesized that for postinfarction ventricular tachycardia, 1) pacing during sinus rhythm at reentry circuit sites distant from the exit from the scar would produce a QRS configuration different from the tachycardia; and 2) a stimulus to QRS delay during pace mapping may be a useful guide to reentry circuit slow conduction zones. Methods. Catheter mapping and ablation were performed in 18 consecutive patients with ventricular tachycardia after myocardial infarction. At 85 endocardial sites in 13 patients, 12-lead electrocardiograms (ECGs) were recorded during pace mapping, and participation of each site in a reentry circuit was then evaluated by entrainment techniques during induced ventricular tachycardia or by application of radiofrequency current. Results. Pace maps resembled tachycardia at <30% of likely reentry circuit sites identified by entrainment criteria and at only 1 (9%) of 11 sites where radiofrequency current terminated tachycardia. Analysis of the stimulus to QRS interval during entrainment with concealed fusion shelved that the conduction time from the pacing site to the exit from the scar was longer at sites where the pace map did not resemble tachycardia. Evidence of slow conduction during pace mapping, with a stimulus to QRS interval >40 ms was observed at greater than or equal to 70% of reentry circuit sites. Conclusions. At many sites in postinfarction ventricular reentry circuits, the QRS configuration during pace mapping does not resemble the ventricular tachycardia QRS complex, consistent with relatively large reentry circuits or regions of functional conduction block during ventricular tachycardia. A stimulus to QRS delay during pace mapping is consistent with slow conduction and may aid in targeting endocardial sites for further evaluation during tachycardia. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV CARDIOVASC,BOSTON,MA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,SCH MED & MED CTR,DIV CARDIOL,LOS ANGELES,CA. NR 29 TC 92 Z9 93 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG PY 1995 VL 26 IS 2 BP 481 EP 488 DI 10.1016/0735-1097(95)80026-D PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RM094 UT WOS:A1995RM09400027 PM 7608454 ER PT J AU DRINKA, PJ JOCHEN, AL CUISINIER, M BLOOM, R RUDMAN, I RUDMAN, D AF DRINKA, PJ JOCHEN, AL CUISINIER, M BLOOM, R RUDMAN, I RUDMAN, D TI POLYCYTHEMIA AS A COMPLICATION OF TESTOSTERONE REPLACEMENT THERAPY IN NURSING-HOME MEN WITH LOW TESTOSTERONE LEVELS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Note ID OBSTRUCTIVE SLEEP-APNEA; HYPOGONADAL MEN C1 UNIV WISCONSIN,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. VET ADM MED CTR,MILWAUKEE,WI 53295. MED COLL WISCONSIN,MILWAUKEE,WI. RP DRINKA, PJ (reprint author), WISCONSIN VET HOME,KING,WI 54946, USA. FU PHS HHS [V01-A610383] NR 12 TC 63 Z9 66 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 1995 VL 43 IS 8 BP 899 EP 901 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RM829 UT WOS:A1995RM82900010 PM 7636099 ER PT J AU PAN, Y LO, EH MATSUMOTO, K HAMBERG, L JIANG, H AF PAN, Y LO, EH MATSUMOTO, K HAMBERG, L JIANG, H TI QUANTITATIVE AND DYNAMIC MRI OF NEUROPROTECTION IN EXPERIMENTAL STROKE SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE FOCAL CEREBRAL ISCHEMIA; DELAYED HYPOPERFUSION; GLUTAMATE; NEUROPROTECTION; NMDA; RABBIT ID FOCAL CEREBRAL-ISCHEMIA; GLUTAMATE ANTAGONIST MK-801; BLOOD-FLOW; BRAIN-DAMAGE; RAT-BRAIN; CATS; INFARCTION; CONTRAST; VOLUME; MODEL AB Experimental studies of stroke in animal models have traditionally relied on histological endpoints for the measurement of neuroprotection. In this study, we used in vivo and dynamic MRI to quantify the neuroprotective effects of the non-competitive NMDA antagonist MK801. Four hours of occlusion followed by 6 h of reperfusion was performed in a rabbit model of focal cerebral ischemia. Spin-echo T2-weighted (T2W) MRI was used to quantify ischemic lesion volumes. Hemispheric measurements of perfusion deficits were assessed by using dynamic susceptibility-contrast MRI to map the first-pass transit of injected GdDTPA. Histological correlates of infarction were quantified using tetrazolium staining. Animals treated with 2 mg/kg MK801 infused immediately post-occlusion (n = 6) were compared with untreated controls (n = 8). T2W MRI scans obtained after 6 h of reperfusion showed high-intensity lesions in the ischemic basal ganglia and cortex. MK801-treated animals showed significantly decreased lesion volumes compared to untreated controls (7.3 +/- 3.2% treated vs 20.7 +/- 4.8% control, p < 0.05). Lesion volumes measured with MRI were significantly correlated with tetrazolium-defined infarct volumes (r = 0.766, p = 0.004). Dynamic MRI demonstrated the phenomenon of delayed hypoperfusion in the ischemic hemisphere during the late reperfusion phase; relative cerebral blood volume (rCBV) was 45.2 +/- 10.3% in untreated animals. MK801 slightly improved these deficits although the differences did not reach statistical significance (rCBV = 77.0 +/- 9.7%, p = 0.128). However, impairment of hemispheric perfusion measured with dynamic MRI were significantly correlated with T2W MRI-defined lesion sizes (r = -0.798, p = 0.018). These results demonstrate that MRI can quantitatively measure neuroprotection and that these clinically applicable measures are significantly correlated with traditional histological outcomes. Furthermore, dynamic MRI can offer insight into the effects of therapy on cerebral perfusion. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,SCH MED,DEPT RADIOL,BOSTON,MA 02129. NR 35 TC 18 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD AUG PY 1995 VL 131 IS 2 BP 128 EP 134 DI 10.1016/0022-510X(95)00103-9 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RK481 UT WOS:A1995RK48100003 PM 7595637 ER PT J AU BRANNEY, SW WOLFE, RE MOORE, EE ALBERT, NP HEINIG, M MESTEK, M EULE, J AF BRANNEY, SW WOLFE, RE MOORE, EE ALBERT, NP HEINIG, M MESTEK, M EULE, J TI QUANTITATIVE SENSITIVITY OF ULTRASOUND IN DETECTING FREE INTRAPERITONEAL FLUID SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID BLUNT ABDOMINAL-TRAUMA; DIAGNOSTIC PERITONEAL-LAVAGE; ULTRASONOGRAPHY; SONOGRAPHY; LAPAROTOMY; INJURIES AB The minimum volume of intraperitoneal fluid that is detectable in Morison's pouch with ultrasound in the trauma setting is not well defined. To evaluate this question, we used diagnostic peritoneal lavage (DPL) as a model for intraperitoneal hemorrhage and undertook a blinded prospective study of the sensitivity of ultrasound in detecting intraperitoneal fluid, Participants included attending physicians and residents in emergency medicine, radiology, and surgery, During the infusion of the DPL fluid, participants continuously scanned Morison's pouch until they detected fluid, All participants were blinded to the rate of infusion and the volume infused, One hundred patients were entered into the study, The mean volume of fluid detected was 619 mt. Only 10% of participants detected fluid volumes less than 400 mL and the overall sensitivity at one liter was 97%. We conclude that reliable detection of intraperitoneal fluid in Morison's pouch requires a greater volume than has been previously described. C1 DENVER HLTH & HOSP RESIDENCY EMERGENCY MED,DENVER,CO. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV COLORADO,HLTH SCI CTR,DENVER,CO. RP BRANNEY, SW (reprint author), DENVER GEN HOSP,777 BANNOCK ST,BOX 0108,DENVER,CO 80204, USA. NR 30 TC 107 Z9 109 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Inf. Crit. Care PD AUG PY 1995 VL 39 IS 2 BP 375 EP 380 DI 10.1097/00005373-199508000-00032 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA RT208 UT WOS:A1995RT20800032 PM 7674411 ER PT J AU BIANCONE, L ANDRES, G AHN, H DEMARTINO, C STAMENKOVIC, I AF BIANCONE, L ANDRES, G AHN, H DEMARTINO, C STAMENKOVIC, I TI INHIBITION OF THE CD40-CD40LIGAND PATHWAY PREVENTS MURINE MEMBRANOUS GLOMERULONEPHRITIS SO KIDNEY INTERNATIONAL LA English DT Article ID HYPER-IGM SYNDROME; HELPER T-CELLS; HUMAN B-CELLS; VIVO CD40-GP39 INTERACTIONS; DEPENDENT HUMORAL IMMUNITY; RECOMBINANT CD40 LIGAND; CARDIAC ALLOGRAFT; HEYMANN NEPHRITIS; ANTIBODY; CYTOKINES AB Several forms of glomerulonephritis are induced by antibodies against self or foreign antigens. Normal B lymphocyte antibody production requires T cell costimulatory signals provided in part by T cell surface expression of gp39/CD40ligand (CD40L) that engages the B cell receptor CD40 and induces B cell differentiation and immunoglobulin class switching. We assessed the effect of disrupting the CD40L-CD40 costimulatory pathway, using a CD40-Ig fusion protein, on the development of membranous glomerulonephritis (MGN) in the mouse. MGN is induced by mouse antibodies that recognize and bind to exogenously administered rabbit anti-mouse renal tubular brush border (RbAMBB) IgG immobilized in the glomerular capillary wall. MGN did not occur in nude mice, showing the need of the T cell function. C57Bl/10 mice immunized with RbAMBB and treated with CD40-Ig fusion protein displayed a delayed autologous response and absence of MGN lesions, while control fusion proteins failed to prevent the development of the disease. These observations provide evidence that disruption of the CD40-CD40L costimulatory pathway can prevent the development of MGN by suppressing T cell-dependent antibody production. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. IST DERMATOL S MARIA & S GALLICANO,ROME,ITALY. FU NCI NIH HHS [CA55735]; NIDDK NIH HHS [DK-36807] NR 58 TC 41 Z9 41 U1 0 U2 0 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 AUG PY 1995 VL 48 IS 2 BP 458 EP 468 DI 10.1038/ki.1995.314 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA RK810 UT WOS:A1995RK81000016 PM 7564113 ER PT J AU MEGERIAN, CA MCKENNA, MJ NUSS, RC MANIGLIA, AJ OJEMANN, RG PILCH, BZ NADOL, JB AF MEGERIAN, CA MCKENNA, MJ NUSS, RC MANIGLIA, AJ OJEMANN, RG PILCH, BZ NADOL, JB TI ENDOLYMPHATIC SAC TUMORS - HISTOPATHOLOGIC CONFIRMATION, CLINICAL CHARACTERIZATION, AND IMPLICATION IN VON HIPPEL-LINDAU DISEASE SO LARYNGOSCOPE LA English DT Article ID MIDDLE-EAR; CHOROID-PLEXUS; TEMPORAL BONE; ADENOMA; ADENOCARCINOMA AB The term ''endolymphatic sac tumor'' (ELST) was coined to identify the likely origin of aggressive papillary tumors of the temporal bone. To evaluate the validity of this designation, the temporal bone collection at the Massachusetts Eye and Ear Infirmary was accessed in an effort to determine the pathologic relationship between these tumors and the endolymphatic sac. The search resulted in the identification of a de-novo papillary epithelial lesion arising within the confines of the endolymphatic sac in a patient with von Hippel-Lindau (VHL) disease who harbored a large, destructive ELST in the opposite temporal bone. This finding provides the most substantial evidence to date regarding the origin of the ELST and the accuracy of its nomenclature. Seven additional clinical cases of ELST were identified and analyzed in order to define the natural history of these tumors. All patients had a history of sensorineural hearing loss diagnosed an average of 10.6 years prior to tumor discovery. The presence of a polypoid external auditory canal mass, facial paralysis, and evidence of a destructive mass arising on the posterior fossa surface of the temporal bone were common physical and radiographic findings. The management of these patients, as well as those who are probably prone to such tumors (i.e., VHL patients), is discussed. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. CASE WESTERN RESERVE UNIV,UNIV HOSP CLEVELAND,SCH MED,CLEVELAND,OH. NR 36 TC 85 Z9 89 U1 0 U2 1 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 1995 VL 105 IS 8 BP 801 EP 808 DI 10.1288/00005537-199508000-00006 PN 1 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA RM279 UT WOS:A1995RM27900005 PM 7630290 ER PT J AU AVERY, RK SALMAN, SD BAKER, AS AF AVERY, RK SALMAN, SD BAKER, AS TI RHINOSCLEROMA TREATED WITH CIPROFLOXACIN - A CASE-REPORT SO LARYNGOSCOPE LA English DT Article ID KLEBSIELLA-RHINOSCLEROMATIS; SCLEROMA AB Rhinoscleroma, a chronic progressive infection of the nose and associated structures caused by Klebsiella rhinoscleromatis, has posed a therapeutic dilemma since its identification in the late 1800s. Although a number of antibiotics have been found to be effective in this relapsing disorder,(1-6) the lengthy duration of treatment can lead to problems with adverse effects and compliance, especially with the traditional therapies of streptomycin and tetracycline. We report on a patient with extensive nasal rhinoscleroma who achieved pathologic and bacteriologic resolution during treatment with oral ciprofloxacin after previous courses of tetracycline and trimethoprim-sulfamethoxazole. Ciprofloxacin may prove to be useful in the therapy of rhinoscleroma because his convenient for oral administration, achieves good tissue levels, is concentrated in macrophages,(7) and is generally well tolerated as long-term therapy. As mentioned in a recent review of patients with rhinoscleroma at the Mayo Clinic, the fluoroquinolones deserve further study as potentially highly effective agents for this uncommon but significant infectious condition.(8) C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 18 TC 8 Z9 8 U1 1 U2 1 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 1995 VL 105 IS 8 BP 854 EP 856 DI 10.1288/00005537-199508000-00016 PN 1 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA RM279 UT WOS:A1995RM27900015 PM 7630299 ER PT J AU PETTERSSON, A WINER, ES WEKSLERZANGEN, S LERNMARK, A JACOB, HJ AF PETTERSSON, A WINER, ES WEKSLERZANGEN, S LERNMARK, A JACOB, HJ TI PREDICTABILITY OF HETEROZYGOSITY SCORES AND POLYMORPHISM INFORMATION-CONTENT VALUES FOR RAT GENETIC-MARKERS SO MAMMALIAN GENOME LA English DT Article AB Construction of a genetic linkage map of the laboratory rat, Rattus norvegicus, establishes the rat as a genetic model. Allele sizes were reported for 432 simple sequence length polymorphisms (SSLPs) genotyped in 12 different substrains belonging to nine different inbred strains of rats. However, these nine strains represent only a fraction of the more than 140 inbred strains available. If allele sizes are not known, alternative indices of markers' polymorphism content can be used, such as heterozygosity (H) and polymorphism information content (PIC). Here, we have determined heterozygosity scores and PIC values for all markers of the rat genetic linkage map, and we evaluate the predictability of the heterozygosity and the PIC values. Correlation analysis between the nine inbred strains reported for the rat map and ten ''test'' strains yielded r = 0.42 and r = 0.44 for heterozygosity and PIC values, respectively. While the correlation of the indices between the two groups of animals is low, these indices do provide a means of predicting whether a genetic marker will be informative in strains where allele sizes are not known. C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,BOSTON,MA 02129. KAROLINSKA HOSP,DEPT MOLEC MED,ENDOCRINE & DIABET UNIT,S-17176 STOCKHOLM,SWEDEN. NR 7 TC 4 Z9 4 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD AUG PY 1995 VL 6 IS 8 BP 512 EP 520 DI 10.1007/BF00356167 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RN370 UT WOS:A1995RN37000005 PM 8589519 ER PT J AU PASTERNAK, RC AF PASTERNAK, RC TI PSYCHOLOGIC FACTORS AND COURSE AFTER MYOCARDIAL-INFARCTION - MATURING OF A RISK FACTOR SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID CORONARY-ARTERY DISEASE; FOLLOW-UP; SURVIVAL RP PASTERNAK, RC (reprint author), MASSACHUSETTS GEN HOSP,32 FRUIT ST,JACKSON 1402,BOSTON,MA 02114, USA. NR 11 TC 2 Z9 2 U1 0 U2 1 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD AUG PY 1995 VL 70 IS 8 BP 809 EP 810 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RN551 UT WOS:A1995RN55100016 PM 7630224 ER PT J AU WAGNER, EH BARRETT, P BARRY, MJ BARLOW, W FOWLER, FJ AF WAGNER, EH BARRETT, P BARRY, MJ BARLOW, W FOWLER, FJ TI THE EFFECT OF A SHARED DECISION-MAKING PROGRAM ON RATES OF SURGERY FOR BENIGN PROSTATIC HYPERPLASIA - PILOT RESULTS SO MEDICAL CARE LA English DT Article C1 MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,BOSTON,MA 02114. GRP HLTH COOPERAT PUGET SOUND,CTR HLTH STUDIES,SEATTLE,WA 98101. KAISER PERMANENTE MED CARE PROGRAM,DENVER,CO. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. UNIV MASSACHUSETTS,SURVEY RES CTR,BOSTON,MA 02125. FU AHRQ HHS [HS 06336, HS 06540, HS 08397] NR 5 TC 93 Z9 93 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 1995 VL 33 IS 8 BP 765 EP 770 DI 10.1097/00005650-199508000-00002 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA RN219 UT WOS:A1995RN21900002 PM 7543638 ER PT J AU BARRY, MJ FOWLER, FJ MULLEY, AG HENDERSON, JV WENNBERG, JE AF BARRY, MJ FOWLER, FJ MULLEY, AG HENDERSON, JV WENNBERG, JE TI PATIENT REACTIONS TO A PROGRAM DESIGNED TO FACILITATE PATIENT PARTICIPATION IN TREATMENT DECISIONS FOR BENIGN PROSTATIC HYPERPLASIA SO MEDICAL CARE LA English DT Article DE BENIGN PROSTATIC HYPERTROPHY; PROSTATECTOMY; PATIENT EDUCATION; PATIENT PARTICIPATION; VIDEODISC ID TRANS-URETHRAL RESECTION; MEDICAL-CARE; PREFERENCES; PROSTATECTOMY; OUTCOMES; INFORMATION; AUTONOMY AB Patients often want considerable information about their conditions, and enhanced patient participation might reduce unwanted practice variation and improve medical decisions. The authors assessed how men with benign prostatic hyperplasia reacted to an educational program designed to facilitate participation in decisionmaking, and how strongly ratings of their symptom state and the prospect of complications predicted their treatment choice. A prospective cohort study was conducted in three hospital-based urology practices: two in prepaid group practices, and one Veterans Administration clinic. Four hundred twenty-one men with symptomatic benign prostatic hyperplasia without prior prostatectomy or benign prostatic hyperplasia complications were enrolled, and 373 provided usable ratings. Subjects participated in an interactive videodisc-based shared decisionmaking program about benign prostatic hyperplasia and its treatment options, prostatectomy, and ''watchful waiting.'' They rated the length, clarity, balance, and value of the program and were followed for 3 months to determine if they underwent surgery. Patients rated the program as generally clear, informative, and balanced. Across all three sites, 77% of patients were very positive and 16% were generally positive about the program's usefulness in making a treatment decision. Logistic models predicting choice of surgical treatment documented the independent importance of negative ratings of the current symptom state (odds ratio 7.0, 95% confidence interval 2.9-16.6), as well as the prospect of postoperative sexual dysfunction (odds ratio 0.20, 95% confidence interval 0.08-0.48) in decisionmaking. Patients rated the Shared Decisionmaking Program very positively and made decisions consistent with their assessed preferences. These results suggest that patients can be helped to participate in treatment decisions, and support a randomized trial of the Shared decisionmaking Program. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. UNIV MASSACHUSETTS,SURVEY RES CTR,BOSTON,MA 02125. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,INTERACT MEDIA LAB,HANOVER,NH 03756. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,CTR EVALUAT CLIN SCI,HANOVER,NH 03756. RP BARRY, MJ (reprint author), MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,50 STANIFORD ST,9TH FLOOR,BOSTON,MA 02114, USA. FU AHRQ HHS [HS 06336, HS 06540, HS 08397] NR 27 TC 198 Z9 200 U1 2 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 1995 VL 33 IS 8 BP 771 EP 782 DI 10.1097/00005650-199508000-00003 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA RN219 UT WOS:A1995RN21900003 PM 7543639 ER PT J AU SHEKELLE, PG MARKOVICH, M LOUIE, R AF SHEKELLE, PG MARKOVICH, M LOUIE, R TI FACTORS ASSOCIATED WITH CHOOSING A CHIROPRACTOR FOR EPISODES OF BACK PAIN CARE SO MEDICAL CARE LA English DT Article DE CHIROPRACTIC; BACK PAIN ID FAMILY PHYSICIANS; HEALTH; COST AB Back pain is a common illness and chiropractors provide a large proportion of back pain care in the United States. This is the first study to systematically compare chiropractic patients with those who saw other providers for back pain. The authors analyzed data from the RAND Health Insurance Experiment, a community-based study of the use of health services. insurance claims forms were examined for all visits specified by the patient as occurring for back pain. Visits were grouped into episodes using decision rules and clinical judgment. The primary provider of back pain care was defined as the provider who delivered most of the services. Sociodemographic and health status and attitudes variables of patients were examined for association with the choice of chiropractor. Multivariate logistic regression models were constructed to calculate adjusted odds ratios for independent predictors. There were 1020 episodes of back pain care made by 686 different persons and encompassing 8825 visits. Results indicated that chiropractors were the primary provider for 40% of episodes, and retained as primary provider a greater percentage of their patients (92%) who had a second episode of back pain care than did medical doctors. Health insurance experiment site, white race, male sex, and high school education were independent predictors of choosing a chiropractor. Conclusions suggested that chiropractors were the choice of one third of all patients who sought back pain care, and provided care for 40% of all episodes of care. Geographic site, education, gender, and income were independent patient factors;predicting chiropractic use. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RAND CORP,GRAD SCH,SANTA MONICA,CA 90407. CALIF STATE UNIV LOS ANGELES,SCH PUBL HLTH,DEPT HLTH SERV,LOS ANGELES,CA 90032. FU AHRQ HHS [1R03HS06920-01] NR 26 TC 50 Z9 50 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 1995 VL 33 IS 8 BP 842 EP 850 DI 10.1097/00005650-199508000-00008 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA RN219 UT WOS:A1995RN21900008 PM 7637405 ER PT J AU GERVAIS, DA MUELLER, PR AF GERVAIS, DA MUELLER, PR TI CASE-REPORT - ESOPHAGEAL ANASTOMOTIC LEAK COMPLICATED BY BILATERAL EMPYEMAS - NONOPERATIVE MANAGEMENT BY AN INTERVENTIONAL RADIOLOGY SERVICE SO MINIMALLY INVASIVE THERAPY LA English DT Note DE EMPYEMA; ESOPHAGEAL RUPTURE; CHEST TUBE; ANASTOMOTIC LEAK; INTERVENTIONAL RADIOLOGY AB Complicated oesophageal perforation is considered a life-threatening surgical emergency for which open thoracotomy and primary repair are indicated. However, several reports of successful conservative management consisting of non-operative drainage exist in the literature. The various imaging modalities and catheter techniques available through an interventional radiology service make interventional radiologists ideally suited for management of this complex problem. We present a case successfully managed by image-guided catheter placement and manipulations. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0961-625X J9 MINIMAL INVASIV THER JI Minim. Invasive Ther. PD AUG PY 1995 VL 4 IS 4 BP 239 EP 242 DI 10.3109/13645709509152786 PG 4 WC Surgery SC Surgery GA RZ161 UT WOS:A1995RZ16100012 ER PT J AU PETRINI, JHJ XIAO, YH WEAVER, DT AF PETRINI, JHJ XIAO, YH WEAVER, DT TI DNA LIGASE-I MEDIATES ESSENTIAL FUNCTIONS IN MAMMALIAN-CELLS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SISTER-CHROMATID EXCHANGES; EMBRYONIC STEM-CELLS; BLOOMS SYNDROME CELLS; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; CATALYTIC DOMAIN; GENE; CDNA; REPLICATION; EXPRESSION AB DNA replication, repair, and recombination are essential processes in mammalian cells. Hence, the application of gene targeting to the study of these DNA metabolic pathways requires the creation of nonnull mutations. We have developed a method for introducing partially defective mutants in murine embryonic stem cells that circumvents the problem of cellular lethality of targeted mutations at essential loci. Using this approach, we have determined that mammalian DNA ligase I is essential for cell viability. Thus, DNA ligases II and III are not redundant with DNA ligase I for the function(s) associated,vith cell proliferation. Partial complementation of the lethal DNA ligase I null mutation allowed the creation of deficient embryonic stem cell lines. We found that a wild-type DNA ligase I cDNA, as well as a variant DNA ligase I cDNA, was able to rescue the lethality of the homozygous null mutation, whereas an N-terminal deletion mutant consisting of the minimal DNA ligase I catalytic domain was not. This observation demonstrates that sequences outside the DNA ligase I catalytic domain are essential for DNA ligase I function in vivo. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. FU NCI NIH HHS [CA52694] NR 50 TC 56 Z9 56 U1 1 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 AUG PY 1995 VL 15 IS 8 BP 4303 EP 4308 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RJ779 UT WOS:A1995RJ77900034 PM 7623824 ER PT J AU PONS, S ASANO, T GLASHEEN, E MIRALPEIX, M ZHANG, YT FISHER, TL MYERS, MG SUN, XJ WHITE, MF AF PONS, S ASANO, T GLASHEEN, E MIRALPEIX, M ZHANG, YT FISHER, TL MYERS, MG SUN, XJ WHITE, MF TI THE STRUCTURE AND FUNCTION OF P55(PIK) REVEAL A NEW REGULATORY SUBUNIT FOR PHOSPHATIDYLINOSITOL 3-KINASE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BACULOVIRUS EXPRESSION SYSTEM; INSULIN-RECEPTOR SUBSTRATE-1; EPIDERMAL GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; ENDOGENOUS SUBSTRATE; RAT ADIPOCYTES; PROTEIN IRS-1; CELLS; BINDING; KINASE AB Phosphatidylinositol 3-kinase (PI-3 kinase) is implicated in the regulation of diverse cellular processes, including insulin-stimulated glucose transport. PI-3 kinase is composed of a 110-kDa catalytic subunit and an 85-kDa regulatory subunit. Here, we describe p55(PIK), regulatory subunit that was isolated by screening expression libraries with tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1). p55(PIK) is composed of a unique 30-residue NH2 terminus followed by a proline-rich motif and two Src homology 2 (SH2) domains with significant sequence identity to those in p85. p55(PIK) mRNA is expressed early during development, remains abundant in adult mouse brain and testis tissues, and is detectable in adult adipocytes and heart and kidney tissues. p55(PIK) forms a stable complex with p110, and it associates with IRS-1 during insulin stimulation. Moreover, the activated insulin receptor phosphorylates p55(PIK) in Sf9 cells, and insulin stimulates p55(PIK) phosphorylation in CHOIR/p55(PIK) cells. The unique features of p55(PIK) suggest that it is important in receptor signaling. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RI Pons , Sebastian/K-7794-2014 OI Pons , Sebastian/0000-0003-1027-0621 FU NIDDK NIH HHS [DK 36836, DK 38712, DK 43808] NR 69 TC 205 Z9 220 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1995 VL 15 IS 8 BP 4453 EP 4465 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RJ779 UT WOS:A1995RJ77900050 PM 7542745 ER PT J AU KOTKOW, KJ ORKIN, SH AF KOTKOW, KJ ORKIN, SH TI DEPENDENCE OF GLOBIN GENE-EXPRESSION IN MOUSE ERYTHROLEUKEMIA-CELLS ON THE NF-E2 HETERODIMER SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LOCUS-CONTROL REGION; DOMINANT CONTROL REGION; TRANSCRIPTION FACTOR NF-E2; POLYMERASE CHAIN-REACTION; PROTEIN DNA INTERACTIONS; LEUCINE ZIPPER PROTEIN; REGULATORY ELEMENT; ERYTHROID-CELLS; V-MAF; ENHANCER AB High-level, tissue-specific expression of the beta-globin genes requires the presence of an upstream locus control region (LCR), The overall enhancer activity of the beta-globin complex LCR (P-LCR) is dependent on the integrity of the tandem NF-E2 sites of HS-2, The NF-E2 protein which binds these sites is a heterodimeric basic leucine zipper protein composed of a tissue-specific subunit, p45 NF-E2, and a smaller subunit, p18 NF-E2, that is widely expressed, In these studies, we sought to investigate the role of NF-E2 in globin expression, We show that expression of a dominant-negative mutant p18 greatly reduces the amount of functional NF-E2 complex in the cell, Reduced levels of both alpha- and beta-globin were associated with the lower levels of NF-E2 activity in this cell line, Globin expression was fully restored upon the introduction of a tethered p35-p18 heterodimer. We also examined CB3 cells, a mouse erythroleukemia (MEL) cell line that does not express endogenous p45 NF-E2, and demonstrated that the restoration of globin gene expression was dependent upon the levels of expressed tethered NF-E2 heterodimer. Results of DNase I hypersensitivity mapping and in vivo footprinting assays showed no detectable chromatin alterations in beta-LCR HS-2 due to loss of NF-E2. Finally, we examined the specificity of NF-E2 for globin gene expression in MEL cells. These experiments indicate a critical role for the amino-terminal domain of p45 NF-E2 and show that a related protein, LCRF1, is unable to restore globin gene expression in p45 NF-E2-deficient cells, From these results, we conclude that NF-E2 is specifically required for high-level globin gene expression in MEL cells. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. NR 49 TC 143 Z9 143 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 AUG PY 1995 VL 15 IS 8 BP 4640 EP 4647 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RJ779 UT WOS:A1995RJ77900070 PM 7623856 ER PT J AU KIM, TW WU, K XU, JL MCAULIFFE, G TANZI, RE WASCO, W BLACK, IB AF KIM, TW WU, K XU, JL MCAULIFFE, G TANZI, RE WASCO, W BLACK, IB TI SELECTIVE LOCALIZATION OF AMYLOID PRECURSOR-LIKE PROTEIN-1 IN THE CEREBRAL-CORTEX POSTSYNAPTIC DENSITY SO MOLECULAR BRAIN RESEARCH LA English DT Article DE AMYLOID PRECURSOR-LIKE PROTEIN; AMYLOID BETA PROTEIN PRECURSOR; POSTSYNAPTIC DENSITY; SYNAPSE; CEREBRAL CORTEX ID CENTRAL NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; RAT-BRAIN; MOLECULAR-CLONING; BETA; GENE; CDNA; IDENTIFICATION; MEMBRANE; HOMOLOG AB Senile plaques, a hallmark of Alzheimer's disease (AD), contain amyloid beta-peptide (A beta), which is generated from the larger amyloid beta protein precursor (APP). In addition to APP, several APP-related proteins have been recently identified in different organisms, including Drosophila amyloid precursor protein-like protein (APPL). Deficiency of APPL causes behavioral deficits in Drosophila, implicating a role in brain function. Moreover, mouse and human cDNA clones encoding amyloid precursor-like proteins (APLP1 and APLP2) have been identified and exhibit extensive sequence similarity to the APPL and APP genes. To define the potential role of APLP in the mammalian brain, we sought to directly localize APLP1 within the complex cortical synaptic structure. We focused on the postsynaptic density (PSD), which appears to be central to synaptic function. We now report that the 90 kDa APLP1, the first known APLP, is localized to the PSD from rat and human cerebral cortex. APLP1 increased during cortical synaptic development, suggesting a role in synaptogenesis or synaptic maturation. In contrast, APP was predominantly expressed in the synaptic membrane fraction, but was barely detectable in the PSD, indicating different subcellular distributions of APP and APLP1. Our observations raise the possibility that APLP1, a homologue of APPL, which appears to be necessary for normal behavior in Drosophila, participates in brain synaptic function in mammals. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. RUTGERS STATE UNIV,UNIV MED & DENT NEW JERSEY,RW JOHNSON MED SCH,DEPT NEUROSCI & CELL BIOL,PISCATAWAY,NJ 08854. RUTGERS STATE UNIV,PROGRAM PHYSIOL & NEUROBIOL,PISCATAWAY,NJ 08854. RP KIM, TW (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,GENET & AGING LAB,13TH ST,BLDG 149,BOSTON,MA 02129, USA. NR 51 TC 48 Z9 51 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD AUG PY 1995 VL 32 IS 1 BP 36 EP 44 DI 10.1016/0169-328X(95)00328-P PG 9 WC Neurosciences SC Neurosciences & Neurology GA RL355 UT WOS:A1995RL35500004 ER PT J AU WAGNER, L AVERY, RK BENSINGER, L KUSINITZ, F HIBBERD, PL PASTERNACK, MS AF WAGNER, L AVERY, RK BENSINGER, L KUSINITZ, F HIBBERD, PL PASTERNACK, MS TI INHIBITION OF CYTOTOXIC T-LYMPHOCYTE-TRIGGERED APOPTOSIS BY TARGET-CELL SURFACE-COUPLED APROTININ SO MOLECULAR IMMUNOLOGY LA English DT Article DE CYTOTOXIC T-LYMPHOCYTE; CELL-MEDIATED CYTOTOXICITY; PROTEASE INHIBITION; APROTININ; GRANZYME A; APOPTOSIS ID GRANZYME-A; DNA FRAGMENTATION; CYTO-TOXICITY; PROTEASES; BREAKDOWN; LEUKEMIA; PROTEIN; ATP AB A variety of recent investigations have implicated granzymes A and/or B in the target cell nuclear injury which accompanies cytotoxic T-lymphocyte-mediated cytolysis. Since soluble antiproteases have had limited efficacy in inhibiting CTL-mediated lysis, we developed a method to couple aprotinin, a peptide inhibitor of serine proteases, to the surface of target cells. Aprotinin modified by N-succinimidyl 3-(2-pyridyldithio)propionate retained trypsin-inhibitory activity, and target cells modified with aprotinin had demonstrable cell surface trypsin-inhibitory activity. Flow cytometry demonstrated that aprotinin was detectable on the target cell surface but underwent modulation at a rather rapid rate. When radiolabeled, aprotinin-coupled target cells were studied in 1-2 hr CTL assays, Cr-51 release was little affected, but (125)IUdR release was reduced up to 75% compared to controls. Corresponding apoptosis analysed by agarose gel electrophoresis and direct cytologic visualization was similarly reduced. Thus, aprotinin bound to the surface of target cells selectively protected target cells against CTL-mediated nuclear injury, and may serve as a model for the development of novel inhibitors of CTL-mediated lysis. C1 UNIV VIENNA,DEPT ENDOCRINOL & METAB,INNERE MED KLIN 3,VIENNA,AUSTRIA. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,INFECT DIS UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. FU NCI NIH HHS [CA 45658] NR 23 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD AUG PY 1995 VL 32 IS 12 BP 853 EP 864 DI 10.1016/0161-5890(95)00054-I PG 12 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA RX381 UT WOS:A1995RX38100002 PM 7565812 ER PT J AU HURFORD, RK DRANOFF, G MULLIGAN, RC TEPPER, RI AF HURFORD, RK DRANOFF, G MULLIGAN, RC TEPPER, RI TI GENE-THERAPY OF METASTATIC CANCER BY IN-VIVO RETROVIRAL GENE TARGETING SO NATURE GENETICS LA English DT Article ID BRAIN-TUMORS; CELLS; INTERLEUKIN-4; EXPRESSION; GENERATION; IMMUNITY; POTENT; INVIVO; IL-2 AB We have achieved efficient transduction of tumour metastases in vivo by the vascular delivery of retroviral producer cells. Experimental liver metastases in mice were created by intrasplenic injection of tumour cells into the portal venous circulation. Following the establishment of micrometastases, delivery of retroviral producer cells by the same route with a vector containing the Escherichia coli beta-galactosidase (lacZ) gene demonstrated selective in vivo gene transfer to tumour deposits. By this approach, two retroviral producer cell lines encoding cytokines (IL-4 and IL-2) directed tumoricidal inflammatory responses to established metastases. Cytokine gene targeting inhibited metastasis formation and caused significant overall reduction in tumour burden, These results suggest a novel therapeutic approach for the treatment of disseminated cancer. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02129 USA. WHITEHEAD INST BIOMED RES, CAMBRIDGE, MA 02142 USA. NR 18 TC 67 Z9 68 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD AUG PY 1995 VL 10 IS 4 BP 430 EP 435 DI 10.1038/ng0895-430 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA RM375 UT WOS:A1995RM37500016 PM 7670493 ER PT J AU HALLAHAN, DE MAUCERI, HJ SEUNG, LP DUNPHY, EJ WAYNE, JD HANNA, NN TOLEDANO, A HELLMAN, S KUFE, DW WEICHSELBAUM, RR AF HALLAHAN, DE MAUCERI, HJ SEUNG, LP DUNPHY, EJ WAYNE, JD HANNA, NN TOLEDANO, A HELLMAN, S KUFE, DW WEICHSELBAUM, RR TI SPATIAL AND TEMPORAL CONTROL OF GENE-THERAPY USING IONIZING-RADIATION SO NATURE MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; ADENOVIRUS TYPE-5; CELLS; TNF AB Activation of transcription of the Egr-1 gene by X-rays is regulated by the promoter region of this gene. We linked the radiation-inducible promoter region of the Egr-1 gene to the gene encoding the radiosensitizing and tumoricidal cytokine, tumour necrosis factor-alpha (TNF-alpha) and used a replication-deficient adenovirus to deliver the Egr-TNF construct to human tumours growing in nude mice. Combined treatment with AdS.EgrTNF and 5,000 cGy (rad) resulted in increased intratumoral TNF-a production and increased tumour control compared with treatment with Ad5.Egr-TNF alone or with radiation alone. The increase in tumour control was achieved without an increase in normal tissue damage when compared to tissue injury from radiation alone. Control of gene transcription by ionizing radiation in vivo represents a novel method of spatial and temporal regulation of gene-based medical treatments. C1 UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. UNIV CHICAGO,PRITZKER SCH MED,CHICAGO,IL 60637. UNIV CHICAGO,DEPT SURG,CHICAGO,IL 60637. UNIV CHICAGO,DEPT ANESTHESIA & CRIT CARE,CHICAGO,IL 60637. DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA37435, CA41068, CA58508] NR 34 TC 280 Z9 287 U1 1 U2 5 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD AUG PY 1995 VL 1 IS 8 BP 786 EP 791 DI 10.1038/nm0895-786 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RM635 UT WOS:A1995RM63500035 PM 7585181 ER PT J AU ILIOPOULOS, O KIBEL, A GRAY, S KAELIN, WG AF ILIOPOULOS, O KIBEL, A GRAY, S KAELIN, WG TI TUMOR SUPPRESSION BY THE HUMAN VON HIPPEL-LINDAU GENE-PRODUCT SO NATURE MEDICINE LA English DT Article ID RETINOBLASTOMA SUSCEPTIBILITY GENE; BINDING; DNA; IDENTIFICATION; TRANSLATION; COMPLEX; DOMAIN AB A partial cDNA sequence for the gene linked to the von Hippel-Lindau (VHL) syndrome was reported in 1993. Mutation or loss of both VHL alleles has been documented in sporadic renal cell carcinomas and in the neoplasms that arise in von Hippel-Lindau kindreds. We have determined that the protein product of the VHL gene is an approximately 30 kilodalton cytoplasmic protein. The renal carcinoma cell line 786-0 is known to harbour a VHL mutation and, as shown here, fails to produce a wild-type VHL protein. Reintroduction of wild-type, but not mutant, VHL into these cells had no demonstrable effect on their growth in vitro but inhibited their ability to form tumours in nude mice. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Bell, Tiffany/F-4403-2010 NR 30 TC 460 Z9 468 U1 4 U2 9 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD AUG PY 1995 VL 1 IS 8 BP 822 EP 826 DI 10.1038/nm0895-822 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RM635 UT WOS:A1995RM63500041 PM 7585187 ER PT J AU BAUMAN, ML KEMPER, TL ARIN, DM AF BAUMAN, ML KEMPER, TL ARIN, DM TI PERVASIVE NEUROANATOMICAL ABNORMALITIES OF THE BRAIN IN 3 CASES OF RETTS-SYNDROME SO NEUROLOGY LA English DT Article ID NEUROPATHOLOGY; AUTISM AB Rett's syndrome (RS) is a clinically defined disorder that appears to be unique to girls and is characterized by apparent cognitive and motor skill loss early in life. We report our findings in the brains of three girls with RS, which were studied in comparison with age-matched controls by means of gapless serial section. Reduced neuronal cell size and increased cell-packing density were present throughout the cortical and subcortical regions of the brain in all cases without evidence of active degeneration. These observations appear to be consistent with a curtailment of development. Further, the degree of abnormality in each case correlates more closely with the clinical presentation of the patient at the time of death than with the age of the patient or duration of symptoms. C1 BOSTON CITY HOSP,DEPT NEUROL,BOSTON,MA 02118. MASSACHUSETTS INST ALLIED HLTH PROFESS,BOSTON,MA. RP BAUMAN, ML (reprint author), MASSACHUSETTS GEN HOSP,CHILDRENS NEUROL SERV,BOSTON,MA 02114, USA. FU NICHD NIH HHS [HD 24448-04] NR 45 TC 103 Z9 105 U1 1 U2 4 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1995 VL 45 IS 8 BP 1581 EP 1586 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA RP304 UT WOS:A1995RP30400028 PM 7644058 ER PT J AU DAGGETT, LP SACAAN, AI AKONG, M RAO, SP HESS, SD LIAW, C URRUTIA, A JACHEC, C ELLIS, SB DREESSEN, J KNOPFEL, T LANDWEHRMEYER, GB TESTA, CM YOUNG, AB VARNEY, M JOHNSON, EC VELICELEBI, G AF DAGGETT, LP SACAAN, AI AKONG, M RAO, SP HESS, SD LIAW, C URRUTIA, A JACHEC, C ELLIS, SB DREESSEN, J KNOPFEL, T LANDWEHRMEYER, GB TESTA, CM YOUNG, AB VARNEY, M JOHNSON, EC VELICELEBI, G TI MOLECULAR AND FUNCTIONAL-CHARACTERIZATION OF RECOMBINANT HUMAN METABOTROPIC GLUTAMATE-RECEPTOR SUBTYPE-5 SO NEUROPHARMACOLOGY LA English DT Article DE METABOTROPIC GLUTAMATE RECEPTORS (HUMAN); CLONING; SPLICE VARIANTS; IN SITU HYBRIDIZATION; EXPRESSION (TRANSIENT); INSP FORMATION; INTRACELLULAR CALCIUM; BINDING; EXPRESSION (STABLE); IMMUNOBLOT ANALYSIS; EXPRESSION (FUNCTIONAL) ID SIGNAL TRANSDUCTION; RAT-BRAIN; EXPRESSION; PROTEIN; BINDING; MEMBRANES; SEQUENCE; PATTERNS; CELLS AB We have isolated and characterized overlapping cDNAs that encode two isoforms of the human metabotropic glutamate receptor subtype 5 (hmGluR5). The deduced amino acid sequences of human and rat mGluR5a are 94.5% identical. However, a region in the putative cytoplasmic domain (SER926-ALA1121) displays significant sequence divergence. Genomic analysis of this region showed that the sequence divergence results from species-specific differences in the genomic sequences, not from alternative splicing. The distribution of mGluR5 mRNA in human brain was most strongly detected throughout the hippocampus, with moderate levels in the caudate-putamen, cerebral cortex, thalamus, and deep cerebellar nuclei, and at low levels in the cerebellar cortex. Activation of both hmGluR5a and hmGluR5b transiently expressed in Xenopus oocytes and HEK293 cells was coupled to inositol phosphate (InsP) formation and elevation of the intracellular free calcium ([Ca2+](i)). The agonist rank order of potency for activating recombinant hmGluR5a receptors in either system was quisqualate > L-glutamate > IS,3R-ACPD. Both the quisqualate stimulated InsP and [Ca2+](i) were inhibited by (+)-MCPG. Recombinant human mGluR5a was also stably expressed in mouse fibroblast Ltk(-) cells, in which the efficacy and potency of quisqualate were unchanged for more than 30 cell passages. C1 SIBIA INC,LA JOLLA,CA 92037. CIBA GEIGY AG,CNS RES,CH-4002 BASEL,SWITZERLAND. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RI Knopfel, Thomas/B-1128-2008 OI Knopfel, Thomas/0000-0002-5718-0765 NR 40 TC 78 Z9 80 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD AUG PY 1995 VL 34 IS 8 BP 871 EP 886 DI 10.1016/0028-3908(95)00085-K PG 16 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA RT974 UT WOS:A1995RT97400009 PM 8532169 ER PT J AU BADR, IA HUSSAIN, HM JABAK, M WAGONER, MD AF BADR, IA HUSSAIN, HM JABAK, M WAGONER, MD TI EXTRACAPSULAR CATARACT-EXTRACTION WITH OR WITHOUT POSTERIOR CHAMBER INTRAOCULAR LENSES IN EYES WITH CATARACT AND HIGH MYOPIA SO OPHTHALMOLOGY LA English DT Article ID RETINAL-DETACHMENT; CAPSULE OPACIFICATION; NATIONAL OUTCOMES; SURGERY; COMPLICATIONS; PREVALENCE; EYES; RISK AB Purpose: To compare the results of insertion of low-power or zero-power posterior chamber intraocular lenses (PC IOLs) after cataract extraction in eyes with high myopia with leaving the eye aphakic. Methods: The outcome of extracapsular cataract extraction (ECCE) with low-power or zero-power PC IOLs in 184 consecutive highly myopic (axial length = 26.0 mm or longer) eyes was compared with 184 consecutive highly myopic eyes receiving ECCE without PC IOLs, Axial length, preoperative visual acuity, age, sex, and follow-up were similar between both groups. Results: In the pseudophakic eyes, there was a statistically significantly better visual outcome (P = 0.006), decreased incidence of posterior capsule, opacification (13.6% versus 33.2%, P < 0.01), and decreased requirement for YAG capsulotomy (6.5% versus 17.9%, P < 0.01). There were two retinal detachments in the pseudophakic eyes compared with four in the aphakic eyes. There were no sight-threatening complications in 12 pseudophakic eyes after YAG capsulotomy. There were four sight-threatening complications (2 retinal detachments, 2 cases of uveitis with secondary glaucoma) in 33 aphakic eyes after YAG capsulotomy. Conclusions: The use of PC IOLs may result in a lower complication rate and better visual outcome after ECCE in eyes with cataract and high myopia. C1 KING KHALID EYE SPECIALIST HOSP,DEPT OPHTHALMOL,RES DEPT,RIYADH 11462,SAUDI ARABIA. KING SAUD UNIV,SCH MED,RIYADH,SAUDI ARABIA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,CORNEA SERV,BOSTON,MA. RP BADR, IA (reprint author), KING KHALID EYE SPECIALIST HOSP,MED LIB,DEPT OPHTHALMOL,DIV ANTERIOR SEGMENT EXTERNAL DIS,RIYADH 11462,SAUDI ARABIA. NR 24 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 1995 VL 102 IS 8 BP 1139 EP 1143 PG 5 WC Ophthalmology SC Ophthalmology GA RN760 UT WOS:A1995RN76000009 PM 9097738 ER PT J AU POWER, WJ NEVES, RA RODRIGUEZ, A DUTT, JE FOSTER, CS AF POWER, WJ NEVES, RA RODRIGUEZ, A DUTT, JE FOSTER, CS TI INCREASING THE DIAGNOSTIC YIELD CONJUNCTIVAL BIOPSY IN PATIENTS WITH SUSPECTED OCULAR CICATRICIAL PEMPHIGOID SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 30-NOV 03, 1994 CL SAN FRANCISCO, CA SP Amer Acad Ophthalmol ID IMMUNOSUPPRESSIVE THERAPY; SYSTEMIC CHEMOTHERAPY AB Background: Ocular cicatricial pemphigoid is a chronic, progressive, autoimmune disease that scars mucous membranes and may lead to blindness. It is of critical importance to be able to make the diagnosis as early as possible to allow early treatment. Conjunctival biopsy facilitates the early diagnosis of this condition. Materials and Methods: Conjunctival biopsy results of 166 consecutive patients seen over a 7-year period, in whom the diagnosis of ocular cicatricial pemphigoid was considered, were reviewed. Results: One hundred twenty-one patients ultimately received a diagnosis of ocular cicatricial pemphigoid. Immunofluorescence studies demonstrated characteristic deposition of immunoreactants at the epithelial basement membrane zone in 63 patients (sensitivity = 52%). When immunofluorescent-negative or inconclusive biopsies were processed further using an immunoperoxidase technique an additional 37 diagnoses were made. This represented an increase in sensitivity from 52% with immunofluorescence only to 83% with the addition of the immunoperoxidase technique. Conclusion: The routine use of the immunoperoxidase technique in immunofluorescent-negative biopsies, allied with appropriate harvesting and handling of biopsied conjunctiva, should significantly increase the diagnostic yield in patients with clinically suspect ocular cicatricial pemphigoid. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,HILLES IMMUNOL LAB,IMMUNOL & UVEITIS SERV,BOSTON,MA 02114. NR 13 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 1995 VL 102 IS 8 BP 1158 EP 1163 PG 6 WC Ophthalmology SC Ophthalmology GA RN760 UT WOS:A1995RN76000012 PM 9097741 ER PT J AU TANIISHII, N WANG, CY STASHENKO, P AF TANIISHII, N WANG, CY STASHENKO, P TI IMMUNOLOCALIZATION OF BONE-RESORPTIVE CYTOKINES IN RAT PULP AND PERIAPICAL LESIONS FOLLOWING SURGICAL PULP EXPOSURE SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE CYTOKINES; INTERLEUKIN-1-ALPHA; TUMOR NECROSIS FACTOR; PERIAPICAL LESION; DENTAL PULP ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; MESSENGER-RNA; INTERLEUKIN-1-BETA PRODUCTION; INSITU HYBRIDIZATION; RESORBING ACTIVITY; IMMUNE CYTOKINES; FIBROBLASTS; CELLS; PATHOGENESIS AB The bone-resorptive cytokines interleukin 1 (IL-1) and tumor necrosis factor (TNF) have been implicated in the pathogenesis of many chronic inflammatory diseases, including pulpitis and apical periodontitis. To further elucidate their role in these disorders, we have identified cells that express IL-1 alpha and TNF alpha in infected pulps and in developing rat periapical lesions after surgical pulp exposure. As detected by immunohistochemistry, IL-1 alpha- and TNF alpha-positive cells were present as early as 2 days after pulp exposure in both the pulp and periapical region. The numbers of cytokine-expressing cells increased up to day 4 in the pulp and up to day 30 in the periapex. In contrast, cells expressing IL-1 beta and TNF beta, the homologous forms of these mediators, were not found in pulp or periapical lesions during this period. Cells expressing IL-1 alpha and TNF alpha were identified primarily as macrophages and fibroblasts, with occasional staining of polymorphonuclear leukocytes. Osteoblasts and osteoclasts were also positive, whereas lymphocytes were negative. In general, cytokine-expressing cells were located proximal to abscesses and the root apex. These findings demonstrate that cells that express bone-resorptive cytokines IL-1 alpha and TNF alpha are present immediately after pulp exposure in this model, which supports the hypothesis that these mediators play a key role in pulpal and periapical pathogenesis, including the concomitant bone destruction. They also indicate that both resident connective tissue cells as well as infiltrating cells express bone-resorptive cytokines in response to infection in these lesions. C1 FORSYTH DENT CTR,DEPT CYTOKINE BIOL,BOSTON,MA 02115. FU NIDCR NIH HHS [DE-09018] NR 28 TC 110 Z9 112 U1 0 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD AUG PY 1995 VL 10 IS 4 BP 213 EP 219 DI 10.1111/j.1399-302X.1995.tb00145.x PG 7 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA RK500 UT WOS:A1995RK50000004 PM 8602333 ER PT J AU LUCARELLI, MJ BILYK, JR SHORE, JW RUBIN, PAD YAREMCHUK, MJ AF LUCARELLI, MJ BILYK, JR SHORE, JW RUBIN, PAD YAREMCHUK, MJ TI ANEURYSMAL BONE-CYST OF THE ORBIT ASSOCIATED WITH FIBROUS DYSPLASIA SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Note ID LESIONS C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,EYE PLAST & ORBIT SERV,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT PLAST SURG,BOSTON,MA 02114. NR 24 TC 13 Z9 13 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD AUG PY 1995 VL 96 IS 2 BP 440 EP 445 DI 10.1097/00006534-199508000-00029 PG 6 WC Surgery SC Surgery GA RM618 UT WOS:A1995RM61800029 PM 7624420 ER PT J AU KATSURA, T VERBAVATZ, JM FARINAS, J MA, TH AUSIELLO, DA VERKMAN, AS BROWN, D AF KATSURA, T VERBAVATZ, JM FARINAS, J MA, TH AUSIELLO, DA VERKMAN, AS BROWN, D TI CONSTITUTIVE AND REGULATED MEMBRANE EXPRESSION OF AQUAPORIN-1 AND AQUAPORIN-2 WATER CHANNELS IN STABLY TRANSFECTED LLC-PK1 EPITHELIAL-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID KIDNEY COLLECTING TUBULE; RAT-KIDNEY; ANTIDIURETIC-HORMONE; COATED PITS; ENDOCYTOSIS; PROTEIN; LOCALIZATION; TRANSPORT; ENDOSOMES; PATHWAYS AB The aquaporins (AQPs) are a family of homologous water-channel proteins that can be inserted into epithelial cell plasma membranes either constitutively (AQP1) or by regulated exocytosis following vasopressin stimulation (AQP2). LLC-PK1 porcine renal epithelial cells were stably transfected with cDNA encoding AQP2 (tagged with a C-terminal c-Myc epitope) or rat kidney AQP1 cDNA in an expression vector containing a cytomegalovirus promoter. Immunofluorescence staining revealed that AQP1 was mainly localized to the plasma membrane, whereas AQP2 was predominantly Located on intracellular vesicles, After treatment with vasopressin or forskolin for 10 min, AQP2 was relocated to the plasma membrane, indicating that this relocation was induced by cAMP. The location of AQP1 did not change. The basal water permeability of AQP1-transfected cells was 2-fold greater than that of nontransfected cells, whereas the permeability of AQP2-transfected cells increased significantly only after vasopressin treatment. Endocytotic uptake of fluorescein isothiocyanate-coupled dextran was stimulated 6-fold by vasopressin in AQP2-transfected cells but was only slightly increased in wild-type or AQP1-transfected cells. This vasopressin-induced endocytosis was inhibited in low-K+ medium, which selectively affects clathrin-mediated endocytosis. These water channel-transfected cells represent an in vitro system that will allow the detailed dissection of mechanisms involved in the processing, targeting, and trafficking of proteins via constitutive versus regulated intracellular transport pathways. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. RP KATSURA, T (reprint author), MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK35124, DK38452] NR 36 TC 148 Z9 155 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 1 PY 1995 VL 92 IS 16 BP 7212 EP 7216 DI 10.1073/pnas.92.16.7212 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RM722 UT WOS:A1995RM72200017 PM 7543677 ER PT J AU FRENETTE, PS JOHNSON, RC HYNES, RO WAGNER, DD AF FRENETTE, PS JOHNSON, RC HYNES, RO WAGNER, DD TI PLATELETS ROLL ON STIMULATED ENDOTHELIUM IN-VIVO - AN INTERACTION MEDIATED BY ENDOTHELIAL P-SELECTIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GRANULE MEMBRANE-PROTEIN; WEIBEL-PALADE BODIES; VASCULAR ENDOTHELIUM; ACTIVATED PLATELETS; GLYCOPROTEIN LIGAND; PLASMA-MEMBRANE; ADHESION; CELLS; THROMBIN; LEUKOCYTES AB P-selectin, found in storage granules of platelets and endothelial cells, can be rapidly expressed upon stimulation, Mice lacking this membrane receptor exhibit a severe impairment of leukocyte rolling, We observed that, in addition to leukocytes, platelets were rolling in mesenteric venules of wild-type mice, To investigate the role of P-selectin in this process, resting or activated platelets from wild-type or P-selectin-deficient mice were fluorescently labeled and transfused into recipients of either genotype, Platelet-endothelial interactions were monitored by intravital microscopy, We observed rolling of either wild-type or P-selectin-deficient resting platelets on wild-type endothelium. Endothelial stimulation with the calcium ionophore A23187 increased the number of platelets rolling I-fold, Activated P-selectin-deficient platelets behaved similarly, whereas activated wildtype platelets bound to leukocytes and were seen rolling together, Platelets of either genotype, resting or activated, interacted minimally with mutant endothelium even after A23187 treatment. The velocity of platelet rolling was 6- to 9-fold greater than that of leukocytes. Our results demonstrate that (i) platelets roll on endothelium in vivo, (ii) this interaction requires endothelial but not platelet P-selectin, and (iii) platelet rolling appears to be independent of platelet activation, indicating constitutive expression of a P-selectin ligand(s) on platelets, We have therefore observed an interesting parallel between platelets and leukocytes in that both of these blood cell types roll on stimulated vessel wall and that this process is dependent on the expression of endothelial P-selectin. RP FRENETTE, PS (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. RI Frenette, Paul/J-8272-2012 FU NHLBI NIH HHS [HL41002, P01 HL41484] NR 47 TC 327 Z9 335 U1 2 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 1 PY 1995 VL 92 IS 16 BP 7450 EP 7454 DI 10.1073/pnas.92.16.7450 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RM722 UT WOS:A1995RM72200065 PM 7543682 ER PT J AU STEDMAN, JM NEFF, JA KOPEL, K DONAHOE, CP HAYS, JR AF STEDMAN, JM NEFF, JA KOPEL, K DONAHOE, CP HAYS, JR TI APPLICANT CHARACTERIZATION OF THE MOST DESIRABLE INTERNSHIP TRAINING-PROGRAM SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article ID PSYCHOLOGY AB One month after Uniform Notification Day, 148 predoctoral internship applicants (49% return rate) were asked to rate their first-, intermediate-, and last-choice sites on 25 variables related to internship program characteristics. Results showed that 8 variables clearly differentiated all three types, and 11 variables differentiated first from last choices. These first-choice characteristics and their implications for program construction and applicant site comparisons are discussed. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. VET ADM MED CTR,HOUSTON,TX 77211. UNIV TEXAS,SCH MED,DEPT PSYCHIAT & BEHAV SCI,HARRIS CTY PSYCHIAT CTR,HOUSTON,TX. RP STEDMAN, JM (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 16 TC 9 Z9 9 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD AUG PY 1995 VL 26 IS 4 BP 396 EP 400 DI 10.1037//0735-7028.26.4.396 PG 5 WC Psychology, Multidisciplinary SC Psychology GA RL505 UT WOS:A1995RL50500008 ER PT J AU TSAI, GC COYLE, JT AF TSAI, GC COYLE, JT TI N-ACETYLASPARTATE IN NEUROPSYCHIATRIC DISORDERS SO PROGRESS IN NEUROBIOLOGY LA English DT Review ID MAGNETIC-RESONANCE SPECTROSCOPY; PROTON MR SPECTROSCOPY; L-ASPARTIC ACID; ACETYL-L-ASPARTATE; AMYOTROPHIC-LATERAL-SCLEROSIS; L-GLUTAMIC ACID; CHROMATOGRAPHY MASS-SPECTROMETRY; CEREBRAL METABOLIC ALTERATIONS; ALPHA-ASPARTYLGLUTAMIC ACID; PERIPHERAL NERVOUS TISSUES AB N-Acetyl aspartate (NAA) is the second most abundant amino acid in the human brain. NAA is synthesized by L-aspartate N-acetyl transferase or by cleavage from N-acetyl aspartyl glutamate by N-acylated alpha-linked L-amino dipeptidase (NAALADase); and it is catabolized to acetate and aspartate by N-acetyl aspartate amino hydrolase (amino acylase II). NAA is localized primarily to neurons, where it is concentrated in the cytosol. Although NAA is devoid of neurophysiological effects, it serves as an acetyl donor, an initiator of protein synthesis or a carbon transfer source across the mitochondrial membrane. The concentration of NAA in human brain increases 3-fold between midgestation and adulthood. In Canavan's Disease, an autosomal recessive disorder due to a null mutation in amino acylase II, NAA levels in brain are markedly increased and disrupt myelination. NAA levels have been found to be reduced in neurodegenerative disorders, including Alzheimer's Disease and Huntington's Disease. Since endogenous NAA can be readily detected in human brain by magnetic resonance spectroscopy, it is increasingly being exploited asa marker for functional and structural integrity of neurons in an expanding number of disorders. C1 HARVARD UNIV,MCLEAN HOSP,SCH MED,DEPT PSYCHIAT,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,MOLEC & DEV NEUROSCI LAB,BELMONT,MA 02178. FU NIMH NIH HHS [R0 1 MH 51290-01]; NINDS NIH HHS [R0 1 NS13584-16] NR 167 TC 291 Z9 306 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD AUG PY 1995 VL 46 IS 5 BP 531 EP 540 DI 10.1016/0301-0082(95)00014-M PG 10 WC Neurosciences SC Neurosciences & Neurology GA RU150 UT WOS:A1995RU15000003 PM 8532851 ER PT J AU WILENS, TE PRINCE, JB BIEDERMAN, J SPENCER, TJ FRANCES, RJ AF WILENS, TE PRINCE, JB BIEDERMAN, J SPENCER, TJ FRANCES, RJ TI ATTENTION-DEFICIT HYPERACTIVITY DISORDER AND COMORBID SUBSTANCE USE DISORDERS IN ADULTS SO PSYCHIATRIC SERVICES LA English DT Note ID PSYCHIATRIC STATUS; METABOLISM; BOYS C1 MASSACHUSETTS GEN HOSP,RES PROGRAM,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ACUTE PSYCHIAT SERV,BOSTON,MA 02114. HACKENSACK MED CTR,DEPT PSYCHIAT,HACKENSACK,NJ. RP WILENS, TE (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL CLIN,WACC 725,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 23 TC 20 Z9 20 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD AUG PY 1995 VL 46 IS 8 BP 761 EP & PG 0 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA RM039 UT WOS:A1995RM03900003 PM 7583473 ER PT J AU HUGDAHL, K BERARDI, A THOMPSON, WL KOSSLYN, SM MACY, R BAKER, DP ALPERT, NM LEDOUX, JE AF HUGDAHL, K BERARDI, A THOMPSON, WL KOSSLYN, SM MACY, R BAKER, DP ALPERT, NM LEDOUX, JE TI BRAIN MECHANISMS IN HUMAN CLASSICAL-CONDITIONING - PET BLOOD-FLOW STUDY SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,CAMBRIDGE,MA 02138. UNIV BERGEN,N-5007 BERGEN,NORWAY. NYU,NEW YORK,NY 10003. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SOC PSYCHOPHYSIOL RES PI WASHINGTON PA 1010 VERMONT AVE NW SUITE 1100, WASHINGTON, DC 20005 SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD AUG PY 1995 VL 32 SU 1 BP S42 EP S42 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA RT160 UT WOS:A1995RT16000168 ER PT J AU MCHORNEY, CA TARLOV, AR AF MCHORNEY, CA TARLOV, AR TI INDIVIDUAL-PATIENT MONITORING IN CLINICAL-PRACTICE - ARE AVAILABLE HEALTH-STATUS SURVEYS ADEQUATE SO QUALITY OF LIFE RESEARCH LA English DT Review DE CLINICAL PRACTICE; HEALTH STATUS ASSESSMENT; INDIVIDUAL PATIENT APPLICATIONS; MEASUREMENT STANDARDS RELIABILITY; SCORE DISTRIBUTIONS; VALIDITY ID QUALITY-OF-LIFE; FUNCTIONAL STATUS QUESTIONNAIRE; PRIMARY CARE PATIENTS; PERCEIVED HEALTH; RHEUMATOID-ARTHRITIS; MEDICAL OUTCOMES; RANDOMIZED TRIAL; SUBJECTIVE HEALTH; STATUS INSTRUMENT; OXYGEN-THERAPY AB Interest has increased in recent years in incorporating health status measures into clinical practice for use at the individual-patient level, We propose six measurement standards for individual-patient applications: (1) practical features, (2) breadth of health measured, (3) depth of health measured, (4) precision for cross-sectional assessment, (5) precision for longitudinal monitoring and (6) validity, We evaluate five health status surveys (Functional Status Questionnaire, Dartmouth COOP Poster Charts, Nottingham Health Profile, Duke Health Profile, and SF-36 Health Survey) that have been proposed for use in clinical practice, We conducted an analytical literature review to evaluate the six measurement standards for individual-patient applications across the five surveys, The most problematic feature of the five surveys was their lack of precision for individual-patient applications, Across all scales, reliability standards for individual assessment and monitoring were not satisfied, and the 95% Cls were very wide, There was little evidence of the validity of the five surveys for screening, diagnosing, or monitoring individual patients, The health status surveys examined in this paper may not be suitable for monitoring the health and treatment status of individual patients, Clinical usefulness of existing measures might be demonstrated as clinical experience is broadened, At this time, however, it seems that new instruments, or adaptation of existing measures and scaling methods, are needed for individual-patient assessment and monitoring. C1 UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,HLTH SERV RES & DEV PROGRAM,MADISON,WI. HARVARD UNIV,SCH PUBL HLTH,NEW ENGLAND MED CTR,INST HLTH,BOSTON,MA 02115. TUFTS UNIV,BOSTON,MA 02111. RP MCHORNEY, CA (reprint author), UNIV WISCONSIN,DEPT PREVENT MED,MADISON,WI 53706, USA. NR 141 TC 813 Z9 817 U1 5 U2 27 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD AUG PY 1995 VL 4 IS 4 BP 293 EP 307 DI 10.1007/BF01593882 PG 15 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA RP357 UT WOS:A1995RP35700001 PM 7550178 ER PT J AU ZIMMER, C WEISSLEDER, R OCONNOR, D LAPOINTE, L BRADY, TJ ENOCHS, WS AF ZIMMER, C WEISSLEDER, R OCONNOR, D LAPOINTE, L BRADY, TJ ENOCHS, WS TI CEREBRAL IRON-OXIDE DISTRIBUTION - IN-VIVO MAPPING WITH MR-IMAGING SO RADIOLOGY LA English DT Article DE BRAIN, BLOOD FLOW; BRAIN, MR; BRAIN, PERFUSION; IRON; MAGNETIC RESONANCE (MR), CONTRAST ENHANCEMENT ID CONTRAST AGENT; BRAIN; DELIVERY; RAT AB PURPOSE: To map the distribution of an iron oxide label in the central nervous system with in vivo magnetic resonance (MR) imaging. MATERIALS AND METHODS: Unilateral osmotic disruption of the blood-brain barrier (BBB) in rats (n = 40) was followed by injection of monocrystalline iron oxide nanoparticles (MION) into the carotid artery. MR images (1.5 T) were obtained in and ex vivo, and results were correlated with histologic section-matched iron maps. RESULTS: A mean of 0.2% of the injected MION was found in the brain 24 hours after unilateral osmotic disruption of the BBB. The spatial distribution of iron oxide within the brain correlated with areas known to have high relative perfusion. Iron was found in cell bodies and dendrites of cortical neurons and astrocytes and in the interstitial space. The threshold in concentration for detection of MION in the brain was 62.2 ng Fe/mm(2). CONCLUSION: MR imaging is well suited to noninvasive in vive mapping of the intracerebral iron oxide distribution. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR NUCL MAGNET RESONANCE,BOSTON,MA 02129. FU NCI NIH HHS [R01 CA59649-01] NR 28 TC 21 Z9 21 U1 1 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 1995 VL 196 IS 2 BP 521 EP 527 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RK619 UT WOS:A1995RK61900037 PM 7617871 ER PT J AU MERKEL, PA LETOURNEAU, EN POLISSON, RP AF MERKEL, PA LETOURNEAU, EN POLISSON, RP TI INVESTIGATIONAL AGENTS FOR RHEUMATOID-ARTHRITIS SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID 5-LIPOXYGENASE INHIBITOR; AMIPRILOSE HYDROCHLORIDE; MYCOPHENOLIC-ACID; MORPHOLINOETHYL ESTER; COLLAGEN ARTHRITIS; ANTIRHEUMATIC DRUG; TENIDAP SODIUM; CYCLOSPORINE-A; RS-61443; RATS AB Agents ranging from simple analgesics to antiinflammatory drugs to powerful immunomodulators have been used for the treatment of rheumatoid arthritis with varying success. Despite the availability of agents that are believed to be ''second line'' or ''disease modifying,'' many patients either do not respond adequately to available agents or must discontinue their use because of intolerable or dangerous adverse reactions. For this reason, researchers continue to search for more efficacious and less toxic agents for patients with rheumatoid arthritis. This article describes pharmaceutical agents currently under investigation for use in rheumatoid arthritis, including the antiinflammatory agents, zileuton and tenidap, and the immunosuppressive agents, leflunomide, mycophenolic acid (RS-61443), tacrolimus (FK-506), sirolimus (rapamycin), amiprilose (therafectin), cladribine (2- chlorodeoxyadenosine), and azaribine. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP MERKEL, PA (reprint author), MASSACHUSETTS GEN HOSP,ARTHRIT UNIT,BULFINCH 165,32 FRUIT ST,BOSTON,MA 02114, USA. NR 85 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD AUG PY 1995 VL 21 IS 3 BP 779 EP 796 PG 18 WC Rheumatology SC Rheumatology GA RQ405 UT WOS:A1995RQ40500011 PM 8619099 ER PT J AU STRAUSS, GM LYNCH, TJ ELIAS, AD JACOBS, C KWIATKOWSKI, DJ SHULMAN, LN CAREY, RW GROSSBARD, ML JAUSS, S SUGARBAKER, DJ SKARIN, AT AF STRAUSS, GM LYNCH, TJ ELIAS, AD JACOBS, C KWIATKOWSKI, DJ SHULMAN, LN CAREY, RW GROSSBARD, ML JAUSS, S SUGARBAKER, DJ SKARIN, AT TI A PHASE-I STUDY OF IFOSFAMIDE CARBOPLATIN ETOPOSIDE PACLITAXEL IN ADVANCED LUNG-CANCER SO SEMINARS IN ONCOLOGY LA English DT Article ID RANDOMIZED TRIAL; CHEMOTHERAPY; CISPLATIN; TAXOL(R) C1 BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV EXPTL MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV THORAC SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,HEMATOL ONCOL UNIT,BOSTON,MA 02114. RP STRAUSS, GM (reprint author), DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 26 TC 15 Z9 15 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 1995 VL 22 IS 4 SU 9 BP 70 EP 74 PG 5 WC Oncology SC Oncology GA RQ171 UT WOS:A1995RQ17100015 PM 7544029 ER PT J AU DEWHIRST, MW LARUE, SM GERWECK, L AF DEWHIRST, MW LARUE, SM GERWECK, L TI TUMOR PHYSIOLOGY AND CELL-KINETICS SO SEMINARS IN VETERINARY MEDICINE AND SURGERY-SMALL ANIMAL LA English DT Article C1 COLORADO STATE UNIV,DEPT RADIOL HLTH SCI,FT COLLINS,CO 80523. MASSACHUSETTS GEN HOSP,DEPT RADIAT MED,BOSTON,MA 02114. RP DEWHIRST, MW (reprint author), DUKE UNIV,MED CTR,DEPT RADIAT ONCOL,DUMC-3455,DURHAM,NC 27710, USA. FU NCI NIH HHS [CA40355, CA29582, CA42745] NR 0 TC 10 Z9 11 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0882-0511 J9 SEMIN VET MED SURG JI Semin. Vet. Med. Surg.-Small Anim. PD AUG PY 1995 VL 10 IS 3 BP 148 EP 157 PG 10 WC Surgery; Veterinary Sciences SC Surgery; Veterinary Sciences GA RW264 UT WOS:A1995RW26400004 PM 8532970 ER PT J AU PAN, M FISCHER, CP WASA, M LUKASZEWICZ, G STEVENS, BR BODE, BP ABCOUWER, SF SOUBA, WW AF PAN, M FISCHER, CP WASA, M LUKASZEWICZ, G STEVENS, BR BODE, BP ABCOUWER, SF SOUBA, WW TI AMINO-ACID-METABOLISM AND THE VASCULAR ENDOTHELIUM - REGULATION AND DISEASE IMPLICATIONS SO SHOCK LA English DT Review ID NITRIC-OXIDE; RELAXING FACTOR; L-ARGININE; GLUTAMINE TRANSPORT; ADENINE-NUCLEOTIDES; CELLS; BIOSYNTHESIS; GLUTATHIONE; PLATELET; RELEASE AB Amino acid metabolism by the vascular endothelium is a complex process that often begins with the carrier-mediated uptake of circulating amino acids into the endothelial cytoplasm. Amino acids are essential for maintaining intact endothelial functions, which include cell proliferation, regulation of blood flow and vascular tone, coagulation and fibrinolysis, and metabolism of a variety of macromolecules. The disturbances in endothelial amino acid transport and metabolism that occur during infection and inflammation are due, in part, to changes in substrate availability and to the local and/or systemic elaboration of specific mediators. An improved understanding of endothelial amino acid metabolism will not only provide new knowledge regarding disease mechanisms and regulation, but may also lead to new treatment strategies that may include the clinical use of specific nutritional formulas. C1 MASSACHUSETTS GEN HOSP,DIV SURG ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,NUTR SUPPORT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV FLORIDA,COLL MED,DEPT PHYSIOL,GAINESVILLE,FL 32610. OI Abcouwer, Steven F/0000-0003-2580-1288 FU NHLBI NIH HHS [HL44986] NR 92 TC 5 Z9 5 U1 0 U2 0 PU BIOMEDICAL PRESS PI AUGUSTA PA 1021 15TH ST, BIOTECH PARK STE 9, AUGUSTA, GA 30901 SN 1073-2322 J9 SHOCK JI Shock PD AUG PY 1995 VL 4 IS 2 BP 79 EP 88 DI 10.1097/00024382-199508000-00001 PG 10 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA RN500 UT WOS:A1995RN50000002 PM 7496902 ER PT J AU SHEKELLE, PG MARKOVICH, S LOUIE, R AF SHEKELLE, PG MARKOVICH, S LOUIE, R TI AN EPIDEMIOLOGIC-STUDY OF EPISODES OF BACK PAIN CARE SO SPINE LA English DT Article AB Study Design. This was a prospective community-based, observational design. Objective. To describe the epidemiology and risk/prognostic factors for back pain episodes of care in a population representing the nonelderly in the United States. Summary of Background Data. Previous United States studies of the epidemiology of back pain care have used defined industrial populations or have relied on the patient's recall of symptoms and care. Methods. Claims forms from the RAND Health Insurance Experiment, a randomized controlled trial of the use of health services, were analyzed. Claims forms were selected if one of the patient-designated reasons for the visit was back pain. Visits were grouped into episodes of care. Descriptive statistics were calculated for episodes. Multivariate logistic regression was used to calculate adjusted odds ratios for independent explanatory sociodemographic and health status variables associated with back pain episodes of care. Results. The 3105 adults in the Health Insurance Experiment had a combined 11,171 person-years of exposure. Six-hundred-eighty-six persons (22%) had a total 1020 episodes of back pain care, representing 8825 visits. Seventy-one percent of persons had a single episode during the Health Insurance Experiment, and 40% of these episodes consisted of a single visit. There were 9.1 episodes per 100 person-years. Insurance status, geographic site, white race, lesser education, poorer physical functioning, and greater pain at baseline all were independently associated with having a back pain episode of care. Conclusions. Back pain episodes of care occur commonly in the adult U.S. population, but usually are brief and recur infrequently. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT HLTH SERV,LOS ANGELES,CA 90024. RP SHEKELLE, PG (reprint author), RAND CORP,GRAD SCH,1700 MAIN ST,POB 2138,SANTA MONICA,CA 90407, USA. FU AHRQ HHS [1R03HS06920-01] NR 0 TC 66 Z9 67 U1 2 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0362-2436 J9 SPINE JI SPINE PD AUG 1 PY 1995 VL 20 IS 15 BP 1668 EP 1673 DI 10.1097/00007632-199508000-00004 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA RM966 UT WOS:A1995RM96600004 PM 7482015 ER PT J AU CHAUHAN, D UCHIYAMA, H URASHIMA, M YAMAMOTO, K ANDERSON, KC AF CHAUHAN, D UCHIYAMA, H URASHIMA, M YAMAMOTO, K ANDERSON, KC TI REGULATION OF INTERLEUKIN-6 IN MULTIPLE-MYELOMA AND BONE-MARROW STROMAL CELLS SO STEM CELLS LA English DT Article DE INTERLEUKIN 6; MULTIPLE MYELOMA; ADHESION MOLECULES; NF-KAPPA-B; MYELOMA CELL LINES; BONE MARROW STROMAL CELLS; PARACRINE MYELOMA CELL GROWTH ID AUTOCRINE GROWTH; GENE-EXPRESSION; SERUM LEVELS; LINES; DISEASE; PROLIFERATION; LEUKEMIA; ADHESION AB We and others have shown that some freshly isolated multiple myeloma (MM) cells and derived cell lines express interleukin 6 (IL-6) receptors and proliferate in vitro in response to IL-6; a subset of MM cells also expresses IL-6 mRNA, is intracytoplasmic IL-6 positive and secretes IL-6, We have shown that MM cells express the cell surface adhesion molecules CD29/CDw49d(VLA-4), CD18/CD11a(LFA-1) and CD44, and may localize to marrow via specific adherence to both extracellular matrix proteins and to bone marrow stromal cells (BMSCs). MM cell adhesion triggers IL-6 secretion by normal and MM BMSCs and related IL-6-mediated tumor cell growth, Our attempts to block MM I cell adhesion to BMSC-induced IL-6 secretion by using antibodies to CD29/CDw49d, CD18/11a, and/or CD44 demonstrated minimal effects, suggesting that another ligand-receptor interaction triggers IL-6 secretion when MM cells and BMSCs are juxtaposed, Both MM cells and BMSCs express CD40, Triggering of MM cells and BMSCs via CD40 upregulates IL-6 secretion in both MM cells and MM-derived cell lines, as well as BMSCs and BMSC lines, suggesting the possibility of both autocrine and paracrine MM cell growth triggered via CD40, Finally, experiments using the LP 101 BMSC line transiently transfected with IL-6 promoter fragments linked to chloramphenicol acetyltransferase reporter gene demonstrate that adhesion of MM cells induces IL-6 gene transcription in BMSCs, which is conferred via the NF-kappa B binding motif, Further characterization of mechanisms of IL-6 regulation in MM cells and BMSCs may provide new therapeutic strategies based upon interruption of IL-6-mediated autocrine and paracrine tumor cell growth. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. KANAZAWA UNIV,CANC RES INST,DEPT MOLEC PATHOL,KANAZAWA,ISHIKAWA,JAPAN. FU NCI NIH HHS [CA 50947] NR 25 TC 30 Z9 30 U1 0 U2 1 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PD AUG PY 1995 VL 13 SU 2 BP 35 EP 39 PG 5 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA RT151 UT WOS:A1995RT15100006 PM 8520509 ER PT J AU ALSINA, M BOYCE, BF MUNDY, GR ROODMAN, GD AF ALSINA, M BOYCE, BF MUNDY, GR ROODMAN, GD TI AN IN-VIVO MODEL OF HUMAN MULTIPLE-MYELOMA BONE-DISEASE SO STEM CELLS LA English DT Article DE MULTIPLE MYELOMA; BONE DISEASE; OSTEOCLAST; OSTEOBLAST ID CELLS; INTERLEUKIN-1; CYTOKINE; GROWTH AB Osteolytic bone destruction and its complications, such as hypercalcemia, pathologic fractures and nerve compression, are the major source of morbidity in patients with multiple myeloma (MM). The bone destruction in MM is due to increased osteoclast activity, but the mechanisms responsible are not entirely clear. We have utilized a human plasma cell leukemia cell line, ARH-77, that has disseminated growth in mice with severe combined immunodeficiency (SCID) and expresses immunoglobulin G kappa (IgG kappa), as a model for human MM. Fifteen SCID mice were irradiated with 400R and 10 of these were injected with 10(6) ARH-77 cells i.v., 24 h after irradiation, Five mice were used as a control group, Development of bone disease was assessed by blood calcium levels, x-rays and histology, Seven out of seven mice that survived irradiation and received ARH-77 cells developed hind limb paralysis 28-35 days after injection, One hundred percent of these mice developed hypercalcemia (1.35-1.46 mmol/l), a mean of five days after becoming paraplegic, Lytic bone lesions were detected by x-ray in all the hypercalcemic mice examined, No lytic lesions or hypercalcemia developed in the controls, Mice were then sacrificed after developing hypercalcemia. Histologic examination of the ARH-77 mice showed infiltration of myeloma cells in the liver and spleen, Marked infiltration by the tumor was found in vertebrae and long bones, with loss of bony trabeculae and increased osteoclast numbers, Thus, we have developed a model of human MM bone disease which should be very useful to study the pathogenesis of the bone destruction in MM, and to develop novel therapeutic strategies to improve or arrest the bone disease in these patients. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. FU NCI NIH HHS [CA01723, CA-40035]; NIADDK NIH HHS [AM35188] NR 8 TC 9 Z9 9 U1 0 U2 0 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PD AUG PY 1995 VL 13 SU 2 BP 48 EP 50 PG 3 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA RT151 UT WOS:A1995RT15100008 PM 8520511 ER PT J AU ABCOUWER, SF LUKASCEWICZ, GC RYAN, US SOUBA, WW AF ABCOUWER, SF LUKASCEWICZ, GC RYAN, US SOUBA, WW TI MOLECULAR REGULATION OF LUNG ENDOTHELIAL GLUTAMINE-SYNTHETASE EXPRESSION SO SURGERY LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Society-of-University-Surgeons CY FEB 09-11, 1995 CL DENVER, CO SP Soc Univ Surgeons ID GENE; METABOLISM; CELLS; RATS; RNA AB Background. The lungs play a crucial role in maintaining amino acid homeostasis by exporting glutamine. Lung glutamine release is increased markedly in patients with sepsis, and in rat models injection of endotoxin causes up-regulation of glutamine synthetase (GS), the principal enzyme of glutamine synthesis. To investigate the molecular regulation of this response in the lung microvasculature we studied the effects of several hormones and cytokines that mediate the septic response on the expression of GS in rat microvascular pulmonary endothelial cells (MPECs). Methods. MPECs were grown to confluence and incubated with the synthetic glucocorticoid dexamethasone, prostaglandins, cytokines, or activated complement C5a. Cellular lysates were prepared and total cellular RNA was extracted, hybridized with a GS complementary DNA derived probe, and normalized to reduced glyceraldehyde-phosphate dehydrogenase. GS protein content was determined by Western blotting with a GS antibody. Results. Of the compounds tested, only dexamethasone caused a marked increase (tenfold or greater) of GS messenger RNA and protein levels in MPECs. Dexamethasone-induced accumulation of GS messenger RNA was rapid, dose-dependent, and maximal after 4 hours of exposure. GS protein levels were maximal after 8 hours and remained elevated for at least 48 hours. The dose of dexamethasone sufficient to induce 50% of maximal GS messenger RNA and protein level increase was approximately 10 nmol/L. The dexamethasone-induced increase of GS messenger RNA level was completely blocked by the glucocorticoid receptor antagonist RU38486 and by the transcriptional inhibitor actinomycin D but was not inhibited by the translational inhibitor cycloheximide. Conclusions. Glucocorticoids augment GS expression in rat lung microvascular endothelial cells in a manner consistent with a direct transcriptional response via glucocorticoid receptors. Other septic response mediators had minimal effect on GS expression. Induction of GS expression by adrenocorticoids is likely to contribute to the marked ability of the lungs to augment glutamine production during septic states. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV SURG ONCOL,BOSTON,MA 02114. OI Abcouwer, Steven F/0000-0003-2580-1288 FU NHLBI NIH HHS [R01-HL44986] NR 21 TC 20 Z9 20 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 1995 VL 118 IS 2 BP 325 EP 335 DI 10.1016/S0039-6060(05)80341-1 PG 11 WC Surgery SC Surgery GA RM965 UT WOS:A1995RM96500028 PM 7638749 ER PT J AU REED, GL LUKACOVA, D AF REED, GL LUKACOVA, D TI GENERATION AND MECHANISM OF ACTION OF A POTENT INHIBITOR OF FACTOR-XIII FUNCTION SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID FIBRIN-STABILIZING FACTOR; THROMBIN-CATALYZED ACTIVATION; COAGULATION FACTOR-XIII; CROSS-LINKING; BLOOD-COAGULATION; ALPHA-2-PLASMIN INHIBITOR; MONOCLONAL-ANTIBODY; HUMAN-MONOCYTES; PROTEINS; BINDING AB Although known to play a critical role in thrombosis, the precise role of factor XIII in other processes like wound healing and gestation remains to be elucidated. Because a specific, potent inhibitor could help define the function of factor XIII in these processes, or determine the potential benefits of factor XIII suppression in thrombotic disease, we have derived and characterized a monoclonal antibody inhibitor of factor XIII activation. This immunoinhibitor, 9C11, reacts specifically with both plasma and platelet forms of factor XIII. When added to human plasma, either as whole immunoglobulin or as Fab fragments, 9C11 completely prevented thrombin-activated factor XIII activity with small molecular weight substrates like C-14-putrescine. In addition, when clotted with plasma, 9C11 ablated the gamma chain crosslinking of fibrin catalyzed by factor XIII and markedly accelerated the fibrinolysis of plasma clots by urokinase. Studies of the mechanism of action showed that 9C11 inhibited the cleavage and activation of factor XIII by thrombin, but did not affect the catalytic function of previously activated factor XIII. Although it inhibited thrombin activation, experiments indicated that it bound comparably to both factor XIII zymogen and the thrombin-cleaved zymogen, and did not bind to the thrombin cleavage site of the molecule. Taken together these experiments indicated that 9C11 acted as an inhibitor of the thrombin cleavage and activation of the factor XIII A-subunit. Its potency and specificity make it a useful agent for studying thrombin-activatable factor XIII function in biological systems. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. RP REED, GL (reprint author), HARVARD UNIV,SCH PUBL HLTH,II-127,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [K08 HL02348] NR 38 TC 9 Z9 9 U1 0 U2 1 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1995 VL 74 IS 2 BP 680 EP 685 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA RQ326 UT WOS:A1995RQ32600020 PM 8585006 ER PT J AU HSU, SIH THADHANI, RI DANIELS, GH AF HSU, SIH THADHANI, RI DANIELS, GH TI ACUTE COMPARTMENT SYNDROME IN A HYPOTHYROID PATIENT SO THYROID LA English DT Note ID RENAL-FAILURE; MUSCLE; MYOPATHY; RHABDOMYOLYSIS; POLYNEUROPATHY; MYXEDEMA AB Acute compartment syndrome (ACS) is caused by conditions that either decrease the size of the compartment or increase the content of the compartment. Intracompartmental pressures are raised, thereby initiating a sequence of events that results in myoneural injury. Although limb trauma is the most common and well-recognized etiology of ACS, the cause is frequently not readily apparent, Thyroid disease is not a commonly recognized cause of ACS; only one case of ACS associated with hypothyroidism has been previously reported. We now describe a second case of ACS in a patient with severe hypothyroidism and discuss the possible pathogenesis of this association. C1 MASSACHUSETTS GEN HOSP,DEPT MED,MED SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,THYROID UNIT,BOSTON,MA 02114. RP HSU, SIH (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,RENAL UNIT,5 FRUIT ST,BOSTON,MA 02114, USA. NR 39 TC 14 Z9 14 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD AUG PY 1995 VL 5 IS 4 BP 305 EP 308 DI 10.1089/thy.1995.5.305 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RV688 UT WOS:A1995RV68800012 PM 7488873 ER PT J AU GIPSON, IK SPURRMICHAUD, SJ TISDALE, AS KUBLIN, C CINTRON, C KEUTMANN, H AF GIPSON, IK SPURRMICHAUD, SJ TISDALE, AS KUBLIN, C CINTRON, C KEUTMANN, H TI STRATIFIED SQUAMOUS EPITHELIA PRODUCE MUCIN-LIKE GLYCOPROTEINS SO TISSUE & CELL LA English DT Article DE CORNEAL EPITHELIUM; LARYNGEAL EPITHELIUM; VAGINAL EPITHELIUM; STRATIFIED EPITHELIUM; MUCINS ID MENSTRUAL-CYCLE; VAGINAL EPITHELIUM; MUCUS; EXPRESSION; VESICLES; PROTEINS; CLONING; CELLS AB The stratified squamous epithelia of the ocular surface, larynx, and vagina are mucus-coated epithelia, apices of which are subject to abrasive pressure from epithelia - epithelia interactions from eyelid, vocal cords, or vaginal folds, respectively. Mucus coats on these epithelia have generally been considered to be derived from the specialized mucin-producing cells embedded either in the epithelia or in adjacent tissues. Here we report the isolation, partial characterization, and cellular localization of a mucin-like glycoprotein produced by these stratified epithelia. In all three epithelia, the mucin-like molecule is present on cytoplasmic vesicles in subapical cells. As cells differentiate to their apical-most position adjacent to their mucus coat, the mucin-like molecule moves to the cell membrane where it is particularly prominent on microplicae folds. Lectin affinity chromatography was used to isolate the molecule from rat vaginal and corneal epithelium. Isolated material was approximately 60% carbohydrate and 40% protein. The major monosaccharide was N-acetylgalactosamine with lesser amounts of N-acetylglucosamine, galactose, mannose, xylose and fucose. Amino acid analysis demonstrated the predominant amino acids to be glycine, serine, threonine and proline. These data plus PAS and Alcian blue binding to the isolate indicate a mucin-like glycoprotein. C1 HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP GIPSON, IK (reprint author), SCHEPENS EYE RES INST,20 STANIFORD ST,BOSTON,MA 02114, USA. NR 37 TC 34 Z9 34 U1 1 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0040-8166 J9 TISSUE CELL JI Tissue Cell PD AUG PY 1995 VL 27 IS 4 BP 397 EP 404 DI 10.1016/S0040-8166(95)80060-3 PG 8 WC Anatomy & Morphology; Cell Biology SC Anatomy & Morphology; Cell Biology GA RQ254 UT WOS:A1995RQ25400004 PM 7570576 ER PT J AU RICHARDSON, JH MARASCO, WA AF RICHARDSON, JH MARASCO, WA TI INTRACELLULAR ANTIBODIES - DEVELOPMENT AND THERAPEUTIC POTENTIAL SO TRENDS IN BIOTECHNOLOGY LA English DT Article ID RETROVIRAL VECTORS; GENE-THERAPY; EXPRESSION AB Single-chain antibodies, synthesized by the cell and targeted to a particular cellular compartment, can be used to interfere in a highly specific manner with cell growth and metabolism. Recent applications of this technology include the phenotypic knockout of growth-factor receptors, the functional inactivation of p21(ras) and the inhibition of HIV-1 replication. Intracellular antibodies are likely to have a widespread impact in biological research as a simple and effective alternative to other forms of gene inactivation; they demonstrate clear potential as reagents for cancer therapy and for the control of infectious diseases. RP RICHARDSON, JH (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 28 TC 82 Z9 82 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD AUG PY 1995 VL 13 IS 8 BP 306 EP 310 DI 10.1016/S0167-7799(00)88970-2 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA RN506 UT WOS:A1995RN50600007 PM 7662306 ER PT J AU MYERS, MG WHITE, MF AF MYERS, MG WHITE, MF TI NEW FRONTIERS IN INSULIN-RECEPTOR SUBSTRATE SIGNALING SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE KINASES; SH3 DOMAINS; PROTEIN; IRS-1; GRB2; ASSOCIATION; EXPRESSION; CELLS; P85 AB Although most tyrosine kinase growth factor receptors directly bind Src homology 2 (SH2) proteins, the insulin receptor, and a select group of other hormone receptors-including an emerging group of cytokine receptors-phosphorylate intracellular insulin receptor substrate (IRS) proteins, which subsequently bind SH2 proteins. There are currently two members of the IRS family (IRS-1 and IRS-2); these IRS proteins contain elements of substantial similarity, bur may also play divergent roles in mammalian physiology. The engagement of IRS proteins by other receptors suggests that IRS proteins mediate diverse biological signals. C1 HARVARD UNIV,SCH MED,DIV MED SCI,BOSTON,MA 02115. RP MYERS, MG (reprint author), JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 71 TC 64 Z9 64 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD AUG PY 1995 VL 6 IS 6 BP 209 EP 215 DI 10.1016/1043-2760(95)00092-V PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RV681 UT WOS:A1995RV68100004 PM 18406704 ER PT J AU ROHRWILD, M ALPAN, RS LIANG, P PARDEE, AB AF ROHRWILD, M ALPAN, RS LIANG, P PARDEE, AB TI INOSINE-CONTAINING PRIMERS FOR MESSENGER-RNA DIFFERENTIAL DISPLAY SO TRENDS IN GENETICS LA English DT Note ID POLYMERASE CHAIN-REACTION; MESSENGER-RNA C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. RP ROHRWILD, M (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA61232] NR 6 TC 9 Z9 12 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD AUG PY 1995 VL 11 IS 8 BP 300 EP 300 DI 10.1016/S0168-9525(00)89085-X PG 1 WC Genetics & Heredity SC Genetics & Heredity GA RP103 UT WOS:A1995RP10300005 PM 8585126 ER PT J AU COLEY, CM BARRY, MJ FLEMING, C WASSON, JH FAHS, MC OESTERLING, JE AF COLEY, CM BARRY, MJ FLEMING, C WASSON, JH FAHS, MC OESTERLING, JE TI SHOULD MEDICARE PROVIDE REIMBURSEMENT FOR PROSTATE-SPECIFIC ANTIGEN TESTING FOR EARLY DETECTION OF PROSTATE-CANCER .2. EARLY DETECTION STRATEGIES SO UROLOGY LA English DT Review ID DIGITAL RECTAL EXAMINATION; SERUM PSA CONCENTRATION; TRANSRECTAL ULTRASONOGRAPHY; DETECTION-PROJECT; SCREENING-TEST; INTRAEPITHELIAL NEOPLASIA; PREDICTIVE VALUE; PATIENT AGE; MEN; BENIGN C1 MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,BOSTON,MA 02114. HLTH OUTCOMES ASSOC,VANCOUVER,WA. DARTMOUTH COLL SCH MED,CTR EVALUAT CLIN SCI,HANOVER,NH 03756. MT SINAI SCH MED,DEPT COMMUNITY MED,DIV HLTH ECON,NEW YORK,NY 10029. MT SINAI SCH MED,US INT LONGEV CTR,NEW YORK,NY 10029. UNIV MICHIGAN,DEPT SURG,DIV UROL,ANN ARBOR,MI 48109. FU AHRQ HHS [HS08397, HS06336] NR 127 TC 31 Z9 32 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD AUG PY 1995 VL 46 IS 2 BP 125 EP 141 DI 10.1016/S0090-4295(99)80181-2 PG 17 WC Urology & Nephrology SC Urology & Nephrology GA RM641 UT WOS:A1995RM64100001 PM 7542817 ER PT J AU SUIT, H AF SUIT, H TI SARCOMA OF SOFT-TISSUES - RADIATION SENSITIVITY, TREATMENT FIELD MARGINS, PATHOLOGICAL MARGINS, AND DOSE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material RP SUIT, H (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 30 PY 1995 VL 32 IS 5 BP 1545 EP 1546 DI 10.1016/0360-3016(95)00265-Z PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA RM878 UT WOS:A1995RM87800036 PM 7635802 ER PT J AU BERNARDS, A AF BERNARDS, A TI NEUROFIBROMATOSIS TYPE-1 AND RAS-MEDIATED SIGNALING - FILLING IN THE GAPS SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review ID GTPASE-ACTIVATING PROTEIN; GUANINE-NUCLEOTIDE EXCHANGE; EPIDERMAL GROWTH-FACTOR; FULL-LENGTH NEUROFIBROMIN; TRANSGENIC MOUSE MODEL; T-CELL ACTIVATION; GENE-PRODUCT; NF1 GENE; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; SACCHAROMYCES-CEREVISIAE RP BERNARDS, A (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 277 TC 51 Z9 51 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD JUL 28 PY 1995 VL 1242 IS 1 BP 43 EP 59 DI 10.1016/0304-419X(95)00003-X PG 17 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA RP914 UT WOS:A1995RP91400004 PM 7626654 ER PT J AU MING, M EWEN, ME PEREIRA, MEA AF MING, M EWEN, ME PEREIRA, MEA TI TRYPANOSOME INVASION OF MAMMALIAN-CELLS REQUIRES ACTIVATION OF THE TGF-BETA SIGNALING PATHWAY SO CELL LA English DT Article ID TRANSFORMING GROWTH-FACTOR; II RECEPTOR; CRUZI; INHIBITION; PROTEIN; KINASE; TRYPOMASTIGOTES; DIFFERENTIATION; IDENTIFICATION; PROLIFERATION AB Trypanosoma cruzi invades most nucleated mammalian cells by as yet unknown mechanisms, We report here that while T. cruzi attaches to epithelial cells lacking signaling transforming growth factor beta (TGF beta) receptor I or II, the adherent parasites cannot penetrate and replicate inside the mutant cells, as they do in parental cells, Invasion of the mutants is restored by transfection with the TGF beta receptor genes, as are biological responses to TGF beta. Similar rescue of both TGF beta antiproliferative response and T. cruzi invasion was demonstrated in a hybrid of TGF beta-resistant bladder and colon carcinoma cells. In addition, T. cruzi did not efficiently invade epithelial cells with dysfunction of the intracellular signaling cascade caused by the constitutive expression of the cyclin-dependent kinase cdk4 or of the oncogene H-ras. Treatment with TGF beta, but not with other antiproliferative agents of nonphagocytic cells, greatly enhances T. cruzi invasion. Moreover, infective, but not noninfective, trypanosomes strongly induce a TGF beta-responsive reporter gene in TGF beta-sensitive, but not in TGF beta-insensitive, cell lines. Thus, T. cruzi itself may directly trigger activation of the TGF beta signaling pathway required for parasite entry into the mammalian cells. C1 TUFTS UNIV,NEW ENGLAND MED CTR,TUPPER RES INST,DIV GEOG MED & INFECT DIS,TROP DIS RES UNIT,BOSTON,MA 02111. HARVARD UNIV,SCH MED,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. NR 50 TC 114 Z9 118 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 28 PY 1995 VL 82 IS 2 BP 287 EP 296 DI 10.1016/0092-8674(95)90316-X PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RL760 UT WOS:A1995RL76000016 PM 7628017 ER PT J AU KOUNNAS, MZ MOIR, RD REBECK, GW BUSH, AI ARGRAVES, WS TANZI, RE HYMAN, BT STRICKLAND, DK AF KOUNNAS, MZ MOIR, RD REBECK, GW BUSH, AI ARGRAVES, WS TANZI, RE HYMAN, BT STRICKLAND, DK TI LDL RECEPTOR-RELATED PROTEIN, A MULTIFUNCTIONAL APOE RECEPTOR, BINDS SECRETED BETA-AMYLOID PRECURSOR PROTEIN AND MEDIATES ITS DEGRADATION SO CELL LA English DT Article ID DENSITY-LIPOPROTEIN RECEPTOR; SPORADIC ALZHEIMERS-DISEASE; ACTIVATOR INHIBITOR TYPE-1; ALPHA-2-MACROGLOBULIN RECEPTOR; APOLIPOPROTEIN-E; PLASMINOGEN-ACTIVATOR; MESSENGER-RNA; NEXIN-II; CELL; PURIFICATION AB The secreted form of beta-amyloid precursor protein (APP) containing the Kunitz proteinase inhibitor (KPI) domain, also called protease nexin II, is internalized and degraded by cells. We show that the low density lipoprotein (LDL) receptor-related protein (LRP) is responsible for the endocytosis of secreted APP. APP(S)770 degradation is inhibited by an LRP antagonist called the receptor-associated protein (RAP) and by LRP antibodies and is greatly diminished in fibroblasts genetically deficient in LRP. APP(S)695, which lacks the KPI domain, isa poor LRP ligand, Since LRP also binds apolipoprotein E (apoE)-enriched lipoproteins and inheritance of the epsilon 4 allele of the apoE gene is a risk factor for Alzheimer's disease (AD), these data link in a single metabolic pathway two molecules strongly implicated in the pathophysiology of AD. C1 AMER RED CROSS,HOLLAND LABS,DEPT BIOCHEM,ROCKVILLE,MD 20855. MASSACHUSETTS GEN HOSP,GENET & AGING LAB,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NHLBI NIH HHS [HL50787]; NIDDK NIH HHS [DK45598]; NIGMS NIH HHS [GM42581] NR 76 TC 395 Z9 404 U1 2 U2 14 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 28 PY 1995 VL 82 IS 2 BP 331 EP 340 DI 10.1016/0092-8674(95)90320-8 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RL760 UT WOS:A1995RL76000020 PM 7543026 ER PT J AU BARTKIEWICZ, M HERNANDO, N REDDY, SV ROODMAN, GD BARON, R AF BARTKIEWICZ, M HERNANDO, N REDDY, SV ROODMAN, GD BARON, R TI CHARACTERIZATION OF THE OSTEOCLAST VACUOLAR H+-ATPASE B-SUBUNIT SO GENE LA English DT Article DE PROTON PUMP; V-ATPASE; ION TRANSPORT; BONE RESORPTION; CHICKEN; CDNA CLONING; 1,25-DIHYDROXYVITAMIN D-3 ID CARBONIC ANHYDRASE-II; PROTON PUMP; BONE-RESORPTION; MESSENGER-RNA; BOVINE KIDNEY; EXPRESSION; CELLS; LOCALIZATION; MEMBRANES; ISOFORM AB During bone resorption, osteoclasts acidify the extracellular bone resorbing compartment via a vacuolar H+-ATPase (V-ATPase), which resides in the ruffled-border membrane. In an effort to characterize the composition of the osteoclast V-ATPase catalytic domain, we have isolated a cDNA clone that encodes the V-ATPase B-subunit from a cDNA library constructed from highly purified chicken osteoclasts. Comparison of the predicted amino-acid sequence with the published sequences of isoforms of V-ATPase B-subunits from other sources revealed that the chicken osteoclast B-subunit is brain type and not kidney type. Furthermore, only clones encoding the brain type isoform of subunit B could be generated by PCR from a cDNA library prepared from human osteoclastoma osteoclast-like cells. Northern blot analysis revealed that two B-subunit mRNAs, approx. 1.7 and 3.5 kb in length, are expressed in chicken bone marrow mononuclear cells, brain and kidney, although the relative amounts of these two transcripts were different in each tissue. In brain, the 3.5-kb mRNA was predominantly expressed. In bone marrow cells, the levels of the 1.7-kb mRNA were higher than in other tissues and expression of this message was increased by 1,25-dihydroxyvitamin D-3, suggesting that this mRNA is specifically upregulated during osteoclast differentiation. These results indicate that the B-subunit isoforms present in the catalytic domains of the osteoclast and kidney V-H+-ATPases are different and further suggest that selective expression of isoforms of the B-subunit in these two tissues could provide a structural basis for some of the differences we have reported in the pharmacology and catalytic properties of these two enzymes. C1 YALE UNIV,SCH MED,DEPT ORTHOPED,NEW HAVEN,CT 06520. YALE UNIV,SCH MED,DEPT CELL BIOL,NEW HAVEN,CT 06520. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. FU NIAMS NIH HHS [AR 41339] NR 33 TC 16 Z9 17 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 JUL 28 PY 1995 VL 160 IS 2 BP 157 EP 164 DI 10.1016/0378-1119(95)00228-X PG 8 WC Genetics & Heredity SC Genetics & Heredity GA RP177 UT WOS:A1995RP17700003 PM 7642089 ER PT J AU HOLZ, GG LEECH, CA HABENER, JF AF HOLZ, GG LEECH, CA HABENER, JF TI ACTIVATION OF A CAMP-REGULATED CA2+-SIGNALING PATHWAY IN PANCREATIC BETA-CELLS BY THE INSULINOTROPIC HORMONE GLUCAGON-LIKE PEPTIDE-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GASTRIC-INHIBITORY POLYPEPTIDE; CYCLIC ADENOSINE-MONOPHOSPHATE; ADENYLATE-CYCLASE; FUNCTIONAL EXPRESSION; SIGNAL TRANSDUCTION; GENE-EXPRESSION; ELECTRICAL-ACTIVITY; DIABETES-MELLITUS; INCRETIN HORMONE; CYTOSOLIC CA-2+ AB Glucagon-like peptide-1 (GLP-1) is an intestinally derived insulinotropic hormone that is currently under investigation for use in the treatment of diabetes mellitus. To investigate the Ca2+ signaling pathways by which GLP-1 may stimulate the secretion of insulin from pancreatic beta-cells, we examined its effects on the concentration of free intracellular Ca2+ ([Ca2+](i)) while simultaneously determining what action it exerts on ion channel function. Measurements of [Ca2+](i) were obtained from single rat beta-cells and from beta TC6 and HIT-T15 insulinoma cells loaded with the Ca2+ indicator fura-2, and changes in membrane potential and current were monitored using the perforated patch clamp technique. We report a previously undocumented action of GLP-1 and analogs of cAMP (8-bromo-cAMP, Sp- or Rp-adenosine 3',5'-cyclic monophosphothionate triethylamine) to raise [Ca2+](i) that is attributable to the activation of a prolonged inward current designated here as I-cAMP. Activation of I-cAMP is associated with an increased membrane conductance, membrane depolarization, and triggers large increases of [Ca2+]. I-cAMP is primarily a Na+ current that is blocked by extracellularly applied La3+ or by intracellular administration of Ca2+ chelators (1,2-bis(2- aminophenoxy)ethane N,N,N',N'-tetraacetic acid/acetoxy-methyl EGTA) and which exhibits a reversal potential of about -26 mV. We propose that I-cAMP results from the opening of nonselective cation channel that are activated by intracellular Ca2+ and cAMP and which might play an important role in the regulation of insulin secretion from pancreatic beta-cells. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,MOLEC ENDOCRINOL LAB,BOSTON,MA 02114. RP HOLZ, GG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIABET UNIT,WELLMAN 320,50 BLOSSOM ST,BOSTON,MA 02114, USA. RI Holz, George/A-3386-2012 FU NIDDK NIH HHS [DK45817, R01 DK030834, DK30834, R01 DK045817] NR 67 TC 142 Z9 143 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 28 PY 1995 VL 270 IS 30 BP 17749 EP 17757 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RM266 UT WOS:A1995RM26600021 PM 7543091 ER PT J AU BERDITCHEVSKI, F BAZZONI, G HEMLER, ME AF BERDITCHEVSKI, F BAZZONI, G HEMLER, ME TI SPECIFIC ASSOCIATION OF CD63 WITH THE VLA-3 AND VLA-6 INTEGRINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-ADHESION RECEPTORS; CYTOPLASMIC DOMAIN; MONOCLONAL-ANTIBODIES; ALPHA-SUBUNIT; ONCOGENIC TRANSFORMATION; MEMBRANE GLYCOPROTEIN; EXTRACELLULAR-MATRIX; FIBRONECTIN RECEPTOR; MOLECULAR-CLONING; ENDOTHELIAL-CELLS AB We screened monoclonal antibodies to cell surface proteins and selected an antibody, called 6H1, that recognizes a putative integrin-associated protein. The 6H1 monoclonal antibody (mAb) indirectly coprecipitated alpha(3) beta(1) and/or alpha(6) beta(1) but not alpha(2) beta(1), or alpha(5) beta(1) from Brij 96 detergent lysates of multiple cell lines. Large scale purification using the 6H1 mAb yielded a single protein of 45-60 kDa with an amino-terminal sequence that exactly matched CD63. Confirming that the 6H1 mAb recognized the CD63 protein, 6H1 and a known anti-CD63 mAb yielded identical coprecipitation results and identical colocalization into lysosomal granules containing cathepsin D. Furthermore, we used an established anti-CD63 mAb to detect this protein in an alpha(3) beta(1) immunoprecipitate, and also we observed VLA-3 and CD63 colocalization in cellular ''footprints.'' Notably, the cytoplasmic domain of alpha(3) was neither required nor sufficient for CD63 association, suggesting that it occurred elsewhere within the alpha(3) beta(1) complex. Knowledge of these specific CD63-alpha(3) beta(1), and CD63-alpha(6) beta(1) biochemical associations should lead to critical insights into the specialized functions of alpha(3) beta(1), alpha(6) beta(1) and CD63. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NIGMS NIH HHS [GM46526] NR 72 TC 135 Z9 135 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 28 PY 1995 VL 270 IS 30 BP 17784 EP 17790 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RM266 UT WOS:A1995RM26600026 PM 7629079 ER PT J AU KOLAKOWSKI, LF LU, B GERARD, C GERARD, NP AF KOLAKOWSKI, LF LU, B GERARD, C GERARD, NP TI PROBING THE MESSAGE-ADDRESS SITES FOR CHEMOATTRACTANT BINDING TO THE C5A RECEPTOR - MUTAGENESIS OF HYDROPHILIC AND PROLINE RESIDUES WITHIN THE TRANSMEMBRANE SEGMENTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; BETA-ADRENERGIC-RECEPTOR; LIGAND-BINDING; INTERLEUKIN-8 RECEPTOR; CYSTEINE RESIDUE-110; SUBTYPE SPECIFICITY; BOVINE RHODOPSIN; AMINO TERMINUS; ANAPHYLATOXIN; IDENTIFICATION AB The C5a anaphylatoxin ligand receptor interaction on polymorphonuclear granulocytes stimulates chemotaxis, degranulation, and the oxidative burst. The receptor is a member of the large G-protein-coupled family. The ligand is a cationic peptide of 72 amino acids derived from the C5 component of complement and has been shown to have a number of structural requirements for interaction with the receptor. In order to probe the potential interaction sites between ligand and receptor, we constructed a series of mutated receptor molecules, targeting cysteines, prolines, and additional amino acids of interest because of combinations of charge or hydrophobicity and putative location with respect to the membrane. Transfected mutant receptors were analyzed for cell surface expression, ligand binding, and ligand-activated phospholipase C activity. The receptors created can be placed generally in four distinct classes: those which bind and signal like the natural receptor; those which bind but fail to transduce signals; those which are expressed but neither bind nor transduce signal; and those which are not expressed at the cell surface. C1 CHILDRENS HOSP,INA SUE PERLMUTTER LAB,BOSTON,MA 02115. CHILDRENS HOSP,DEPT PEDIAT,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA. HARVARD UNIV,CTR BLOOD RES,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,THORNDIKE LAB,BOSTON,MA 02115. FU NHLBI NIH HHS [HL36162, HL71910] NR 46 TC 45 Z9 46 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 28 PY 1995 VL 270 IS 30 BP 18077 EP 18082 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RM266 UT WOS:A1995RM26600068 PM 7629117 ER PT J AU SIEVER, LJ ROTTER, M LOSONCZY, M GUO, SL MITROPOULOU, V TRESTMAN, R APTER, S ZEMISHLANY, Z SILVERMAN, J HORVATH, TB DAVIDSON, M MOHS, R DAVIS, KL AF SIEVER, LJ ROTTER, M LOSONCZY, M GUO, SL MITROPOULOU, V TRESTMAN, R APTER, S ZEMISHLANY, Z SILVERMAN, J HORVATH, TB DAVIDSON, M MOHS, R DAVIS, KL TI LATERAL VENTRICULAR ENLARGEMENT IN SCHIZOTYPAL PERSONALITY-DISORDER SO PSYCHIATRY RESEARCH LA English DT Article DE COMPUTED TOMOGRAPHY; VENTRICLE-BRAIN RATIO; SCHIZOPHRENIA; PERSONALITY DISORDER ID SCHIZOPHRENIC MOTHERS; BRAIN ABNORMALITIES; HOMOVANILLIC-ACID; INTERVIEW; DEFICITS; SIZE AB Although an increase in the ratio of ventricular space to brain (ventricle-brain ratio, VBR) on computed tomography (CT) has been among the most robust findings in chronic schizophrenia, VBR has not been investigated in a large, well-characterized clinical population of patients with schizotypal personality disorder (SPD), a clinical entity with a phenomenologic, genetic, biological, and treatment response relationship to chronic schizophrenia. Accordingly, CT scans were obtained in 36 male SPD patients, 23 males with other personality disorders, 133 male schizophrenic patients, and 42 male normal volunteers, The mean body of the lateral VER was significantly greater in the SPD patients than in the patients with other personality disorders. The VBR of the SPD patients did not differ significantly from either that of the normal volunteers or the schizophrenic patients but was intermediate between the two groups, There were no correlations with either psychotic-like or deficit-related symptoms of SPD in either the SPD or total personality disorder cohorts, SPD patients, like schizophrenic patients, may have increased VBRs compared with patients with other personality disorders; their VBRs fall between the means of schizophrenic patients and normal control subjects. C1 CUNY MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. BRONX PSYCHIAT CTR,NEW YORK,NY 10461. VET ADM MED CTR,FDR,PSYCHIAT SERV 116A,MONTROSE,NY 10548. NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY 10032. NORTHPORT VET ADM MED CTR,PSYCHIAT SERV,NORTHPORT,NY 11768. RP SIEVER, LJ (reprint author), BRONX VET ADM MED CTR,PSYCHIAT SERV 116A,130 W KINGSBRIDGE RD,BRONX,NY 10468, USA. FU NCRR NIH HHS [RR-0071]; NIA NIH HHS [AG-02219]; NIMH NIH HHS [MH-41131] NR 34 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUL 28 PY 1995 VL 57 IS 2 BP 109 EP 118 DI 10.1016/0165-1781(95)02645-D PG 10 WC Psychiatry SC Psychiatry GA RQ448 UT WOS:A1995RQ44800003 PM 7480378 ER PT J AU MAEDA, T TAKEKAWA, M SAITO, H AF MAEDA, T TAKEKAWA, M SAITO, H TI ACTIVATION OF YEAST PBS2 MAPKK BY MAPKKKS OR BY BINDING OF AN SH3-CONTAINING OSMOSENSOR SO SCIENCE LA English DT Article ID SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; PATHWAY; ALLELE AB The role of mitogen-activated protein (MAP) kinase cascades in integrating distinct upstream signals was studied in yeast. Mutants that were not able to activate PBS2 MAP kinase kinase (MAPKK; Pbs2p) at high osmolarity were characterized. Pbs2p was activated by two independent signals that emanated from distinct cell-surface osmosensors. Pbs2p was activated by MAP kinase kinase kinases (MAPKKKs) Ssk2p and Ssk22p that are under the control of the SLN1-SSK1 two-component osmosensor. Alternatively, Pbs2p was activated by a mechanism that involves the binding of its amino terminal proline-rich motif to the Src homology 3 (SH3) domain of a putative transmembrane osmosensor Sho1p. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV TUMOR IMMUNOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02115 USA. NR 23 TC 490 Z9 510 U1 2 U2 9 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JUL 28 PY 1995 VL 269 IS 5223 BP 554 EP 558 DI 10.1126/science.7624781 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RL495 UT WOS:A1995RL49500033 PM 7624781 ER PT J AU UEDA, P HALL, D AF UEDA, P HALL, D TI GIANT COLONIC DIVERTICULUM SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note RP UEDA, P (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 6 Z9 7 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 27 PY 1995 VL 333 IS 4 BP 228 EP 228 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RK423 UT WOS:A1995RK42300005 PM 7791839 ER PT J AU YOKOYAMA, H BARAONA, E LIEBER, CS AF YOKOYAMA, H BARAONA, E LIEBER, CS TI COMPARISON OF THE ADH7 GENE STRUCTURE IN CAUCASIAN AND JAPANESE SUBJECTS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ALCOHOL-DEHYDROGENASE; STOMACH; ENZYME AB The ADH 7 gene, encoding the sigma-alcohol dehydrogenase isozyme, was cloned from a Caucasian genomic DNA library. Comparison of the nucleotide sequence of its exon 7 with that of an ADH 7 previously cloned from a Japanese subject revealed a substitution of the glycine-287 in the Caucasian sigma isozyme with valine in the Japanese. Since a possible mutation at this site could account for ethnic differences in the gastric activity of this isozyme, the frequency of this change was examined in both races. The exon 7 of the ADH 7 was amplified by PCR from 7 Caucasian and 7 Japanese genomic DNA and applied to restriction fragment length polymorphism analysis, using Ava II to digest the sequence encoding glycine -287 and Mae III to digest that encoding valine-287. Regardless of ethnicity, all PCR amplicons were digested by Ava II and none by Mae III, suggesting that the ethnic difference in the 287 amino acid may represent an uncommon mutation, which does not account for the high frequency of minimal activity of the sigma-alcohol dehydrogenase in the Japanese stomach compared to those of non-Orientals. (C) 1995 Academic Press, Inc. C1 MT SINAI SCH MED,NEW YORK,NY 10468. RP YOKOYAMA, H (reprint author), BRONX VET ADM MED CTR,ALCOHOL RES CTR,NEW YORK,NY 10468, USA. NR 10 TC 7 Z9 7 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 JUL 26 PY 1995 VL 212 IS 3 BP 875 EP 878 DI 10.1006/bbrc.1995.2050 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RL363 UT WOS:A1995RL36300021 PM 7626124 ER PT J AU NABHAN, C XIONG, YT XIE, LY ABOUSAMRA, AB AF NABHAN, C XIONG, YT XIE, LY ABOUSAMRA, AB TI THE ALTERNATIVELY SPLICED TYPE-II CORTICOTROPIN-RELEASING FACTOR-RECEPTOR, STABLY EXPRESSED IN LLCPK-1 CELLS, IS NOT WELL COUPLED TO THE G-PROTEIN(S) SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; ANTERIOR-PITUITARY RECEPTOR; HORMONE-RELATED PEPTIDE; FUNCTIONAL EXPRESSION; PARATHYROID-HORMONE; MOLECULAR-CLONING; ADENOSINE-3',5'-MONOPHOSPHATE; IDENTIFICATION; ACCUMULATION; POLYPEPTIDE AB Two alternatively spliced corticotropin-releasing factor receptor (CRF-R) cDNAs, type I and type II, were recently isolated from a human cDNA library. The two cDNAs are identical except that the type II cDNA encodes an additional 29 amino acid inserted in the first putative cytoplasmic loop. Since the first cytoplasmic loop is highly conserved in all the members of the hCRF receptor family we have examined whether the presence of the 29 amino acid cassette in CRF-RII influences G protein coupling in LLCPK-1 cells stably expressing the type I and type II hCRF receptors. Whether measured in intact cells or in membrane preparations, LLCPK-1 cells stably expressing CRF-RII have a 4-5-fold lower binding affinity. Maximal CRF-stimulated cAMP accumulation in LLCPK-1 cells stably expressing CRF-RT was 10-15-fold higher than that in LLCPK-1 cells expressing CRF-RII. The EC50 for CRF-stimulated cAMP accumulation in hCRF-RI-expressing cells was in the range of 0.5 +/- 0.2 nM. In contrast, the EC50 for CRF-stimulated cAMP accumulation in hCRF-RII expressing cells was 7.7 +/- 0.2 nM. hCRF increased phosphoinositide turnover in LLCPK-1 cells stably expressing CRF-RI but not in those expressing CRF-RII; this effect required hCRF concentrations of 100 nM and higher. In membrane preparations, GTP-gamma-S inhibited hCRF binding to CRF-RII and shifted the binding Kd from 4.5 nM to 16.7 nM. Conversely, GTP-gamma-S did not influence hCRF binding to CRF-RII in broken cell membranes. Additionally, CRF-stimulated adenylate cyclase activity in cell membranes expressing CRF-RI was potentiated by GTP, whereas CRF-stimulated adenylate cyclase activity in cell membranes expressing CRF-RII was insensitive to GTP. These data indicate that CRF-RII is not well coupled to the G protein. Since the only difference between the CRF-RII and CRF-RI is the insert in the first putative cytoplasmic loop, these data indicate that the first cytoplasmic loop plays a crucial role in hCRF receptor coupling to the G protein. (C) 1995 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. OI Abou-Samra, Abdul/0000-0001-8735-1142 NR 31 TC 38 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 JUL 26 PY 1995 VL 212 IS 3 BP 1015 EP 1021 DI 10.1006/bbrc.1995.2071 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RL363 UT WOS:A1995RL36300042 PM 7626087 ER PT J AU GOLDMANN, WH SENGER, R KAUFMANN, S ISENBERG, G AF GOLDMANN, WH SENGER, R KAUFMANN, S ISENBERG, G TI DETERMINATION OF THE AFFINITY OF TALIN AND VINCULIN TO CHARGED LIPID VESICLES - A LIGHT SCATTER STUDY SO FEBS LETTERS LA English DT Article DE LIPID BINDING AFFINITY; TALIN; VINCULIN; LIGHT SCATTERING ID BINDING-PROTEIN; ALPHA-ACTININ AB Recent experimental findings have demonstrated that both talin and vinculin bind to phospholipids and insert into the hydrophobic region of lipid membranes. Here, we show that the light scatter method can be used for measuring the affinity of proteins to phospholipid membranes, Large unilamellar DMPC/DMPG vesicles were produced by the extrusion technique (LUVETs). We have used repeated heating/cooling scans between 15 degrees C and 35 degrees C to ensure protein-lipid interaction/insertion. A molar affinity of talin, K = 2.9 x 10(6) M(-1) and of vinculin, K = 3.3 x 10(5) M(-1) to lipid vesicles, respectively, was determined from the plot; light scatter signal at 380 nm against protein concentrations by fitting the term, In (I-o/I-1) = A - K x c to the data. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG RES UNIT,BOSTON,MA 02129. RP GOLDMANN, WH (reprint author), TECH UNIV MUNICH,D-85747 GARCHING,GERMANY. RI Goldmann, Wolfgang/H-5572-2013 NR 21 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 24 PY 1995 VL 368 IS 3 BP 516 EP 518 DI 10.1016/0014-5793(95)00678-3 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA RM339 UT WOS:A1995RM33900029 PM 7635211 ER PT J AU FREEMAN, GJ AF FREEMAN, GJ TI HOT PAPERS - IMMUNOLOGY - CLONING OF B7-2 - A CTLA-4 COUNTER-RECEPTOR THAT COSTIMULATES HUMAN T-CELL PROLIFERATION BY FREEMAN.G.J., GRIBBEN,J.G., BOUSSIOTIS,V.A., NG,J.W., RESTIVO,V.A., LOMBARD,L.A., GRAY,G.S., NADLER,L.M. SO SCIENTIST LA English DT Editorial Material RP FREEMAN, GJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 5 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD JUL 24 PY 1995 VL 9 IS 15 BP 13 EP 13 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA RK416 UT WOS:A1995RK41600014 ER PT J AU FREEMAN, GJ AF FREEMAN, GJ TI HOT PAPERS - IMMUNOLOGY - UNCOVERING OF FUNCTIONAL ALTERNATIVE CTLA-4 COUNTER-RECEPTOR IN B-7 DEFICIENT MICE BY FREEMAN,G.J., BORRIELLO,F., HODES,R.J., RESIER,H., HATHCOCK,K.S., LASZLO,G., MCKNIGHT,A.J., KIM,J., DU,L., LOMBARD,D.B., GRAY,G.S., NADLER,L.M., SHARPE,A.H. SO SCIENTIST LA English DT Editorial Material RP FREEMAN, GJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 5 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD JUL 24 PY 1995 VL 9 IS 15 BP 13 EP 13 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA RK416 UT WOS:A1995RK41600013 ER PT J AU FREEMAN, GJ AF FREEMAN, GJ TI HOT PAPERS - IMMUNOLOGY - MURINE B7-2, AN ALTERNATIVE CTLA-4 COUNTER-RECEPTOR THAT COSTIMULATES T-CELL PROLIFERATION AND INTERLEUKIN-2 PRODUCTION - FREEMAN,G.J., BORRIELLO,F., HODES,R.J., RESIER,H., GRIBBEN,J.G., NG,J.W., KIM,J., GOLDBERG,J.M., HATHCOCK,K.S., LASZLO,G., LOMBARD,L.A., WANG,S., GRAY,G.S., NADLER,L.M., SHARPE,A.H. SO SCIENTIST LA English DT Editorial Material RP FREEMAN, GJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 5 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD JUL 24 PY 1995 VL 9 IS 15 BP 13 EP 13 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA RK416 UT WOS:A1995RK41600015 ER PT J AU RYAN, TC CRUIKSHANK, WW KORNFELD, H COLLINS, TL CENTER, DM AF RYAN, TC CRUIKSHANK, WW KORNFELD, H COLLINS, TL CENTER, DM TI THE CD4-ASSOCIATED TYROSINE KINASE P56(LCK) IS REQUIRED FOR LYMPHOCYTE CHEMOATTRACTANT FACTOR-INDUCED T-LYMPHOCYTE MIGRATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BEARING MONONUCLEAR-CELLS; PROTEIN-KINASE; SIGNAL TRANSDUCTION; CD4 RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; FUNCTIONAL-CHARACTERISTICS; SURFACE-ANTIGENS; HERBIMYCIN-A; MYOSIN-I; ACTIVATION AB Lymphocyte chemoattractant factor (LCF) is a polypeptide cytokine which induces both cell motility and activation of T lymphocytes. These LCF-induced events demonstrate an absolute requirement for the cell surface expression of CD4, Because many CD4-mediated T lymphocyte activation events have been demonstrated to require the association of the src-related tyrosine kinase p56(lck) with the cytoplasmic domain of CD4, we examined the role of p56(lck) in LCF-induced lymphocyte migration in a murine T cell hybridoma line expressing transfected human CD4. LCF induces the catalytic activity of CD4 associated p56(lck) at chemoattractant concentrations of cytokine, Hybridoma cells that express CD4 with cytoplasmic point mutations which uncouple the CD4-lck association lack both lck enzymatic activity and chemotactic responses to LCF. The enzymatic activity of lck however does not appear to be required for CD4-mediated migratory signal, First, the protein tyrosine kinase inhibitor herbimycin A blocked LCF-induced p56(lck) activation but had no effect on the LCF-induced motile response. Second, T cell hybridomas expressing a chimeric receptor combining the extracellular domain of human CD4 and murine p56(lck) which lacked the kinase domain had a normal LCF-induced motile response, We conclude from these observations that CD4-lck coupling is essential for LCF-induced T lymphocyte migration but the motile response is independent of the enzymatic activity of CD4-associated p56(lck). C1 BOSTON UNIV, SCH MED, CTR PULM, BOSTON, MA 02118 USA. HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV PEDIAT ONCOL, BOSTON, MA 02115 USA. FU NHLBI NIH HHS [HL32802] NR 41 TC 68 Z9 69 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 21 PY 1995 VL 270 IS 29 BP 17081 EP 17086 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RK689 UT WOS:A1995RK68900008 PM 7615501 ER PT J AU YOSHIDA, T WAEBER, C HUANG, ZH MOSKOWITZ, MA AF YOSHIDA, T WAEBER, C HUANG, ZH MOSKOWITZ, MA TI INDUCTION OF NITRIC-OXIDE SYNTHASE ACTIVITY IN RODENT BRAIN FOLLOWING MIDDLE CEREBRAL-ARTERY OCCLUSION SO NEUROSCIENCE LETTERS LA English DT Article DE NITRIC OXIDE SYNTHASE; INDUCIBLE ISOFORM; SPECIES DIFFERENCE; MIDDLE CEREBRAL ARTERY OCCLUSION; LIPOPOLYSACCHARIDE ID NADPH-DIAPHORASE; L-ARGININE; RAT-BRAIN; ISCHEMIA; CELLS; LOCALIZATION; MACROPHAGES; CALMODULIN; ENZYME AB The conversion of L-[H-3]arginine to L-[H-3]citrulline in the absence of calcium can be used to assay selectively the activity of inducible nitric oxide synthase (NOS) in rat spleen homogenates 6 h after lipopolysaccharide administration. Using similar assay conditions, changes in inducible NOS activity were measured within ischemic brain tissue between 2 h and 7 days following permanent middle cerebral artery (MCA) occlusion in Sprague-Dawley rats and SV-129 mice. Total (constitutive and inducible) NOS activity was measured in the presence of 0.5 mM CaCl2. Whereas total NOS activity in rat decreased dramatically to 16% and 6% of baseline 6 and 12 h after MCA occlusion, inducible NOS activity remained undetectable before 2 days after occlusion, became maximal at 3 days, and decreased to less than 10% of maximal iNOS activity at 7 days. In the mouse, total NOS activity decreased after MCA occlusion but inducible NOS activity was undetectable from 2 h to 4 days after occlusion, Sustained NO production by inducible NOS activity does not contribute to ischemic injury within 24 h after MCA occlusion, but may contribute to infarct maturation 2-4 days after ischemia in some but not all species. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROSURG & NEUROL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NINDS NIH HHS [NS 10828, NS 26361] NR 29 TC 71 Z9 72 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 21 PY 1995 VL 194 IS 3 BP 214 EP 218 DI 10.1016/0304-3940(95)11752-I PG 5 WC Neurosciences SC Neurosciences & Neurology GA RL701 UT WOS:A1995RL70100017 PM 7478241 ER PT J AU EKLAND, EH SZOSTAK, JW BARTEL, DP AF EKLAND, EH SZOSTAK, JW BARTEL, DP TI STRUCTURALLY COMPLEX AND HIGHLY-ACTIVE RNA LIGASES DERIVED FROM RANDOM RNA SEQUENCES SO SCIENCE LA English DT Article ID RIBOZYMES; SUBSTRATE AB Seven families of RNA ligases, previously isolated from random RNA sequences, fall into three classes on the basis of secondary structure and regiospecificity of ligation. Two of the three classes of ribozymes have been engineered to act as true enzymes, catalyzing the multiple-turnover transformation of substrates into products. The most complex of these ribozymes has a minimal catalytic domain of 93 nucleotides. An optimized version of this ribozyme has a k(cat), exceeding one per second, a value far greater than that of most natural RNA catalysts and approaching that of comparable protein enzymes. The fact that such a large and complex ligase emerged from avery limited sampling of sequence space implies the existence of a large number of distinct RNA structures of equivalent complexity and activity. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RP EKLAND, EH (reprint author), WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142, USA. NR 23 TC 233 Z9 238 U1 3 U2 15 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 21 PY 1995 VL 269 IS 5222 BP 364 EP 370 DI 10.1126/science.7618102 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RK427 UT WOS:A1995RK42700038 PM 7618102 ER PT J AU DUYAO, MP AUERBACH, AB RYAN, A PERSICHETTI, F BARNES, GT MCNEIL, SM GE, P VONSATTEL, JP GUSELLA, JF JOYNER, AL MACDONALD, ME AF DUYAO, MP AUERBACH, AB RYAN, A PERSICHETTI, F BARNES, GT MCNEIL, SM GE, P VONSATTEL, JP GUSELLA, JF JOYNER, AL MACDONALD, ME TI INACTIVATION OF THE MOUSE HUNTINGTONS-DISEASE GENE HOMOLOG HDH SO SCIENCE LA English DT Article ID FRAGILE-X-SYNDROME; EXPRESSION; FMR-1; CELLS; MICE AB Huntington's disease (HD) is a dominant neurodegenerative disorder caused by expansion of a CAG repeat in the gene encoding huntingtin, a protein of unknown function. To distinguish between ''loss of function'' and ''gain of function'' models of HD, the murine HD homolog Hdh was inactivated by gene targeting. Mice heterozygous for Hdh inactivation were phenotypically normal, whereas homozygosity resulted in embryonic death. Homozygotes displayed abnormal gastrulation at embryonic day 7.5 and were resorbing by day 8.5. Thus, huntingtin is critical early in embryonic development, before the emergence of the nervous system. That Hdh inactivation does not mimic adult HD neuropathology suggests that the human disease involves a gain of function. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. MT SINAI HOSP,DIV MOLEC & DEV BIOL,TORONTO,ON M5G 1X5,CANADA. MASSACHUSETTS GEN HOSP,MOLEC NEUROPATHOL LAB,BOSTON,MA 02129. FU NINDS NIH HHS [NS16367, NS32765] NR 31 TC 386 Z9 394 U1 1 U2 15 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 21 PY 1995 VL 269 IS 5222 BP 407 EP 410 DI 10.1126/science.7618107 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RK427 UT WOS:A1995RK42700050 PM 7618107 ER PT J AU STEINGRIMSSON, E SAWADOGO, M GILBERT, DJ ZERVOS, AS BRENT, R BLANAR, MA FISHER, DE COPELAND, NG JENKINS, NA AF STEINGRIMSSON, E SAWADOGO, M GILBERT, DJ ZERVOS, AS BRENT, R BLANAR, MA FISHER, DE COPELAND, NG JENKINS, NA TI MURINE CHROMOSOMAL LOCATION OF 5 BHLH-ZIP TRANSCRIPTION FACTOR GENES SO GENOMICS LA English DT Article ID MAJOR LATE PROMOTER; FACTOR USF; FACTOR BINDS; LINKAGE MAP; MOUSE; IDENTIFICATION; PROTEIN; LOCALIZATION; UPSTREAM; CLONING AB The genes for the bHLH-Zip transcription factors Tfap4, Mxi1, Tcfeb, Usf1, and Usf2 have been mapped in mouse by interspecific backcross analysis. Mxi1, Usf1, and Usf2 have been mapped previously by in situ hybridization, but their positions on the meiotic linkage map had not been determined, The other two genes have not previously been mapped in mouse. These transcription factors belong to a growing family of transcriptional regulators, some of which are known to form a complex network of interacting proteins that control cell proliferation and apoptosis. As expected, based on mapping studies of other bHLH-Zip genes, these loci were well distributed among mouse chromosomes. In addition, some of the probes used in this study detected multiple, independently segregating loci, suggesting the possible existence of additional family members or species-specific pseudogenes. (C) 1995 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MOLEC GENET,HOUSTON,TX 77030. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT CARDIOVASC MOLEC & CELLULAR BIOL,PRINCETON,NJ 08543. DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [N01-CO-46000] NR 34 TC 19 Z9 19 U1 1 U2 4 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 JUL 20 PY 1995 VL 28 IS 2 BP 179 EP 183 DI 10.1006/geno.1995.1129 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RN465 UT WOS:A1995RN46500007 PM 8530024 ER PT J AU EVANS, E COOLEY, J REMOLDODONNELL, E AF EVANS, E COOLEY, J REMOLDODONNELL, E TI CHARACTERIZATION AND CHROMOSOMAL LOCALIZATION OF ELANH2, THE GENE ENCODING HUMAN MONOCYTE/NEUTROPHIL ELASTASE INHIBITOR SO GENOMICS LA English DT Article ID CORTICOSTEROID-BINDING GLOBULIN; MOLECULAR CHARACTERIZATION; CHICKEN OVALBUMIN; HUMAN-MONOCYTES; SHORT ARM; SEQUENCE; ALPHA-1-ANTITRYPSIN; EXPRESSION; ORGANIZATION; SERPINS AB Human monocyte/neutrophil elastase inhibitor (HEI) is a protease inhibitor of the serpin superfamily that rapidly inactivates neutrophil elastase, proteinase-3, and possibly cathepsin-G in vitro and, by regulating these potent proteases, is thought to prevent tissue damage at inflammatory sites. The HEI gene (ELANH2) was characterized by amplifying intron regions using cDNA-specific primers. Intron positions of ELANH2 were found to be homologous to intron positions in the genes for the serpin molecules chicken ovalbumin and human plasminogen activator inhibitor-2 (PLANH2). Because serpin superfamily genes in general have widely different organizational patterns, the shared organization of these genes strengthens the evidence that they form a subgroup or family, the ''ovalbumin-related serpin'' (''Ov-serpin'') family. By amplifying DNA of a somatic cell hybrid panel, ELANH2 was unambiguously localized to chromosome 6. The use of a panel of radiation and somatic cell hybrids specific for chromosome 6 refined the localization of ELANH2 to the short arm telomeric of D6S89, F13A, and D6S202 at 6p24-pter. Another Ov-serpin gene PI6 (placental thrombin inhibitor) was colocalized to the same region, thus defining an Ov-serpin locus on chromosome 6 in addition to the previously defined PLANH2-containing Ov-serpin locus on chromosome 18. (C) 1995 Academic Press, Inc. C1 CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-41579] NR 39 TC 22 Z9 22 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 JUL 20 PY 1995 VL 28 IS 2 BP 235 EP 240 DI 10.1006/geno.1995.1136 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RN465 UT WOS:A1995RN46500014 PM 8530031 ER PT J AU MARCHUK, DA GALLIONE, CJ MORRISON, LA CLERICUZIO, CL HART, BL KOSOFSKY, BE LOUIS, DN GUSELLA, JF DAVIS, LE PRENGER, VL AF MARCHUK, DA GALLIONE, CJ MORRISON, LA CLERICUZIO, CL HART, BL KOSOFSKY, BE LOUIS, DN GUSELLA, JF DAVIS, LE PRENGER, VL TI A LOCUS FOR CEREBRAL CAVERNOUS MALFORMATIONS MAPS TO CHROMOSOME 7Q IN 2 FAMILIES SO GENOMICS LA English DT Article ID ANGIOMAS; BRAIN AB Cavernous malformations (angiomas) affecting the central nervous system and retina can be inherited in autosomal dominant pattern (OMIM 116860). These vascular lesions may remain clinically silent or lead to a number of neurological symptoms including seizure, intracranial hemorrhage, focal neurological deficit, and migraine. We have mapped a gene for this disorder in two families, one of Italian-American origin and one of Mexican-American origin, to markers on proximal 7q, with a combined maximum lod score of 3.92 (theta of zero) with marker D7S479, Haplotype analysis of these families places the locus between markers D7S502 proximally and D7S515 distally, an interval of approximately 41 cM. The location distinguishes this disorder from an autosomal dominant vascular malformation syndrome where lesions are primarily cutaneous and that maps to 9p21. (C) 1995 Academic Press, Inc. C1 UNIV NEW MEXICO,SCH MED,DEPT NEUROL,ALBUQUERQUE,NM 87131. UNIV NEW MEXICO,SCH MED,DEPT PEDIAT,ALBUQUERQUE,NM 87131. UNIV NEW MEXICO,SCH MED,DEPT RADIOL,ALBUQUERQUE,NM 87131. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV MARYLAND,SCH MED,DEPT OBSTET & GYNECOL,DIV HUMAN GENET,BALTIMORE,MD 21201. RP MARCHUK, DA (reprint author), DUKE UNIV,MED CTR,DEPT GENET,BOX 3175,DURHAM,NC 27710, USA. FU NINDS NIH HHS [NS24279] NR 16 TC 73 Z9 73 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 JUL 20 PY 1995 VL 28 IS 2 BP 311 EP 314 DI 10.1006/geno.1995.1147 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RN465 UT WOS:A1995RN46500025 PM 8530042 ER PT J AU WESTMAYS, JA STRISSEL, KJ SADOW, PM FINI, ME AF WESTMAYS, JA STRISSEL, KJ SADOW, PM FINI, ME TI COMPETENCE FOR COLLAGENASE GENE-EXPRESSION BY TISSUE FIBROBLASTS REQUIRES ACTIVATION OF AN INTERLEUKIN-1-ALPHA AUTOCRINE LOOP SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RABBIT SYNOVIAL FIBROBLASTS; SIGNAL TRANSDUCTION; METALLOPROTEINASE EXPRESSION; CELL-SURFACE; MATRIX; STROMELYSIN; RECEPTOR; STIMULATION; INHIBITORS; CULTURE AB The enzyme collagenase (EC 3.4.24.7), a key mediator in biological remodeling, can be induced in early-passage fibroblasts by a wide variety of agents and conditions. In contrast, at least some primary tissue fibroblasts are incompetent to synthesize collagenase in response to many of these stimulators. In this study, we investigate mechanisms controlling response to two of the conditions in question: (i) trypsin or cytochalasin B, which disrupt actin stress fibers, or (ii) phorbol 12-myristate 13-acetate (PMA), which activates growth factor signaling pathways. We demonstrate that collagenase expression stimulated by trypsin or cytochalasin B is regulated entirely through an autocrine cytokine, interleukin 1 alpha (IL-1 alpha). The IL-1 alpha intermediate also constitutes the major mechanism by which PMA stimulates collagenase expression, although a second signaling pathway(s) contributes to a minor extent. Elevation of the IL-1 alpha level in response to stimulators is found to be sustained by means of an autocrine feedback loop in early-passage fibroblast cultures. In contrast, fibroblasts freshly isolated from the tissue are incompetent to activate and sustain the IL-1 alpha feedback loop, even though they synthesize collagenase in response to exogenous IL-1. We conclude that this is the reason why tissue fibroblasts are limited, in comparison with subcultured fibroblasts, in their capacity to synthesize collagenase. Activation of the IL-1 alpha feedback loop, therefore, seems likely to be an important mechanism by which resident tissue cells adopt the remodeling phenotype. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02129. FU NEI NIH HHS [EY08408, EY09828]; NIAMS NIH HHS [AR07098] NR 37 TC 87 Z9 88 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 JUL 18 PY 1995 VL 92 IS 15 BP 6768 EP 6772 DI 10.1073/pnas.92.15.6768 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RJ892 UT WOS:A1995RJ89200021 PM 7624317 ER PT J AU IRIKURA, K HUANG, PL MA, JY LEE, WS DALKARA, T FISHMAN, MC DAWSON, TM SNYDER, SH MOSKOWITZ, MA AF IRIKURA, K HUANG, PL MA, JY LEE, WS DALKARA, T FISHMAN, MC DAWSON, TM SNYDER, SH MOSKOWITZ, MA TI CEREBROVASCULAR ALTERATIONS IN MICE LACKING NEURONAL NITRIC-OXIDE SYNTHASE GENE-EXPRESSION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE KNOCKOUT MICE; N-OMEGA-NITRO-L-ARGININE; CEREBRAL BLOOD FLOW; ACETYLCHOLINE; HYPERCAPNIA ID CEREBRAL BLOOD-FLOW; EXTRACELLULAR ACIDOSIS; HYPERCAPNIA; BICARBONATE; INCREASES; RATS AB Nitric oxide (NO) is known to mediate increases in regional cerebral blood flow elicited by CO2 inhalation, In mice with deletion of the gene for neuronal NO synthase (NOS), CO2 inhalation augments cerebral blood flow to the same extent as in wild-type mice. However, unlike wild-type mice, the increased flow in mutants is not blocked by the NOS inhibition, N-omega-nitro-L-arginine, and CO2 exposure fails to increase brain levels of cGMP, Topical acetylcholine elicits vasodilation in the mutants which is blocked by N-omega-nitro-L-arginine, indicating normal functioning of endothelial NOS. Moreover, immunohistochemical staining for endothelial NOS is normal in the mutants. Thus, following loss of neuronal NOS, the cerebral circulatory response is maintained by a compensatory system not involving NO. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT MED,MED SERV,CARDIOVASC RES CTR,BOSTON,MA 02114. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. RI Moskowitz, Michael/D-9916-2011 FU NIDA NIH HHS [DA0074]; NIMH NIH HHS [MH18501]; NINDS NIH HHS [NS10828] NR 28 TC 109 Z9 109 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 JUL 18 PY 1995 VL 92 IS 15 BP 6823 EP 6827 DI 10.1073/pnas.92.15.6823 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RJ892 UT WOS:A1995RJ89200032 PM 7542777 ER PT J AU BROUILLET, E HANTRAYE, P FERRANTE, RJ DOLAN, R LEROYWILLIG, A KOWALL, NW BEAL, MF AF BROUILLET, E HANTRAYE, P FERRANTE, RJ DOLAN, R LEROYWILLIG, A KOWALL, NW BEAL, MF TI CHRONIC MITOCHONDRIAL ENERGY IMPAIRMENT PRODUCES SELECTIVE STRIATAL DEGENERATION AND ABNORMAL CHOREIFORM MOVEMENTS IN PRIMATES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MITOCHONDRIA; EXCITOTOXICITY; HUNTINGTON DISEASE; STRIATUM ID D-ASPARTATE RECEPTOR; HUNTINGTONS-DISEASE; 3-NITROPROPIONIC ACID; QUINOLINIC ACID; CAUDATE-PUTAMEN; NEURONS; LESIONS; EXCITOTOXIN; METABOLISM; MECHANISMS AB Although the gene defect responsible for Huntington disease (HD) has recently been identified, the pathogenesis of the disease remains obscure. One potential mechanism is that the gene defect may lead to an impairment of energy metabolism followed by slow excitotoxic neuronal injury. In the present study we examined whether chronic administration of 3-nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase, can replicate the neuropathologic and clinical features of HD in nonhuman primates. After 3-6 weeks of 3-NP administration, apomorphine treatment induced a significant increase in motor activity as compared with saline-treated controls. Animals showed both choreiform movements, as well as foot and limb dystonia, which are characteristic of HD. More prolonged 3-NP treatment in two additional primates resulted in spontaneous dystonia and dyskinesia accompanied by lesions in the caudate and putamen seen by magnetic resonance imaging. Histologic evaluation showed that there was a depletion of calbindin neurons, astrogliosis, sparing of NADPH-diaphorase neurons, and growth-related proliferative changes in dendrites of spiny neurons similar to changes in HD. The striosomal organization of the striatum and the nucleus accumbens were spared. These findings show that chronic administration of 3-NP to nonhuman primates can replicate many of the characteristic motor and histologic features of HD, further strengthening the possibility that a subtle impairment of energy metabolism may play a role in its pathogenesis. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROCHEM LAB,BOSTON,MA 02114. CEA,DEPT RECH IMAGERIE PHARMACOL & PHYSIOL,SERV HOSP FREDERIC JOLIOT,DIRECT SCI VIVANT,CNRS,F-91401 ORSAY,FRANCE. RI Kowall, Neil/G-6364-2012; Brouillet, Emmanuel/B-4784-2014 OI Kowall, Neil/0000-0002-6624-0213; Brouillet, Emmanuel/0000-0001-6322-7403 FU NINDS NIH HHS [NS 16367, NS 31579] NR 32 TC 346 Z9 353 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 18 PY 1995 VL 92 IS 15 BP 7105 EP 7109 DI 10.1073/pnas.92.15.7105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RJ892 UT WOS:A1995RJ89200091 PM 7624378 ER PT J AU KITABAYASHI, I ECKNER, R ARANY, Z CHIU, R GACHELIN, G LIVINGSTON, DM YOKOYAMA, KK AF KITABAYASHI, I ECKNER, R ARANY, Z CHIU, R GACHELIN, G LIVINGSTON, DM YOKOYAMA, KK TI PHOSPHORYLATION OF THE ADENOVIRUS E1A-ASSOCIATED 300 KDA PROTEIN IN RESPONSE TO RETINOIC ACID AND E1A DURING THE DIFFERENTIATION OF F9 CELLS SO EMBO JOURNAL LA English DT Article DE ADENOVIRUS E1A; CELL DIFFERENTIATION; C-JUN; P300; RETINOIC ACID ID RETINOBLASTOMA GENE-PRODUCT; EMBRYONAL CARCINOMA-CELLS; TRANSCRIPTION FACTOR E2F; DNA-BINDING PROTEIN; REGION 1A PROTEINS; C-JUN; CYCLIN-A; TERATOCARCINOMA CELLS; PHYSICAL ASSOCIATION; CELLULAR PROTEINS AB Transcription of the c-jun gene is up-regulated by either retinoic acid (RA) or adenovirus E1A during the differentiation of F9 cells, We show here that RA and E1A induce phosphorylation of the E1A-associated 300 kDa protein (p300) during the differentiation of F9 cells. The region of EIA that is required for interaction with cellular protein p300 overlaps with the region of E1A required for EIA to induce expression of the c-jun gene. Treatment of F9 cells with RA or infection of the cells by adenovirus led to a decrease in the electrophoretic mobility of p300. Phosphatase treatment of p300 from RA-treated or adenovirus-infected F9 cells reversed the changes in migration of p300, indicating that RA- and E1A-mediated changes in the mobility of p300 were due to phosphorylation. We also found factors, designated DRF1 and DRF2, that bound specifically to a sequence element that is necessary and sufficient for RA- and E1A-mediated up-regulation of the c-jun gene. The mobility of DRF complexes was changed by E1A or RA and the complexes were supershifted by addition of a polyclonal p300 antiserum. Moreover, overexpression of p300 resulted in an increase in the level of DRF1 complex. p300 fused to the DNA binding domain of the E2 protein of papilloma virus stimulated E2-dependent reporter activity in response to RA or E1A in F9 cells. Our results suggest that p300 is part of the DRF complexes, that it is differentially phosphorylated in undifferentiated versus differentiated cells and that it is likely involved in regulating transcription of the c-jun gene during F9 cell differentiation. C1 RIKEN,TSUKUBA LIFE SCI CTR,INST PHYS & CHEM RES,TSUKUBA,IBARAKI 305,JAPAN. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV CALIF LOS ANGELES,SCH MED,DEPT SURG ONCOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90024. INST PASTEUR,DEPT IMMUNOL,F-75724 PARIS 15,FRANCE. NR 90 TC 95 Z9 95 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 17 PY 1995 VL 14 IS 14 BP 3496 EP 3509 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RL494 UT WOS:A1995RL49400022 PM 7628451 ER PT J AU ROWE, JM ANDERSEN, JW MAZZA, JJ BENNETT, JM PAIETTA, E HAYES, FA OETTE, D CASSILETH, PA STADTMAUER, EA WIERNIK, PH AF ROWE, JM ANDERSEN, JW MAZZA, JJ BENNETT, JM PAIETTA, E HAYES, FA OETTE, D CASSILETH, PA STADTMAUER, EA WIERNIK, PH TI A RANDOMIZED PLACEBO-CONTROLLED PHASE-III STUDY OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN ADULT PATIENTS (GREATER-THAN-55 TO 70 YEARS OF AGE) WITH ACUTE MYELOGENOUS LEUKEMIA - A STUDY OF THE EASTERN-COOPERATIVE-ONCOLOGY-GROUP (E1490) SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOBLASTIC-LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; GM-CSF; CLONOGENIC CELLS; THERAPY; GROWTH AB The treatment of adult patients greater than 55 to 70 years of age with acute myelogenous leukemia (AML) is associated with a treatment-related mortality of approximately 25%. This prospective, double-blind randomized study was designed to see if the use of granulocyte-macrophage colony stimulating factor (GM-CSF; yeast-derived) could shorten the period of neutropenia and to determine any effect this would have on therapy-related morbidity and mortality. A total of 124 patients entered this study. Induction consisted of standard daunorubicin and cytarabine. A day-10 bone marrow was examined; if this was aplastic without leukemia, patients received blinded placebo or GM-CSF from day 11 until neutrophil recovery, Patients who entered complete remission received the identical study medication (blinded GM-CSF or placebo) in consolidation that they had received during induction. The overall complete remission rate was 52%; 60% for the GM-CSF arm and 44% for the placebo arm (P = .08). Median times to neutrophil recovery were significantly shortened on the GM-CSF arm. The overall treatment-related toxicity from start of GM-CSF/placebo was reduced on the GM-CSF arm (P = .049). Similarly, the infectious toxicity was significantly reduced on the GM-CSF arm (P = .015). The median survival for all patients was 10.6 months in the GM-CSF group and 4.8 months in the placebo arm (P = .048). It appears that GM-CSF is safe and efficacious for adult patients greater than 55 to 70 years of age with AML; its major impact is in reducing the duration of neutropenia and therapy-related mortality and morbidity. This may result in a better response rate. (C) 1995 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. MARSHFIELD CLIN FDN MED RES & EDUC,MARSHFIELD,WI. MONTEFIORE & ALBERT EINSTEIN CANC CTR,BRONX,NY. IMMUNEX CORP,SEATTLE,WA. HOECHST ROUSSEL PHARMACEUT PROPRIETARY LTD,SOMERVILLE,NJ 08876. UNIV MIAMI,SCH MED,MIAMI,FL. UNIV PENN,CTR CANC,PHILADELPHIA,PA 19104. RP ROWE, JM (reprint author), UNIV ROCHESTER,MED CTR,HEMATOL UNIT,POB 610,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. FU NCI NIH HHS [CA 11083, CA 23318, CA 35412] NR 21 TC 331 Z9 337 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 JUL 15 PY 1995 VL 86 IS 2 BP 457 EP 462 PG 6 WC Hematology SC Hematology GA RH801 UT WOS:A1995RH80100006 PM 7605984 ER PT J AU SU, LK BURRELL, M HILL, DE GYURIS, J BRENT, R WILTSHIRE, R TRENT, J VOGELSTEIN, B KINZLER, KW AF SU, LK BURRELL, M HILL, DE GYURIS, J BRENT, R WILTSHIRE, R TRENT, J VOGELSTEIN, B KINZLER, KW TI APC BINDS TO THE NOVEL PROTEIN EB1 SO CANCER RESEARCH LA English DT Note ID FAMILIAL ADENOMATOUS POLYPOSIS; MULTIPLE INTESTINAL NEOPLASIA; GENE-PRODUCT; COLI GENE; MUTATIONS; IDENTIFICATION; ASSOCIATION; CHROMOSOME-5Q21; REGION; LOCUS AB Mutations of the APC gene play a critical role in both sporadic and familial forms of colorectal cancer. The vast majority of these mutations result in the loss of the carboxyl terminus of the protein. To further elucidate the function of APC, we searched for cellular proteins that associate with its carboxyl terminus. One million human cDNA clones were screened with the use of the interaction trap two-hybrid system, and 67 clones were found to have a phenotype suggestive of an APC-interacting protein. Nucleotide sequence analysis revealed that 48 of these clones were derived from a single novel gene named EB1. The association of APC and EB1 proteins was confirmed with in vitro binding assays. mAbs against EB1 were then produced and used to demonstrate the association of APC and EB1 in vivo. The EB1 gene was predicted to encode a 268-amino acid protein without significant homology to proteins with known function. However, searches of nucleotide databases did identify evidence for at least two related human genes and a yeast homologue. This conservation suggests an essential function for EB1 that might provide clues to the mechanism through which APC suppresses colonic neoplasia. C1 JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21231. HOWARD HUGHES MED INST,BALTIMORE,MD 21231. ONCOGENE SCI,CAMBRIDGE,MA 02142. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RI Hill, David/B-6617-2011 FU NCI NIH HHS [CA-57345] NR 33 TC 361 Z9 365 U1 0 U2 6 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 JUL 15 PY 1995 VL 55 IS 14 BP 2972 EP 2977 PG 6 WC Oncology SC Oncology GA RH802 UT WOS:A1995RH80200005 PM 7606712 ER PT J AU MAO, L MERLO, A BEDI, G SHAPIRO, GI EDWARDS, CD ROLLINS, BJ SIDRANSKY, D AF MAO, L MERLO, A BEDI, G SHAPIRO, GI EDWARDS, CD ROLLINS, BJ SIDRANSKY, D TI A NOVEL P16(INK4A) TRANSCRIPT SO CANCER RESEARCH LA English DT Note AB p16(INK4A) and p15(INK4B) were initially identified as potent inhibitors of activated cyclin/cyclin-dependent kinase complexes. These genes were colocalized to chromosome 9p21, and p16 was subsequently found to be mutated in familial melanoma and deleted in a wide variety of sporadic cancers. We recently found that de novo methylation of a 5' CpG island led to transcriptional block of full-length p16 in many neoplasms. However, the presence of a truncated p16 transcript in methylated cell lines led us to investigate the presence of an alternative promoter or initiation site. We have now identified an abundant alternative p16 transcript in both methylated and unmethylated cell lines generated from a novel sequence (exon 1 beta) potentially involved in the complex regulation of these critical cell cycle genes. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT OTOLARYNGOL HEAD & NECK SURG,DIV HEAD & NECK CANC RES,BALTIMORE,MD 21205. DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NCI NIH HHS [CA-58184-01, CA94550] NR 18 TC 339 Z9 358 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1995 VL 55 IS 14 BP 2995 EP 2997 PG 3 WC Oncology SC Oncology GA RH802 UT WOS:A1995RH80200010 PM 7541708 ER PT J AU ORKIN, SH AF ORKIN, SH TI REGULATION OF GLOBIN GENE-EXPRESSION IN ERYTHROID-CELLS SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Review DE GLOBIN GENES; TRANSCRIPTION FACTORS; CHROMATIN; ERYTHROID CELLS; LOCUS CONTROL ID HUMAN GAMMA-GLOBIN; DOMINANT CONTROL REGION; LOCUS-CONTROL REGION; MURINE ERYTHROLEUKEMIA-CELLS; YEAST ARTIFICIAL CHROMOSOME; TRANSCRIPTION FACTOR GATA-1; LEUCINE ZIPPER PROTEIN; STAGE SELECTOR ELEMENT; TRANSGENIC MICE; DNA-BINDING AB Study of globin gene regulation has served as a useful paradigm for cell-specific and developmental control of transcription in higher eukaryotic cells. Recent work directed toward the identification and characterization of the cis-regulatory elements and transcription factors important for both aspects of control is reviewed. Particular emphasis is placed on the organization and function of globin locus control regions, mechanisms of switching of globin gene expression during development, and functions of the major erythroid-specific nuclear regulatory proteins. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. RP ORKIN, SH (reprint author), CHILDRENS HOSP,DIV HEMATOL ONCOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 114 TC 135 Z9 137 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JUL 15 PY 1995 VL 231 IS 2 BP 271 EP 281 DI 10.1111/j.1432-1033.1995.tb20697.x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RJ250 UT WOS:A1995RJ25000001 PM 7635138 ER PT J AU ZHU, L HARLOW, E DYNLACHT, BD AF ZHU, L HARLOW, E DYNLACHT, BD TI P107 USES A P21(CIP1)-RELATED DOMAIN TO BIND CYCLIN CDK2 AND REGULATE INTERACTIONS WITH E2F SO GENES & DEVELOPMENT LA English DT Article DE PRB; P107; CYCLIN-DEPENDENT-KINASE (CDK); CYCLIN-DEPENDENT KINASE INHIBITOR (CKI); SEQUENCE CONSERVATION ID RETINOBLASTOMA PROTEIN; DEPENDENT KINASES; INHIBITION; SUPPRESSION; EXPRESSION; ASSOCIATE; FAMILY; P21 AB The kinase activities of the cyclin/cdk complexes can be regulated in a number of ways. The most recently discovered mechanism of regulation is the association of cdk inhibitors (CKIs), such as p21, p27, and p57, with these complexes. In this report we demonstrate that the pRB-related protein p107, like the p21 family of cdk inhibitors, can inhibit the phosphorylation of target substrates by cyclin A/cdk2 and cyclin E/cdk2 complexes, and the associations of p107 and p21 with cyclin/cdk2 rely on a structurally and functionally related interaction domain. Furthermore, interactions between p107 or p21 with cyclin/cdk2, complexes are mutually exclusive. In cells treated with DNA-damaging agents elevated levels of p21 cause a dissociation of p107/cyclin/cdk2 complexes to yield p21/cyclin/cdk2 complexes. finally, the consequences of cyclin/cdk2 interactions with p107 have been examined. The activation of the p107-bound cyclin/cdk kinases leads to dissociation of p107 from the transcription factor E2F. Together, these results suggest that cyclin/cdk complexes can be regulated by protein molecules from different families in a mutually exclusive manner in response to certain signals and that these inhibitory proteins may have a potential role in regulating macromolecular assembly. RP ZHU, L (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129, USA. NR 49 TC 236 Z9 243 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 JUL 15 PY 1995 VL 9 IS 14 BP 1740 EP 1752 DI 10.1101/gad.9.14.1740 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA RM081 UT WOS:A1995RM08100006 PM 7622038 ER PT J AU OKUNIEFF, P MORGAN, D NIEMIERKO, A SUIT, HD AF OKUNIEFF, P MORGAN, D NIEMIERKO, A SUIT, HD TI RADIATION DOSE-RESPONSE OF HUMAN TUMORS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE TUMOR CONTROL PROBABILITY; ADJUVANT THERAPY; METASTASIS; TOLERANCE DOSE; GAMMA(50) ID PROPHYLACTIC CRANIAL IRRADIATION; SMALL CELL-CARCINOMA; ADJUVANT POSTOPERATIVE RADIOTHERAPY; THERAPY-ONCOLOGY-GROUP; BREAST-CANCER; LUNG-CANCER; RANDOMIZED TRIAL; STAGE-III; LOCAL-CONTROL; COMBINATION CHEMOTHERAPY AB Purpose: The dose of radiation that locally controls human tumors treated electively or for gross disease is rarely well defined, These doses can be useful in understanding the dose requirements of novel therapies featuring inhomogeneous dosimetry and in an adjuvant setting, The goal of this study was to compute the dose of radiation that locally controls 50% (TCD50) of tumors in human subjects. Methods and Materials: Legit regression was used with data collected from single institutions or from combinations of local control data accumulated from several institutions treating the same disease. Results: 90 dose response curves were calculated; 62 of macroscopic tumor therapy, 28 of elective therapy with surgery for primary control, The mean and median TCD50 for gross disease were 50.0 and 51.9 Gy, respectively, The mean and median TCD50 for microscopic disease control were 39.3 and 37.9 Gy, respectively, At the TCD50 an additional dose of 1 Gy controlled an additional 2.5 % (median) additional patients with macroscopic disease and 4.2% (median) additional patients with microscopic disease, For both macro-and microscopic disease, an increase of 1% of dose at the TCD50 increased control rates approximate to 1% (median) or 2-3% (mean), A predominance of dose response curves had shallow slopes accounting for the discrepancy between mean and median values. Conclusion: Doses to control microscopic disease are approximately 12 Gy less than that required to control macroscopic disease, and are about 79 % of the dose required to control macroscopic disease, The percentage increase in cures expected for a 1% increase in dose is similar for macroscopic and microscopic disease, with a median value of approximate to 1%/% and a mean of approximate to 2.7%/%. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. RP OKUNIEFF, P (reprint author), NCI,RADIAT ONCOL BRANCH,BLDG 10,ROOM B3B69,BETHESDA,MD 20892, USA. NR 94 TC 153 Z9 156 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 15 PY 1995 VL 32 IS 4 BP 1227 EP 1237 DI 10.1016/0360-3016(94)00475-Z PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA RL555 UT WOS:A1995RL55500038 PM 7607946 ER PT J AU KRENGER, W SNYDER, KM BYON, JCH FALZARANO, G FERRARA, JLM AF KRENGER, W SNYDER, KM BYON, JCH FALZARANO, G FERRARA, JLM TI POLARIZED TYPE-2 ALLOREACTIVE CD4(+) AND CD8(+) DONOR T-CELLS FAIL TO INDUCE EXPERIMENTAL ACUTE GRAFT-VERSUS-HOST DISEASE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; MONOCLONAL-ANTIBODY; INTERFERON-GAMMA; TH2 CELLS; IFN-GAMMA; INVIVO; MACROPHAGE; SUBSETS; MOUSE AB Acute graft-vs-host disease (GVHD) is thought to be mediated by alloreactive T cells with a type 1 cytokine phenotype. To prevent the development of acute GVHD, we have successfully polarized mature donor T cells toward a type 2 cytokine phenotype ex-vivo by incubating them with murine rIL-4 in a primary MLC. Polarized type 2 T cells were then transplanted with T cell-depleted bone marrow cells into irradiated recipients across either MHC class II (bm12-->C57BL/6) or class I (bm1-->C57BL/6) barriers, and the intensity of GVHD was measured by assessment of several in vitro and in vivo parameters. The injection of polarized type 2 T cells abrogated the mitogen-induced production of IFN-gamma by splenocytes from transplanted hosts on day 13 after bone marrow transplantation (BMT). Injection of polarized type 2 T cells failed to induce secretion of the effector phase cytokine TNF-alpha by splenocytes stimulated with LPS both in vitro and in vivo, and survival of transplanted mice after i.v. injection with LPS was significantly improved. Furthermore, cell-mixing experiments revealed that polarized type 2 T cells were able to inhibit type 1 cytokine responses induced by naive T cells after BMT. These data demonstrate that both polarized CD4(+) and CD8(+) type 2 alloreactive donor T cells can be generated in vitro from mature T cell populations. These cells function in vivo to inhibit type 1 T cell responses, and such inhibition attenuates the systemic morbidity of GVHD after BMT across both MHC class II or class I barriers in mice. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP KRENGER, W (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,D1638,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 39542]; NIAID NIH HHS [AI 30018] NR 62 TC 156 Z9 160 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1995 VL 155 IS 2 BP 585 EP 593 PG 9 WC Immunology SC Immunology GA RG973 UT WOS:A1995RG97300010 PM 7608537 ER PT J AU PETRUZZELLI, L MADUZIA, L SPRINGER, TA AF PETRUZZELLI, L MADUZIA, L SPRINGER, TA TI ACTIVATION OF LYMPHOCYTE FUNCTION-ASSOCIATED MOLECULE-1 (CD11A/CD18) AND MAC-1 (CD11B/CD18) MIMICKED BY AN ANTIBODY-DIRECTED AGAINST CD18 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; INTERCELLULAR-ADHESION MOLECULE-1; LEUKOCYTE INTEGRIN LFA-1; MONOCLONAL-ANTIBODY; BETA-SUBUNIT; CELL-ADHESION; ENDOTHELIAL-CELLS; COUNTER-RECEPTOR; TRANSENDOTHELIAL MIGRATION; CR3-DEPENDENT ADHESION AB The beta(2)-integrin (CD18) family members bind to their ligands subsequent to activation of a number of well defined and diverse signal transduction pathways. The precise molecular changes associated with activation of the integrin family members have remained elusive. Here, we characterize a monoclonal, CBR LFA-1/2, that binds to the beta(2)-subunit and is able to mimic activation induced upon stimulation by phorbol esters. The Ab induces binding of the LFA-1-expressing cell line, JY, to ICAM-1 (CD54) and ICAM-3 (CD50). Activation of binding by this Ab is independent of Fc interactions and does not occur through cross-linking at the cell surface, because the Fab fragment of the Ab is able to modulate the same effect. Stimulation of neutrophils with CBR LFA-1/2 induces binding to ICAM-1 through activation of both LFA-1 and Mac-1. Activation of Mac-1 by CBR LFA-1/2 was further confirmed by stimulation of neutrophil binding to fibrinogen, a ligand for Mac-1. CBR LFA-1/2 lowers by 10-fold the concentration of Mg2+ required to achieve maximal binding of LFA-1 to ICAM-1. It therefore appears that CBR LFA-1/2 induces a conformational change that directly increases the avidity of beta(2)-integrins for ligands. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. FU NCI NIH HHS [CA31799, CA31798] NR 67 TC 71 Z9 73 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1995 VL 155 IS 2 BP 854 EP 866 PG 13 WC Immunology SC Immunology GA RG973 UT WOS:A1995RG97300040 PM 7608563 ER PT J AU TREDE, NS TSYTSYKOVA, AV CHATILA, T GOLDFELD, AE GEHA, RS AF TREDE, NS TSYTSYKOVA, AV CHATILA, T GOLDFELD, AE GEHA, RS TI TRANSCRIPTIONAL ACTIVATION OF THE HUMAN TNF-ALPHA PROMOTER BY SUPERANTIGEN IN HUMAN MONOCYTIC CELLS - ROLE OF NF-KAPPA-B SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; HUMAN-IMMUNODEFICIENCY-VIRUS; SHOCK SYNDROME TOXIN-1; BINDING-PROTEIN; MICROBIAL SUPERANTIGENS; GENE-REGULATION; T-CELL; LIPOPOLYSACCHARIDE; EXPRESSION; MACROPHAGE AB We have studied the transcriptional activation of the human TNF-alpha gene by the superantigen staphylococcal enterotoxin A (SEA) in the human premonocytic cell line THP-1. Nuclear proteins from SEA-stimulated THP-1 cells bound strongly to kappa 3, the most proximal of three putative NF-kappa B binding sites (kappa 1-kappa 3) found in the 5' regulatory region of the TNF-alpha gene, but only weakly to kappa 1,the most distal of the NF-kappa B binding sites, and showed no binding to kappa 2. The mobility of the kappa 3-nucleoprotein complex was identical to that of complexes formed between nuclear proteins and the consensus NF-kappa B sequence. Moreover, both 5' and 3' mutants of kappa 3 were unable to displace kappa 3 binding, suggesting that the kappa 3 binding complex induced by SEA has the characteristics of NF-kappa B. Studies using Abs directed against the NF-kappa B subunits p50 and p65 suggested that both p50 and p65 bind to the kappa 3 sequence. Reporter gene assays showed that deletion of kappa 3 (-99 to -89 bp) and point mutation of the three 5' guanine bases in the kappa 3 sequence reduced the inducibility of the TNF-alpha promoter by SEA and LPS. These results indicate that superantigen induces NF-kappa B in human monocytic cells and suggest that binding of NF-kappa B to the kappa 3 site of the TNF-alpha promoter plays an important role in the transcriptional activation of the TNF-alpha gene by superantigen. C1 DANA FARBER CANC CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP TREDE, NS (reprint author), CHILDRENS HOSP,DIV IMMUNOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI-27411, AI-30550]; NICHD NIH HHS [HD-07321] NR 26 TC 112 Z9 117 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1995 VL 155 IS 2 BP 902 EP 908 PG 7 WC Immunology SC Immunology GA RG973 UT WOS:A1995RG97300045 PM 7608567 ER PT J AU ASHAR, HR FEJZO, MS TKACHENKO, A ZHOU, X FLETCHER, JA WEREMOWICZ, S MORTON, CC CHADA, K AF ASHAR, HR FEJZO, MS TKACHENKO, A ZHOU, X FLETCHER, JA WEREMOWICZ, S MORTON, CC CHADA, K TI DISRUPTION OF THE ARCHITECTURAL FACTOR HMGI-C - DNA-BINDING AT HOOK MOTIFS FUSED IN LIPOMAS TO DISTINCT TRANSCRIPTIONAL REGULATORY DOMAINS SO CELL LA English DT Article ID PULMONARY CHONDROID HAMARTOMA; NF-KAPPA-B; DIAGNOSTIC RELEVANCE; DROSOPHILA-TRITHORAX; ACUTE LEUKEMIAS; INSULIN GENE; ALL-1 GENE; PROTEINS; TRANSLOCATION; TUMORS AB Lipomas are one of the most common mesenchymal neoplasms in humans. They are characterized by consistent cytogenetic aberrations involving chromosome 12 in bands q14-15. Interestingly, this region is also the site of rearrangement for other mesenchymally derived tumors. This study demonstrates that HMGI-C, an architectural factor that functions in transcriptional regulation, has been disrupted by rearrangement at the 12q14-15 chromosomal breakpoint in lipomas. Chimeric transcripts were isolated from two lipomas in which HMGI-C DNA-binding domains (AT hook motifs) are fused to either a LIM or an acidic transactivation domain. These results, identifying a gene rearranged in a benign neoplastic process that does not proceed to a malignancy, suggest a role for HMGI-C in adipogenesis and mesenchyme differentiation. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP ASHAR, HR (reprint author), UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT BIOCHEM,PISCATAWAY,NJ 08854, USA. FU NCI NIH HHS [1K11 CA 01498]; NICHD NIH HHS [HD30498]; NIGMS NIH HHS [GM38731] NR 69 TC 360 Z9 366 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 14 PY 1995 VL 82 IS 1 BP 57 EP 65 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RK424 UT WOS:A1995RK42400009 PM 7606786 ER PT J AU TETI, A PANICCIA, R GOLDRING, SR AF TETI, A PANICCIA, R GOLDRING, SR TI CALCITONIN INCREASES CYTOSOLIC-FREE CALCIUM-CONCENTRATION VIA CAPACITATIVE CALCIUM INFLUX SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PAROTID ACINAR-CELLS; INOSITOL PHOSPHATE; EXTRACELLULAR CALCIUM; RECEPTOR; ENTRY; CA2+; CLONING; OSTEOCLASTS; EXPRESSION; ACTIVATION AB The calcitonin receptor has been proposed to function as an extracellular Ca2+ concentration ([Ca2+](o)) sensor (Stroop, S. D., Thompson, D. L., Kuestner, R. E., and Moore, E. E. (1993) J, Biol. Chem, 268, 19927-19930). To test this hypothesis we studied the LLC-PK1 renal tubular cells and the PC, cells, a cell line stably transfected with the cloned porcine calcitonin receptor. [Ca2+](i) was measured by fura-a single cell microfluorometry. Addition to the cells equilibrated in 1.25 mM Ca2+-containing media of 1-10 mM extracellular Ca2+ did not result in a significant increase of [Ca2+](i). Treatment with 10(-7) M salmon calcitonin (sCT) elicited a rapid, persistent elevation of [Ca2+](i). Addition of 1-10 mM extracellular Ca2+ in the presence of sCT induced a significant [Ca2+](i) elevation, about 10-fold that observed in the absence of the hormone. Ca2+ influx was inhibited by lanthanum. The rise of [Ca2+](i) at elevated [Ca2+](o) was not due to a Ca2+ sensing mechanism with release of Ca2+ from intracellular stores, since it was prolonged, and was not abolished by prior depletion of Ca2+ stores with 10(-6) M thapsigargin. On the contrary, this agent potentiated Ca2+ influx after addition of 1-10 mM Ca2+ by 13-fold versus control. Prior stimulation of [Ca2+](i) with 10(-7) M arginine-vasopressin had similar effects, enhancing the subsequent Ca2+ influx. Enhancement of Ca2+ influx by sCT was confirmed by increased Mn2+ quenching of fura-2 fluorescence. In conclusion, arginine-vasopressin or calcitonin enhance Ca2+ influx in LLC-PK1 cells via a Ca2+ release-activated conductance, probably dependent upon capacitative Ca2+ entry. Thus, these effects are not unique to the calcitonin receptor and argue against the receptor functioning as a [Ca2+](o) sensor. C1 IST DERMOPAT IMMACOLATA,I-00167 ROME,ITALY. UNIV ROMA LA SAPIENZA,INST HISTOL & GEN EMBRYOL,I-00161 ROME,ITALY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02129. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,BOSTON,MA 02129. HARVARD UNIV,BAPTIST MEM HOSP,SCH MED,BOSTON,MA 02129. RP TETI, A (reprint author), UNIV LAQUILA,SCH MED,DEPT EXPTL MED,VIA VETOIO,COPPITO 2,I-67100 LAQUILA,ITALY. OI Teti, Anna Maria/0000-0002-5887-4419 FU NIAMS NIH HHS [AR-03564]; NIDDK NIH HHS [DK-46773] NR 35 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 14 PY 1995 VL 270 IS 28 BP 16666 EP 16670 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RJ347 UT WOS:A1995RJ34700034 PM 7622475 ER PT J AU HOSOKAWA, Y TU, T TAHARA, H SMITH, AP ARNOLD, A AF HOSOKAWA, Y TU, T TAHARA, H SMITH, AP ARNOLD, A TI ABSENCE OF CYCLIN D1/PRAD1 POINT MUTATIONS IN HUMAN BREAST CANCERS AND PARATHYROID ADENOMAS AND IDENTIFICATION OF A NEW CYCLIN D1 GENE POLYMORPHISM SO CANCER LETTERS LA English DT Article DE PRAD1; POLYMERASE CHAIN REACTION (PCR); SINGLE-STRAND CONFORMATIONAL POLYMORPHISM (SSCP); BREAST CANCER; PARATHYROID ADENOMA ID CENTROCYTIC LYMPHOMA; PUTATIVE ONCOGENE; PRAD1/CYCLIN D1; EXPRESSION; PRAD1; CHROMOSOME-11Q13; TRANSLOCATION; AMPLIFICATION; BCL-1; CELL AB PRAD1 (cyclin D1) has been implicated in the molecular pathogenesis of a variety of tumors, including parathyroid adenomas, t(11;14)-bearing B-lymphoid tumors, and breast cancer. The sequence of the overexpressed PRAD1 genes has been directly analyzed in only two tumor specimens, a benign parathyroid adenoma and a malignant centrocytic lymphoma. Thus, little is known about PRAD1 sequence in the vast majority of human primary tumors, including breast cancers. Using single-strand conformational polymorphism (SSCP) analysis, we have examined the coding region of the PRAD1 gene in 30 primary breast cancers and 25 parathyroid adenomas. Polymerase chain reaction (PCR)-SSCP analysis of the coding region of exons 1-5 of the PRAD1 gene did not reveal any tumor-specific mutations. During the course of screening for mutations, we found and established the sequence variants of a new DNA polymorphism at codon 241 within exon 4 of the PRAD1 gene. Since this polymorphism is located within the coding region of the PRAD1 gene, it will allow determination of allele-specific expression of the gene and the detection of allele imbalance. At least in breast and parathyroid neoplasms, overexpression of the wild-type PRAD1 sequence, rather than point mutational activation, appears to be the predominant mechanism by which PRAD1 exerts its oncogenic action. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE ONCOL LAB,BOSTON,MA 02114. FU NCI NIH HHS [CA55909]; NIDDK NIH HHS [DK11794] NR 22 TC 43 Z9 46 U1 0 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUL 13 PY 1995 VL 93 IS 2 BP 165 EP 170 DI 10.1016/0304-3835(95)03805-7 PG 6 WC Oncology SC Oncology GA RL183 UT WOS:A1995RL18300003 PM 7621424 ER PT J AU LIU, D BIENKOWSKA, J PETOSA, C COLLIER, RJ FU, H LIDDINGTON, R AF LIU, D BIENKOWSKA, J PETOSA, C COLLIER, RJ FU, H LIDDINGTON, R TI CRYSTAL-STRUCTURE OF THE ZETA-ISOFORM OF THE 14-3-3 PROTEIN SO NATURE LA English DT Article AB THE 14-3-3 family of proteins have recently been identified as regulatory elements in intracellular signalling pathways(1): 14-3-3 proteins bind to oncogene and proto-oncogene products, including c-Raf-1 (refs 2-5), c-Bcr (ref. 6) and polyomavirus middle-T antigen(7); overexpression of 14-3-3 activates Raf kinase in yeast(2,3) and induces meiotic maturation in Xenopus oocytes(5). Here we report the crystal structure of the major isoform of mammalian 14-3-3 proteins at 2.9 Angstrom resolution. Each subunit of the dimeric protein consists of a bundle of nine antiparallel helices that form a palisade around an amphipathic groove. The groove is large enough to accommodate a tenth helix, and we propose that binding to an amphipathic helix represents a general mechanism for the interaction of 14-3-3 with diverse cellular proteins. The residues in the dimer interface and the putative ligand-binding surface are invariant among vertebrates, yeast and plants, suggesting a conservation of structure and function throughout the 14-3-3 family. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. EMORY UNIV,SCH MED,DEPT PHARMACOL,ATLANTA,GA 30322. RP LIU, D (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. OI Collier, R John/0000-0002-2427-4239 NR 21 TC 371 Z9 383 U1 3 U2 18 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUL 13 PY 1995 VL 376 IS 6536 BP 191 EP 194 DI 10.1038/376191a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RJ028 UT WOS:A1995RJ02800066 PM 7603574 ER PT J AU DRANOFF, G AF DRANOFF, G TI HOT PAPERS - VACCINOLOGY - VACCINATION WITH IRRADIATED TUMOR-CELLS ENGINEERED TO SECRETE MURINE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR STIMULATES POTENT, SPECIFIC, AND LONG-LASTING ANTITUMOR IMMUNITY - DRANOFF,G, JAFFEE,E, LAZENBY,A, GOLUMBEK,P, LEVITSKY,H, BROSE,K, JACKSON,V, HAMADA,H, PARDOLL,D, MULLIGAN,RC - COMMENTS SO SCIENTIST LA English DT Editorial Material AB Immunologist Glenn Dranoff discusses engineering tumor cells to fight cancer. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP DRANOFF, G (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD JUL 10 PY 1995 VL 9 IS 14 BP 15 EP 15 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA RK415 UT WOS:A1995RK41500013 ER PT J AU UDDIN, S YENUSH, L SUN, XJ SWEET, ME WHITE, MF PLATANIAS, LC AF UDDIN, S YENUSH, L SUN, XJ SWEET, ME WHITE, MF PLATANIAS, LC TI INTERFERON-ALPHA ENGAGES THE INSULIN-RECEPTOR SUBSTRATE-1 TO ASSOCIATE WITH THE PHOSPHATIDYLINOSITOL 3'-KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID PROTEIN-TYROSINE KINASE; SIGNAL-TRANSDUCTION; TRANSCRIPTION FACTOR; HEMATOPOIETIC-CELLS; SH3 DOMAINS; PHOSPHORYLATION; IRS-1; STIMULATION; EXPRESSION; JAK AB Interferon-alpha (IFN alpha) induces rapid tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), a docking protein with multiple tyrosine phosphorylation sites that bind to the Src homology 2 (SH2) domains of various signaling proteins. During IFN alpha stimulation, the p85 regulatory subunit of the phosphatidylinositol 3'-kinase binds via its SH2 domains to tyrosine-phosphorylated IRS-1, and phosphatidylinositol 3'-kinase activity is detected in association with IRS-1. Thus, IFN alpha responses occur by activation of the IRS signaling system, which it shares with insulin, insulin-like growth factor-1, and interleukin-4. C1 EDWARD HINES VET ADM MED CTR,HINES,IL 60141. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. RP UDDIN, S (reprint author), LOYOLA UNIV,DIV HEMATOL ONCOL,BLDG 112,2160 S 1ST AVE,MAYWOOD,IL 60153, USA. RI Yenush, Lynne/J-8815-2014 OI Yenush, Lynne/0000-0001-8589-7002 FU NIDDK NIH HHS [DK43808, DK38712] NR 30 TC 165 Z9 167 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 7 PY 1995 VL 270 IS 27 BP 15938 EP 15941 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RH226 UT WOS:A1995RH22600007 PM 7608146 ER PT J AU ROSOWSKY, A FORSCH, RA QUEENER, SF AF ROSOWSKY, A FORSCH, RA QUEENER, SF TI 2,4-DIAMINOPYRIDO[3,2-D]PYRIMIDINE INHIBITORS OF DIHYDROFOLATE-REDUCTASE FROM PNEUMOCYSTIS-CARINII AND TOXOPLASMA-GONDII SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID LIPID-SOLUBLE ANTIFOLATE; POTENTIAL ANTIPNEUMOCYSTIS; ANTITOXOPLASMA; TRIMETREXATE; PIRITREXIM; SYNTHETASE; ANALOGS; AGENTS; DRUGS AB Six previously unknown 2,4-diamino-6-(anilinomethyl)- and 2,4-diamino-6-[(N-methylanilino)methyl]pyrido[3,2-d]pyrimidines (5-10) were synthesized from 2,4-diamino-6-(bromomethyl)-pyrido[3,2-d]pyrimidine hydrobromide (11 . HBr) by treatment with the appropriate aniline or N-methylaniline in dimethylformamide at room temperature, with or without NaHCO3 present. Compounds 5-10 were tested as inhibitors of dihydrofolate reductase from Pneumocystis carinii, Toxoplasma gondii, and rat liver as a part of a larger effort directed toward the discovery of lipophilic nonclassical antifolates combining high enzyme selectivity and high potency. Of the six analogues tested, the most potent and selective against T. gondii DHFR was 2,4-diamino-6-[(3',4',5'-trimethoxy-N-methylanilino)methyl]pyrido[3,2-d]pyrimidine (7), which had an IC50 of 0.0047 mu M against this enzyme as compared with 0.026 mu M against the rat liver enzyme. The potency of 7 against T. gondii DHFR was similar to that of trimetrexate (TMQ, 1) and piritrexim (PTX, 2) but was > 500-fold greater than that of trimethoprim (TMP, 3). However, while 7 was more selective than either TMQ (19x) or PTX (63x) against this enzyme, its selectivity in comparison with TMP was 8-fold lower. 2,4-Diamino-6-[(3',4',5'-trimethoxyanilino)methyl]pyrido[3,2-d]pyrimidine (6) was 17-fold less active than 7 and was also less selective. 2,4-Diamino-6-[(3',4'-dichloro-N-methylanilino)methyl]pyrido[3,2-d]pyrimidine (10) had an IC50 of 0.022 CIM against P. carinii DHFR and was comparable in potency to TMQ and PTX. The species selectivity of 10 for P. carinii versus rat liver DHFR was greater than that of either TMQ (21-fold) or PTX (31-fold). On the other hand, even though 10 was slightly more active than TMQ against the P. carinii enzyme, its selectivity was 7-fold lower than that of TMP. Thus, the goal of combining high enzyme binding activity, which is characteristic of the fused-ring compounds TMQ and PTX, with high selectivity for T. gondii and P. carinii DHFR versus rat liver DHFR, which is characteristic of the monocyclic compound TMP, remained unmet in this limited series. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. INDIANA UNIV,SCH MED,DEPT PHARMACOL & TOXICOL,INDIANAPOLIS,IN 46202. RP ROSOWSKY, A (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [N01-AI35171, R01-AI29904] NR 33 TC 30 Z9 32 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 7 PY 1995 VL 38 IS 14 BP 2615 EP 2620 DI 10.1021/jm00014a014 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA RJ014 UT WOS:A1995RJ01400014 PM 7629801 ER PT J AU FUCHS, CS MAYER, RJ AF FUCHS, CS MAYER, RJ TI MEDICAL PROGRESS - GASTRIC-CARCINOMA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID HELICOBACTER-PYLORI INFECTION; STOMACH-CANCER; HIGH-RISK; DIETARY FACTORS; PEPTIC-ULCER; ALCOHOL-CONSUMPTION; CURATIVE RESECTION; PERNICIOUS-ANEMIA; COLORECTAL-CANCER; C-ERBB-2 PROTEIN C1 BRIGHAM & WOMENS HOSP,DEPT MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RP FUCHS, CS (reprint author), DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 158 TC 502 Z9 514 U1 3 U2 20 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 6 PY 1995 VL 333 IS 1 BP 32 EP 41 DI 10.1056/NEJM199507063330107 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA RG735 UT WOS:A1995RG73500007 PM 7776992 ER PT J AU PRICE, BD HUGHESDAVIES, L PARK, SJ AF PRICE, BD HUGHESDAVIES, L PARK, SJ TI CDK2 KINASE PHOSPHORYLATES SERINE-315 OF HUMAN P53 IN-VITRO SO ONCOGENE LA English DT Article DE P53; CDK2; PHOSPHORYLATION; DNA DAMAGE; TRANSCRIPTION ID CELL-CYCLE CONTROL; WILD-TYPE P53; TUMOR-SUPPRESSOR PROTEIN; DNA-BINDING; RETINOBLASTOMA PROTEIN; DEPENDENT KINASES; MAMMALIAN-CELLS; GENE; INHIBITION; P34CDC2 AB DNA damage increases p53 protein levels and activates transcription of the p21 gene. The p21 protein binds to and inhibits cdk2 kinase, causing G1 arrest. Here, we have investigated if a p53 fusion protein is a substrate for cdk2 kinase in vitro. Cdk2 kinase was immunoprecipitated from NIH3T3 cells and allowed to phosphorylate a human p53-GST (glutathione-s-transferase) fusion protein. Cdk2 and cyclin E-cdk2 efficiently phosphorylated both wild-type (wt) and mutant p53-GST. Cdk2 immunoprecipitated from cells in Go and early G1 exhibited minimal p53 kinase activity, whereas cells in S-phase displayed high levels of p53 kinase activity. If NIH3T3 cells were X-ray irradiated to induce DNA damage, cdk2 p53 kinase activity was rapidly inhibited within 1 h, but had recovered by 4 h post irradiation. Mutation of serine 315 of p53 to alanine (p53-S315A) abolished phosphorylation by cdk2 kinase. However, wtp53 and p53-S315A were equally effective at activating transcription when cotransfected with a p53 reporter construct. The results demonstrate that ser 315 of p53 is phosphorylated by cdk2 in vitro. However, ser 315 of wtp53 is not required for transcriptional activity in vivo, suggesting that cdk2 phosphorylation of p53 may be involved in regulating other cellular functions of wtp53. RP PRICE, BD (reprint author), DANA FARBER CANC INST,JOINT CTR RADIAT THERAPY,STRESS PROT GRP,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA64585] NR 55 TC 50 Z9 51 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 6 PY 1995 VL 11 IS 1 BP 73 EP 80 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RJ295 UT WOS:A1995RJ29500009 PM 7624134 ER PT J AU HEGARTY, SJ AF HEGARTY, SJ TI RESTORING PUBLIC TRUST SO HOSPITALS & HEALTH NETWORKS LA English DT Editorial Material C1 DANA FARBER CANC INST,BOSTON,MA. RP HEGARTY, SJ (reprint author), MASSACHUSETTS HOSP ASSOC,BOSTON,MA, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HOSPITAL PUBL INC PI CHICAGO PA 211 E CHICAGO AVE, SUITE 700, CHICAGO, IL 60611 SN 1068-8838 J9 HOSP HEALTH NETWORK JI Hosp. Health Netw. PD JUL 5 PY 1995 VL 69 IS 13 BP 50 EP 50 PG 1 WC Health Policy & Services SC Health Care Sciences & Services GA RG641 UT WOS:A1995RG64100017 PM 7795707 ER PT J AU BATES, DW CULLEN, DJ LAIRD, N PETERSEN, LA SMALL, SD SERVI, D LAFFEL, G SWEITZER, BJ SHEA, BF HALLISEY, R VANDERVLIET, M NEMESKAL, R LEAPE, LL AF BATES, DW CULLEN, DJ LAIRD, N PETERSEN, LA SMALL, SD SERVI, D LAFFEL, G SWEITZER, BJ SHEA, BF HALLISEY, R VANDERVLIET, M NEMESKAL, R LEAPE, LL TI INCIDENCE OF ADVERSE DRUG EVENTS AND POTENTIAL ADVERSE DRUG EVENTS - IMPLICATIONS FOR PREVENTION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HOSPITALIZED-PATIENTS; HEALTH-CARE; MEDICATION AB Objectives.-To assess incidence and preventability of adverse drug events (ADEs) and potential ADEs. To analyze preventable events to develop prevention strategies. Design.-Prospective cohort study. Participants.-All 4031 adult admissions to a stratified random sample of 11 medical and surgical units in two tertiary care hospitals over a 6-month period. Units included two medical and three surgical intensive care units and four medical and two surgical general care units. Main Outcome Measures.-Adverse drug events and potential ADEs. Methods.-Incidents were detected by stimulated self-report by nurses and pharmacists and by daily review of all charts by nurse investigators. Incidents were subsequently classified by two independent reviewers as to whether they represented ADEs or potential ADEs and as to severity and preventability. Results.-Over 6 months, 247 ADEs and 194 potential ADEs were identified. Extrapolated event rates were 6.5 ADEs and 5.5 potential ADEs per 100 nonobstetrical admissions, for mean numbers per hospital per year of approximately 1900 ADEs and 1600 potential ADEs. Of all ADEs, 1% were fatal (none preventable), 12% life-threatening, 30% serious, and 57% significant. Twenty-eight percent were judged preventable. Of the life-threatening and serious ADEs, 42% were preventable, compared with 18% of significant ADEs, Errors resulting in preventable ADEs occurred most often at the stages of ordering (56%) and administration (34%); transcription (6%) and dispensing errors (4%) were less common. Errors were much more likely to be intercepted if the error occurred earlier in the process: 48% at the ordering stage vs 0% at the administration stage, Conclusion.-Adverse drug events were common and often preventable; serious ADEs were more likely to be preventable. Most resulted from errors at the ordering stage, but many also occurred at the administration stage. Prevention strategies should target both stages of the drug delivery process. C1 BRIGHAM & WOMENS HOSP,DEPT PHARM,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PHARM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BOSTON,MA 02115. APM INC,NEW YORK,NY. RP BATES, DW (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,DIV GEN MED & PRIMARY CARE,75 FRANCIS ST,BOSTON,MA 02115, USA. FU AHRQ HHS [R01-HS07107-01] NR 41 TC 1669 Z9 1735 U1 12 U2 75 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 JUL 5 PY 1995 VL 274 IS 1 BP 29 EP 34 DI 10.1001/jama.274.1.29 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA RG233 UT WOS:A1995RG23300027 PM 7791255 ER PT J AU LEAPE, LL BATES, DW CULLEN, DJ COOPER, J DEMONACO, HJ GALLIVAN, T HALLISEY, R IVES, J LAIRD, N LAFFEL, G NEMESKAL, R PETERSEN, LA PORTER, K SERVI, D SHEA, BF SMALL, SD SWEITZER, BJ THOMPSON, BT VANDERVLIET, M AF LEAPE, LL BATES, DW CULLEN, DJ COOPER, J DEMONACO, HJ GALLIVAN, T HALLISEY, R IVES, J LAIRD, N LAFFEL, G NEMESKAL, R PETERSEN, LA PORTER, K SERVI, D SHEA, BF SMALL, SD SWEITZER, BJ THOMPSON, BT VANDERVLIET, M TI SYSTEMS-ANALYSIS OF ADVERSE DRUG EVENTS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PREVENTION; FAILURES; COMPUTER; ERRORS AB Objective.-To identify and evaluate the systems failures that underlie errors causing adverse drug events (ADEs) and potential ADEs. Design.-Systems analysis of events from a prospective cohort study. Participants.-All admissions to 11 medical and surgical units in two tertiary care hospitals over a 6-month period. Main Outcome Measures.-Errors, proximal causes, and systems failures. Methods.-Errors were detected by interviews of those involved. Errors were classified according to proximal cause and underlying systems failure by multidisciplinary teams of physicians, nurses, pharmacists, and systems analysts. Results.-During this period, 334 errors were detected as the causes of 264 preventable ADEs and potential ADEs. Sixteen major systems failures were identified as the underlying causes of the errors. The most common systems failure was in the dissemination of drug knowledge, particularly to physicians, accounting for 29% of the 334 errors. Inadequate availability of patient information, such as the results of laboratory tests, was associated with 18% of errors. Seven systems failures accounted for 78% of the errors; all could be improved by better information systems. Conclusions.-Hospital personnel willingly participated in the detection and investigation of drug use errors and were able to identify underlying systems failures. The most common defects were in systems to disseminate knowledge about drugs and to make drug and patient information readily accessible at the time it is needed. Systems changes to improve dissemination and display of drug and patient data should make errors in the use of drugs less likely. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,DIV GEN MED & PRIMARY CARE,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PHARM,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NURSING,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PHARM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. APM INC,NEW YORK,NY. RP LEAPE, LL (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU AHRQ HHS [R01-HS07107-01] NR 31 TC 1110 Z9 1147 U1 2 U2 40 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 JUL 5 PY 1995 VL 274 IS 1 BP 35 EP 43 DI 10.1001/jama.274.1.35 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA RG233 UT WOS:A1995RG23300028 PM 7791256 ER PT J AU AXELSSON, K LJUNG, BME MOORE, DH THOR, AD CHEW, KL EDGERTON, SM SMITH, HS MAYALL, BH AF AXELSSON, K LJUNG, BME MOORE, DH THOR, AD CHEW, KL EDGERTON, SM SMITH, HS MAYALL, BH TI TUMOR ANGIOGENESIS AS A PROGNOSTIC ASSAY FOR INVASIVE DUCTAL BREAST-CARCINOMA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HAZARDS REGRESSION-MODEL; CANCER PATIENTS; INDICATOR; SURVIVAL; EXPRESSION; PROTEIN AB Background: Tumor angiogenesis, as assayed by microvessel density, has been proposed as an independent prognostic marker for clinical outcome in breast cancer patients, Purpose: The present study evaluated the microvessel density assay and assessed its utility, alone and together with the evaluation of other tumor characteristics, in predicting out-come in patients with invasive ductal carcinomas, Methods: In a blinded design, cases of invasive ductal carcinoma were selected from a registry containing the records of and tumor specimens from 386 breast cancer patients treated at the Massachusetts General Hospital from 1977 through 1982, After the exclusion of ineligible patients and inadequate specimens, 220 patients were included in the study; their median time of follow-up was 11.5 years, Half of these patients (n = 110) were positive for axillary lymph node metastases. Histologic sections of the tumors were stained immunocytochemically for factor VIII, a coagulation protein expressed by blood vessel endothelium, and for p53 protein, Independently, two analysts counted microvessels in three microscope fields selected from separate vascular regions of the tumor, Variability in microvessel scores between analysts and among different fields of the same tumor was summarized by the coefficient of variation, The kappa statistic tested for agreement between the analysts while correcting for chance agreement, The effects of tumor characteristics on metastasis-free survival and overall survival were tested univariately by the Harrington-Fleming rank test procedure, The effect of multiple factors on survival was tested under a Cox multivariate proportional hazards model, Results: Microvessel count showed considerable variability between the two analysts and among regions within each tumor, with an overall concordance for tumor classification of 73%, Univariate analysis revealed no association between microvessel count and any other tumor or patient characteristic, Multivariate analysis indicated, for these patients, that nodal status and p53 staining predicted metastasis-free survival and that nodal status, estrogen receptor (ER) status, and tumor grade predicted overall survival, Conclusions: Microvessel count showed much variation among different regions of each tumor, It did not predict metastasis-free survival or overall survival, Nodal status was the most powerful criterion to stratify these patients with invasive ductal carcinoma of the breast into different survival groups, Only ER status, tumor grade, and p53 staining had additional prognostic utility for these patients after they had been stratified by nodal status. C1 UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PATHOL,SAN FRANCISCO,CA. CALIF PACIFIC MED CTR,GERALDINE BRUSH CANC RES INST,SAN FRANCISCO,CA 94115. UNIV VERMONT,MED CTR,DEPT PATHOL,BURLINGTON,VT 05405. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU NCI NIH HHS [2PO1CA44768] NR 41 TC 194 Z9 197 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 5 PY 1995 VL 87 IS 13 BP 997 EP 1008 DI 10.1093/jnci/87.13.997 PG 12 WC Oncology SC Oncology GA RF706 UT WOS:A1995RF70600013 PM 7543156 ER PT J AU VOS, BP STRASSMAN, AM AF VOS, BP STRASSMAN, AM TI FOS EXPRESSION IN THE MEDULLARY DORSAL HORN OF THE RAT AFTER CHRONIC CONSTRICTION INJURY TO THE INFRAORBITAL NERVE SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE NEUROPATHIC PAIN; OROFACIAL PAIN; TRIGEMINAL NUCLEUS CAUDALIS; TRIGEMINAL NERVE; ANIMAL MODEL ID EXPERIMENTAL PERIPHERAL NEUROPATHY; PRIMARY AFFERENT NEURONS; SPINAL-CORD NEURONS; PROTEIN-LIKE IMMUNOREACTIVITY; REDUCE NOCICEPTIVE BEHAVIORS; PAIN-RELATED BEHAVIORS; UNMYELINATED C FIBERS; SCIATIC-NERVE; THERMAL-STIMULATION; ROOT-GANGLIA AB Chronic constriction injury to the rat's infraorbital nerve (IoN-CCI) induces asymmetric face grooming directed to the injured nerve territory and, beginning at 7-12 days postoperative, hyperresponsiveness to mechanical stimulation in this territory (B.P. Vos, A.M. Strassman, and R.J. Maciewicz, 1994, J. Neurosci. 14:2708-2723). To examine central mechanisms involved in these behavioral alterations, changes in nonevoked and mechanical stimulation-evoked fos-like immunoreactivity (fos-LI) following IoN-CCI were quantified in the medullary dorsal horn. Following the appearance of hyperresponsiveness in IoN-CCI rats, experimental and matched sham-operated rats were anesthetized with urethane and received either no stimulation or repeated stimulation with either a 2- or 15-g von Frey hair applied to the hairy skin between vibrissae B3-4/C3-4 on the operated side. Unstimulated IoN-CCI rats had increased fos-LI in laminae I-IV of the ipsilateral medullary dorsal horn. In both groups, mechanical stimulation produced a distinct pattern of fos-LI in the ipsilateral medullary dorsal horn, the quantity of which was related to stimulus intensity. For both stimulus intensities, the total amount and the rostrocaudal spread of evoked fos-LI were significantly larger in IoN-CCI rats. In IoN-CCI rats, stimulation-evoked increases in fos-LI were proportionally larger in laminae I-II than in III-IV. This laminar effect was also present in sham-operated rats but only for 15-g stimulation. Neither condition nor stimulus intensity affected fos-LI in the contralateral medullary dorsal horn. Positive correlations were found between the behavioral parameters of increased trigeminal nociceptive activity and the total amount of fos-LI in the ipsilateral medullary dorsal horn. The results demonstrate that IoN-CCI induces significant alterations in the central processing of afferent signals, which may underlie behavioral manifestations of increased nociceptive activity. (C) 1995 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. FU NINDS NIH HHS [NS-24594] NR 113 TC 36 Z9 38 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 3 PY 1995 VL 357 IS 3 BP 362 EP 375 DI 10.1002/cne.903570304 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA RF040 UT WOS:A1995RF04000003 PM 7673473 ER PT J AU SAKIHAMA, T SMOLYAR, A REINHERZ, EL AF SAKIHAMA, T SMOLYAR, A REINHERZ, EL TI OLIGOMERIZATION OF CD4 IS REQUIRED FOR STABLE BINDING TO CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX PROTEINS BUT NOT FOR INTERACTION WITH HUMAN-IMMUNODEFICIENCY-VIRUS GP120 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTIGEN RECOGNITION; AIDS; T-CELL RECEPTOR; CROSS-LINKING; DOMINANT NEGATIVE MUTATION ID MHC CLASS-II; T-CELLS; MONOCLONAL-ANTIBODY; CRYSTAL-STRUCTURE; ATOMIC-STRUCTURE; LYMPHOCYTES-T; SOLUBLE CD4; ANTIGEN; DOMAIN; SITE AB Previous studies have failed to detect an interaction between monomeric soluble CD4 (sCD4) and class II major histocompatibility complex (MHC) proteins, suggesting that oligomerization of CD4 on the cell surface may be required to form a stable class II MHC binding site. To test this possibility, we transfected the F43I CD4 mutant, which is incapable of binding to class II MHC or human immunodeficiency virus (HIV) gp120, into COS-7 cells together with wild-type CD4 (wtCD4). Expression of F43I results in a dominant negative effect: no class II MHC binding is observed even though wtCD4 expression is preserved. Apparently, F43I associates with wtCD4 oligomers and interferes with the formation of functional class II MHC binding structures. In contrast, F43I does not affect the binding of gp120 to wtCD4, implying that gp120 binds to a CD4 monomer. By production and characterization of chimeric CD4 molecules, rye show that domains 3 and/or 4 appear to be involved in oligomerization. Several models of the CD4-class II MHC interaction are offered, including the possibility that one or two CD4 molecules initially interact with class II MHC dimers and further associate to create larger complexes important for facilitating T-cell receptor crosslinking. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP SAKIHAMA, T (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI27336] NR 32 TC 92 Z9 98 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 3 PY 1995 VL 92 IS 14 BP 6444 EP 6448 DI 10.1073/pnas.92.14.6444 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RG736 UT WOS:A1995RG73600047 PM 7604010 ER PT J AU KAUFMAN, DS SCHOON, RA ROBERTSON, MJ LEIBSON, PJ AF KAUFMAN, DS SCHOON, RA ROBERTSON, MJ LEIBSON, PJ TI INHIBITION OF SELECTIVE SIGNALING EVENTS IN NATURAL-KILLER-CELLS RECOGNIZING MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-TYROSINE KINASE; NK CLONES; PHOSPHORYLATION; RECOGNITION; CYTOTOXICITY; SPECIFICITY; ASSOCIATION; EXPRESSION; ACTIVATION; MOLECULES AB Many studies have characterized the transmembrane signaling events initiated after T-cell antigen receptor recognition of major histocompatibility complex (MHC)-bound peptides, Yet, little is known about signal transduction from a set of MHC class I recognizing receptors on natural killer (NK) cells whose ligation dramatically inhibits NK cell-mediated killing. In this study we evaluated the influence of MHC recognition on the proximal signaling events in NK cells binding tumor targets. We utilized two experimental models where NK cell-mediated cytotoxicity was fully inhibited by the recognition of specific MHC class I molecules, NK cell binding to either class I-deficient or class I-transfected target cells initiated rapid protein tyrosine kinase activation, In contrast, whereas NR cell binding to class I-deficient targets led to inositol phosphate release and increased intracellular free calcium ([Ca2+](i)), NK recognition of class I-bearing targets did not induce the activation of these phospholipase C-dependent signaling events, The recognition of class I by NK cells clearly had a negative regulatory effect since blocking this interaction using anti-class I F(ab')(2) fragments increased inositol 1,4,5-trisphosphate release and [Ca2+](i) and increased the lysis of the targets. These results suggest that one of the mechanisms by which NK cell recognition of specific MHC class I molecules can block the development of cell-mediated cytotoxicity is by inhibiting specific critical signaling events. C1 MAYO CLIN & MAYO FDN,DEPT IMMUNOL,ROCHESTER,MN 55905. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. FU NCI NIH HHS [CA47752] NR 33 TC 78 Z9 79 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 JUL 3 PY 1995 VL 92 IS 14 BP 6484 EP 6488 DI 10.1073/pnas.92.14.6484 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RG736 UT WOS:A1995RG73600055 PM 7604018 ER PT J AU PETROPOULOS, AE SCHAFFER, BK CHENEY, ML ENOCHS, S ZIMMER, C WEISSLEDER, R AF PETROPOULOS, AE SCHAFFER, BK CHENEY, ML ENOCHS, S ZIMMER, C WEISSLEDER, R TI MR-IMAGING OF NEURONAL TRANSPORT IN THE GUINEA-PIG FACIAL-NERVE - INITIAL FINDINGS SO ACTA OTO-LARYNGOLOGICA LA English DT Article DE FACIAL NERVE; MAGNETIC RESONANCE IMAGING; NERVOUS SYSTEM; AXONAL TRANSPORT; IRON OXIDE; WHEAT GERM AGGLUTININ ID SLOW AXONAL-TRANSPORT; MANAGEMENT AB Certain dextran coated iron oxides such as MION (monocrystalline iron oxide nanocompound) coupled to wheat germ agglutinin (MION-WGA) have been shown to exhibit i) neuronal uptake ii) axonal transport and iii) strong magnetic effects on tissues (superparamagnetism) in which they are localized. In the current study, we utilized such an agent to visualize axonal transport in the facial nerve in vivo by magnetic resonance (MR) imaging. Following injection of the compound into the facial nerves of guinea pigs, MR images were obtained at multiple time points (1, 3 and 5 days) and the imaged tissues were processed for subsequent histological examination. In nerves that had been injected with MION-WGA, the entire nerve appeared as a uniformly hypointense structure with a calculated transport rate of 5 mm/day. By 3 days, the agent within the facial nerve was traceable by MRI from a site of injection in the buccal branch to the stylomastoid foramen. Fluorescence and autoradiography studies confirmed axonal transport. These results show that MION-based magnetopharmaceuticals can be used to demonstrate slow axonal transport, and thereby visualize functional peripheral nerves in vivo by MR imaging. The method holds promise for developmental neuroscience research as well as a method to detect neural abnormalities by MR imaging. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,MAGNET RESONANCE PHARMACEUT PROGRAM,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02114. FU NCI NIH HHS [1ROI CA 54886-01]; NIDCD NIH HHS [5T32 DC00020] NR 17 TC 12 Z9 12 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD JUL PY 1995 VL 115 IS 4 BP 512 EP 516 DI 10.3109/00016489509139358 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA RF524 UT WOS:A1995RF52400009 PM 7572127 ER PT J AU WEISSMAN, NJ PALACIOS, IF WEYMAN, AE AF WEISSMAN, NJ PALACIOS, IF WEYMAN, AE TI DYNAMIC EXPANSION OF THE CORONARY-ARTERIES - IMPLICATIONS FOR INTRAVASCULAR ULTRASOUND MEASUREMENTS SO AMERICAN HEART JOURNAL LA English DT Article ID ANGIOPLASTY AB The majority of coronary artery blood flow occurs in diastole; however, systolic epicardial coronary artery expansion has been described. With the advent of intravascular ultrasound, precise measurements of arterial structures with excellent spacial and temporal resolution are now readily available. However, the effect of dynamic expansion of the coronary arteries on routine intravascular ultrasound measurements has not been assessed. The purpose of thisstudy was to determine in vivo the presence, timing, and extent of dynamic changes in the coronary arteries and saphenous vein grafts and to assess their implications for intravascular ultrasound measurements. Intravascular ultrasound images were obtained with simultaneous electrocardiographic monitoring in 202 coronary artery and 50 saphenous vein graft sites in 32 patients with varying plaque burden and morphologic features. Arterial, luminal, and plaque area were measured at end-diastole and early, mid-, and end-systole. Coronary luminal diameter increased 2.1%; luminal area increased 8.1%; arterial area increased 3.7%; and plaque area decreased 4.9% during mid and late systole (p < 0.01). There was no detectable cyclic change in saphenous vein graft dimensions. In coronary arteries there was significant systolic expansion of the artery and lumen and systolic thinning of the plaque. The magnitude of dynamic luminal area change was greater than the variability in measurement and thus warrants gating to the cardiac cycle. The lack of dynamic change in saphenous vein grafts and the relatively small dynamic change in luminal diameter and arterial and plaque areas suggest nominal utility in gating these measurements to the cardiac cycle. C1 MASSACHUSETTS GEN HOSP,CARDIAC ULTRASOUND LAB,BOSTON,MA. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CARDIAC CATHETERIZAT LAB,BOSTON,MA. NR 9 TC 26 Z9 27 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUL PY 1995 VL 130 IS 1 BP 46 EP 51 DI 10.1016/0002-8703(95)90234-1 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RG311 UT WOS:A1995RG31100008 PM 7611122 ER PT J AU CHUN, SH SAGER, PT STEVENSON, WG NADEMANEE, K MIDDLEKAUFF, HR SINGH, BN AF CHUN, SH SAGER, PT STEVENSON, WG NADEMANEE, K MIDDLEKAUFF, HR SINGH, BN TI LONG-TERM EFFICACY OF AMIODARONE FOR THE MAINTENANCE OF NORMAL SINUS RHYTHM IN PATIENTS WITH REFRACTORY ATRIAL-FIBRILLATION OR FLUTTER SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LOW-DOSE AMIODARONE; VENTRICULAR TACHYARRHYTHMIAS; QUINIDINE THERAPY; CONVERSION; CARDIOVERSION; ARRHYTHMIAS; STROKE AB The purpose of this study was to examine the efficacy and safety of amiodarone to maintain sinus rhythm in patients with refractory atrial fibrillation or flutter. One hundred ten patients with atrial fibrillation or flutter, refractory to greater than or equal to 1 class I antiarrhythmic agents (mean +/- SD 2.5 +/- 1.5, median 2), were given low-dose amiodarone (mean maintenance dose 268 +/- 100 mg/day) to determine its efficacy to maintain normal sinus rhythm after chemical or electrical cardioversion. Fifty-three patients had chronic and 57 patients had paroxysmal atrial fibrillation or flutter. Mean age of the study population was 60 +/- 13 years, and the mean follow-up was 36 +/- 38 months (range 31 days to 137 months). Actuarial rates for maintenance of sinus rhythm were 0.87, 0.70, and 0.55 at 1, 3, and 5 years, respectively. Twenty-one patients (19%) with arrhythmia recurrence had an increase in amiodarone dose, and after a mean additional follow-up of 2.5 years, 86% remained in normal sinus rhythm. The only observed predictor of atrial fibrillation or flutter recurrence was paroxysmal arrhythmia (40% recurrence vs 9% in patients with chronic atrial fibrillation or flutter; p<0.001). Actuarial rates for withdrawal because of adverse effects were 0.08, 0.22, and 0.30 at 1, 3, and 5 years, respectively. The most frequent adverse effects necessitating withdrawal were skin discoloration (4.5%), pulmonary fibrosis (3.6%; none fatal), and thyroid toxicity (2.7%). No deaths occurred during the study period. In conclusion, amiodarone has a high degree of efficacy for maintaining normal sinus rhythm in patients with atrial fibrillation or flutter, with a relatively low incidence of adverse effects necessitating withdrawal. C1 W LOS ANGELES VET AFFAIRS MED CTR,DIV CARDIOL,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DIV CARDIOL,LOS ANGELES,CA 90024. NR 22 TC 144 Z9 155 U1 0 U2 0 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 JUL 1 PY 1995 VL 76 IS 1 BP 47 EP 50 DI 10.1016/S0002-9149(99)80799-1 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RE738 UT WOS:A1995RE73800009 PM 7793402 ER PT J AU LEAF, DA CONNOR, WE BARSTAD, L SEXTON, G AF LEAF, DA CONNOR, WE BARSTAD, L SEXTON, G TI INCORPORATION OF DIETARY N-3 FATTY-ACIDS INTO THE FATTY-ACIDS OF HUMAN ADIPOSE-TISSUE AND PLASMA-LIPID CLASSES SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE ADIPOSE TISSUE; FISH OIL; EICOSAPENTAENOIC ACID; DOCOSAHEXAENOIC ACID ID CORONARY HEART-DISEASE; EICOSAPENTAENOIC ACID; DOCOSAHEXAENOIC ACID; FISH CONSUMPTION; MEN; OIL; MORTALITY AB The consumption of n-3 fatty acids from seafood has been related to a lower incidence of coronary artery disease. Adipose tissue composition has served as a biological marker of chronic ingestion of many dietary polyunsaturated fatty acids. However, the incorporation of n-3 fatty acids into the fat depots has not been studied in humans. Daily dietary supplementation with greater than or equal to 10 g n-3 fatty acids from fish oil for > 12 mo resulted in significantly greater 20:5n-3, 22:5n-3, and 22:6n-3 concentrations in fatty acids of adipose tissue, and a greater 20:5n-3 fatty acid content in plasma Lipid classes (cholesterol esters, phospholipids, and free fatty acids) of supplemented subjects compared with nonsupplemented control subjects. Combined values for all subjects indicated that fatty acid concentrations of n-3 plasma lipid classes, including 20:5n-3, 22:5n-3, 22:6n-3, and total n-3, significantly correlated with corresponding concentrations of fatty acids in adipose tissue. These findings indicate that the long-term ingestion of large amounts of n-3 fatty acids in humans resulted in their incorporation into the adipose tissue fatty acids. Incorporation of the fatty acids into adipose tissue warrants consideration for use in clinical studies requiring precise documentation of long-term n-3 fatty acid consumption. C1 OREGON HLTH SCI UNIV,DEPT MED,PORTLAND,OR 97201. RP LEAF, DA (reprint author), UNIV CALIF LOS ANGELES,W LOS ANGELES VET ADM MED CTR,DEPT MED,DIV GEN INTERNAL MED 69111G,LOS ANGELES,CA 90073, USA. NR 35 TC 84 Z9 85 U1 0 U2 5 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 JUL PY 1995 VL 62 IS 1 BP 68 EP 73 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RG808 UT WOS:A1995RG80800009 PM 7598068 ER PT J AU SHIH, VE FRINGER, JM MANDELL, R KRAUS, JP BERRY, GT HEIDENREICH, RA KORSON, MS LEVY, HL RAMESH, V AF SHIH, VE FRINGER, JM MANDELL, R KRAUS, JP BERRY, GT HEIDENREICH, RA KORSON, MS LEVY, HL RAMESH, V TI A MISSENSE MUTATION (1278T) IN THE CYSTATHIONINE BETA-SYNTHASE GENE PREVALENT IN PYRIDOXINE-RESPONSIVE HOMOCYSTINURIA, AND ASSOCIATED WITH MILD CLINICAL PHENOTYPE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DEFICIENCY; PATIENT AB Cystathionine beta-synthase (CBS) deficiency is an autosomal recessive disorder characterized by homocystinuria and multisystem clinical disease. Patients responsive to pyridoxine usually have a milder clinical phenotype than do nonresponsive patients, and we studied the molecular pathology of this disorder in an attempt to understand the molecular basis of the clinical variation. We previously reported a T833C transition in exon 8 causing a substitution of threonine for isoleucine at codon 278 (I278T). By PCR amplification and sequencing of exon 8 from genomic DNA we have now detected the I278T mutation in 7 of 11 patients with in vivo pyridoxine responsiveness and in 0 of 27 pyridoxine-nonresponsive patients. Two pyridoxine-responsive patients are homezygous and five are heterozygous for I278T. We have now observed the I278T mutation in 41% (9 of 22) of the independent alleles in pyridoxine-responsive patients of varied ethnic backgrounds. In two of the compound heterozygotes we identified a novel mutation (G139R and E144K) in the other allele. The finding that the two patients who are homozygous for I278T have only ectopia lentis and mild bone demineralization suggests that this mutation is associated with both in vivo pyridoxine responsiveness and mild clinical disease. Compound heterozygous patients who have one copy of this missense mutation are likely to retain some degree of pyridoxine responsiveness. C1 MASSACHUSETTS GEN HOSP,AMINO ACID DISORDER LAB,CHILDRENS SERV,BOSTON,MA 02129. CHILDRENS HOSP,BOSTON,MA. UNIV COLORADO,SCH MED,DENVER,CO. CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA 19104. UNIV ARIZONA,TUCSON,AZ. RP SHIH, VE (reprint author), MASSACHUSETTS GEN HOSP,AMINO ACID DISORDER LAB,NEUROL SERV,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NINDS NIH HHS [NS05096] NR 14 TC 42 Z9 44 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 JUL PY 1995 VL 57 IS 1 BP 34 EP 39 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA RE629 UT WOS:A1995RE62900004 PM 7611293 ER PT J AU CLARK, EC SILVER, SM HOLLICK, GE RINALDI, MG AF CLARK, EC SILVER, SM HOLLICK, GE RINALDI, MG TI CONTINUOUS AMBULATORY PERITONEAL-DIALYSIS COMPLICATED BY AUREOBASIDIUM-PULLULANS PERITONITIS SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Note DE PERITONITIS; CONTINUOUS AMBULATORY PERITONEAL DIALYSIS; AUREOBASIDIUM; AMPHOTERICIN B; DEMATIACEOUS FUNGUS ID FUNGAL PERITONITIS; INFECTION; PATIENT; CHILDREN AB We describe a case of peritonitis caused by Aureobasidium pullulans in a patient on continuous ambulatory peritoneal dialysis (CAPD). This dematiaceous fungus rarely causes infection in humans and to date has not been reported as an etiology of CAPD-associated peritonitis. The patient was managed successfully with peritoneal catheter removal and a prolonged course of intravenous amphotericin B, allowing resumption of CAPD. In vitro susceptibility testing confirmed sensitivity of this organism to amphotericin B. C1 ROCHESTER GEN HOSP,DEPT PATHOL & LAB MED,ROCHESTER,NY 14621. UNIV TEXAS,AUDIE L MURPHY MEM VET HOSP,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78285. RP CLARK, EC (reprint author), UNIV ROCHESTER,ROCHESTER GEN HOSP,SCH MED & DENT,DEPT MED,NEPHROL UNIT,1425 PORTLAND AVE,ROCHESTER,NY 14621, USA. NR 20 TC 25 Z9 25 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PD JUL-AUG PY 1995 VL 15 IS 4 BP 353 EP 355 DI 10.1159/000168863 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA RL424 UT WOS:A1995RL42400015 PM 7573197 ER PT J AU KRUG, J CHIAVELLI, M BERRY, I EVANS, C JOYNER, M KITTAY, R MELANSON, A STOUT, K WAY, R EPSTEIN, ODD BERSON, F LATINA, M MELAMED, S JOHNSON, E LINDENMEYER, A MCGEE, R PIVABOWE, D SMITH, TJ WILENSKY, J TESSLER, H FROHLICHSTEIN, D ANDERSON, J JEDNOCK, N PETERSON, R NAIL, C MILLMAN, K SIEGEL, H SPIGELMAN, V SPRINCZ, M BECKMAN, H CYRLIN, M CZEDIK, C RITCH, R PODOLSKY, M STEINBERGER, D STOCK, L ABDULAZIM, J JOHNSON, M KRANTZ, J SWEENEY, V CUNNINGHAM, J MARANAN, L TERRERO, A THEERTHAM, M SPAETH, G KATZ, LJ BECKERSHOFF, C DEPIANO, D MOLINEAUX, J NICHOLS, J PETRAKIS, P SLAGLE, J CAPRIOLI, J SIMMONS, S STRANG, S CAPONE, M SAMMARTINO, M SANDY, R WILSON, R WITTKOWSKI, D VELATHOMAS, MA HARBIN, T LEEF, D GOMEZ, S GEMMILL, M GILMAN, J MOORE, K SWORDS, R WRIGHT, J CAMPBELL, D CARLTON, S FRANK, MK LASALLE, J MAIO, M NICHOLAS, P SNIPES, C WEBER, P KAPETANSKY, F MCKINNEY, K CLARK, M MOORE, D SIMMONS, L JONES, S RADIUS, R KLEWIN, K SOPA, J GUNDERSEN, B RICHIE, M WIPPLINGER, W BAUER, D LANGE, C BENCE, D HELT, P KAVANAGH, J WOLF, C LEE, PF HSU, CT PLACHTE, S CHERRIER, K MEHU, M MINCKLER, D BAERVELDT, G BENAVENTE, A CLARK, T DELGADO, S GOODMAN, M GRIFFAY, E TRUJILLO, M ZIMMERMAN, T AREND, L LARSON, K THIELE, R VICKERS, N HERSCHLER, J DURANT, W DAVIS, M HAYMORE, D MEINERT, C STERNBERG, A AMENDLIBERCCI, D BROWN, V DODGE, J GERCZAK, C ISAACSON, M LEVINE, C MAGUIRE, M MEINERT, J TONASCIA, J TONASCIA, S WETZEL, D HAWKINS, B BONDS, B CANNER, J CONNER, K DICKERSIN, K GUNTHER, G THOMAS, B TU, N XU, C SLAGLE, S BARONE, L GROSS, P JACKSON, M MORGANSTERN, S STRONG, C CRABTREE, J SUNDERMEYER, S DUDLEY, P SURAN, A LACHIN, J DUEKER, D GAASTERLAND, D KAUFMAN, P LESKE, C AF KRUG, J CHIAVELLI, M BERRY, I EVANS, C JOYNER, M KITTAY, R MELANSON, A STOUT, K WAY, R EPSTEIN, ODD BERSON, F LATINA, M MELAMED, S JOHNSON, E LINDENMEYER, A MCGEE, R PIVABOWE, D SMITH, TJ WILENSKY, J TESSLER, H FROHLICHSTEIN, D ANDERSON, J JEDNOCK, N PETERSON, R NAIL, C MILLMAN, K SIEGEL, H SPIGELMAN, V SPRINCZ, M BECKMAN, H CYRLIN, M CZEDIK, C RITCH, R PODOLSKY, M STEINBERGER, D STOCK, L ABDULAZIM, J JOHNSON, M KRANTZ, J SWEENEY, V CUNNINGHAM, J MARANAN, L TERRERO, A THEERTHAM, M SPAETH, G KATZ, LJ BECKERSHOFF, C DEPIANO, D MOLINEAUX, J NICHOLS, J PETRAKIS, P SLAGLE, J CAPRIOLI, J SIMMONS, S STRANG, S CAPONE, M SAMMARTINO, M SANDY, R WILSON, R WITTKOWSKI, D VELATHOMAS, MA HARBIN, T LEEF, D GOMEZ, S GEMMILL, M GILMAN, J MOORE, K SWORDS, R WRIGHT, J CAMPBELL, D CARLTON, S FRANK, MK LASALLE, J MAIO, M NICHOLAS, P SNIPES, C WEBER, P KAPETANSKY, F MCKINNEY, K CLARK, M MOORE, D SIMMONS, L JONES, S RADIUS, R KLEWIN, K SOPA, J GUNDERSEN, B RICHIE, M WIPPLINGER, W BAUER, D LANGE, C BENCE, D HELT, P KAVANAGH, J WOLF, C LEE, PF HSU, CT PLACHTE, S CHERRIER, K MEHU, M MINCKLER, D BAERVELDT, G BENAVENTE, A CLARK, T DELGADO, S GOODMAN, M GRIFFAY, E TRUJILLO, M ZIMMERMAN, T AREND, L LARSON, K THIELE, R VICKERS, N HERSCHLER, J DURANT, W DAVIS, M HAYMORE, D MEINERT, C STERNBERG, A AMENDLIBERCCI, D BROWN, V DODGE, J GERCZAK, C ISAACSON, M LEVINE, C MAGUIRE, M MEINERT, J TONASCIA, J TONASCIA, S WETZEL, D HAWKINS, B BONDS, B CANNER, J CONNER, K DICKERSIN, K GUNTHER, G THOMAS, B TU, N XU, C SLAGLE, S BARONE, L GROSS, P JACKSON, M MORGANSTERN, S STRONG, C CRABTREE, J SUNDERMEYER, S DUDLEY, P SURAN, A LACHIN, J DUEKER, D GAASTERLAND, D KAUFMAN, P LESKE, C TI THE GLAUCOMA LASER TRIAL (GLT) .6. TREATMENT GROUP-DIFFERENCES IN VISUAL-FIELD CHANGES SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID AUTOMATED PERIMETRY; THRESHOLD PERIMETRY; PATIENT EXPERIENCE; VARIABILITY AB PURPOSE: To determine the differences in visual fields during 42 months (3 1/2 years) of follow up between eyes treated with argon laser trabeculoplasty first and eyes treated with topical medication first in patients with newly diagnosed primary open-angle glaucoma. METHODS: Visual field examinations were obtained at enrollment, three and six months, and at six-month intervals thereafter during follow-up of 271 patients enrolled in the Glaucoma Laser Trial, Numeric analyses of the examination results, including global indices and patterns of localized changes, as well as masked subjective clinical impression, were used to compare the two treatment groups. RESULTS: The mean threshold for eyes treated with laser trabeculoplasty first was 0.3 dB better than that for eyes treated with topical medication first averaged over follow-up (95% confidence interval, [-0.1, 0.7]; P = .17), More eyes treated with topical medication first (82 [31%] of 261 eyes) than eyes treated with laser trabeculoplasty first (61 [23%] of 261 eyes) had confirmed localized deterioration at least once during follow-up (P = .02), Improvement was nearly twice as common as deterioration on masked subjective impression in both groups through 30 months (2 1/2 years), Eyes treated with laser trabeculoplasty first were judged to have slightly more improvement and slightly less deterioration than eyes treated with topical medication first. CONCLUSION: During follow up, measures of visual field status for eyes treated with laser trabeculoplasty first were slightly better than those for eyes treated with topical medication first, Statistical significance was attained for only some of the differences, and the clinical implications of such small differences are not known. C1 MASSACHUSETTS EYE & EAR INFIRM, BOSTON, MA 02114 USA. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, CTR GLAUCOMA LASER TRIAL COORDINATING, BALTIMORE, MD 21205 USA. NEW YORK EYE & EAR INFIRM, NEW YORK, NY 10003 USA. EMORY EYE CTR, ATLANTA, GA USA. OHIO STATE UNIV, COLUMBUS, OH 43210 USA. MED COLL WISCONSIN, MILWAUKEE, WI 53226 USA. ALBANY MED COLL, ALBANY, NY USA. ESTELLE DOHENY EYE FDN, LOS ANGELES, CA 90033 USA. ALTON OCHSNER MED FDN & OCHSNER CLIN, NEW ORLEANS, LA 70121 USA. UNIV ARIZONA, TUCSON, AZ USA. WILLS EYE HOSP & RES INST, CTR DISC STEREOPHOTOG READING, PHILADELPHIA, PA USA. UNIV ILLINOIS, EYE & EAR INFIRM, CTR VISUAL FIELD READING, CHICAGO, IL 60612 USA. SINAI HOSP DETROIT, CHAIRMANS OFF, DETROIT, MI USA. NEI, PROJECT OFF, BETHESDA, MD 20892 USA. RI Dickersin, Kay/A-4576-2008 NR 23 TC 20 Z9 20 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 1995 VL 120 IS 1 BP 10 EP 22 PG 13 WC Ophthalmology SC Ophthalmology GA RH066 UT WOS:A1995RH06600002 ER PT J AU MEGERIAN, CA SOFFERMAN, RA MCKENNA, MJ EAVEY, RD NADOL, JB AF MEGERIAN, CA SOFFERMAN, RA MCKENNA, MJ EAVEY, RD NADOL, JB TI FIBROUS DYSPLASIA OF THE TEMPORAL BONE - 10 NEW CASES DEMONSTRATING THE SPECTRUM OF OTOLOGIC SEQUELAE SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Otological-Society CY MAY 07-08, 1994 CL PALM BEACH, FL SP Amer Otol Soc ID OSSIFYING FIBROMA AB Fibrous dysplasia involving the temporal bone is unusual. The most common initial findings are stenosis of the external auditory canal and conductive hearing loss. The frequency of sensorineural hearing loss and facial paresis as complications of fibrous dysplasia have been poorly documented in the past. Forty-three cases of fibrous dysplasia of the temporal bone previously published in the otolaryngologic literature are reviewed, and 10 new cases are reported. in addition to age, sex, and frequency of various presenting complaints, the audiometric, radiographic, and surgical data are evaluated in both groups to better describe the manifestations of disease, degree and type of hearing loss, and success of surgical intervention. In nearly 70% of cases in this study, fibrous dysplasia was monostotic. Although most patients had a conductive hearing loss, 17% of patients demonstrated profound sensorineural hearing loss ascribable to the lesion, and facial nerve sequelae were noted in nearly 10% of cases. Cholesteatoma complicated almost 40% of cases, usually in the form of a canal cholesteatoma. Ten new cases of temporal bone fibrous dysplasia are described not only to further clarify the spectrum of otologic sequelae but also to help illustrate available treatment options. In addition, th is report documents, in th ree new cases, the previously undescribed progression of conductive hearing loss to profound sensorineural deafness secondary to fibrous dysplasia. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. UNIV VERMONT,SCH MED,DEPT SURG,DIV OTOLARYNGOL,BURLINGTON,VT 05405. NR 49 TC 44 Z9 49 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD JUL PY 1995 VL 16 IS 4 BP 408 EP 419 PG 12 WC Otorhinolaryngology SC Otorhinolaryngology GA RG142 UT WOS:A1995RG14200003 PM 8588639 ER PT J AU ROSOWSKI, JJ MERCHANT, SN AF ROSOWSKI, JJ MERCHANT, SN TI MECHANICAL AND ACOUSTIC ANALYSIS OF MIDDLE-EAR RECONSTRUCTION SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article ID MEASURING SYSTEM; UMBO VIBRATION; STAPEDECTOMY; STAPEDOTOMY AB Existing mechanical and acoustic models of the human middle ear are used to investigate the expected performance of various middle ear reconstructive procedures. Although the results of these analyses generally are consistent with observed surgical results, such an analytic approach enables the formation of some simple rules for maximizing middle ear function after stapedectomy and tympanomastoid surgery. Model analyses predict the following: (1) stapes prostheses of 0.6 to 0.8 mm in diameter produce air-bone gaps of less than 12 dB; smaller diameter prostheses produce larger air-bone gaps; (2) the mass of a stapedectomy or ossicular replacement prosthesis can be 16 times greater than that of the stapes with little effect on the hearing result; (3) the volume of the middle ear air spaces after tympanomastoid surgery should be at least 0.5 cc for optimal acoustic results; and (4) in a type IV tympanoplasty, the effectiveness of the round window graft (acoustic shield) is an important parameter determining the hearing result; the shield should be as impedant (stiff) as possible for optimal postoperative hearing. The model framework described in this report hopefully can be used to investigate the effect of variations in other surgical procedures and help define new procedures. C1 MIT,ELECTR RES LAB,CAMBRIDGE,MA 02139. RP ROSOWSKI, JJ (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,EATON PEABODY LAB,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [K08 DC 00088, P01 DC 00119] NR 59 TC 87 Z9 91 U1 2 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD JUL PY 1995 VL 16 IS 4 BP 486 EP 497 PG 12 WC Otorhinolaryngology SC Otorhinolaryngology GA RG142 UT WOS:A1995RG14200014 PM 8588650 ER PT J AU HSU, DW EFIRD, JT HEDLEYWHYTE, ET AF HSU, DW EFIRD, JT HEDLEYWHYTE, ET TI PROGNOSTIC ROLE OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR IN HUMAN GLIOMAS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HUMAN-BRAIN TUMORS; BREAST-CANCER; MONOCLONAL-ANTIBODY; EARLY RELAPSE; TISSUE; CELL; LOCALIZATION; CARCINOMAS; INHIBITION; ASTROCYTOMAS AB Urokinase-type plasminogen activator (u-PA) is a 54-kd enzyme shown to participate an tissue degradation under certain normal and pathological conditions, including cancer invasion and metastasis. Increased u-PA expression has been found in cancers of the breast, lung, colon, and prostate, and correlated with worse outcome in patients with lung and breast cancer. We examined the correlation between u-PA expression in gliomas and patient survival. Seventy-seven gliomas from 41 men and 36 women (ages 2 to 73) were immunostained for u-PA using monoclonal antibody 394 directed against human urokinase. The tumors included 32 grade 4, 16 grade 3, and 20 grade 2 astrocytomas (Daumas-Duport scale), and 9 pilocytic astrocytomas. Strong cytoplasmic staining was found in tumor cells of all grade 4, most of the grade 3, and a few of the lower grade tumors. Adjacent normal brain tissue showed faint staining associated with subpial cell processes and white matter fibers. The fiber staining was stronger in brain tissue infiltrated by tumor cells. Cytoplasmic u-PA staining in tumor cells was scored from 0 (no staining) to 6 (strong and widespread staining). The mean u-PA scores were 5.08 +/- 0.19 (mean +/- SEM) for grade 4, 3.97 +/- 0.46 for grade 3, 1.65 +/- 0.39 for grade 2, and 1.22 +/- 0.60 for pilocytic astrocytomas. The statistical analysis was based on cytoplasmic staining only. Analysis of variance revealed significant differences between the mean u-PA scores of different grades (P < 0.02 between grades 4 and 3, and P = 0.0001 between grades 4 or 3 and 2, and between grades 4 or 3 and pilocytic), except between grade 2 and pilocytic astrocytomas. Univariate analysis indicated that u-PA score greater than or equal to 4 (P = 0.0001), tumor grade 4 (P = 0.01), and age >50 (P < 0.001) were all significant predictors for shorter disease survival. A three-way interaction model by multivariate analysis indicated that u-PA score greater than or equal to 4, tumor grade 4, and age >50, taken together, were significant factors for shorter patient survival (P < 0.02). We conclude that u-PA may be used as a prognostic tool in conjunction with tumor grade and patients' age in predicting survival for patients with gliomas. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT RADIAT THERAPY,BOSTON,MA. RP HSU, DW (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,DIV NEUROPATHOL,WARREN 3,BOSTON,MA 02114, USA. NR 55 TC 83 Z9 86 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1995 VL 147 IS 1 BP 114 EP 123 PG 10 WC Pathology SC Pathology GA RH023 UT WOS:A1995RH02300012 PM 7604873 ER PT J AU SIMON, FR LEFFERT, HL ELLISMAN, M IWAHASHI, M DEERINCK, T FORTUNE, J MORALES, D DAHL, R SUTHERLAND, E AF SIMON, FR LEFFERT, HL ELLISMAN, M IWAHASHI, M DEERINCK, T FORTUNE, J MORALES, D DAHL, R SUTHERLAND, E TI HEPATIC NA+-K+-ATPASE ENZYME-ACTIVITY CORRELATES WITH POLARIZED BETA-SUBUNIT EXPRESSION SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE IMMUNOFLUORESCENCE; IMMUNOGOLD LABELING; SINUSOIDAL; BILE CANALICULAR; BASOLATERAL DOMAIN; SODIUM-POTASSIUM ADENOSINE-TRIPHOSPHATASE ID NA+,K+-ATPASE ALPHA-SUBUNIT; TISSUE-SPECIFIC EXPRESSION; MEMBRANE LIPID FLUIDITY; RAT-BRAIN; CATALYTIC SUBUNIT; IMMUNOELECTRON MICROSCOPY; ADENOSINE-TRIPHOSPHATASE; DIFFERENTIAL EXPRESSION; PLASMA-MEMBRANES; NERVOUS-SYSTEM AB We have examined underlying causes for observations made in hepatocytes in which catalytic subunits of Na+-K+-ATPase are found both in bile canalicular (apical) and sinusoidal (basolateral) membrane domains, whereas functional activity is associated preferentially with sinusoidal membrane sites. In a series of parallel studies, we determined by both light and electron microscopy that Na+-K+-ATPase alpha-subunits were localized to both membrane domains of hepatocytes. With the use of purified liver plasma membrane subfractions, ouabain inhibition curves demonstrated similar inhibition constants (inhibition constant 10(-5) M), and immunoblots using alpha(1)-, alpha(2)-, alpha(3)-polyclonal and monoclonal antibodies demonstrated antigenic sites predominantly for alpha(1) in both membrane fractions. Also, Northern blot hybridization analysis revealed only the alpha(1)-isoform in hepatocytes. In contrast to the bipolar distribution of the alpha(1)-subunit, the beta-subunit was identified only at the sinusoidal surface using fluorescence labeling with a monoclonal antibody. The beta(1)-isoform was demonstrated by Northern blot analysis and was present predominantly at the sinusoidal domain by immunoblotting with polyclonal antibodies. In addition to the bipolar distribution of oil, immunoblotting of liver plasma membrane subfractions demonstrated a symmetrical distribution of fodrin, ankyrin, actin, and E-cadherin at both domains. These results suggest that functionally competent alpha/beta-complexes form at the sinusoidal domain, whereas only alpha(1)-subunits are present at the apical pole. C1 DENVER VET AFFAIRS HOSP, DEPT MED, DENVER, CO 80262 USA. UNIV CALIF SAN DIEGO, DEPT PHARMACOL, LA JOLLA, CA 92093 USA. UNIV CALIF SAN DIEGO, CTR MOLEC GENET & NEUROBIOL, LA JOLLA, CA 92093 USA. RP SIMON, FR (reprint author), UNIV COLORADO, SCH MED, DEPT MED B145, HEPATOBILIARY RES CTR, 4200 E 9TH AVE, DENVER, CO 80262 USA. FU NIDDK NIH HHS [DK-28215, DK-34914, DK-15851] NR 51 TC 18 Z9 18 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 1995 VL 269 IS 1 BP C69 EP C84 PG 16 WC Cell Biology; Physiology SC Cell Biology; Physiology GA RK171 UT WOS:A1995RK17100011 PM 7631761 ER PT J AU LEWANDOWSKI, ED DAMICO, LA WHITE, LT YU, X AF LEWANDOWSKI, ED DAMICO, LA WHITE, LT YU, X TI CARDIAC RESPONSES TO INDUCED LACTATE OXIDATION - NMR ANALYSIS OF METABOLIC EQUILIBRIA SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE C-13; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; HEART; METABOLISM ID FATTY-ACID METABOLISM; PERFUSED RAT-HEART; C-13 NMR; INFARCT SIZE; IN-VIVO; MYOCARDIUM; SUBSTRATE; PYRUVATE; RECOVERY; CYCLE AB The role of lactate as a source of pyruvate oxidation in supporting cardiac work, energetics, and formation of oxidative metabolites was examined in normal myocardium. C-13 and P-31-nuclear magnetic resonance (NMR) spectra were acquired from isolated rabbit hearts supplied 2.5 mM [3-C-13]lactate or [3-C-13]pyruvate with or without stimulation of pyruvate dehydrogenase (PDH) by dichloroacetate (DCA). Similar workloads determined by rate-pressure products were noted with pyruvate (21,700 +/- 2,400; mean +/- SE) and lactate (18,970 +/- 1,510). Oxygen consumption was similar in all four groups with means between 19.0 and 22.2 mu mol . min(-1). g dry weight(-1) (SE = 1.6-2.0) as was the ratio of phosphocreatine to ATP with means between 1.8 and 2.1 (SE = 0.1-0.6). Intracellular pH, determined from P-31-NMR spectra, was essentially the same with pyruvate (1.06 +/- 0.02) and lactate (7.05 +/- 0.04). C-13 enrichment of glutamate was higher with lactate (92%) than with pyruvate (70%). Pyruvate plus DCA induced no change in glutamate content at 9-10 mu mol/g, but C-13 enrichment increased to 83%, while lactate plus DCA maintained enrichment at 90%. Levels of alpha-ketoglutarate were lower with lactate (1.81 mu mol/g) than with pyruvate (2.36 mu mol/g). Lactate plus DCA elevated glutamate by 60% with a proportional increase in alpha-ketoglutarate. Thus the balance between glutamate and alpha-ketoglutarate was affected by substrate supply only and not by PDH activation. The results suggest that the equilibrium between alpha-ketoglutarate and glutamate is sensitive to cytosolic redox state, an important consideration for C-13-NMR analyses that rely on glutamate. In conclusion, lactate and pyruvate are able to support similar function and energetics through differences in the balance of oxidative, intermediary metabolites. RP LEWANDOWSKI, ED (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL, CTR NUCL MAGNET RESONANCE, BLDG 149, BOSTON, MA 02129 USA. FU NHLBI NIH HHS [R01-HL-49244] NR 41 TC 16 Z9 16 U1 1 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 JUL PY 1995 VL 269 IS 1 BP H160 EP H168 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA RK177 UT WOS:A1995RK17700023 PM 7631845 ER PT J AU KIM, DK FUKUDA, T THOMPSON, BT COCKRILL, B HALES, C BONVENTRE, JV AF KIM, DK FUKUDA, T THOMPSON, BT COCKRILL, B HALES, C BONVENTRE, JV TI BRONCHOALVEOLAR LAVAGE FLUID PHOSPHOLIPASE A(2) ACTIVITIES ARE INCREASED IN HUMAN ADULT-RESPIRATORY-DISTRESS-SYNDROME SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE PHOSPHOLIPIDS; LIPASES; LUNG; EICOSANOIDS; FATTY ACIDS ID TUMOR-NECROSIS-FACTOR; ACUTE LUNG INJURY; SEPTIC SHOCK; RAT LUNG; PURIFICATION; PLATELETS; FORM; PANCREATITIS; NEUTROPHILS; SURFACTANT AB The role of phospholipase A(2) (PLA(2)) in lung injury in humans is unclear. Previous studies have failed to identify an increase in PLA(2) activity in bronchoalveolar lavage fluids (BALF) of patients with the adult respiratory distress syndrome (ARDS). In this study, increased phospholipase A(2) (PLA(2)) activity was detected in BALF from patients with ARDS. PLA(2) levels in BALF correlated positively with lung injury score in patients with lung disease. BALF PLA(2) activity in patients with ARDS was resolved into heparin binding and nonbinding activities. Both PLA(2) activities were increased in BALF of ARDS patients. The PLA(2) activity that bound to heparin was identified as a group II PLA(2) by its chromatographic characteristics, its inhibition by dithiothreitol, its substrate specificity, and its approximate molecular mass of 14 kDa. The second PLA(2) activity was further purified and found to require Ca2+ at a concentration > 2 x 10(-4) M for activity. This form of PLA(2) exhibited a neutral and broad pH optimum (pH 6.0-8.0) and hydrolyzed both phospha tidylethanolamine and phosphatidylcholine effectively. Its apparent molecular mass was estimated to be 80-90 M)a. Neither anti-pancreatic PLA(2) antiserum nor anti-pig spleen cytosolic 100-kDa PLA(2) antiserum immunoprecipitated the enzymatic activity. Thus at least two forms of PLA(2) are increased in activity in BALF of patients with ARDS, a group II PLA(2) and a biochemically and immunochemically form distinct from group I, group II, and cytosolic PLA(2). Increased lung PLA(2) activity may be important for the pathophysiology of ARDS. C1 MASSACHUSETTS GEN HOSP, MED SERV, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. FU NIDDK NIH HHS [DK-39773, DK-38452]; NINDS NIH HHS [NS-10828] NR 37 TC 75 Z9 79 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUL PY 1995 VL 269 IS 1 BP L109 EP L118 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA RJ961 UT WOS:A1995RJ96100017 PM 7631805 ER PT J AU DRAZEN, JM EVANS, JF STEVENS, RL SHIPP, MA AF DRAZEN, JM EVANS, JF STEVENS, RL SHIPP, MA TI INFLAMMATORY EFFECTOR MECHANISMS IN ASTHMA SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ENDOPEPTIDASE 24.11 ENKEPHALINASE; LEUKEMIA ANTIGEN CALLA; NEUTRAL ENDOPEPTIDASE; 5-LIPOXYGENASE-ACTIVATING PROTEIN; MEMBRANE-PROTEIN; CELL; IDENTIFICATION; LUNG; MODULATION; PROTEASES C1 BRIGHAM & WOMENS HOSP,DEPT IMMUNOL & RHEUMATOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,MERCK FROSST CTR THERAPEUT RES,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA 02115. RP DRAZEN, JM (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,DIV PULM,75 FRANCIS ST,BOSTON,MA 02115, USA. RI Drazen, Jeffrey/E-5841-2012 NR 23 TC 7 Z9 7 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUL PY 1995 VL 152 IS 1 BP 403 EP 407 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RH678 UT WOS:A1995RH67800064 PM 7599856 ER PT J AU LEE, FT DELONE, DR BEAN, DW BROGHAMMER, BG MACK, E PERLMAN, SB WEISS, JW AF LEE, FT DELONE, DR BEAN, DW BROGHAMMER, BG MACK, E PERLMAN, SB WEISS, JW TI ACUTE CHOLECYSTITIS IN AN ANIMAL-MODEL - FINDINGS ON COLOR DOPPLER SONOGRAPHY SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID GALLBLADDER; MANAGEMENT; OPERATION; DIAGNOSIS AB OBJECTIVE. The purpose of our study was to evaluate the color Doppler findings of acute cholecystitis in a controlled canine model. MATERIALS AND METHODS. Fourteen animals had a laparotomy: cystic duet ligation was done in eight, and incision with closure was performed in six control subjects. Animals were scanned in a blinded fashion preoperatively, immediately postoperatively, and on postoperative days 1-5. On postoperative day 5, a hepatobiliary scan was done with 2 mCi (74 MBq) Tc-99m-mebrofenin. Blinded histopathology was performed and correlated with imaging. RESULTS. Flow was seen in the wall of each gallbladder at some point during the postoperative course, demonstrating vascular patency Hepatobiliary scintigraphy confirmed cystic duct status in 12 cases; two animals died before radionuclide imaging was complete. Color Doppler signal decreased in the gallbladder wall in ligated dogs from postoperative day 1 to postoperative day 3 (p = .03 versus controls at postoperative day 2) and increasingly returned by postoperative day 5. Hyperemia was seen in only two cases (both with severe necrotizing cholecystitis) and only at postoperative day 5. Although not statistically significant, a weak trend of increasing flow with more severe pathologic grades of cholecystitis was observed (p = .20). CONCLUSIONS. in this animal model, loss of vascular signal (not hyperemia) at postoperative day 2 was the finding to diagnose early acute cholecystitis, although lack of flow can also be seen in some normal subjects. Flow tended to return by postoperative day 5, and it increased in some of the more severe cases of cholecystitis. Hyperemia was a somewhat useful sign of acute necrotizing cholecystitis. C1 UNIV WISCONSIN HOSP & CLIN,DEPT SURG,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT PATHOL,MADISON,WI 53705. RP LEE, FT (reprint author), UNIV WISCONSIN HOSP & CLIN,DEPT RADIOL,600 HIGHLAND AVE,MADISON,WI 53792, USA. OI DeLone, David/0000-0002-4211-8790 NR 23 TC 4 Z9 4 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1995 VL 165 IS 1 BP 85 EP 90 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RE240 UT WOS:A1995RE24000023 PM 7785640 ER PT J AU MAYOSMITH, WW LEE, MJ MCNICHOLAS, MMJ HAHN, PF BOLAND, GW SAINI, S AF MAYOSMITH, WW LEE, MJ MCNICHOLAS, MMJ HAHN, PF BOLAND, GW SAINI, S TI CHARACTERIZATION OF ADRENAL MASSES (LESS-THAN-5 CM) BY USE OF CHEMICAL-SHIFT MR-IMAGING - OBSERVER PERFORMANCE VERSUS QUANTITATIVE MEASURES SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID DIFFERENTIATION; CARCINOMA; BENIGN AB OBJECTIVE. The purposes of this study were to evaluate the ability of chemical shift MR imaging to differentiate 1- to 5-cm adrenal adenomas from metastases and to compare subjective interpretation with several different quantitative measures. SUBJECTS AND METHODS. Forty-three patients with 46 proved adrenal lesions (28 adenomas and 18 metastases) had MR imaging with a gradient-echo breath-hold technique and echo time varied to obtain in-phase and out-of-phase images. Qualitative analysis of the MR images was done by three experienced observers, who reported their confidence in diagnosing the benignity versus the malignancy of the adrenal masses on the basis of signal loss on out-of-phase images. Quantitative analysis was performed by calculating the difference in signal intensity between in-phase and out-of-phase images by use of regions of interest (signal intensity index) and by use of adrenal-liver, adrenal-spleen, and adrenal-muscle signal intensity ratios. Results between quantitative and qualitative measures were compared by use of receiver operating characteristic (ROC) analysis. RESULTS. The mean signal intensity was significantly different between adenomas and metastases on out-of-phase images (64 versus 98) (p < .0005) but not in-phase images (130 versus 122) (p = .47). The adrenal-spleen ratio discriminated between adenomas and metastases better than did the adrenal-liver ratio, the adrenal-muscle ratio, or the signal intensity index. No significant difference in interpretation among the three observers was evident (areas under the ROC curves, 0.93, 0.95, and 0.96). The performance of the observers was comparable to the results obtained with the adrenal-spleen ratio measurement (area under the ROC curve, 0.97). CONCLUSION. Experienced observers were able to differentiate adrenal adenomas from metastases just as well as quantitative measures. The adrenal-spleen ratio is the best quantitative means of distinguishing benign from malignant adrenal masses. Chemical shift MR imaging is a good but imperfect discriminator of adrenal adenomas. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP MAYOSMITH, WW (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,WHITE 2,FRUIT ST,BOSTON,MA 02114, USA. NR 18 TC 143 Z9 146 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1995 VL 165 IS 1 BP 91 EP 95 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RE240 UT WOS:A1995RE24000024 PM 7785642 ER PT J AU NIELSEN, GP DICKERSIN, GR PROVENZAL, JM ROSENBERG, AE AF NIELSEN, GP DICKERSIN, GR PROVENZAL, JM ROSENBERG, AE TI LIPOMATOUS HEMANGIOPERICYTOMA - A HISTOLOGIC, ULTRASTRUCTURAL AND IMMUNOHISTOCHEMICAL STUDY OF A UNIQUE VARIANT OF HEMANGIOPERICYTOMA SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE LIPOMA; HEMANGIOPERICYTOMA; SOFT TISSUE ID SPINDLE-CELL LIPOMA; SOFT-TISSUE; MICROVASCULAR PERICYTES; SMOOTH-MUSCLE; GLOMUS TUMORS; FOLLOW-UP; LIPOSARCOMA; DIFFERENTIATION; REASSESSMENT; EXPRESSION AB We report three cases of a unique, previously undescribed soft tissue tumor composed of mature adipocytes and hemangiopericytomatous areas, for which we propose the term lipomatous hemangiopericytoma. The tumors occurred in adults and were located in the sinonasal area, the soft tissue of the shoulder, and the retroperitoneum. The tumors ranged in size from 4 to 10 cm in greatest diameter and grossly were solid and ranged from tan to yellow. Histologically, they were composed of a variable admixture of benign lipomatous and hemangiopericytomatous components. Immunohistochemically, they stained with antibodies to vimentin and not to alpha-smooth-muscle actin, muscle-specific actin, desmin, S-100 protein, glial fibrillary acidic protein, epithelial membrane antigen, or keratin. Ultrastructurally, the cells constituting the hemangiopericytomatous areas had the features of pericytes, and no lipoblasts or transitional forms between lipocytes and pericytes were found. The histologic differential diagnosis of this neoplasm includes spindle-cell lipoma, angiolipoma, liposarcomas, tumors showing smooth muscle and adipocytic differentiation, and hemangiopericytoma infiltrating fat. Because of the small number of cases and the limited follow-up, we cannot be certain of their biologic behavior, although we expect that they are benign. Lipomatous hemangiopericytoma represents a distinctive pathologic entity that should be recognized and studied further. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA. DUKE UNIV,MED CTR,DEPT RADIOL,DURHAM,NC 27710. NR 37 TC 58 Z9 61 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 1995 VL 19 IS 7 BP 748 EP 756 DI 10.1097/00000478-199507000-00002 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA RD294 UT WOS:A1995RD29400002 PM 7793472 ER PT J AU OLIVA, E YOUNG, RH CLEMENT, PB BHAN, AK SCULLY, RE AF OLIVA, E YOUNG, RH CLEMENT, PB BHAN, AK SCULLY, RE TI CELLULAR BENIGN MESENCHYMAL TUMORS OF THE UTERUS - A COMPARATIVE MORPHOLOGIC AND IMMUNOHISTOCHEMICAL ANALYSIS OF 33 HIGHLY CELLULAR LEIOMYOMAS AND 6 ENDOMETRIAL STROMAL NODULES, 2 FREQUENTLY CONFUSED TUMORS SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE UTERUS; HIGHLY CELLULAR LEIOMYOMA; ENDOMETRIAL STROMAL NODULE ID SMOOTH-MUSCLE DIFFERENTIATION; MITOTICALLY ACTIVE LEIOMYOMAS; UTERINE LEIOMYOMAS; NEOPLASMS; SARCOMA; STROMOMYOMA; EXPRESSION; DIAGNOSIS AB Thirty-three highly cellular leiomyomas of the uterus from patients 29 to 65 (mean, 46) years of age and six endometrial stromal nodules from patients 41 to 53 (mean, 46) years of age are described. The patients usually presented with irregular uterine bleeding. Twenty-eight of the leiomyomas were intramural and five, submucosal. Eleven of 18 whose consistency is known were soft, fish-flesh, or rubbery, 10 were yellow or yellow-tan; one had a prominent cystic component. The tumors ranged from 0.5 to 15 cm (mean, 4.6 cm) in maximum dimension. On microscopic examination, they were densely cellular and composed of cells that ranged from round to spindle-shaped and had scanty cytoplasm. A focal fascicular pattern was present in all of the cases. Blood vessels were typically large; thick muscular walls and focally dilated lumens were a conspicuous feature of the majority of the neoplasms. Arterioles were evident focally in most of the tumors but were prominent in only one of them. Cleft-like spaces, some representing compressed vessels, others due to internodular edema, were present in 24 of the tumors and were conspicuous in 15 of them. The neoplasms typically exhibited focal irregular extension into the adjacent myometrium, and this feature was conspicuous in 18 of them. They often merged almost imperceptibly with the adjacent myometrium. All tumors were immunoreactive for desmin and 32 of 32 for alpha-smooth muscle actin. Two of the stromal nodules were polypoid intracavitary masses, three were submucosal, and one intramural. Five were completely or predominantly solid with cysts present focally in three of them; one tumor was predominantly cystic. The solid tissue was frequently yellow. Microscopic examination disclosed a diffuse growth of closely packed small cells with scanty cytoplasm and nuclei that lacked atypia. Three neoplasms contained cells with abundant foamy cytoplasm that were immunoreactive for CD68, indicating that they were histiocytes and not neoplastic cells. All the neoplasms had a prominent component of arterioles, which in one tumor had hyalinized walls. Five tumors were entirely well circumscribed and one predominantly well circumscribed with limited extension into the adjacent myometrium. The tumors were immunohistochemically negative for desmin. Four of the tumors were focally or diffusely immunoreactive for a-smooth muscle actin and muscle actin. The highly cellular leiomyomas caused frequent problems in diagnosis on routine staining. Nine of them were submitted for consultation with the diagnosis of an endometrial stromal tumor, either low-grade endometrial stromal sarcoma or endometrial stromal nodule, and in an additional nine cases, the contributing pathologist was uncertain of the differential between leiomyoma and an endometrial stromal tumor. Features contributing to this diagnostic confusion were the dense cellularity of the tumors, their prominent vascularity, and their irregular margins. Features favoring a diagnosis of highly cellular leiomyoma over a stromal tumor included a fascicular growth pattern, vessels of large caliber with thick muscular walls (contrasting with the small caliber and thinner walls of the typical arterioles of an endometrial stromal neoplasm), merging with the adjacent myometrium, the presence of cleft-like spaces, an absence of foamy histiocytes, and immunoreactivity for desmin. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. UNIV BRITISH COLUMBIA,VANCOUVER GEN HOSP,DEPT PATHOL,VANCOUVER,BC V5Z 1M9,CANADA. NR 36 TC 71 Z9 79 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 1995 VL 19 IS 7 BP 757 EP 768 DI 10.1097/00000478-199507000-00003 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA RD294 UT WOS:A1995RD29400003 PM 7793473 ER PT J AU JONES, MA YOUNG, RH SCULLY, RE AF JONES, MA YOUNG, RH SCULLY, RE TI MALIGNANT MESOTHELIOMA OF THE TUNICA VAGINALIS - A CLINICOPATHOLOGICAL ANALYSIS OF 11 CASES WITH REVIEW OF THE LITERATURE SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE TESTIS; MESOTHELIOMA; TUNICA VAGINALIS ID PAPILLARY MESOTHELIOMA; TESTICULAR TUNICA; TESTIS; TUMORS; PERITONEUM; CARCINOMA; SACS AB Eleven malignant mesotheliomas of the testicular tunica vaginalis occurred in patients aged 12 to 76 (mean, 54.1) years. Hydrocele, with or without an associated mass, or appreciation of a paratesticular mass accounted for the clinical presentation. One patient had a history of asbestos exposure. Grossly, the tumors typically presented as multiple nodules studding a hydrocele sac, frequently associated with a mass infiltrating the spermatic cord or adjacent testis. Microscopically, five tumors were epithelial and six biphasic, with the typical architectural and cytologic features of mesothelioma. Mixtures of papillary, tubular, and solid patterns predominated in the epithelial areas; interlacing fascicles of spindle cells with scanty stroma characterized the sarcomatous components. All eight of the tumors that were stained for keratin (AE1/AE3) were positive, four of five fbr epithelial membrane antigen, and four of five for vimentin. Seven of seven tumors were carcinoembryonic antigen negative and five of five B72.3, Leu-Mi, and Ber-Ep4 negative. Follow-up ranging from 1 to 15 (mean, 4.3) years was available for seven patients. Three died of disease after 4, 4, and 3 years, and three are alive with disease 2, 2, and 15 years after diagnosis. Two of the latter three patients had extensive local recurrences, one 15 years after the diagnosis of a well-differentiated papillary mesothelioma, the other 2 years following treatment with hydrocelectomy only. One patient who has been followed for only 1 year has no evidence of disease. This series emphasizes a number of important features of testicular mesothelioma: (a) a wide age range with occasional occurrence at a young age, (b) a wide morphologic spectrum with regard to degree of differentiation, and (c) an aggressive natural history with a potential for late recurrence or metastasis of even well-differentiated tumors, suggesting the need for initial aggressive surgical treatment. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA. RP JONES, MA (reprint author), MAINE MED CTR,DEPT PATHOL,22 BRAMHALL ST,PORTLAND,ME 04102, USA. NR 56 TC 97 Z9 99 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 1995 VL 19 IS 7 BP 815 EP 825 DI 10.1097/00000478-199507000-00010 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA RD294 UT WOS:A1995RD29400010 PM 7793480 ER PT J AU HUNT, DK BADGETT, RG WOODLING, AE PUGH, JA AF HUNT, DK BADGETT, RG WOODLING, AE PUGH, JA TI MEDICAL-STUDENT CAREER CHOICE - DO PHYSICAL DIAGNOSIS PRECEPTORS INFLUENCE DECISIONS SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE MEDICAL EDUCATION; CAREER CHOICE; MEDICAL STUDENTS; PHYSICAL EXAMINATION ID INTERNAL-MEDICINE; SPECIALTY; SCHOOL; ATTITUDES AB The authors attempted to measure the influence of a physical diagnosis course and its preceptors on the career decisions of second-year medical students. They designed pre- and post-course questionnaires for 204 second-year medical students in a University of Texas Health Science Center at San Antonio Advanced Physical Diagnosis course. They found that 48% of students changed their career choice during the study period, 75% believed their preceptor was a very good role model, and 39% thought their preceptor influenced their career choice. Students who believed their preceptor was a good role model were 31 times more likely to consider their preceptors' career (confidence interval [CI] 95, 4.1-236). In results from students precepted by primary care physicians, there was a nonsignificant trend toward choosing a primary care career (Odds Ratio [OR]) 1.6 [CI95, 0.7-3.3]). Factors associated with a final career choice of primary care were a primary care career choice at baseline (OR 8.5 [CI95, 3.8-19.0]) and a belief that physical diagnosis skills would be important to a future career (OR 4.7 [CI95, 1.1-20.0]). By multivariable analysis, only a primary care career choice at baseline remained significant (OR 8.7 [CI95, 3.5-21.3]). The authors concluded that good role models can influence students to consider alternative career choices, but this effect is still overshadowed by a student's baseline career choice. This reinforces the importance of selecting medical school applicants already inclined toward a primary care career. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. MEXICAN AMER MED TREATMENT EFFECTIVENESS CTR,SAN ANTONIO,TX. RP HUNT, DK (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GEN INTERNAL MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. OI Pugh, Jacqueline/0000-0003-4933-141X FU AHRQ HHS [UO1-HS07397]; NIDDK NIH HHS [R01-DK38392] NR 20 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JUL PY 1995 VL 310 IS 1 BP 19 EP 23 DI 10.1097/00000441-199507000-00007 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA RG997 UT WOS:A1995RG99700006 PM 7604834 ER PT J AU YANG, BH YANG, BL GOETINCK, PF AF YANG, BH YANG, BL GOETINCK, PF TI BIOTINYLATED HYALURONIC-ACID AS A PROBE FOR IDENTIFYING HYALURONIC ACID-BINDING PROTEINS SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID CHONDROITIN SULFATE PROTEOGLYCAN; RECEPTOR; HEPARIN; CELLS; CD44; SURFACE; CLONING; IDENTIFICATION; PLASMINOGEN; VERSICAN AB The glycosaminoglycans hyaluronan (HA), heparin, and chondroitin sulfate were biotinylated using biotin-x-hhydrazide (biotin-epsilon-aminocaproyl hydrozyde) in conjunction with N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride, an activating agent for carboxyl groups. The biotin-x-hydrazide was shown to be coupled directly to the glycosaminoglycans in enzymatic digestions and competition experiments. The biotinylated HA was shown to bind to link protein and receptor for hyaluronic acid-mediated motility, two proteins known to bind HA. The labeled HA was used as a probe to detect known HA-binding proteins in chicken cartilage extract and to identify new HA-binding motifs in the G3 domain of the proteoglycan aggrecan. The significance of the biotinylation of HA, heparin, and chondroitin sulfate A are discussed. (C) 1995 Academic Press, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. FU NICHD NIH HHS [HD 22016] NR 46 TC 38 Z9 38 U1 0 U2 4 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 JUL 1 PY 1995 VL 228 IS 2 BP 299 EP 306 DI 10.1006/abio.1995.1354 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA RH245 UT WOS:A1995RH24500017 PM 8572310 ER PT J AU ICHINOSE, F HUANG, PL ZAPOL, WM AF ICHINOSE, F HUANG, PL ZAPOL, WM TI EFFECTS OF TARGETED NEURONAL NITRIC-OXIDE SYNTHASE GENE DISRUPTION AND NITRO(G)-L-ARGININE METHYLESTER ON THRESHOLD FOR ISOFLURANE ANESTHESIA SO ANESTHESIOLOGY LA English DT Article DE ANESTHETICS, VOLATILE, ISOFLURANE; ANESTHETIC POTENCY, MINIMUM ALVEOLAR CONCENTRATION; ANIMAL, MOUSE; GENETICS, NITRIC OXIDE SYNTHASE; NEUROTRANSMITTER, NITRIC OXIDE; PHARMACOLOGY, NITRIC OXIDE SYNTHASE INHIBITOR ID EXHIBITS ANTINOCICEPTIVE ACTIVITY; HALOTHANE ANESTHESIA; NITROUS-OXIDE; ARGININE; BRAIN; MOUSE; INHIBITION; ESTER; ACTIVATION; RESISTANCE AB Background: Considerable evidence suggests that nitric oxide plays a role in synaptic transmission in the central and peripheral nervous system, Nonselective inhibition of nitric oxide synthase by nitro(G)-L-arginine methylester (L-NAME) reduces the minimum alveolar concentration of halothane anesthesia. The effects of selective neuronal nitric oxide synthase inhibition on the anesthetic requirements in mice congenitally deficient in neuronal nitric oxide synthase (knockout mice) were examined. Methods: Isoflurane minimum alveolar concentration and righting reflex ED(50) (RRED(50)) were determined in knockout and wild-type mice, Subsequently, the effects of intraperitoneal L-NAME on minimum alveolar concentration and RRED(50) of knockout and wild-type mice were examined, In a separate experiment, the effects of week-long administration of L-NAME were examined In wild-type mice, Isoflurane minimum alveolar concentration and RRED(50) were measured on the 8th day and were repeated after an acute intraperitoneal dose of L-NAME. Results: Targeted disruption of the neuronal nitric oxide synthase gene did not modify isoflurane minimum alveolar concentration and RRED(50) of knockout mice. Acute intraperitoneal L-NAME decreased the minimum alveolar concentration and RRED(50) of wild-type but did not alter those values in knockout mice. The wild-type mice, when given L-NAME for a week, showed a minimum alveolar concentration and RRED(50) identical to that of untreated wild-type mice. Conclusions Although acute nonselective inhibition of nitric oxide synthase reduces the anesthetic requirements of wildtype mice, a chronic congenital deficiency of neuronal nitric oxide synthase or a week of L-NAME treatment of wild-type mice does not produce a state of greater sensitivity to the effects of isoflurane anesthesia. C1 MASSACHUSETTS GEN HOSP,DEPT ANAESTHESIA,BOSTON,MA 02114. FU NHLBI NIH HHS [HL42397]; NINDS NIH HHS [P01-NS10828-19, R01-NS3335-01] NR 38 TC 65 Z9 68 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 1995 VL 83 IS 1 BP 101 EP 108 DI 10.1097/00000542-199507000-00013 PG 8 WC Anesthesiology SC Anesthesiology GA RH999 UT WOS:A1995RH99900013 PM 7541615 ER PT J AU HIBBERD, PL TOLKOFFRUBIN, NE CONTI, D STUART, F THISTLETHWAITE, JR NEYLAN, JF SNYDMAN, DR FREEMAN, R LORBER, MI RUBIN, RH AF HIBBERD, PL TOLKOFFRUBIN, NE CONTI, D STUART, F THISTLETHWAITE, JR NEYLAN, JF SNYDMAN, DR FREEMAN, R LORBER, MI RUBIN, RH TI PREEMPTIVE GANCICLOVIR THERAPY TO PREVENT CYTOMEGALOVIRUS DISEASE IN CYTOMEGALOVIRUS ANTIBODY-POSITIVE RENAL-TRANSPLANT RECIPIENTS - A RANDOMIZED CONTROLLED TRIAL SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE GANCICLOVIR; KIDNEY TRANSPLANTATION; CYTOMEGALOVIRUS INFECTIONS; ANTILYMPHOCYTE SERUM ID VIRUS DISEASE; OKT3; PROPHYLAXIS; VIREMIA; ALLOGRAFTS; INFECTION; GLOBULIN; MALG AB Objective: To determine whether preemptive ganciclovir therapy administered daily during antilymphocyte antibody therapy can prevent cytomegalovirus disease in renal transplant recipients who are positive for cytomegalovirus antibody. Design: Randomized, controlled, multicenter trial. Setting: 6 university-affiliated transplantation centers. Patients: 113 renal transplant recipients who were positive for cytomegalovirus antibody. Intervention: Patients were randomly assigned to receive either 1) ganciclovir, 2.5 mg/kg body weight administered intravenously on every day that antilymphocyte antibody therapy was administered or 2) no anticytomegalovirus therapy. Measurements: Patients were observed for 6 months after completion of antilymphocyte antibody therapy for development of cytomegalovirus disease and cytomegalovirus viremia. Results: Cytomegalovirus disease occurred in 14% of patients (9 of 64) who received preemptive ganciclovir therapy and in 33% of controls (16 of 49) (P = 0.018). Cytomegalovirus was isolated from buffy-coat specimens from 17% of patients (11 of 64) receiving preemptive ganciclovir and from 35% of controls (17 of 49) (P = 0.03). Controlling for the reason (induction or treatment of rejection) for using antilymphocyte antibodies in a Cox proportional hazards model, we found that preemptive ganciclovir still protected against cytomegalo-virus disease (adjusted relative risk, 0.27; 95% CI, 0.12 to 0.64). No adverse events were attributed to preemptive ganciclovir therapy during or within 6 months of its administration. Conclusions: Preemptive ganciclovir therapy administered daily during courses of treatment with antilymphocyte antibodies reduced the excessive occurrence of cytomegalovirus disease in renal transplant recipients who were positive for cytomegalovirus antibody. This approach, which links the most potent immuno-suppression to intensive antimicrobial therapy, allows preventive therapy to be given to those patients at greatest risk for developing infectious complications. These patients are likely to benefit most from the preventive strategy. C1 MASSACHUSETTS GEN HOSP,DEPT TRANSPLANTAT,BOSTON,MA 02114. ALBANY MED COLL,DEPT SURG,ALBANY,NY 12208. NW MEM HOSP,DIV ORGAN TRANSPLANTAT,CHICAGO,IL 60611. EMORY UNIV,SCH MED,ATLANTA,GA 30322. TUFTS UNIV NEW ENGLAND MED CTR,DEPT SURG,BOSTON,MA 02111. YALE UNIV,SCH MED,DIV ORGAN TRANSPLANTAT,NEW HAVEN,CT 06150. UNIV CHICAGO,MED CTR,DEPT TRANSPLANT SURG,CHICAGO,IL 60637. RP HIBBERD, PL (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,FRUIT ST,GRJ-504,BOSTON,MA 02114, USA. RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 NR 28 TC 192 Z9 195 U1 0 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 1 PY 1995 VL 123 IS 1 BP 18 EP 26 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA RE665 UT WOS:A1995RE66500003 PM 7762909 ER PT J AU HARTSTEIN, J PACE, U HARTSTEIN, ME TANZI, RE BUSH, AI AF HARTSTEIN, J PACE, U HARTSTEIN, ME TANZI, RE BUSH, AI TI ZINC AND MACULAR DEGENERATION SO ANNALS OF OPHTHALMOLOGY-GLAUCOMA LA English DT Editorial Material ID ALZHEIMERS-DISEASE; DOWNS-SYNDROME; TASTE ACUITY; ORAL ZINC; PLASMA; AGE C1 WASHINGTON UNIV,SCH MED,ST LOUIS,MO. INNOVIR LABS,NEW YORK,NY. NYU,SCH MED,NEW YORK,NY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GENET & AGING UNIT,BOSTON,MA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 22 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CONTEMPORARY OPHTHALMOLOGY PI SKOKIE PA 4711 GOLF RD, SUITE 408, SKOKIE, IL 60076-1242 SN 1079-4794 J9 ANN OPHTHALMOL-GLAUC JI Ann. Ophthal.-Glauc. PD JUL-AUG PY 1995 VL 27 IS 4 BP 194 EP 196 PG 3 WC Ophthalmology SC Ophthalmology GA RT721 UT WOS:A1995RT72100001 ER PT J AU VARVARES, MA MONTGOMERY, WW HILLMAN, RE AF VARVARES, MA MONTGOMERY, WW HILLMAN, RE TI TEFLON GRANULOMA OF THE LARYNX - ETIOLOGY, PATHOPHYSIOLOGY, AND MANAGEMENT SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE GRANULOMA; LARYNX; LASER; TEFLON ID VOCAL CORD PARALYSIS; POLYTEF TEFLON; INJECTION; REMOVAL; FOLD AB Intralaryngeal Teflon injection for correction of unilateral vocal cord paralysis is known to produce a foreign body giant cell reaction. In our practice, we have seen increasing numbers of patients who had developed dysphonia related to Teflon injection. This patient series was reviewed, as were the surgical technique to correct this condition, voice results, and acoustic analysis of a subset of the patient series. We conclude that dysphonia, secondary to Teflon injection, can be either from overinjection of Teflon or inappropriate injection, or from the proliferative granulomatous response of the larynx to the Teflon. Our technique of laser incision into the superior aspect of the Teflon implant, followed by vaporization and preservation of a margin of mucosa of the cord medially, resulted in improved voice in 8 of 11 patients treated in this manner. Acoustic and aerodynamic analyses reveal significant deficits in vocal function that may persist after procedures used to correct this condition. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA. NR 22 TC 47 Z9 47 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JUL PY 1995 VL 104 IS 7 BP 511 EP 515 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA RJ908 UT WOS:A1995RJ90800002 PM 7598361 ER PT J AU LEGLER, CM HAYES, DF AF LEGLER, CM HAYES, DF TI DOXORUBICIN FOR INFLAMMATORY BREAST-CANCER - A RED HUMOR FOR A RED TUMOR SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CTR BREAST EVALUAT,BOSTON,MA 02115. NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUL PY 1995 VL 2 IS 4 BP 283 EP 285 DI 10.1007/BF02307057 PG 3 WC Oncology; Surgery SC Oncology; Surgery GA RF062 UT WOS:A1995RF06200001 PM 7552614 ER PT J AU PERRINE, K DEVINSKY, O LUCIANO, DJ CHOI, IS NELSON, PK AF PERRINE, K DEVINSKY, O LUCIANO, DJ CHOI, IS NELSON, PK TI CORRELATES OF ARTERIAL-FILLING PATTERNS IN THE INTRACAROTID AMOBARBITAL PROCEDURE SO ARCHIVES OF NEUROLOGY LA English DT Article ID TEMPORAL LOBECTOMY; EPILEPTIC PATIENTS; MEMORY; SODIUM; INJECTION; IMPAIRMENT AB Objective: To determine behavioral correlates of anterior cerebral artery (ACA) and posterior cerebral artery (PCA) perfusion patterns in the intracarotid amobarbital sodium procedure. Design: Multivariate analysis of covariance and partial correlations of behavioral measures to ACA crossflow and PCA filling. Setting: Angiography and the intracarotid amobarbital procedure at a comprehensive epilepsy center. Subjects: Forty-two patients with intractable epilepsy (right-hemisphere seizure focus [n-23]; left-hemisphere seizure fetus [n=19]). Measurements: Internal carotid angiography was performed both at a standard injection rate (8 mL of contrast per second) and at 1 mL/s, which matched the rate of the subsequent amobarbital injection. The degree of ipsilateral PCA and contralateral ACA filling were graded on a seven-point scale and compared with postinjection behavior, language, and memory measures. Results: The ACA crossflow did not correlate significantly with that of any measure. The degree of PCA-filling pattern correlated significantly only with the level of consciousness (r=.31, P<.004), but it was not significant after accounting for the effects of seizure laterality, injection side, and amobarbital dosage. Neither ACA crossflow nor PCA filling correlated significantly with memory. The degree of ACA and PCA filling was overestimated at standard angiography (8 mL of contrast medium per second) injection rates. Conclusions: Although the degree of PCA filling correlates mildly with the level of consciousness postinjection, possibly by perfusion of thalamic or mesencephalic branches, it is not reliably predictive and is less contributory than the injection side and seizure laterality. The PCA filling is not required to produce valid memory assessment in the intracarotid amobarbital procedure, and ACA crossflow is not predictive of behavioral responses. C1 NYU,SCH MED,DEPT NEURORADIOL,NEW YORK,NY. MASSACHUSETTS GEN HOSP,DEPT NEURORADIOL,BOSTON,MA 02114. RP PERRINE, K (reprint author), HOSP JOINT DIS & MED CTR,DEPT NEUROL,301 E 17TH ST,NEW YORK,NY 10003, USA. NR 24 TC 11 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 1995 VL 52 IS 7 BP 712 EP 716 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA RH241 UT WOS:A1995RH24100014 PM 7619028 ER PT J AU REMULLA, JFC PINEDA, R GAUDIO, AR MILAM, AH AF REMULLA, JFC PINEDA, R GAUDIO, AR MILAM, AH TI CUTANEOUS MELANOMA-ASSOCIATED RETINOPATHY WITH RETINAL PERIPHLEBITIS SO ARCHIVES OF OPHTHALMOLOGY LA English DT Note ID CELLS C1 MASSACHUSETTS EYE & EAR INFIRM,BERMAN GUND LAB,BOSTON,MA 02114. FU NEI NIH HHS [EYO1730, EY02317, EY01311] NR 4 TC 18 Z9 19 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 1995 VL 113 IS 7 BP 854 EP 855 PG 2 WC Ophthalmology SC Ophthalmology GA RH816 UT WOS:A1995RH81600014 PM 7605271 ER PT J AU JELLINEK, M LITTLE, M MURPHY, JM PAGANO, M AF JELLINEK, M LITTLE, M MURPHY, JM PAGANO, M TI THE PEDIATRIC SYMPTOM CHECKLIST - SUPPORT FOR A ROLE IN A MANAGED CARE ENVIRONMENT SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID PSYCHOSOCIAL DYSFUNCTION; MENTAL-HEALTH; RISK-FACTORS; DISADVANTAGED-CHILDREN; PSYCHOPATHOLOGY; PARENT; RELIABILITY; PREVALENCE; DISORDERS; DIAGNOSES AB Objectives: To gather data based on studies of the Pediatric Symptom Checklist, identify risk factors associated with high levels of dysfunction in primary care pediatric settings, and explore the relationship between common risk factors and psychosocial problems identified by pediatricians. Design: Retrospective review and cross-sectional, case-referent survey. Setting: Subjects were selected from three primary care pediatric clinics in Massachusetts: a private practice in a predominantly white, middle-class suburb, an urban health maintenance organization clinic, and an inner-city clinic. Participants: Of 423 outpatients aged 6 to 12 years screened for psychosocial problems, 72 children and their families were seen for in-depth structured and clinical interviews (24 from each site). Interventions: None. Measurements/Main Results: Children with a single parent and/or those who were economically disadvantaged were significantly more likely to show psychosocial impairment. The specificity of the Pediatric Symptom Checklist was 100% in samples with a lower socioeconomic status compared with 68% in middle-class samples, and sensitivity was 95% in middle-class samples compared with 80% in lower-class samples. Pediatricians identified psychosocial problems in eight of 15 children with a history of familial mental illness or substance abuse and seven of eight children with a history of physical or sexual abuse, but only six of 17 cases from single-parent families and four of 11 cases from poor families. Conclusions: Pediatricians should be sensitive to psychosocial dysfunction especially in single-parent and low-income families. Use of the Pediatric Symptom Checklist for psychosocial screening in a managed health care delivery system could target capitated resources efficiently by providing early identification and secondary prevention of psychosocial morbidity. RP JELLINEK, M (reprint author), MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,15 PARKMAN ST,ACC 725,BOSTON,MA 02114, USA. FU PHS HHS [86MO43903501D] NR 47 TC 33 Z9 33 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JUL PY 1995 VL 149 IS 7 BP 740 EP 746 PG 7 WC Pediatrics SC Pediatrics GA RH540 UT WOS:A1995RH54000004 PM 7795763 ER PT J AU LANGBEIN, WE MAKI, KC AF LANGBEIN, WE MAKI, KC TI PREDICTING OXYGEN-UPTAKE DURING COUNTERCLOCKWISE ARM CRANK ERGOMETRY IN MEN WITH LOWER-LIMB DISABILITIES SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID PHYSIOLOGICAL-RESPONSES; EXERCISE AB Objective: This study was conducted to develop a new equation for predicting oxygen uptake (VO2) during counterclockwise arm crank ergometry (ACE) in men with lower limb disabilities, cross-validate the new equation in a similar group of men, and compare the predictive accuracy of the new equation to previously published equations for clockwise ACE. Patients: The metabolic responses of 55 men, 17 to 69 years of age, with spinal cord injuries (n = 50) or lower limb fractures (n = 5) were recorded during maximal ACE-graded exercise tests. Participants were volunteers from area hospital rehabilitation centers, and wheelchair sport teams. Design: Subjects were partitioned by level of injury and randomly assigned to a prediction (PRE) or validation (VAL) group. Results: No differences were found between the PRE and VAL groups for age, anthropometric or peak exercise variables. Using stepwise regression, a prediction equation (EXP) was derived from the PRE group data. The resulting model: VO2 (mL/min) = 127.06 + 7.201 (Watts) + 4.502 (weight in kg) + 0.033 (Watts(2)) explained 89.8% of the variance in the PRE group VO2, standard error of estimate (SEE) = 151.9mL/min. The equation performed similarly in the VAL group (SEE = 144.0mL/min). Conclusions: In this sample, the EXP equation had less prediction error than equations derived for clockwise ACE. Accuracy was not substantially influenced by level of injury. Comparison of the data to that published previously for clockwise ACE by men with paraplegia suggests greater metabolic economy for counterclockwise as compared with clockwise ACE. (C) 1995 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation RP LANGBEIN, WE (reprint author), US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,CTR REHABIL RES & DEV,POB 20,HINES,IL 60141, USA. NR 16 TC 9 Z9 9 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 1995 VL 76 IS 7 BP 642 EP 646 DI 10.1016/S0003-9993(95)80633-4 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA RH676 UT WOS:A1995RH67600007 PM 7605183 ER PT J AU TEMPEL, M GOLDMANN, WH ISENBERG, G SACKMANN, E AF TEMPEL, M GOLDMANN, WH ISENBERG, G SACKMANN, E TI INTERACTION OF THE 47-KDA TALIN FRAGMENT AND THE 32-KDA VINCULIN FRAGMENT WITH ACIDIC PHOSPHOLIPIDS - A COMPUTER-ANALYSIS SO BIOPHYSICAL JOURNAL LA English DT Article ID CYTOSKELETAL PROTEIN VINCULIN; ROUS-SARCOMA VIRUS; SECONDARY STRUCTURE; ALPHA-ACTININ; BINDING-SITE; TRANSBILAYER HELICES; HYDROPHOBIC MOMENT; EMBRYO FIBROBLASTS; MEMBRANE-PROTEINS; AMPHIPATHIC HELIX AB In recent in vitro experiments, it has been demonstrated that the 47-kDa fragment of the talin molecule and the 32-kDa fragment of the vinculin molecule interact with acidic phospholipids. By using a computer analysis method, we determined the hydrophobic and amphipathic stretches of these fragments and, by applying a purpose-written matrix method, we ascertained the molecular amphipathic structure of alpha-helices. Calculations for the 47-kDa mouse talin fragment (residues 1-433; NH2-terminal region) suggest specific interactions of residues 21-39, 287-342, and 385-406 with acidic phospholipids and a general lipid-binding domain for mouse talin (primary amino acid sequence 385-401) and for Dictyostelium talin (primary amino acid sequence 348-364). Calculations for the 32-kDa chicken embryo vinculin fragment (residues 858-1066; COOH-terminal region) and from nematode vinculin alignment indicate for chicken embryo vinculin residues 935-978 and 1020-1040 interactions with acidic phospholipids. Experimental confirmation has been given for vinculin (residues 916-970), and future detailed experimental analyses are now needed to support the remaining computational data. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. RP TEMPEL, M (reprint author), TECH UNIV MUNICH,DEPT BIOPHYS,E22,JAMES FRANCK ST,D-85747 GARCHING,GERMANY. RI Goldmann, Wolfgang/H-5572-2013 NR 84 TC 55 Z9 56 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1995 VL 69 IS 1 BP 228 EP 241 PG 14 WC Biophysics SC Biophysics GA RH661 UT WOS:A1995RH66100022 PM 7669900 ER PT J AU STEGMAIER, K PENDSE, S BARKER, GF BRAYWARD, P WARD, DC MONTGOMERY, KT KRAUTER, KS REYNOLDS, C SKLAR, J DONNELLY, M BOHLANDER, SK ROWLEY, JD SALLAN, SE GILLILAND, DG GOLUB, TR AF STEGMAIER, K PENDSE, S BARKER, GF BRAYWARD, P WARD, DC MONTGOMERY, KT KRAUTER, KS REYNOLDS, C SKLAR, J DONNELLY, M BOHLANDER, SK ROWLEY, JD SALLAN, SE GILLILAND, DG GOLUB, TR TI FREQUENT LOSS OF HETEROZYGOSITY AT THE TEL GENE LOCUS IN ACUTE LYMPHOBLASTIC-LEUKEMIA OF CHILDHOOD SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; DNA-BINDING DOMAIN; T-CELL LEUKEMIA; CHROMOSOMAL TRANSLOCATION; MYELOID-LEUKEMIA; PRE-B; PROTEIN; FUSION; REGION; INVOLVEMENT AB TEL is a new member of the ETS family of transcription factors which is rearranged in a number of hematologic malignancies with translocations involving chromosome band 12p13. In some cases, both TEL alleles are affected, resulting in loss of wild-type TEL function in the leukemic cells. In addition, 5% of children with acute lymphoblastic leukemia (ALL) have 12p12-p13 deletions, suggesting that a tumor suppressor gene resides on 12p. These observations led us to consider whether TEL loss of function may contribute to the pathogenesis of ALL. In this report we show that the TEL gene maps between the polymorphic markers D12S89 and D12S98, and we use these flanking markers to screen paired diagnosis and remission samples from 81 children with ALL for loss of heterozygosity (LOH) at the TEL gene locus. Fifteen percent of informative patients showed TEL LOH which was not evident on cytogenetic analysis, Detailed examination of patients with LOH at this locus showed that the critically deleted region included two candidate tumor suppressor genes: TEL and KIP1, the gene encoding the cyclin-dependent kinase inhibitor p27, These studies show that LOH at the TEL locus is a frequent finding in childhood ALL. (C) 7995 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. YALE UNIV,DEPT GENET,NEW HAVEN,CT. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT CELL BIOL,BRONX,NY. DANA FARBER CANC INST,CTR QUAL CONTROL,DIV BIOSTAT,BOSTON,MA 02115. UNIV CHICAGO,HEMATOL ONCOL SECT,CHICAGO,IL 60637. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV PEDIAT ONCOL,BOSTON,MA 02115. OI Bohlander, Stefan/0000-0002-2202-9088 FU NCI NIH HHS [CA 42557, CA 57261]; NHGRI NIH HHS [P01HG00965] NR 41 TC 115 Z9 117 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1995 VL 86 IS 1 BP 38 EP 44 PG 7 WC Hematology SC Hematology GA RF984 UT WOS:A1995RF98400005 PM 7795247 ER PT J AU MACCOLLIN, M AF MACCOLLIN, M TI CNS YOUNG INVESTIGATOR AWARD LECTURE - MOLECULAR ANALYSIS OF THE NEUROFIBROMATOSIS-2 TUMOR-SUPPRESSOR SO BRAIN & DEVELOPMENT LA English DT Article DE NEUROFIBROMATOSIS 2; ACOUSTIC NEUROMA; SCHWANNOMA; MENINGIOMA; TUMOR SUPPRESSOR GENE; MUTATIONAL ANALYSIS; CHROMOSOME 22 ID BILATERAL ACOUSTIC NEUROFIBROMATOSIS; FAMILIAL ADENOMATOUS POLYPOSIS; TYPE-2 NEUROFIBROMATOSIS; RETINOBLASTOMA GENE; POINT MUTATIONS; IDENTIFICATION; SEQUENCE; DISEASE; PROTEIN; MOESIN AB Neurofibromatosis 2 (NF2), also known as bilateral acoustic neurofibromatosis or central neurofibromatosis, is a severe autosomal dominant disease characterized by the development of multiple nervous system tumors. The tumors of NF2, which include schwannomas, meningiomas and ependymomas, are histologically benign; however, their location and multiplicity led to great morbidity and mortality. These tumors commonly affect the general population in their isolated form, and have been found to undergo loss of chromosome 22 material in many studies; because of this the NF2 gene has been postulated to he a classic tumor suppressor, The NF2 gene has recently been isolated and found to encode a new member of the protein 4.1 family of cytoskeletal associated proteins which we have named merlin, To define the molecular basis of NF2 in germline and turner specimens, we have used single-stranded conformation polymorphism (SSCP) analysis to scan the exons of the NF2 gene. We have located and characterized underlying causative mutation in 21 of 33 unrelated affected individuals studied, and 32 of 38 schwannomas. DNA sequence analysis revealed that over 90% of NF2 mutations are predicted to lead to a truncated protein due to frameshift, creation of a stop codon, or interference with normal RNA splicing. Current studies focus on relating the highly variable NF2 phenotype to its genotype, defining alternative NF2 related phenotypes, and elucidating the parental origin of new mutation in this disease. RP MACCOLLIN, M (reprint author), MASSACHUSETTS GEN HOSP EAST,DEPT NEUROL,BOSTON,MA 02129, USA. NR 64 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0387-7604 J9 BRAIN DEV-JPN JI Brain Dev. PD JUL-AUG PY 1995 VL 17 IS 4 BP 231 EP 238 DI 10.1016/0387-7604(95)00044-C PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA RR681 UT WOS:A1995RR68100001 PM 7503383 ER PT J AU DENMAN, W GOUDSOUZIAN, N AF DENMAN, W GOUDSOUZIAN, N TI MIVACURIUM INFUSION REQUIREMENTS FOLLOWING VECURONIUM - DIFFERENT RESPONSE BETWEEN ADULTS AND CHILDREN SO CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Article DE ANESTHESIA, PEDIATRIC, ADULT; NEUROMUSCULAR RELAXANTS, MIVACURIUM, VECURONIUM; INTERACTION (DRUGS), MIVACURIUM, VECURONIUM ID NEUROMUSCULAR BLOCKING-AGENTS; ACETYLCHOLINE-RECEPTOR; D-TUBOCURARINE; PANCURONIUM; ANESTHESIA; POTENTIATION; BLOCKADE; ATRACURIUM; HALOTHANE; RECOVERY AB The mivacurium infusion requirements following vecuronium were evaluated in 15 adults and 15 children in an open prospective clinical study. This study was undertaken to elucidate whether potentiation of effect occurred when a mivacurium infusion was administered after vecuronium was used for the facilitation of tracheal intubation. The adult patients were anaesthetized with N2O:O-2, propofol and fentanyl, the children with halothane (1%) N2O:O-2. Vecuronium 100 mu g . kg(-1) was administered during stimulation of the ulnar nerve with train-of-four stimuli at 0.1 Hz. The force of contraction of the adductor pollicis was recorded. Upon recovery of the twitch response from vecuronium, a mivacurium infusion was started at 4 mu g . kg(-1). min(-1), thereafter adjustments were made to maintain the first twitch of the train-of-four (T-1) at 1-10% of control. The mean (+/-SE) initial infusion requirements in children of mivacurium was 4.3 (0.4) mu g . kg-1 . min(-1) which increased linearly (P < 0.001) over the next 90 min to 10 mu g . kg(-1)min(-1). In adults the infusion requirement was lower than in children and remained at approximately 3 mu g . kg(-1). min(-1) over the next 75 min. At the end of the surgical procedure, the children recovered faster than the adults with no child requiring reversal. Because of prolonged recovery (>20 min), seven adults required reversal with 15-70 mu g . kg(-1) neostigmine. Mivacurium infusion requirements following vecuronium are higher in children than adults. Potentiation of the effects of mivacurium were seen when vecuronium preceeded mivacurium. This potentiation of effect lasted longer in adults than in children. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02114. NR 36 TC 3 Z9 3 U1 0 U2 0 PU CANADIAN ANAESTHETISTS SOC INC PI TORONTO PA 1 EGLINTON AVE EAST, SUITE 208, TORONTO ON M4P 3A1, CANADA SN 0832-610X J9 CAN J ANAESTH JI Can. J. Anaesth.-J. Can. Anesth. PD JUL PY 1995 VL 42 IS 7 BP 597 EP 602 PG 6 WC Anesthesiology SC Anesthesiology GA RG234 UT WOS:A1995RG23400006 PM 7553995 ER PT J AU CHENG, TJ CHRISTIANI, DC XU, XP WAIN, JC WIENCKE, JK KELSEY, KT AF CHENG, TJ CHRISTIANI, DC XU, XP WAIN, JC WIENCKE, JK KELSEY, KT TI GLUTATHIONE-S-TRANSFERASE MU-GENOTYPE, DIET, AND SMOKING AS DETERMINANTS OF SISTER-CHROMATID EXCHANGE FREQUENCY IN LYMPHOCYTES SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LUNG-CANCER PATIENTS; BETA-CAROTENE; CYTOGENETIC DAMAGE; VITAMIN-E; SUSCEPTIBILITY; RISK; POPULATION; SMOKERS; GENE; POLYMORPHISMS AB Polymorphisms in inherited metabolic traits and intake of dietary antioxidants have been reported to be associated with risk for the development of lung cancer in smokers, This increased risk of lung cancer is presumably attributable to the accumulation of DNA damage, We conducted a study to investigate whether genetic metabolic variants and antioxidant consumption affected the sister chromatid exchange (SCE) level in lymphocytes. Study subjects were 78 friends and spouses of cases from a case-control study of lung cancer designed to investigate the association of metabolic polymorphisms with lung cancer, The metabolic traits studied included glutathione S-transferase class mu and variants of P-450 isoenzymes CYP1A1 and CYP2D6. Intake of antioxidants including vitamins A, C, and E and selenium was determined through the administration of a validated, semiquantitative food frequency questionnaire, Detailed information on smoking, family history of cancer, medical history, and environmental and occupational exposures was also obtained in an interviewer-administered questionnaire, Smoking status was found to be significantly associated with SCE frequency, In addition, SCE frequency decreased with the period of time since quitting smoking, The presence of one or more glutathione S-transferase class mu alleles was associated with significantly lower SCE, Higher intake of vitamin A and selenium was also inversely associated with SCE level, Thus, the results suggest that glutathione Stransferase class mu and the intake of vitamin A and selenium may modulate the accumulation of chromosomal damage in lymphocytes. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PULM & CRIT CARE UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,THORAC SURG UNIT,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,DEPT EPIDEMIOL & BIOSTAT,MOLEC EPIDEMIOL LAB,SAN FRANCISCO,CA 94143. RI Cheng, Tsun-Jen /D-3495-2012; Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [ES-00002, ES-06409] NR 62 TC 54 Z9 55 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL-AUG PY 1995 VL 4 IS 5 BP 535 EP 542 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA RJ656 UT WOS:A1995RJ65600016 PM 7549811 ER PT J AU WANG, X CHRISTIANI, DC WIENCKE, JK FISCHBEIN, M XU, XP CHENG, TJ MARK, E WAIN, JC KELSEY, KT AF WANG, X CHRISTIANI, DC WIENCKE, JK FISCHBEIN, M XU, XP CHENG, TJ MARK, E WAIN, JC KELSEY, KT TI MUTATIONS IN THE P53 GENE IN LUNG-CANCER ARE ASSOCIATED WITH CIGARETTE-SMOKING AND ASBESTOS EXPOSURE SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TUMOR-SUPPRESSOR GENE; CELL; CARCINOGENESIS; ABNORMALITIES; HYDROCARBONS; CARCINOMAS; EXPRESSION; FREQUENT; FIBERS; MODEL AB It has been proposed that the patterns of mutations in the p53 tumor suppressor gene will provide clues to the mechanisms of cancer occurrence, Cigarette smoking is known to be the greatest risk factor for lung cancer, Epidemiological evidence has also implicated radon and asbestos as exposures that significantly increase this disease risk; asbestos exposure synergistically enhances the lung cancer risk of smokers, Previous studies of the mutational spectra of the p53 gene in lung cancer have shown cigarette smoke and radon exposure to be associated with the induction of particular lesions or classes of lesions, We have investigated the p53 gene in surgically resectable lung cancers in 85 patients from the Massachusetts General Hospital, We found 25 (29%) patients to have somatic p53 mutations in their tumors, The patients with p53 mutations who were current smokers were significantly older (75.1 versus 59.8 years; P < 0.01) and had smoked for significantly more years (56.8 vel sus 41.2 years; P < 0.01) than had those without p53 changes, Consistent with other reports, we observed a large number (40%) of G:C to T:A transversion mutations, noting that their occurrence increased with increasing cumulative exposure to cigarette smoke, Interestingly, we also found that p53 mutations occurred significantly more frequently in patients with a history of occupational exposure to asbestos [3 of 60 (5%) for patients without p53 mutations versus 5 of 25 (20%) of those with p53 mutations; P < 0.05]. Additionally, 4 of the 5 patients with asbestos exposure and p53 alterations had G:C to T:A transversion mutations, and 3 of 3 double mutations that were seen in the p53 gene occurred in patients who smoked and had a history of asbestos exposure, This suggests that asbestos exposure may increase the frequency of G:C to T:A transversion mutations in the p53 gene, Because these lesions can be induced by polyaromatic compounds found in cigarette smoke, our data also suggest that one possible important role of asbestos may be to increase delivery of these substances to the respiratory epithelium. Asbestos might also act to alter clonal selection through other mechanisms, including apoptosis, oxyradical generation, or altered proliferation. C1 HARVARD UNIV, SCH PUBL HLTH, DEPT CANC BIOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH PUBL HLTH, OCCUPAT HLTH PROGRAM, BOSTON, MA 02115 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, PULM & CRIT CARE UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT SURG, BOSTON, MA 02114 USA. UNIV CALIF SAN FRANCISCO, DEPT EPIDEMIOL & BIOSTAT, MOLEC EPIDEMIOL LAB, SAN FRANCISCO, CA 94143 USA. RI Cheng, Tsun-Jen /D-3495-2012; Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [ES-00002, P01 ES-06409] NR 40 TC 54 Z9 56 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL-AUG PY 1995 VL 4 IS 5 BP 543 EP 548 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA RJ656 UT WOS:A1995RJ65600017 PM 7549812 ER PT J AU COLDITZ, GA FRAZIER, AL AF COLDITZ, GA FRAZIER, AL TI MODELS OF BREAST-CANCER SHOW THAT RISK IS SET BY EVENTS OF EARLY-LIFE - PREVENTION EFFORTS MUST SHIFT FOCUS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; AGE; GONADOTROPIN; IRRADIATION; DISEASE; HEALTH; BIRTH AB We have recently published a mathematical model of the etiology of breast cancer based on the data from the Nurses Health Study that extends the Pike model of breast cancer (see Appendix), The most salient feature of the model is that it identifies the years before the first birth of a child as the most crucial in establishing future risk of breast cancer, The extended model includes several additional details of reproductive risk factors, allowing us to quantify the relative importance of the each of the reproductive risk factors and to estimate the effect of changes in key determinants of breast cancer. In this review, we present the evidence from both animal studies and epidemiological research that corroborate the critical importance of the exposures that occur before first birth. We argue that research and preventive interventions should now focus on youth, Population-wide prevention strategies are necessary because the inherited genetic risk for breast cancer accounts for no more than 10-15% of all breast cancer cases, leaving 85% of cases diagnosed among women who are not in this high-risk subgroup of the population. An example of a population-based intervention would be the promotion of increased physical activity among young girls that could result in the delay of menarche, An example of additional research that focuses on the importance of early life exposures would be an analysis of the relation between diet and other lifestyle factors during adolescence and the subsequent risk of breast cancer and studies of precursor lesions (atypical hyperplasia). Shifting the focus of breast cancer prevention to this age group is urgently needed. C1 HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, CHANNING LAB, BOSTON, MA 02115 USA. HARVARD UNIV, SCH PUBL HLTH, CTR CANC PREVENT, BOSTON, MA 02115 USA. DANA FARBER CANC INST, BOSTON, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA 40356, KO7CA62252-01A1] NR 46 TC 248 Z9 250 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL-AUG PY 1995 VL 4 IS 5 BP 567 EP 571 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA RJ656 UT WOS:A1995RJ65600021 PM 7549816 ER PT J AU REED, JA LOGANZO, F SHEA, CR WALKER, GJ FLORES, JF GLENDENING, JM BOGDANY, JK SHIEL, MJ HALUSKA, FG FOUNTAIN, JW ALBINO, AP AF REED, JA LOGANZO, F SHEA, CR WALKER, GJ FLORES, JF GLENDENING, JM BOGDANY, JK SHIEL, MJ HALUSKA, FG FOUNTAIN, JW ALBINO, AP TI LOSS OF EXPRESSION OF THE P16/CYCLIN-DEPENDENT KINASE INHIBITOR 2 TUMOR-SUPPRESSOR GENE IN MELANOCYTIC LESIONS CORRELATES WITH INVASIVE STAGE OF TUMOR PROGRESSION SO CANCER RESEARCH LA English DT Note ID FAMILIAL MELANOMA; NEVI AB Sporadic and familial malignant melanoma susceptibility has been linked to defects in the chromosomal region 9p21. Recently, a putative 9p21 tumor suppressor gene, the cyclin dependent kinase inhibitor 2 (CDKN2) or pld gene, has been shown to be deleted, mutated, or rearranged in a high percentage of sporadic melanoma cell lines, as well as mutated in the germline of a proportion of familial melanoma patients. CDKN2 encodes a M(r) 16,000 protein (p16) that plays a key role in cell cycle control by binding to the cyclin-dependent kinase 4 enzyme and inhibiting its ability to phosphorylate critical substrates necessary for transition past the G(1) phase of the cell cycle. Thus, mutations or deletions of the CDKN2 gene could result in abnormal proliferation via defective cell cycle control. The correlation of 9p21 cytogenetic and molecular alterations with the clinical stages of melanoma progression suggests that dysfunction of a gene within this chromosomal region is critical to the evolution of melanoma. However, it remains unclear whether this gene is the CDKN2 gene. If so, then loss of p16 is potentially an initiating or early event in melanoma progression To address the issues of what is the potential involvement of the CDKN2 gene in sporadic melanoma and precisely when during the clinically evident stages of melanoma progression defects in CDKN2, occur, we have evaluated by immunohistochemistry the expression of p16 protein in 103 melanocytic lesions representing all stages in the progression of melanoma. Our results suggest that loss of p16 protein expression is (a) not necessary for tumor initiation in malignant melanoma because all melanomas in situ and the majority of primary invasive melanomas retain expression of this protein; and (b) potentially more related to invasiveness or the ability to metastasize, because 52% of primary invasive tumors and 72% of metastatic lesions show partial or complete loss of expression of p16. C1 MEM SLOAN KETTERING CANC CTR,DEPT IMMUNOL,NEW YORK,NY 10021. NEW YORK HOSP,CORNELL MED CTR,DEPT PATHOL,NEW YORK,NY 10021. NEW YORK HOSP,CORNELL MED CTR,DEPT DERMATOL,NEW YORK,NY 10021. MASSACHUSETTS GEN HOSP,DEPT ONCOL,CAMBRIDGE,MA 02139. UNIV SO CALIF,SCH MED,DEPT BIOCHEM,LOS ANGELES,CA 90033. UNIV SO CALIF,SCH MED,DEPT BIOL MOLEC,LOS ANGELES,CA 90033. INST MED GENET,LOS ANGELES,CA 90033. QUEENSLAND INST MED RES,BRISBANE,QLD 4029,AUSTRALIA. NR 30 TC 246 Z9 254 U1 1 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 JUL 1 PY 1995 VL 55 IS 13 BP 2713 EP 2718 PG 6 WC Oncology SC Oncology GA RF496 UT WOS:A1995RF49600001 PM 7796391 ER PT J AU GIAMBRO, NJ PROSTAK, K DENBESTEN, PK AF GIAMBRO, NJ PROSTAK, K DENBESTEN, PK TI CHARACTERIZATION OF FLUOROSED HUMAN ENAMEL BY COLOR REFLECTANCE, ULTRASTRUCTURE, AND ELEMENTAL COMPOSITION SO CARIES RESEARCH LA English DT Article DE COLORIMETER; DENTAL FLUOROSIS; ENAMEL MORPHOLOGY; SCANNING ELECTRON MICROSCOPY ID FLUORIDE CONCENTRATIONS; DENTAL FLUOROSIS; FEATURES AB Mature fluorosed human enamel has been described as a subsurface enamel hypomineralization, with porosity increasing relative to the degree of fluorosis. The purpose of the current study was to quantitatively measure the color of the fluorosed enamel by light reflectance, and to further characterize the enamel by scanning electron microscopy. Teeth with varying degrees of fluorosis were obtained and divided in groups of mild, moderate and severe fluorosis using Dean's index for fluorosis. The color of the labial enamel surface was measured using a Minolta Chroma Meter CR241 (Minolta, Ramsey, N.J., USA). The teeth were further characterized for elemental composition using an energy-dispersive spectrometer, and imaged in both secondary and backscattered electron modes. The results of this study showed that the moderately and severely fluorosed enamel contained an uneven distribution of areas which were more electron-absorbent with a relatively increased carbon content. The changes in the physical characteristics of the teeth could be quantitated by measurements of light reflectance. The color of the teeth was significantly different between groups, with all groups significantly different than normal. C1 EASTMAN DENT CTR,ROCHESTER,NY 14620. FORSYTH DENT CTR,BOSTON,MA 02115. NR 22 TC 10 Z9 12 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6568 J9 CARIES RES JI Caries Res. PD JUL-AUG PY 1995 VL 29 IS 4 BP 251 EP 257 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RE145 UT WOS:A1995RE14500002 PM 7656293 ER PT J AU MOHAGHEGHPOUR, N ABEL, K LAPAGLIA, N EMANUELE, NV AZAD, N AF MOHAGHEGHPOUR, N ABEL, K LAPAGLIA, N EMANUELE, NV AZAD, N TI SIGNAL REQUIREMENTS FOR PRODUCTION OF LUTEINIZING-HORMONE RELEASING-HORMONE BY HUMAN T-CELLS SO CELLULAR IMMUNOLOGY LA English DT Article ID PROTEIN KINASE-C; CYTOPLASMIC FREE CALCIUM; TYROSINE PHOSPHORYLATION; SURFACE MOLECULES; ANTIGEN RECEPTOR; PHOSPHOLIPASE C-GAMMA-1; INTERLEUKIN-2 RECEPTOR; LHRH RECEPTORS; PHORBOL ESTERS; MESSENGER-RNA AB We have previously demonstrated that both human CD4(+) and CD8(+) T lymphocytes produce enhanced levels of luteinizing hormone-releasing hormone (LHRH) mRNA and peptide upon stimulation with monoclonal antibody directed at the CD3 component of the T cell receptor for antigen (TCR) or mitogenic lectin, In the current study, we define the signaling pathways that control TCR-mediated LHRH production by using agents known to affect distinct signals, and compare the messenger systems required for LHRH response to other T-cell-associated activation responses, such as expression of CD69 and interleukin-2 receptor (IL-2R) molecules and production of interleukin-2 (IL-2), Results indicate that the activation of protein kinase C (PKC) is essential for LHRH production by previously nonstimulated T cells, not increased concentration of cytosolic-free calcium ([Ca2+](i)), Phorbol ester (PMA), a direct activator of PKC, provoked LHRH production and cell surface expression of CD69 and IL-BR molecules by T cells, but not IL-2 synthesis, The synthesis of IL-2 by T cells required costimulation with PMA and ionomycin, a Ca2+ ionophore, Consistent with these observations, H7, an inhibitor of PKC, prevented T cells from producing LHRH upon activation with mitogen, However, LHRH production was not suppressed by HA1004, which inhibits all cyclic nucleotide-dependent protein kinases except for PKC, Genistein, a selective inhibitor of protein tyrosine kinase, blocked PMA-induced increase in LHRH production, but not CD69 and IL-2R expression, suggesting that protein tyrosine phosphorylation events distal from PKC activation may play a role in regulating LHRH response, (C) 1995 Academic Press, Inc. C1 US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,RES SERV,HINES,IL 60141. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,MED SERV,HINES,IL 60141. LOYOLA UNIV,STRITCH SCH MED,DEPT MED,MAYWOOD,IL 60153. LOYOLA UNIV,STRITCH SCH MED,PROGRAM MOLEC BIOL,MAYWOOD,IL 60153. RP MOHAGHEGHPOUR, N (reprint author), CALIF PACIFIC MED CTR,RES INST,KUZELL INST ARTHRITIS & INFECT DIS,2200 WEBSTER ST,SUITE 305,SAN FRANCISCO,CA 94115, USA. NR 60 TC 7 Z9 7 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 JUL PY 1995 VL 163 IS 2 BP 280 EP 288 DI 10.1006/cimm.1995.1127 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA RH853 UT WOS:A1995RH85300015 PM 7606799 ER EF