FN Thomson Reuters Web of Science™ VR 1.0 PT J AU JUPPNER, H FLANNERY, MR MCCLURE, I ABOUSAMRA, AB GARDELLA, TJ GOLDRING, SR AF JUPPNER, H FLANNERY, MR MCCLURE, I ABOUSAMRA, AB GARDELLA, TJ GOLDRING, SR TI CHIMERAS BETWEEN THE RECEPTORS FOR CALCITONIN (CT) AND PARATHYROID-HORMONE (PTH) PTH-RELATED PEPTIDE (PTHRP) DEFINE FUNCTIONALLY IMPORTANT DOMAINS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,ARTHRIT UNIT,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S183 EP S183 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500267 ER PT J AU KONG, XF JOUN, H JUEPPNER, H SEGRE, GV KRONENBERG, H ABOUSAMRA, AB AF KONG, XF JOUN, H JUEPPNER, H SEGRE, GV KRONENBERG, H ABOUSAMRA, AB TI CHARACTERIZATION OF THE RAT GENE ENCODING THE RECEPTOR FOR PARATHYROID-HORMONE (PTH) AND PTH-RELATED PEPTIDE (PTHRP) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S183 EP S183 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500265 ER PT J AU LANSKE, BKM KARAPLIS, AC KRONENBERG, HM AF LANSKE, BKM KARAPLIS, AC KRONENBERG, HM TI TARGETED DISRUPTION OF THE PTH PTHRP RECEPTOR GENE BY HOMOLOGOUS RECOMBINATION IN MOUSE EMBRYONIC STEM-CELLS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. MCGILL UNIV,JEWISH GEN HOSP,SMBD,MONTREAL H3T 1E2,QUEBEC,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S189 EP S189 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500290 ER PT J AU LANSKE, BKM HIOUTIM, FFT KRONENBERG, HM KARAPLIS, AC AF LANSKE, BKM HIOUTIM, FFT KRONENBERG, HM KARAPLIS, AC TI TARGETED DISRUPTION OF THE MURINE PTH GENE IN EMBRYONIC STEM-CELLS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MCGILL UNIV,JEWISH GEN HOSP,DIV ENDOCRINOL,SMBD,MONTREAL H3T 1E2,QUEBEC,CANADA. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S189 EP S189 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500289 ER PT J AU LEBOFF, MS JANICEK, M ANGELL, JE BLUMSACK, R HAYES, D SHAPIRO, CL AF LEBOFF, MS JANICEK, M ANGELL, JE BLUMSACK, R HAYES, D SHAPIRO, CL TI MONITORING BONE METASTASES IN BREAST-CANCER PATIENTS USING DUAL X-RAY ABSORPTIOMETRY SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S243 EP S243 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500506 ER PT J AU LEE, K KARAPLIS, AC DEEDS, JD LANSKE, B KRONENBERG, HM SEGRE, GV AF LEE, K KARAPLIS, AC DEEDS, JD LANSKE, B KRONENBERG, HM SEGRE, GV TI MOLECULAR ANALYSIS OF ABNORMAL ENDOCHONDRAL BONE-FORMATION IN PTHRP-LESS MICE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 3 Z9 3 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S145 EP S145 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500116 ER PT J AU MACKEY, SL HEYMONT, JL KRONENBERG, HM DEMAY, MB AF MACKEY, SL HEYMONT, JL KRONENBERG, HM DEMAY, MB TI CHARACTERIZATION OF 1,25(OH)2D(3) RECEPTOR INTERACTIONS WITH TARGET SEQUENCES IN THE HPTH GENE 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 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S138 EP S138 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500086 ER PT J AU MCCAULEY, LK BEECHER, CA MELTON, ME WERKMEISTER, JR JUPPNER, H ABOUSAMRA, AB SEGRE, GV ROSOL, TJ AF MCCAULEY, LK BEECHER, CA MELTON, ME WERKMEISTER, JR JUPPNER, H ABOUSAMRA, AB SEGRE, GV ROSOL, TJ TI REGULATION OF THE PARATHYROID-HORMONE (PTH) RECEPTOR BY TRANSFORMING GROWTH FACTOR-BETA(1) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV MICHIGAN,ANN ARBOR,MI 48109. OHIO STATE UNIV,COLUMBUS,OH 43210. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S181 EP S181 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500258 ER PT J AU NANES, MS KUNO, H DEMAY, M TITUS, L CATHERWOOD, BD RUBIN, J AF NANES, MS KUNO, H DEMAY, M TITUS, L CATHERWOOD, BD RUBIN, J TI THE VITAMIN-D RESPONSE ELEMENT MEDIATES THE INHIBITORY EFFECT OF TNF-ALPHA ON OSTEOCALCIN GENE-TRANSCRIPTION SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 EMORY UNIV,SCH MED,ATLANTA,GA 30322. VET ADM MED CTR,ATLANTA,GA 30033. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S163 EP S163 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500184 ER PT J AU RAO, LG SUTHERLAND, M MUZAFFAR, S WYLIE, J MCBROOM, R WADDELL, J JUPPNER, H MURRAY, TM AF RAO, LG SUTHERLAND, M MUZAFFAR, S WYLIE, J MCBROOM, R WADDELL, J JUPPNER, H MURRAY, TM TI ESTROGEN AFFECTS OSTEOBLASTIC MARKER MESSENGER-RNA LEVELS IN NORMAL HUMAN OSTEOBLASTS FROM FEMORAL BUT NOT ILIAC CREST TRABECULAR BONE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 ST MICHAELS HOSP,CALCIUM RES LAB,TORONTO M5B 1W8,ONTARIO,CANADA. ST MICHAELS HOSP,DEPT ENDOCRINOL,TORONTO M5B 1W8,ONTARIO,CANADA. ST MICHAELS HOSP,DEPT ORTHOPED,TORONTO M5B 1W8,ONTARIO,CANADA. UNIV TORONTO,DEPT MED,TORONTO M5S 1A1,ONTARIO,CANADA. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S300 EP S300 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500734 ER PT J AU REDDY, SV TAKAHASHI, S CHIRGWIN, JM ROODMAN, GD AF REDDY, SV TAKAHASHI, S CHIRGWIN, JM ROODMAN, GD TI MOLECULAR-CLONING AND INITIAL CHARACTERIZATION OF AN AUTOCRINE STIMULATORY FACTOR (SF) THAT INCREASES HUMAN OSTEOCLAST-LIKE CELL-FORMATION 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 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 1993 VL 8 SU 1 BP S166 EP S166 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500199 ER PT J AU SCHIPANI, E WEINSTEIN, LS BERGWITZ, C WHYTE, MP MURRAY, T SCHMIDTKE, J KRONENBERG, HM SEGRE, GV JUPPNER, H AF SCHIPANI, E WEINSTEIN, LS BERGWITZ, C WHYTE, MP MURRAY, T SCHMIDTKE, J KRONENBERG, HM SEGRE, GV JUPPNER, H TI MOLECULAR HETEROGENEITY OF THE PTH/PTHRP RECEPTOR IN PATIENTS WITH PSEUDOHYPOPARATHYROIDISM SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 SHRINERS HOSP CRIPPLED CHILDREN, ST LOUIS, MO USA. MASSACHUSETTS GEN HOSP, DEPT MED, ENDOCRINE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PEDIAT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. NIH, BETHESDA, MD 20892 USA. HANNOVER MED SCH, W-3000 HANNOVER 61, GERMANY. ST MICHAELS HOSP, TORONTO M5B 1W8, ONTARIO, CANADA. NR 0 TC 1 Z9 1 U1 0 U2 2 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 1993 VL 8 SU 1 BP S132 EP S132 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500061 ER PT J AU TAKAHASHI, S SINGER, FR ROODMAN, GD AF TAKAHASHI, S SINGER, FR ROODMAN, GD TI PAGETIC MARROW STROMAL CELL-LINES ENHANCE CFU-GM AND OSTEOCLAST-LIKE CELL-FORMATION 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. ST JOHNS HOSP, CTR BONE, LOS ANGELES, CA 90404 USA. NR 0 TC 3 Z9 3 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 1993 VL 8 SU 1 BP S285 EP S285 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500672 ER PT J AU TAKAHASHI, S GOLDRING, S ROODMAN, GD AF TAKAHASHI, S GOLDRING, S ROODMAN, GD TI DETECTION OF CALCITONIN RECEPTOR (CTR) MESSENGER-RNA AT MULTIPLE STAGES IN THE OSTEOCLAST (OCL) LINEAGE BY THE POLYMERASE CHAIN-REACTION (PCR) 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. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. NR 1 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 1993 VL 8 SU 1 BP S381 EP S381 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20501058 ER PT J AU URENA, P KUBRUSLY, M MANNSTADT, M TRINH, MM SEGRE, GV DRUEKE, T AF URENA, P KUBRUSLY, M MANNSTADT, M TRINH, MM SEGRE, GV DRUEKE, T TI UNDEREXPRESSION OF RENAL PTH PTHRP RECEPTOR MESSENGER-RNA IN UREMIC RATS WITH SECONDARY HYPERPARATHYROIDISM SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HOP NECKER ENFANTS MALAD,INSERM,U90,F-75730 PARIS 15,FRANCE. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S169 EP S169 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500210 ER PT J AU UY, HL DALLAS, M WRIGHT, K BOYCE, B ROODMAN, GD MUNDY, GR AF UY, HL DALLAS, M WRIGHT, K BOYCE, B ROODMAN, GD MUNDY, GR TI MULTIPOTENT HEMATOPOIETIC OSTEOCLAST PRECURSORS ARE INCREASED BY INTERLEUKIN-1 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 INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S388 EP S388 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20501083 ER PT J AU WANG, JT GORN, AH JUPPNER, H SCHIPANI, E GOLDRING, SR AF WANG, JT GORN, AH JUPPNER, H SCHIPANI, E GOLDRING, SR TI HUMAN GIANT-CELL TUMORS OF BONE (GCT) - CHARACTERIZATION OF CELL PHENOTYPE AND DIRECT DEMONSTRATION OF RECEPTORS FOR CALCITONIN (CTR) AND PARATHYROID-HORMONE PARATHYROID-HORMONE RELATED PEPTIDE (PTHR) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,ARTHRIT UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S393 EP S393 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20501103 ER PT J AU WU, H LIU, X BYRNE, M KRANE, S JAENISCH, R AF WU, H LIU, X BYRNE, M KRANE, S JAENISCH, R TI GERM-LINE TRANSMISSION OF A COLLAGENASE-RESISTANT COL1-ALPHA-1 GENE PRODUCED BY HOMOLOGOUS RECOMBINATION IN EMBRYONIC STEM-CELLS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MIT,WHITEHEAD INST,CAMBRIDGE,MA 02142. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S146 EP S146 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500120 ER PT J AU WU, S OKANO, K PIROLA, CJ WANG, HM JUEPPNER, H ABOUSAMRA, AB SEGRE, GV FAGIN, JA CLEMENS, TL AF WU, S OKANO, K PIROLA, CJ WANG, HM JUEPPNER, H ABOUSAMRA, AB SEGRE, GV FAGIN, JA CLEMENS, TL TI ANGIOTENSIN-II DOWN-REGULATES PTHRP RECEPTOR MESSENGER-RNA IN RAT AORTIC SMOOTH-MUSCLE CELLS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S187 EP S187 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500280 ER PT J AU WUCHERPFENNIG, AL LI, YP STETLERSTEVENSON, WG ROSENBERG, AE STASHENKO, P AF WUCHERPFENNIG, AL LI, YP STETLERSTEVENSON, WG ROSENBERG, AE STASHENKO, P TI EXPRESSION OF GELATINASE-B/92 KDA TYPE-IV COLLAGENASE IN HUMAN OSTEOCLASTS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 FORSYTH RES INST,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S164 EP S164 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500189 ER PT J AU YAMIN, M FLANNERY, MR TAPP, DR GORN, AH KRANE, SM GOLDRING, SR AF YAMIN, M FLANNERY, MR TAPP, DR GORN, AH KRANE, SM GOLDRING, SR TI ANALYSIS OF A UNIQUE MURINE BRAIN CALCITONIN RECEPTOR (CTR) CDNA AND PRELIMINARY CHARACTERIZATION OF THE MURINE CTR GENE - EVIDENCE FOR THE EXISTENCE OF FUNCTIONALLY DISTINCT ISOFORMS OF THE CTR SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ARTHRIT UNIT,BOSTON,MA 02114. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. NR 0 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S129 EP S129 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500050 ER PT J AU SAMUELS, MH VELDHUIS, J CAWLEY, C URBAN, RJ LUTHER, M BAUER, R MUNDY, G AF SAMUELS, MH VELDHUIS, J CAWLEY, C URBAN, RJ LUTHER, M BAUER, R MUNDY, G TI PULSATILE SECRETION OF PARATHYROID-HORMONE IN NORMAL YOUNG SUBJECTS - ASSESSMENT BY DECONVOLUTION ANALYSIS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LUTEINIZING-HORMONE; GROWTH-HORMONE; IMMUNORADIOMETRIC ASSAY; FREQUENCY-MODULATION; PITUITARY INVITRO; TRABECULAR BONE; DOWN-REGULATION; PLASMA; RELEASE; FRAGMENT AB Preliminary reports suggest that PTH is secrete in a pulastile fashion. However, available studies have not attempted to calculate actual PTH secretion rates in healthy individuals. To accurately characterize PTH secretory dynamics in healthy subjects, we studied seven young women and six young men, all of whom had hip and spine bone densities by dual photon densitometry in the upper tertile for age-matched control subjects. PTH concentrations were measured by immunoradiometric assay in blood sampled every 2 min over 6 h. Ionized calcium levels were obtained during the second and third hours of the study. Plasma PTH profiles were subjected to deconvolution analysis, which resolves measured hormone levels into secretion and clearance components. Cross-correlation analysis was performed to assess direct or inverse correlations between serum PTH and ionized calcium concentrations at various time lags. In these subjects, PTH was secreted in a dual fashion, with significant basal (tonic) secretion and PTH pulses approximately every 20 min. Pulsatile PTH secretion accounted for approximately 25% of the total secreted PTH. There were no differences in PTH secretory parameters between men and women, nor were there any significant correlations between PTH and ionized calcium concentrations. We conclude that in normal subjects, the predominant mode of PTH secretion is tonic, with superimposed PTH pulses of small amplitude but high frequency. The clinical significance of this complex physiological pattern of secretion awaits further study. C1 UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX 78284 USA. AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. UNIV TEXAS MED BRANCH, GALVESTON, TX 77555 USA. UNIV VIRGINIA, HLTH SCI CTR, CHARLOTTESVILLE, VA 22908 USA. FU NCRR NIH HHS [M01-RR-01-346]; NICHD NIH HHS [NICHHD LK04-HD-00634] NR 33 TC 22 Z9 23 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 1993 VL 77 IS 2 BP 399 EP 403 DI 10.1210/jc.77.2.399 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR719 UT WOS:A1993LR71900021 PM 8345044 ER PT J AU FRISCH, RE SNOW, RC JOHNSON, LA GERARD, B BARBIERI, R ROSEN, B AF FRISCH, RE SNOW, RC JOHNSON, LA GERARD, B BARBIERI, R ROSEN, B TI MAGNETIC-RESONANCE-IMAGING OF OVERALL AND REGIONAL BODY-FAT, ESTROGEN METABOLISM, AND OVULATION OF ATHLETES COMPARED TO CONTROLS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN ADIPOSE-TISSUE; DELAYED MENARCHE; CELL METABOLISM; WOMEN; WEIGHT; AMENORRHEA; ESTRADIOL; RUNNERS; CANCER; ONSET AB The association of menstrual dysfunction of athletes with changes in body composition has been controversial, because most estimations of body fatness have been indirect. Using magnetic resonance imaging, we quantified the sc and internal fat over a specific volume from the fifth thoracic vertebra to femoral fat in the upper thigh and at 4 other anatomical landmarks of 17 athletes (13 oarswomen and 4 runners) compared to that in 11 nonathletic controls. The magnetic resonance imaging data were also analyzed for the athletes and controls in relation to ovulatory status, which was determined by assay of urinary pregnanediol glucuronide, and in relation to the extent of 2-hydroxylation of estradiol to a nonpotent metabolite, 2-hydroxyestrone, which was evaluated by radiometric analysis. We found that 1) the relative and absolute body fat values of the athletes were significantly less (P < 0.05) than those of the controls overall and at each of the six regional sites, although the body weights of the rowers were significantly heavier than those of the controls, and the runners did not differ from the controls; 2) the ratio of sc fat to internal fat was 80%:20% among both athletes and controls, even though the athletes had significantly less fat; 3) the extent of estradiol 2-hydroxylation was significantly (P = 0.005) inversely related to total fat as a percentage of the total volume and to sc fat as a percentage of the total volume (P = 0.004) overall and at each of the regional fat depots; 4) athletes with menstrual disorders had significantly decreased sc and internal fat overall and at all regional sites compared to controls; and 5) a subgroup of ovulatory rowers had an apparent increase or lack of decrease in internal fat at the level of vertebrae lumbar 4, sacral 1, and sacral 4, compared to controls, whereas their sc fat was decreased at these sites compared to that in controls. Changes in regional fat deposits of both sc and internal fat may be involved in the menstrual dysfunction of the athletes in addition to their decreased overall fatness. The body weight and body mass index of well trained athletes can be a misleading index of body composition. C1 HARVARD UNIV, SCH PUBL HLTH, DEPT POPULAT SCI & INT HLTH, BOSTON, MA 02115 USA. UNIV CALIF SAN DIEGO, MED CTR, DEPT RADIOL, SAN DIEGO, CA 92103 USA. MASSACHUSETTS GEN HOSP, DEPT RADIOL, BOSTON, MA 02114 USA. SUNY, HLTH SCI CTR, DEPT OBSTET & GYNECOL, LONG ISL, NY USA. MASSACHUSETTS GEN HOSP, CTR NUCL MAGNET RESONANCE IMAGING, BOSTON, MA 02139 USA. RP FRISCH, RE (reprint author), HARVARD UNIV, SCH PUBL HLTH, CTR POPULAT & DEV STUDIES, 9 BOW ST, CAMBRIDGE, MA 02138 USA. FU NICHD NIH HHS [NICHHD HD-23536] NR 27 TC 21 Z9 21 U1 1 U2 2 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 1993 VL 77 IS 2 BP 471 EP 477 DI 10.1210/jc.77.2.471 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR719 UT WOS:A1993LR71900034 PM 8345054 ER PT J AU BECKER, PS TSE, WT LUX, SE FORGET, BG AF BECKER, PS TSE, WT LUX, SE FORGET, BG TI BETA-SPECTRIN KISSIMMEE - A SPECTRIN VARIANT ASSOCIATED WITH AUTOSOMAL-DOMINANT HEREDITARY SPHEROCYTOSIS AND DEFECTIVE BINDING TO PROTEIN 4.1 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CONGENITAL HEMOLYTIC ANEMIA; CYTOSKELETON; POLYMERASE CHAIN REACTION; ERYTHROCYTE MEMBRANE; ACANTHOCYTES ID MEMBRANE SKELETAL PROTEINS; ERYTHROCYTE SPECTRIN; ESCHERICHIA-COLI; SEQUENCE; ACTIN; IDENTIFICATION; ELLIPTOCYTOSIS; PURIFICATION; DEFICIENCY; MUTATION AB We analyzed the DNA sequence of the cDNA encoding the NH2 terminal region of beta spectrin from members of a kindred with autosomal dominant hereditary spherocytosis associated with defective protein 4.1 binding. We found a point mutation at codon 202 within the 272 amino acid NH2-terminal region of beta-spectrin. TGG was changed to CGG, resulting in the replacement of tryptophan by arginine. The base change eliminates a normally occurring PvuII restriction site and creates a new MspI site. This finding enabled rapid detection or exclusion of the mutation at the DNA level among the family members, including one member for whom this analysis was performed prenatally. The mutation was found only in the affected family members and occurred as a de novo mutation in the proband. It has not been found in 20 other kindreds. The recombinant peptide derived from the normal cDNA retains the capacity to sediment with protein 4.1 and F-actin. The mutant peptide spontaneously degrades. This variant represents both the first point mutation and the first beta spectrin mutation demonstrated in autosomal dominant hereditary spherocytosis. Furthermore, the mutation is located within a conserved sequence among spectrinlike proteins and may define an amino acid critical for protein 4.1 binding activity. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT INTERNAL MED,HEMATOL SECT,NEW HAVEN,CT 06510. CHILDRENS HOSP MED CTR,DIV HEMATOL ONCOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-02656, HL-07262]; NIDDK NIH HHS [DK-19842] NR 27 TC 50 Z9 52 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1993 VL 92 IS 2 BP 612 EP 616 DI 10.1172/JCI116628 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LT169 UT WOS:A1993LT16900011 PM 8102379 ER PT J AU SAPHNER, T TROXEL, AB TORMEY, DC NEUBERG, D ROBERT, NJ PANDYA, KJ EDMONSON, JH ROSENBLUTH, RJ ABELOFF, MD AF SAPHNER, T TROXEL, AB TORMEY, DC NEUBERG, D ROBERT, NJ PANDYA, KJ EDMONSON, JH ROSENBLUTH, RJ ABELOFF, MD TI PHASE-II STUDY OF GOSERELIN FOR PATIENTS WITH POSTMENOPAUSAL METASTATIC BREAST-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HORMONE-RELEASING HORMONE; LHRH-AGONIST TREATMENT; ICI 118630; CELL-LINES; MEDICAL CASTRATION; ANALOG LEUPROLIDE; GROWTH; ANTAGONISTS; ZOLADEX; LEUPRORELIN C1 HACKENSACK MED CTR,BERGEN PASSAIC COMMUNITY CLIN ONCOL PROGRAM,ONCOL PROGRAM,HACKENSACK,NJ. UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI 53706. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FAIRFAX HOSP,FALLS CHURCH,VA 22046. UNIV ROCHESTER,CTR CANC,ROCHESTER,NY 14627. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. FU NCI NIH HHS [CA 23318, CA 21076, CA 21115] NR 50 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1993 VL 11 IS 8 BP 1529 EP 1535 PG 7 WC Oncology SC Oncology GA LR480 UT WOS:A1993LR48000015 PM 8336191 ER PT J AU CHAHINIAN, AP ANTMAN, K GOUTSOU, M CORSON, JM SUZUKI, Y MODEAS, C HERNDON, JE AISNER, J ELLISON, RR LEONE, L VOGELZANG, NJ GREEN, MR AF CHAHINIAN, AP ANTMAN, K GOUTSOU, M CORSON, JM SUZUKI, Y MODEAS, C HERNDON, JE AISNER, J ELLISON, RR LEONE, L VOGELZANG, NJ GREEN, MR TI RANDOMIZED PHASE-II TRIAL OF CISPLATIN WITH MITOMYCIN OR DOXORUBICIN FOR MALIGNANT MESOTHELIOMA BY THE CANCER AND LEUKEMIA GROUP-B SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PLEURAL MESOTHELIOMA; COMBINATION; EXPERIENCE C1 UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032. RHODE ISL HOSP,DEPT MED ONCOL,PROVIDENCE,RI 02902. UNIV CHICAGO,JOINT SECT HEMATOL ONCOL,CHICAGO,IL 60637. UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92103. UNIV CALIF SAN DIEGO,CTR CANC,SAN DIEGO,CA 92103. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV SURG PATHOL,BOSTON,MA 02115. FRONTIER SCI & TECHNOL RES FDN INC,AMHERST,NY. DUKE UNIV,MED CTR,CTR STAT,CANC & LEUKEMIA GRP B,DURHAM,NC 27710. CUNY MT SINAI SCH MED,DEPT NEOPLAST DIS,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT COMMUNITY MED & PATHOL,NEW YORK,NY 10029. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. FU NCI NIH HHS [CA-11789, CA-33601, CA-12046] NR 24 TC 121 Z9 122 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1993 VL 11 IS 8 BP 1559 EP 1565 PG 7 WC Oncology SC Oncology GA LR480 UT WOS:A1993LR48000019 PM 8336195 ER PT J AU TEPLER, I CANNISTRA, SA FREI, E GONIN, R ANDERSON, KC DEMETRI, G NILOFF, J GOODMAN, H MUNTZ, H MUTO, M SHEETS, E ELIAS, AD MAZANET, R WHEELER, C AYASH, L SCHWARTZ, G MCCAULEY, M GAYNES, L HARVEY, S SCHNIPPER, LE ANTMAN, KH AF TEPLER, I CANNISTRA, SA FREI, E GONIN, R ANDERSON, KC DEMETRI, G NILOFF, J GOODMAN, H MUNTZ, H MUTO, M SHEETS, E ELIAS, AD MAZANET, R WHEELER, C AYASH, L SCHWARTZ, G MCCAULEY, M GAYNES, L HARVEY, S SCHNIPPER, LE ANTMAN, KH TI USE OF PERIPHERAL-BLOOD PROGENITOR CELLS ABROGATES THE MYELOTOXICITY OF REPETITIVE OUTPATIENT HIGH-DOSE CARBOPLATIN AND CYCLOPHOSPHAMIDE CHEMOTHERAPY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; HEMATOPOIETIC STEM-CELLS; NON-LYMPHOBLASTIC LEUKEMIA; REFRACTORY OVARIAN-CANCER; BREAST-CANCER; HODGKINS-DISEASE; PHASE-I; G-CSF; COMBINATION CHEMOTHERAPY C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV GYNECOL ONCOL,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV GYNECOL ONCOL,BOSTON,MA 02115. RP TEPLER, I (reprint author), BETH ISRAEL HOSP,DIV HEMATOL ONCOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 65 TC 83 Z9 83 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 1993 VL 11 IS 8 BP 1583 EP 1591 PG 9 WC Oncology SC Oncology GA LR480 UT WOS:A1993LR48000022 PM 8101563 ER PT J AU POLLACK, MH OTTO, MW TESAR, GE COHEN, LS MELTZERBRODY, S ROSENBAUM, JF AF POLLACK, MH OTTO, MW TESAR, GE COHEN, LS MELTZERBRODY, S ROSENBAUM, JF TI LONG-TERM OUTCOME AFTER ACUTE TREATMENT WITH ALPRAZOLAM OR CLONAZEPAM FOR PANIC DISORDER SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID 2-YEAR FOLLOW-UP; AGORAPHOBIA; DISCONTINUATION; THERAPY; IMIPRAMINE; DEPRESSION; MAINTENANCE AB The relative effectiveness of the available treatments for panic disorder may best be understood in the context of the longitudinal course of the disorder. This study examines a number of clinically relevant issues, including long-term outcome after acute treatment, the proportion of patients remaining on single-agent treatment or requiring multiple medications or nonpharmacologic interventions over time, evidence for dose escalation during maintenance high-potency benzodiazepine therapy, and predictors of acute and long-term response to treatment. Fifty-nine panic disorder patients originally randomized to treatment in a controlled trial comparing alprazolam, clonazepam, and placebo were reevaluated in a follow-up study. At a mean follow-up of 1.5 years, 78% of patients remained on medication and the mean dosage of alprazolam and clonazepam did not increase. Our data suggest that most patients maintain benefit with long-term pharmacotherapy but that residual symptomatology may require more intensive or additional treatment strategies. Response at the endpoint of the acute trial was significantly associated with pretrial baseline Clinical Global Impression Scale score and the presence of dysthymia. Poor outcome at follow-up was associated with total duration of the disorder, agoraphobic subtype, and the presence of comorbid social phobia. We underscore the potential importance of comorbid affective and anxiety disorders as well as phobic patterns in determining long-term response to treatment. RP POLLACK, MH (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,WACC 815-15 PARKMAN ST,BOSTON,MA 02114, USA. NR 34 TC 79 Z9 80 U1 0 U2 5 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 1993 VL 13 IS 4 BP 257 EP 263 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA LM936 UT WOS:A1993LM93600005 PM 8376613 ER PT J AU KASSNER, PD HEMLER, ME AF KASSNER, PD HEMLER, ME TI INTERCHANGEABLE ALPHA-CHAIN CYTOPLASMIC DOMAINS PLAY A POSITIVE ROLE IN CONTROL OF CELL-ADHESION MEDIATED BY VLA-4, A BETA(1) INTEGRIN SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PHORBOL ESTER TREATMENT; ACTIVATED T-CELLS; MONOCLONAL-ANTIBODY; GPIIB-IIIA; REGULATED EXPRESSION; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; LYMPHOCYTES-T; INDUCED PHOSPHORYLATION; FIBRONECTIN MOLECULES AB Integrins can exist in a range of functional states, depending on the cell type and its state of activation. Although the mechanism that controls activity is unknown, it has been suggested that for some integrins, alpha chain cytoplasmic domains may exert either a negative effect or no effect on adhesion function. To address this issue for VLA-4 (an alpha4beta1, heterodimer), we constructed an alpha4 cytoplasmic deletion mutant and chimeric alpha chains composed of the extracellular domains of alpha4 and the cytoplasmic domains of alpha2, alpha4, or alpha5. Upon stable transfection of wild-type alpha4, VLA-4 heterodimer was obtained that mediated (a) poor adhesion to CS1 peptide, fibronectin, or vascular cell adhesion molecule 1 (VCAM-1) (in K562 cells); (b) poor adhesion to CS1 peptide but moderate adhesion to VCAM-1 (in MIP101 cells); and (c) moderate adhesion to both CS1 peptide and VCAM-1 (in PMWK cells). Chimeric alpha4 constructs and wild-type alpha4 yielded similar results in these cell lines. In contrast, truncation of the alpha4 cytoplasmic domain (after the conserved GFFKR motif) caused an almost complete loss of adhesive activity in all three cell lines. Thus, several interchangeable alpha chain cytoplasmic domains play a fundamentally positive role in determining the state of constitutive activity for VLA-4. The alpha chain cytoplasmic domain is also required for agonist-stimulated adhesion, since phorbol ester stimulated the cell adhesion mediated by wild-type and chimeric alpha chains, but not by the cytoplasmic deletion mutant. The inactivity of both wild-type VLA-4 (in K562 cells), and truncated VLA-4 (in all three cell lines) was overcome by the addition of a stimulatory anti-beta1 monoclonal antibody. Thus, the alpha cytoplasmic domain-dependent cellular mechanism controlling both constitutive and agonist-stimulated VLA-4 activity could be bypassed by external manipulation of the integrin. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,M613,44 BINNEY ST,BOSTON,MA 02115. FU NIGMS NIH HHS [GM-46526] NR 76 TC 88 Z9 88 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1993 VL 178 IS 2 BP 649 EP 660 DI 10.1084/jem.178.2.649 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LP830 UT WOS:A1993LP83000030 PM 7688030 ER PT J AU MANTHEY, CL QURESHI, N STUTZ, PL VOGEL, SN AF MANTHEY, CL QURESHI, N STUTZ, PL VOGEL, SN TI LIPOPOLYSACCHARIDE ANTAGONISTS BLOCK TAXOL-INDUCED SIGNALING IN MURINE MACROPHAGES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; DIPHOSPHORYL-LIPID-A; RHODOPSEUDOMONAS-SPHAEROIDES; BINDING-PROTEIN; EXPRESSION; ENDOTOXIN; LPS; NEUTROPHILS; DERIVATIVES; RECEPTORS AB Taxol is the prototype of a new class of microtubule stabilizing agents with promising anticancer activity. Several studies show that taxol mimics the actions of lipopolysaccharide (LPS) on murine macrophages. To investigate the mechanism of taxol-induced macrophage stimulation, we evaluated the ability of Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA) and SDZ 880.431 to block taxol-induced effects. RsDPLA and SDZ 880.431 are lipid A analogues that lack LPS-like activity, but inhibit the actions of LPS, presumably by blocking critical cellular binding sites. We report that RsDPLA and SDZ 880.431 potently inhibited taxol-induced TNF secretion, gene activation, and protein-tyrosine phosphorylation. The role of microtubules in taxol signaling was investigated. Taxol-induced microtubule bundling in primary and transformed RAW 264.7 macrophages was not blocked by RsDPLA or SDZ 880.431. Taxotere, a semisynthetic taxoid, was more potent than taxol as an inducer of microtubule bundling, but did not induce tumor necrosis factor alpha secretion and gene activation. These data dissociate the microtubule effects of taxol from macrophage stimulation and suggest that taxol stimulates macrophages through an LPS receptor-dependent mechanism. The results underscore the potential of taxol as a tool for studying LPS receptor activation and provide insights into possible therapeutic actions of this new class of drugs. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL,4301 JONES BRIDGE RD,BETHESDA,MD 20814. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MYCOBACTERIOL RES LAB,MADISON,WI 53705. UNIV WISCONSIN,SCH AGR & LIFE SCI,DEPT BACTERIOL,MADISON,WI 53706. SANDOZ GMBH,A-1235 VIENNA,AUSTRIA. FU NIAID NIH HHS [AI-08451, AI-18797] NR 41 TC 108 Z9 108 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1993 VL 178 IS 2 BP 695 EP 702 DI 10.1084/jem.178.2.695 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LP830 UT WOS:A1993LP83000035 PM 8101863 ER PT J AU EAGLE, KA BLANK, DJ AGUIAR, E FIRTH, LM AF EAGLE, KA BLANK, DJ AGUIAR, E FIRTH, LM TI ECONOMIC-IMPACT OF REGRESSION OF LEFT-VENTRICULAR HYPERTROPHY BY ANTIHYPERTENSIVE DRUGS SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article AB We examined the long-term cost effectiveness of treating hypertensive patients aged 47 to 65 yrs with agents that promote regression of left ventricular hypertrophy (LVH). Beta-blockers, calcium channel blockers, and ACE inhibitors were compared with standard therapy. To estimate the effect of drug therapy on LVH regression, we pooled data from 25 studies. We estimated the effects of LVH regression on cardiovascular outcomes using Framingham data and the studies of Devereux. The estimated costs of differing treatment strategies included average costs of drug therapy and follow-up care, and direct costs of lost productivity owing to untoward outcomes. Patients were classified by initial left ventricular mass index (LVMI) as low (<95 g/m2), moderate (95-125 g/m2) and high risk (>125 g/m2). The data suggested that all three agents reduce LVMI in moderate- and high-risk groups. The respective average reductions in LVMI in high risk and moderate risk were 20% and 12% for ACE inhibitors, 18% and 8% for beta-blockers, and 5% and 6% for calcium channel blockers. We estimated the relative improvement in cardiovascular morbidity/mortality from LVH reversal required for overall cost savings with each drug class compared with a standard regimen. Patients treated with calcium channel blockers needed to realise at least 72% of the expected reduction in cardiovascular outcomes from LVH regression for this strategy to be less costly. For ACE inhibitors and beta-blockers, only 32% and 26%, respectively, of the expected reduction in poor outcomes from LVH reversal were required for these agents to be more cost effective. Long-term costs of treatment with ACE inhibitors versus beta-blockers were similar. A 25% higher treatment cost of ACE inhibitors was offset by a greater effectiveness in reversing LVH with attendant lower rates of cardiovascular complications. RP EAGLE, KA (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD AUG PY 1993 VL 7 IS 4 BP 341 EP 351 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LV962 UT WOS:A1993LV96200005 PM 8105082 ER PT J AU GUSTAFSSON, K GERMANA, S SUNDT, TM SACHS, DH LEGUERN, C AF GUSTAFSSON, K GERMANA, S SUNDT, TM SACHS, DH LEGUERN, C TI EXTENSIVE ALLELIC POLYMORPHISM IN THE CDR2-LIKE REGION OF THE MINIATURE SWINE CD4 MOLECULE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; ANTIGEN-PRESENTING CELLS; CLASS-II MHC; MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; MUTATIONAL ANALYSIS; STRUCTURAL-ANALYSIS; GP120 BINDING; HIV-1 GP120 AB MHC class II polymorphism is well documented whereas only minimal polymorphism has been reported for the CD4 molecule with which it interacts. We report on the structural basis of an allelic polymorphism of the CD4 molecule in miniature swine. Eleven of 13 nucleotide differences between the 2 alleles cause amino acid replacements. A majority of these replacements are clustered in a region protruding as a loop structure, termed Ig CDR2-like, from the surface of the amino terminal domain. This part of the human CD4 appears to comprise the binding site for the human immunodeficiency virus gp120 protein. The loop structure has also been implicated in the binding of CD4 to MHC class II, but this is currently a matter of some controversy. Our previous results have indicated that the porcine CD4 polymorphism, that we now show is situated in this loop, does not significantly affect the binding to class II. However, because the polymorphism appears to have been selected for and is situated in a very exposed part of the molecule, it is likely to be of functional significance. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,MGH-E,BLDG 149,13TH ST,BOSTON,MA 02129. NCI,TRANSPLANTAT BIOL SECT,IMMUNOL BRANCH,BETHESDA,MD 20892. NR 30 TC 18 Z9 20 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1993 VL 151 IS 3 BP 1365 EP 1370 PG 6 WC Immunology SC Immunology GA LP725 UT WOS:A1993LP72500021 PM 8335933 ER PT J AU MANJUNATH, N JOHNSON, RS STAUNTON, DE PASQUALINI, R ARDMAN, B AF MANJUNATH, N JOHNSON, RS STAUNTON, DE PASQUALINI, R ARDMAN, B TI TARGETED DISRUPTION OF CD43 GENE ENHANCES T-LYMPHOCYTE ADHESION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID WISKOTT-ALDRICH SYNDROME; SIALOPHORIN CD43; SURFACE SIALOGLYCOPROTEIN; MONOCLONAL-ANTIBODY; HOMOTYPIC ADHESION; PHORBOL ESTER; CROSS-LINKING; CELL-ADHESION; MOLECULE; GLYCOPROTEINS AB CD43 is a major leukocyte surface glycoprotein thought to have important functions for T lymphocyte adhesion and activation. We investigated the function of CD43 by using gene targeting to eliminate CD43 expression in the human T lymphocyte line CEM and then testing their adhesive phenotype. Loss of CD43 expression by the CEM cells enhanced their homotypic adhesion and binding to two distinct ligands, fibronectin and HIV-1 gp120. The enhanced homotypic adhesion was blocked specifically by an anti-beta1 integrin mAb, and the enhanced binding to fibronectin and gp120 was blocked specifically by anti-beta1 integrin and anti-CD4 mAb, respectively. Partial reconstitution of CD43 expression in the CD43-negative cells resulted in a corresponding reversion to a less adhesive phenotype. These data suggest that CD43 interferes with T lymphocyte adhesion and that CD43 can regulate lymphocyte adhesion by providing a threshold that must be overcome for cell-cell and cell-ligand interactions to occur. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,750 WASHINGTON ST,BOX 245,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,DEPT PATHOL,BOSTON,MA 02115. OI Johnson, Randall/0000-0002-4084-6639 NR 43 TC 121 Z9 121 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 1 PY 1993 VL 151 IS 3 BP 1528 EP 1534 PG 7 WC Immunology SC Immunology GA LP725 UT WOS:A1993LP72500039 PM 8335945 ER PT J AU CAMPBELL, TB YOUNG, RK ERON, JJ DAQUILA, RT TARPLEY, WG KURITZKES, DR AF CAMPBELL, TB YOUNG, RK ERON, JJ DAQUILA, RT TARPLEY, WG KURITZKES, DR TI INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION IN-VITRO BY THE BISHETEROARYLPIPERZINE ATEVIRDINE (U-87201E) IN COMBINATION WITH ZIDOVUDINE OR DIDANOSINE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID REVERSE-TRANSCRIPTASE INHIBITORS; HIV-1 REPLICATION; SYNERGISTIC INHIBITION; RIBAVIRIN ANTAGONIZES; INTERFERON-ALPHA; THERAPY; SENSITIVITY; RESISTANT; AZT; DERIVATIVES AB The bisheteroarylpiperazine nonnucleoside reverse transcriptase (RT) inhibitor atevirdine effectively inhibits human immunodeficiency virus type 1 (HIV-1) in vitro. Clinical isolates with a wide range of 50% inhibitory concentrations (IC50s) of zidovudine (IC50, 0.003 to >2.0 muM) and didanosine (IC50, 0.02 to > 10.0 muM) were inhibited by atevirdine (median IC50, 0.74 muM; range, 0.06-1.60). Cross-resistance to atevirdine in zidovudine- or didanosine-resistant isolates was not observed. Combinations of atevirdine and zidovudine were highly synergistic against zidovudine-resistant clinical isolates of HIV-1. By contrast, these combinations were mostly additive when tested against zidovudine-susceptible isolates. Combinations of atevirdine and didanosine were additive in their effects against both didanosine-susceptible and -resistant isolates. These data suggest that the interaction of atevirdine with HIV-1 RT is different than that of other nonnucleoside RT inhibitors and that combinations of atevirdine and zidovudine may be useful in patients with AIDS who have initially received monotherapy with zidovudine. C1 VET ADM MED CTR,DENVER,CO 80220. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UPJOHN CO,LABS,KALAMAZOO,MI 49001. RP CAMPBELL, TB (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT MED,DIV INFECT DIS,CAMPUS BOX B-168,4200 E 9TH AVE,DENVER,CO 80262, USA. FU NIAID NIH HHS [AI-32770, AI-08764] NR 35 TC 23 Z9 23 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1993 VL 168 IS 2 BP 318 EP 326 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LN813 UT WOS:A1993LN81300009 PM 7687641 ER PT J AU DUNKEL, EC DEFREITAS, D SCHEER, DI SIEGEL, ML ZHU, Q WHITLEY, RJ SCHAFFER, PA PAVANLANGSTON, D AF DUNKEL, EC DEFREITAS, D SCHEER, DI SIEGEL, ML ZHU, Q WHITLEY, RJ SCHAFFER, PA PAVANLANGSTON, D TI A RABBIT MODEL FOR HUMAN CYTOMEGALOVIRUS-INDUCED CHORIORETINAL DISEASE (RETRACTED ARTICLE. SEE VOL 177, PG 1778, 1998) SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Retracted Publication ID IMMUNE-DEFICIENCY SYNDROME; VIRUS RETINITIS; INTRAVITREAL GANCICLOVIR; MOLECULAR-CLONING; GUINEA-PIG; INFECTION; THERAPY; RETINOPATHY; ZIDOVUDINE; INVIVO AB AD169, a well-characterized laboratory strain of human cytomegalovirus (HCMV), was used to establish an animal model of progressive HCMV chorioretinal disease by injection of 10(5) pfu into the rabbit vitreous. Chorioretinal, vitreous, and pulmonary disease were monitored by HCMV recovery, clinical observation, antigen localization, and histopathology. Vitritis and focal areas of immune cellular infiltrates were seen in inner retinal layers on days 2-4 after inoculation. Disease progressed with more severe vitritis and to involve the outer retinal layers in areas of mixed monocytic cellular infiltrates, retinal destruction, choroidal edema, and congestion. HCMV was recovered from chorioretinal cell sonicate cultures in titers ranging from 10(4) to 10(5) pfu during peak disease, and HCMV antigens were detected focally by immunofluorescence in retinal layers on days 2 and 4 after inoculation. A rabbit model of HCMV chorioretinitis similar to human CMV disease allows investigation of HCMV pathogenesis and new antiviral therapies and evaluation of immune system modulation of the HCMV ocular infection. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. SCHEER & CO, BRANFORD, CT USA. UNIV ALABAMA, DEPT PEDIAT, BIRMINGHAM, AL 35294 USA. RP DUNKEL, EC (reprint author), HARVARD UNIV, SCH MED, SCHEPENS EYE RES INST, DEPT OPHTHALMOL, 20 STANIFORD ST, BOSTON, MA 02114 USA. RI Freitas, Denise/G-9374-2015 OI Freitas, Denise/0000-0002-3389-6021 FU NEI NIH HHS [EY-08851]; NIAID NIH HHS [AI-15100] NR 31 TC 12 Z9 12 U1 0 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1993 VL 168 IS 2 BP 336 EP 344 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LN813 UT WOS:A1993LN81300012 PM 8393056 ER PT J AU SOLNICK, JV OROURKE, J LEE, A PASTER, BJ DEWHIRST, FE TOMPKINS, LS AF SOLNICK, JV OROURKE, J LEE, A PASTER, BJ DEWHIRST, FE TOMPKINS, LS TI AN UNCULTURED GASTRIC SPIRAL ORGANISM IS A NEWLY IDENTIFIED HELICOBACTER IN HUMANS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACTIVE CHRONIC GASTRITIS; GASTROSPIRILLUM-HOMINIS; CAMPYLOBACTER-PYLORI; SHAPED BACTERIA; ANIMAL-MODEL; SP-NOV; MUCOSA; MUSTELAE; DISEASE; ULTRASTRUCTURE AB ''Gastrospirillum hominis'' is an uncultivated spiral bacterium in human gastric mucosa that is larger and more tightly coiled than Helicobacter pylori. In an attempt to determine if this organism is a new species of Helicobacter, its 16S rRNA gene was cloned and sequenced. Gastric mucosa from 2 patients infected with ''Gastrospirillum hominis'' was fed to specific pathogen-free mice. Electron microscopy of gastric tissue confirmed that the mice became colonized with ''Gastrospirillum hominis.'' The 16S rRNA gene from bacterial target sequences was amplified directly from mouse stomach tissue by the polymerase chain reaction (PCR), cloned into Escherichia coli, and sequenced. Both fragments were 16S rRNA genes from the Helicobacter genus that were most closely related to Helicobacter felis. ''Gastrospirillum hominis'' is probably a newly recognized Helicobacter infection in humans. Because this is the only Helicobacter organism that infects both humans and small animals, it may be particularly suited for studies of pathogenesis. C1 UNIV NEW S WALES,DEPT MICROBIOL & IMMUNOL,SYDNEY,NSW,AUSTRALIA. FORSYTH DENT CTR,BOSTON,MA 02115. RP SOLNICK, JV (reprint author), STANFORD UNIV,MED CTR,SCH MED,DEPT MED,DIV INFECT DIS,STANFORD,CA 94305, USA. OI Solnick, Jay/0000-0002-7435-8393 FU NIAID NIH HHS [AI-23796] NR 45 TC 191 Z9 194 U1 1 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1993 VL 168 IS 2 BP 379 EP 385 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LN813 UT WOS:A1993LN81300018 PM 8335974 ER PT J AU VELEZ, JD ALLENDOERFER, R LUTHER, M RINALDI, MG GRAYBILL, JR AF VELEZ, JD ALLENDOERFER, R LUTHER, M RINALDI, MG GRAYBILL, JR TI CORRELATION OF IN-VITRO AZOLE SUSCEPTIBILITY WITH IN-VIVO RESPONSE IN A MURINE MODEL OF CRYPTOCOCCAL MENINGITIS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; AMPHOTERICIN-B; CONTROLLED TRIAL; FLUCONAZOLE AB Correlations between in vitro susceptibility and in vivo responses to fluconazole were sought in a mouse model of cryptococcal meningitis. Twenty clinical isolates were used. Two distinct populations were noted. Eight high-virulence isolates had an LD50 of less-than-or-equal-to 252 cfu of Cryptococcus neoformans. Twelve low-virulence isolates had an LD50 of >252 cfu. For 7 low-virulence isolates, the LD50 was >20,000 cfu. C. neoformans also had a broad range of in vitro susceptibilities (MICs of 1.25 to >80 mug/mL) at 24 h. A correlation was found between the MIC and the minimum effective dose of fluconazole in mice. This was observed with both survival and tissue counts as parameters of efficacy. This study documents for the first time the in vivo relevance of in vitro susceptibility to an azole antifungal for C. neoformans. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. RP VELEZ, JD (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,DIV INFECT DIS,MAIL CODE 111,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 10 TC 55 Z9 55 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1993 VL 168 IS 2 BP 508 EP 510 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LN813 UT WOS:A1993LN81300043 PM 8335995 ER PT J AU TYAN, ML AF TYAN, ML TI EFFECT OF PROMETHAZINE ON LUMBAR VERTEBRAL BONE MASS IN POSTMENOPAUSAL WOMEN SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE CALCIUM; ESTROGEN; OSTEOPENIA; PROMETHAZINE; POSTMENOPAUSAL ID AGE-RELATED OSTEOPENIA; OSTEOPOROSIS; CELLS; MOUSE AB Objectives. Work in mice suggests that the age-related loss of bone mineral noted in that species is caused by an intrinsic defect in a haematopoietic cell population which results directly or indirectly in increased bone resorption. This age-related loss of bone mineral is prevented or reversed by well-tolerated doses of promethazine HCL. The present study was undertaken to determine if promethazine would retard or reverse bone loss in postmenopausal women. Design. Postmenopausal women whose spine (L2 to L4) bone mineral content (BMC) was two standard deviations below young normal values were assigned randomly to receive calcium or promethazine and calcium daily. Subjects who had been taking oral oestrogen for more than 4 years also were assigned randomly but independently to the calcium or promethazine groups. Setting. AU subjects were seen in the out-patient clinic of the Department of Medicine, School of Medicine, University of California, Los Angeles. Subjects. Healthy, ambulatory postmenopausal females were recruited by word of mouth and by advertisement from the local community. Fifty-four subjects completed the first 6 months of the study and 43 completed 30 months. Interventions. The subjects were assigned randomly to receive 1 000 mg calcium daily or promethazine 50 mg and calcium 1000 mg daily throughout the period of the study. Main outcome measures. Bone mineral content of the lumbar vertebrae (L2 to L4) was determined by dual photon densitometry every 6 months. Dorsolumbar spine X-rays were obtained yearly and at the completion of the study to detect new compression fractures. Results. In the groups not taking oestrogen, BMC decreased at the rate of 1.53% year-1 in the group given only calcium; in contrast, BMC increased at 3.22% year-1 in the group given promethazine and calcium (P < 0.001). Among the women taking oestrogen, increases in mean BMC were noted in both groups, but those taking promethazine and calcium had a greater rate of increase than observed in the group taking only calcium (5.62% vs. 1.97% per year-1, P < 0.001). Conclusions. These results suggest that promethazine can induce a modest increase in vertebral BMC in postmenopausal women who are not taking oestrogen and greater increases in those who are. C1 UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA USA. RP TYAN, ML (reprint author), W LOS ANGELES VAMC, W111M, WILSHIRE & SAWTELLE BLVD, LOS ANGELES, CA 90073 USA. FU FDA HHS [FD-R-00296] NR 18 TC 13 Z9 13 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD AUG PY 1993 VL 234 IS 2 BP 143 EP 148 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA LQ918 UT WOS:A1993LQ91800006 PM 8340736 ER PT J AU HUTCHISON, FN AF HUTCHISON, FN TI ENDOTHELIN - A NEW ROLE FOR AN OLD FRIEND SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Editorial Material ID INDUCED DIABETIC RATS; IMMUNOREACTIVITY C1 RALPH H JOHNSON VET AFFAIRS MED CTR,CHARLESTON,SC. RP HUTCHISON, FN (reprint author), MED UNIV S CAROLINA,CHARLESTON,SC 29425, USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD AUG PY 1993 VL 122 IS 2 BP 126 EP 127 PG 2 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA LR502 UT WOS:A1993LR50200001 PM 8340696 ER PT J AU ROBINSON, DR XU, LL KNOELL, CT TATENO, S OLESIAK, W AF ROBINSON, DR XU, LL KNOELL, CT TATENO, S OLESIAK, W TI MODIFICATION OF SPLEEN PHOSPHOLIPID FATTY-ACID COMPOSITION BY DIETARY FISH-OIL AND BY N-3 FATTY-ACID ETHYL-ESTERS SO JOURNAL OF LIPID RESEARCH LA English DT Article DE EICOSAPENTAENOIC ACID; DOCOSAHEXAENOIC ACID; RETROCONVERSION ID PERFORMANCE LIQUID-CHROMATOGRAPHY; EICOSAPENTAENOIC ACID; RHEUMATOID-ARTHRITIS; DOCOSAHEXAENOIC ACIDS; SUPPLEMENTATION; MICE; ENRICHMENT; GENERATION; METABOLISM; RATS AB We have compared the effects of diets containing purified ethyl esters of either eicosapentaenoic acid, docosahexaenoic acid, or a mixture of both of these compounds, with diets containing either purified fish oil or beef tallow on spleen phospholipid fatty acid composition. Autoimmune mice, the (NZB x NZW)F1 strain, were fed with experimental diets for 14 weeks, after which spleen phospholipids were extracted and separated into classes by HPLC, and the alkenylacyl, alkylacyl, and diacyl subclasses of glycerylphosphatidylethanolamine and glycerylphosphatidylcholine were resolved as their benzoyl esters by HPLC. Fatty acids were analyzed by capillary gas-liquid chromatography of their methyl esters. Each of the marine lipid diets suppressed n-6 fatty acids and elevated n-3 fatty acids in all phospholipids. The eicosapentaenoic acid ethyl ester diets led to high levels of eicosapentaenoic acid and docosapentaenoic acid (C22:5n-3), but little or no increase in docosahexaenoic acid. The docosahexaenoic acid ethyl ester diets elevated docosahexaenoic acid, docosapentaenoic acid, and eicosapentaenoic acid in all phospholipids, indicating that extensive retroconversion of 22 carbon n-3 fatty acids had occurred. These results document changes in the fatty acid composition of mammalian phospholipids that are induced by dietary fish oil triglycerides and by dietary long chain n-3 fatty acid ethyl esters. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. RP ROBINSON, DR (reprint author), MASSACHUSETTS GEN HOSP,MED SERV,ARTHRITIS UNIT,BOSTON,MA 02114, USA. FU NIAID NIH HHS [AI 28465]; NIAMS NIH HHS [AR 03564, AR 19427] NR 37 TC 26 Z9 26 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD AUG PY 1993 VL 34 IS 8 BP 1423 EP 1434 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ598 UT WOS:A1993LQ59800015 PM 8409773 ER PT J AU ROBINSON, DR XU, LL TATENO, S GUO, MY COLVIN, RB AF ROBINSON, DR XU, LL TATENO, S GUO, MY COLVIN, RB TI SUPPRESSION OF AUTOIMMUNE-DISEASE BY DIETARY N-3 FATTY-ACIDS SO JOURNAL OF LIPID RESEARCH LA English DT Article DE (NZB X NZW)F1 MICE; EICOSAPENTAENOIC ACID ETHYL ESTER; DOCOSAHEXAENOIC ACID ETHYL ESTER; FISH OIL; AUTOIMMUNE GLOMERULONEPHRITIS ID EICOSAPENTAENOIC ACID; MURINE LUPUS; FISH OIL; MICE; ENRICHMENT; ABSORPTION; NEPHRITIS; ESTERS AB Previous studies have demonstrated that dietary fish oil preparations have anti-inflammatory effects in humans and in experimental animals, but the individual components of fish oils that are responsible for their anti-inflammatory effects have not been documented. We therefore investigated in (NZB x NZW)Fl mice, a model for human systemic lupus erythematosus, the effects of diets containing ethyl esters of two purified n-3 fatty acids, eicosapentaenoic acid (EPA-E) and docosahexaenoic acid (DHA-E), a refined fish oil triglyceride (FO) which contained 55% n-3 fatty acids, and beef tallow (BT) which contains no n-3 fatty acids. The diets were initiated prior to the development of overt renal disease at age 22 weeks, and continued for 14 weeks. The extent of the renal disease was quantified by light microscopy and by proteinuria. Diets containing either 10 wt% FO, 10% EPA-E, or 6% or 10% DHA-E alleviated the severity of the renal disease, compared to the BT diet, whereas diets containing either 3% or 6% EPA-E or 3% DHA-E were less effective. Two diets containing approximately 3:1 mixtures of EPA-E and DHA-E alleviated the renal disease to a greater extent than expected for either of these fatty acids given singly. We believe that these experiments provide the first demonstration of anti-inflammatory effects of individual dietary n-3 fatty acids. The results also indicate that the anti-inflammatory effects of fish oils depend on synergistic effects of at least two n-3 fatty acids. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,DEPT PATHOL,BOSTON,MA 02114. RP ROBINSON, DR (reprint author), MASSACHUSETTS GEN HOSP,MED RES LABS,ARTHRITIS UNIT,BOSTON,MA 02114, USA. FU NIAID NIH HHS [AI28465]; NIAMS NIH HHS [AR19427, ARO3564] NR 15 TC 58 Z9 59 U1 1 U2 3 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD AUG PY 1993 VL 34 IS 8 BP 1435 EP 1444 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ598 UT WOS:A1993LQ59800016 PM 8409774 ER PT J AU ADLER, EM FINK, JS AF ADLER, EM FINK, JS TI CALCIUM REGULATION OF VASOACTIVE INTESTINAL POLYPEPTIDE MESSENGER-RNA ABUNDANCE IN SH-SY5Y HUMAN NEUROBLASTOMA-CELLS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE VASOACTIVE INTESTINAL POLYPEPTIDE; CALCIUM; CYCLIC AMP; NEUROPEPTIDE; SH-SY5Y CELLS; NEURONAL PLASTICITY ID DEPENDENT PROTEIN-KINASE; IMMEDIATE-EARLY GENES; LONG-TERM POTENTIATION; NEURO-BLASTOMA CELLS; SQUID GIANT SYNAPSE; CYCLIC-AMP; MEMBRANE DEPOLARIZATION; C-FOS; TYROSINE-HYDROXYLASE; SOMATOSTATIN GENE AB Second messenger regulation of gene expression provides a mechanism by which neurons can transduce environmental stimuli into long-term changes in the expression of molecules involved in neuronal signaling. We have investigated calcium-dependent induction of vasoactive intestinal polypeptide (VIP) mRNA and compared it with induction of VIP mRNA by cyclic AMP. Depolarization with 60 mM KCl or exposure to the calcium ionophore A23187 increases VIP mRNA levels in SH-SY5Y cells. The increase in VIP mRNA content in response to Ca2+ mobilization is slow, independent of adenylate cyclase activation, and requires de novo protein synthesis. The increase in VIP mRNA content in response to elevation of cyclic AMP levels by forskolin/isobutylmethylxanthine is independent of Ca2+ influx and does not require new protein synthesis. The mRNA for the transcription factors ATF-3, c-fos, c-jun, junB, and zif/268 is induced by A23187. Of these, ATF-3 showed the greatest relative induction by A23187 compared with induction by forskolin/isobutylmethylxanthine. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROBIOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. FU NINDS NIH HHS [NS 27514] NR 69 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1993 VL 61 IS 2 BP 727 EP 737 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA LM753 UT WOS:A1993LM75300040 PM 7687662 ER PT J AU WAKASUGI, S FISCHMAN, AJ BABICH, JW ARETZ, HT CALLAHAN, RJ NAKAKI, M WILKINSON, R STRAUSS, HW AF WAKASUGI, S FISCHMAN, AJ BABICH, JW ARETZ, HT CALLAHAN, RJ NAKAKI, M WILKINSON, R STRAUSS, HW TI METAIODOBENZYLGUANIDINE - EVALUATION OF ITS POTENTIAL AS A TRACER FOR MONITORING DOXORUBICIN CARDIOMYOPATHY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID CONGESTIVE HEART-FAILURE; RADIONUCLIDE ANGIOGRAPHY; ENDOMYOCARDIAL BIOPSY; CARDIOTOXICITY; ADRIAMYCIN; SCINTIGRAPHY; THERAPY AB We evaluated alterations in cardiac adrenergic neuron activity and progression of left ventricular dysfunction in comparison with the severity of structural changes using a rat model of adriamycin cardiomyopathy. Rats were treated with adriamycin (2 mg/kg s.c. once a week) for 6, 7, 8 and 9 wk. Accumulation of I-125-metaiodobenzylguanidine (MIBG) 4 hr after intravenous administration was determined and left ventricular ejection fraction (LVEF) was calculated from gated blood-pool images. H & E and Masson-Trichrome stained specimens of the myocardium were examined by light microscopy. Histopathologic examination demonstrated dose-dependent myocyte damage, although there were no differences between the 8-wk and 9-wk groups. LVEF did not differ between controls and the 6-wk group (81.3% +/- 5.5% versus 82.1% +/- 4.8%, p = ns). LVEF began to decrease slightly in the 7-wk group (75.0% +/- 5.7%, p < 0.05) and showed a remarkable decrease in the 8-wk group (53.7% +/-2.6%, p < 0.001). In the 9-wk group, LVEF diminished to 47.9% +/- 3.1% (p < 0.001), accompanied by massive pleural effusions and ascites. MIBG accumulation in the heart (%ID/heart) significantly and progressively diminished; 1.42% +/- 0.15% in the 6-wk group, 1.06% +/- 0.16% in the 7-wk group, 0.77% +/- 0.13% in the 8-wk group and 0.34% +/- 0.11% in the 9-wk group, respectively p < 0.001, compared to controls (1.99% +/- 0.30%). These results demonstrate that MIBG accumulation in the heart showed a greater and more linear dose-dependent decrease than LVEF. Furthermore, MIBG uptake was significantly reduced in the 6-wk group where only mild myocyte damage (isolated vacuolation or myofibrillar loss) was observed. Thus, MIBG may be a sensitive biochemical marker of adriamycin cardiomyopathy. C1 MASSACHUSETTS GEN HOSP, DIV NUCL MED, 55 FRUIT ST, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT RADIOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT RADIOL, BOSTON, MA 02115 USA. MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA. NEW ENGLAND DEACONESS HOSP, DEPT PATHOL, BOSTON, MA 02215 USA. NEW ENGLAND DEACONESS HOSP, DEPT RADIOL, BOSTON, MA 02215 USA. NR 25 TC 25 Z9 25 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 1993 VL 34 IS 8 BP 1282 EP 1286 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LP023 UT WOS:A1993LP02300013 ER PT J AU YAOITA, H FISCHMAN, AJ WILKINSON, R KHAW, BA JUWEID, M STRAUSS, HW AF YAOITA, H FISCHMAN, AJ WILKINSON, R KHAW, BA JUWEID, M STRAUSS, HW TI DISTRIBUTION OF DEOXYGLUCOSE AND TECHNETIUM-99M-GLUCARATE IN THE ACUTELY ISCHEMIC MYOCARDIUM SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID REPERFUSED CANINE MYOCARDIUM; VOLUME REGULATION; METABOLISM; INJURY; INFARCTION; DOG; ABNORMALITIES; DEPLETION; INTEGRITY; ZONES AB The regional myocardial distribution of Tc-99m-glucarate was compared to H-3-deoxyglucose in 22 rabbits with left circumflex marginal artery occlusion. In 12 rabbits, tissue radioactivity measurements were compared to the results of triphenyl tetrazolium chloride staining and light microscopy. In 10 additional rabbits, the myocardial sodium space ((NaCl)-Na-24), an indicator of tissue edema induced by injury, was compared to the distribution of deoxyglucose and glucarate. Technetium-99m-glucarate accumulated in injured myocardium within 6 hr after coronary ligation and myocardial concentration was greatest in the most severely injured zones (TTC unstained). Hydrogen-3-deoxyglucose behaved as a marker of ischemia but concentrated in tissue with injury ranging from mild ischemia (TTC stained) to transmural infarction (TTC unstained). Both Tc-99m-glucarate and H-3-deoxyglucose concentrated in acute, severely injured myocardial tissue. These studies suggest that Tc-99m-glucarate is a useful tracer for evaluating myocardial injury. In addition, it appears that Tc-99m-glucarate and H-3-deoxyglucose demarcate different points in the spectrum of myocardial injury. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,32 FRUIT ST,BOSTON,MA 02114. WASHINGTON UNIV,MED CTR,MALLINCKRODT INST RADIOL,ST LOUIS,MO 63130. NR 20 TC 22 Z9 23 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 1993 VL 34 IS 8 BP 1303 EP 1308 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LP023 UT WOS:A1993LP02300016 PM 8326389 ER PT J AU NAKAI, K AHMAD, M NAKAKI, M WILKINSON, R CALLAHAN, RJ ELMALEH, DR FISCHMAN, AJ STRAUSS, HW AF NAKAI, K AHMAD, M NAKAKI, M WILKINSON, R CALLAHAN, RJ ELMALEH, DR FISCHMAN, AJ STRAUSS, HW TI SERIAL COURSE OF LEFT-VENTRICULAR FUNCTION, PERFUSION AND FATTY-ACID UPTAKE IN THE CARDIOMYOPATHIC HAMSTER SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID CALCIUM-ANTAGONIST RECEPTORS; SYRIAN-HAMSTER; MYOCARDIAL-METABOLISM; HEPTADECANOIC ACID; HEART; ACCUMULATION; HEREDITARY; VERAPAMIL; TRACER; MODEL AB To determine the relationship of metabolic and perfusion changes to alterations in ventricular function in the course of cardiomyopathy, we performed serial measurements of ejection fraction, myocardial perfusion, fatty acid uptake of 3-methyl-p[I-123]-phenyl-pentadecanoic acid ([I-123]3MPDA) and myocardial histology in Syrian hamsters genetically predisposed to the development of congestive cardiomyopathy (Bio T0-2) (n = 30) and normal age-matched control animals (Bio F1B) (n = 13). To obtain high-resolution information about the myocardium at the time of onset of the first noticeable decrease in ventricular function, a multitracer autoradiographic study using Tc-99m-pyrophosphate, Tl-201 and [C-14]3MPDA was obtained at 90 days of age. Baseline ejection fraction recorded at 60 days averaged 60.3%; by 90 days, it decreased to 54.3% (p < 0.05), falling to 41.3% at 180 days (p < 0.01) and declining to 30% at the end of the study. A progressive increase in the extent of myocytolysis, fibrosis and calcification was seen in the histologic studies as the animals aged. The ratio of fatty acid-to-thallium uptake dropped from 0.51 +/- 0.09 to 0.45 +/- 0.11 (p < 0.01), which is in parallel with the reduction in ejection fraction. The thallium lung-to-heart ratio increased from 0.51 at 90 days to 0.59 at 270 days (p < 0.05), which corresponds to the worsening of cardiac function. The macroautoradiographic studies demonstrated slight uptake of pyrophosphate in the myopathic hamster hearts and minimal changes in the regional distribution of fatty acid compared to that of perfusion. We conclude that the decrease in ventricular function parallels the severity of myocytolysis and fibrosis. Although decreased fatty acid uptake was apparent at an early stage, the extent of the change is modest and is difficult to detect from external images. C1 MASSACHUSETTS GEN HOSP,DIV NUCL MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. NR 34 TC 8 Z9 8 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 1993 VL 34 IS 8 BP 1309 EP 1315 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LP023 UT WOS:A1993LP02300017 PM 8326390 ER PT J AU STRAUSS, HW AF STRAUSS, HW TI THE AGNOSTICS PRAYER SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material RP STRAUSS, HW (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 1993 VL 34 IS 8 BP A3 EP A3 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LP023 UT WOS:A1993LP02300001 ER PT J AU SOCRANSKY, SS HAFFAJEE, AD AF SOCRANSKY, SS HAFFAJEE, AD TI EFFECT OF THERAPY ON PERIODONTAL INFECTIONS SO JOURNAL OF PERIODONTOLOGY LA English DT Article; Proceedings Paper CT SYMP ON HOST/PARASITE INTERVENTION IN THE TREATMENT OF PERIODONTAL DISEASE : PROSPECTS FOR THE FUTURE CY MAY 02, 1992 CL HARVARD SCH DENT MED, BOSTON, MA SP UPJOHN HO HARVARD SCH DENT MED DE PERIODONTAL DISEASES DRUG THERAPY; PERIODONTAL DISEASES MICROBIOLOGY; SURGICAL FLAPS; SCALING; ANTIBIOTICS THERAPEUTIC USE ID ATTACHMENT LOSS; BACTERIAL INVASION; RADICULAR DENTIN; RISK INDICATORS; DISEASE; CEMENTUM; HUMANS; TEETH AB PERIODONTAL DISEASE PROGRESSION REQUIRES the simultaneous presence of high numbers of pathogens, low numbers of compatible or beneficial species, a conducive local environment, and a susceptible host. Effective therapy acts by altering one or more of these factors. Data from an ongoing study were used to examine the biological basis of treatment success or failure. Seventeen subjects showing disease progression were treated by Widman flap surgery at deep sites, scaling at shallow sites, and 1 of 4 randomly-assigned, systemically-administered adjunctive agents including amoxicillin/clavulanate potassium (Au) (n = 3), ibuprofen (n = 3), tetracycline (n = 9), or a placebo (n = 2). Clinical measurements and microbiological samples (enumerated using DNA probes) taken from the mesial aspect of each tooth pre-treatment and 12 months post-treatment were compared and 418 pre- and 418 post-therapy plaque samples were enumerated. Overall, the 4 treatments resulted in pocket depth reduction and ''gain'' in attachment. After therapy, the percentage of sites colonized by Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens, and Bacteroides forsythus was decreased and counts > 10(6) were less frequent. Large attachment level gains were accompanied by major decreases in these species and were more frequent in subjects receiving antibiotics. A small number of sites in each treatment group became deeper and/or lost attachment. More than half of these sites were detected in 2 subjects who were older (65 vs. 44), had higher serum antibody to Actinobacillus actinomycetemcomitans serotype a (506 vs. 125 ELISA units), A. actinomycetemcomitans serotype b (518 vs. 130), and Campylobacter rectus (39 vs. 18). They also had the lowest mean total viable subgingival counts (1.1 vs. 12.3 x 10(6)) and the lowest counts of each species pre-therapy. In the total subject group, increased mean counts of P. gingivalis and B. forsythus were seen at sites showing attachment loss > 1 mm after therapy, while counts decreased at sites showing no attachment change or ''gain'' > 1 mm. RP SOCRANSKY, SS (reprint author), FORSYTH DENT CTR,DEPT PERIODONTOL,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE02487] NR 17 TC 45 Z9 47 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 1993 VL 64 IS 8 SU S BP 754 EP 759 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA LW334 UT WOS:A1993LW33400003 PM 8410615 ER PT J AU CHAMBERLAIN, J OFFORD, SJ WOLFE, BB TYAU, LS WANG, HL FRAZER, A AF CHAMBERLAIN, J OFFORD, SJ WOLFE, BB TYAU, LS WANG, HL FRAZER, A TI POTENCY OF 5-HYDROXYTRYPTAMINE(1A) AGONISTS TO INHIBIT ADENYLYL-CYCLASE ACTIVITY IS A FUNCTION OF AFFINITY FOR THE LOW-AFFINITY STATE OF [H-3] 8-HYDROXY-N,N-DIPROPYLAMINOTETRALIN ([H-3]8-OH-DPAT) BINDING SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RAT HIPPOCAMPAL MEMBRANES; BETA-ADRENERGIC-RECEPTOR; PHARMACOLOGICAL AGONISM; 5-HT1A RECEPTOR; MULTIPLE STATES; FRONTAL-CORTEX; G-PROTEINS; GTP; CELLS; SITES AB In this study, the radiolabeled 5-hydroxytryptamine1A agonist, [H-3]8-hydroxy-N,N-dipropylamino tetralin ([H-3]B-OH-DPAT), was shown to have both a high (K(d), 0.7 +/- 0.2 nM) and a low (K(d), 17 +/- 4 nM) affinity binding component in rat hippocampal homogenate preparations in the absence of guanine nucleotides. The high-affinity binding component was markedly reduced by the elimination of Mg++ from the incubation medium and the addition of both the nonhydrolyzable guanine nucleotide guanylylimidodiphosphate (Gpp(NH)p) (100 muM) and 1.0 mM EDTA to the incubation medium. Under these latter conditions, a single binding affinity component was observed with a K(d) of 11 +/- 1 nM, a value in good agreement with the value for the low-affinity component measured in the absence of Gpp(NH)p. Further, the B(max) value for the single low-affinity binding component measured in the presence of Gpp(NH)p was essentially equivalent to the total of the two B(max) values found in the absence of Gpp(NH)p. A binding assay was developed using 15 nM [H-3]8-OH-DPAT to determine the affinities of serotonergic drugs for the low-affinity component of [H-3]8-OH-DPAT binding and these values were compared with their affinities for the high-affinity binding component as well as their potencies in a hippocampal adenylyl cyclase assay. For agonists, the K(i) value for the high-affinity binding component was always less than the low-affinity K(i) value, whereas the antagonist spiperone had similar values for both the high-affinity and low-affinity binding components. Furthermore, when K(i) values of the agonists for the high-affinity [H-3]8-OH-DPAT binding component were compared to their EC50 values for inhibition of forskolin-stimulated adenylyl cyclase activity, K(i)/EC50 ratios were 1 5-1 00. By contrast, the ratio of the K(i) values for the low-affinity component to the EC50 values were near unity for these drugs. It appears that the potency of agonists to elicit 5-hydroxytryptamine1A-Mediated responses is quantitatively better related to their affinity for the low-affinity state of [H-3]8-OH-DPAT binding than for the high-affinity state. C1 UNIV PENN,SCH MED,DEPT VET AFFAIRS MED CTR,NEUROPSYCHOPHARMACOL UNIT 151E,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19104. GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,WASHINGTON,DC 20057. FU NIMH NIH HHS [MH 14654, MH 48125] NR 46 TC 27 Z9 27 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1993 VL 266 IS 2 BP 618 EP 625 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LT482 UT WOS:A1993LT48200020 PM 8355195 ER PT J AU SHEA, SA ANDRES, LP SHANNON, DC BANZETT, RB AF SHEA, SA ANDRES, LP SHANNON, DC BANZETT, RB TI VENTILATORY RESPONSES TO EXERCISE IN HUMANS LACKING VENTILATORY CHEMOSENSITIVITY SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CENTRAL HYPOVENTILATION SYNDROME; ANAEROBIC THRESHOLD; CHILDREN AB 1. In healthy humans during aerobic exercise ventilation increases and mean arterial P(CO2) usually remains constant over a wide range of CO2 production. 2. Congenital central hypoventilation syndrome (CCHS) is associated with ineffective chemoreceptor regulation of breathing and severe hypoventilation during sleep (requiring mechanical ventilation) reflecting abnormalities in the brainstem respiratory complex or its chemoreceptor input. Such patients can have adequate spontaneous ventilation during resting wakefulness and participate in normal activities. 3. If children with CCHS have normal ventilatory responses to exercise then chemoreceptors are not necessary for this ventilatory response or the resultant control of P(a,CO2) during exercise. We studied five children with CCHS (aged 8-17 years) with abnormally low ventilatory responses to steady-state increased end-tidal P(CO2) ( < 9 ml min-1 kg-1 mmHg-1) and five age -matched controls. 4. Depth and rate of breathing, end-tidal P(CO2), end-tidal P(O2), CO2 production, 02 utilization and heart rate were monitored during the following conditions: whilst subjects stood at rest; following the onset of treadmill exercise (4 m.p.h.); during steady-state exercise (4 m.p.h.); during an incremental maximal exercise test; and during recovery from exercise. 5. There were no significant differences in the ventilatory responses between CCHS subjects and controls during the onset of treadmill exercise, in the dynamic response in achieving the steady-state exercise, during steady-state exercise, in the recovery from steady-state exercise, or during incremental exercise (up to the point of presumed blood lactate accumulation, as indicated by gas exchange criteria). There was a very small mean increase in P(CO2) in both groups during steady-state exercise (controls 1.4 mmHg; CCHS 2.2 mmHg). 6. The only differences which emerged between groups were (i) slightly more variability in P(CO2) in the CCHS group during steady-state exercise, and (ii) the OCHS subjects did not hyperventilate, as the controls did, at exercise levels above the point of presumed blood lactate accumulation. 7. Breath-by-breath coefficient of variation of ventilation was significantly reduced in both groups during steady-state exercise compared to rest. There were no differences between groups in either state. 8. We conclude that chemoreceptors are not necessary for an appropriate ventilatory response to aerobic exercise. Hence, other stimuli, such as afferent information from the exercising limbs or signals related to activation of the motor cortex, can increase alveolar ventilation in close proportion to CO2 production. 9. The lack of hyperventilatory response to blood lactate accumulation during heavy exercise provides good evidence that these CCHS patients have ineffective peripheral chemoreception. C1 MASSACHUSETTS GEN HOSP,PEDIAT PULM UNIT,BOSTON,MA 02114. RP SHEA, SA (reprint author), HARVARD UNIV,SCH PUBL HLTH,PHYSIOL PROGRAM,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL19170, HL46690, HL07118] NR 26 TC 72 Z9 72 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD AUG PY 1993 VL 468 BP 623 EP 640 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA LU086 UT WOS:A1993LU08600037 PM 8254528 ER PT J AU Vandervoort, PM Thoreau, DH Rivera, JM Levine, RA Weyman, AE Thomas, JD AF Vandervoort, Pieter M. Thoreau, David H. Rivera, J. Miguel Levine, Robert A. Weyman, Arthur E. Thomas, James D. TI Automated Flow Rate Calculations Based on Digital Analysis of Flow Convergence Proximal to Regurgitant Orifices SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article AB Objectives. The purpose of the study was to develop and validate an automated method for calculating regurgitant flow rate using color Doppler echocardiography. Background. The proximal flow convergence method is a promising approach to quantitate valvular regurgitation noninvasively because it allows one to calculate regurgitant flow rate and regurgitant orifice area; however, defining the location of the regurgitant orifice is often difficult and can lead to significant error in the calculated flow rates. To overcome this problem we developed an automated algorithm to locate the orifice and calculate flow rate based on the digital Doppler velocity map. Methods. This algorithm compares the observed velocities with the anticipated relative velocities, cos phi/2 pi r(2). The orifice is localized as the point with maximal correlation between predicted and observed velocity, whereas flow rate is specified as the slope of the regression line. We validated this algorithm in an in vitro model for flow through circular orifices with planar surroundings and a porcine bioprosthesis. Results. For flow through circular orifices, flow rates calculated on individual Doppler maps and on an average of eight velocity maps showed excellent agreement with true flow, with r = 0.977 and Delta Q = -3.7 +/- 15.8 cm(3)/s and r = 0.991 and Delta Q = -4.3 +/- 8.5 cm(3)/s, respectively. Calculated flow rates through the bioprosthesis correlated well but underestimated true flow, with r = 0.97, Delta Q = -10.9 +/- 12.5 cm(3)/s, suggesting flow convergence over an >2 pi. This systematic underestimation was corrected by assuming an effective convergence angle of 212 degrees. Conclusions. This algorithm accurately locates the regurgitant orifice and calculates regurgitant flow rate for circular orifices with planar surroundings. Automated analysis of the proximal flow field is also applicable to more physiologic surfaces surrounding the regurgitant orifice; however, the convergence angle should be adjusted. This automated algorithm should make quantification of regurgitant flow rate and regurgitant orifice area more reproducible and readily available in clinical cardiology practice. C1 [Thoreau, David H.; Levine, Robert A.; Weyman, Arthur E.] Massachusetts Gen Hosp, Noninvas Cardiac Lab, Boston, MA 02114 USA. [Thoreau, David H.; Levine, Robert A.; Weyman, Arthur E.] Harvard Univ, Sch Med, Boston, MA USA. [Vandervoort, Pieter M.; Rivera, J. Miguel; Thomas, James D.] Cleveland Clin Fdn, Dept Cardiol, Desk F15,9500 Euclid Ave, Cleveland, OH 44195 USA. RP Thomas, JD (reprint author), Cleveland Clin Fdn, Dept Cardiol, Desk F15,9500 Euclid Ave, Cleveland, OH 44195 USA. FU Bayer Fund for Cardiovascular Research, New York, New York FX Dr. Thomas is supported in part by the Bayer Fund for Cardiovascular Research, New York, New York. NR 18 TC 66 Z9 66 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG PY 1993 VL 22 IS 2 BP 535 EP 541 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V42RN UT WOS:000209631000026 PM 8335826 ER PT J AU Brooks, R Torchiana, D Vlahakes, GJ Ruskin, JN McGovern, BA Garan, H AF Brooks, Ross Torchiana, David Vlahakes, Gus J. Ruskin, Jeremy N. McGovern, Brian A. Garan, Hasan TI Successful Implantation of Cardioverter-Defibrillator Systems in Patients With Elevated Defibrillation Thresholds SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article AB Objectives. The purpose of this study was to conduct a retrospective analysis of 16 patients with high initial defibrillation thresholds in whom a three-electrode system was used to lower defibrillation thresholds and permit implantation of a cardioverter-defibrillator system. Background. Patients with high defibrillation thresholds (>25 J) are uncommon but may be problematic to physicians implanting cardioverter-defibrillator systems. Most conventional systems use two defibrillating electrodes, most commonly two epicardial patches. When defibrillation thresholds remain elevated despite extensive testing of a two-electrode system, a third electrode can be incorporated and tested. However, few published data exist on the use of a three-electrode system in patients with high defibrillation thresholds. Methods. After failure to achieve satisfactory defibrillation thresholds <25 J with a two-patch electrode system, a third electrode was incorporated and tested. In all cases, two electrodes were joined to form a common cathode or anode, while a single electrode was used as the opposite polarity electrode. Various three-electrode configurations were then tested. Results. In all 16 patients, satisfactory defibrillation thresholds were achieved and a cardioverter-defibrillator was implanted (95% confidence interval [CI] = 0% to 21%). The mean final defibrillation threshold using the revised three-electrode system was 19.5 +/- 3.7 J (p < 0.0001). A mean of 6 +/- 3 electrode configurations/patient were tested before the final configuration was selected. A total of nine different electrode configurations were used in the 16 study patients; the most common of these incorporated left and right ventricular patches as combined cathode and a superior vena cava coil (n = 5) or right atrial patch electrode (n = 3) as single anode. Conclusion. Patients with high initial defibrillation thresholds can generally undergo successful cardioverter-defibrillator implantation with a three-electrode system if enough electrode configurations are tested after a third electrode is incorporated. C1 [Brooks, Ross; Torchiana, David; Vlahakes, Gus J.; Ruskin, Jeremy N.; McGovern, Brian A.; Garan, Hasan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Boston, MA USA. RP Brooks, R (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. NR 23 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG PY 1993 VL 22 IS 2 BP 569 EP 574 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V42RN UT WOS:000209631000031 PM 8335831 ER PT J AU BARRY, MJ COCKETT, ATK HOLTGREWE, HL MCCONNELL, JD SIHELNIK, SA WINFIELD, HN AF BARRY, MJ COCKETT, ATK HOLTGREWE, HL MCCONNELL, JD SIHELNIK, SA WINFIELD, HN TI RELATIONSHIP OF SYMPTOMS OF PROSTATISM TO COMMONLY USED PHYSIOLOGICAL AND ANATOMICAL MEASURES OF THE SEVERITY OF BENIGN PROSTATIC HYPERPLASIA SO JOURNAL OF UROLOGY LA English DT Article DE PROSTATIC HYPERTROPHY; SYMPTOMS; URODYNAMICS ID TRANSURETHRAL RESECTION; URODYNAMIC FINDINGS; NATURAL-HISTORY; RESIDUAL URINE; PROSTATECTOMY; HYPERTROPHY; MORTALITY; MEN; UROFLOWMETRY; REOPERATION AB In previous studies the severity of symptoms of prostatism in men with benign prostatic hyperplasia have not correlated well with prostate size, degree of bladder trabeculation, uroflowmetry or post-void residual volume. As part of a prospective cohort study of benign prostatic hyperplasia treatment effectiveness in 4 university-based urology practices, we correlated symptom severity and these commonly used measures of disease severity. Symptom severity was quantified using the American Urological Association symptom index. Analyses were based on 198 outpatients completing a standardized evaluation (84 of these men have completed 6 months of followup after treatment with prostatectomy, balloon dilation, terazosin or watchful waiting). At baseline, symptom severity was not correlated with uroflowmetry, post-void residual, prostate size and degree of bladder trabeculation. However, symptom severity was much more strongly related to overall health status than the other measures. Reduction in symptoms with treatment did correlate with improvements in uroflowmetry. This poor baseline correlation with symptoms may reflect unreliability in measurement of the physiological/anatomical variables. Alternatively, these parameters may be measuring different pathophysiological phenomena. C1 SW MED CTR,DEPT UROL,DIV UROL,DALLAS,TX. AMER UROL ASSOC,DEPT UROL,BALTIMORE,MD. UNIV IOWA,COLL MED,DEPT UROL,IOWA CITY,IA 52242. WALTER REED ARMY MED CTR,DEPT UROL,UROL SERV,WASHINGTON,DC 20307. UNIV ROCHESTER,SCH MED,DEPT UROL,ROCHESTER,NY 14627. JOHNS HOPKINS UNIV,SCH MED,DEPT UROL,BALTIMORE,MD 21205. RP BARRY, MJ (reprint author), MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,BOSTON,MA 02114, USA. FU AHRQ HHS [HS 06336, HS 06689] NR 36 TC 279 Z9 284 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1993 VL 150 IS 2 BP 351 EP 358 PN 1 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA LM765 UT WOS:A1993LM76500018 PM 7686980 ER PT J AU MCDOUGAL, WS BYRNE, JC AF MCDOUGAL, WS BYRNE, JC TI RADIONUCLIDE CONSTANT-PRESSURE PERFUSION SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 CORNELL UNIV, MED CTR, NEW YORK HOSP, DIV UROL, NEW YORK, NY 10021 USA. RP MCDOUGAL, WS (reprint author), MASSACHUSETTS GEN HOSP, DEPT UROL, BOSTON, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1993 VL 150 IS 2 BP 426 EP 426 PN 1 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA LM765 UT WOS:A1993LM76500041 ER PT J AU MCDOUGAL, WS AF MCDOUGAL, WS TI RADIONUCLIDE CONSTANT-PRESSURE PERFUSION SO JOURNAL OF UROLOGY LA English DT Editorial Material RP MCDOUGAL, WS (reprint author), MASSACHUSETTS GEN HOSP, DEPT UROL, BOSTON, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1993 VL 150 IS 2 BP 426 EP 426 PN 1 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA LM765 UT WOS:A1993LM76500040 ER PT J AU SANDERS, R BISSADA, NK BIELSKY, S AF SANDERS, R BISSADA, NK BIELSKY, S TI URETEROENTERIC ANASTOMOTIC STRICTURES - TREATMENT WITH PALMAZ PERMANENT INDWELLING STENTS SO JOURNAL OF UROLOGY LA English DT Note DE URETER; URETERAL OBSTRUCTION; URINARY DIVERSION; STENTS; ANASTOMOSIS, SURGICAL ID IMPLANTED URETHRAL STENT; MANAGEMENT AB A 70-year-old man with bilateral ureteroenteric anastomotic strictures and recurrent urinary tract sepsis that continued despite bilateral Double-J dagger ureteral stents and nephrostomy tubes was successfully treated with bilateral Palmaz double dagger indwelling permanent stents. C1 MED UNIV S CAROLINA,DIV UROL ONCOL,171 ASHLEY AVE,CHARLESTON,SC 29425. RALPH JOHNSON MED CTR,CHARLESTON,SC. NR 12 TC 19 Z9 20 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 AUG PY 1993 VL 150 IS 2 BP 469 EP 470 PN 1 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA LM765 UT WOS:A1993LM76500060 PM 8326581 ER PT J AU ATALA, A CIMA, LG KIM, W PAIGE, KT VACANTI, JP RETIK, AB VACANTI, CA AF ATALA, A CIMA, LG KIM, W PAIGE, KT VACANTI, JP RETIK, AB VACANTI, CA TI INJECTABLE ALGINATE SEEDED WITH CHONDROCYTES AS A POTENTIAL TREATMENT FOR VESICOURETERAL REFLUX SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT 1992 ANNUAL MEETING OF THE SECTION ON UROLOGY OF THE AMERICAN ACADEMY OF PEDIATRICS CY OCT 10-15, 1992 CL SAN FRANCISCO, CA SP AMER ACAD PEDIAT, SECT UROL DE VESICOURETERAL REFLUX; ENDOSCOPY; CARTILAGE ID URINARY-INCONTINENCE; POLYTETRAFLUOROETHYLENE INJECTION; ENDOSCOPIC INJECTION; TEFLON-INJECTION; GROWTH; MIGRATION; CULTURES AB Injection of polytetrafluoroethylene (Teflon) or collagen has been used in the endoscopic treatment of vesicoureteral reflux. Although the principle of an endoscopic treatment is valid, there are concerns regarding the long-term safety and effectiveness of these substances. The goal of several investigators has been to find alternate implant materials that would be safe for human use. Toward this goal we conducted a study to determine the effect of chondrocytes using a biodegradable polymer solution as a template. Hyaline cartilage was obtained from the articular surfaces of calf shoulders and chondrocytes were harvested. Chondrocyte suspensions were concentrated to 20, 30 and 40 x 10(6) cells per cc and mixed with dry alginate powder (a biodegradable polymer) to form a gel. Twelve athymic mice were injected subcutaneously with a chondrocyte-alginate solution. Each mouse had 4 injection sites, consisting of control, 10, 15 and 20 x 10(6) chondrocyte cells (48 injection sites). Mice were sacrificed at 2, 4, 6 and 12 weeks after injection. Histological examination of the injection sites demonstrated evidence of cartilage formation in 34 of the 36 experimental injection sites. Gross examination of the injection sites with increasing time showed that the polymer gels were progressively replaced by cartilage. The ultimate size of the cartilage formed was related to the initial chondrocyte concentration injected, and appeared to be uniform and stable within each category. There was no evidence of cartilage formation in the 12 controls. Histological analyses of distant organs showed no evidence of cartilage or alginate gel migration, or granuloma formation. In conclusion, chondrocyte-alginate gel suspensions are injectable, appear to be nonmigratory and are able to conserve their volume. In addition, the use of autologous cartilage cells would preclude an immunological reaction. These preliminary studies indicate that autologous cartilage-polymer gel solutions may be potentially useful in the endoscopic treatment of reflux. C1 CHILDRENS HOSP MED CTR,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02114. RP ATALA, A (reprint author), CHILDRENS HOSP MED CTR,DEPT PLAST SURG,DIV PERINATAL MED,BOSTON,MA 02115, USA. OI Atala, Anthony/0000-0001-8186-2160 NR 23 TC 145 Z9 152 U1 0 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1993 VL 150 IS 2 BP 745 EP 747 PN 2 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA LM767 UT WOS:A1993LM76700043 PM 8326638 ER PT J AU GERTLER, JP OCASIO, VH DALMAN, RL PORTER, J PATERSON, I EDWARDS, J THOMPSON, MM AF GERTLER, JP OCASIO, VH DALMAN, RL PORTER, J PATERSON, I EDWARDS, J THOMPSON, MM TI ENDOTHELIN PRODUCTION BY HYPOXIC HUMAN ENDOTHELIUM SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID CELLS; EXPRESSION; PEPTIDE; INJURY AB Purpose: The physiologic significance of endothelin remains incompletely defined. Procoagulant and antifibrinolytic activities are increased in hypoxic cultured human umbilical venous endothelial cells (HUVEC). We examined the effect of hypoxia on HUVEC endothelin-I production in vitro to determine whether a correlation existed between the procoagulant and antifibrinolytic response to hypoxia previously observed and an increase in vasoconstrictor peptide secretion by hypoxic HUVEC. Methods: Cultured HUVEC were rendered hypoxic (Po, = 40 mm Hg) or control (PO2 = 120 mm Hg) for 24 hours. Media were either standard, 5 gm glucose/L (high glucose), or contained 500 units superoxide dismutase/ml (SOD). Endothelin-like immunoreactivity for endothelin-I (ET-IR) in conditioned media was measured by radioimmunoassay and expressed as mean femtomoles per milliliter (+/- SD) per 100,000 cells. Viability of HUVEC was assessed by trypan blue exclusion. Significance was determined by use of Student's t test. Results. Conditioned media from hypoxic cells contained 76% more ET-IR than was found in control counterparts (p < 0.004). The addition of high glucose or SOD did not diminish ET-IR; a trend to higher ET-IR was present in both these groups versus standard media (303% and 226%, respectively, p < 0.03). Conclusions: Thus 24 hours of hypoxia caused an increase in conditioned-media ET-IR in cultured HUVEC. Because SOD or greater substrate availability did not diminish endothelin presence in conditioned media, it seems that hypoxic induction of endothelin-1 production or secretion is signaled in a fashion unrelated to cell toxicity from the hypoxic period. C1 SUNY HLTH SCI CTR,DEPT SURG,BROOKLYN,NY. RP GERTLER, JP (reprint author), MASSACHUSETTS GEN HOSP,DIV VASC SURG,15 PARKMAN ST,SUITE 464,BOSTON,MA 02114, USA. NR 27 TC 26 Z9 28 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD AUG PY 1993 VL 18 IS 2 BP 178 EP 184 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA LT175 UT WOS:A1993LT17500004 PM 8350426 ER PT J AU WYATT, R SULLIVAN, N THALI, M REPKE, H HO, D ROBINSON, J POSNER, M SODROSKI, J AF WYATT, R SULLIVAN, N THALI, M REPKE, H HO, D ROBINSON, J POSNER, M SODROSKI, J TI FUNCTIONAL AND IMMUNOLOGICAL CHARACTERIZATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEINS CONTAINING DELETIONS OF THE MAJOR VARIABLE REGIONS SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; EXPERIMENTALLY INFECTED CHIMPANZEES; RECOMBINANT SOLUBLE CD4; NEUTRALIZING ANTIBODIES; MEMBRANE-FUSION; HTLV-III; TRANSMEMBRANE GLYCOPROTEIN; SYNCYTIUM FORMATION; HIV-1 INFECTIVITY; RECEPTOR-BINDING AB Deletions of the major variable regions (V1/V2, V3, and V4) of the human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein were created to study the role of these regions in function and antigenicity. Deletion of the V4 region disrupted processing of the envelope glycoprotein precursor. In contrast, the deletion of the V1/V2 and/or V3 regions yielded processed exterior envelope glycoproteins that retained the ability to interact with the gp41 transmembrane glycoprotein and the CD4 receptor. Shedding of the gp120 exterior glycoprotein by soluble CD4 was observed for the mutant with the V3 deletion but did not occur for the V1/V2-deleted mutant. None of the deletion mutants formed syncytia or supported virus entry. Importantly, the affinity of neutralizing antibodies directed against the CD4-binding region for the multimeric envelope glycoprotein complex was increased dramatically by the removal of both the V1/V2 and V3 structures. These results indicate that, in addition to playing essential roles in the induction of membrane fusion, the major variable regions mask conserved neutralization epitopes of the HIV-1 gp120 glycoprotein from antibodies. These results explain the temporal pattern associated with generation of HIV-1-neutralizing antibodies following infection and suggest stratagems for eliciting improved immune responses to conserved gp120 epitopes. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. NYU,SCH MED,AARON DIAMOND AIDS RES CTR CITY NEW YORK,NEW YORK,NY 10003. UNIV CONNECTICUT,HLTH SERV,DEPT PEDIAT,FARMINGTON,CT 06030. FU NIAID NIH HHS [AI31783, AI24755, T32 AI07386] NR 87 TC 199 Z9 200 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1993 VL 67 IS 8 BP 4557 EP 4565 PG 9 WC Virology SC Virology GA LM272 UT WOS:A1993LM27200013 PM 8331723 ER PT J AU MOORE, JP THALI, M JAMESON, BA VIGNAUX, F LEWIS, GK POON, SW CHARLES, M FUNG, MS SUN, B DURDA, PJ AKERBLOM, L WAHREN, B HO, DD SATTENTAU, QJ SODOROSKI, J AF MOORE, JP THALI, M JAMESON, BA VIGNAUX, F LEWIS, GK POON, SW CHARLES, M FUNG, MS SUN, B DURDA, PJ AKERBLOM, L WAHREN, B HO, DD SATTENTAU, QJ SODOROSKI, J TI IMMUNOCHEMICAL ANALYSIS OF THE GP120 SURFACE GLYCOPROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 - PROBING THE STRUCTURE OF THE C4-DOMAIN AND V4-DOMAIN AND THE INTERACTION OF THE C4-DOMAIN WITH THE V3-LOOP SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING MONOCLONAL-ANTIBODIES; CD4 BINDING-SITE; ENVELOPE GLYCOPROTEIN; RECEPTOR-BINDING; AMINO-ACIDS; SOLUBLE CD4; HIV-1; REGION; EPITOPE; DOMAIN AB We have probed the structure of the C4 and V3 domains of human immunodeficiency virus type 1 gp120 by immunochemical techniques. Monoclonal antibodies (MAbs) recognizing an exposed gp120 sequence, (E/K)VGKAMYAPP, in C4 were differentially sensitive to denaturation of gp120, implying a conformational component to some of the epitopes. The MAbs recognizing conformation-sensitive C4 structures failed to bind to a gp120 mutant with an alteration in the sequence of the V3 loop, and their binding to gp120 was inhibited by both V3 and C4 MAbs. This implies an interaction between the V3 and C4 regions of gp120, which is supported by the observation that the binding of some MAbs to the V3 loop was often enhanced by amino acid changes in and around the C4 region. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. JEFFERSON CANC INST,PHILADELPHIA,PA 19107. CTR IMMUNOL MARSEILLE LUMINY,F-13288 MARSEILLE,FRANCE. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. TANOX BIOSYST INC,HOUSTON,TX 77025. GENZYME CORP,CAMBRIDGE,MA 02139. BIOMED CTR,S-75123 UPPSALA,SWEDEN. KAROLINSKA INST,NATL BACTERIOL LAB,S-10521 STOCKHOLM,SWEDEN. RP MOORE, JP (reprint author), NYU,SCH MED,AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016, USA. FU NIAID NIH HHS [AI 25542-05A1, AI 24755, 1 P30 AI27742-04] NR 46 TC 129 Z9 130 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1993 VL 67 IS 8 BP 4785 EP 4796 PG 12 WC Virology SC Virology GA LM272 UT WOS:A1993LM27200038 PM 7687303 ER PT J AU MCKEATING, JA SHOTTON, C CORDELL, J GRAHAM, S BALFE, P SULLIVAN, N CHARLES, M PAGE, M BOLMSTEDT, A OLOFSSON, S KAYMAN, SC WU, Z PINTER, A DEAN, C SODROSKI, J WEISS, RA AF MCKEATING, JA SHOTTON, C CORDELL, J GRAHAM, S BALFE, P SULLIVAN, N CHARLES, M PAGE, M BOLMSTEDT, A OLOFSSON, S KAYMAN, SC WU, Z PINTER, A DEAN, C SODROSKI, J WEISS, RA TI CHARACTERIZATION OF NEUTRALIZING MONOCLONAL-ANTIBODIES TO LINEAR AND CONFORMATION-DEPENDENT EPITOPES WITHIN THE 1ST AND 2ND VARIABLE DOMAINS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120 SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN GP120; CD4 RECEPTOR-BINDING; SOLUBLE CD4; HOMOSEXUAL MEN; T4 MOLECULE; V3 DOMAIN; I GP120; HIV-1; CHIMPANZEES; INFECTION AB A number of linear and conformation-dependent neutralizing monoclonal antibodies (MAbs) have been mapped to the first and second variable (V1 and V2) domains of human immunodeficiency virus type 1 (HIV-1) gp120. The majority of these MAbs are as effective at neutralizing HIV-1 infectivity as MAbs to the V3 domain and the CD4 binding site. The linear MAbs bind to amino acid residues 162 to 171, and changes at residues 183/184 (PI/SG) and 191/192/193 (YSL/GSS) within the V2 domain abrogate the binding of the two conformation-dependent MAbs, 11/68b and CRA-4, respectively. Surprisingly, a change at residue 435 (Y/H or Y/S), in a region of gp120 near the CD4 binding site (M. Kowalski, J. Potz, L. Basiripour, T. Dorfman, W. C. Goh, E. Terwilliger, A. Dayton, C. Rosen, W. Haseltine, and J. Sodroski, Science 237:1351-1355, 1987; L. A. Lasky, G. M. Nakamura, D. H. Smith, C. Fennie, C. Shimasaki, E. Patzer, P. Berman, T. Gregory, and D. Capon, Cell 50:975-985, 1987; and U. Olshevsky, E. Helseth, C. Furman, J. Li, W. Haseltine, and J. Sodroski, J. Virol. 64:5701-5707, 1990), abrogated gp120 recognition by both of the conformation-dependent MAbs. However, both MAbs 11/68b and CRA-4 were able to bind to HIV-1 V1V2 chimeric fusion proteins expressing the V1V2 domains in the absence of C4, suggesting that residues in C4 are not components of the epitopes but that amino acid changes in C4 may affect the structure of the V1V2 domains. This is consistent with the ability of soluble CD4 to block 11/68b and CRA-4 binding to both native cell surface-expressed gp120 and recombinant gp120 and suggests that the binding of the neutralizing MAbs to the virus occurs prior to receptor interaction. Since the reciprocal inhibition, i.e., antibody inhibition of CD4-gp120 binding, was not observed, the mechanism of neutralization is probably not a blockade of virus-receptor interaction. Finally, we demonstrate that linear sequences from the V2 region are immunogenic in HIV-1-infected individuals, suggesting that the primary neutralizing response may be directed to both V2 and V3 epitopes. C1 INST CANC RES, CHESTER BEATTY LABS, LONDON SW3 6JB, ENGLAND. NATL INST BIOL STAND & CONTROLS, HERTFORD ENG 30G, ENGLAND. UCL, SCH MED, DEPT VIROL, LONDON W1P GDB, ENGLAND. MRC, INST VIROL, VIROL UNIT, GLASGOW G11 5JR, SCOTLAND. GOTHENBURG UNIV, DEPT CLIN VIROL, S-41346 GOTHENBURG, SWEDEN. PUBL HLTH RES INST CITY NEW YORK INC, NEW YORK, NY 10016 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV HUMAN RETROVIROL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH PUBL HLTH, BOSTON, MA 02115 USA. OI McKeating, Jane/0000-0002-7229-5886 FU NIAID NIH HHS [AI23884, AI24755, AI31783]; Wellcome Trust NR 65 TC 138 Z9 139 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1993 VL 67 IS 8 BP 4932 EP 4944 PG 13 WC Virology SC Virology GA LM272 UT WOS:A1993LM27200054 PM 7687306 ER PT J AU WARPINSKI, JR FOLGERT, J VOSS, M BUSH, RK AF WARPINSKI, JR FOLGERT, J VOSS, M BUSH, RK TI FISH SURFACE MUCIN HYPERSENSITIVITY SO JOURNAL OF WILDERNESS MEDICINE LA English DT Article DE FISH; MUCIN; HYPERSENSITIVITY AB Most reports of allergy to fish describe systemic symptoms upon ingestion of fish muscle or contact urticaria in commercial fish handlers. We report three recreational fishermen with symptoms of asthma, angioedema, rhinitis and urticaria upon exposure to surface mucin from bluegills (Lepomis machrochirus). All three had symptoms upon handling bluegills. Subsequently, two of them experienced wheezing and/or angioedema while in proximity to contaminated fishing clothing. One of them later developed symptoms upon eating bluegills. Prick skin testing was positive to crude bluegill surface mucin in all three individuals and to bluegill and cod muscle in one. Bluegill surface mucin was defatted in ether and acetone and extracted in phosphate buffered saline. Sodium dodecyl-polyacrylamide gel electrophoresis (SDS-PAGE) showed at least 20 distinct protein bands by Coomassie Blue staining. Many of these were glycoproteins by periodic acid schiff (PAS) staining. Immunoblotting showed at least seven IgE binding protein bands with molecular weights between 10 and 100 kDa. Radioallergosorbent (RAST) assay using a bluegill surface-mucin solid phase demonstrated that serum IgE binding in the three individuals was 4-25 times that of pooled serum from nonatopic controls. IgE binding using a serum pool from the three allergic patients was inhibited by extracts of bluegill mucin and muscle and cod muscle but not by tuna, crab or peanut. Our results demonstrate that bluegill surface mucin contains specific glycoproteins which bind IgE in sensitive individuals. Hypersensitivity to these surface proteins may cause systemic allergic symptoms. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,2500 OVERLOOK TERRACE,MADISON,WI 53705. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0953-9859 J9 J WILDERNESS MED PD AUG PY 1993 VL 4 IS 3 BP 261 EP 269 DI 10.1580/0953-9859-4.3.261 PG 9 WC Medicine, General & Internal; Physiology SC General & Internal Medicine; Physiology GA LQ272 UT WOS:A1993LQ27200005 ER PT J AU MICHAELSON, J AF MICHAELSON, J TI CELLULAR-SELECTION IN THE GENESIS OF MULTICELLULAR ORGANIZATION SO LABORATORY INVESTIGATION LA English DT Review ID LIVER HYPERPLASIA; DEATH APOPTOSIS; CELLS; DIFFERENTIATION; MOUSE; GROWTH; INDUCTION; EXPRESSION; COMPLEXITY; REGRESSION C1 MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CTR CANC, BOSTON, MA 02114 USA. RP MICHAELSON, J (reprint author), HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. FU NCI NIH HHS [CA37374] NR 112 TC 36 Z9 36 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD AUG PY 1993 VL 69 IS 2 BP 136 EP 151 PG 16 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA LT608 UT WOS:A1993LT60800002 PM 8350596 ER PT J AU PFLEIDERER, B ACKERMAN, JL GARRIDO, L AF PFLEIDERER, B ACKERMAN, JL GARRIDO, L TI IN-VIVO LOCALIZED PROTON NMR-SPECTROSCOPY OF SILICONE SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE H-1 NMR; SILICONE; IMPLANTS; MIGRATION ID STIMULATED ECHOES; GEL PROSTHESES; BREAST-TISSUE; DIFFUSION AB H-1 NMR localized spectroscopy (STEAM) can assess unambiguously the presence of free chemically unchanged silicone in animal tissue after injection of silicone oil. Although the signal-to-noise ratio obtained in H-1 imaging is sufficient to detect the distribution of relatively large amounts of silicone in vivo, the specificity of silicone detection can be improved by using H-1 localized spectroscopy techniques. The sensitivity of the STEAM experiments is sufficient to detect silicone at a concentration of 0.5% in a voxel of 27 MM3. Preliminary results from rats with silicone gel-filled implants show no detectable amounts of silicone in sites such as lymph nodes, the liver or the spleen, 3 or 6 months after implantation. C1 MASSACHUSETTS GEN HOSP,CTR NMR,DEPT RADIOL,BLDG 149 13TH ST,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. RI Garrido, Leoncio/K-3092-2014; Ackerman, Jerome/E-2646-2015 OI Garrido, Leoncio/0000-0002-7587-1260; Ackerman, Jerome/0000-0001-5176-7496 NR 30 TC 12 Z9 12 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD AUG PY 1993 VL 30 IS 2 BP 149 EP 154 DI 10.1002/mrm.1910300202 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LP882 UT WOS:A1993LP88200001 PM 8366795 ER PT J AU LIVINGSTON, EH AF LIVINGSTON, EH TI THE STOMACH AS A SYSTEM AND THE PATHOGENESIS OF EXPERIMENTAL ULCER SO MEDICAL HYPOTHESES LA English DT Article ID GASTRIC-MUCOSAL MICROCIRCULATION; ACID; RAT AB The stomach is prone to ulceration because of the hostile environment that exists within its lumen. The most important etiologic factor remains a topic of debate. We have considered the stomach as a system to lend insight into which pathophysiologic mechanisms might be most important. Systems are described by their content, hierarchy, entropy and interactions. The states of health, disease and death (i.e. ulceration) are represented by progressively increasing levels of entropy. It is argued that many of the purported causes of ulcer disease, such as acid back-diffusion or alcohol related necrosis, represent alterations in the system that affect small groups of cells that are low in the hierarchy and cause the tissue to enter the diseased state. We hypothesize that because blood flow is high within the hierarchy it represents the major homeostatic mechanism. If blood flow responds appropriately the system may return to the healthy state. If it does not the death of the system results in ulceration. Experimental evidence to support these contentions is presented. C1 UNIV CALIF LOS ANGELES, SCH MED, W LOS ANGELES VAMC, RES SERV, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, W LOS ANGELES VAMC, SURG SERV, LOS ANGELES, CA 90073 USA. FU NIADDK NIH HHS [AM 25891] NR 4 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD AUG PY 1993 VL 41 IS 2 BP 173 EP 176 DI 10.1016/0306-9877(93)90065-X PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LT972 UT WOS:A1993LT97200014 PM 8231998 ER PT J AU BYERS, HR ETOH, T LEE, KW MIHM, MC GATTONICELLI, S AF BYERS, HR ETOH, T LEE, KW MIHM, MC GATTONICELLI, S TI ORGAN-SPECIFIC METASTASES IN IMMUNODEFICIENT MICE INJECTED WITH HUMAN-MELANOMA CELLS - A QUANTITATIVE PATHOLOGICAL ANALYSIS SO MELANOMA RESEARCH LA English DT Article; Proceedings Paper CT MELANOMA SYMP, AT THE 18TH WORLD CONGRESS OF DERMATOLOGY CY JUN 12-18, 1992 CL NEW YORK, NY DE IMMUNODEFICIENT MICE; MELANOMA; METASTASES; ORGAN SPECIFICITY AB Pathological and morphometric techniques were used to investigate the potential of two human melanoma cell lines for organ colonization in three different immunodeficient mouse strains; nude (nu/nu), NIH triple immunodeficient (TID: nu/nu, bg/bg, xid/xid) and severe combined immunodeficient (SCID) mice. The MM-RU cell line gave rise exclusively to lung metastases, whereas the MM-AN cell line gave rise to lung and extrapulmonary metastases. Although the TID mice showed more pancreatic and brown fat lesions than nude or SCID mice, the overall pattern of distribution of organ metastases among the strains was similar, suggesting that cellular properties intrinsic to the melanoma cells are important for the colonization of specific organs. The metastatic nodules were well circumscribed in all organs and exhibited peripherally located macrophages, except for brain metastases, where a more invasive pattern along vasculature was observed. The differences in cellular infiltrate and infiltrative patterns of the tumors implicate features of the host microenvironment (organ-specific factors) which are, at least in part, independent of the host's genetic background or degree of immunodeficiency. Our findings suggest that intrinsic malignant cellular properties play an important role in organ-specific colonization by haematogenously metastasizing cells. RP BYERS, HR (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,100 BLOSSOM ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [R29 CA45587] NR 0 TC 13 Z9 13 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD AUG PY 1993 VL 3 IS 4 BP 247 EP 253 PG 7 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA LZ178 UT WOS:A1993LZ17800005 PM 8219757 ER PT J AU WOLPERT, HA STEEN, SN ISTFAN, NW SIMONSON, DC AF WOLPERT, HA STEEN, SN ISTFAN, NW SIMONSON, DC TI INSULIN MODULATES CIRCULATING ENDOTHELIN-1 LEVELS IN HUMANS SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID ESSENTIAL-HYPERTENSION; PLASMA ENDOTHELIN; SODIUM RETENTION; SKELETAL-MUSCLE; GLUCOSE; RESISTANCE; CELLS; MECHANISM; RELEASE C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT INTERNAL MED,BOSTON,MA 02115. RP WOLPERT, HA (reprint author), NEW ENGLAND DEACONESS HOSP,JOSLIN DIABET CTR,DEPT INTERNAL MED,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NHLBI NIH HHS [HL39392]; NIDDK NIH HHS [DK36836, DK43505] NR 26 TC 74 Z9 76 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD AUG PY 1993 VL 42 IS 8 BP 1027 EP 1030 DI 10.1016/0026-0495(93)90018-J PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR001 UT WOS:A1993LR00100018 PM 8345807 ER PT J AU BIRGE, RB FAJARDO, JE REICHMAN, C SHOELSON, SE SONGYANG, Z CANTLEY, LC HANAFUSA, H AF BIRGE, RB FAJARDO, JE REICHMAN, C SHOELSON, SE SONGYANG, Z CANTLEY, LC HANAFUSA, H TI IDENTIFICATION AND CHARACTERIZATION OF A HIGH-AFFINITY INTERACTION BETWEEN V-CRK AND TYROSINE-PHOSPHORYLATED PAXILLIN IN CT10-TRANSFORMED FIBROBLASTS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PHOSPHOTYROSINE-CONTAINING PROTEINS; GROWTH-FACTOR RECEPTORS; ONCOGENE PRODUCT; PHOSPHOLIPASE-C; TRANSFORMING PROTEIN; SIGNAL TRANSDUCTION; CRYSTAL-STRUCTURE; KINASE-ACTIVITY; SH2 DOMAINS; ASSOCIATION AB The genome of avian sarcoma virus CT10 encodes a fusion protein in which viral Gag sequences are fused to cellular Crk sequences containing primarily Src homology 2 (SH2) and Src homology 3 (SH3) domains. Transformation of chicken embryo fibroblasts (CEF) with the Gag-Crk fusion protein results in the elevation of tyrosine phosphorylation on specific cellular proteins with molecular weights of 130,000, 110,000, and 70,000 (p130, p110, and p70, respectively), an event which has been correlated with cell transformation. In this study, we have identified the 70-kDa tyrosine-phosphorylated protein in CT10-transformed CEF (CT10-CEF) as paxillin, a cytoskeletal protein suggested to be important for organizing the focal adhesion. Tyrosine-phosphorylated paxillin was found to be complexed with v-Crk in vivo as evident from coimmunoprecipitation studies. Moreover, a bacterially expressed recombinant glutathione S-transferase (GST)-CrkSH2 fragment bound paxillin in vitro with a subnanomolar affinity, suggesting that the SH2 domain of v-Crk is sufficient for binding. Mapping of the sequence specificity of a GST-CrkSH2 fusion protein with a partially degenerate phosphopeptide library determined a motif consisting of pYDXP, and in competitive coprecipitation studies, an acetylated A(p)YDAPA hexapeptide was able to quantitatively inhibit the binding of GST-CrkSH2 to paxillin and p130, suggesting that it meets the minimal structural requirements necessary for the interaction of CrkSH2 with physiological targets. To investigate the mechanism by which v-Crk elevates the tyrosine phosphorylation of paxillin in vivo, we have treated normal CEF and CT10-CEF with sodium vanadate to inhibit protein tyrosine phosphatase activity. Although many additional cellular proteins became hyperphosphorylated on tyrosine in the vanadate-treated CT10-CEF, the GST-CrkSH2 fragment still bound preferentially to the paxillin and 130-kDa proteins, suggesting a high degree of specificity in the interaction of CrkSH2 with these proteins. Paxillin phosphorylation was highly sensitive to vanadate treatment in both normal CEF and CT10-CEF, and the elevation in tyrosine phosphorylation resulted in increased binding to GST-CrkSH2. Moreover, binding of full-length GST-v-Crk to tyrosine-phosphorylated paxillin in vitro protected paxillin from dephosphorylation by cellular protein tyrosine phosphatase activity. These data suggest that paxillin is involved in a highly dynamic kinase-phosphatase interplay in normal CEF and that v-Crk binding may interrupt this balance to increase the steady-state level of tyrosine phosphorylation. By contrast, the 130-kDa protein was not tyrosine phosphorylated upon vanadate treatment of normal CEF and only weakly affected in the CT10-CEF, suggesting that a different mechanism may be involved in its phosphorylation. C1 ROCKEFELLER UNIV,MOLEC ONCOL LAB,1230 YORK AVE,NEW YORK,NY 10021. HARVARD UNIV,BRIGHAM & WOMENS HOSP,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [CA44356] NR 49 TC 262 Z9 262 U1 0 U2 6 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 1993 VL 13 IS 8 BP 4648 EP 4656 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LN405 UT WOS:A1993LN40500021 PM 7687742 ER PT J AU RIEDEL, H SU, LH HANSEN, H AF RIEDEL, H SU, LH HANSEN, H TI YEAST PHENOTYPE CLASSIFIES MAMMALIAN PROTEIN-KINASE-C CDNA MUTANTS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PHORBOL ESTER BINDING; SACCHAROMYCES-CEREVISIAE; REGULATORY DOMAIN; ENDOTHELIAL-CELLS; GENE-EXPRESSION; CA-2+ CHANNELS; TRANSFORMATION; ACTIVATION; SEQUENCE; AUTOPHOSPHORYLATION AB The phorbol ester receptor protein kinase C (PKC) gene family encodes essential mediators of eukaryotic cellular signals. Molecular dissection of their mechanisms of action has been limited in part by the lack of random mutagenesis approaches and by the complexity of signaling pathways in mammalian cells which involve multiple PKC isoforms. Here we present a rapid screen which permits the quantification of mammalian PKC activity phenotypically in the yeast Saccharomyces cerevisiae. Bovine PKCalpha cDNA is functionally expressed in S. cerevisiae. This results in a phorbol ester response: a fourfold increase in the cell doubling time and a substantial decrease in yeast colony size on agar plates. We have expressed pools of bovine PKCalpha cDNAs mutagenized by Bal 31 deletion of internal, amino-terminal, or carboxyl-terminal sequences and have identified three classes of mutants on the basis of their distinct yeast phenotypes. Representatives of each class were analyzed. An internal deletion of amino acids (aa) 172 to 225 displayed ligand-dependent but reduced catalytic activity, an amino-terminal truncation of aa 1 to 153 displayed elevated and ligand-independent activity, and a carboxyl-terminal 26-aa truncation (aa 647 to 672) lacked activity under any conditions. Additional mutations confirmed the distinct functional characteristics of these classes. Our data show that deletion of the V1 and C1 regions results in elevated basal catalytic activity which is still Ca2+ responsive. Internal deletions in the V2 and C2 regions do not abolish phorbol ester or Ca2+ regulation of PKC activity, suggesting that most of the C2 domain is not essential for phorbol ester stimulation and most of the regulatory domain is dispensable for Ca2+ regulation of PKC activity. These distinct activities of the PKC mutants correlate with a specific and proportional yeast phenotype and are quantified on agar plates by yeast colony size. This provides a phenotypic screen which is suitable to identify rare, randomly altered but active mammalian PKC mutants. It quantifies their catalytic and biological activities in response to PKC activators or inhibitors for a systematic mapping of PKC structure and function or PKC-drug interaction. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. RP RIEDEL, H (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,JOSLIN DIABET CTR,MOLEC BIOL,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK36836] NR 48 TC 20 Z9 20 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 1993 VL 13 IS 8 BP 4728 EP 4735 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LN405 UT WOS:A1993LN40500028 PM 8336710 ER PT J AU TONTONOZ, P KIM, JB GRAVES, RA SPIEGELMAN, BM AF TONTONOZ, P KIM, JB GRAVES, RA SPIEGELMAN, BM TI ADD1 - A NOVEL HELIX-LOOP-HELIX TRANSCRIPTION FACTOR ASSOCIATED WITH ADIPOCYTE DETERMINATION AND DIFFERENTIATION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-BINDING; ACHAETE-SCUTE; GENE-EXPRESSION; MESSENGER-RNA; ENHANCER BINDING; LEUCINE-ZIPPER; PROTEIN; MYOD; MYC; IDENTIFICATION AB DNA-binding proteins containing the basic helix-loop-helix (bHLH) domain have been implicated in lineage determination and the regulation of specific gene expression in a number of cell types. By oligonucleotide screening of an adipocyte cDNA expression library, we have identified a novel member of the bHLH-leucine zipper transcription factor family designated ADD1. ADD1 mRNA is expressed predominantly in brown adipose tissue in vivo and is regulated during both determination and differentiation of cultured adipocyte cell lines. ADD1 can function as a sequence-specific transcriptional activator in that it stimulates expression of a chloramphenicol acetyltransferase vector containing multiple ADD1 binding sequences but is unable to activate the myosin light-chain enhancer, which contains multiple binding sites for another bHLH factor, MyoD. ADD1 can also activate transcription through a binding site present in the 5'-flanking region of the fatty acid synthetase gene which is expressed in a differentiation-dependent manner in adipose cells. These data suggest that ADD1 plays a role in the regulation of determination- and differentiation-specific gene expression in adipocytes. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHANNING LAB,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. OI KIM, Jae Bum/0000-0003-2337-6935 FU NIDDK NIH HHS [DK31405-11]; NIGMS NIH HHS [T32 GM007753, T32 GM07753-14] NR 52 TC 496 Z9 508 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1993 VL 13 IS 8 BP 4753 EP 4759 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LN405 UT WOS:A1993LN40500031 PM 8336713 ER PT J AU PANKA, DJ VERY, DL JACOBSON, BA KUSSIE, PH PARHAMISEREN, B MARGOLIES, MN MARSHAKROTHSTEIN, A AF PANKA, DJ VERY, DL JACOBSON, BA KUSSIE, PH PARHAMISEREN, B MARGOLIES, MN MARSHAKROTHSTEIN, A TI DEFINING THE STRUCTURAL CORRELATES RESPONSIBLE FOR LOSS OF ARSONATE AFFINITY IN AN ID(CR) ANTIBODY ISOLATED FROM AN AUTOIMMUNE MOUSE SO MOLECULAR IMMUNOLOGY LA English DT Article ID CROSS-REACTIVE IDIOTYPE; PARA-AZOPHENYLARSONATE ANTIBODIES; CHAIN VARIABLE REGION; SITE-DIRECTED MUTAGENESIS; AMINO-ACID-SEQUENCE; SINGLE GERMLINE VH; STRAIN-A MOUSE; JUNCTIONAL DIVERSITY; IMMUNE-RESPONSE; MONOCLONAL-ANTIBODIES AB Immunization of the autoimmune mouse strain (M x A) Id/lpr with Ars-KLH, has been shown to elicit a prolonged anti-Ars Id(CR) response similar to that found in A/J mice. Cell fusion of splenocytes from a diseased mouse previously immunized with Ars-KLH resulted in a monoclonal antibody, 1-52.30, that was found to express the strain A major cross-reactive idiotype, but failed to bind Ars. Nucleotide sequence analysis demonstrated that 1-52.30: (a) used the ''canonical'' combination of gene segments associated with this idiotype, and (b) exhibited a pattern of somatic mutation consistent with selection for high affinity Ars binding. Two amino acids, V(L) 91 and 93, were mutated in 36-65, the germline equivalent of the Id(CR) antibodies, to 1-52.30-like residues (91G-->D, 93T-->M). The results of the mutagenesis showed that changing a single light chain residue, V, 91, from glycine to aspartic acid, resulted in a dramatic loss of Ars binding activity. C1 BOSTON UNIV,SCH MED,DEPT MICROBIOL,BOSTON,MA 02118. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. FU NCI NIH HHS [CA24432]; NIAMS NIH HHS [AR-35230, AR-01684] NR 50 TC 4 Z9 4 U1 1 U2 4 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 1993 VL 30 IS 11 BP 1013 EP 1020 DI 10.1016/0161-5890(93)90126-V PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA LT928 UT WOS:A1993LT92800006 PM 8350871 ER PT J AU HORWITZ, JI TONER, M TOMPKINS, RG YARMUSH, ML AF HORWITZ, JI TONER, M TOMPKINS, RG YARMUSH, ML TI IMMOBILIZED IL-2 PRESERVES THE VIABILITY OF AN IL-2 DEPENDENT CELL-LINE SO MOLECULAR IMMUNOLOGY LA English DT Article ID SOLID-PHASE INTERLEUKIN-2; HUMAN T-CELLS; RECOMBINANT INTERLEUKIN-2; SIGNAL TRANSDUCTION; MONOCLONAL-ANTIBODY; CYTO-TOXICITY; GROWTH-FACTOR; RECEPTOR; PROTEIN; EXPRESSION AB The mouse T-cell line CTLL-2 is known to be dependent on interleukin-2 (IL-2) for both growth and viability. These cells possess high affinity IL-2 receptors and have been shown to internalize IL-2 after binding. To determine if internalization of IL-2 is required for the mediation of its signal, IL-2 was covalently coupled to an insoluble matrix via glutaraldehyde cross-linking and CTLL-2 cells were incubated with the immobilized lymphokine matrix. This covalent cross-linking prevents the free lateral diffusion and internalization of the bound IL-2 receptors (IL-2R) while still permitting specific binding between the cells and the immobilized ligands. Although only very limited proliferation was observed during the incubation as assessed by H-3-thymidine incorporation, the viability of the CTLL-2 cells on the immobilized IL-2 matrix was preserved. Cells incubated on the immobilized IL-2 surface could proliferate in response to exogenous soluble IL-2 that was added to the cultures after 36 hours whereas control cultures incubated with an immobilized BSA matrix had died. This indicates that immobilized IL-2 can mediate some of the activity of soluble IL-2 and that internalization of the IL-2 receptor may not be required for at least part of the IL-2 mediated effect. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BIGELOW 1302,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. RUTGERS UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. NR 24 TC 27 Z9 27 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 1993 VL 30 IS 11 BP 1041 EP 1048 DI 10.1016/0161-5890(93)90129-Y PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA LT928 UT WOS:A1993LT92800009 PM 8350874 ER PT J AU DUYAO, M AMBROSE, C MYERS, R NOVELLETTO, A PERSICHETTI, F FRONTALI, M FOLSTEIN, S ROSS, C FRANZ, M ABBOTT, M GRAY, J CONNEALLY, P YOUNG, A PENNEY, J HOLLINGSWORTH, Z SHOULSON, I LAZZARINI, A FALEK, A KOROSHETZ, W SAX, D BIRD, E VONSATTEL, J BONILLA, E ALVIR, J CONDE, JB CHA, JH DURE, L GOMEZ, F RAMOS, M SANCHEZRAMOS, J SNODGRASS, S DEYOUNG, M WEXLER, N MOSCOWITZ, C PENCHASZADEH, G MACFARLANE, H ANDERSON, M JENKINS, B SRINIDHI, J BARNES, G GUSELLA, J MACDONALD, M AF DUYAO, M AMBROSE, C MYERS, R NOVELLETTO, A PERSICHETTI, F FRONTALI, M FOLSTEIN, S ROSS, C FRANZ, M ABBOTT, M GRAY, J CONNEALLY, P YOUNG, A PENNEY, J HOLLINGSWORTH, Z SHOULSON, I LAZZARINI, A FALEK, A KOROSHETZ, W SAX, D BIRD, E VONSATTEL, J BONILLA, E ALVIR, J CONDE, JB CHA, JH DURE, L GOMEZ, F RAMOS, M SANCHEZRAMOS, J SNODGRASS, S DEYOUNG, M WEXLER, N MOSCOWITZ, C PENCHASZADEH, G MACFARLANE, H ANDERSON, M JENKINS, B SRINIDHI, J BARNES, G GUSELLA, J MACDONALD, M TI TRINUCLEOTIDE REPEAT LENGTH INSTABILITY AND AGE-OF-ONSET IN HUNTINGTONS-DISEASE SO NATURE GENETICS LA English DT Article ID BULBAR MUSCULAR-ATROPHY; MYOTONIC-DYSTROPHY; FRAGILE-X; DNA MARKERS; CTG REPEAT; REGION; GENE; RECOMBINATION; DIAGNOSIS; EXPANSION AB The initial observation of an expanded and unstable trinucleotide repeat in the Huntington's disease gene has now been confirmed and extended in 150 independent Huntington's disease families. HD chromosomes contained 37-86 repeat units, whereas normal chromosomes displayed 11-34 repeats. The HD repeat length was inversely correlated with the age of onset of the disorder. The HD repeat was unstable in more than 80% of meiotic transmissions showing both increases and decreases in size with the largest increases occurring in paternal transmissions. The targeting of spermatogenesis as a particular source of repeat instability is reflected in the repeat distribution of HD sperm DNA. The analysis of the length and instability of individual repeats in members of these families has profound implications for presymptomatic diagnosis. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. UNIV ROMA TOR VERGATA,DEPT BIOL,ROME,ITALY. CNR,INST MED SPERIMENTALE,ROME,ITALY. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21205. INDIANA UNIV,MED CTR,DEPT MED GENET,INDIANAPOLIS,IN 46202. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. UNIV ROCHESTER,MED CTR,DEPT NEUROL,ROCHESTER,NY 14642. UNIV MED & DENT NEW JERSEY,DEPT NEUROL,NEW BRUNSWICK,NJ 08903. EMORY UNIV,SCH MED,DEPT PSYCHIAT,ATLANTA,GA 30306. HARVARD UNIV,MCLEAN HOSP,CTR BRAIN TISSUE RESOURCE,BELMONT,MA 02178. HARVARD UNIV,SCH MED,DEPT NEUROPATHOL,BELMONT,MA 02178. UNIV ZULIA,MARACAIBO,VENEZUELA. LONG ISL JEWISH MED CTR,GLEN OAKS,NY 11004. BAYOR UNIV,COLL MED,HOUSTON,TX 77009. KENNEDY KREIGER INST,NEUROSCI LAB,BALTIMORE,MD 21205. HOSP VIRGEN CAMINO,SERV GENET,E-31008 PAMPLONA,SPAIN. UNIV MIAMI,DEPT NEUROL,MIAMI,FL 33136. UNIV MISSISSIPPI,MED CTR,JACKSON,MS 39216. COLUMBIA UNIV COLL PHYS & SURG,DEPT NEUROL & PSYCHIAT,NEW YORK,NY 10032. HEREDITARY DIS FDN,SANTA MONICA,CA 90401. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. RI Dure, Leon/B-3243-2008; Sanchez-Ramos, Juan/A-1188-2009; OI Sanchez-Ramos, Juan/0000-0002-3391-7857; Novelletto, Andrea/0000-0002-1146-7680 FU NINDS NIH HHS [NS16367, NS16375, NS17978] NR 34 TC 665 Z9 674 U1 5 U2 35 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 1993 VL 4 IS 4 BP 387 EP 392 DI 10.1038/ng0893-387 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA LQ178 UT WOS:A1993LQ17800017 PM 8401587 ER PT J AU SNELL, RG MACMILLAN, JC CHEADLE, JP FENTON, I LAZAROU, LP DAVIES, P MACDONALD, ME GUSELLA, JF HARPER, PS SHAW, DJ AF SNELL, RG MACMILLAN, JC CHEADLE, JP FENTON, I LAZAROU, LP DAVIES, P MACDONALD, ME GUSELLA, JF HARPER, PS SHAW, DJ TI RELATIONSHIP BETWEEN TRINUCLEOTIDE REPEAT EXPANSION AND PHENOTYPIC VARIATION IN HUNTINGTONS-DISEASE SO NATURE GENETICS LA English DT Article ID MYOTONIC-DYSTROPHY; TRANSMISSION; PATTERNS; REGION; ONSET; GENE; AGE AB The molecular analysis of a specific CAG repeat sequence in the Huntington's disease gene in 440 Huntington's disease patients and 360 normal controls reveals a range of 30-70 repeats in affected individuals and 9-34 in normals. We find significant negative correlations between the number of repeats on the HD chromosome and age at onset, regardless of sex of the transmitting parent, and between the number of repeats on the normal paternal allele and age at onset in individuals with maternally transmitted disease. This effect of the normal paternal allele may account for the weaker age at onset correlation between affected sib pairs with disease of maternal as opposed to paternal origin and suggests that normal gene function varies because of the size of the repeat in the normal range and a sex-specific modifying effect. C1 UNIV WALES COLL MED,INST MED GENET,HEATH PK,CARDIFF CF4 4XN,S GLAM,WALES. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RI MacMillan, John/C-9591-2011 FU Wellcome Trust NR 22 TC 503 Z9 508 U1 2 U2 20 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 1993 VL 4 IS 4 BP 393 EP 397 DI 10.1038/ng0893-393 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA LQ178 UT WOS:A1993LQ17800018 PM 8401588 ER PT J AU PARK, S SCHALLING, M BERNARD, A MAHESWARAN, S SHIPLEY, GC ROBERTS, D FLETCHER, J SHIPMAN, R RHEINWALD, J DEMETRI, G GRIFFIN, J MINDEN, M HOUSMAN, DE HABER, DA AF PARK, S SCHALLING, M BERNARD, A MAHESWARAN, S SHIPLEY, GC ROBERTS, D FLETCHER, J SHIPMAN, R RHEINWALD, J DEMETRI, G GRIFFIN, J MINDEN, M HOUSMAN, DE HABER, DA TI THE WILMS-TUMOR GENE WT1 IS EXPRESSED IN MURINE MESODERM-DERIVED TISSUES AND MUTATED IN A HUMAN MESOTHELIOMA SO NATURE GENETICS LA English DT Article ID ZINC-FINGER GENE; MALIGNANT MESOTHELIOMA; CELLS; DELETION; MUTATIONS; KIDNEY; LOCUS; REPRESSION; ONCOGENE; SYSTEM AB The tumour suppressor gene WT1 encodes a transcription factor expressed in tissues of the genito-urinary system. Inactivation of this gene is associated with the development of Wilms tumour a pediatric kidney cancer. We show that WT1 is also expressed at high levels in many supportive structures of mesodermal origin in the mouse. We also describe a case of adult human mesothelioma, a tumour derived from the peritoneal lining, that contains a homozygous point mutation within WT1. This mutation, within the putative transactivation domain, converts the protein from a transcriptional repressor of its target sequence to a transcriptional activator. The role of WT1 in normal development thus extends to diverse structures derived from embryonic mesoderm and disruption of WT1 function contributes to the onset of adult, as well as pediatric, tumours. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, CTR CANC, BOSTON, MA 02129 USA. MIT, CTR CANC RES, CAMBRIDGE, MA 02139 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, DEPT PATHOL, DIV WOMENS & PERINATAL PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, DIV SOLID TUMOUR CYTOGENET, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. KANTONSSPITAL, DEPT RES, CH-4031 BASEL, SWITZERLAND. BIOSURFACE TECHNOL INC, CAMBRIDGE, MA 02139 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. PRINCESS MARGARET HOSP, TORONTO M4X 1KG, ON, CANADA. FU NCI NIH HHS [CA58596]; NIGMS NIH HHS [GM27882] NR 41 TC 182 Z9 186 U1 0 U2 2 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 1993 VL 4 IS 4 BP 415 EP 420 DI 10.1038/ng0893-415 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA LQ178 UT WOS:A1993LQ17800022 PM 8401592 ER PT J AU ROEDER, T NATHANSON, JA AF ROEDER, T NATHANSON, JA TI CHARACTERIZATION OF INSECT NEURONAL OCTOPAMINE RECEPTORS (OA3 RECEPTORS) SO NEUROCHEMICAL RESEARCH LA English DT Article DE ADRENERGIC RECEPTOR; OCTOPAMINE; INSECT; G-PROTEIN ID SENSITIVE ADENYLATE-CYCLASE; LOCUSTA-MIGRATORIA; POTENT; AGONISTS AB Octopamine receptors in the nervous tissue of insects were investigated using a ligand-receptor assay with [H-3]NC-5Z or [H-3]octopamine as the radioligands. Both ligands recognized a homogenous class of binding sites with the properties of an octopamine receptor. This receptor has been characterized pharmacologically. Both high-affinity agonists (e.g. NC 7, K1 = 0.3 nM) and antagonists (e.g. maroxepine, K1 = 1.02 nM) were investigated. The neuronal octopamine receptor belongs to a receptor class that can easily be distinguished from peripheral octopamine receptors. Initial investigations of the localization of octopamine receptors within the insect nervous tissue show the greatest receptor density in the optic lobes. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROPHARMACOL RES LAB,BOSTON,MA 02114. RP ROEDER, T (reprint author), UNIV HAMBURG,INST ZOOL,MARTIN LUTHER KING PL 3,W-2000 HAMBURG 13,GERMANY. RI Roeder, Thomas/B-9016-2011 OI Roeder, Thomas/0000-0002-3489-3834 FU NIAID NIH HHS [AI29533] NR 21 TC 51 Z9 51 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 AUG PY 1993 VL 18 IS 8 BP 921 EP 925 DI 10.1007/BF00998278 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA LN214 UT WOS:A1993LN21400010 PM 8371834 ER PT J AU WEINRIEB, RM OBRIEN, CP AF WEINRIEB, RM OBRIEN, CP TI PERSISTENT COGNITIVE DEFICITS ATTRIBUTED TO SUBSTANCE-ABUSE SO NEUROLOGIC CLINICS LA English DT Article ID CHRONIC COCAINE ABUSERS; NEUROPSYCHOLOGICAL IMPAIRMENT; FOLLOW-UP; CANNABIS USE; PERFORMANCE; DRUGS; HYPNOTICS; MARIJUANA; SEQUELAE; MEMORY C1 PHILADELPHIA VET AFFAIRS MED CTR,PHILADELPHIA,PA. RP WEINRIEB, RM (reprint author), UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104, USA. NR 62 TC 9 Z9 9 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD AUG PY 1993 VL 11 IS 3 BP 663 EP 691 PG 29 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA LT632 UT WOS:A1993LT63200013 PM 8377749 ER PT J AU SAUNDERS, AM STRITTMATTER, WJ SCHMECHEL, D GEORGEHYSLOP, PHS PERICAKVANCE, MA JOO, SH ROSI, BL GUSELLA, JF CRAPPERMACLACHLAN, DR ALBERTS, MJ HULETTE, C CRAIN, B GOLDGABER, D ROSES, AD AF SAUNDERS, AM STRITTMATTER, WJ SCHMECHEL, D GEORGEHYSLOP, PHS PERICAKVANCE, MA JOO, SH ROSI, BL GUSELLA, JF CRAPPERMACLACHLAN, DR ALBERTS, MJ HULETTE, C CRAIN, B GOLDGABER, D ROSES, AD TI ASSOCIATION OF APOLIPOPROTEIN-E ALLELE EPSILON-4 WITH LATE-ONSET FAMILIAL AND SPORADIC ALZHEIMERS-DISEASE SO NEUROLOGY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; GENETIC-LINKAGE; MISSENSE MUTATION; E POLYMORPHISM; BETA-PEPTIDE; CHROMOSOME-19; PEDIGREE; DEMENTIA; LOCUS AB Apolipoprotein E, type epsilon4 allele (APOE epsilon4), is associated with late-onset familial Alzheimer's disease (AD). There is high avidity and specific binding of amyloid beta-peptide with the protein ApoE. To test the hypothesis that late-onset familial AD may represent the clustering of sporadic AD in families large enough to be studied, we extended the analyses of APOE alleles to several series of sporadic AD patients. APOE epsilon4 is significantly associated with a series of probable sporadic AD patients (0.36 +/- 0.042, AD, versus 0.16 +/- 0.027, controls [allele frequency estimate +/-standard error], p = 0.00031). Spouse controls did not differ from CEPH grandparent controls from the Centre d'Etude du Polymorphisme Humain (CEPH) or from literature controls. A large combined series of autopsy-documented sporadic AD patients also demonstrated highly significant association with the APOE epsilon4 allele (0.40 +/- 0.026, p less-than-or-equal-to 0.00001). These data support the involvement of ApoE epsilon4 in the pathogenesis of late-onset familial and sporadic AD. ApoE isoforms may play an important role in the metabolism of beta-peptide, and APOE epsilon4 may operate as a susceptibility gene (risk factor) for the clinical expression of AD. C1 DUKE UNIV,MED CTR,DEPT MED NEUROL,BOX 2900,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT NEUROBIOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,JOSEPH & KATHLEEN BRYAN ALZHEIMERS DIS RES CTR,DURHAM,NC 27710. UNIV TORONTO,CTR RES NEURODEGENERAT DIS,DEPT MED NEUROL,TORONTO M5S 1A1,ONTARIO,CANADA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. SUNY,DEPT PSYCHIAT,STONY BROOK,NY 11794. FU NCRR NIH HHS [M01-RR-30]; NIA NIH HHS [NIA AG-05128, NIA AG-07922] NR 45 TC 2732 Z9 2775 U1 16 U2 174 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1993 VL 43 IS 8 BP 1467 EP 1472 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA LR500 UT WOS:A1993LR50000004 PM 8350998 ER PT J AU HUANG, CC LU, CS CHU, NS HOCHBERG, F LILIENFELD, D OLANOW, W CALNE, DB AF HUANG, CC LU, CS CHU, NS HOCHBERG, F LILIENFELD, D OLANOW, W CALNE, DB TI PROGRESSION AFTER CHRONIC MANGANESE EXPOSURE SO NEUROLOGY LA English DT Article ID PARKINSONISM; INTOXICATION AB We report a longitudinal follow-up study on six patients with chronic manganese-induced parkinsonism following cessation of manganese exposure. Compared with the 1987 study, their parkinsonian symptoms showed a slow progression, particularly in gait disturbances such as freezing during turning and walking backward with retropulsion. The mean disability scores on the King's College Hospital Rating Scale were 15.0 +/- 4.2 in 1987 and 28.3 +/- 6.7 in 1991 (p = 0.003, paired t test). Review of the video records also confirmed a worsening of parkinsonism, especially in difficulty turning. Three of six patients receiving levodopa treatment had an initial improvement. The response decreased after 2 to 3 years. During the therapy, they did not develop on-off fluctuation or dyskinesia. We conclude that patients with manganese-induced parkinsonism may develop increasing neurologic dysfunction long after cessation of exposure and that their responses to levodopa are different from those of patients with Parkinson's disease. C1 CHANG GUNG MED COLL,DEPT NEUROL,TAIPEI,TAIWAN. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. MT SINAI MED CTR,DEPT COMMUNITY MED,NEW YORK,NY 10029. UNIV S FLORIDA,DEPT NEUROL,TAMPA,FL 33620. UNIV BRITISH COLUMBIA,CTR NEURODEGENERAT DISORDERS,DIV NEUROL,VANCOUVER V6T 1W5,BC,CANADA. RP HUANG, CC (reprint author), CHANG GUNG MEM HOSP,DEPT NEUROL,199 TUNG HWA N RD,TAIPEI,TAIWAN. NR 24 TC 157 Z9 161 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1993 VL 43 IS 8 BP 1479 EP 1483 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA LR500 UT WOS:A1993LR50000006 PM 8351000 ER PT J AU PAVEZA, GJ AF PAVEZA, GJ TI SOCIAL-SERVICES AND THE ALZHEIMERS-DISEASE PATIENT - AN OVERVIEW SO NEUROLOGY LA English DT Article ID DEMENTIA PATIENTS; SENILE DEMENTIA; FAMILY MEMBERS; CAREGIVERS; DEPRESSION; PREDICTORS; CARE; INTERVENTIONS; IMPAIRMENT AB With the number of patients and families affected by Alzheimer's disease increasing, many physicians will find themselves having to refer these patients and family members to social services. Many physicians, however, lack of understanding of the available social services. This article provides a contextual framework for the social service system, discussing social services according to three principal domains: assessment, counseling, and behavioral management. From the information presented, physicians will be able to assess the level of services provided by different social workers and refer patients and families to the social worker most likely to meet their needs. RP PAVEZA, GJ (reprint author), US DEPT VET AFFAIRS,CTR LONG TERM MENTAL HLTH EVALUAT,GREAT LAKES HLTH SERV,ANN ARBOR,MI 48113, USA. NR 48 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1993 VL 43 IS 8 SU 4 BP S11 EP S15 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA LV411 UT WOS:A1993LV41100003 ER PT J AU OGILVY, CS MOAYERI, N GOLDEN, JA RIGAMONTI, D KELLY, PJ AF OGILVY, CS MOAYERI, N GOLDEN, JA RIGAMONTI, D KELLY, PJ TI APPEARANCE OF A CAVERNOUS HEMANGIOMA IN THE CEREBRAL-CORTEX AFTER A BIOPSY OF A DEEPER LESION SO NEUROSURGERY LA English DT Note DE CAVERNOUS HEMANGIOMA; GROWTH; PATHOLOGY; VASCULAR MALFORMATION ID MALFORMATIONS; ANGIOMAS AB CAVERNOUS HEMANGIOMAS ARE vascular malformations that can occur throughout the central nervous system. In certain patients, multiple lesions are known to occur. We present a patient with multiple cavernous hemangiomas who had a computed tomography-guided biopsy of a deep parieto-occipital lesion through a burr hole. Several passes of a biopsy needle were used. During a 5-year interval, the patient developed a new lesion directly under the burr hole on the cortical surface. The new lesion appears to have occurred from the implantation and growth of a cavernous hemangioma secondary to the biopsy. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL & NEUROPATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP OGILVY, CS (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,FRUIT ST,BOSTON,MA 02114, USA. NR 10 TC 40 Z9 40 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD AUG PY 1993 VL 33 IS 2 BP 307 EP 309 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA LP279 UT WOS:A1993LP27900019 PM 8367053 ER PT J AU EGAN, KM WALSH, SM SEDDON, JM GRAGOUDAS, ES AF EGAN, KM WALSH, SM SEDDON, JM GRAGOUDAS, ES TI AN EVALUATION OF THE INFLUENCE OF REPRODUCTIVE FACTORS ON THE RISK OF METASTASES FROM UVEAL MELANOMA SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 1992 ANNUAL MEETING OF THE AMERICAN ACADEMY OF OPHTHALMOLOGY CY NOV, 1992 CL DALLAS, TX SP AMER ACAD OPHTHALMOL ID PROTON-BEAM IRRADIATION; MALIGNANT-MELANOMA; EPIDEMIOLOGIC ASPECTS; FEMALE HORMONES; SURVIVAL; PREGNANCY; ESTROGEN; EYE; WOMEN; SEX AB Background. There is a paucity of data concerning the possible role played by hormonal factors in the risk of metastases from intraocular melanomas. Methods: The authors studied the influence of post-diagnosis pregnancy and oral contraceptive use in a group of women of reproductive age (45 or younger) who were treated for uveal melanoma by proton beam irradiation. A baseline reproductive history had been collected before irradiation for all women, and interim reproductive data were collected by mailed questionnaire. Results: In this age group, the overall rate of metastasis among women was similar to that of men treated during the same interval (adjusted rate ratio: 1.28; 95% confidence interval: 0.62-2.67). A total of 24 full-term pregnancies were reported among the 139 women still menstruating at diagnosis. Twenty-three women reported regular oral contraceptive use. Metastases developed in 15 of the 139 women. Compared with other women in the series, rates of metastases were not higher among the women who reported pregnancies (P = 0.932) or oral contraceptive use (P = 0.424) after diagnosis. Conclusion: Although based on limited numbers, results suggest that the hormonal environment has no appreciable influence on risk of metastases in younger women with uveal melanoma. C1 MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,243 CHARLES ST,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,EPIDEMIOL UNIT,BOSTON,MA 02114. NR 34 TC 10 Z9 11 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 1993 VL 100 IS 8 BP 1160 EP 1166 PG 7 WC Ophthalmology SC Ophthalmology GA LQ627 UT WOS:A1993LQ62700013 PM 8341495 ER PT J AU KAUFMAN, AH FOSTER, CS AF KAUFMAN, AH FOSTER, CS TI CATARACT-EXTRACTION IN PATIENTS WITH PARS PLANITIS SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 1992 ANNUAL MEETING OF THE AMERICAN ACADEMY OF OPHTHALMOLOGY CY NOV, 1992 CL DALLAS, TX SP AMER ACAD OPHTHALMOL ID UVEITIS; SURGERY; CRYOTHERAPY; MANAGEMENT; LENSECTOMY; VITRECTOMY AB Background. The authors analyzed the results of cataract surgery performed on patients with pars planitis from January 1985 through August 1992. Methods: One hundred twenty-six patients with pars planitis were evaluated and treated during this period. Cataracts that warranted surgery developed in 12 patients (18 eyes) f rom this tertiary referral population. These 1 2 patients were evaluated with respect to pars planitis duration, systemic disease association, treatment regimens, macular and disc pathology, and final visual result. Results: The average final visual acuity of these 18 eyes was 20/38, and 83% of the patients achieved a final visual acuity better than or equal to 20/40. The factors that limited visual recovery to this level were primarily macular and optic nerve pathology (cystoid macular edema [CME], macular epiretinal membrane, and optic atrophy). Control of inflammation required regional steroids in all patients, systemic steroids in ten patients, and immunosuppression in four patients. Posterior chamber lens implantation accompanied the surgery in 14 eyes (10 patients). Recurrent episodes of inflammation in two patients (3 eyes) resulted in accumulation of deposits on the posterior chamber intraocular lens (IOL) surface. Deposits were removed by a YAG laser lens ''polishing'' session. Conclusion: Absolute control of inflammation in patients with pars planitis through a stepladder approach may reduce the incidence of cataract development, and can certainly improve visual rehabilitation after cataract extraction. Implantation of a posterior chamber lens can be well tolerated in selected cases. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,IMMUNOL SERV,243 CHARLES ST,BOSTON,MA 02114. NR 35 TC 32 Z9 32 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 1993 VL 100 IS 8 BP 1210 EP 1217 PG 8 WC Ophthalmology SC Ophthalmology GA LQ627 UT WOS:A1993LQ62700023 PM 8341504 ER PT J AU ODAY, DM ADAMS, AJ CASSEM, EH DONLON, JV DOUGHMAN, DJ FRIEDMAN, DB GLYNNMILLEY, C KNOPF, HL WHITAKER, B MAZZAFERRI, EL OBSTBAUM, SA PAPPAS, CJ SKINNER, EN SOMMER, A TERRY, AC VADER, LA WEBER, JR WONG, IG AF ODAY, DM ADAMS, AJ CASSEM, EH DONLON, JV DOUGHMAN, DJ FRIEDMAN, DB GLYNNMILLEY, C KNOPF, HL WHITAKER, B MAZZAFERRI, EL OBSTBAUM, SA PAPPAS, CJ SKINNER, EN SOMMER, A TERRY, AC VADER, LA WEBER, JR WONG, IG TI MANAGEMENT OF FUNCTIONAL IMPAIRMENT DUE TO CATARACT IN ADULTS SO OPHTHALMOLOGY LA English DT Review ID LASER POSTERIOR CAPSULOTOMY; INTRAOCULAR-LENS IMPLANTATION; CYSTOID MACULAR EDEMA; POSTOPERATIVE VISUAL-ACUITY; ELEVATION FOLLOWING NEODYMIUM; RHEGMATOGENOUS RETINAL-DETACHMENT; PSEUDOPHAKIC BULLOUS KERATOPATHY; OPACITIES CLASSIFICATION-SYSTEM; ENDOTHELIAL-CELL DENSITY; BLUE FIELD ENTOPTOSCOPY AB Cataract surgery performed to redress functional impairment due to cataract in the adult is the most common surgical procedure performed on Americans age 65 and over. As a result, cataract surgery is a significant item in the Medicare budget. It is important to recognize the impact of cataract-related disability on an individual's ability to function autonomously. The goal of the guideline is to promote appropriate management of adults with functional impairment due to cataract. The Guideline Report consists of recommendations for providing the highest quality of care, based on an extensive review of the relevant literature and on expert opinion and panel consensus. Functional impairment due to cataract is a broad topic that includes the following considerations: ethical issues, natural history and risk factors, access to and referral for care, setting of care, preoperative tests, various aspects of surgery and preoperative management, postoperative care, rehabilitation, and YAG capsulotomy. The Guideline Report is the basis for three companion publications that serve as references for clinicians and patients: the Clinical Practice Guideline, the Quick Reference Guide for Clinicians, and the Patient's Guide. C1 UNIV CALIF BERKELEY, SCH OPTOMETRY, BERKELEY, CA 94720 USA. MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT, BOSTON, MA 02114 USA. MASSACHUSETTS EYE & EAR INFIRM, DEPT ANESTHESIOL, BOSTON, MA 02114 USA. UNIV MINNESOTA HOSP & CLIN, DEPT OPHTHALMOL, MINNEAPOLIS, MN 55455 USA. MASSACHUSETTS EYE & EAR INFIRM, VIS REHABIL SERV, BEVERLY, MA USA. SPECIALTY NURSING AGCY INC, SANTA CLARA, CA USA. WASHINGTON UNIV, SCH MED, DEPT OPHTHALMOL & VISUAL SCI, ST LOUIS, MO 63110 USA. UNIV TEXAS HLTH SCI CTR SAN ANTONIO, SCH NURSING, SAN ANTONIO, TX 78284 USA. OHIO STATE UNIV, COLL MED, DEPT INTERNAL MED, COLUMBUS, OH 43210 USA. CORNELL UNIV, SCH MED, NEW YORK, NY 10021 USA. LENOX HILL HOSP, DEPT OPHTHALMOL, NEW YORK, NY 10021 USA. UNIV MIAMI, SCH MED, BASCOM PALMER EYE INST, MIAMI, FL 33152 USA. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, BALTIMORE, MD 21218 USA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. UNIV MICHIGAN, KELLOGG EYE CTR, ANN ARBOR, MI 48109 USA. UNIV ARKANSAS, DEPT FAMILY & COMMUNITY MED, JACKSONVILLE, AR USA. KAISER PERMANENTE MED CTR, DEPT OPHTHALMOL, REDWOOD CITY, CA USA. UNIV CALIF SAN FRANCISCO, REDWOOD CITY, CA USA. RP ODAY, DM (reprint author), VANDERBILT UNIV, MED CTR, SCH MED, DEPT OPHTHALMOL & VISUAL SCI, NASHVILLE, TN 37232 USA. NR 444 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 1993 VL 100 IS 8 SU S BP RS1 EP S342 PG 0 WC Ophthalmology SC Ophthalmology GA LR214 UT WOS:A1993LR21400001 ER PT J AU GREENBERG, JT AUSUBEL, FM AF GREENBERG, JT AUSUBEL, FM TI ARABIDOPSIS MUTANTS COMPROMISED FOR THE CONTROL OF CELLULAR-DAMAGE DURING PATHOGENESIS AND AGING SO PLANT JOURNAL LA English DT Article ID POLYMORPHISM LINKAGE MAP; SYRINGAE PV TOMATO; PISUM-SATIVUM L; ELECTROLYTE LEAKAGE; DISEASE RESISTANCE; THALIANA; PLANT; GENES; IDENTIFICATION; BIOSYNTHESIS AB Mutants of Arabidopsis thaliana which exhibit accelerated cell death in response to pathogens were isolated and characterized to gain insight into how symptom severity and disease resistance are modulated. This paper describes mutants that fall into one of two complementation groups that were identified. A novel feature of these mutants is that they are unable to control the rate and extent of cell death after exposure to a variety of stimuli that induce senescence responses. Thus, accelerated cell death (acd1) mutants show rapid, spreading necrotic responses to both virulent and avirulent Pseudomonas syringae pv. maculicola or pv. tomato pathogens and to ethylene. In addition, they develop necrotic lesions as they age and are sensitive to mechanical stress in a developmentally controlled manner. The acd1 mutants are also susceptible to opportunistic pathogens and show decreased growth inhibition of a heterologous pathogen of bean. The signal for lesion formation is not necessarily due to pathogens or wounding since plants grown aseptically also develop necrotic lesions. The lesions formed under a variety of conditions resemble those produced during a pathogen-induced rapid cell death response (the hypersensitive response, HR). Analysis of these acd1 mutants may help to explain the molecular basis of the HR and the relationship between this response and the normal process of senescence. C1 HARVARD UNIV,SCH MED,DEPT GENET,25 SHATTUCK ST,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. OI Greenberg, Jean/0000-0002-7213-7618 FU NIGMS NIH HHS [GM48707] NR 44 TC 193 Z9 203 U1 1 U2 6 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7412 J9 PLANT J JI Plant J. PD AUG PY 1993 VL 4 IS 2 BP 327 EP 341 DI 10.1046/j.1365-313X.1993.04020327.x PG 15 WC Plant Sciences SC Plant Sciences GA LT721 UT WOS:A1993LT72100010 PM 8220484 ER PT J AU KONIECZNY, A AUSUBEL, FM AF KONIECZNY, A AUSUBEL, FM TI A PROCEDURE FOR MAPPING ARABIDOPSIS MUTATIONS USING CODOMINANT ECOTYPE-SPECIFIC PCR-BASED MARKERS SO PLANT JOURNAL LA English DT Article ID FRAGMENT-LENGTH-POLYMORPHISM; POLYMERASE CHAIN-REACTION; LINKAGE MAP; MOLECULAR-CLONING; SYNTHASE GENES; SATIVA L; THALIANA; GENOME; DNA; SEQUENCE AB A set of mapping markers have been designed for Arabidopsis thaliana that correspond to DNA fragments amplified by the polymerase chain reaction (PCR). The ecotype of origin of these amplified fragments can be determined by cleavage with a restriction endonuclease. Specifically, 18 sets of PCR primers were synthesized, each of which amplifies a single mapped DNA sequence from the Columbia and Landsberg erecta ecotypes. Also identifed was at least one restriction endonuclease for each of these PCR products that generates ecotype-specific digestion patterns. Using these co-dominant cleaved amplified polymorphic sequences (CAPS), an Arabidopsis gene can be unambiguously mapped to one of the 10 Arabidopsis chromosome arms in a single cross using a limited number of F2 progeny. C1 HARVARD UNIV,SCH MED,DEPT GENET,25 SHATTUCK ST,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 39 TC 1190 Z9 1251 U1 4 U2 55 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7412 J9 PLANT J JI Plant J. PD AUG PY 1993 VL 4 IS 2 BP 403 EP 410 DI 10.1046/j.1365-313X.1993.04020403.x PG 8 WC Plant Sciences SC Plant Sciences GA LT721 UT WOS:A1993LT72100017 PM 8106085 ER PT J AU HWANG, I GOODMAN, HM AF HWANG, I GOODMAN, HM TI CLONING OF AN ARABIDOPSIS RIBOSOMAL-PROTEIN S28 CDNA SO PLANT PHYSIOLOGY LA English DT Article ID ORGANIZATION; GENE C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 10 TC 6 Z9 7 U1 0 U2 0 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD AUG PY 1993 VL 102 IS 4 BP 1357 EP 1358 DI 10.1104/pp.102.4.1357 PG 2 WC Plant Sciences SC Plant Sciences GA LR969 UT WOS:A1993LR96900044 PM 8278557 ER PT J AU FLEMINGTON, EK SPECK, SH KAELIN, WG AF FLEMINGTON, EK SPECK, SH KAELIN, WG TI E2F-1-MEDIATED TRANSACTIVATION IS INHIBITED BY COMPLEX-FORMATION WITH THE RETINOBLASTOMA SUSCEPTIBILITY GENE-PRODUCT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CELL CYCLE; GROWTH SUPPRESSOR ID CELLULAR TRANSCRIPTION FACTOR; LARGE T-ANTIGEN; BINDING PROTEIN; ADENOVIRUS-E1A PREVENTS; TUMOR-ANTIGEN; FACTOR E2F; RB GENE; DOMAIN; SUPPRESSION; INTERACT AB Previous studies have shown that the carboxyl-terminal region of E2F-1 (residues 368-437) can support transcriptional activation when linked to the DNA-binding domain of the yeast transcription factor GAL4. This region also contains an 18-residue retinoblastoma (RB)-binding sequence, raising the possibility that RB binding might inhibit the ability of E2F-1 to form protein-protein contacts required for activation. Here we report a further analysis of the E2F-1 activation domain. In addition, we show that overexpression of RB, but not the RB mutant, RBd22, can inhibit GAL4/E2F-1 activity in vivo. Moreover, expression of the simian virus 40 large tumor antigen (T antigen), but not the RB-binding defective T antigen point mutant, K1, can overcome this repression. Three different GAL4/E2F-1 mutants that activate transcription, but fail to bind to RB, are not significantly affected by overexpression of RB. These findings support a model wherein RB suppresses E2F-1-mediated transcriptional activation through direct physical association. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA 02115. RP FLEMINGTON, EK (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [5RO1 CA-43143, K11 CA01528-03] NR 33 TC 288 Z9 293 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 1 PY 1993 VL 90 IS 15 BP 6914 EP 6918 DI 10.1073/pnas.90.15.6914 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LQ335 UT WOS:A1993LQ33500005 PM 8346196 ER PT J AU KONRADI, C KOBIERSKI, LA NGUYEN, TV HECKERS, S HYMAN, SE AF KONRADI, C KOBIERSKI, LA NGUYEN, TV HECKERS, S HYMAN, SE TI THE CAMP-RESPONSE-ELEMENT-BINDING PROTEIN INTERACTS, BUT FOS PROTEIN DOES NOT INTERACT, WITH THE PROENKEPHALIN ENHANCER IN RAT STRIATUM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AP-1 PROTEINS; HALOPERIDOL ID CYCLIC-AMP; C-FOS; GENE-EXPRESSION; MESSENGER-RNA; STRIATOPALLIDAL NEURONS; ENKEPHALIN; TRANSCRIPTION; HALOPERIDOL; INCREASE; AP-1 AB The proenkephalin gene is a well-studied model of transcription factor-target gene interaction in the nervous system and has been proposed as a regulatory target of the protein product of the immediate-early gene c-fos. This regulatory mechanism has been proposed, in part, because the cAMP response element 2 (CRE-2) site, the key DNA regulatory element within the proenkephalin second-messenger-inducible enhancer, avidly binds AP-1 proteins, including Fos, in vitro. However, we observe a dissociation in the time course of activation of c-fos and proenkephalin mRNA in rat striatum after administration of the dopamine D2 receptor antagonist haloperidol. This result prompted us to investigate the composition of protein complexes in striatal nuclear extracts that bind to the CRE-2 site. Even though our striatal nuclear extracts had substantial basal and haloperidol-inducible AP-1-binding activities that contained Fos, we could not detect Fos in complexes bound to the CRE-2 element. Instead, as determined by antibody supershift analysis, we detect CRE-binding protein (CREB)-like proteins binding to CRE-2 in both basal and haloperidol-stimulated conditions. Finally, we show that haloperidol induces CREB protein phosphorylation in striatum. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT NEUROL,BOSTON,MA 02215. RP KONRADI, C (reprint author), MASSACHUSETTS GEN HOSP,MOLEC & DEV NEUROSCI LAB,BOSTON,MA 02114, USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 FU NIDA NIH HHS [DA07134, R01 DA007134, R01 DA007134-14]; NIMH NIH HHS [MH00892, MH44160] NR 28 TC 150 Z9 150 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 1993 VL 90 IS 15 BP 7005 EP 7009 DI 10.1073/pnas.90.15.7005 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LQ335 UT WOS:A1993LQ33500024 PM 8346209 ER PT J AU BOOTHMAN, DA MEYERS, M FUKUNAGA, N LEE, SW AF BOOTHMAN, DA MEYERS, M FUKUNAGA, N LEE, SW TI ISOLATION OF X-RAY-INDUCIBLE TRANSCRIPTS FROM RADIORESISTANT HUMAN-MELANOMA CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DIFFERENTIAL HYBRIDIZATION; CDNA CLONING; IONIZING RADIATION; GENE EXPRESSION ID IONIZING-RADIATION; PLASMINOGEN-ACTIVATOR; GENE-EXPRESSION; INDUCTION; SEQUENCE; CDNA; HYBRIDIZATION; ONCOGENE; PROTEIN; REPAIR AB Twelve x-ray-induced transcripts (xips), differentially expressed 8- to 230-fold in x-irradiated versus unirradiated radioresistant human melanoma (U1-Mel) cells, were isolated as cDNA clones (xip1 through xip12) after four rounds of differential hybridization. Northern analyses revealed rare, medium, and abundant xips, ranging in size from 1.2 to 10 kb. All transcripts were transiently expressed and induced by low, but not by high (>600 cGy), doses of radiation. Three transcripts (xip4, -7, and -12) were induced only by ionizing radiation, and many (i.e., xip1, -2, -3, -5, -6, -8, -9, -10, and -11) were also induced by UV irradiation or phorbol 12-myristate 13-acetate. Heat shock did not induce any of the xips, but it decreased basal levels of xip4, -7, -11, and -12. Three xip cDNA clones were identified as encoding thymidine kinase, DT diaphorase, and tissue-type plasminogen activator. The remaining nine cDNA clones showed little homology to known genes. Three clones contained regions homologous to c-fes/fps protooncogene, recombination activating gene 1, or the human angiogenesis factor gene. X-ray-inducible genes may function in damaged cells to regulate DNA repair, apoptosis, mutagenesis, and carcinogenesis. C1 UNIV WISCONSIN, DEPT HUMAN ONCOL, MADISON, WI 53792 USA. UNIV MICHIGAN, DEPT RADIAT ONCOL, DIV CANC BIOL, ANN ARBOR, MI 48109 USA. RP BOOTHMAN, DA (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. FU NCI NIH HHS [R01 CA078530] NR 26 TC 121 Z9 122 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 1 PY 1993 VL 90 IS 15 BP 7200 EP 7204 DI 10.1073/pnas.90.15.7200 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LQ335 UT WOS:A1993LQ33500064 PM 8346236 ER PT J AU CHEATHAM, B SHOELSON, SE YAMADA, K GONCALVES, E KAHN, CR AF CHEATHAM, B SHOELSON, SE YAMADA, K GONCALVES, E KAHN, CR TI SUBSTITUTION OF THE ERBB-2 ONCOPROTEIN TRANSMEMBRANE DOMAIN ACTIVATES THE INSULIN-RECEPTOR AND MODULATES THE ACTION OF INSULIN AND INSULIN-RECEPTOR SUBSTRATE-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-FACTOR RECEPTOR; SIGNAL TRANSDUCTION; TYROSINE KINASE; POINT MUTATION; BETA-SUBUNIT; PROTEIN; IRS-1; AUTOPHOSPHORYLATION; DIMERIZATION; STIMULATION AB The mechanism through which insulin binding to the extracellular domain of the insulin receptor activates the intrinsic tyrosine kinase in the intracellular domain of the protein is unknown. For the c-neu/erbB-2 (c-erbB-2) protooncogene, a single point mutation within the transmembrane (TM) domain converting Val-664 to Glu (erbB-2V-->E) results in elevated levels of tyrosine kinase activity and cellular transformation. We report the construction of a chimeric insulin receptor in which the TM domain of the receptor has been substituted with that encoded by erbB-2V-->E. When expressed in Chinese hamster ovary cells this chimeric receptor displays maximal levels of autophosphorylation and kinase activity in the absence of insulin. This activity results in an increase in the level of insulin-receptor substrate 1 phosphorylation but a down-regulation in insulin-receptor substrate 1 protein and desensitization to insulin stimulation of glycogen synthesis. By contrast, basal levels of DNA synthesis are elevated to levels almost-equal-to 60% of those observed in serum-stimulated cells. Over-expression of chimeric insulin receptors containing the c-erbB-2 TM domain or a single point mutation in the insulin receptor TM domain of Val-938-->Asp, on the other hand, shows none of these alterations. Thus, the TM domain encoded by erbB-2V-->E contains structural features that can confer ligand-independent activation in a heterologous protein. Constitutive activation of the insulin receptor results in a relative increase in basal levels of DNA synthesis, but an apparent resistance to the metabolic effects of insulin. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. FU NIDDK NIH HHS [DK31036, DK36836, DK43123] NR 30 TC 44 Z9 44 U1 1 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 1 PY 1993 VL 90 IS 15 BP 7336 EP 7340 DI 10.1073/pnas.90.15.7336 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LQ335 UT WOS:A1993LQ33500092 PM 7688476 ER PT J AU PRASAD, KVS JANSSEN, O KAPELLER, R RAAB, M CANTLEY, LC RUDD, CE AF PRASAD, KVS JANSSEN, O KAPELLER, R RAAB, M CANTLEY, LC RUDD, CE TI SRC-HOMOLOGY-3 DOMAIN OF PROTEIN-KINASE P59(FYN) MEDIATES BINDING TO PHOSPHATIDYLINOSITOL 3-KINASE IN T-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECEPTOR TYROSINE KINASES; EPIDERMAL GROWTH-FACTOR; ANTIGEN RECEPTOR; LYMPHOCYTES-T; SH3 DOMAIN; PHOSPHOLIPASE C-GAMMA-1; SIGNAL TRANSDUCTION; CROSS-LINKING; SRC; IDENTIFICATION AB The Src-related tyrosine kinase p59fyn(T) plays an important role in the generation of intracellular signals from the T-cell antigen receptor TCRzeta/CD3 complex. A key question concerns the nature and the binding sites of downstream components that interact with this Src-related kinase. p59fyn(T) contains Src-homology 2 and 3 domains (SH2 and SH3) with a capacity to bind to intracellular proteins. One potential downstream target is phosphatidylinositol 3-kinase (PI 3-kinase). In this study, we demonstrate that anti-CD3 and anti-Fyn immunoprecipitates possess PI 3-kinase activity as assessed by TLC and HPLC. Both free and receptor-bound p59fyn(T) were found to bind to the lipid kinase. Further, our results indicate that Src-related kinases have developed a novel mechanism to interact with PI 3-kinase. Precipitation using GST fusion proteins containing Fyn SH2, SH3, and SH2/SH3 domains revealed that PI 3-kinase bound principally to the SH3 domain of Fyn. Fyn SH3 bound directly to the p85 subunit of PI 3-kinase as expressed in a baculoviral system. Anti-CD3 crosslinking induced an increase in the detection of Fyn SH3-associated PI 3-kinase activity. Thus PI 3-kinase is a target of SH3 domains and is likely to play a major role in the signals derived from the TCRzeta/CD3-p59fyn complex. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT PHYSIOL,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PHYSIOL,BOSTON,MA 02115. RI Janssen, Ottmar/E-9735-2010; Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [CA51887-02]; NIGMS NIH HHS [R01 GM041890, GM36624, GM41890] NR 59 TC 174 Z9 175 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 1 PY 1993 VL 90 IS 15 BP 7366 EP 7370 DI 10.1073/pnas.90.15.7366 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LQ335 UT WOS:A1993LQ33500098 PM 8394019 ER PT J AU GOTTLINGER, HG DORFMAN, T COHEN, EA HASELTINE, WA AF GOTTLINGER, HG DORFMAN, T COHEN, EA HASELTINE, WA TI VPU PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENHANCES THE RELEASE OF CAPSIDS PRODUCED BY GAG GENE CONSTRUCTS OF WIDELY DIVERGENT RETROVIRUSES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CAPSID RELEASE; PROTEOLYTIC PROCESSING; MYRISTOYLATION ID MURINE LEUKEMIA-VIRUS; MYRISTOYLATION; REPLICATION; INFECTIVITY; MATURATION; EXPRESSION; PARTICLES; SEQUENCE; COMPLEX; HIV-1 AB The Vpu protein of human immunodeficiency virus type 1 facilitates the release of virus particles from the surface of infected cells. The ability of the Vpu protein to facilitate release of Gag proteins from retroviruses that lack a Vpu-like protein was examined. The results of these experiments show that Vpu significantly increases the release of the Gag proteins of human immunodeficiency virus type 2, visna virus, and Moloney murine leukemia virus from HeLa cells. The results indicate that Vpu-mediated enhancement of particle release requires neither amino-terminal myristoylation of the Gag precursor nor cleavage of the Gag precursor by the viral protease. The results raise the possibility that Vpu modifies a cellular pathway common to the release of all retroviruses from the cell surface. C1 UNIV MONTREAL,DEPT MICROBIOL & IMMUNOL,MONTREAL H3C 3J7,QUEBEC,CANADA. RP GOTTLINGER, HG (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI29873] NR 28 TC 177 Z9 182 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 1 PY 1993 VL 90 IS 15 BP 7381 EP 7385 DI 10.1073/pnas.90.15.7381 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LQ335 UT WOS:A1993LQ33500101 PM 8346259 ER PT J AU LIBERMAN, RP CORRIGAN, PW AF LIBERMAN, RP CORRIGAN, PW TI DESIGNING NEW PSYCHOSOCIAL TREATMENTS FOR SCHIZOPHRENIA SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID SOCIAL SKILLS; PSYCHIATRIC-INPATIENTS; DEVELOPMENTAL COURSE; MANAGEMENT; DYSFUNCTIONS; DISORDERS; STRESS; TRIAL; LIFE AB SCHIZOPHRENIA is a disease characterized by cognitive, psychophysiological, and interpersonal deficits that result in a marked vulnerability to stress (Dawson and Nuechterlein 1984; Nuechterlein 1977; Strauss et al. 1987). Episodes of illness occur in vulnerable individuals who experience stressful life events (G. W. Brown and Rutter 1966; Lukoff et al. 1984) or stressful interactions with family members (G. W. Brown et al. 1972; Imber Mintz et al. 1987; Leff and Vaughn 1985). Similarly, overstimulating therapeutic environments have been shown to exacerbate psychosis (Drake and Sederer 1986; Liberman 1982; Linn et al. 1980; Van Putten 1976). A full understanding of disease-specific deficits resulting from stress and vulnerability is necessary for developing psychosocial treatment programs that augment pharmacotherapies in significantly ameliorating the symptoms and disabilities of schizophrenia. RP LIBERMAN, RP (reprint author), UNIV CALIF LOS ANGELES, CAMARILLO CLIN RES CTR SCHIZOPHRENIA & PSYCHIAT RE, W LOS ANGELES VA MED CTR, LOS ANGELES, CA 90073 USA. NR 56 TC 40 Z9 40 U1 2 U2 4 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD AUG PY 1993 VL 56 IS 3 BP 238 EP 249 PG 12 WC Psychiatry SC Psychiatry GA LT868 UT WOS:A1993LT86800002 PM 8416005 ER PT J AU JACKSON, VP HENDRICK, RE FEIG, SA KOPANS, DB AF JACKSON, VP HENDRICK, RE FEIG, SA KOPANS, DB TI IMAGING OF THE RADIOGRAPHICALLY DENSE BREAST SO RADIOLOGY LA English DT Article DE BREAST; BREAST, RADIONUCLIDE STUDIES; BREAST; BREAST NEOPLASMS, DIAGNOSIS; BREAST RADIOGRAPHY; STATE-OF-ART REVIEWS ID MAMMOGRAPHIC PARENCHYMAL PATTERNS; SCREEN-FILM MAMMOGRAPHY; DUAL-ENERGY MAMMOGRAPHY; CANCER RISK; GD-DTPA; DIGITAL MAMMOGRAPHY; AUTOMATIC EXPOSURE; SPOT COMPRESSION; CARCINOMA; CONTRAST AB Despite recent improvements in mammography equipment and technique, the radiographically dense breast remains difficult to image. The problems in imaging the dense breast account for a large percentage of the cases of mammographically ''missed'' carcinomas. Other imaging modalities-such as ultrasonography, transillumination, thermography, computed tomography, magnetic resonance imaging, and radionuclide imaging-have been investigated for use in breast cancer detection. This overview discusses the current problems associated with imaging of the radiographically dense breast and suggests some avenues for investigation to develop solutions to these problems. C1 INDIANA UNIV,SCH MED,INDIANAPOLIS,IN 46202. UNIV COLORADO,HLTH SCI CTR,DEPT RADIOL,DENVER,CO 80262. THOMAS JEFFERSON UNIV,DEPT RADIOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,PHILADELPHIA,PA 19107. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP JACKSON, VP (reprint author), INDIANA UNIV,MED CTR,DEPT RADIOL,1001 W 10TH ST,INDIANAPOLIS,IN 46202, USA. NR 72 TC 211 Z9 215 U1 0 U2 4 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 1993 VL 188 IS 2 BP 297 EP 301 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LM849 UT WOS:A1993LM84900002 PM 8327668 ER PT J AU KASPER, CE MCNULTY, AL OTTO, AJ THOMAS, DP AF KASPER, CE MCNULTY, AL OTTO, AJ THOMAS, DP TI ALTERATIONS IN SKELETAL-MUSCLE RELATED TO IMPAIRED PHYSICAL MOBILITY - AN EMPIRICAL-MODEL SO RESEARCH IN NURSING & HEALTH LA English DT Article ID HINDLIMB SUSPENSION; CONTRACTILE PROPERTIES; LIMB IMMOBILIZATION; PROTEIN-TURNOVER; SOLEUS MUSCLE; TIME COURSE; RAT; HYPOKINESIA; ATROPHY; RECOVERY AB The objective of this investigation was to study impaired physical mobility and the resulting skeletal muscle atrophy. An animal model was used to study morphological adaptations of the soleus and plantaris muscles to decreased loading induced by hindlimb suspension of an adult rat for 7, 14, and 28 consecutive days. Alterations in weight, skeletal muscle growth, and changes in fiber type composition were studied in synergistic plantar flexors of the rat hindlimb. Body weight and the soleus muscle mass to body mass ratio demonstrated significant progressive atrophy over th 28-day experimental period with the most significant changes occurring in the first 7 days of hindlimb suspension. Hindlimb suspension produced atrophy of Type I and Type IIa muscle fibers as demonstrated by significant decreases in fiber cross-sectional area (mum2). These latter changes account for the loss of contractile force production reported in the rat following hindlimb unloading. When compared to traditional models of hindlimb suspension and immobilization, the ISC model produces a less severe atrophy while maintaining animal mobility and health. We conclude that it is the preferred animal model to address nursing questions of impaired physical mobility. (C) 1993 John Wiley & Sons, Inc. C1 UNIV WISCONSIN,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. UNIV WYOMING,COLL HLTH SCI,HUMAN ENERGY RES LAB,LARAMIE,WY 82071. RP KASPER, CE (reprint author), UNIV CALIF LOS ANGELES,SCH NURSING,10833 LE CONTE AVE,LOS ANGELES,CA 90024, USA. FU DRS NIH HHS [BRSG2507]; NINR NIH HHS [NR02204, NR05866] NR 34 TC 18 Z9 21 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD AUG PY 1993 VL 16 IS 4 BP 265 EP 273 DI 10.1002/nur.4770160405 PG 9 WC Nursing SC Nursing GA LM486 UT WOS:A1993LM48600004 PM 8378556 ER PT J AU SHEA, SA ANDRES, LP SHANNON, DC GUZ, A BANZETT, RB AF SHEA, SA ANDRES, LP SHANNON, DC GUZ, A BANZETT, RB TI RESPIRATORY SENSATIONS IN SUBJECTS WHO LACK A VENTILATORY RESPONSE TO CO2 SO RESPIRATION PHYSIOLOGY LA English DT Article DE CHEMOSENSITIVITY, AIR HUNGER; CONTROL OF BREATHING, CO2 RESPONSE; HYPERCAPNIA, AIR HUNGER, LACK CO2 RESPONSIVENESS; HYPOVENTILATION, CONGENITAL CENTRAL HYPOVENTILATION SYNDROME; MAMMALS, HUMANS ID CENTRAL HYPOVENTILATION SYNDROME; AIR HUNGER; BREATHLESSNESS; QUADRIPLEGICS; CHILDREN; HUMANS; BREATH; SLEEP AB An urge to breathe is perceived during breath hold and hypercapnia (termed 'air hunger') and during heavy exercise (often termed 'shortness of breath'). To better understand the neural mechanisms responsible for these sensations we studied five patients (8-17 years old) with congenital central hypoventilation syndrome (CCHS) who lack ventilatory response to CO2. CCHS patients reported no respiratory discomfort during CO2 inhalation or during maximal breath hold which was of much longer duration than age-matched controls. However, all 3 CCHS patients who exercised heavily reported some sensations akin to shortness of breath (they increased breathing nearly as much as controls). Our results are consistent with two possibilities. First, the air hunger of hypercapnia and breath hold is caused by projection to the forebrain of respiratory chemoreceptor afferents which bypass the respiratory centers, while exercise shortness of breath is caused by direct projections of limb afferents or locomotory center activity. Second, air hunger and shortness of breath share the same origin - projection of increased brain stem respiratory center motor activity (corollary discharge) to the forebrain. C1 CHARING CROSS & WESTMINSTER MED SCH,DEPT MED,LONDON,ENGLAND. MASSACHUSETTS GEN HOSP,PEDIAT PULM UNIT,BOSTON,MA 02114. RP SHEA, SA (reprint author), HARVARD UNIV,SCH PUBL HLTH,PHYSIOL PROGRAM,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL46690, HL07118, HL19170]; Wellcome Trust NR 24 TC 54 Z9 55 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0034-5687 J9 RESP PHYSIOL JI Respir. Physiol. PD AUG PY 1993 VL 93 IS 2 BP 203 EP 219 DI 10.1016/0034-5687(93)90006-V PG 17 WC Physiology; Respiratory System SC Physiology; Respiratory System GA LT518 UT WOS:A1993LT51800006 PM 8210759 ER PT J AU GRAHAM, DY GO, MF LEW, GM GENTA, RM REHFELD, JF AF GRAHAM, DY GO, MF LEW, GM GENTA, RM REHFELD, JF TI HELICOBACTER-PYLORI INFECTION AND EXAGGERATED GASTRIN-RELEASE - EFFECTS OF INFLAMMATION AND PROGASTRIN PROCESSING SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE AMMONIUM; BIOPSY; CLINICAL TRIAL; GASTRIN PROCESSING; GASTRIN, REGULATION; HELICOBACTER-PYLORI; PROGASTRIN; TRIPLE THERAPY; UREA ID DUODENAL-ULCER PATIENTS; PLASMA GASTRIN; HYPERGASTRINEMIA; ERADICATION; CHILDREN; INFUSION AB Helicobacter pylori infection is associated with exaggerated gastrin release. We investigated whether this abnormality was due to the bacteria or the immune response. Fasting and meal-stimulated 'total' and amidated gastrin were measured in 10 H. pylori-infected volunteers before eradication therapy, after 2 and 14 days of therapy, and 4 weeks after completion of therapy. The exaggerated meal-stimulated gastrin concentration remained unchanged after 2 days of therapy, although the polymorphonuclear cell infiltrate and H. pylori bacteria were no longer evident. The expected fall in gastrin concentration after 14 days of therapy was associated with a reduction in the density of mucosal mononuclear cells, suggesting exaggerated gastrin release was related to chronic inflammation or to H. pylori or its products. The effect of H. pylori on normal progastrin processing was also assessed; 2 control groups were included: 10 H. pylori-uninfected volunteers and 13 patients with H. pylori peptic ulcers. There was a significant difference in the proportion of circulating gastrins that were biologically active amidated gastrins between ulcer patients and uninfected controls (56,7 +/- 4% versus 33.8 +/- 4%, p < 0.001). The proportion of amidated to total gastrins did not increase after successful eradication. C1 UNIV COPENHAGEN,RIGSHOSP,DEPT CLIN BIOCHEM,DK-2100 COPENHAGEN,DENMARK. BAYLOR COLL MED,DEPT PATHOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,DIV MOLEC VIROL,HOUSTON,TX 77030. RP GRAHAM, DY (reprint author), VET AFFAIRS MED CTR 111D,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. FU NIDDK NIH HHS [DK 39919] NR 27 TC 62 Z9 63 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PD AUG PY 1993 VL 28 IS 8 BP 690 EP 694 DI 10.3109/00365529309098274 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LT598 UT WOS:A1993LT59800008 PM 8210984 ER PT J AU STERN, RG KAHN, RS HARVEY, PD AMIN, F APTER, SH HIRSCHOWITZ, J AF STERN, RG KAHN, RS HARVEY, PD AMIN, F APTER, SH HIRSCHOWITZ, J TI EARLY RESPONSE TO HALOPERIDOL TREATMENT IN CHRONIC-SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Article DE HALOPERIDOL; EARLY TREATMENT RESPONSE; RESPONSE PREDICTION; (SCHIZOPHRENIA) ID PLASMA HOMOVANILLIC-ACID; NEUROLEPTIC TREATMENT; PREDICTION; SYMPTOMS; INPATIENTS; REGIMENS; MODEL AB This study examined the time-course of treatment response to haloperidol in chronic schizophrenia. Furthermore the predictive value of baseline psychopathology and early therapeutic changes for the identification of the eventual treatment outcome was examined. After a two-week drug-free period forty-three chronic schizophrenic patients were treated with haloperidol for five weeks. Psychopathology was assessed on the last drug-free day and on the third and eighth day from the initiation of treatment, and then at weekly intervals. At the end of the study based on a priori criteria patients were classified as responders or non-responders to haloperidol. Seventeen patients met criteria for treatment response at the end of five weeks of treatment, while 26 did not. Already by the third day of treatment, in the responders there was a significant decrease in total BPRS and in the subscales scores for psychosis, tension and anergia, but not for hostility-suspiciousness and depression. These decreases represented approximately half of the eventual improvement obtained by the end of the study. Discriminant function analysis showed that severity of symptoms at baseline and improvement by day 3 correctly classified overall outcome in 72% of the cases. RP STERN, RG (reprint author), BRONX VET ADM MED CTR,MT SINAI SCH MED,DEPT PSYCHIAT,1 GUSTAVE LEVY PL,NEW YORK,NY 10029, USA. FU NIMH NIH HHS [NIMH RO1 37922-07] NR 31 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 1993 VL 10 IS 2 BP 165 EP 171 DI 10.1016/0920-9964(93)90052-K PG 7 WC Psychiatry SC Psychiatry GA LU408 UT WOS:A1993LU40800010 PM 8398949 ER PT J AU REYES, H SIMON, FR AF REYES, H SIMON, FR TI INTRAHEPATIC CHOLESTASIS OF PREGNANCY - AN ESTROGEN-RELATED DISEASE SO SEMINARS IN LIVER DISEASE LA English DT Review ID ADENOSYL-L-METHIONINE; INTRA-HEPATIC CHOLESTASIS; PLASMA-MEMBRANE FLUIDITY; ESTRADIOL-INDUCED CHOLESTASIS; ORGANIC ANION TRANSPORT; ATP-DEPENDENT TRANSPORT; BILE SECRETORY FAILURE; D-RING GLUCURONIDES; MUTANT TR RATS; ETHINYL ESTRADIOL C1 UNIV COLORADO,SCH MED,HEPATOBILIARY RES CTR,CAMPUS BOX B-145,4200 E 9TH AVE,DENVER,CO 80262. UNIV CHILE,HOSP SALVADOR,SCH MED,DEPT MED,SANTIAGO,CHILE. DENVER VET AFFAIRS MED CTR,DENVER,CO. UNIV COLORADO,SCH MED,DEPT MED,DENVER,CO 80262. UNIV CHILE,HOSP SALVADOR,SCH MED,DEPT EXPTL MED,SANTIAGO,CHILE. FU NIDDK NIH HHS [P30-DK-34914, DK-15851] NR 138 TC 108 Z9 118 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD AUG PY 1993 VL 13 IS 3 BP 289 EP 301 DI 10.1055/s-2007-1007357 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LZ816 UT WOS:A1993LZ81600007 PM 8235718 ER PT J AU WOLLERT, PS MENCONI, MJ OSULLIVAN, BP WANG, HL LARKIN, V FINK, MP SUGARMAN, HJ MOORE, EE FLETCHER, R AF WOLLERT, PS MENCONI, MJ OSULLIVAN, BP WANG, HL LARKIN, V FINK, MP SUGARMAN, HJ MOORE, EE FLETCHER, R TI LY255283, A NOVEL LEUKOTRIENE-B4 RECEPTOR ANTAGONIST, LIMITS ACTIVATION OF NEUTROPHILS AND PREVENTS ACUTE LUNG INJURY-INDUCED BY ENDOTOXIN IN PIGS SO SURGERY LA English DT Article; Proceedings Paper CT 54TH ANNUAL MEETING OF THE SOC OF UNIVERSITY SURGEONS CY FEB 11-13, 1992 CL SEATTLE, WA SP SOC UNIV SURGEONS ID RESPIRATORY-DISTRESS SYNDROME; BRONCHOALVEOLAR LAVAGE FLUID; ESCHERICHIA-COLI ENDOTOXIN; ENDOTHELIAL-CELLS; PULMONARY-EDEMA; SHEEP; INHIBITION; RESPONSES; C-4; RAT AB Background. Polymorphonuclear neutrophils (PMNs) have been implicated in the pathogenesis of the adult respiratory distress syndrome (ARDS). Because leukotriene B4 (LTB4) is a potent activator of PMNs, we sought to determine whether LY255283, an LTB4 receptor antagonist, could block PMN activation and lung injury in a porcine model of lipopolysaccharide-induced ARDS. Methods. Eighteen hours before being studied, pigs were injected with lipopolysaccharide (20 mug/kg). From 0 to 60 minutes, pigs received either Ringer's lactate solution (n = 5) or lipopolysaccharide (250 mug/kg). Among the pigs that were infused with lipopolysaccharide, nine received no other treatment, six received a low dose of LY255283 (30 mg/kg loading dose; 3 mg/kg-hr infusion), and six received a high dose of LY255283 (30 mg/kg loading dose, 30 mg/kg-hr). In vivo PMN activation was assessed with an automated chemiluminescence assay wherein results are expressed as CORE/MORE (i.e., the ratio of complement-opsonized zymosan receptor expression on circulating cells [CORE] divided by the maximal complement-opsonized zymosan receptor expression induced by incubating the cells in vitro with LTB4 or platelet-activating factor [MORE]). Results. In control pigs, lipopolysaccharide induced hypoxemia, pulmonary hypertension, and neutrophil activation (increased CORE/MORE ratio). These changes were attenuated by LY255283, particularly when pigs were infused with the higher dose of the compound. The drug also blunted lipopolysaccharide-induced recruitment of PMNs in pulmonary air spaces, as assessed by bronchoalveolar lavage performed at 240 minutes, although the degree of pulmonary leukosequestration caused by lipopolysaccharide was not affected. Conclusions. In a dose-dependent fashion, LY255283 ameliorated lipopolysaccharide-induced ARDS in pigs, possibly by blocking the recruitment of activated PMNs into alveoli. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. UNIV MASSACHUSETTS,MED CTR,DEPT PEDIAT,WORCESTER,MA 01605. FU NIGMS NIH HHS [R29 GM37631 05] NR 25 TC 26 Z9 26 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 1993 VL 114 IS 2 BP 191 EP 198 PG 8 WC Surgery SC Surgery GA LQ384 UT WOS:A1993LQ38400008 PM 8393594 ER PT J AU STOLER, JM DOODY, DP HOLMES, LB AF STOLER, JM DOODY, DP HOLMES, LB TI A CASE OF A CLOSED PARTIAL CLOACAL SEPTATION DEFECT WITH A PATENT URACHUS SO TERATOLOGY LA English DT Article ID EXSTROPHY AB A boy with a closed partial cloacal septation defect with a patent urachus is reported. He had an intact abdominal wall, a patent urachus, a colovesical fistula, intact genitalia and urethra, imperforate anus, and a lipomyelocystocoele. Patients with similar constellation of findings have been reported as cloacal exstrophy variants. What distinguishes this case from the other reported variants is the intact abdominal wall with the patent urachus, the small and normally formed phallus and urethra, and the presence of a lipomyelocystocoele. We discuss the possible embryologic mechanism responsible for this boy's findings and possible relationship with the cloacal exstrophy spectrum. We also discuss new terminology for the epispadias-exstrophy spectrum. Furthermore this case reminds us that there is considerable variability within the epispadiasexstrophy spectrum. C1 MASSACHUSETTS GEN HOSP,DEPT PEDIAT SURG,BOSTON,MA 02114. RP STOLER, JM (reprint author), MASSACHUSETTS GEN HOSP,CHILDRENS SERV,EMBRYOL TERATOL UNIT,BOSTON,MA 02114, USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD AUG PY 1993 VL 48 IS 2 BP 97 EP 103 DI 10.1002/tera.1420480203 PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA LQ401 UT WOS:A1993LQ40100002 PM 8211824 ER PT J AU CASCINO, I DALFONSO, S CAPPELLO, N GIORDANO, M PUGLIESE, A AWDEH, Z ALPER, CA RICHIARDI, PM AF CASCINO, I DALFONSO, S CAPPELLO, N GIORDANO, M PUGLIESE, A AWDEH, Z ALPER, CA RICHIARDI, PM TI GAMETIC ASSOCIATION OF HSP70-1 PROMOTER REGION ALLELES AND THEIR INCLUSION IN EXTENDED HLA HAPLOTYPES SO TISSUE ANTIGENS LA English DT Article DE EXTENDED HAPLOTYPES; HLA; HSP70-1 PROMOTER; POLYMORPHISM ID HISTOCOMPATIBILITY COMPLEX HAPLOTYPES; GENES AB Gametic associations of a three-allele polymorphism of the HSP70-1 promoter region were analyzed in a random North Italian population, in 69 HLA homozygous cell lines and in 29 families in Boston, all typed for HLA class 1, class 11 and complement alleles. Significant phenotypic associations were detected in the random population between HSP70-1 alleles and several HLA markers carried by extended haplotypes. The inclusion of HSP70-1 alleles in extended haplotypes, suggested by population analysis, was confirmed in genotyped cells, including 10W HLA homozygous cell lines and families, selected for the presence of the whole set of alleles reported for conserved extended haplotypes. Every tested extended haplotype was exclusively associated with a given HSP70-1 allele, except those carrying DR1. HSP70-1 C was included in both [HLA-B8, SC01, DR3] and [HLA-B18, FIC30, DR3] extended haplotypes, accounting for the previously observed strong association with DR3. In addition the same allele was found on the [HLA-B13, SC31, DR7], on the [HLA-B62, SB42, DR4] and on the [HLA-B60, SC02, DR13] extended haplotypes. The HSP70-1 A allele was carried by all DR4+ extended haplotypes except the one above cited. HSP70-1 B correlated with DR10, DQB1*0501 and BF*E Thus the HSP70-1 promoter alleles provide new precisely located markers of extended haplotypes. C1 UNIV TURIN,DEPT GENET BIOL & MED CHEM,I-10124 TURIN,ITALY. CNR,CTR IMMUNOGENET & HISTOCOMPATIBIL,TURIN,ITALY. UNIV COLORADO,HLTH SCI CTR,BARBARA DAVIS CTR CHILDHOOD DIABETES,DENVER,CO 80262. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RP CASCINO, I (reprint author), CNR,INST CELL BIOL,VIALE MARX 43,I-00137 ROME,ITALY. RI Cappello, Nazario/D-9530-2012; D'Alfonso, Sandra/K-7295-2014 OI D'Alfonso, Sandra/0000-0002-3983-9925 FU NHLBI NIH HHS [HL 29583]; NIAID NIH HHS [AI 14157]; NICHD NIH HHS [HD 17461] NR 15 TC 24 Z9 24 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD AUG PY 1993 VL 42 IS 2 BP 62 EP 66 PG 5 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA MA320 UT WOS:A1993MA32000002 PM 7903489 ER PT J AU OHZATO, H PORTER, J MONACO, AP MONTANA, E MAKI, T AF OHZATO, H PORTER, J MONACO, AP MONTANA, E MAKI, T TI MINIMUM NUMBER OF ISLETS REQUIRED TO MAINTAIN EUGLYCEMIA AND THEIR REDUCED IMMUNOGENICITY AFTER TRANSPLANTATION INTO DIABETIC MICE SO TRANSPLANTATION LA English DT Article ID MULTIPLE-DONOR ALLOTRANSPLANTATION; PANCREATIC-ISLETS; INSULIN-SECRETION; RAT ISLETS; BETA-CELLS; ALLOGRAFTS; LANGERHANS; SURVIVAL; INTERLEUKIN-1; RELEASE AB In streptozocin (SZ)-induced diabetic mice, 200 islets, but not 50 islets, consistently restore euglycemia within 1 week of transplantation. To determine the minimum number of islets sufficient to maintain euglycemia in a diabetic mouse, we first transplanted 50 and 150 syngeneic islets simultaneously into the right (RK) and left kidney (LK), respectively, and then removed the LK 1 week post-transplantation. The remaining 50 islets maintained euglycemia in 8 of 11 mice with normal intravenous glucose tolerance tests (IVGTT). Protection of 50 islets for at least 7 days was necessary because removal of the 150 islets at 5 or 3 days resulted in a much lower incidence of persistent euglycemia. Similarly, 25 islets were capable of maintaining euglycemia in 2 of 9 mice once hyperglycemia was reversed by split-transplantation of 25 (RK) and 175 (LK) islets. To examine if 50-islet allografts survive longer than 200-islet allografts, we split-transplanted 50 DBA/2 islets in the RK and 150 islets of either B6 (syngeneic), DBA/2 (allogeneic), or C3H/He (third party allogeneic) mouse origin in the LK in 3 groups of diabetic C57BL/6 (B6) mice. The survival of 50 DBA/2 islets in each group after removal of the LK on day 7 was compared to that of 200 DBA/2 islets in control B6 mice. Maximum prolongation of allograft survival was obtained with 50 DBA/2 islets that were split-transplanted with syngeneic B6 islets. These results clearly demonstrate that 50 islets are sufficient to maintain normal glucose tolerance once euglycemia is induced by transplantation of a larger number (i.e., 200) of islets and that 50 islet allografts are much less immunogenic than 200-islet allografts. C1 NEW ENGLAND DEACONESS HOSP,DIV ORGAN TRANSPLANT,185 PILGRIM RD,BOSTON,MA 02215. JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NIAID NIH HHS [AI14551]; NIDDK NIH HHS [DK35449, DK41255] NR 26 TC 17 Z9 17 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG PY 1993 VL 56 IS 2 BP 270 EP 274 DI 10.1097/00007890-199308000-00003 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA LT250 UT WOS:A1993LT25000003 PM 8356579 ER PT J AU GREGERMAN, RI AF GREGERMAN, RI TI SOLITARY THYROID-NODULES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP GREGERMAN, RI (reprint author), AUDIE L MURPHY MEM VET AFFAIRS HOSP,SAN ANTONIO,TX 78284, USA. NR 0 TC 1 Z9 1 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 29 PY 1993 VL 329 IS 5 BP 360 EP 360 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LN621 UT WOS:A1993LN62100019 PM 8321268 ER PT J AU WEISS, RB VOGELZANG, NJ PETERSON, BA PANASCI, LC CARPENTER, JT GAVIGAN, M SARTELL, K FREI, E MCINTYRE, OR AF WEISS, RB VOGELZANG, NJ PETERSON, BA PANASCI, LC CARPENTER, JT GAVIGAN, M SARTELL, K FREI, E MCINTYRE, OR TI A SUCCESSFUL SYSTEM OF SCIENTIFIC-DATA AUDITS FOR CLINICAL-TRIALS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MISCONDUCT; PROGRAM AB Objective.-To report on data collected during on-site audits of source documents in the Cancer and Leukemia Group B (CALGB). Design.-A retrospective review of audit reports in four audit cycles. Setting.-A cooperative group of institutions conducting clinical trials in cancer treatment. Participants.-Patients taking part in clinical trials at collaborating CALGB institutions, members of the CALGB Data Audit Committee, and group chairmen of CALGB. Main Outcome Measure.-The results of 691 institutional audits conducted by the CALGB in 1982 through 1992 with comparisons of main CALGB institutions vs affiliates. Results.-In four full reviews of all participating institutions in the CALGB, 3787 patients have had their on-site medical records compared with data submitted to the CALGB Data Management Center. Compliance with federal regulations for oversight by an institutional review board improved from a deficiency rate of 28.0% among the main institutions and 49.6% of the affiliate institutions in the first audit cycle to respective figures of 13.3% and 28.2% in the fourth cycle. Consent form deficiencies also dropped overall from 18.5% in the first cycle to 3.9% in the fourth. Patient eligibility was verified by auditors in 94.5%, and assessment of tumor changes in response to treatment was verified in 96.4% in the fourth cycle; both figures were only slightly lower in the first cycle. Two instances of scientific impropriety were discovered for a rate of only 0.28% of all audits. Both occurred prior to 1984, and none have occurred since. Major protocol deviations in drug dosing have held steady at about 11% over four audit cycles. Over the 11-year period of audits, three main institutions and 96 affiliate institutions have discontinued CALGB membership due solely, or at least partly, to unfavorable audit results. Conclusion.-Scientific improprieties have occurred very rarely in clinical trials conducted by the CALGB. Protocol compliance in assessing patient eligibility and tumor responses has been high. Attention to administrative matters of consent forms, institutional review board approval, and ancillary data submission has measurably improved in the CALGB, which is at least partly due to the pressure from this on-site peer review of investigator performance. C1 MCGILL CANC CTR,DEPT MED,MONTREAL,PQ,CANADA. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. CANC & LEUKEMIA GRP B,CENT OFF,LEBANON,NH. UNIV MINNESOTA,DEPT MED,MINNEAPOLIS,MN 55455. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27514. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT MED,HANOVER,NH 03756. RP WEISS, RB (reprint author), WALTER REED ARMY MED CTR,DEPT MED,MED ONCOL SECT,WASHINGTON,DC 20307, USA. FU NCI NIH HHS [CA 16450, CA 26806, CA 41287] NR 17 TC 52 Z9 53 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 28 PY 1993 VL 270 IS 4 BP 459 EP 464 DI 10.1001/jama.270.4.459 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA LN426 UT WOS:A1993LN42600024 PM 8320783 ER PT J AU NAGAYA, T JAMESON, JL AF NAGAYA, T JAMESON, JL TI THYROID-HORMONE RECEPTOR DIMERIZATION IS REQUIRED FOR DOMINANT-NEGATIVE INHIBITION BY MUTATIONS THAT CAUSE THYROID-HORMONE RESISTANCE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINOIC ACID RECEPTORS; LIGAND-BINDING DOMAIN; RAT GROWTH-HORMONE; GENERALIZED RESISTANCE; RESPONSE ELEMENTS; AUXILIARY PROTEIN; BETA GENE; TRANSCRIPTIONAL ACTIVITY; MAMMALIAN-CELLS; DNA-BINDING AB The syndrome of thyroid hormone resistance (THR) is caused by multiple distinct mutations of the ligand-binding domain of the thyroid hormone beta receptor. Although the mutant receptors are transcriptionally inactive, they inhibit normal receptor function in a dominant negative manner to cause hormone resistance. Because most of the naturally occurring mutations are clustered within two areas that lie on either side of a putative dimerization region, we hypothesized that receptor dimerization was important for dominant negative inhibition. In gel mobility shift assays, two THR mutants (G345R and P453H) formed homodimers as well as heterodimers with the the retinoic acid X receptor alpha. In contrast, an artificial mutation (L428R) in one of the hydrophobic heptad repeats of the putative receptor dimerization domain impaired heterodimerization with retoinoic acid X receptor alpha without altering the formation of homodimers. Double mutants containing either of the THR mutations along with the dimerization mutation formed homodimers but not heterodimers, reflecting the properties of the dimerization mutant alone. In transient expression assays using positively (TRETKLuc) or negatively (TSHalphaLuc) regulated reporter genes, the dominant negative activity of the THR mutants was eliminated by the addition of the dimerization mutation. These results support a mechanism for dominant negative activity by THR mutants in which functionally inactive heterodimers bind to DNA to inhibit access by normal receptors. C1 MASSACHUSETTS GEN HOSP,THYROID UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [HD 28138]; NIDDK NIH HHS [DK 42144] NR 48 TC 123 Z9 124 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 25 PY 1993 VL 268 IS 21 BP 15766 EP 15771 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN305 UT WOS:A1993LN30500066 PM 8340402 ER PT J AU KYRIAKIS, JM FORCE, TL RAPP, UR BONVENTRE, JV AVRUCH, J AF KYRIAKIS, JM FORCE, TL RAPP, UR BONVENTRE, JV AVRUCH, J TI MITOGEN REGULATION OF C-RAF-1 PROTEIN-KINASE ACTIVITY TOWARD MITOGEN-ACTIVATED PROTEIN KINASE-KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; THREONINE TYROSINE KINASE; ERK-1 GENE-PRODUCT; MAP KINASE; SIGNAL TRANSDUCTION; RAF-1 KINASE; S6 KINASE; PHOSPHORYLATION; INSULIN; SERINE AB The c-raf-1 protooncogene encodes a Ser/Thr protein kinase. A mitogen-activated protein kinase-kinase (MAPKK) purified from bovine brain is phosphorylated and activated 4-9-fold in vitro by c-Raf-1 from mitogen-treated cells. c-Raf-1 protein kinase activity, measured by the phosphorylation of brain MAPKK substrate, is detectably activated within 1 min after addition of platelet-derived growth factor (PDGF) to 3T3 cells, increasing more rapidly than the endogenous NIH 3T3 cell MAPKK activity. c-Raf-1 activation is also induced by insulin, phorbol ester, thrombin, and endothelin. PDGF-, epidermal groth factor-, and insulin-stimulated P-32-c-Raf-1 yield very similar, complex tryptic P-32-peptide maps, wherein only 2 of 10 P-32-peptides appear entirely de novo after growth factor addition. Mitogen-activated protein kinase/extracellular signal-regulated kinase-2 can phosphorylate c-Raf-1 in vitro on 4-6 tryptic P-32-peptides, all of which comigrate with tryptic P-32-peptides derived from c-Raf-1 labeled in situ. Mitogen-activated protein kinase phosphorylation of c-Raf-1 in vitro, however, does not 1) generate P-32-peptides that comigrate with those that appear de novo after PDGF or insulin treatment in situ; 2) does not convert c-Raf-1 polypeptides to a slower mobility on SDS-polyacrylamide gel electrophoresis as is seen after PDGF or insulin; 3) does not alter c-Raf-1 kinase activity toward MAPKK. Thus, based on overlapping site specificity, Erk-2 is a viable candidate to be among the PDGF-stimulated c-Raf-1 kinases. Although PDGF/insulin-stimulated c-Raf-1 Ser/Thr phosphorylation may be necessary to sustain the active state, a role for mitogen-activated protein kinase/extracellular signal-regulated kinase-2 phosphorylation in the initiation of c-Raf-1 activation is unlikely. C1 MASSACHUSETTS GEN HOSP,DIABET UNIT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,MED SERV,CARDIOL UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02129. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. OI Force, Thomas/0000-0002-0450-8659 FU NIDDK NIH HHS [DK38452, DK01986]; NIGMS NIH HHS [GM46577] NR 40 TC 97 Z9 97 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 25 PY 1993 VL 268 IS 21 BP 16009 EP 16019 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN305 UT WOS:A1993LN30500096 PM 8340422 ER PT J AU BATSON, SC RIMSKY, S SUNDSETH, R HANSEN, U AF BATSON, SC RIMSKY, S SUNDSETH, R HANSEN, U TI ASSOCIATION OF NUCLEOSOME-FREE REGIONS AND BASAL TRANSCRIPTION FACTORS WITH IN-VIVO-ASSEMBLED CHROMATIN TEMPLATES ACTIVE IN-VITRO SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA POLYMERASE-II; SIMIAN VIRUS-40 CHROMATIN; ADENOVIRUS-2 MAJOR LATE; SV40 MINI-CHROMOSOMES; INITIATION-FACTOR; SACCHAROMYCES-CEREVISIAE; PREINITIATION COMPLEXES; POSITIONED NUCLEOSOMES; HYPERSENSITIVE REGION; FUNCTIONAL-ANALYSIS AB Using SV40 minichromosomes assembled in vivo, we have studied the relationship between a nucleosome-free promoter-region and initiation of transcription by RNA polymerase II on chromatin templates in vitro. Our data suggest that accessibility of DNA to transcription factors, programmed into the structure of the chromatin, is crucial for initiation of transcription. First, minichromosomes competent to be transcribed in vitro contained nucleosome-free promoter regions. Second, tsC219 minichromosomes, most of which contain the nucleosome-free promoter region, supported transcription more efficiently both in vivo and in vitro than wild-type minichromosomes, in which only a subset contain the nucleosome-free region. We have also identified basal transcription factors associated with the in vivo-assembled chromatin templates. A striking correlation was observed between minichromosomes associated with in vivo initiated RNA polymerases and those associated with the basal transcription factors TFIID and TFIIE/F, and to a lesser extent, TFIIB. Of these associated factors, only TFIID was poised for ready assembly into preinitiation complexes and therefore for subsequent initiation of transcription. However, an active chromatin template could also be maintained in the absence of the binding of TFIID. Finally, our data are consistent with the presence of TFIIF in elongating ternary complexes on the chromatin templates. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,EUKARYOT TRANSCRIPT LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. FU NCI NIH HHS [T32 CA09361]; NIGMS NIH HHS [GM 36667] NR 83 TC 12 Z9 12 U1 0 U2 0 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 JUL 25 PY 1993 VL 21 IS 15 BP 3459 EP 3468 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ083 UT WOS:A1993LQ08300017 PM 8393989 ER PT J AU KAMEOKA, J TANAKA, T NOJIMA, Y SCHLOSSMAN, SF MORIMOTO, C AF KAMEOKA, J TANAKA, T NOJIMA, Y SCHLOSSMAN, SF MORIMOTO, C TI DIRECT ASSOCIATION OF ADENOSINE-DEAMINASE WITH A T-CELL ACTIVATION ANTIGEN, CD26 SO SCIENCE LA English DT Article ID DIPEPTIDYL PEPTIDASE-IV; AMINO-ACID-SEQUENCE; COMPLEXING PROTEIN; MONOCLONAL-ANTIBODIES; BINDING-PROTEIN; SURFACE; EXPRESSION; 1F7; CHROMOSOME-2; ASSIGNMENT AB CD26, the T cell activation molecule dipeptidyl peptidase IV (DPPIV), associates with a 43-kilodalton protein. Amino acid sequence analysis and immunoprecipitation studies demonstrated that this 43-kilodalton protein was adenosine deaminase (ADA). ADA was coexpressed with CD26 on the Jurkat T cell lines, and an in vitro binding assay showed that the binding was through the extracellular domain of CD26. ADA deficiency causes severe combined immunodeficiency disease (SCID) in humans. Thus, ADA and CD26 (DPPIV) interact on the T cell surface, and this interaction may provide a clue to the pathophysiology of SCID caused by ADA deficiency. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIAID NIH HHS [AI29530, AI12069]; NIAMS NIH HHS [AR33713] NR 35 TC 380 Z9 385 U1 2 U2 20 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 23 PY 1993 VL 261 IS 5120 BP 466 EP 469 DI 10.1126/science.8101391 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LN623 UT WOS:A1993LN62300034 PM 8101391 ER PT J AU CARLSON, KJ NICHOLS, DH SCHIFF, I AF CARLSON, KJ NICHOLS, DH SCHIFF, I TI INDICATIONS FOR HYSTERECTOMY - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP CARLSON, KJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 22 PY 1993 VL 329 IS 4 BP 276 EP 276 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LM682 UT WOS:A1993LM68200014 ER PT J AU ENG, C LI, FP ABRAMSON, DH ELLSWORTH, RM WONG, FL GOLDMAN, MB SEDDON, J TARBELL, N BOICE, JD AF ENG, C LI, FP ABRAMSON, DH ELLSWORTH, RM WONG, FL GOLDMAN, MB SEDDON, J TARBELL, N BOICE, JD TI MORTALITY FROM 2ND TUMORS AMONG LONG-TERM SURVIVORS OF RETINOBLASTOMA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NON-OCULAR CANCER; BILATERAL RETINOBLASTOMA; HUMAN SARCOMAS; OSTEO-SARCOMA; SUSCEPTIBILITY GENE; MALIGNANT NEOPLASMS; NONOCULAR TUMORS; BONE SARCOMAS; EXPRESSION; DELETION AB Background: Children diagnosed with retinoblastoma, a rare cancer of the eye, tend to develop and die of second primary cancers in childhood and adolescence, but few investigations have followed patients into adulthood. Retinoblastoma is frequently caused by inherited mutations of the RB1 tumor suppressor gene. Most patients with germline (hereditary) mutations have bilateral disease. Purpose: We sought to quantify the mortality from second malignancies among long-term survivors of retinoblastoma and to identify factors that predispose to these deaths. Methods: A retrospective cohort study examined mortality among 1603 patients enrolled at 1 year after diagnosis of retinoblastoma during the period 1914-1984. Data on demography, family history, and retinoblastoma treatment were collected by medical chart review and questionnaire interview. Number of deaths, by cause, was compared with the corresponding expected figure based on U.S. mortality data for the general population for 1925-1990. Results: Follow-up was complete for 1458 patients (91%) for a median of 17 years after retinoblastoma diagnosis. A total of 305 deaths occurred, 167 of them from retinoblastoma. There were 96 deaths from second primary tumors (relative risk [RR] = 30), 21 from other known causes (RR = 1.0), and 21 from ill-defined or unknown causes. Statistically significant excess mortality was found for second primary cancers of bone, connective tissue, and malignant melanoma and benign and malignant neoplasms of brain and meninges. Among 919 children with bilateral retinoblastoma, 90 deaths from second primary tumors occurred (RR = 60). Deaths from second tumors were more frequent among females (RR = 39) than males (RR = 22) (P = .007). The cumulative probability of death from second primary neoplasms was 26% at 40 years after bilateral retinoblastoma diagnosis, and additional cancer deaths occurred thereafter. Radiotherapy for retinoblastoma further increased the risk of mortality from second neoplasms. An excess of mortality from a second cancer, not seen in prior studies, was found among the 684 children with unilateral disease (RR = 3.1; 95% confidence interval = 1.0-7.3). Conclusions: These findings implicate germinal mutations in the retinoblastoma gene in second cancer mortality. Radiotherapy treatment for retinoblastoma appears to further enhance the inborn susceptibility to development of a second cancer. Implications: Patients with retinoblastoma, particularly bilateral retinoblastoma, should have careful follow-up, and interventions should be developed to reduce mortality from a second cancer. C1 NCI,RADIAT EPIDEMIOL BRANCH,EPN 408,6130 EXECUT BLVD,ROCKVILLE,MD 20852. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. BOSTON CHILDRENS HOSP,JOINT CTR RADIAT THERAPY,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. CORNELL UNIV,MED CTR,NEW YORK HOSP,CTR OPHTHALM ONCOL,NEW YORK,NY 10021. HARVARD UNIV,SCH PUBL HLTH,CAMBRIDGE,MA 02138. RI Wong, Fuhin/M-8360-2013; OI Eng, Charis/0000-0002-3693-5145 FU NCI NIH HHS [N01CP85604, N01CPO5609] NR 54 TC 376 Z9 382 U1 0 U2 9 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 21 PY 1993 VL 85 IS 14 BP 1121 EP 1128 DI 10.1093/jnci/85.14.1121 PG 8 WC Oncology SC Oncology GA LM449 UT WOS:A1993LM44900011 PM 8320741 ER PT J AU WANG, PH AF WANG, PH TI TIGHT GLUCOSE CONTROL AND DIABETIC COMPLICATIONS SO LANCET LA English DT Editorial Material RP WANG, PH (reprint author), HARVARD UNIV, SCH MED, JOSLIN DIABET CTR, BOSTON, MA 02115 USA. NR 6 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD JUL 17 PY 1993 VL 342 IS 8864 BP 129 EP 129 DI 10.1016/0140-6736(93)91338-M PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LN042 UT WOS:A1993LN04200004 PM 8101249 ER PT J AU KOPANS, DB AF KOPANS, DB TI MAMMOGRAPHIC SCREENING SO LANCET LA English DT Letter RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 5 TC 1 Z9 1 U1 1 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 17 PY 1993 VL 342 IS 8864 BP 183 EP 183 DI 10.1016/0140-6736(93)91394-2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LN042 UT WOS:A1993LN04200061 PM 8101286 ER PT J AU SILVER, PA WAY, JC AF SILVER, PA WAY, JC TI EUKARYOTIC DNAJ HOMOLOGS AND THE SPECIFICITY OF HSP70 ACTIVITY SO CELL LA English DT Review ID HEAT-SHOCK PROTEIN; ENDOPLASMIC-RETICULUM; SACCHAROMYCES-CEREVISIAE; YEAST HOMOLOG; GENE; TRANSLOCATION; REPLICATION; INITIATION; BINDING C1 RUTGERS UNIV,DEPT BIOL,PISCATAWAY,NJ 08855. RP SILVER, PA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115, USA. NR 25 TC 187 Z9 193 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 16 PY 1993 VL 74 IS 1 BP 5 EP 6 DI 10.1016/0092-8674(93)90287-Z PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LN625 UT WOS:A1993LN62500002 PM 8334705 ER PT J AU WALSH, CT AF WALSH, CT TI VANCOMYCIN RESISTANCE - DECODING THE MOLECULAR LOGIC SO SCIENCE LA English DT Editorial Material ID VANA C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP WALSH, CT (reprint author), HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115, USA. NR 20 TC 155 Z9 157 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 16 PY 1993 VL 261 IS 5119 BP 308 EP 309 DI 10.1126/science.8392747 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM678 UT WOS:A1993LM67800024 PM 8392747 ER PT J AU WOOG, JJ METSON, R PULIAFITO, CA AF WOOG, JJ METSON, R PULIAFITO, CA TI HOLMIUM - YAG ENDONASAL LASER DACRYOCYSTORHINOSTOMY SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB Previously described techniques of endonasal laser-assisted dacryocystorhinostomy appear to offer several advantages over conventional external dacryocystorhinostomy, including the following: (1) decreased disruption of medial canthal anatomy, (2) enhanced hemostasis, and (3) avoidance of a cutaneous scar. Although good results were achieved, several limitations of early laser-assisted techniques have been noted, including difficulty in removal of the thick bone of the anterior lacrimal crest and inability to obtain specimens of lacrimal sac mucosa for biopsy purposes. In a series of 40 consecutive, primary endonasal dacryocystorhinostomy procedures, we used the holmium:YAG (Ho:YAG) laser for bone removal and endoscopic sinus surgical instrumentation to obtain lacrimal sac biopsy specimens. Intraoperative hemostasis was excellent and medial canthal scarring was avoided in all patients. The overall long-term ostium patency rate in our series was 82%. Several technical modifications adopted in the latter part of our series, including use of a small drill for supplemental bone removal, extensive removal of lacrimal sac mucosa, and use of a double stent, appeared to enhance this success rate. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. TUFTS UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02111. CTR EYE RES,BOSTON,MA. NR 14 TC 123 Z9 132 U1 0 U2 2 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL 15 PY 1993 VL 116 IS 1 BP 1 EP 10 PG 10 WC Ophthalmology SC Ophthalmology GA LL410 UT WOS:A1993LL41000001 PM 8328525 ER PT J AU RIZZO, JF LESSELL, S AF RIZZO, JF LESSELL, S TI TOBACCO AMBLYOPIA SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB Tobacco amblyopia, once an important cause of bilateral optic neuropathy, has become so rare in the United States that some investigators doubt its existence. However, we treated two men who appeared to have this disorder. These two patients demonstrate that tobacco amblyopia can develop without malnutrition, alcoholism, or disordered vitamin B-12 metabolism. Both patients recovered, one with cessation of smoking and the other with intramuscular administration of hydroxocobalamin despite continued smoking. C1 HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02115. RP RIZZO, JF (reprint author), MASSACHUSETTS EYE & EAR INFIRM,NEURO OPHTHALMOL UNIT,243 CHARLES ST,BOSTON,MA 02114, USA. NR 11 TC 40 Z9 40 U1 0 U2 2 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL 15 PY 1993 VL 116 IS 1 BP 84 EP 87 PG 4 WC Ophthalmology SC Ophthalmology GA LL410 UT WOS:A1993LL41000014 PM 8328548 ER PT J AU BODIS, S HAREGEWOIN, A AF BODIS, S HAREGEWOIN, A TI EVIDENCE FOR THE RELEASE AND POSSIBLE NEURAL REGULATION OF NITRIC-OXIDE IN HUMAN SALIVA SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article C1 SHIELDS WARREN RES LABS,BOSTON,MA 02115. RP BODIS, S (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,JOINT CTR RADIAT THERAPY,50 BINNEY ST,BOSTON,MA 02115, USA. NR 6 TC 51 Z9 54 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 15 PY 1993 VL 194 IS 1 BP 347 EP 350 DI 10.1006/bbrc.1993.1826 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LM603 UT WOS:A1993LM60300051 PM 8333849 ER PT J AU DEFRANCO, C RO, M GROSSEL, M ENGLISH, MA HANSEN, UM WAGNER, JA LICHT, JD AF DEFRANCO, C RO, M GROSSEL, M ENGLISH, MA HANSEN, UM WAGNER, JA LICHT, JD TI NGFIA (EGR1) CONTAINS TRANSCRIPTION ACTIVATING DOMAINS IN BOTH THE AMINO-TERMINAL AND CARBOXYL-TERMINAL REGIONS OF THE PROTEIN SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GENE-EXPRESSION; DNA-BINDING; DISSECTION; ENCODES C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,EUKARYOT TRANSCRIPT LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. FU NCI NIH HHS [CA22427, NRSA CA 0880, CA 01272] NR 16 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 15 PY 1993 VL 194 IS 1 BP 425 EP 431 DI 10.1006/bbrc.1993.1837 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LM603 UT WOS:A1993LM60300062 PM 8392841 ER PT J AU ENG, C CUNNINGHAM, D QUADE, BJ SCHWAMM, L KANTOFF, PW SKARIN, AT AF ENG, C CUNNINGHAM, D QUADE, BJ SCHWAMM, L KANTOFF, PW SKARIN, AT TI MENINGEAL CARCINOMATOSIS FROM TRANSITIONAL-CELL CARCINOMA OF THE BLADDER SO CANCER LA English DT Article DE BLADDER CANCER; TRANSITIONAL CELL CARCINOMA; BRAIN METASTASES; MENINGEAL CARCINOMATOSIS; MAGNETIC RESONANCE IMAGING ID BRAIN METASTASES; MENINGITIS; METHOTREXATE; VINBLASTINE; DOXORUBICIN; CISPLATIN AB Response rates of over 50% can be achieved in patients with metastatic transitional cell carcinoma of the bladder treated with cisplatin-based chemotherapy. With prolonged survival, intraparenchymal brain metastases may occur in as many as 12% of patients who received methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy. Meningeal carcinomatosis from urothelial cancer is rare, however. A 71-year-old man, with metastatic, transitional cell carcinoma of the bladder, attained an excellent partial response to M-VAC chemotherapy. He subsequently presented with an acute confusional state 6 months after diagnosis. Head computed tomographic studies were nondiagnostic. Gadolinium-enhanced magnetic resonance images (MRI), however, demonstrated multifocal 1-cm nodules in the brain parenchyma and enhancement of the meninges. Meningeal carcinomatosis was confirmed by lumbar puncture. Records of 40 patients with advanced transitional cell carcinoma of the bladder treated with chemotherapy between 1977 and 1992 at a cancer center were reviewed retrospectively for the occurrence of documented meningeal carcinomatosis, intraparenchymal brain metastases, or both. Among 13 responders, only 1 other patient, a 64-year-old man, was identified who had minimal metastatic disease and attained a complete response to methotrexate and cisplatin. The patient relapsed 2 years after response, with cerebellar metastases and meningeal carcinomatosis. Central nervous system (CNS) metastases in patients with transitional cell carcinoma of the bladder are unusual. Although parenchymal brain metastases may be more common after prolonged remissions induced by combination chemotherapy, meningeal carcinomatosis remains uncommon. MRI may be a useful adjunct in the diagnosis of CNS metastases. A high index of clinical suspicion for the occurrence of CNS metastases from transitional cell carcinoma is encouraged. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. OI Eng, Charis/0000-0002-3693-5145; Cunningham, David/0000-0001-5158-1069 NR 9 TC 20 Z9 20 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUL 15 PY 1993 VL 72 IS 2 BP 553 EP 557 DI 10.1002/1097-0142(19930715)72:2<553::AID-CNCR2820720236>3.0.CO;2-Z PG 5 WC Oncology SC Oncology GA LL905 UT WOS:A1993LL90500035 PM 8319186 ER PT J AU KEYOMARSI, K SAMET, J MOLNAR, G PARDEE, AB AF KEYOMARSI, K SAMET, J MOLNAR, G PARDEE, AB TI THE THYMIDYLATE SYNTHASE INHIBITOR, ICI-D1694, OVERCOMES TRANSLATIONAL DETAINMENT OF THE ENZYME SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID N-10-PROPARGYL-5,8-DIDEAZAFOLIC ACID; MESSENGER-RNA; COLON-CARCINOMA; BREAST-CANCER; CELL-LINE; CB 3717; ANTIFOLATE; TUMOR; SYNTHETASE; INVIVO AB We have investigated the mechanism of inactivation of thymidylate synthase (TS) by ICI D1694 (a folate-based quinazoline) in normal versus tumor-derived human mammary epithelial cells. ICI D1694 is a very potent cytotoxic agent against these cells with IC50 values of 1-2 nM. Its growth inhibitory activity was completely reversed by the addition of thymidine, confirming that TS is its sole target in these cells. Remarkably, TS protein levels rose by 10-40-fold following treatment with ICI D1694, depending on cell type, while TS mRNA levels remained constant. The mechanism appears to be a release of ''detainment'' of TS translation, since addition of cycloheximide, a translational inhibitor, blocked the TS protein levels from rising. But coadministration of 5,6-dichlorobenzimidazole, a transcriptional inhibitor, did not overcome protein accumulation, nor did thymidine which overcomes growth inhibition by ICI D1694. 5,10-Methylenetetrahydrofolate (via folinic acid), however, did block the effects of ICI D1694, showing that the drug has its effect upon both detainment and enzyme inhibition by binding to the folate substrate site of TS. In addition, in the presence of ICI D1694, TS protein was no longer cell cycle-regulated as evident by its constitutive expression in synchronized cells. This accumulation and constitutive expression of TS induced by D1694 should increase drug resistance under a clinical setting. We suggest that an ideal inhibitor of TS would target the TS allosteric site that binds to TS mRNA, responsible for specific translation of the protein, thereby complimenting inactivation of the enzyme. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP KEYOMARSI, K (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,44 BINNEY ST,RM D810B,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 22427, CA08949-02]; NCRR NIH HHS [S07RR05526-29] NR 51 TC 80 Z9 82 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 15 PY 1993 VL 268 IS 20 BP 15142 EP 15149 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LL759 UT WOS:A1993LL75900087 PM 8325888 ER PT J AU FATHALLAH, DM CHERIF, D DELLAGI, K ARNAOUT, MA AF FATHALLAH, DM CHERIF, D DELLAGI, K ARNAOUT, MA TI MOLECULAR-CLONING OF A NOVEL HUMAN HSP70 FROM A B-CELL LINE AND ITS ASSIGNMENT TO CHROMOSOME-5 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PEPTIDE-BINDING; SECONDARY-STRUCTURE; STRESS PROTEINS; BETA-SUBUNIT; SHOCK; DEFICIENCY; SEQUENCE; FAMILY; TRANSLOCATION; PRECURSOR AB A 2391-bp cDNA encoding a novel human hsp70, named hsp70 RY, is described. It was cloned from a cDNA library constructed using mRNA derived from an established EBV-transformed B cell line from a patient with leukocyte adhesion molecule deficiency. hsp70 RY is 701 amino acids long, has the characteristic N-terminal ATP-binding domain and the C-terminal peptide binding domain, and contains four potential N-glycosylation sites. Northern blotting revealed a single mRNA species of 3.0 kb in total RNA prepared from the patient's EBV cell line. In situ hybridization localized the single copy hsp70 RY gene to the long arm of chromosome 5 at 5 q31.1-5 q31.2. C1 MASSACHUSETTS GEN HOSP,DEPT MED,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,8TH FLOOR,149TH & 13TH ST,BOSTON,MA 02114. CTR ETUD POLYMORPHISME HUMAIN,PARIS,FRANCE. HARVARD UNIV,SCH MED,BOSTON,MA 02115. INSERM,U301,F-75005 PARIS,FRANCE. OI Abid, sayda/0000-0003-2488-1431 FU NIAID NIH HHS [AI-21964] NR 30 TC 45 Z9 47 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 1993 VL 151 IS 2 BP 810 EP 813 PG 4 WC Immunology SC Immunology GA LN986 UT WOS:A1993LN98600027 PM 8335910 ER PT J AU JAIN, JN MINER, Z RAO, A AF JAIN, JN MINER, Z RAO, A TI ANALYSIS OF THE PREEXISTING AND NUCLEAR FORMS OF NUCLEAR FACTOR OF ACTIVATED T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; LYMPHOCYTE-SPECIFIC FACTORS; PROTEIN-KINASE-C; CYCLOSPORINE-A; INTERLEUKIN-2 GENE; TRANSCRIPTION FACTOR; DNA-BINDING; MONOCLONAL-ANTIBODIES; ANTIGEN RECEPTOR; EXPRESSION AB The nuclear factor of activated T cells (NF-AT)3 is an inducible DNA-binding protein that is essential for transcriptional induction of the IL-2 gene during T cell activation. NF-AT is thought to consist of two components: a ubiquitous, inducible nuclear component that we have identified as Fos and Jun proteins, and a preexisting, T cell-specific component (NF-AT(p)) which is the target for the immunosuppressive agents cyclosporin A (CsA) and FK506. We have previously shown that nuclear extracts from activated T cells form two inducible NF-AT complexes with an oligonucleotide corresponding to the distal NF-AT site of the murine IL-2 promoter, although hypotonic extracts of unstimulated T cells form a single complex containing NF-AT(p). We show that the ability to detect NF-AT(p) in a gel shift assay, which is essential for purification and biochemical studies of this protein, is strikingly dependent on the precise sequence of the NF-AT oligonucleotide used as the labeled probe. Moreover we present evidence that the component that forms the faster-migrating (''lower'') nuclear NF-AT complex is derived by a calcium-dependent, cyclosporin-sensitive, posttranslational modification of NF-AT(p), and that Fos and Jun proteins stabilize its interaction with DNA. The results are discussed in the context of a model relating the two nuclear NF-AT complexes to NF-AT(p). C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,MAYER BLDG,ROOM 613,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA42471] NR 42 TC 126 Z9 128 U1 3 U2 5 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 1993 VL 151 IS 2 BP 837 EP 848 PG 12 WC Immunology SC Immunology GA LN986 UT WOS:A1993LN98600030 PM 8335913 ER PT J AU RABB, H MICHISHITA, M SHARMA, CP BROWN, D ARNAOUT, MA AF RABB, H MICHISHITA, M SHARMA, CP BROWN, D ARNAOUT, MA TI CYTOPLASMIC TAILS OF HUMAN-COMPLEMENT RECEPTOR TYPE-3 (CR3, CD11B CD18) REGULATE LIGAND AVIDITY AND THE INTERNALIZATION OF OCCUPIED RECEPTORS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COMMON BETA-SUBUNIT; INTERCELLULAR-ADHESION MOLECULE-1; CELL-SURFACE EXPRESSION; LEU-CAM DEFICIENCY; MONOCLONAL-ANTIBODIES; HUMAN-NEUTROPHILS; FIBRONECTIN RECEPTOR; INDUCED PHOSPHORYLATION; ALPHA-SUBUNITS; INTEGRIN AB To evaluate the role of the cytoplasmic tails of CD11b and CD18 in ligand binding and internalization of the human complement receptor type 3 (CR3, CD11b/CD18), wild type, and truncation mutants of CD11b and CD18 cDNA were expressed in COS fibroblastoid cells and assayed for surface membrane expression, ligand binding, and internalization. Truncated CD11b (alpha1119T) and CD18 (beta728T) subunits retaining, respectively, two and five residues of the putative cytoplasmic tails were generated by in vitro mutagenesis. Binding of alpha1119Tbeta and alphabeta728T heterodimeric receptors to iC3b was increased by 330% and 210%, respectively, relative to wild type CR3, suggesting that both cytoplasmic tails of CR3 negatively control receptor avidity. Internalization of antibody cross-linked wild type CR3 occurred predominantly through coated pits. Truncation of the cytoplasmic tail of CD18 but not of CD11b markedly reduced coated pit internalization of CR3, an effect also produced by a single F754A mutation involving one of two putative NPXF internalization signals in CD18. C1 MASSACHUSETTS GEN HOSP,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,RENAL UNIT,8TH FLOOR,E 149 13TH ST,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02129. FU NIAID NIH HHS [AI 21964] NR 60 TC 53 Z9 54 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 1993 VL 151 IS 2 BP 990 EP 1002 PG 13 WC Immunology SC Immunology GA LN986 UT WOS:A1993LN98600046 PM 8101539 ER PT J AU ZAPOL, WM FALKE, KJ ROSSAINT, R AF ZAPOL, WM FALKE, KJ ROSSAINT, R TI INHALED NITRIC-OXIDE FOR THE ADULT-RESPIRATORY-DISTRESS-SYNDROME - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 FREE UNIV BERLIN,KLINIKUM RUDOLF VIRCHOW,W-1000 BERLIN 65,GERMANY. RP ZAPOL, WM (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 15 PY 1993 VL 329 IS 3 BP 207 EP 207 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LL460 UT WOS:A1993LL46000015 ER PT J AU GIMMI, CD FREEMAN, GJ GRIBBEN, JG GRAY, G NADLER, LM AF GIMMI, CD FREEMAN, GJ GRIBBEN, JG GRAY, G NADLER, LM TI HUMAN T-CELL CLONAL ANERGY IS INDUCED BY ANTIGEN PRESENTATION IN THE ABSENCE OF B7 COSTIMULATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PRESENTING CELLS; ACTIVATION ANTIGEN-B7; MONOCLONAL-ANTIBODIES; HUMAN-LYMPHOCYTES; MESSENGER-RNA; CD28 PATHWAY; EXPRESSION; INTERLEUKIN-2; RECEPTOR; GENE AB The maximal T-cell response to its antigen requires presentation of the antigen by a major histocompatibility complex class II molecule as well as the delivery of one or more costimulatory signals provided by the antigen-presenting cell (APC). Although a number of candidate molecules have been identified that are capable of delivering a costimulatory signal, increasing evidence suggests that one such critical pathway involves the interaction of the T-cell surface antigen CD28 with its ligand B7, expressed on APCs. In view of the number of potential costimulatory molecules that might be expressed on the cell surface of APCs, artificial APCs were constructed by stable transfection of NIH 3T3 cells with HLA-DR7, B7, or both. Here, we show that in a human antigen-specific model system, when tetanus toxoid peptide antigen is presented by cells cotransfected with HLA-DR7 and B7, optimal T-cell proliferation and interleukin 2 production result. In contrast, antigen presentation, in the absence of B7 costimulation, results in T-cell clonal anergy. These results demonstrate that it is possible to induce antigen-specific clonal tolerance in human T cells that have been previously sensitized to antigen. The artificial antigen-presenting system provides a useful model for the investigation of the biochemical events involved in the generation of tolerance and for the study of signals necessary to overcome tolerance. C1 REPLIGEN CORP,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP GIMMI, CD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA40216] NR 28 TC 537 Z9 546 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 15 PY 1993 VL 90 IS 14 BP 6586 EP 6590 DI 10.1073/pnas.90.14.6586 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM681 UT WOS:A1993LM68100044 PM 7688125 ER PT J AU WINOGRAD, CH GERETY, MB AF WINOGRAD, CH GERETY, MB TI GERIATRIC-MEDICINE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HIP FRACTURE; FALLS; RISK C1 VET AFFAIRS MED CTR,PALO ALTO,CA. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. RP WINOGRAD, CH (reprint author), STANFORD UNIV,MED CTR,SCH MED,STANFORD,CA 94305, USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 14 PY 1993 VL 270 IS 2 BP 213 EP 216 DI 10.1001/jama.270.2.213 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA LL368 UT WOS:A1993LL36800022 PM 8315736 ER PT J AU WOOD, KW AF WOOD, KW TI HOT PAPERS - CELL BIOLOGY - RAS MEDIATES NERVE GROWTH-FACTOR RECEPTOR MODULATION OF 3 SIGNAL-TRANSDUCING PROTEIN-KINASES - MAP KINASE, RAF-1, AND RSK BY WOOD,K.W., SARNECKI,C., ROBERTS,T.M., BLENIS,J. SO SCIENTIST LA English DT Article RP WOOD, KW (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD JUL 12 PY 1993 VL 7 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 LL356 UT WOS:A1993LL35600015 ER PT J AU LIANG, P AVERBOUKH, L PARDEE, AB AF LIANG, P AVERBOUKH, L PARDEE, AB TI DISTRIBUTION AND CLONING OF EUKARYOTIC MESSENGER-RNAS BY MEANS OF DIFFERENTIAL DISPLAY - REFINEMENTS AND OPTIMIZATION SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; TUMOR AB Differential display has been developed as a tool to detect and characterize altered gene expression in eukaryotic cells. The basic principle is to systematically amplify messenger RNAs and then distribute their 3' termini on a denaturing polyacrylamide gel. Here we provide methodological details and examine in depth the specificity, sensitivity and reproducibility of the method. We show that the number of anchored oligo-dT primers can be reduced from twelve to four that are degenerate at the penultimate base from the 3' end. We also demonstrate that using optimized conditions described here, multiple RNA samples from related cells can be displayed simultaneously. Therefore process-specific rather than cell-specific genes could be more accurately identified. These results enable further streamlining of the technique and make it readily applicable to a broad spectrum of biological systems. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP LIANG, P (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 22427]; NIGMS NIH HHS [GM24571] NR 16 TC 880 Z9 986 U1 1 U2 5 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 JUL 11 PY 1993 VL 21 IS 14 BP 3269 EP 3275 DI 10.1093/nar/21.14.3269 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN960 UT WOS:A1993LN96000017 PM 8341601 ER PT J AU MCCARTHY, JG FREDERICK, CA NICOLAS, A AF MCCARTHY, JG FREDERICK, CA NICOLAS, A TI A STRUCTURAL-ANALYSIS OF THE BENT KINETOPLAST DNA FROM CRITHIDIA-FASCICULATA BY HIGH-RESOLUTION CHEMICAL PROBING SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DIETHYL PYROCARBONATE; CURVED DNA; CURVATURE; SEQUENCE; BINDING; CONFORMATION; FRAGMENT; DISTAMYCIN; ADENINE; TRACTS AB The chemical probes potassium permanganate (KMnO4) and diethylpyrocarbonate (DEPC) have been used to study the conformation of bent kinetoplast DNA from Crithidia fasciculata at different temperatures. Chemical reactivity data shows that the numerous short A-tracts of this bent DNA adopt a similar structure at 43-degrees-C. This conformation appears to be very similar to the conformation of A-tracts in DNA exhibiting normal gel mobility. The A-tract structure detected by chemical probing is characterized by a high degree of base stacking on the thymine strand, and by an abrupt conformational change at the 3' end of the adenine strand. In general, no major alteration of this A-tract specific structure was detected between 4-53-degrees-C. However, probing with KMnO4 revealed two unusual features of the C. fasciculata sequence that may contribute to the highly aberrant gel mobility of this DNA: 1) the B DNA/A-tract junction 5' dC/A3-6 3'. 5' dT3-6/G 3' is disproportionately represented and is conformationally distinct from other 5' end junctions, and 2) low temperature favors a novel strand-specific conformational distortion over a 20 base pair region of the bent kinetoplast DNA. Presence of the minor groove binding drug distamycin had little detectable effect on the A-tract conformation. However, distamycin did inhibit formation of the novel KMnO4 sensitive low temperature structure and partially eliminated the anomalous gel mobility of the kinetoplast DNA. Finally, we describe a simple and reproducible procedure for the production of an adenine-specific chemical DNA sequence ladder. C1 UNIV PARIS 11,INST GENET & MICROBIOL,F-91405 ORSAY,FRANCE. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 49 TC 9 Z9 9 U1 0 U2 0 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 JUL 11 PY 1993 VL 21 IS 14 BP 3309 EP 3317 DI 10.1093/nar/21.14.3309 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN960 UT WOS:A1993LN96000023 PM 8393564 ER PT J AU GALE, GR SMITH, AB JONES, MM SINGH, PK AF GALE, GR SMITH, AB JONES, MM SINGH, PK TI MESO-2,3-DIMERCAPTOSUCCINIC ACID MONOALKYL ESTERS - EFFECTS ON MERCURY LEVELS IN MICE SO TOXICOLOGY LA English DT Article DE MERCURY; MESO-2,3-DIMERCAPTOSUCCINIC ACID (DMSA); DMSA MONOESTERS; 2,3-DIMERCAPTOPROPANE-1-SULFONATE (DMPS); MICE; KIDNEY ID MESO-DIMERCAPTOSUCCINIC ACID; INTRACELLULAR CADMIUM; MOBILIZATION; 2,3-DIMERCAPTOPROPANOL; EXCRETION; INVIVO; AGENTS; LEAD AB Seven monoesters of meso-2,3-dimercaptosuccinic acid (DMSA) were evaluated for relative activities in mobilizing and promoting excretion of mercury in mercury-laden mice. Compounds assessed were the ethyl (M-EDMS), n-propyl (Mn-PDMS), isopropyl (Mi-PDMS), n-butyl (Mn-BDMS), isobutyl (Mi-BDMS), n-amyl (Mn-ADMS), and isoamyl (Mi-ADMS) esters. 2,3-Dimercaptopropane-1-sulfonate (DMPS) and DMSA were used as positive controls. After the first oral dose of each compound at 0.5 mmol/kg, DMSA and DMPS reduced the corporal mercury burden 16% and 24%, respectively, compared to controls, while the monoesters effected reductions of 35% (M-EDMS) to 49% (Mi-ADMS). After the second treatment at the same dose, the respective reductions produced by DMSA and DMPS were 24% and 38%, and those conferred by the monoesters ranged from 52% (M-EDMS) to 61% (Mn-BDMS). Determination of the comparative dose-response relationships of DMSA and Mi-ADMS on corporal and renal mercury concentrations revealed the monoester to be more active than DMSA on both parameters at each dose used. The cumulative amount of mercury excreted in urine by control mice over a 3-day period was 7.08 mug; this was increased 22%, 85%, and 94% by daily i.p. injections of DMSA, DMPS, and Mi-ADMS, respectively, at a daily dose of 0. 1 mmol/kg. The respective cumulative 3-day totals recovered in feces from control mice and from mice treated with DMSA, DMPS, and Mi-ADMS were 9.76, 8.2 1, 10.44, and 11.73 mug. Parallel daily measurements of retained whole body radioactivity from Hg-203 in mice were in good agreement with the values calculated from the excretion data. C1 MED UNIV S CAROLINA,DEPT PHARMACOL,CHARLESTON,SC 29401. VANDERBILT UNIV,DEPT CHEM,NASHVILLE,TN 37235. VANDERBILT UNIV,CTR MOLEC TOXICOL,NASHVILLE,TN 37235. RP GALE, GR (reprint author), RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,RES SERV,109 BEE ST,CHARLESTON,SC 29401, USA. FU NIEHS NIH HHS [ES-02638, ES-0267] NR 16 TC 39 Z9 40 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 11 PY 1993 VL 81 IS 1 BP 49 EP 56 DI 10.1016/0300-483X(93)90155-L PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA LV764 UT WOS:A1993LV76400004 PM 8396277 ER PT J AU DODSON, E DODSON, G HUBBARD, R LIDDINGTON, R PAOLI, M TAME, J WILKINSON, A AF DODSON, E DODSON, G HUBBARD, R LIDDINGTON, R PAOLI, M TAME, J WILKINSON, A TI THE STABILITY OF THE LATTICE STRUCTURE IN LOW-SALT T-STATE HEMOGLOBIN CRYSTALS SO PROCEEDINGS OF THE ROYAL SOCIETY-MATHEMATICAL AND PHYSICAL SCIENCES LA English DT Article ID HEMOGLOBIN; OXYGEN AB The reconstruction of the electron density of molecules in crystals from X-ray diffraction measurements depends on the exactness of the packing of the molecules in the unit cell and the crystal lattice. Crystals of T-state haemoglobin, the low affinity form of the molecule, grow from high salt solutions or from low salt solutions in the presence of polyethylene glycol. The low salt lattice has the special property that it allows the haemoglobin molecule to bind oxygen and other ligands without the crystal breaking up. The stability of the low salt T-state crystals appears to arise from a small number of well-defined salt bridges and hydrogen bonds that are concentrated in specific lattice directions. These together form a framework within which the molecule can make adjustments which are sufficient to accommodate ligand binding but in which the larger quaternary movements normally associated with oxygenation are prevented. In these crystals therefore interactions with ligands can be studied directly by X-ray diffraction and the structural basis of the T-state's low affinity for oxygen can be analysed. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RP DODSON, E (reprint author), UNIV YORK, DEPT CHEM, YORK YO1 5DD, N YORKSHIRE, ENGLAND. NR 18 TC 3 Z9 3 U1 0 U2 0 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8444 J9 P R SOC-MATH PHYS SC JI P. Roy. Soc.-Math. Phys. Sci. PD JUL 8 PY 1993 VL 442 IS 1914 BP 193 EP 205 DI 10.1098/rspa.1993.0099 PG 13 GA LL727 UT WOS:A1993LL72700014 ER PT J AU DATTA, AK TAKAYAMA, K AF DATTA, AK TAKAYAMA, K TI ISOLATION AND PURIFICATION OF TREHALOSE 6-MONO-CORYNOMYCOLATES AND 6,6'-DI-CORYNOMYCOLATES FROM CORYNEBACTERIUM-MATRUCHOTII - STRUCTURAL CHARACTERIZATION BY H-1-NMR SO CARBOHYDRATE RESEARCH LA English DT Note ID BACTERIONEMA-MATRUCHOTII C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MYCOBACTERIOL RES LAB,MADISON,WI 53705. UNIV WISCONSIN,COLL PSYCHOL,DEPT BACTERIOL,MADISON,WI 53706. FU NCRR NIH HHS [RR02301, RR02031]; NIGMS NIH HHS [GM-36054] NR 19 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD JUL 5 PY 1993 VL 245 IS 1 BP 151 EP 158 DI 10.1016/0008-6215(93)80068-P PG 8 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA LL889 UT WOS:A1993LL88900014 PM 8358747 ER PT J AU CARTER, ME GULICK, T RAISHER, BD CAIRA, T LADIAS, JAA MOORE, DD KELLY, DP AF CARTER, ME GULICK, T RAISHER, BD CAIRA, T LADIAS, JAA MOORE, DD KELLY, DP TI HEPATOCYTE NUCLEAR FACTOR-IV ACTIVATES MEDIUM-CHAIN ACYL-COA DEHYDROGENASE GENE-TRANSCRIPTION BY INTERACTING WITH A COMPLEX REGULATORY ELEMENT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STEROID-RECEPTOR SUPERFAMILY; MOLECULAR-CLONING; TISSUE; DEFICIENCY; EXPRESSION; MEMBER; ALPHA-1-ANTITRYPSIN; TRANSTHYRETIN; EFFICIENCY; PROTEINS AB We have recently identified a complex transcriptional regulatory element in the medium chain acyl-CoA dehydrogenase (MCAD) gene promoter region that confers response to retinoids through interaction with receptors for all-trans-retinoic acid (RARs) and 9-cis-retinoic acid (RXRs) (Raisher, B. D., Gulick, T., Zhang, Z., Strauss, A. W., Moore, D. D., and Kelly, D. P. (1992) J. Biol. Chem. 267, 20264-20269). We examined the interaction of this element (RARE(MCAD)) with hepatocyte nuclear factor-4 (HNF-4), an orphan receptor with a tissue expression pattern similar to that of MCAD. Electrophoretic mobility shift assays and cotransfection experiments showed that HNF-4 binds with high affinity to RARE(MCAD) to activate transcription by an RXR-independent mechanism. Mutational analysis revealed that the MCAD HNF-4 response element consists of an imperfect direct repeat homologous to the consensus sequence for binding to the thyroid receptor/RAR/RXR subgroup of receptors and that distinct sequence requirements dictate HNF-4 binding and transactivation. Mobility shift assays with anti-HNF-4 antiserum demonstrated that the MCAD HNF-4 response element binds endogenous rat liver HNF-4 supporting its role in the regulation of MCAD gene expression in vivo. Thus, HNF-4 activates MCAD gene transcription via a complex regulatory element, the architecture of which carries important implications for the structure of HNF-4 response elements in general. C1 WASHINGTON UNIV,DEPT MED,ST LOUIS,MO 63130. WASHINGTON UNIV,DEPT PEDIAT,ST LOUIS,MO 63130. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. FU NIDDK NIH HHS [DK45416] NR 40 TC 66 Z9 67 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 5 PY 1993 VL 268 IS 19 BP 13805 EP 13810 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LJ825 UT WOS:A1993LJ82500009 PM 8314750 ER PT J AU EDER, JP CHAN, VTW NIEMIERKO, E TEICHER, BA SCHNIPPER, LE AF EDER, JP CHAN, VTW NIEMIERKO, E TEICHER, BA SCHNIPPER, LE TI CONDITIONAL EXPRESSION OF WILD-TYPE TOPOISOMERASE-II COMPLEMENTS A MUTANT ENZYME IN MAMMALIAN-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HAMSTER OVARY CELLS; DNA TOPOISOMERASES; CROSS-RESISTANCE; FUNCTIONAL EXPRESSION; LINE; GENE; RECOMBINATION; RECEPTOR; VM-26 AB Alterations in the amino acid composition, phosphorylation pattern, or intracellular levels of topoisomerase II have been associated with resistance to antineoplastic agents whose effects are mediated through interactions with this enzyme. To develop a model system with which to investigate the determinants of topoisomerase II sensitivity or resistance to antineoplastic agents that target this enzyme, a cDNA encoding the wild-type Drosophila melanogaster topoisomerase II was ligated into a mammalian expression vector containing a glucocorticoid-inducible mouse mammary tumor virus promoter and transfected into an epipodophyllotoxin-resistant Chinese hamster ovary cell line (VPM(r)-5). In two transfectants carrying an intact, full-length Drosophila topoisomerase II cDNA, exposure to the inducing agent, dexamethasone (10 muM), resulted in complementation of the endogenous mutant topoisomerase II and phenotypic reversion to etoposide sensitivity. In the presence of glucocorticoid, etoposide-induced cytotoxicity increased 20-fold, despite the fact that Drosophila topoisomerase II mRNA expression was only 0.1% of that of the endogenous mammalian topoisomerase II. Induced cells demonstrated a marked increase in DNA single strand breaks compared with uninduced resistant cells, thereby providing biochemical evidence supporting increased DNA strand cleavage due to activation of the Drosophila enzyme. These observations demonstrate the ability of a wild-type Drosophila topoisomerase II to complement a mutant mammalian enzyme and suggest that transfectants capable of conditional topoisomerase II expression represent a useful model for studies of the biochemical pharmacology and structure-function relationships of normal and mutant enzymes. C1 BETH ISRAEL HOSP,CHARLES A DANA RES LABS,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP EDER, JP (reprint author), BETH ISRAEL HOSP,DEPT MED,DIV MED ONCOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NCI NIH HHS [P01-CA-38493, K08 CA01412] NR 32 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 5 PY 1993 VL 268 IS 19 BP 13844 EP 13849 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LJ825 UT WOS:A1993LJ82500015 PM 8390979 ER PT J AU BREUER, W GLICKSTEIN, H KARTNER, N RIORDAN, JR AUSIELLO, DA CABANTCHIK, IZ AF BREUER, W GLICKSTEIN, H KARTNER, N RIORDAN, JR AUSIELLO, DA CABANTCHIK, IZ TI PROTEIN-KINASE-C MEDIATES DOWN-REGULATION OF CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR LEVELS IN EPITHELIAL-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CFTR CHLORIDE CHANNEL; R-DOMAIN; GENE; TRANSPORT; PHOSPHORYLATION; EXPRESSION AB Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in epithelial cells is known to be down-regulated by the action of phorbol myristate acetate (PMA). We show here that in addition to suppressing the rate of transcription of the CFTR gene, PMA treatment stimulates degradation of the CFTR protein. HT-29 colon epithelial cells and the CFTR-transfected pancreatic cells PLJ-4.7 lost 55-80% of their CFTR protein after 3-6 h of treatment with 100 nm PMA, as analyzed by quantitative Western blotting. In contrast to PMA, actinomycin D and cycloheximide reduced the CFTR protein content by 19 and 9% in HT-29 cells and by 22 and 40% in PLJ-4.7 cells, respectively, while inhibiting total cellular RNA and protein synthesis by over 80%. The PMA-induced loss of CFTR was partially reversed by the protein kinase C inhibitor GF109203X. The PMA-induced degradation of CFTR may represent a regulatory pathway for terminating CFTR-mediated chloride and mucin secretion. C1 HOSP SICK CHILDREN,RES INST,TORONTO M5G 1X8,ONTARIO,CANADA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,RENAL SECT,CHARLESTON,MA 02113. RP BREUER, W (reprint author), HEBREW UNIV JERUSALEM,INST LIFE SCI,DEPT BIOL CHEM,IL-91904 JERUSALEM,ISRAEL. FU NHLBI NIH HHS [HL-40158] NR 35 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 5 PY 1993 VL 268 IS 19 BP 13935 EP 13939 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LJ825 UT WOS:A1993LJ82500027 PM 7686146 ER PT J AU KOWALL, NW QUIGLEY, BJ KRAUSE, JE LU, F KOSOFSKY, BE FERRANTE, RJ AF KOWALL, NW QUIGLEY, BJ KRAUSE, JE LU, F KOSOFSKY, BE FERRANTE, RJ TI SUBSTANCE-P AND SUBSTANCE-P RECEPTOR HISTOCHEMISTRY IN HUMAN NEURODEGENERATIVE DISEASES SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT INTERNATIONAL SYMP ON SUBSTANCE P AND RELATED PEPTIDES : PAINS, INFLAMMATION, VISCERAL AND CNS FUNCTIONS CY NOV 03-06, 1992 CL SHIZUOKA, JAPAN SP PHARM MANUFACTURERS ASSOC TOKYO, OSAKA PHARM MANUFACTURERS ASSOC DE SUBSTANCE-P; IMMUNOCYTOCHEMISTRY; RECEPTOR; IN-SITU HYBRIDIZATION; HUMAN BRAIN; ALZHEIMERS DISEASE; HUNTINGTONS DISEASE ID CONTAINING STRIATAL NEURONS; CENTRAL NERVOUS-SYSTEM; HUNTINGTONS-DISEASE; BASAL GANGLIA; MESSENGER-RNA; HUMAN-BRAIN; MOLECULAR CHARACTERIZATION; IMMUNOREACTIVE NEURONS; FUNCTIONAL CDNA; RAT AB Substance P immunoreactivity is localized in discrete subsets of neurons in the human cerebral cortex and basal ganglia. In the normal human cerebral cortex, a subset of aspiny local circuit neurons in deep cortical layers and the cortical subplate contain preprotachykinin mRNA and substance P immunoreactive. These neurons, which contain NADPH diaphorase (NO synthase) activity, are strikingly depleted in Alzheimer's disease - in contrast to other local circuit neurons - suggesting that they may be an early target of the degenerative process. In the human basal ganglia, substance P immunoreactivity and mRNA are localized in a subset of spiny striatal neurons that project to the internal segment of the globus pallidus. These neurons are enriched in D1 dopamine receptors and dynorphin, and are calbindin and DARP 32 immunoreactive. A separate subset of aspiny striatal local circuit neurons also contain substance P immunoreactivity. Fiber and terminal staining is prominent in the matrix compartment of the ventromedial striatum and persists dorsally as a rim outlining patches that contain lesser amounts of immunoreactivity. Intense fiber and terminal staining is found in the pars reticulata of the substantia nigra. In Huntington's disease, substance P is depleted in the striatum in parallel with the dorsoventral gradient of neuronal loss. Terminal staining is progressively depleted in the pallidum and substantia nigra in tandem with striatal atrophy. Substance P receptor immunoreactivity, defined with two polyclonal antisera raised against synthetic peptides derived from the substance P receptor sequence, intensely labels a subset of large neurons in the nucleus basalis and striatum identical to neurons labeled with choline acetyltransferase and nerve growth factor receptor antibodies (although striatal cholinergic neurons do not contain nerve growth factor receptor immunoreactivity in the human). These cholinergic neurons resist degeneration in Huntington's disease but are sensitive to degeneration in Alzheimer's disease. Less intensely labeled neurons include pyramidal neurons in the hippocampal CA2 field, nonpyramidal neurons in CA1-4, pyramidal and nonpyramidal neurons in deep neocortical layers and in the cortical subplate. Substance P receptor immunoreactivity is not well defined in the human globus pallidus or substantia nigra. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. WASHINGTON UNIV,SCH MED,DEPT ANAT & NEUROBIOL,ST LOUIS,MO 63110. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP KOWALL, NW (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114, USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NIA NIH HHS [AG05134]; NINDS NIH HHS [NS 21937, NS 25588] NR 48 TC 43 Z9 43 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD JUL 2 PY 1993 VL 46 IS 1-2 BP 174 EP 185 DI 10.1016/0167-0115(93)90028-7 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA LM858 UT WOS:A1993LM85800028 PM 7692486 ER PT J AU SCHUTTEN, M MCKNIGHT, A HUISMAN, RC THALI, M MCKEATING, JA SODROSKI, J GOUDSMIT, J OSTERHAUS, AD AF SCHUTTEN, M MCKNIGHT, A HUISMAN, RC THALI, M MCKEATING, JA SODROSKI, J GOUDSMIT, J OSTERHAUS, AD TI FURTHER CHARACTERIZATION OF AN ANTIGENIC SITE OF HIV-1 GP120 RECOGNIZED BY VIRUS NEUTRALIZING HUMAN MONOCLONAL-ANTIBODIES SO AIDS LA English DT Article DE HIV-1; NEUTRALIZING ANTIBODIES; HUMAN MONOCLONAL ANTIBODY; GP120; CD4-BINDING SITE; VIRUS NEUTRALIZATION; PASSIVE IMMUNIZATION ID PASSIVE-IMMUNIZATION; IMMUNODEFICIENCY; BINDING; EPITOPE; AIDS; CD4; IDENTIFICATION; INFECTION AB Objective: The aim of this study is to characterize antigenic sites on HIV-1 gp120 which may be important for the development of active and passive immunization strategies against HIV-1 infection. Design: Two HIV-1-seropositive individuals were selected from the Amsterdam cohort and Epstein-Barr virus (EBV)-transformed B cells were generated from their peripheral blood mononuclear cells, which produce HIV-1-specific human monoclonal antibodies (HuMAb). Methods: HuMAb were generated and selected based on their reactivities with native gp120. Reactivity with HIV-1 strains from phylogenetically different subfamilies was determined by immunostaining and virus neutralization assays. Specificity for the CD4-binding site was tested by an inhibition enzyme-linked immunosorbent assay and amino acids (aa) involved in the binding of the HuMAb were identified with a set of gp120 molecules with single aa substitutions. Results: Three HuMAb (GP13, GP44, GP68) were generated, all recognizing a conserved conformation dependent epitope within, or topographically near, the CD4-binding site of gp120. HuMAb GP13 and GP68 neutralized a broad range of HIV-1 strains from phylogenetically different subfamilies, whereas HuMAb GP44 exhibited a more restricted pattern of neutralizing activity. The patterns of gp120 aa involved in their binding were unique for each of these HuMAb. Conclusions: The pattern of reactivities of these three HIV-1-neutralizing HuMAb developed in these studies is similar to, but distinct from other human and rodent MAb that recognize this antigenic site of HIV-1 gp120. C1 NATL INST PUBL HLTH & ENVIRONM PROTECT,IMMUNOBIOL LAB,POB 1,3720 BA BILTHOVEN,NETHERLANDS. INST CANC RES,CHESTER BEATTY RES INST,SUTTON SM2 5PX,SURREY,ENGLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIROL,BOSTON,MA 02115. UNIV AMSTERDAM,ACAD MED CTR,RETROVIROL LAB,1105 AZ AMSTERDAM,NETHERLANDS. OI McKeating, Jane/0000-0002-7229-5886 FU Medical Research Council [G117/547] NR 28 TC 28 Z9 28 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JUL PY 1993 VL 7 IS 7 BP 919 EP 923 DI 10.1097/00002030-199307000-00003 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LL492 UT WOS:A1993LL49200003 PM 7689324 ER PT J AU SCHOENFELD, DA FINKELSTEIN, DM RICHMAN, DD AF SCHOENFELD, DA FINKELSTEIN, DM RICHMAN, DD TI DESIGNING PHASE-II STUDIES OF CHEMOTHERAPY FOR HIV-INFECTION USING CD4 AS AN END-POINT SO AIDS LA English DT Note DE CLINICAL TRIAL DESIGN; SURROGATE MARKERS; CD4; ANTIVIRAL CHEMOTHERAPY; HIV; ZIDOVUDINE ID PLACEBO-CONTROLLED TRIAL; AIDS-RELATED COMPLEX; DOUBLE-BLIND; ZIDOVUDINE; EFFICACY; AZT AB Objective: To provide information that will be helpful in designing AIDS clinical trials that use CD4 as an end-point. Design: Meta-analysis of randomized AIDS clinical trials comparing zidovudine and placebo. Setting: Tertiary care. Patients: Eight hundred and twenty-seven patients with HIV infection. Interventions. Treatment with zidovudine at various dosages compared with placebo. Main outcome measure: Differences in the log-ratio CD4 count. Results: The mean difference in the log-ratio CD4 count divided by its standard deviation varied from 0.31 to 0.76 depending on the study. Of the variation in CD4 count 63% is short-term variation. Conclusion: Trials of 12 weeks duration can be used to test for the effect of a new drug on CD4 counts. Testing combination therapies may require somewhat longer trial periods. The sample size for clinical trials can be reduced by replicating baseline and follow-up measurements. Trials of new agents should test for an increase in CD4 over baseline. Such trials will require between 25 and 190 patients per arm depending on the patient population. Trials that compare combinations to standard therapies will require between 32 and 235 patients per arm depending on disease stage and prior therapy of study participants. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH PUBL HLTH,BOSTON,MA 02114. UNIV CALIF SAN DIEGO,DEPT PATHOL & MED,SAN DIEGO,CA 92103. SAN DIEGO VET AFFAIRS MED CTR,AIDS & HIV INFECT RES CTR,SAN DIEGO,CA. RP SCHOENFELD, DA (reprint author), MASSACHUSETTS GEN HOSP,CTR BIOSTAT,BOSTON,MA 02114, USA. FU NIAID NIH HHS [AI 27670, AI 30885, N01-AI 95030] NR 6 TC 6 Z9 6 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JUL PY 1993 VL 7 IS 7 BP 955 EP 958 DI 10.1097/00002030-199307000-00008 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LL492 UT WOS:A1993LL49200008 PM 8102853 ER PT J AU MOORE, J SATTENTAU, Q JAMESON, B SODROSKI, J AF MOORE, J SATTENTAU, Q JAMESON, B SODROSKI, J TI MONOCLONAL-ANTIBODIES TO HIV-1 GP120 - A REQUEST SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Note C1 CTR IMMUNOL & MARSEILLE LUMINY,F-13288 MARSEILLE 09,FRANCE. JEFFERSON CANC INST,PHILADELPHIA,PA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. RP MOORE, J (reprint author), AARON DIAMOND AIDS RES CTR,455 1ST AVE,NEW YORK,NY 11215, USA. NR 0 TC 0 Z9 0 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 JUL PY 1993 VL 9 IS 7 BP 695 EP 695 DI 10.1089/aid.1993.9.695 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LQ607 UT WOS:A1993LQ60700015 PM 8369173 ER PT J AU PICARD, MH WILKINS, GT RAY, P WEYMAN, AE AF PICARD, MH WILKINS, GT RAY, P WEYMAN, AE TI LONG-TERM EFFECTS OF ACUTE THROMBOLYTIC THERAPY ON VENTRICULAR SIZE AND FUNCTION SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; CANINE LEFT-VENTRICLE; INTRACORONARY THROMBOLYSIS; ANEURYSM FORMATION; NATURAL-HISTORY; EXPANSION; REPERFUSION; PREDICTION; OCCLUSION AB To investigate the influence of thrombolytic therapy on the natural history of left ventricular size and regional function after myocardial infarction, 32 patients treated with acute thrombolytic therapy (treatment group) were studied by echocardiography on admission to the hospital and at 1 week, 3 months, and 1 year after myocardial infarction; they were compared with 40 patients who did not receive acute intervention (control group). The endocardial surface area index (cm2/m2) and the area of abnormal wall motion (cm2) were calculated from left ventricular dimensions and measurements of abnormal wall motion. Although no differences in the endocardial surface area index were noted over the year for the groups as a whole, a significant difference was noted in treated anterior infarctions with early functional infarct expansion compared with untreated infarct expansion (treatment group: 85.8 +/- 2.0 cm2/m2 [entry] to 77.4 +/- 2.7 cm2/m2 [1 week] to 69.9 +/- 4.2 cm2/m2 [3 months] to 67.2 +/- 6.4 cm2/m2 [1 year] versus control group: 84.0 +/- 6.4 cm2/M2 [entry] to 83.7 +/- 8.5 cm2/m2 [1 week] to 96.3 +/- 8.6 cm2/m2 [3 months] to 81.5 +/- 4.2 cm2/m2 [1 year]; p < 0.01). When early expansion was present, those receiving thrombolysis exhibited a consistent decrease in the initially enlarged endocardial surface area in contrast to control subjects, who demonstrated continued increases in endocardial surface area during the first 3 months. In all groups a decrease in the area of abnormal wall motion was observed during the year of follow-up. However, the magnitude and timing of the improvement was accelerated in the treatment group. Thus acute thrombolytic therapy alters the natural history of left ventricular size and function with a more rapid recovery of abnormal endocardial segments and reversal of functional infarct expansion. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP PICARD, MH (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC NONINVAS LAB,CARDIAC UNIT,VINCENT BURNHAM 5,FRUIT ST,BOSTON,MA 02114, USA. OI Picard, Michael/0000-0002-9264-3243 NR 37 TC 16 Z9 16 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUL PY 1993 VL 126 IS 1 BP 1 EP 10 DI 10.1016/S0002-8703(07)80003-2 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LL210 UT WOS:A1993LL21000001 PM 8322649 ER PT J AU ALPER, JS NATOWICZ, MR AF ALPER, JS NATOWICZ, MR TI GENETIC DISCRIMINATION AND THE PUBLIC ENTITIES AND PUBLIC ACCOMMODATIONS TITLES OF THE AMERICANS-WITH-DISABILITIES-ACT SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID INFORMATION AB The introduction of newly developed medical genetic diagnostic tests has been accompanied by social problems involving privacy issues and genetic discrimination. Previous studies of genetic discrimination have focused on the areas of employment and insurance. In this paper, we provide six hypothetical illustrative cases of genetic discrimination involving access to public entities and to private entities considered to be public accommodations. We argue that many of these forms of genetic discrimination that arise in both the public and private sectors should be prohibited by Titles II and III, respectively, of the Americans with Disabilities Act of 1990. C1 EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV MED GENET,200 TRAPELO RD,WALTHAM,MA 02254. UNIV MASSACHUSETTS,DEPT CHEM,BOSTON,MA 02125. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 26 TC 10 Z9 10 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 1993 VL 53 IS 1 BP 26 EP 32 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA LJ385 UT WOS:A1993LJ38500005 PM 8317491 ER PT J AU FARRER, LA CUPPLES, LA WIATER, P CONNEALLY, PM GUSELLA, JF MYERS, RH AF FARRER, LA CUPPLES, LA WIATER, P CONNEALLY, PM GUSELLA, JF MYERS, RH TI THE NORMAL HUNTINGTON DISEASE (HD) ALLELE, OR A CLOSELY LINKED GENE, INFLUENCES AGE AT ONSET OF HD SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PRION PROTEIN; CHOREA; HETEROGENEITY; INHERITANCE; TRANSMISSION; CHROMOSOME-4; RELIABILITY; FAMILIES; HISTORY AB We evaluated the hypothesis that Huntington disease (HD) is influenced by the normal HD allele by comparing transmission patterns of genetically linked markers at the D4S10 locus in the normal parent against age at onset in the affected offspring. Analysis of information from 21 sibships in 14 kindreds showed a significant tendency for sibs who have similar onset ages to share the same D4S10 allele from the normal parent. Affected sibs who inherited different D4S10 alleles from the normal parent tended to have more variable ages at onset. These findings suggest that the expression of HD is modulated by the normal HD allele or by a closely linked locus. C1 BOSTON UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL & BIOSTAT,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BOSTON,MA 02114. INDIANA UNIV,SCH MED,DEPT MED GENET,INDIANAPOLIS,IN 46202. RP FARRER, LA (reprint author), BOSTON UNIV,SCH MED,DEPT NEUROL,80 E CONCORD ST,BOSTON,MA 02118, USA. OI Farrer, Lindsay/0000-0001-5533-4225 NR 38 TC 46 Z9 47 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 1993 VL 53 IS 1 BP 125 EP 130 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA LJ385 UT WOS:A1993LJ38500016 PM 8317477 ER PT J AU BARNHILL, RL LEVY, MA AF BARNHILL, RL LEVY, MA TI REGRESSING THIN CUTANEOUS MALIGNANT MELANOMAS (LESS-THAN-OR-EQUAL-TO-1.0 MM) ARE ASSOCIATED WITH ANGIOGENESIS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PROGNOSTIC-SIGNIFICANCE; TUMOR PROGRESSION; VASCULARITY; METASTASES; THICKNESS; SURVIVAL; LESIONS AB In previous studies, we have shown that angiogenesis is often first noted in cutaneous malignant melanomas (CMMs) under 1.0 mm in thickness. Because angiogenesis may signal a more aggressive tumor phenotype, it is important to establish the circumstances associated with onset of angiogenesis. In the present study, we have quantified tumor vascularity in a series of CMMs under 1.0 mm in thickness and either associated with or lacking histologic regression. Microvessels were identified with the lectin Ulex europaeus agglutinin I and tge vessels in five fields counted within an ocular grid (area 7.84 x 10(-2) mm) at 400 x magnification. CMMs (mean 0.48 mm) with regression had greater microvessel counts (27.2 +/- 5.1) compared with CMMs (mean 0.61 mm) without regression (mean 20.1 +/- 7.9) (P < 0.01). However, of particular interest, CMMs in the radial growth phase only and associated with regression (mean 0.40 mm) had strikingly greater vascularity (mean 28.7 +/- 6.9) versus radial growth phase CMMs (mean 0.44 mm) lacking regression (mean 16.4 +/- 6.6) (P = 0.0013). CMMs in tge vertical growth phase (mean 0.81 mm) without regression had slightly less vascularity (mean 24.4 +/- 7.3) compared with vertical growth phase CMMs with regression (mean microvessels 27.2 +/- 5.1) (P = 0.1878) but significantly greater microvessels versus radial growth phase CMMs without regression (P = 0.0213). These results suggest that the onset of angiogenesis in thin CMMs is related to at least two phenomena) inflammatory regression and 2) development of tge vertical growth phase. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP BARNHILL, RL (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV DERMATOPATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 33 TC 79 Z9 79 U1 1 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1993 VL 143 IS 1 BP 99 EP 104 PG 6 WC Pathology SC Pathology GA LM085 UT WOS:A1993LM08500012 PM 7686347 ER PT J AU WONG, DTW DONOFF, RB YANG, J SONG, BZ MATOSSIAN, K NAGURA, N ELOVIC, A MCBRIDE, J GALLAGHER, G TODD, R CHIANG, T CHOU, LSS YUNG, CM GALLI, SJ WELLER, PF AF WONG, DTW DONOFF, RB YANG, J SONG, BZ MATOSSIAN, K NAGURA, N ELOVIC, A MCBRIDE, J GALLAGHER, G TODD, R CHIANG, T CHOU, LSS YUNG, CM GALLI, SJ WELLER, PF TI SEQUENTIAL EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA AND FACTOR-BETA(1) BY EOSINOPHILS DURING CUTANEOUS WOUND-HEALING IN THE HAMSTER SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID FACTOR-BETA; GENE; RAT AB Transforming growth factor-alpha (TGF-alpha) and TGF-beta1, have been proposed as important regulators of processes critical to successful wound heating. Although various cells present in wounds represent potential sources of either TGF-alpha and/or TGF-beta, including macrophages, neutrophils, keratinocytes, fibroblasts, and endothelial cells, we recently identified eosinophils as an additional potential source of these cytokines. We therefore used in situ hybridization and immunohistochemistry to determine whether eosinophils represent significant sources of TGF-alpha and/or TGF-beta1 in skin wounds in the hamster. We found that these wounds developed a prominent infiltration of eosinophils, and that eosinophils were a cellular source of both TGF-alpha and TGF-beta1 mRNAs. TGF-alpha and TGF-beta1 proteins were detectable both within eosinophils and extracellularly. Moreover, there was a sequential pattern of TGF-alpha and TGF-beta1 expression by infiltrating eosinophils, with the onset of eosinophil-associated TGF-alpha expression preceding that of TGF-beta1. This sequential pattern of TGF expression suggests that eosinophils may help to regulate critical biological processes during wound healing. C1 MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02114. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. BETH ISRAEL HOSP,CHARLES A DANA RES INST,BOSTON,MA 02215. RP WONG, DTW (reprint author), HARVARD UNIV,SCH DENT MED,DEPT ORAL MED & ORAL PATHOL,188 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI-22674, AI-23990]; NIDCR NIH HHS [DE-08680] NR 29 TC 71 Z9 74 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1993 VL 143 IS 1 BP 130 EP 142 PG 13 WC Pathology SC Pathology GA LM085 UT WOS:A1993LM08500015 PM 8317544 ER PT J AU PRAT, AG BERTORELLO, AM AUSIELLO, DA CANTIELLO, HF AF PRAT, AG BERTORELLO, AM AUSIELLO, DA CANTIELLO, HF TI ACTIVATION OF EPITHELIAL NA+ CHANNELS BY PROTEIN KINASE-A REQUIRES ACTIN-FILAMENTS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SODIUM ION CHANNEL; ADENOSINE 3',5'-CYCLIC MONOPHOSPHATE-DEPENDENT PROTEIN KINASE; PROTEIN PHOSPHORYLATION ID TOAD URINARY-BLADDER; F-ACTIN; PHOSPHORYLATION; VASOPRESSIN; SUBUNIT; BINDING; WATER; CELLS; POLYMERIZATION; STABILIZATION AB We have recently demonstrated a novel role for ''short'' actin filaments, a distinct species of polymerized actin different from either monomeric (G-actin) or long actin filaments (F-actin), in the activation of epithelial Na+ channels. In the present study, the role of actin in the activation of apical Na+ channels by the adenosine 3',5'-cyclic monophosphate-dependent protein kinase A (PKA) was investigated by patch-clamp techniques in A6 epithelial cells. In excised inside-out patches, addition of deoxyribonuclease I, which prevents actin polymerization, inhibited Na+ channel activation mediated by PKA. Disruption of endogenous actin filament organization with cytochalasin D for at least 1 h prevented the PKA-mediated activation of Na+ channels but not activation following the addition of actin to the cytosolic side of the patch. To assess the role of PKA on actin filament organization, actin was used as a substrate for the specific phosphorylation by the PKA. Actin was phosphorylated by PKA with an equilibrium stoichiometry of 2:1 mol PO4-actin monomer. Actin was phosphorylated in its monomeric form, but only poorly once polymerized. Furthermore, phosphorylated actin reduced the rate of actin polymerization. Thus actin allowed to polymerize for at least 1 h in the presence of PKA and ATP to obtain phosphorylated actin filaments induced Na+ channel activity in excised inside-out patches, in contrast to actin polymerized either in the absence of PKA or in the presence of PKA plus a PKA inhibitor (nonphosphorylated actin filaments). This was also confirmed by using purified phosphorylated G-actin incubated in a polymerizing buffer for at least 1 h at 37-degrees-C. These data suggest that the form of actin required for Na+ channel activation (i.e., ''short'' actin filaments) may be favored by the phosphorylation of G-actin and may thus mediate or facilitate the activation of Na+ channels by PKA. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,149 13TH ST,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 41 TC 116 Z9 118 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1993 VL 265 IS 1 BP C224 EP C233 PN 1 PG 10 WC Physiology SC Physiology GA LP431 UT WOS:A1993LP43100030 PM 8393280 ER PT J AU PRAT, AG AUSIELLO, DA CANTIELLO, HF AF PRAT, AG AUSIELLO, DA CANTIELLO, HF TI VASOPRESSIN AND PROTEIN KINASE-A ACTIVATE G-PROTEIN-SENSITIVE EPITHELIAL NA+ CHANNELS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SODIUM ION CHANNELS ID SODIUM-CHANNEL; TOAD BLADDER; AMILORIDE; SUBUNIT; RECORDINGS; TRANSPORT; A6-CELLS; BINDING; CELLS; CAMP AB To determine the molecular steps involved in the vasopressin-induced renal Na+ reabsorption, the patch-clamp technique was utilized to study the role of this hormone in the regulation of apical Na+ channels in renal epithelial A6 cells. Addition of arginine vasopressin (AVP) induced and/or enhanced Na+ channel activity within 5 min of addition under cell-attached conditions. The AVP-induced channel activity was a reflection of both an increase in the average apparent channel number (0.2-1.7) and the percent open time (2-56%). Addition of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, the adenosine 3',5'-cyclic monophosphate (cAMP) analogues, 8-(4-chlorophenylthio)-cAMP and 8-bromo-cAMP, or forskolin elicited a comparable effect to that of AVP. The induced channels had similar properties to Na+ channels previously reported, including a channel conductance of 9 pS, Na+-to-K+ selectivity of 3-5:1, and high amiloride sensitivity. The cAMP-dependent protein kinase A (PKA) in the presence of ATP induced and/or enhanced Na+ channel activity in excised inside-out patches with a change in average apparent channel number and percent open probability similar to those observed with either AVP or cAMP analogues in intact cells. Addition of activated pertussis toxin (100 ng/ml) completely blocked the AVP- or PKA-induced Na+ channel activity in excised inside-out patches, whereas incubation of intact cells with the toxin completely prevented the effect of both activators. The data indicate that AVP mediates its effect through a cAMP-dependent pathway involving PKA activation whose target is the G protein pathway that regulates apical epithelial Na+ channel activity. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,149 13TH ST,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIDDK NIH HHS [DK-19406] NR 28 TC 60 Z9 61 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1993 VL 265 IS 1 BP C218 EP C223 PN 1 PG 6 WC Physiology SC Physiology GA LP431 UT WOS:A1993LP43100029 PM 8393279 ER PT J AU GARRICK, T GRIJALVA, CV TRAUNER, M AF GARRICK, T GRIJALVA, CV TRAUNER, M TI LATERAL HYPOTHALAMIC-LESIONS CAUSE GASTRIC INJURY BY STIMULATING GASTRIC CONTRACTILITY SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE GASTRIC MOTILITY; PEPTIC ULCERS; GASTRIC MUCOSAL DAMAGE ID EFFERENT CONNECTIONS; SOLITARY TRACT; BRAIN-STEM; RATS; PROJECTIONS; NUCLEUS; AREA; APHAGIA; SECRETION; PATHOLOGY AB Changes in gastric contractility following lateral hypothalamic (LH) lesions with and without bilateral cervical vagotomy were measured in urethan-anesthetized rats. LH lesions were induced with direct current passed through stereotaxically placed electrodes. Gastric contractility was recorded continuously for 4 h with acutely implanted strain gauge force transducers and analyzed by computer. LH lesions consistently stimulated gastric contractility and caused more gastric mucosal injury than control conditions. Vagotomy blocked both gastric mucosal injury and high-amplitude gastric contractions. In rats with LH lesions and exogenously infused intragastric hydrochloric acid, atropine methyl nitrate inhibited high-amplitude gastric contractions and gastric erosions. These findings indicate that LH lesions stimulate vagally mediated high-amplitude gastric contractions, which, in the presence of hydrochloric acid, cause gastric mucosal erosions. C1 W LOS ANGELES VET AFFAIRS MED CTR,CTR ULCER RES & EDUC,DEPT RES,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PSYCHOL,LOS ANGELES,CA 90024. RP GARRICK, T (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CTR ULCER RES & EDUC,DEPT PSYCHIAT,PSYCHIAT SERV W116A,LOS ANGELES,CA 90073, USA. NR 39 TC 7 Z9 9 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1993 VL 265 IS 1 BP G138 EP G142 PN 1 PG 5 WC Physiology SC Physiology GA LP431 UT WOS:A1993LP43100082 PM 8338162 ER PT J AU SAXE, GN VANDERKOLK, BA BERKOWITZ, R CHINMAN, G HALL, K LIEBERG, G SCHWARTZ, J AF SAXE, GN VANDERKOLK, BA BERKOWITZ, R CHINMAN, G HALL, K LIEBERG, G SCHWARTZ, J TI DISSOCIATIVE DISORDERS IN PSYCHIATRIC-INPATIENTS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MULTIPLE PERSONALITY-DISORDER; BORDERLINE; SCHIZOPHRENIA; INTERVIEW; SYMPTOMS; TRAUMA; ABUSE AB Objective: This study attempted to determine 1) the prevalence of dissociative disorders in psychiatric inpatients, 2) the degree of reported childhood trauma in patients with dissociative disorders, and 3) the degree to which dissociative experiences are recognized in psychiatric patients. Method: A total of 110 patients consecutively admitted to a state psychiatric hospital were given the Dissociative Experiences Scale. Patients who scored above 25 were matched for age and gender with a group of patients who scored below 5 on the scale. All patients in the two groups were then interviewed in a blind manner, and the Dissociative Disorders Interview Schedule, the Traumatic Antecedent Questionnaire, and the posttraumatic stress disorder (PTSD) module of the Structured Clinical Interview for DSM-III-R, Nonpatient Version, were administered. Chart reviews were also conducted on all patients. Results: Fifteen percent of the psychiatric patients scored above 25 on the Dissociative Experiences Scale; 100% of these patients met DSM-III criteria for a dissociative disorder. These patients bad significantly higher rates of major depression, PTSD, substance abuse, and borderline personality than did the comparison patients, and they also reported significantly higher rates of childhood trauma. Chart review data revealed that dissociative symptoms were largely unrecognized. Conclusions: A high proportion of psychiatric inpatients have significant dissociative pathology, and these symptoms are underrecognized by clinicians. The proper diagnosis of these patients has important implications for their clinical course. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS MENTAL HLTH CTR,DEPT PSYCHIAT,TRAUMA CLIN,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. OI Saxe, Glenn/0000-0002-4756-1169 NR 40 TC 183 Z9 186 U1 4 U2 10 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 JUL PY 1993 VL 150 IS 7 BP 1037 EP 1042 PG 6 WC Psychiatry SC Psychiatry GA LL398 UT WOS:A1993LL39800008 PM 8317573 ER PT J AU BARSKY, AJ COEYTAUX, RR SARNIE, MK CLEARY, PD AF BARSKY, AJ COEYTAUX, RR SARNIE, MK CLEARY, PD TI HYPOCHONDRIACAL PATIENTS BELIEFS ABOUT GOOD HEALTH SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SOMATOSENSORY AMPLIFICATION; ILLNESS; BEHAVIOR AB Objective: The authors hypothesized that hypochondriacal patients mistakenly believe good health to be a symptom-free state and that they consider more symptoms to be indicative of disease than do nonhypochondriacal patients. Method: The Health Norms Sorting Task was developed to assess the standard used to decide whether one is sick or healthy; the respondent must classify 24 common and ambiguous symptoms as 'healthy'' or ''not healthy.'' This instrument demonstrated good test-retest reliability and intrascale consistency. It was then administered to 60 patients with DSM-III-R hypochondriasis and 60 nonhypochondriacal patients randomly selected from the same general medicine clinic. Results: Hypochondriacal patients considered significantly more symptoms to be indicative of disease than did the comparison group. Health Norms Sorting Test scores were correlated with hypochondriacal symptoms, somatization, and self-reported bodily amplification (sensitivity to bodily sensation). Test scores were not related to aggregate medical morbidity, medical care utilization, or sociodemographic characteristics. Conclusions: These data are compatible with the hypothesis that patients with DSM-III-R hypochondriasis believe good health to be relatively symptom free and consider more symptoms indicative of sickness. This may contribute to some of the clinical features of hypochondriasis, including the numerous somatic symptoms, bodily preoccupation, resistance to reassurance, and pursuit of medical care. C1 HARVARD UNIV, SCH MED, DEPT PSYCHIAT, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, PRIMARY CARE PROGRAM, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT HLTH CARE POLICY, BOSTON, MA 02115 USA. RP BARSKY, AJ (reprint author), MASSACHUSETTS GEN HOSP, PSYCHIAT SERV, WARREN 631, FRUIT ST, BOSTON, MA 02114 USA. FU NIMH NIH HHS [NIMH MH40487] NR 22 TC 82 Z9 83 U1 2 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 1993 VL 150 IS 7 BP 1085 EP 1089 PG 5 WC Psychiatry SC Psychiatry GA LL398 UT WOS:A1993LL39800017 PM 8317581 ER PT J AU ZIMMER, WE CHEW, FS AF ZIMMER, WE CHEW, FS TI PULMONARY ALVEOLAR PROTEINOSIS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 3 TC 5 Z9 5 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1993 VL 161 IS 1 BP 26 EP 26 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LW015 UT WOS:A1993LW01500004 PM 8517314 ER PT J AU FRANK, H GLOBITS, S GLOGAR, D NEUHOLD, A KNEUSSL, M MLCZOCH, J AF FRANK, H GLOBITS, S GLOGAR, D NEUHOLD, A KNEUSSL, M MLCZOCH, J TI DETECTION AND QUANTIFICATION OF PULMONARY-ARTERY HYPERTENSION WITH MR-IMAGING - RESULTS IN 23 PATIENTS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID MAGNETIC-RESONANCE; ECHOCARDIOGRAPHY; DISEASE; CT AB OBJECTIVE. A study was performed to determine the value of MR imaging in detecting pulmonary artery hypertension and in determining pulmonary artery pressure semiquantitatively. SUBJECTS AND METHODS. MR studies were performed in 23 patients with pulmonary artery hypertension to measure right ventricular function (right ventricular ejection fraction, end-diastolic and end-systolic volumes, stroke volume), right ventricular wall thickness, and the diameters of the great vessels. The findings were compared with similar MR measurements made in eight control subjects. The cause of the pulmonary hypertension was primary pulmonary hypertension (eight patients), combined mitral valve disease (five patients), dilative cardiomyopathy (four patients), chronic pulmonary embolism (four patients), atrial septal defect (one patient), and pulmonary fibrosis (one patient). MR studies were done on a 0.5-T magnet using a double-angulation projection (equivalent to a four-chamber view) with a multislice-multiphase spin-echo technique and a blood flow-sensitive fast gradient-echo sequence. Pulmonary artery pressures were verified by catheterization of the pulmonary artery. RESULTS. In patients with pulmonary artery hypertension, MR imaging showed right ventricular enlargement with hypertrophy, right atrial enlargement, and abnormal septal motion. Fast gradient-echo images showed tricuspid regurgitation in all cases. In cases in which the mean pressures in the pulmonary artery were greater than 70 mm Hg, systolic slow-flow phenomena were detected. Linear correlations were seen between the mean pressure in the pulmonary artery and the end-diastolic thickness of the right ventricular wall (r = .83, p less-than-or-equal-to .0001), the diameter of the inferior vena cava (r .73, p less-than-or-equal-to .0001), and the diameter of the main pulmonary artery (r =.48, p less-than-or-equal-to .02). CONCLUSION. Our results show that MR imaging is a useful noninvasive technique for the detection of pulmonary artery hypertension and for the semiquantitative assessment of pulmonary artery pressure. C1 RUDOLFINERHAUS,MR CTR,A-1190 VIENNA,AUSTRIA. RP FRANK, H (reprint author), MASSACHUSETTS GEN HOSP,NMR CTR,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 21 TC 46 Z9 50 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1993 VL 161 IS 1 BP 27 EP 31 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LW015 UT WOS:A1993LW01500005 PM 8517315 ER PT J AU YOUNG, RH SCULLY, RE AF YOUNG, RH SCULLY, RE TI MINIMAL-DEVIATION ENDOMETRIOID ADENOCARCINOMA OF THE UTERINE CERVIX - A REPORT OF 5 CASES OF A DISTINCTIVE NEOPLASM THAT MAY BE MISINTERPRETED AS BENIGN SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE CERVIX; ADENOCARCINOMA; ENDOMETRIOID; MINIMAL DEVIATION ID ADENOMA MALIGNUM; METAPLASIA AB We describe five cervical adenocarcinomas with unusual, deceptively benign histological features that occurred in women 34 to 42 years of age and caused problems in interpretation. The tumors were incidental findings in hysterectomy or cone-biopsy specimens in four patients; the fifth patient was investigated because abnormal glandular cells were found on a Papanicolaou smear. One patient had been exposed in utero to diethylstilbestrol. The cervix is known to have been abnormal on gross evaluation in only one case. Microscopic examination disclosed a deceptively benign-appearing proliferation of glands and cysts for the most part unassociated with a stromal reaction. Cilia were present in four neoplasms and apical snouts in three. Features that indicated the neoplastic nature of the glandular proliferation in these cases, to varying extents in individual cases, included the number of glands and their distribution, the shapes of the glands, their presence deep in the cervical wall, the focal presence of a stromal reaction, and moderate cytologic atypicality with occasional mitotic figures. None of the tumors is known to have recurred or metastasized. In our opinion, these distinctive neoplasms represent minimal-deviation endometrioid adenocarcinomas of the cervix. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. NR 15 TC 35 Z9 37 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 1993 VL 17 IS 7 BP 660 EP 665 DI 10.1097/00000478-199307000-00002 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA LJ011 UT WOS:A1993LJ01100002 PM 8317607 ER PT J AU SPENCE, CR THOMPSON, BT JANSSENS, SP STEIGMAN, DM HALES, CA AF SPENCE, CR THOMPSON, BT JANSSENS, SP STEIGMAN, DM HALES, CA TI EFFECT OF AEROSOL HEPARIN ON THE DEVELOPMENT OF HYPOXIC PULMONARY-HYPERTENSION IN THE GUINEA-PIG SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Note ID VASCULAR SMOOTH-MUSCLE; RATS; PROLIFERATION; POLYCYTHEMIA; GROWTH; CELLS; SHEEP AB Chronic hypoxia produces pulmonary artery hypertension through vasoconstriction and structural remodeling of the pulmonary vascular bed. The present study was designed to test the effect of heparin administered via aerosol on the development of hypoxic pulmonary hypertension. Anesthetized, intubated, and mechanically ventilated guinea pigs received an aerosol of either 2 ml normal saline (hypoxic control, HC) or 4,500 units of heparin diluted in 2 ml normal saline via an ultrasonic nebulizer (hypoxic heparin, HH). After 24 h of recovery, the animals were placed in a hypoxic chamber (10% O2) for 10 days. Animals kept in room air served as normoxic controls (NC). Hypoxia increased mean pulmonary artery pressure from 11 +/- 1 (SEM) mm Hg in NC to 24 +/- 1 mm Hg in HC (p < 0.05). Pulmonary artery pressure was significantly lower in HH-treated animals (20 +/- 1 mm Hg, p < 0.05 versus HC) as was the total pulmonary vascular resistance (0.15 +/- 0.01 in HH versus 0.20 +/- 0.01 mm Hg/ml/min in HC, p < 0.05). There was no difference in cardiac output (146 +/- 12 in HH versus 126 +/- 7 ml/min in HC), hematocrit (57 +/- 2 in HH versus 56 +/- 2% in HC), partial thromboplastin time (30 +/- 2 in HH versus 32 +/- 3 s in HC), prothrombin time (46 +/- 1 in HH versus 48 +/- 4 s in HC) or room air arterial blood gas values after 10 days of hypoxia. The proportion of thick-walled peripheral vessels (30 +/- 2 in HH and 35 +/- 1 in HC versus 14 +/- 2% in NC, p < 0.05) and the percent medial thickness of pulmonary arteries adjacent to alveolar ducts (7.2 +/- 0.2 in HH and 71 +/- 0.5 in HC versus 4.9 +/- 0.4% in NC, p < 0.05) and to terminal bronchioles (27.0 +/- 2.1 in HH and 26.6 +/- 1.5 in HC versus 16.4 +/- 1.9% in NC, p < 0.05) increased to a similar degree in both hypoxic groups. We conclude that a single dose of heparin when administered by aerosol prior to 10 days of hypoxia reduces the development of pulmonary hypertension. C1 MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU FIC NIH HHS [IF05TW04379-1]; NHLBI NIH HHS [R01 HL039150, HL-07354, HL-39150] NR 30 TC 13 Z9 13 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD JUL PY 1993 VL 148 IS 1 BP 241 EP 244 PG 4 WC Respiratory System SC Respiratory System GA LV447 UT WOS:A1993LV44700042 PM 8317807 ER PT J AU SHORTEN, GD GOUDSOUZIAN, NG ALI, HH AF SHORTEN, GD GOUDSOUZIAN, NG ALI, HH TI HISTAMINE-RELEASE FOLLOWING ATRACURIUM IN THE ELDERLY SO ANAESTHESIA LA English DT Article DE NEUROMUSCULAR RELAXANTS; ATRACURIUM; HISTAMINE; AGE FACTORS; ELDERLY ID HUMANS C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP GOUDSOUZIAN, NG (reprint author), HARVARD UNIV,SCH MED,FRUIT ST,BOSTON,MA 02114, USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0003-2409 J9 ANAESTHESIA JI Anaesthesia PD JUL PY 1993 VL 48 IS 7 BP 568 EP 571 DI 10.1111/j.1365-2044.1993.tb07117.x PG 4 WC Anesthesiology SC Anesthesiology GA LK877 UT WOS:A1993LK87700003 PM 7688494 ER PT J AU GOUDSOUZIAN, NG DHOLLANDER, AA VIBYMOGENSEN, J AF GOUDSOUZIAN, NG DHOLLANDER, AA VIBYMOGENSEN, J TI PROLONGED NEUROMUSCULAR BLOCK FROM MIVACURIUM IN 2 PATIENTS WITH CHOLINESTERASE DEFICIENCY SO ANESTHESIA AND ANALGESIA LA English DT Note ID PLASMA CHOLINESTERASE; NEOSTIGMINE; ANTAGONISM; ATRACURIUM; CHILDREN C1 FREE UNIV BRUSSELS,HOP ERASME,ANESTHESIA SERV,B-1050 BRUSSELS,BELGIUM. UNIV COPENHAGEN,RIGSHOSP,ANESTHESIA SERV,DK-2100 COPENHAGEN,DENMARK. RP GOUDSOUZIAN, NG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ANESTHESIA SERV,BOSTON,MA 02114, USA. NR 16 TC 56 Z9 57 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUL PY 1993 VL 77 IS 1 BP 183 EP 185 PG 3 WC Anesthesiology SC Anesthesiology GA LL119 UT WOS:A1993LL11900035 PM 8317728 ER PT J AU DEARMENDI, AJ FAHEY, M RYAN, JF AF DEARMENDI, AJ FAHEY, M RYAN, JF TI MORPHINE-INDUCED MYOCLONIC MOVEMENTS IN A PEDIATRIC PAIN PATIENT SO ANESTHESIA AND ANALGESIA LA English DT Note ID INFUSION; SPASMS RP DEARMENDI, AJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,FRUIT ST,BOSTON,MA 02114, USA. NR 10 TC 17 Z9 17 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUL PY 1993 VL 77 IS 1 BP 191 EP 192 PG 2 WC Anesthesiology SC Anesthesiology GA LL119 UT WOS:A1993LL11900038 PM 8317732 ER PT J AU ALIFIMOFF, JK BUGGE, B FORMAN, SA MILLER, KW AF ALIFIMOFF, JK BUGGE, B FORMAN, SA MILLER, KW TI STEREOSELECTIVITY OF CHANNEL INHIBITION BY SECONDARY ALKANOL ENANTIOMERS AT NICOTINIC ACETYLCHOLINE-RECEPTORS SO ANESTHESIOLOGY LA English DT Article DE RECEPTORS, ACETYLCHOLINE; STEREOSELECTIVITY, SECONDARY ALCOHOLS ID ION CHANNEL; POSTSYNAPTIC MEMBRANES; CHOLINERGIC RECEPTORS; ANESTHETIC POTENCIES; TORPEDO; ETHANOL; ISOMERS; COMPLEX; SITES AB Background: At the nicotinic acetylcholine receptor, long chain alkanols reduce, whereas short chain alkanols augment endplate currents. Using the enantiomers of five members of a homologous series of secondary alkanols (2-butanol through 2-octanol), we tested the hypothesis that these actions occur at a single hydrophobic site in the lumen of the channel. Small alkanols would bind to this site without blocking the channel, stabilizing the open state and enhancing the apparent affinity of the agonist for channel opening. Long chain alkanols would bind the same site and simply inhibit without affecting the agonist's apparent affinity. Methods: Agonist-stimulated Rb-86+ efflux from acetylcholine receptor-rich vesicles from Torpedo nobiliana was studied by adding agonist and allowing efflux to proceed for 10 s before termination by filtration. Results: All of the 2-alkanols inhibited Rb-86+ efflux elicited by a maximally stimulating concentration of agonist. Inhibitory potency increased logarithmically with the number of carbon atoms in the hydrocarbon chain of the alkanol. The inhibitory potency of the enantiomers of 2-butanol differed twofold, but the other enantiomers exhibited no stereoselectivity. The enantiomers of 2-octanol caused a concentration-dependent depression of carbamylcholine-stimulated Rb-86+ efflux without significantly altering the agonist's apparent dissociation constant. In contrast, the enantiomers of 2-butanol caused: (1) a nonstereoselective decrease in carbachol's apparent dissociation constant and (2) the expected stereoselective decrease in maximal carbamylcholine-stimulated Rb-86+ efflux. Conclusions: The alkanol site that modulates the apparent agonist affinity for channel opening is distinct from the site that results in inhibition of cation flux through the channel. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NIGMS NIH HHS [GM15904] NR 26 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 1993 VL 79 IS 1 BP 122 EP 128 DI 10.1097/00000542-199307000-00018 PG 7 WC Anesthesiology SC Anesthesiology GA LM825 UT WOS:A1993LM82500019 PM 7688196 ER PT J AU CURRY, BH AF CURRY, BH TI TRIBUTE SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material DE PHYSICIAN-PATIENT RELATIONS; KNOWLEDGE, ATTITUDES, PRACTICE; GRIEF AB A physician has an encounter with a patient who has recently suffered a tremendous personal loss. The physician treats the patient and in so doing explores the rationale for and consequences of empathetic participation in the grieving process. C1 DEACONESS MED CTR,BILLINGS,MT 59107. NR 0 TC 1 Z9 1 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 JUL 1 PY 1993 VL 119 IS 1 BP 86 EP 86 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LJ266 UT WOS:A1993LJ26600014 PM 8498769 ER PT J AU GRILLO, HC MARK, EJ MATHISEN, DJ WAIN, JC AF GRILLO, HC MARK, EJ MATHISEN, DJ WAIN, JC TI IDIOPATHIC LARYNGOTRACHEAL STENOSIS AND ITS MANAGEMENT SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 29TH ANNUAL MEETING OF THE SOC OF THORACIC SURGEONS CY JAN 25-27, 1993 CL SAN ANTONIO, TX SP SOC THORAC SURGEONS ID SUBGLOTTIC STENOSIS; TRACHEAL STENOSIS; RECONSTRUCTION; RESECTION; LARYNGEAL; RETROPERITONEAL; FIBROSIS AB We describe idiopathic laryngotracheal and upper tracheal stenosis in 49 patients with no other cause for their stenosis. Traumatic, iatrogenic, infectious, and specific inflammatory processes were excluded. Histopathologically dense fibrosis of keloidal type thickened the lamina propria and choked the ducts of mucous glands but did not destroy cartilage. Thirty-five patients were treated by single-stage resection and reconstruction: 29 by laryngotracheal resection with laryngotracheoplasty and 6 by cricotracheal segmental resection. Thirty-two patients achieved good or excellent results in respiration and voice, 2 needed annual dilations, and 1 required permanent tracheostomy. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP GRILLO, HC (reprint author), MASSACHUSETTS GEN HOSP,GEN THORAC SURG UNIT,BOSTON,MA 02114, USA. NR 21 TC 65 Z9 66 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 1993 VL 56 IS 1 BP 80 EP 87 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA LM764 UT WOS:A1993LM76400013 PM 8328880 ER PT J AU ERON, JJ CHOW, YK CALIENDO, AM VIDELER, J DEVORE, KM COOLEY, TP LIEBMAN, HA KAPLAN, JC HIRSCH, MS DAQUILA, RT AF ERON, JJ CHOW, YK CALIENDO, AM VIDELER, J DEVORE, KM COOLEY, TP LIEBMAN, HA KAPLAN, JC HIRSCH, MS DAQUILA, RT TI POL MUTATIONS CONFERRING ZIDOVUDINE AND DIDANOSINE RESISTANCE WITH DIFFERENT EFFECTS IN-VITRO YIELD MULTIPLY RESISTANT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATES IN-VIVO SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; CONTROLLED TRIAL; AZT; INFECTION; THERAPY; AIDS; SUSCEPTIBILITY; SENSITIVITY; CELLS AB Specific mutations in the human immunodeficiency virus type 1 (HIV-1) pol gene that cause zidovudine (3'-azido-2',3'-dideoxythymidine; AZT) and didanosine (2',3'-dideoxyinosine; ddI) resistance were studied. The 50% inhibitory concentrations (IC50s) of nucleosides for cloned viruses containing these mutations were compared with the IC50s of the corresponding triphosphate analogs for mutant recombinant-expressed reverse transcriptases (RTs). Changes in ddATP inhibition of RNA-dependent DNA polymerase activity fully accounted for the ddl resistance of the virus caused by a Leu-74 --> Val substitution in RT, including an augmentation by the AZT-selected substitutions Thr-215 --> Tyr and Lys-219 --> Gln in RT. In contrast, the AZT-selected substitutions studied did not cause as great a change in the IC50 of AZT-triphosphate (AZT-TP) for polymerase as they did in the IC50 of AZT for mutant virus. In addition, the mutation at codon 74 suppressed AZT resistance in the virus caused by the mutations at codons 215 and 219 but did not suppress the AZT-TP resistance of enzyme containing these same mutations in RT. The mutation at codon 74 was found in clinical isolates whether or not the patient had received AZT prior to starting ddl therapy. AZT resistance coexisted with ddl resistance following acquisition of Leu-74 - Val in three clinical isolates, indicating that the suppressive effect of Val-74 on the AZT resistance of the virus does not occur in all genetic contexts. When this suppression of AZT resistance was seen in the virus, Val-74 did not appear to cause mutually exclusive changes in AZT-TP and ddATP binding to RT in vitro. The results of the in vitro experiments and characterization of clinical isolates suggest that there are differences in the functional effects of these AZT and ddl resistance mutations. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. BOSTON CITY HOSP,HEMATOL ONCOL SECT,BOSTON,MA 02118. BOSTON UNIV,SCH MED,BOSTON,MA 02215. FU NCI NIH HHS [CA 12464]; NIAID NIH HHS [AI 29193] NR 40 TC 49 Z9 50 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 JUL PY 1993 VL 37 IS 7 BP 1480 EP 1487 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA LL214 UT WOS:A1993LL21400018 PM 7689822 ER PT J AU FISHMAN, JA QUEENER, SF ROTH, RS BARTLETT, MS AF FISHMAN, JA QUEENER, SF ROTH, RS BARTLETT, MS TI ACTIVITY OF TOPOISOMERASE INHIBITORS AGAINST PNEUMOCYSTIS-CARINII IN-VITRO AND IN AN INOCULATED MOUSE MODEL SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID ACQUIRED IMMUNODEFICIENCY SYNDROME; RAT MODEL; PENTAMIDINE; PNEUMONIA; PROPHYLAXIS; HUMANS; PEFLOXACIN; INFECTION; CULTURE AB Five topoisomerase II inhibitors (amsacrine [m-AMSA], two epipodophyllotoxins, and two quinolones) and the alkaloid camptothecin (a topoisomerase I inhibitor) were evaluated to assess their activities against Pneumocystis carinii. In vitro, both etoposide (VP-16) and teniposide (VM-26) at 1 mug/ml suppressed P. carinii growth. Amsacrine was toxic to P. carinii and to the feeder cells in vitro. Camptothecin suppressed the growth of P. carinii in vitro only at 100 mug/ml. Studies in immunosuppressed mice demonstrated the efficacy of teniposide against P. carinii pneumonia, but successful administration of teniposide was schedule dependent with significant toxicity at therapeutic dosages. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. INDIANA UNIV,SCH MED,DEPT PHARMACOL & TOXICOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT PATHOL,INDIANAPOLIS,IN 46202. RP FISHMAN, JA (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [K08HL01906, P01HL43510]; NIAID NIH HHS [N01-AI-72647] NR 25 TC 17 Z9 17 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 JUL PY 1993 VL 37 IS 7 BP 1543 EP 1546 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA LL214 UT WOS:A1993LL21400030 PM 8395791 ER PT J AU FILLEY, CM CULLUM, CM AF FILLEY, CM CULLUM, CM TI EARLY DETECTION OF FRONTOTEMPORAL DEGENERATION BY CLINICAL-EVALUATION SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article ID PICKS DISEASE AB Although Alzheimer's Disease (AD) is the most common degenerative dementia, other neuropathological processes are well known to cause dementia syndromes. Fronto-temporal degeneration (FTD) is one such entity, and often produces a clinical presentation distinct from that of AD. Some FTD cases are shown at autopsy to be classic Pick's Disease, but others defy precise classification at this point because they lack characteristic Pick bodies. We describe a case of putative FTD in a 54-year-old man with personality change and complete Kluver-Bucy syndrome. Neuropsychological evaluation disclosed evidence of extensive frontal system dysfunction, with lesser problems in memory, language, and visuospatial skills. Magnetic resonance imaging studies after 17 months of the illness were largely nonspecific, but a follow-up scan 16 months later revealed bifrontal and bitemporal atrophy with ventricular enlargement. Neuromorphometric analysis suggested an increase in cortical atrophy and ventricular dilation over time. This case emphasizes the value of careful clinical evaluation in unusual non-AD degenerative demential and suggests that neuroimaging studies may be less sensitive in the early diagnosis of such cases. C1 DENVER VET AFFAIRS MED CTR,DENVER,CO. UNIV COLORADO,SCH MED,DEPT PSYCHIAT,DENVER,CO 80262. RP FILLEY, CM (reprint author), UNIV COLORADO,SCH MED,DEPT NEUROL,B-183,4200 E 9TH AVE,DENVER,CO 80262, USA. NR 20 TC 6 Z9 6 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD JUL-AUG PY 1993 VL 8 IS 4 BP 359 EP 367 DI 10.1016/0887-6177(93)90025-V PG 9 WC Psychology, Clinical; Psychology SC Psychology GA LM108 UT WOS:A1993LM10800005 PM 14589665 ER PT J AU BAILEY, EM MCDERMOTT, TJ BLOCH, KJ AF BAILEY, EM MCDERMOTT, TJ BLOCH, KJ TI THE URINARY LIGHT-CHAIN LADDER PATTERN - A PRODUCT OF IMPROVED METHODOLOGY THAT MAY COMPLICATE THE RECOGNITION OF BENCE-JONES PROTEINURIA SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ELECTROPHORESIS; IMMUNOFIXATION; JONES,BENCE AB Objective.-To describe the recently reported urinary light-chain ''ladder'' pattern and to indicate that this phenomenon, which may give rise to confusion with Bence Jones protein (BJP), may be observed during routine examination of 50-fold concentrated urine samples tested by high-resolution agarose gel electrophoresis and immunofixation. Methods.-Urine samples that were usually submitted for examination for the presence of BJP were concentrated 50-fold. Concentrated urine samples were subjected to immunoelectrophoresis and agarose gel electrophoresis. Samples that failed to show a BJP on immunoelectrophoresis but which did show a faint banding pattern in the stained agarose gel were subjected to immunofixation. Results.-Samples of urine from 23 patients failed to show a distinct BJP. Nevertheless, these samples did show a kappa, with or without a lambda, light-chain banding pattern. The urine samples came from patients with serum M components associated with neoplasms of either plasma cells (n=2) or lymphocytes (n=2) or with M components of undetermined significance (n=6). The remainder came from patients with infectious (n=8), inflammatory (n=4), or neoplastic (n=1) processes. Some of these patients had no apparent renal disease, while others had variably altered renal function. Conclusions.-The urinary light-chain ladder pattern was found by routine examination of 50-fold concentrated urine samples subjected to agarose gel electrophoresis and immunofixation. The pattern probably reflects the limited heterogeneity of normal human light chains. Detection in the urine samples of some patients may reflect increased synthesis, failure of resorption/degradation in the kidney, or the interference in proximal tubular function by substances producing transient tubular proteinuria. The presence of the light-chain ladder pattern in urine may prevent the detection of small amounts of BJP sharing the electrophoretic mobility of one of the normal light-chain bands. C1 GEN MED SERV,ALLERGY UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. GEN MED SERV,CLIN IMMUNOL UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP BAILEY, EM (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,WARREN 2,BOSTON,MA 02114, USA. NR 15 TC 7 Z9 7 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JUL PY 1993 VL 117 IS 7 BP 707 EP 710 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA LL472 UT WOS:A1993LL47200010 PM 8323434 ER PT J AU POPAT, RA KREBS, DE MANSFIELD, J RUSSELL, D CLANCY, E GILLBODY, KM HOGAN, N AF POPAT, RA KREBS, DE MANSFIELD, J RUSSELL, D CLANCY, E GILLBODY, KM HOGAN, N TI QUANTITATIVE ASSESSMENT OF 4 MEN USING ABOVE-ELBOW PROSTHETIC CONTROL SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE ASSESSMENT; PROSTHETIC PERFORMANCE; UPPER-EXTREMITY BIOMECHANICS ID FUNCTIONAL ASSESSMENT; CONTROL-SYSTEMS C1 MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,10 MERRIMAC ST,BOSTON,MA 02114. MIT,BOSTON,MA. FU NIAMS NIH HHS [R01-AR40029] NR 24 TC 8 Z9 8 U1 0 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 1993 VL 74 IS 7 BP 720 EP 729 DI 10.1016/0003-9993(93)90033-7 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA LM079 UT WOS:A1993LM07900010 PM 8328894 ER PT J AU TRUBETSKOY, VS NARULA, J KHAW, BA TORCHILIN, VP AF TRUBETSKOY, VS NARULA, J KHAW, BA TORCHILIN, VP TI CHEMICALLY OPTIMIZED ANTIMYOSIN FAB CONJUGATES WITH CHELATING POLYMERS - IMPORTANCE OF THE NATURE OF THE PROTEIN-POLYMER SINGLE-SITE COVALENT BOND FOR BIODISTRIBUTION AND INFARCTION LOCALIZATION SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODY; IMMUNOREACTIVITY; IMMUNOTOXINS AB Murine antimyosin Fab fragment was conjugated with In-111-labeled N-terminal-modified DTPA-polylysine using three bifunctional reagents: N-hydroxysuccinimide esters of 3-(2-pyridyldithio)propionic acid (SPDP conjugate), 4-(maleimidomethyl)cyclohexanecarboxylic acid (SMCC conjugate) and bromoacetic acid (BrAc conjugate) for potential localization of experimental myocardial infarction. Using various antibody preparations and a rabbit acute myocardial infarction model the following parameters were observed: (1) an in vitro antigen binding activity of SPDP conjugate = SMCC conjugate > BrAc conjugate, (2) a blood clearance rate of SPDP conjugate > BrAc conjugate > SMCC conjugate, (3) a liver and splenic accumulation of SPDP conjugate > BrAc conjugate > SMCC conjugate, and (4) the infarcted tissue activity showed an accumulation of SMCC conjugate > SPDP conjugate > BrAc conjugate This study exemplifies the importance of rational chemical design of antimyosin Fab-chelating polymer conjugate for improved target tissue localization in vivo. C1 NORTHEASTERN UNIV,BOUVE COLL PHARM & HLTH SCI,CTR DRUG TARGETING & ANALYSIS,BOSTON,MA 02115. RP TRUBETSKOY, VS (reprint author), MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NCI NIH HHS [NCI CA 50505] NR 15 TC 22 Z9 22 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUL-AUG PY 1993 VL 4 IS 4 BP 251 EP 255 DI 10.1021/bc00022a001 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA LV457 UT WOS:A1993LV45700001 PM 8218480 ER PT J AU YEHUDA, R BOISONEAU, D MASON, JW GILLER, EL AF YEHUDA, R BOISONEAU, D MASON, JW GILLER, EL TI GLUCOCORTICOID RECEPTOR NUMBER AND CORTISOL EXCRETION IN MOOD, ANXIETY, AND PSYCHOTIC DISORDERS SO BIOLOGICAL PSYCHIATRY LA English DT Article DE GLUCOCORTICOID RECEPTORS; LYMPHOCYTES; CORTISOL; DEPRESSION; BIPOLAR MANIA; PANIC DISORDER; POSTTRAUMATIC STRESS DISORDER; SCHIZOPHRENIA ID DEXAMETHASONE SUPPRESSION TEST; POSTTRAUMATIC-STRESS-DISORDER; ADRENAL-STEROID RECEPTORS; PANIC DISORDER; DEPRESSION; BINDING; TISSUES; SYSTEM AB In the present study, we measured cytosolic lymphocyte glucocorticoid receptor and 24-hour urinary cortisol excretion in patients with major depressive disorder, bipolar mania, posttraumatic stress disorder, panic disorder, and schizophrenia. Patients with major depression had the smallest, and posttraumatic stress disordered patients the largest, mean number of glucocorticoid receptors per cell compared to patients in the other groups. Bipolar manic and panic patients did not differ from each other in regard to the number of lymphocyte glucocorticoid receptors. Bipolar manic and panic patients did have significantly more glucocorticoid receptors/cell than schizophrenic patients. The mean 24-hour urinary cortisol excretion was significantly higher in patients with major depression and bipolar mania than in those in the other diagnostic groups. Lymphocyte glucocorticoid receptor number and cortisol excretion tended to be inversely related, when the entire sample was considered as a whole, but this effect did not reach statistical significance. It is concluded that lymphocyte glucocorticoid receptors may be modulated by multiple influences, not just ambient cortisol levels. These preliminary data suggest that the assessment of lymphocyte glucocorticoid receptor number in tandem with cortisol levels may provide a more meaningful estimate of hypothalamic-pituitary-adrenal axis activity than is achieved using cortisol alone. C1 W HAVEN VET ADM,PSYCHIAT SERV,W HAVEN,CT. UNIV CONNECTICUT,CTR HLTH,DEPT PSYCHIAT,FARMINGTON,CT 06032. YALE UNIV,SCH MED,DEPT PSYCHIAT,NEW HAVEN,CT 06510. RP YEHUDA, R (reprint author), MT SINAI SCH MED,BRONX VET AFFAIRS MED CTR,DEPT PSYCHIAT,PSYCHIATRY 116-A,130 W KINGSBRIDGE RD,BRONX,NY 10468, USA. FU NIMH NIH HHS [MH 49536-01, MH 49555-01, MH41125-01A2] NR 36 TC 170 Z9 173 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 1993 VL 34 IS 1-2 BP 18 EP 25 DI 10.1016/0006-3223(93)90252-9 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA LQ802 UT WOS:A1993LQ80200005 PM 8373936 ER PT J AU TAKETO, T SAEED, J MANGANARO, T TAKAHASHI, M DONAHOE, PK AF TAKETO, T SAEED, J MANGANARO, T TAKAHASHI, M DONAHOE, PK TI MULLERIAN-INHIBITING SUBSTANCE PRODUCTION ASSOCIATED WITH LOSS OF OOCYTES AND TESTICULAR-DIFFERENTIATION IN THE TRANSPLANTED MOUSE XX GONADAL PRIMORDIUM SO BIOLOGY OF REPRODUCTION LA English DT Article ID OVARIES FOLLOWING TRANSPLANTATION; ROUGH ENDOPLASMIC-RETICULUM; SEX-DETERMINING REGION; ADULT MALE-MICE; DETERMINING GENE; SERTOLI CELLS; MONOCLONAL-ANTIBODY; Y-CHROMOSOME; FEMALE MICE; FETAL AB The mouse XX gonadal primordium develops seminiferous-like tubules after transplantation into the renal subcapsular site of the adult male or female mouse. We examined the ontogeny of Sertoli cell differentiation in XX gonadal grafts by immunocytochemical staining and organ culture bioassay for Mullerian Inhibiting Substance (MIS). During normal in situ development of the XY gonad, MIS staining was first detected in fetal Sertoli cells at 12 days of gestation (d.g.) and remained intense until 4 days postpartum (d.pp.), after which it gradually diminished with progressive testicular development. In the normal in situ XX gonad, MIS was detected in granulosa cells of growing follicles at 7 d.pp. and thereafter. When the XX gonad at 12 d.g. was grafted beneath the renal capsule, a few testicular cords composed of MIS-positive cells appeared on Day 7 post-transplantation (equivalent to 19 d.g.), much earlier than the normal appearance of MIS production in the intact XX ovary. The ovarian region containing germ cells at the meiotic prophase was unstained for MIS in the same sections. The incidence of XX gonadal grafts containing MIS-positive testicular cords and the number of such cords per gonadal graft steadily increased from Day 7 to Day 14 post-transplantation. Germ cells were absent or scarce inside the MIS-positive testicular cords. The MIS bioactivity in both control gonads and gonadal grafts coincided with the immunocytochemical staining for MIS. These results support the hypothesis that XX cells differentiate into Sertoli cells as a consequence of oocyte loss in the gonadal graft. C1 MCGILL UNIV,ROYAL VICTORIA HOSP,DEPT BIOL,MONTREAL H3A 1A1,QUEBEC,CANADA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PEDIAT SURG RES LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV PEDIAT SURG,BOSTON,MA 02114. RP TAKETO, T (reprint author), MCGILL UNIV,ROYAL VICTORIA HOSP,UROL RES LAB,687 PINE AVE W,MONTREAL H3A 1A1,QUEBEC,CANADA. FU NCI NIH HHS [NCI CA17393] NR 49 TC 39 Z9 40 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 1993 VL 49 IS 1 BP 13 EP 23 DI 10.1095/biolreprod49.1.13 PG 11 WC Reproductive Biology SC Reproductive Biology GA LK124 UT WOS:A1993LK12400002 PM 8353178 ER PT J AU CANNON, SC BROWN, RH COREY, DP AF CANNON, SC BROWN, RH COREY, DP TI THEORETICAL RECONSTRUCTION OF MYOTONIA AND PARALYSIS CAUSED BY INCOMPLETE INACTIVATION OF SODIUM-CHANNELS SO BIOPHYSICAL JOURNAL LA English DT Article ID HYPERKALEMIC PERIODIC PARALYSIS; ADYNAMIA EPISODICA HEREDITARIA; FROG SARTORIUS MUSCLE; SKELETAL-MUSCLE; PARAMYOTONIA-CONGENITA; COMPUTER-SIMULATIONS; EXCITABLE CELLS; CL CONDUCTANCE; ALPHA-SUBUNIT; VOLTAGE-CLAMP AB Muscle fibers from individuals with hyperkalemic periodic paralysis generate repetitive trains Of action potentials (myotonia) or large depolarizations and block of spike production (paralysis) when the extracellular K+ is elevated. These pathologic features are thought to arise from mutations of the sodium channel a subunit which cause a partial loss of inactivation (steady-state P(open) almost-equal-to 0.02, compared to < 0.001 in normal channels). We present a model that provides a possible mechanism for how this small persistent sodium current leads to repetitive firing, why the integrity of the T-tubule system is required to produce myotonia, and why paralysis will occur when a slightly larger proportion of channels fails to inactivate. The model consists of a two-compartment system to simulate the surface and T-tubule membranes. When the steady-state sodium channel open probability exceeds 0.0075, trains of repetitive discharges occur in response to constant current injection. At the end of the current injection, the membrane potential may either return to the normal resting value, continue to discharge repetitive spikes, or settle to a new depolarized equilibrium potential. This after-response depends on both the proportion of noninactivating sodium channels and the magnitude of the activity-driven K+ accumulation in the T-tubular space. A reduced form of model is presented in which a two-dimensional phase-plane analysis shows graphically how this diversity of after-responses arises as extracellular [K+] and the proportion of noninactivating sodium channels are varied. C1 MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. CHARLESTOWN NEUROSCI CTR,DAY NEUROMUSCULAR RES LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. RP CANNON, SC (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,WELLMAN 414,BOSTON,MA 02114, USA. OI Corey, David/0000-0003-4497-6016 FU NIAMS NIH HHS [R01 AR41025-1] NR 37 TC 118 Z9 118 U1 0 U2 2 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 1993 VL 65 IS 1 BP 270 EP 288 PG 19 WC Biophysics SC Biophysics GA LL137 UT WOS:A1993LL13700037 PM 8396455 ER PT J AU DANDREA, AD RUP, BJ FISHER, MJ JONES, S AF DANDREA, AD RUP, BJ FISHER, MJ JONES, S TI ANTIERYTHROPOIETIN RECEPTOR (EPO-R) MONOCLONAL-ANTIBODIES INHIBIT ERYTHROPOIETIN BINDING AND NEUTRALIZE BIOACTIVITY SO BLOOD LA English DT Article ID MURINE; EXPRESSION; PROTEINS; CLONING; COMPLEX; CELLS C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. GENET INST INC,CAMBRIDGE,MA. RP DANDREA, AD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [R01 DK43889-01] NR 22 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1993 VL 82 IS 1 BP 46 EP 52 PG 7 WC Hematology SC Hematology GA LL366 UT WOS:A1993LL36600007 PM 7686789 ER PT J AU VONANDRIAN, UH CHAMBERS, JD BERG, EL MICHIE, SA BROWN, DA KAROLAK, D RAMEZANI, L BERGER, EM ARFORS, KE BUTCHER, EC AF VONANDRIAN, UH CHAMBERS, JD BERG, EL MICHIE, SA BROWN, DA KAROLAK, D RAMEZANI, L BERGER, EM ARFORS, KE BUTCHER, EC TI L-SELECTIN MEDIATES NEUTROPHIL ROLLING IN INFLAMED VENULES THROUGH SIALYL LEWIS(X)-DEPENDENT AND LEWIS(X)-INDEPENDENT RECOGNITION PATHWAYS SO BLOOD LA English DT Article ID NODE HOMING RECEPTOR; VASCULAR ENDOTHELIAL-CELLS; CHEMOTACTIC FACTORS; ADHESION MOLECULE; CD18-INDEPENDENT ADHESION; MESENTERIC VENULES; LEUKOCYTE ADHESION; MEL-14 ANTIGEN; LYMPH-NODES; LECAM-1 C1 LA JOLLA INST EXPTL MED,LA JOLLA,CA. LIPOSOME CO,PRINCETON,NJ. US DEPT VET AFFAIRS,CTR MOLEC BIOL MED,PALO ALTO,CA. RP VONANDRIAN, UH (reprint author), STANFORD UNIV,MED CTR L235,DEPT PATHOL,IMMUNOL & VASC BIOL LAB,STANFORD,CA 94305, USA. RI von Andrian, Ulrich/A-5775-2008; Berg, Ellen/D-9076-2014 OI Berg, Ellen/0000-0001-5149-6665 FU NIAID NIH HHS [AI19957]; NIGMS NIH HHS [GM37734, GM41965] NR 56 TC 131 Z9 131 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 1993 VL 82 IS 1 BP 182 EP 191 PG 10 WC Hematology SC Hematology GA LL366 UT WOS:A1993LL36600025 PM 7686786 ER PT J AU RANKIN, AC ZAIM, S POWELL, A ZAIM, B BROOKS, R MCGOVERN, BA GARAN, H RUSKIN, JN AF RANKIN, AC ZAIM, S POWELL, A ZAIM, B BROOKS, R MCGOVERN, BA GARAN, H RUSKIN, JN TI EFFICACY OF A TIERED THERAPY DEFIBRILLATOR SYSTEM USED TO TREAT RECURRENT VENTRICULAR ARRHYTHMIAS REFRACTORY TO DRUGS SO BRITISH HEART JOURNAL LA English DT Article ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; TACHYCARDIA CYCLE LENGTH; LONG-TERM EFFICACY; ANTITACHYCARDIA PACEMAKER; SHOCK THERAPY; TERMINATION; SURVIVAL; TACHYARRHYTHMIAS; COMBINATION; REDUCTION AB Objective-To evaluate an implantable tiered therapy defibrillator system that delivered antitachycardia pacing treatment for slower well tolerated ventricular tachycardias and cardioversion or defibrillation for fast tachycardias or ventricular fibrillation. Methods-A tiered treatment device (Ventritex Cadence V-100) was implanted in 30 patients with ventricular tachycardia that was refractory to drugs. Efficacy was evaluated by the responses of induced or spontaneous arrhythmias to the treatments delivered. Results-Antitachycardia pacing successfully terminated 80% of episodes of ventricular tachycardia induced by non-invasive programmed stimulation, but acceleration was brought about by pacing in six patients in 10% of episodes. During a follow up of two to 17 (mean seven) months, 18 patients (60%) had recurrence of ventricular arrhythmias. Antitachycardia pacing terminated ventricular tachycardia in 17 of 18 patients in 87% of episodes. Twelve patients received shocks for ventricular tachycardia or fibrillation. Failure of pacing, with subsequent cardioversion, occurred in nine patients (50%) in one or more episodes. Acceleration of tachycardia by pacing occurred in 10 patients in 5% of episodes. Only two of these patients had experienced acceleration of previously induced arrhythmia. Five patients had spontaneous fast ventricular tachycardia or fibrillation treated by cardioversion or defibrillation. Spurious treatment was delivered in nine patients (30%), during atrial fibrillation in five, sinus tachycardia in two, and because of fracture of the sensing lead system in two patients. The retrieval of stored intracardiac electrograms was of clinical value in assessing spurious treatment. Conclusions-Tiered treatment was effective in terminating recurrent ventricular arrhythmias in these selected patients. Most episodes were treated successfully by pacing, and resistant tachycardias, pacing induced acceleration, or haemodynamically compromising arrhythmias were treated by shocks. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. NR 35 TC 2 Z9 2 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 JUL PY 1993 VL 70 IS 1 BP 61 EP 69 PG 9 WC Cardiac & Cardiovascular Systems; History & Philosophy Of Science SC Cardiovascular System & Cardiology; History & Philosophy of Science GA LL698 UT WOS:A1993LL69800014 PM 8038001 ER PT J AU FALCONE, PM LOU, PL AF FALCONE, PM LOU, PL TI RESOLUTION OF AN EXTERNAL LAYER MACULAR HOLE ASSOCIATED WITH AN OPTIC-NERVE PIT AFTER LASER PHOTOCOAGULATION SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Note ID VITREOUS SURGERY C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. NR 12 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JUL PY 1993 VL 77 IS 7 BP 457 EP 459 DI 10.1136/bjo.77.7.457 PG 3 WC Ophthalmology SC Ophthalmology GA LK731 UT WOS:A1993LK73100020 PM 8343480 ER PT J AU LEGUERN, C SHIMADA, H EMERY, DW GERMANA, S SACHS, DH AF LEGUERN, C SHIMADA, H EMERY, DW GERMANA, S SACHS, DH TI MOLECULAR TRANSPLANTATION OF MHC CLASS-II GENES AS A MEANS FOR INDUCING TRANSPLANTATION TOLERANCE IN MINIATURE SWINE SO BULLETIN DE L INSTITUT PASTEUR LA English DT Article DE TRANSPLANTATION; MINIATURE SWINE; REVIEW; TOLERANCE; MHC; GENE TRANSFER; RETROVIRUS; BONE MARROW; GENE THERAPY ID MAJOR HISTOCOMPATIBILITY COMPLEX; BONE-MARROW TRANSPLANTATION; RETROVIRUS VECTORS; RENAL-ALLOGRAFTS; ANTILYMPHOCYTE-SERUM; HEMATOPOIETIC-CELLS; ADENOSINE-DEAMINASE; POLIOVIRUS RNA; LYMPHOCYTES-T; MESSENGER-RNA C1 CHIBA UNIV,SCH MED,DEPT SURG 2,CHUOU KU,CHIBA 260,JAPAN. RP LEGUERN, C (reprint author), MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,MGH E,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 74 TC 7 Z9 7 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0020-2452 J9 B I PASTEUR JI Bull. Inst. Pasteur PD JUL-SEP PY 1993 VL 91 IS 3 BP 125 EP 133 PG 9 WC Immunology; Microbiology; Virology SC Immunology; Microbiology; Virology GA MM609 UT WOS:A1993MM60900001 ER PT J AU UEMATSU, M TARBELL, NJ SILVER, B COLEMAN, CN ROSENTHAL, DS SHULMAN, LN CANELLOS, G WEINSTEIN, H MAUCH, P AF UEMATSU, M TARBELL, NJ SILVER, B COLEMAN, CN ROSENTHAL, DS SHULMAN, LN CANELLOS, G WEINSTEIN, H MAUCH, P TI WIDE-FIELD RADIATION-THERAPY WITH OR WITHOUT CHEMOTHERAPY FOR PATIENTS WITH HODGKIN DISEASE IN RELAPSE AFTER INITIAL COMBINATION CHEMOTHERAPY SO CANCER LA English DT Article DE HODGKIN DISEASE; NODAL RECURRENCE; SALVAGE TREATMENT; RADIATION THERAPY; COMBINATION CHEMOTHERAPY ID BONE-MARROW TRANSPLANTATION; COMBINED MODALITY THERAPY; SALVAGE CHEMOTHERAPY; PROGNOSTIC FACTORS; STAGE-IA; MOPP; SURVIVAL; IRRADIATION; EXPERIENCE; FAILURE AB Background. Patients with Hodgkin disease who have relapses after initial chemotherapy (CT) appear to have a poor prognosis, especially if the duration of the first complete remission (CR) was short. The authors performed a retrospective analysis of patients with Hodgkin disease whose relapse after combination CT was limited to nodal sites; their aim was to study the prognosis of this selected subgroup of patients. Methods. In 28 patients with Hodgkin disease who had relapses in nodal sites after combination CT alone, the disease was restaged carefully to rule out simultaneous extranodal recurrences. Then the patients were treated with wide-field, high-dose radiation therapy (RT) with or without additional CT with curative intent between 1971 and 1987 at the Joint Center for Radiation Therapy. Fourteen patients were in first relapse and were treated with combination CT followed by RT. The remaining 14 patients (8 who were in first relapse and 6 who were in second relapse) were treated with RT alone. RT techniques were similar to those recommended for early-stage disease. Results. The 7-year actuarial freedom from relapse and survival rates for the patients retreated with CT and RT were 93% and 85%, respectively, as compared with 36% and 36% for patients retreated with RT alone. There was a significant difference for freedom from relapse (P = 0.002) and survival (P = 0.03), favoring patients retreated with both CT and RT. Conclusions. This retrospective study demonstrates that RT combined with second-line CT can result in a high percentage of durable remissions in patients who have relapses primarily in nodal sites after original treatment with combination CT alone. These durable remissions are seen even in patients who have only a brief CR after initial CT. C1 JOINT CTR RADIAT THERAPY,SO BINNEY ST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. NR 23 TC 23 Z9 23 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 JUL 1 PY 1993 VL 72 IS 1 BP 207 EP 212 DI 10.1002/1097-0142(19930701)72:1<207::AID-CNCR2820720137>3.0.CO;2-A PG 6 WC Oncology SC Oncology GA LH257 UT WOS:A1993LH25700036 PM 7685241 ER PT J AU JACOBSON, JO WILKES, BM KWIATKOWSKI, DJ MEDEIROS, LJ AISENBERG, AC HARRIS, NL AF JACOBSON, JO WILKES, BM KWIATKOWSKI, DJ MEDEIROS, LJ AISENBERG, AC HARRIS, NL TI BCL-2 REARRANGEMENTS IN DENOVO DIFFUSE LARGE-CELL LYMPHOMA - ASSOCIATION WITH DISTINCTIVE CLINICAL-FEATURES SO CANCER LA English DT Article DE BCL-2; T(14; 18); LARGE CELL LYMPHOMA ID BREAKPOINT-CLUSTER REGION; HUMAN FOLLICULAR LYMPHOMA; NON-HODGKINS-LYMPHOMA; CHROMOSOMAL BREAKPOINT; MALIGNANT-LYMPHOMAS; GENE; INVOLVEMENT; PROGRESSION; TISSUE; LOCUS AB Background. The frequency and clinical significance of bcl-2 rearrangement in de novo B-cell diffuse large cell lymphoma is largely unknown. Methods. Using Southern blot hybridization and multiple DNA probes, the status of the protooncogene bcl-2 was investigated in frozen tissue samples from 45 carefully selected cases of de novo diffuse large cell lymphoma of B-cell origin. Results were correlated with the presenting clinical and immunophenotypic features and with the subsequent clinical course. Results. Rearrangements of bcl-2 were identified in nine tumor specimens (20%). The bcl-2-positive cases more often presented as early-stage, nonmucosal associated extranodal tumors (P = 0.06) and were more often HLA-DR negative (P = 0.07). Five-year failure-free survival was poor among the bcl-2-positive cases (11% versus 48%). Overall survival was no different, however, because relapses in bcl-2-positive cases tended to be responsive to further therapy. Conclusions. Analysis of bcl-2 rearrangements in de novo diffuse large cell lymphoma may identify a subset of patients with unusual clinical features. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NCI NIH HHS [CA-30020] NR 33 TC 85 Z9 86 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUL 1 PY 1993 VL 72 IS 1 BP 231 EP 236 DI 10.1002/1097-0142(19930701)72:1<231::AID-CNCR2820720141>3.0.CO;2-5 PG 6 WC Oncology SC Oncology GA LH257 UT WOS:A1993LH25700040 PM 8508412 ER PT J AU BADER, SB WEINSTEIN, H MAUCH, P SILVER, B TARBELL, NJ AF BADER, SB WEINSTEIN, H MAUCH, P SILVER, B TARBELL, NJ TI PEDIATRIC STAGE-IV HODGKIN DISEASE - LONG-TERM SURVIVAL SO CANCER LA English DT Article DE RADIATION THERAPY; STAGE-IV HODGKIN DISEASE; COMBINED-MODALITY THERAPY; CHEMOTHERAPY; PEDIATRIC ID COMBINED MODALITY THERAPY; COMBINATION CHEMOTHERAPY; RADIATION-THERAPY; HOST-DISEASE; FOLLOW-UP; CHILDREN; MOPP; IRRADIATION; CANCER; COMPLICATIONS AB Background. The optimal treatment for Stage IV Hodgkin disease (HD) remains uncertain, particularly the role of radiation therapy (RT). Methods. A retrospective review of 43 children, 18 years of age or younger, who were seen and treated for Stage IV HD between June 1970 and June 1988, was performed. All patients were treated with combination chemotherapy (CT), and 20 patients received RT after CT (combined-modality therapy, CMT). CT consisted of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) in 41 patients and both MOPP and doxorubicin Adriamycin, Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine in two patients. RT was added for patients who had a partial response (PR) to CT (n = 11) and/or for initial bulky thoracic disease (n = 12). Results. With a median follow-up of 83 months, the 7-year actuarial freedom from progression (FFP) and survival rates for all patients were 69% and 78%, respectively. For patients achieving a complete response (CR) to CT, the 7-year FFP rate was 73% and for patients with a PR it was 90% (P value not significant). The actuarial overall survival rates at 7 years were 88% for patients with CR versus 80% for patients with PR. In contrast, patients with either no response (one patient) or progressive disease (four patients) after CT had a significantly worse prognosis than patients with CR, with a 7-year actuarial survival rate of 40% (P = 0.006). FFP after CT alone was significantly more prevalent in patients with Stage IVA (11 of 13 patients) than in patients with Stage IVB disease (2 of 10 patients; P = 0.003). For these symptomatic patients, failures were almost exclusively (seven of eight patients) in sites of initial nodal disease. The addition of adjuvant RT improved the progression-free survival for patients with B symptoms: 2 of 13 patients had relapses after CMT versus 8 of 10 patients treated with CT alone (P 0.003). Conclusions. This retrospective analysis of MOPP alone compared with MOPP plus RT showed a significant difference in FFP in patients with Stage IVB HD favoring CMT. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT RADIAT ONCOL,300 LONGWOOD AVE,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. NR 38 TC 15 Z9 15 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 JUL 1 PY 1993 VL 72 IS 1 BP 249 EP 255 DI 10.1002/1097-0142(19930701)72:1<249::AID-CNCR2820720144>3.0.CO;2-8 PG 7 WC Oncology SC Oncology GA LH257 UT WOS:A1993LH25700043 PM 7685242 ER PT J AU GELBER, RD SALLAN, SE COHEN, HJ DONNELLY, M DALTON, V TOBIA, F CLAVELL, LA TARBELL, NJ AF GELBER, RD SALLAN, SE COHEN, HJ DONNELLY, M DALTON, V TOBIA, F CLAVELL, LA TARBELL, NJ TI CENTRAL-NERVOUS-SYSTEM TREATMENT IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA - LONG-TERM FOLLOW-UP OF PATIENTS DIAGNOSED BETWEEN 1973 AND 1985 SO CANCER LA English DT Article DE PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA; CENTRAL NERVOUS SYSTEM RELAPSE; CRANIAL IRRADIATION; CUMULATIVE INCIDENCE FUNCTIONS; COMPETING RISK ANALYSIS ID ACUTE LYMPHOCYTIC-LEUKEMIA; CANCER-STUDY-GROUP; HIGH-DOSE METHOTREXATE; CRANIAL IRRADIATION; CNS PROPHYLAXIS; INTRATHECAL METHOTREXATE; INTENSIVE ASPARAGINASE; PRESENTING FEATURES; COMPETING RISKS; FREE SURVIVAL AB Background. Despite advances in the treatment of childhood acute lymphoblastic leukemia (ALL), optimal therapy of the central nervous system (CNS) remains controversial. Methods. Between 1973 and 1985, 540 children with ALL (199 standard risk and 341 high risk) were treated on four protocols. Results. The 7-year event-free survival rate (+/- standard error) was 62.1% (+/- 2.1) for the entire group: 71.8% (+/- 3.2) for standard-risk and 56.4% (+/- 2.7) for high-risk patients. Five hundred eighteen of the children entered complete remission and received cranial irradiation with intrathecal methotrexate for CNS treatment; 197 had standard-risk ALL and 321 had high-risk ALL. Thirty-one patients (5 standard risk and 26 high risk) had a CNS relapse with or without concurrent bone marrow relapse as an initial event, the latest of which was observed 49 months after complete remission. The cumulative incidence of CNS relapse was 6.0% (+/- 1.1) for the entire group: 2.5% (+/- 1.1) for standard-risk and 8.2% (+/- 1.5) for high-risk patients (P = 0.01). CNS recurrence of leukemia, whether as an ''isolated'' site or a ''combined'' site of relapse, was a major adverse event. Only 4 of 31 patients were alive for 25+, 28+, 54+, and 71+ months after a CNS relapse. The median survival time after CNS relapse was 22 months: 21 months for the 20 patients who had an isolated CNS relapse, and 23 months for the 11 patients who had a CNS relapse concurrent with a recurrence in other sites. Conclusions. Although attempts to diminish CNS treatment-related morbidity are warranted for standard-risk patients, the authors recommend that intensive CNS treatment be enhanced for the high-risk patients because CNS relapses continue to occur in this population. Furthermore, CNS relapse after cranial irradiation was associated with a very poor prognosis and needs to be treated as intensively as a bone marrow relapse. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. UNIV ROCHESTER,MED CTR,DEPT PEDIAT,ROCHESTER,NY 14642. UNIV PUERTO RICO,DEPT PEDIAT ONCOL,SAN JUAN,PR 00936. CHILDRENS HOSP MED CTR,DEPT RADIAT THERAPY,BOSTON,MA 02115. RP GELBER, RD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT,MAYER 432,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 06516, CA 34183] NR 48 TC 35 Z9 37 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 JUL 1 PY 1993 VL 72 IS 1 BP 261 EP 270 DI 10.1002/1097-0142(19930701)72:1<261::AID-CNCR2820720146>3.0.CO;2-O PG 10 WC Oncology SC Oncology GA LH257 UT WOS:A1993LH25700045 PM 8508416 ER PT J AU TEICHER, BA CHATTERJEE, D LIU, JT HOLDEN, SA ARA, G AF TEICHER, BA CHATTERJEE, D LIU, JT HOLDEN, SA ARA, G TI PROTECTION OF BONE-MARROW GRANULOCYTE-MACROPHAGE COLONY-FORMING-UNITS IN MICE BEARING IN-VIVO ALKYLATING-AGENT-RESISTANT EMT-6 TUMORS SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE CFM-GM; IN-VIVO RESISTANT; TUMOR LINES ID CELL-LINES; RHABDOMYOSARCOMA XENOGRAFT; CROSS-RESISTANCE; CIS-DIAMMINEDICHLOROPLATINUM(II); CYCLOPHOSPHAMIDE; SENSITIVITY; INVITRO; CANCER AB The survival of bone-marrow granulocyte-macrophage colony-forming units (CFU-GM), an alkylating-agent-sensitive normal tissue, was assessed in mice bearing the EMT-6 parental tumor or the in vivo resistant EMT-6/CDDP, EMT-6/CTX, EMT-6/Thio, and EMT-6/Carbo tumors. The survival pattern of the bone-marrow CFU-GM recapitulated the survival of the tumor cells, mimicking the development of resistance and reversion to sensitivity upon removal of the selection pressure for each of the four alkylating agents. When the EMT-6 parental tumor was implanted in the opposite hind limb of animals bearing the EMT-6/CDDP or EMT-6/CTX tumor, the survival of the parental tumor cells after treatment of the animals with the appropriate antitumor alkylating agent was enhanced. The EMT-6/CDDP tumor was cross-resistant to CTX and high-dose L-PAM, whereas the EMT-6/CTX tumor was somewhat resistant to CDDP and markedly sensitive to VP- 1 6. In each case, the survival pattern of the bone-marrow CFU-GM reflected the survival of the tumor cells. These results indicate that the presence of an alkylating-agent-resistant tumor in an animal can affect the drug response of tissues distal to that tumor. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA. RP TEICHER, BA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [R01-CA47379, P01-CA38493] NR 19 TC 18 Z9 18 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 JUL PY 1993 VL 32 IS 4 BP 315 EP 319 DI 10.1007/BF00686178 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA LJ927 UT WOS:A1993LJ92700011 PM 8324874 ER PT J AU YU, JS WEI, MX CHIOCCA, EA MARTUZA, RL TEPPER, RI AF YU, JS WEI, MX CHIOCCA, EA MARTUZA, RL TEPPER, RI TI TREATMENT OF GLIOMA BY ENGINEERED INTERLEUKIN-4-SECRETING CELLS SO CANCER RESEARCH LA English DT Article ID RECURRENT GLIOBLASTOMA-MULTIFORME; PRIMARY INTRACRANIAL TUMORS; STIMULATORY FACTOR-I; ADOPTIVE IMMUNOTHERAPY; BRAIN-TUMOR; RECOMBINANT INTERLEUKIN-2; MALIGNANT GLIOMA; LYMPHOCYTES; EXPRESSION; INFUSIONS AB The ability of interleukin-4 (IL-4) to mediate an antitumor response to human gliomas was studied in vivo in nude mice. To allow the effect of IL-4 to be exerted over a relatively short distance and at an optimal concentration, a transfected tumor cell line expressing a high level of IL-4 was used in mixed tumor transplantation assays. There was a significant inhibition of growth of the U87 human glioma line when the IL-4-secreting cell line, LT-1, was implanted s.c. with the glioma in 5 nude mice when compared to contralateral control tumors consisting of the U87 glioma and IL-4-negative control cells. In addition, there was a prolongation of survival when U87 along with IL-4-secreting cells were implanted intracerebrally in 12 nude mice compared to 12 control nude mice implanted with U87 and IL-4-negative control cells and 11 control animals receiving U87 alone. Histological analysis 4 days after i.c. inoculation revealed the presence of a dramatic eosinophil infiltrate and tumor necrosis. The absence of viable glioma cells as well as resolution of inflammation 19 days after treatment suggests the potential for complete tumor regression without ongoing inflammatory sequelae resulting from cytokine treatment. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,DEPT SURG,MOLEC NEUROGENET LAB,BOSTON,MA 02114. NR 29 TC 129 Z9 135 U1 1 U2 4 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 1 PY 1993 VL 53 IS 13 BP 3125 EP 3128 PG 4 WC Oncology SC Oncology GA LL131 UT WOS:A1993LL13100035 PM 8319220 ER PT J AU SUN, Y OBERLEY, LW OBERLEY, TD ELWELL, JH SIERRARIVERA, E AF SUN, Y OBERLEY, LW OBERLEY, TD ELWELL, JH SIERRARIVERA, E TI LOWERED ANTIOXIDANT ENZYMES IN SPONTANEOUSLY TRANSFORMED EMBRYONIC MOUSE-LIVER CELLS IN CULTURE SO CARCINOGENESIS LA English DT Article ID CHINESE-HAMSTER CELLS; SPONTANEOUS NEOPLASTIC EVOLUTION; MULTISTEP PROGRESSION; CATALASE; LINES AB Normal embryonal mouse liver cells in culture were shown to undergo spontaneous transformation during prolonged subculture. The spontaneously transformed cells lost their anchorage dependence, as measured by a soft agar assay, and gave rise to tumors in nude mice. Accompanying this transformation, the antioxidant enzymes, copper- and zinc-containing superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), catalase (CAT) and glutathione reductase, decreased significantly in activity; the decline in enzymatic activity of CuZnSOD, MnSOD and CAT was due to a decline in the levels of immunoreactive protein. These spontaneously transformed high passage in vitro liver cells appeared similar in morphology, antioxidant enzyme activity and tumorigenicity to their counterparts transformed by N-methyl-N-nitro-N-nitrosoguanidine and Simian virus 40. These data provide experimental evidence that changes in antioxidant enzymes are associated with spontaneous in vitro cellular transformation of mouse embryonal liver cells. C1 UNIV IOWA,MED LABS 14,RADIAT RES LAB,IOWA CITY,IA 52242. WILLIAM S MIDDLETON MEM VET ADM MED CTR,PATHOL SERV,MADISON,WI 53705. FU NCI NIH HHS [R01-CA41267, T32-CA-09125] NR 33 TC 47 Z9 47 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1993 VL 14 IS 7 BP 1457 EP 1463 DI 10.1093/carcin/14.7.1457 PG 7 WC Oncology SC Oncology GA LM978 UT WOS:A1993LM97800033 PM 8330364 ER PT J AU SCHOTT, RJ MORROW, LA AF SCHOTT, RJ MORROW, LA TI GROWTH-FACTORS AND ANGIOGENESIS SO CARDIOVASCULAR RESEARCH LA English DT Review ID ENDOTHELIAL-CELL GROWTH; FACTOR RECEPTOR FAMILY; FACTOR GENE FAMILY; FACTOR-BETA; HEPARIN-BINDING; TGF-BETA; EXTRACELLULAR-MATRIX; MYOCARDIAL ANGIOGENESIS; TRANSFORMED-CELLS; HUMAN-PLATELETS C1 BROCKTON W ROXBURY VET ADM HOSP, CTR GERIATR RES EDUCAT & CLIN, BROCKTON, MA USA. RP SCHOTT, RJ (reprint author), MASSACHUSETTS GEN HOSP, CARDIAC UNIT, BOSTON, MA 02114 USA. NR 108 TC 75 Z9 79 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD JUL PY 1993 VL 27 IS 7 BP 1155 EP 1161 DI 10.1093/cvr/27.7.1155 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LN906 UT WOS:A1993LN90600003 PM 7504584 ER PT J AU YASUDA, T AF YASUDA, T TI HYPOXIA AND REOXYGENATION IN THE ISOLATED RABBIT HEART SO CARDIOVASCULAR RESEARCH LA English DT Letter RP YASUDA, T (reprint author), MASSACHUSETTS GEN HOSP,CELL BIOL UNIT,TILTON 2,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD JUL PY 1993 VL 27 IS 7 BP 1383 EP 1383 DI 10.1093/cvr/27.7.1383 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LN906 UT WOS:A1993LN90600037 PM 8252603 ER PT J AU FAUSTMAN, D AF FAUSTMAN, D TI COMMENTARY ON CLINICAL ISLET TRANSPLANTATION SO CELL TRANSPLANTATION LA English DT Editorial Material RP FAUSTMAN, D (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD JUL-AUG PY 1993 VL 2 IS 4 BP 289 EP 289 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA LJ455 UT WOS:A1993LJ45500004 ER PT J AU RADEMACHER, J CAVINESS, VS STEINMETZ, H GALABURDA, AM AF RADEMACHER, J CAVINESS, VS STEINMETZ, H GALABURDA, AM TI TOPOGRAPHICAL VARIATION OF THE HUMAN PRIMARY CORTICES - IMPLICATIONS FOR NEUROIMAGING, BRAIN MAPPING, AND NEUROBIOLOGY SO CEREBRAL CORTEX LA English DT Article ID POSITRON-EMISSION TOMOGRAPHY; HUMAN VISUAL-CORTEX; LEFT-RIGHT ASYMMETRIES; HUMAN CEREBRAL-CORTEX; PREMOTOR CORTEX; SENSORY STIMULATION; PLANUM TEMPORALE; SPEECH REGION; MOTOR CORTEX; LOCALIZATION AB The relationships of the ''primary'' cytoarchitectonic neocortical fields, 17, 41, 3b, and 4 (Brodmann areas), to salient topographic landmarks have been reconstructed from serial histological sections in 20 human cerebral hemispheres (10 brains). Each of these architectonic fields is found to bear a characteristic relationship to a set of enframing anatomic landmarks, in particular, gyri, fissures, and sulci, that can be readily defined by MRI. Two classes of variability were found characteristic, at least to some extent, of each of the fields. Class 1 variability-variability that is not predictable from visible landmarks-was typical of the polar and for the cuneal and lingual extracalcarine distributions of field 17 and the distribution of field 4 upon the paracentral lobule. Class 2 variability-variability that is closely predictable from visible landmarks-is seen in the marked interindividual or interhemispheric variation in size or shape of a field and was found to be prominent for all four fields. Because of the prominence of class 2 variability, direct reference to the landmarks that frame these fields may be expected to be a more reliable basis for functional mapping than reference to a template or stereotactic coordinate-based system of reference to a standard or idealized brain. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT NEUROL,330 BROOKLINE AVE,BOSTON,MA 02215. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR MORPHOMETR ANAL,BOSTON,MA 02114. HEINRICH HEINE UNIV DUSSELDORF,NEUROL KLIN,W-4000 DUSSELDORF 1,GERMANY. FU NINDS NIH HHS [NS 27119] NR 75 TC 396 Z9 396 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUL-AUG PY 1993 VL 3 IS 4 BP 313 EP 329 DI 10.1093/cercor/3.4.313 PG 17 WC Neurosciences SC Neurosciences & Neurology GA LR363 UT WOS:A1993LR36300004 PM 8400809 ER PT J AU LOFTUS, WC TRAMO, MJ THOMAS, CE GREEN, RL NORDGREN, RA GAZZANIGA, MS AF LOFTUS, WC TRAMO, MJ THOMAS, CE GREEN, RL NORDGREN, RA GAZZANIGA, MS TI 3-DIMENSIONAL QUANTITATIVE-ANALYSIS OF HEMISPHERIC-ASYMMETRY IN THE HUMAN SUPERIOR TEMPORAL REGION SO CEREBRAL CORTEX LA English DT Article ID HUMAN AUDITORY-CORTEX; PLANUM-TEMPORALE; CEREBRAL-CORTEX; HUMAN-BRAIN; SPEECH; HANDEDNESS; LANGUAGE; SURFACE; SIZE AB The recent observations of overall symmetry of the caudal infrasylvian region by Steinmetz et al. (1990) and Witelson and Kigar (1991, 1992) diverge from earlier findings of leftward asymmetry in this region (Geschwind and Levitsky, 1968; Galaburda et al., 1987; Larsen et al., 1989). To address this inconsistency, we measured the entire infrasylvian surface posterior to Heschl's gyrus from coronal magnetic resonance images of 10 young, normal, right-handed subjects. Computer models were constructed by tracing contours of this region and then interpolating a 3D triangle mesh between each pair of adjacent contours. Measurements of these models showed no significant directional asymmetry. The same contour set was used to obtain measurements with a conventional algorithm that does not interpolate a surface between contours. The results obtained with the second method showed significant leftward asymmetry. These results suggest that in some cases, unbalanced distortions due to folding differences of the hemispheres are sufficient to obtain spurious findings of left-right asymmetry. This supports the claim of Steinmetz and Witelson that leftward asymmetry is restricted to the temporal bank of the caudal infrasylvian surface, and is balanced by rightward asymmetry of the parietal bank. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. DARTMOUTH COLL SCH MED,DEPT PSYCHIAT,HANOVER,NH 03755. RP LOFTUS, WC (reprint author), UNIV CALIF DAVIS,CTR NEUROSCI,DAVIS,CA 95616, USA. FU NIDCD NIH HHS [NIDOCD K08-DC00071]; NINDS NIH HHS [NINDS PO1 NS17778-10] NR 44 TC 47 Z9 47 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUL-AUG PY 1993 VL 3 IS 4 BP 348 EP 355 PG 8 WC Neurosciences SC Neurosciences & Neurology GA LR363 UT WOS:A1993LR36300006 PM 8400810 ER PT J AU ZUCKERMAN, DA YUCEL, EK AF ZUCKERMAN, DA YUCEL, EK TI ILIAC ARTERY ANEURYSMS - RADIOGRAPHIC EVALUATION SO CLINICAL IMAGING LA English DT Review DE ILIAC; ANEURYSM; ULTRASOUND; MAGNETIC RESONANCE IMAGING; ARTERIOGRAPHY; COMPUTED TOMOGRAPHY; MAGNETIC RESONANCE ANGIOGRAPHY ID MAGNETIC-RESONANCE ANGIOGRAPHY; MR ANGIOGRAPHY; PROGRESS; DISEASE; DUPLEX; WORK; US AB We present seventeen cases of iliac artery aneurysm employing a variety of different imaging modalities (ultrasound, computed tomography, arteriography, magnetic resonance imaging). The utility of each of these techniques in the patient with iliac artery aneurysm is described. C1 MASSACHUSETTS GEN HOSP,VASC RADIOL SECT,BOSTON,MA 02114. RP ZUCKERMAN, DA (reprint author), ST LOUIS UNIV,MED CTR,DEPT RADIOL,3635 VISTA AVE,ST LOUIS,MO 63110, USA. NR 9 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0899-7071 J9 CLIN IMAG JI Clin. Imaging PD JUL-SEP PY 1993 VL 17 IS 3 BP 213 EP 221 DI 10.1016/0899-7071(93)90114-3 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LU778 UT WOS:A1993LU77800012 PM 8364796 ER PT J AU HEYMAN, P GELBERMAN, RH DUNCAN, K HIPP, JA AF HEYMAN, P GELBERMAN, RH DUNCAN, K HIPP, JA TI INJURIES OF THE ULNAR COLLATERAL LIGAMENT OF THE THUMB METACARPOPHALANGEAL JOINT - BIOMECHANICAL AND PROSPECTIVE CLINICAL-STUDIES ON THE USEFULNESS OF VALGUS STRESS-TESTING SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article AB In an effort to determine whether valgus stress testing of the thumb metacarpophalangeal joint is predictive of a torn and displaced ulnar collateral ligament, anatomic and prospective clinical studies were performed and the results correlated. In the anatomic study on autopsy specimens, dividing the proper collateral ligament resulted in a significant increase in valgus instability of the flexed metacarpophalangeal joint. Significantly less laxity was noted when the joint was tested in extension. When the accessory collateral ligament/palmar plate complex was also divided, valgus instability in extension increased to the extent that it no longer differed significantly from the values obtained when the joint was tested in 30-degrees flexion. In the clinical study, valgus instability of greater than 35-degrees when the joint was positioned in extension and then stressed consistently indicated the presence of tears of the proper and accessory collateral ligaments: A Stener's lesion was present in 15 of 17 such cases (87%). Values on valgus stress testing of the metacarpophalangeal joint in extension and 30-degrees flexion are highly predictive of both disruption and displacement of the ulnar collateral ligament of the thumb. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,WACC 527,BOSTON,MA 02114. BETH ISRAEL HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02215. FU NIAMS NIH HHS [5R01 AR33097] NR 39 TC 51 Z9 51 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUL PY 1993 IS 292 BP 165 EP 171 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA LM057 UT WOS:A1993LM05700021 PM 8519106 ER PT J AU CONN, AKT AF CONN, AKT TI CRITICAL CARE IN THE EMERGENCY DEPARTMENT - STRESS WITHIN THE SYSTEM SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE EMERGENCY DEPARTMENT; CRITICAL ILLNESS; HOSPITAL BED CAPACITY; HOSPITAL ADMISSION; HOSPITAL REFERRAL ID ADMISSION; PATHWAY; COST RP CONN, AKT (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 13 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 1993 VL 21 IS 7 BP 952 EP 953 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA LL552 UT WOS:A1993LL55200002 PM 8031334 ER PT J AU HAMEED, A AHMED, AR AF HAMEED, A AHMED, AR TI MHC REGULATION OF IMMUNE-RESPONSES SO DERMATOLOGIC CLINICS LA English DT Article RP HAMEED, A (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NEI NIH HHS [EY08379]; NIDCR NIH HHS [DE09978] NR 0 TC 4 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 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD JUL PY 1993 VL 11 IS 3 BP 391 EP 398 PG 8 WC Dermatology SC Dermatology GA LP985 UT WOS:A1993LP98500004 PM 8365027 ER PT J AU ARAKI, E SUN, XJ HAAG, BL CHUANG, LM ZHANG, Y YANGFENG, TL WHITE, MF KAHN, CR AF ARAKI, E SUN, XJ HAAG, BL CHUANG, LM ZHANG, Y YANGFENG, TL WHITE, MF KAHN, CR TI HUMAN SKELETAL-MUSCLE INSULIN-RECEPTOR SUBSTRATE-1 - CHARACTERIZATION OF THE CDNA, GENE, AND CHROMOSOMAL LOCALIZATION SO DIABETES LA English DT Article ID TYROSINE KINASE-ACTIVITY; GROWTH FACTOR-I; CONFORMATION POLYMORPHISMS; SIGNAL TRANSDUCTION; PROTEIN; CELLS; PHOSPHORYLATION; REPLACEMENT; TRANSLATION; EXPRESSION AB Insulin receptor substrate-1 is a major substrate of insulin receptor Tyr kinase. We have now cloned the IRS-1 cDNA from human skeletal muscle, one of the most important target tissues of insulin action, localized and cloned the human IRS-1 gene, and studied the expression of the protein in Chinese hamster ovary cells. Human IRS-1 cDNA encodes a 1242 amino acid sequence that is 88% identical with rat liver IRS-1. The 14 potential Tyr phosphorylation sites include 6 Tyr-Met-X-Met motifs and 3 Tyr-X-X-Met motifs that are completely conserved in human IRS-1. Human IRS-1 has >50 possible Ser/Thr phosphorylation sites and one potential ATP-binding site close to the NH2-terminal. The human IRS-1 gene contains the entire 5'-untranslated region and protein coding region in a single exon and was localized on chromosome 2 q36-37 by in situ hybridization. By Northern blot analysis, IRS-1 mRNA is rare and consists of two species of 6.9 and 6 kilobase. By using quantitative polymerase chain reaction after reverse transcription of total RNA from human fetal tissues, IRS-1 mRNA could be identified in all tissues. When human IRS-1 cDNA was expressed in Chinese hamster ovary cells, the protein migrated between 170,000-180,000 M(r) in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was rapidly Tyr phosphorylated upon insulin stimulation. Thus, IRS-1 is widely expressed and highly conserved across species and tissues. Compared with rat protein, human IRS-1 contains more potential Ser/Thr phosphorylation sites and only one nucleotide binding site. The entire protein coding sequence is contained within a single exon. C1 BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. OI CHUANG, LEE-MING/0000-0003-0978-2662 FU NIDDK NIH HHS [DK33201, DK36836, DK43808] NR 48 TC 99 Z9 105 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1993 VL 42 IS 7 BP 1041 EP 1054 DI 10.2337/diabetes.42.7.1041 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LH869 UT WOS:A1993LH86900014 PM 8513971 ER PT J AU ROBAGLIA, C BRUENING, G HASELOFF, J GERLACH, WL AF ROBAGLIA, C BRUENING, G HASELOFF, J GERLACH, WL TI EVOLUTION AND REPLICATION OF TOBACCO RINGSPOT VIRUS SATELLITE RNA MUTANTS SO EMBO JOURNAL LA English DT Article DE HAMMERHEAD RIBOZYME; MOLECULAR EVOLUTION; PLANT VIRUS; RNA CONFORMATION; SATELLITE RNA ID SELF-CLEAVAGE; RECOMBINATION; PLANTS; MODEL; GENE; DNA; COMPLEMENTARY; TRANSCRIPTS; RESISTANCE; DISEASE AB The replication properties of linker insertion-deletion mutants of tobacco ringspot virus satellite RNA have been studied by amplification in plants infected with the helper virus. Sequence analysis of the cDNAs corresponding to the replicated forms shows that only one of the original mutated molecules replicates unaltered, and in general new variants accumulate. Depending on the location of the original mutation three types of sequence modifications were observed: (i) deletion of the mutated region followed by sequence duplication, (ii) sequence duplication and deletion outside of the mutated region and (iii) limited rearrangements at the site of mutation. The mutant that replicates without sequence changes accumulates linear multimeric forms suggesting that self-cleavage is affected although the sequence alteration does not involve the hammerhead catalytic domain. Alternative RNA conformations are likely to play a role in the origin of this phenotype and in the formation of sequence duplications. These results demonstrate the great structural flexibility of this satellite RNA. C1 UNIV CALIF DAVIS, DEPT PLANT PATHOL, DAVIS, CA 95616 USA. MASSACHUSETTS GEN HOSP, DEPT MOLEC BIOL, BOSTON, MA 02114 USA. CSIRO, DIV PLANT IND, CANBERRA, ACT 2601, AUSTRALIA. RP INRA, BIOL CELLULAIRE LAB, F-78026 VERSAILLES, FRANCE. OI Haseloff, Jim/0000-0003-4793-8058 NR 37 TC 15 Z9 17 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 JUL PY 1993 VL 12 IS 7 BP 2969 EP 2976 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LK364 UT WOS:A1993LK36400042 PM 7687543 ER PT J AU JUAN, M VILELLA, R MILA, J YAGUE, J MIRALLES, A CAMPBELL, KS FRIEDRICH, RJ CAMBIER, J VIVES, J DEFOUGEROLLES, AR SPRINGER, TA AF JUAN, M VILELLA, R MILA, J YAGUE, J MIRALLES, A CAMPBELL, KS FRIEDRICH, RJ CAMBIER, J VIVES, J DEFOUGEROLLES, AR SPRINGER, TA TI CDW50 AND ICAM-3 - 2 NAMES FOR THE SAME MOLECULE SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CDW50; ICAM-3; LFA-1 ID COUNTER-RECEPTOR; ADHESION RECEPTORS; LFA-1; ANTIGEN; PROTEINS; CLONING; CELLS; MAC-1 AB CDw50 differentiation antigen is a molecule broadly expressed on hematopoetic cells but not on other cells. Previous experiments showed that CDw50 monoclonal antibodies (mAb) inhibited primary mixed lymphocyte culture (MLC). To understand the function of CDw50 better, we purified it and obtained peptide sequence. At the same time, intercellular adhesion molecule (ICAM)-3, the third ligand of lymphocyte function-associated molecule 1, was described by mAb and subsequent cDNA cloning. Immunochemical, functional, and protein sequencing studies show that ICAM-3 and CDw50 are the same glycoprotein, a 120-kDa surface molecule with presumably an important role in the immune responses. C1 NATL JEWISH CTR IMMUNOL & RESP MED,DEPT PEDIAT,DENVER,CO. HARVARD UNIV,SCH MED,COMM IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA. RP JUAN, M (reprint author), HOSP CLIN BARCELONA,SERV IMMUNOL,E-08036 BARCELONA,SPAIN. NR 21 TC 39 Z9 40 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 1993 VL 23 IS 7 BP 1508 EP 1512 DI 10.1002/eji.1830230717 PG 5 WC Immunology SC Immunology GA LM708 UT WOS:A1993LM70800016 PM 8325327 ER PT J AU FOWLER, FJ BARRY, MJ AF FOWLER, FJ BARRY, MJ TI QUALITY-OF-LIFE ASSESSMENT FOR EVALUATING BENIGN PROSTATIC HYPERPLASIA TREATMENTS - AN EXAMPLE OF USING A CONDITION-SPECIFIC INDEX SO EUROPEAN UROLOGY LA English DT Article; Proceedings Paper CT SYMP ON CURRENT STANDARDS FOR THE EVALUATION AND PHARMACOLOGICAL CARE OF BPH ( BENIGN PROSTATIC HYPERTROPHY ) CY JUL 22, 1992 CL GENOA, ITALY SP SYNTHELABO PHARM, PLESSIS ROBINSON DE QUALITY OF LIFE ASSESSMENT; SYMPTOMS, BPH ID ASSOCIATION SYMPTOM INDEX; MEDICAL OUTCOMES; PROSTATECTOMY AB 546 patients enrolled in a prospective study of patient treatment choices for benign prostatic hyperplasia (BPH) completed a self-administered questionnaire that included a symptom index, two genera measures of quality of life, and a condition-specific measure of the impact of BPH symptoms on patient quality of life. As expected, differences in symptoms of BPH were significantly associated with general measures of quality of life and the condition-specific impact score. However, the condition-specific impact score was more sensitive to differences in symptoms than the general measures. Hence, such measures are likely to be more responsive to treatment effects, may provide more power for statistical analysis, and hence should be considered along with general quality of life measures for use in treatment outcome studies. C1 UNIV MASSACHUSETTS,CTR SURVEY RES,BOSTON,MA 02125. MASSACHUSETTS GEN HOSP,FAC GEN INTERNAL MED,HENRY J KAISER FAMILY FDN,BOSTON,MA 02114. FU AHRQ HHS [HS06336] NR 14 TC 43 Z9 43 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD JUL PY 1993 VL 24 SU 1 BP 24 EP 27 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA LM574 UT WOS:A1993LM57400005 PM 7687555 ER PT J AU KAWAMURA, J TERAYAMA, Y TAKASHIMA, S OBARA, K PAVOL, MA MEYER, JS MORTEL, KF WEATHERS, S AF KAWAMURA, J TERAYAMA, Y TAKASHIMA, S OBARA, K PAVOL, MA MEYER, JS MORTEL, KF WEATHERS, S TI LEUKOARAIOSIS AND CEREBRAL PERFUSION IN NORMAL AGING SO EXPERIMENTAL AGING RESEARCH LA English DT Article ID WHITE MATTER LUCENCIES; ENCEPHALOPATHY BINSWANGERS DISEASE; CEREBROVASCULAR RISK-FACTORS; MAGNETIC-RESONANCE; COMPUTED-TOMOGRAPHY; VASCULAR DEMENTIA; BRAIN LUCENCIES; BLOOD-FLOW; LEUKOENCEPHALOPATHY; ATROPHY AB To clarify the incidence, age relationships and pathogenesis of white matter lesions of unknown origin (leuko-araiosis) detected by neuroimaging among normal elderly volunteers, we measured the severity of leuko-araiosis using computerized tomographic (CT) densitometry among 42 healthy self-supporting men and women of different ages, all with normal neurological and cognitive test performance. Results were correlated with local cerebral perfusion using xenon-contrasted CT. The 42 volunteers, who are followed in this laboratory for studies of normal aging, were divided into two groups in order to determine aging effects by an extremes design. One group consisted of 19 adults below age 60 (M = 53.3, SD 6.0). The index group comprised 23 individuals all over the age of 60 (M = 71.6, SD = 8.7). Leuko-araiosis around the anterior horns of the lateral ventricles (frontal leuko-araiosis) was more severe (p < .01) among the older group, however, occipital leuko-araiosis did not significantly differ between older and younger groups. Cerebral perfusion in frontal, temporal, and parietal cortex was decreased among older compared with younger volunteers (ps < .001, .01, and .05, respectively). Multiple regression analyses disclosed significant and direct relationships between severity of frontal leuko-araiosis and (a) frontal cortical atrophy and (b) reductions of cerebral perfusion within frontal white matter and caudate nucleus. We conclude that cortical atrophy with hypoperfusion and ischemia of frontal white matter play a part in the pathogenesis of frontal leuko-araiosis associated with normal aging and this may be a predictor for later cognitive declines. C1 DEPT VET AFFAIRS MED CTR,CEREBRAL BLOOD FLOW LAB,2002 HOLCOMBE BLVD,ROOM 225,BLDG 110,HOUSTON,TX 77030. BAYLOR COLL MED,HOUSTON,TX 77030. NR 31 TC 29 Z9 30 U1 0 U2 0 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PD JUL-SEP PY 1993 VL 19 IS 3 BP 225 EP 240 DI 10.1080/03610739308253935 PG 16 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA LX513 UT WOS:A1993LX51300004 PM 8223824 ER PT J AU PITKANEN, K KIVINEN, L DECAPRIO, JA LAIHO, M AF PITKANEN, K KIVINEN, L DECAPRIO, JA LAIHO, M TI EXPRESSION OF THE HUMAN RETINOBLASTOMA GENE-PRODUCT IN MOUSE FIBROBLASTS - EFFECTS ON CELL-PROLIFERATION AND SUSCEPTIBILITY TO TRANSFORMATION SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID SV40 LARGE-T; RB GENE; CARCINOMA-CELLS; PHOSPHORYLATION; PROTEIN; BINDING; CYCLE; DNA; SUPPRESSION; ANTIGEN C1 UNIV HELSINKI,DEPT VIROL,HAARTMANINKATU 3,SF-00290 HELSINKI 29,FINLAND. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 42 TC 10 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL PY 1993 VL 207 IS 1 BP 99 EP 106 DI 10.1006/excr.1993.1167 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA LK309 UT WOS:A1993LK30900012 PM 8319776 ER PT J AU KATZ, MS DAX, EM GREGERMAN, RI AF KATZ, MS DAX, EM GREGERMAN, RI TI BETA-ADRENERGIC REGULATION OF RAT-LIVER GLYCOGENOLYSIS DURING AGING SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE ADENYLATE CYCLASE; BETA-ADRENERGIC RECEPTOR; G-PROTEIN; HEPATOCYTE; CATECHOLAMINES ID ADENYLATE-CYCLASE ACTIVITY; AGE-RELATED-CHANGES; C-MYC TRANSCRIPT; CYCLIC-AMP; HEPATIC GLYCOGENOLYSIS; BETA-2-ADRENERGIC RECEPTORS; GLUCOSE-PRODUCTION; HORMONE ACTION; CELLS; PHOSPHORYLASE AB Studies from a number of laboratories demonstrate a biphasic change in beta adrenergic regulation of hepatic glycogenolysis over the life span of the male rat. The beta adrenergic response is prominent in immature animals, declines rapidly during subsequent development to a minimum by the time of young adulthood, and then reemerges during postmaturational development. Age changes in beta adrenergic-responsive adenylate cyclase activity follow a ''U''-shaped curve similar to that described by changes in liver glycogenolytic responsiveness during aging. Developmental and postmaturational changes in beta adrenergic-sensitive adenylate cyclase activation are related to parallel alterations in the density of beta adrenergic receptors and also to functional changes in nonreceptor components of the enzyme. The prevailing view that catecholamines stimulate hepatic glycogenolysis by an alpha adrenergic receptor-mediated, cyclic AMP-independent mechanism is based almost entirely on evidence from young adult male rats. We propose that current concepts of alpha adrenergic-responsive liver glycogenolysis underestimate a physiological role for beta adrenergic responsiveness over the majority of the life span. C1 FAIRFIELD HOSP,NATL HIV REF LAB,FAIRFIELD,VIC 3078,AUSTRALIA. JOHNS HOPKINS UNIV,FRANCIS SCOTT KEY MED CTR,SCH MED,DEPT MED,BALTIMORE,MD 21224. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. RP KATZ, MS (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN 182,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 49 TC 26 Z9 28 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL-OCT PY 1993 VL 28 IS 4-5 BP 329 EP 340 DI 10.1016/0531-5565(93)90060-Q PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA LQ417 UT WOS:A1993LQ41700005 PM 8224032 ER PT J AU HOFFMAN, D BREAKEFIELD, XO SHORT, MP AEBISCHER, P AF HOFFMAN, D BREAKEFIELD, XO SHORT, MP AEBISCHER, P TI TRANSPLANTATION OF A POLYMER-ENCAPSULATED CELL-LINE GENETICALLY-ENGINEERED TO RELEASE NGF SO EXPERIMENTAL NEUROLOGY LA English DT Article ID FIMBRIA-FORNIX TRANSECTION; CHOLINERGIC NEURONS; BRAIN; DOPAMINE; ACETYLTRANSFERASE; EXPRESSION; RETROVIRUS C1 BROWN UNIV,ARTIFICIAL ORGANS BIOMAT & CELLULAR TECHNOL SECT,PROVIDENCE,RI 02912. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. UNIV LAUSANNE,DIV SURG,CH-1000 LAUSANNE 17,SWITZERLAND. RI Aebischer, Patrick/E-1387-2013 FU NINDS NIH HHS [NS01251, NS24279, NS26159] NR 22 TC 106 Z9 107 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 1993 VL 122 IS 1 BP 100 EP 106 DI 10.1006/exnr.1993.1111 PG 7 WC Neurosciences SC Neurosciences & Neurology GA LR102 UT WOS:A1993LR10200011 PM 8339781 ER PT J AU SAGER, R ANISOWICZ, A NEVEU, M LIANG, P SOTIROPOULOU, G AF SAGER, R ANISOWICZ, A NEVEU, M LIANG, P SOTIROPOULOU, G TI IDENTIFICATION BY DIFFERENTIAL DISPLAY OF ALPHA-6 INTEGRIN AS A CANDIDATE TUMOR-SUPPRESSOR GENE SO FASEB JOURNAL LA English DT Note DE ALPHA-6 INTEGRIN; DIFFERENTIAL DISPLAY; POSITIVE SELECTION; TUMOR SUPPRESSOR GENES ID MAMMARY EPITHELIAL-CELLS; BREAST-CANCER; NEOPLASTIC BREAST; DOWN-REGULATION; EXPRESSION; ADHESION; CLONING; SUBUNIT; KERATINOCYTES; RECEPTORS AB A new method of differential expression cloning called differential display (DD) has been used to screen for novel tumor suppressor genes involved in breast cancer. The screen is based on positive selection at the mRNA level for genes expressed in normal mammary epithelial cells but decreased or lost in corresponding tumor cells. A candidate tumor suppressor gene recovered by DD is integrin alpha-6 (alpha6), a component of the heterodimeric integrin receptors alpha6beta1 and alpha6beta4. Loss of alpha6 expression was confirmed in total RNAs by Northern blot analysis and by immunostaining with alpha6 antibodies. Consistent with these cell culture findings, previous immunostaining of mammary tissue sections has identified decreased alpha6 protein expression during breast tumor progression. Southern blot analysis demonstrated that alpha6 gene is present in tumor cell lines, suggesting that re-expression may be inducible by pharmacological intervention. The likelihood that alpha6 may have tumor suppressing activity is supported by growing evidence of a central role for integrins in transducing growth control and differentiation signals from growth factors and the extracellular matrix (ECM). RP SAGER, R (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC GENET,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [P01 CA22427-15, R35 CA3981407] NR 33 TC 162 Z9 165 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 1993 VL 7 IS 10 BP 964 EP 970 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA LQ337 UT WOS:A1993LQ33700022 PM 8344495 ER PT J AU REIMER, P SAINI, S HAHN, PF COHEN, MS BRADY, TJ AF REIMER, P SAINI, S HAHN, PF COHEN, MS BRADY, TJ TI CLINICAL-APPLICATION OF ECHOPLANAR MRT IN DETECTING FOCAL LIVER-LESIONS - RESULTS OF A QUANTITATIVE STUDY SO FORTSCHRITTE AUF DEM GEBIETE DER RONTGENSTRAHLEN UND DER NEUEN BILDGEBENDEN VERFAHREN LA German DT Article DE LIVER; DETECTION; CONVENTIONAL MRI; ECHOPLANAR MRI ID MAGNETIC-RESONANCE; ARTERIAL PORTOGRAPHY; ECHO SEQUENCES; INSTANT IMAGES; FAISE METHOD; DELAYED CT; CONTRAST; FLASH; BODY; DIAGNOSIS AB The purpose of the present study was to investigate the clinical application of echoplanar MR imaging compared to conventional MR imaging in the detection of focal liver lesions. A total of three conventional and 12 echoplanar pulse sequences were acquired in 35 patients with focal liver lesions. Motion artifacts were eliminated because of short acquisition times of 32 ms subsequently improving signal-to-noise. A single-shot spin-echo technique with a TE of 26 ms provided the highest liver signal-to-noise ratio (p<0.05) of all sequences acquired. Contrast-to-noise ratios for a single-shot SE technique with echo times of 50-100 ms were as high as 10-40. C1 MASSACHUSETTS GEN HOSP, DEPT GASTROINTESTINAL RADIOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CTR MAGNET RESONANCE, BOSTON, MA 02114 USA. RP WESTFALISCHE WILHELMS UNIV, INST KLIN RADIOL, ALBERT SCHWEITZER STR 33, D-48149 MUNSTER, GERMANY. FU NCI NIH HHS [P01 CA48279] NR 40 TC 6 Z9 6 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0936-6652 J9 ROFO FORTSCHR RONTG JI Fortschritte Geb. Rontgenstr. Neuen Bildgebenden Verfahren PD JUL PY 1993 VL 159 IS 1 BP 16 EP 21 DI 10.1055/s-2008-1032714 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LP605 UT WOS:A1993LP60500004 PM 8334251 ER PT J AU LORENZSONN, V LLOYD, M OLSEN, WA AF LORENZSONN, V LLOYD, M OLSEN, WA TI IMMUNOCYTOCHEMICAL HETEROGENEITY OF LACTASE-PHLORHIZIN HYDROLASE IN ADULT LACTASE DEFICIENCY SO GASTROENTEROLOGY LA English DT Article ID IMMUNOELECTRON MICROSCOPY; SUCRASE-ISOMALTASE; SMALL-INTESTINE; EXPRESSION; HYPOLACTASIA; LOCALIZATION; ENTEROCYTES; RECEPTOR; ENZYMES; RATS C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR, GASTROENTEROL RES LAB, 2500 OVERLOOK TERRACE, MADISON, WI 53705 USA. UNIV WISCONSIN, DEPT MED, MADISON, WI 53706 USA. FU NIDDK NIH HHS [K08-DK01789, DK-13927] NR 20 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 1993 VL 105 IS 1 BP 51 EP 59 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LJ984 UT WOS:A1993LJ98400007 PM 8514062 ER PT J AU CIACCI, C LIND, SE PODOLSKY, DK AF CIACCI, C LIND, SE PODOLSKY, DK TI TRANSFORMING GROWTH-FACTOR-BETA REGULATION OF MIGRATION IN WOUNDED RAT INTESTINAL EPITHELIAL MONOLAYERS SO GASTROENTEROLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; TGF-BETA; EXPRESSION; FACTOR-BETA-1; REPAIR; PROLIFERATION; INHIBITION; ACTIVATION C1 MASSACHUSETTS GEN HOSP, GASTROINTESTINAL UNIT, JACKSON 7, 32 FRUIT ST, BOSTON, MA 02114 USA. BRIGHAM & WOMENS HOSP, DIV HEMATOL & ONCOL, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, NEW ENGLAND REG PRIMATE RES CTR, BOSTON, MA 02114 USA. RI ciacci, carolina/A-2594-2012 OI ciacci, carolina/0000-0002-7426-1145 FU NHLBI NIH HHS [R01HL42457]; NIDDK NIH HHS [R01DK41557, P30DK43351] NR 38 TC 226 Z9 230 U1 0 U2 1 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 JUL PY 1993 VL 105 IS 1 BP 93 EP 101 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LJ984 UT WOS:A1993LJ98400012 PM 8514065 ER PT J AU GRAHAM, DY GO, MF AF GRAHAM, DY GO, MF TI HELICOBACTER-PYLORI - CURRENT STATUS SO GASTROENTEROLOGY LA English DT Article ID PEPTIC-ULCERATION C1 VET ADM MED CTR 111D,DIV MOLEC VIROL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. RP GRAHAM, DY (reprint author), VET ADM MED CTR 111D,DEPT MED,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. FU NIDDK NIH HHS [DK 39919] NR 24 TC 196 Z9 202 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 1993 VL 105 IS 1 BP 279 EP 282 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LJ984 UT WOS:A1993LJ98400036 PM 8514046 ER PT J AU ZHU, L VANDENHEUVEL, S HELIN, K FATTAEY, A EWEN, M LIVINGSTON, D DYSON, N HARLOW, E AF ZHU, L VANDENHEUVEL, S HELIN, K FATTAEY, A EWEN, M LIVINGSTON, D DYSON, N HARLOW, E TI INHIBITION OF CELL-PROLIFERATION BY P107, A RELATIVE OF THE RETINOBLASTOMA PROTEIN SO GENES & DEVELOPMENT LA English DT Article DE P107; PRB; E1A; E2F; GROWTH SUPPRESSION ID LARGE-T-ANTIGEN; SV40 LARGE-T; E2F TRANSCRIPTION FACTOR; REGION 1A PROTEINS; GENE-PRODUCT; SUSCEPTIBILITY GENE; BINDING; CYCLE; PHOSPHORYLATION; ADENOVIRUS-E1A AB The cellular protein p107 shares many structural and biochemical features with the retinoblastoma gene product, pRB. We have isolated a full-length cDNA for human p107 and have used this clone to study the function of p107. We show that, like pRB, p107 is a potent inhibitor of E2F-mediated trans-activation, and overexpression of p107 can inhibit proliferation in certain cell types, arresting sensitive cells in G1. Several experiments, however, showed that growth inhibition by pRB and p107 did not occur through the same mechanism. First, in the cervical carcinoma cell line C33A, p107 was able to block cell proliferation, whereas pRB could not, even though both proteins were potent inhibitors of E2F-mediated transcription in this cell line. Second, growth arrest by pRB and p107 was rescued differentially by various cell cycle regulators. Third, some mutants of p107 that cannot associate with adenovirus E1A were still able to inhibit cell proliferation, whereas analogous mutants in pRB are known to be unable to block cell growth. Together, these results suggest a biological role of p107 that is related, but not identical, to that of pRB. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP ZHU, L (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129, USA. RI van den Heuvel, Sander/B-8892-2011 NR 63 TC 520 Z9 523 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 PY 1993 VL 7 IS 7A BP 1111 EP 1125 DI 10.1101/gad.7.7a.1111 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA LL403 UT WOS:A1993LL40300001 PM 8319904 ER PT J AU JOHNSON, RS VANLINGEN, B PAPAIOANNOU, VE SPIEGELMAN, BM AF JOHNSON, RS VANLINGEN, B PAPAIOANNOU, VE SPIEGELMAN, BM TI A NULL MUTATION AT THE C-JUN LOCUS CAUSES EMBRYONIC LETHALITY AND RETARDED CELL-GROWTH IN CULTURE SO GENES & DEVELOPMENT LA English DT Article DE AP-1 TRANSCRIPTION FACTOR; C-JUN LOCUS; EMBRYONIC LETHALITY; CELL GROWTH ID DNA-BINDING; FOS; EXPRESSION; GENES; AP-1 AB The AP-1 transcription factors are considered immediate-early response genes and are thought to be involved in a wide range of transcriptional regulatory processes linked to cellular proliferation and differentiation. To study one of the key members of this family, the proto-oncogene c-jun, we have used homologous recombination-mediated gene targeting to produce mice with a c-jun null mutation. c-jun null embryos die at mid-gestation, with an average time of death of 12.5 days postcoitus. Homozygous mutant embryos are indistinguishable from wild-type littermates both grossly and histologically until the time of death. However primary fibroblasts derived from live heterozygous and homozygous mutant embryos show greatly reduced growth rates in culture. The subnormal mitogenic response of these cells cannot be overcome by the addition of a number of purified mitogens. These studies indicate that although c-jun is not required for cellular proliferation and differentiation up to mid-gestation, it is required for survival past that stage as well as for the mitogenic response of embryonic fibroblasts in culture. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. TUFTS UNIV,SCH MED VET,DEPT PATHOL,BOSTON,MA 02111. OI Johnson, Randall/0000-0002-4084-6639 FU NICHD NIH HHS [HD24926, HD27295] NR 27 TC 318 Z9 318 U1 0 U2 2 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 PY 1993 VL 7 IS 7B BP 1309 EP 1317 DI 10.1101/gad.7.7b.1309 PG 9 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA LM680 UT WOS:A1993LM68000002 PM 8330736 ER PT J AU SHOFFNER, JM BROWN, MD TORRONI, A LOTT, MT CABELL, MF MIRRA, SS BEAL, MF YANG, CC GEARING, M SALVO, R WATTS, RL JUNCOS, JL HANSEN, LA CRAIN, BJ FAYAD, M RECKORD, CL WALLACE, DC AF SHOFFNER, JM BROWN, MD TORRONI, A LOTT, MT CABELL, MF MIRRA, SS BEAL, MF YANG, CC GEARING, M SALVO, R WATTS, RL JUNCOS, JL HANSEN, LA CRAIN, BJ FAYAD, M RECKORD, CL WALLACE, DC TI MITOCHONDRIAL-DNA VARIANTS OBSERVED IN ALZHEIMER-DISEASE AND PARKINSON DISEASE PATIENTS SO GENOMICS LA English DT Article ID HEREDITARY OPTIC NEUROPATHY; PRECURSOR PROTEIN GENE; COMPLEX-I DEFICIENCY; LEWY BODY DISEASE; TRANSFER RNALEU(UUR) GENE; SUBUNIT RIBOSOMAL-RNA; OXIDATIVE-PHOSPHORYLATION; RESPIRATORY-CHAIN; MATERNAL INHERITANCE; NUCLEOTIDE-SEQUENCE C1 EMORY UNIV,SCH MED,DEPT GENET & MOLEC MED,1462 CLIFTON RD,ROOM 403,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT NEUROL,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT PATHOL,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT LAB MED,ATLANTA,GA 30322. VET AFFAIRS MED CTR,DECATUR,GA 30033. UNIV CALIF SAN DIEGO,DEPT NEUROSCI,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT PATHOL,LA JOLLA,CA 92093. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27706. RI Torroni, Antonio/E-1557-2011 OI Torroni, Antonio/0000-0002-4163-4478 FU NHLBI NIH HHS [HL45572]; NIGMS NIH HHS [GM46915-01]; NINDS NIH HHS [NS21328] NR 122 TC 346 Z9 352 U1 0 U2 8 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUL PY 1993 VL 17 IS 1 BP 171 EP 184 DI 10.1006/geno.1993.1299 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA LN156 UT WOS:A1993LN15600025 PM 8104867 ER PT J AU CHENG, HM HUGHES, MS LASHKARI, K SANG, D YOSHIDA, A MCMEEL, JW BAKER, AS AF CHENG, HM HUGHES, MS LASHKARI, K SANG, D YOSHIDA, A MCMEEL, JW BAKER, AS TI PROTON MAGNETIC-RESONANCE SPECTROSCOPY OF VITREAL CHANGES IN EXPERIMENTAL STREPTOCOCCAL ENDOPHTHALMITIS SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article AB We used magnetic resonance spectroscopy to examine endophthalmitis in rabbits inoculated with a virulent strain of Streptococcus pneumoniae. On different days after infection, the animals were sacrificed and the vitreous isolated and examined with water-suppressed proton magnetic resonance spectroscopy. A broad resonance corresponding to the methyl envelope of lipoprotein lipids appeared 2 days after infection and persisted until the eyes developed phthisis (around 10 days postinfection). This resonance was absent in the control eye and the bacterial culture; it could be used as the marker of breakdown of blood-vitreous barrier and onset of endophthalmitis-induced changes. C1 HARVARD UNIV,SCH MED,HOWE LAB OPHTHALMOL,BOSTON,MA 02115. SCHEPENS EYE RES INST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INFECT UNIT,BOSTON,MA 02114. RP CHENG, HM (reprint author), MASSACHUSETTS EYE & EAR INFIRM,243 CHARLES ST,BOSTON,MA 02114, USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD JUL PY 1993 VL 231 IS 7 BP 402 EP 404 DI 10.1007/BF00919648 PG 3 WC Ophthalmology SC Ophthalmology GA LM329 UT WOS:A1993LM32900007 PM 8406065 ER PT J AU GOFF, BA RICE, LW FLEISCHHACKER, D MUNTZ, HG FALKENBERRY, SS NIKRUI, N FULLER, AF AF GOFF, BA RICE, LW FLEISCHHACKER, D MUNTZ, HG FALKENBERRY, SS NIKRUI, N FULLER, AF TI UTERINE LEIOMYOSARCOMA AND ENDOMETRIAL STROMAL SARCOMA - LYMPH-NODE METASTASES AND SITES OF RECURRENCE SO GYNECOLOGIC ONCOLOGY LA English DT Article ID MIXED MULLERIAN TUMOR; UTERUS; SPREAD; LINES; OVARY C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. RP GOFF, BA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,VINCENT GYNECOL ONCOL SERV,BOSTON,MA 02114, USA. NR 30 TC 105 Z9 112 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 1993 VL 50 IS 1 BP 105 EP 109 DI 10.1006/gyno.1993.1172 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA LT277 UT WOS:A1993LT27700020 PM 8349151 ER PT J AU JIMERSON, DC HERZOG, DB BROTMAN, AW AF JIMERSON, DC HERZOG, DB BROTMAN, AW TI PHARMACOLOGICAL APPROACHES IN THE TREATMENT OF EATING DISORDERS SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID COGNITIVE-BEHAVIORAL TREATMENT; NORMAL-WEIGHT BULIMIA; PLACEBO-CONTROLLED CROSSOVER; PRIMARY ANOREXIA-NERVOSA; DOUBLE-BLIND CROSSOVER; SHORT-TERM TREATMENT; OBESE BINGE-EATERS; L-TRYPTOPHAN; TREATING BULIMIA; CONTROLLED TRIAL AB Important advances in the treatment of eating disorders, particularly bulimia nervosa, have been made during the past decade. Controlled trials for bulimia nervosa have demonstrated significant benefit from short-term pharmacotherapy with antidepressant medications and from short-term individual and group psychotherapies. Despite these advances, treatment of a patient often involves complex clinical decisions around such issues as choice of initial treatment modality, incomplete resolution of symptoms, and the role of long-term maintenance treatment. To address these questions, this review focuses primarily on summarizing results of published controlled trials of pharmacotherapy in patients with bulimia nervosa. In addition, it outlines the more limited literature on controlled pharmacotherapy trials for anorexia nervosa and for the provisionally identified syndrome of binge eating disorder. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. RP JIMERSON, DC (reprint author), BETH ISRAEL HOSP,DEPT PSYCHIAT,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 111 TC 10 Z9 11 U1 2 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 1993 VL 1 IS 2 BP 82 EP 93 DI 10.3109/10673229309017063 PG 12 WC Psychiatry SC Psychiatry GA MU380 UT WOS:A1993MU38000002 PM 9384834 ER PT J AU COHEN, LS GREER, A APPELBAUM, PS AF COHEN, LS GREER, A APPELBAUM, PS TI ABORTION, PREGNANCY, AND MENTAL-ILLNESS - TREATMENT, LEGAL COMPETENCE, AND THERAPEUTIC INTERVENTIONS SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID EXPOSURE C1 MASSACHUSETTS GEN HOSP,CLIN PHARMACOL UNIT,PSYCHOSOMAT OBSTET & GYNECOL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CLIN RES PROGRAM,DEPT PERINATAL PSYCHIAT,BOSTON,MA 02115. UNIV MASSACHUSETTS,MED CTR,DEPT PSYCHIAT,BOSTON,MA 02125. NR 15 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 1993 VL 1 IS 2 BP 118 EP 122 DI 10.3109/10673229309017067 PG 5 WC Psychiatry SC Psychiatry GA MU380 UT WOS:A1993MU38000006 PM 9384838 ER PT J AU HAMILTON, GA SEIDMAN, RN AF HAMILTON, GA SEIDMAN, RN TI A COMPARISON OF THE RECOVERY PERIOD FOR WOMEN AND MEN AFTER AN ACUTE MYOCARDIAL-INFARCTION SO HEART & LUNG LA English DT Article AB Objectives: To compare return to work, participation in cardiac rehabilitation, and sexual activity in women and men recovering from acute myocardial infarction (AMI). Design: A descriptive survey design was used. Descriptive statistics and chi square analysis were used to compare differences between women and men after an AMI. Setting: The survey was mailed to the subject's home. Subjects: A purposive sample of 20 women and 42 men. Results: Comparing women with men, there were significant differences in the following activities with women evidencing higher percentages in responsibility for household duties before AMI, and cooking, washing dishes, reading, bed making, laundry, dusting and sweeping within 4 weeks after AMI. For those subjects who were sexually active before AMI, all resumed sexual activity after an average of 8 weeks. Women reported a decrease in frequency, less satisfactory relationship, and more reports of chest pain during sexual activity. Subjects reported that nurses gave little or no counseling concerning resumption of household activities, return to work issues, and sexual activity. Women received less counseling than men after AMI. Conclusions: The findings are not generalizable to the population at large; however, the study indicates a need to investigate further the recovery period for women who experience AMI. RP HAMILTON, GA (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 41 Z9 42 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0147-9563 J9 HEART LUNG JI Heart Lung PD JUL-AUG PY 1993 VL 22 IS 4 BP 308 EP 315 PG 8 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA LN687 UT WOS:A1993LN68700006 PM 8360065 ER PT J AU TESAR, GE AF TESAR, GE TI EMERGENCY PSYCHIATRY - THE AGITATED PATIENT .2. PHARMACOLOGICAL TREATMENT SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Article ID RAPID TRANQUILIZATION; AGGRESSIVE-BEHAVIOR; HALOPERIDOL; EFFICACY; ANTIPSYCHOTICS; MANAGEMENT; PSYCHOSIS C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP TESAR, GE (reprint author), MASSACHUSETTS GEN HOSP,ACUTE PSYCHIAT SERV,15 PARKMAN ST,ACC-815,BOSTON,MA 02114, USA. NR 29 TC 7 Z9 7 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD JUL PY 1993 VL 44 IS 7 BP 627 EP 629 PG 3 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA LL283 UT WOS:A1993LL28300005 PM 8354501 ER PT J AU HUDNALL, SD BERENSON, JR AF HUDNALL, SD BERENSON, JR TI CLONAL HEAVY-CHAIN ISOTYPE SWITCHING WITHIN THE PROLIFERATION CENTERS OF A SMALL LYMPHOCYTIC LYMPHOMA - IMPLICATIONS REGARDING THE ORIGIN OF PROLIFERATION CENTERS SO HUMAN PATHOLOGY LA English DT Article DE LYMPHOMA; PROLIFERATION CENTERS; IMMUNOGLOBULIN GENE REARRANGEMENT; CHRONIC LYMPHOCYTIC LEUKEMIA; ISOTYPE SWITCHING ID DIFFUSE HISTIOCYTIC LYMPHOMA; IMMUNOGLOBULIN GENE REARRANGEMENTS; EPSTEIN-BARR VIRUS; B-CELL CLONES; RICHTERS SYNDROME; MULTIPLE-MYELOMA; MALIGNANT-LYMPHOMA; PERIPHERAL-BLOOD; LIGHT-CHAINS; LEUKEMIA C1 UNIV CALIF LOS ANGELES, SCH MED, JONSSON CANC CTR, DEPT PATHOL, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, W LOS ANGELES VET ADM MED CTR,SCH MED, WADSWORTH CANC CTR,DEPT MED, LOS ANGELES, CA USA. NR 55 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUL PY 1993 VL 24 IS 7 BP 796 EP 801 DI 10.1016/0046-8177(93)90018-C PG 6 WC Pathology SC Pathology GA LL763 UT WOS:A1993LL76300018 PM 8319958 ER PT J AU RUBINSTEIN, JT AF RUBINSTEIN, JT TI AXON TERMINATION CONDITIONS FOR ELECTRICAL SIMULATION SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article ID MYELINATED NERVE-FIBERS; AUDITORY-NERVE; FOCAL ELECTRODES; STIMULATION; EXCITATION; CURRENTS; CAT AB The cable model for electrical stimulation near the terminal of a passive fiber is derived for excitation by an arbitrary, time-varying, -applied extracellular field. Unless the termination impedance is comparable to that of mamalian node of Ranvier, the end-conditions require the longitudinal intracellular current at the fiber terminal to be negligibly small. This requirement substantially alters the membrane potential profile from that obtained with a fiber of infinite length. Stimulation near the end of a fiber may result in lower thresholds and may reverse the anodal/cathodal threshold ratio obtained with stimulation in the mid-portion of the fiber. Chronaxie for stimulation near the terminal may be much smaller than at a distance from the terminal and the strength-duration curve may be nonmonotonic. These differences may have significant implications for any application of electrical stimulation where fiber terminations may play a role in the excitatory process. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP RUBINSTEIN, JT (reprint author), MASSACHUSETTS EYE & EAR INFIRM,COCHLEAR IMPLANT RES LAB,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC00361, DC00020] NR 22 TC 30 Z9 31 U1 1 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JUL PY 1993 VL 40 IS 7 BP 654 EP 663 DI 10.1109/10.237695 PG 10 WC Engineering, Biomedical SC Engineering GA MB594 UT WOS:A1993MB59400006 PM 8244426 ER PT J AU AOKI, Y ISSELBACHER, KJ PILLAI, S AF AOKI, Y ISSELBACHER, KJ PILLAI, S TI POLYMORPHISMS INVOLVING THE TRANSMEMBRANE DOMAINS OF HUMAN TAP2 SO IMMUNOGENETICS LA English DT Article ID CLASS-II REGION; MHC; TRANSPORTERS C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC IMMUNOL LAB,BLDG 149,13TH ST,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NIAID NIH HHS [AI-27835] NR 6 TC 21 Z9 21 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD JUL PY 1993 VL 38 IS 5 BP 382 EP 382 PG 1 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA LP122 UT WOS:A1993LP12200015 PM 8344728 ER PT J AU SANDERSON, IR OUELLETTE, AJ CARTER, EA WALKER, WA HARMATZ, PR AF SANDERSON, IR OUELLETTE, AJ CARTER, EA WALKER, WA HARMATZ, PR TI DIFFERENTIAL REGULATION OF B7 MESSENGER-RNA IN ENTEROCYTES AND LYMPHOID-CELLS SO IMMUNOLOGY LA English DT Article ID RAT SMALL-INTESTINE; T-CELLS; EPITHELIAL-CELLS; ANTIGEN; ACTIVATION; EXPRESSION; INTERLEUKIN-2; ANERGY; CD4 AB To investigate the molecular details of antigen presentation by cells of lymphoid or epithelial origin, we compared B7 mRNA regulation in intestinal epithelium with that in spleen, since both cell types express class II major histocompatibility complex (MHC) and present antigen. As measured by cDNA amplification using sequence-specific primers, I-Abeta mRNA content was found to be similar in mouse full-thickness small intestine, isolated intestinal epithelial cells and spleen. However, in contrast to I-Abeta, B7 mRNA intestinal epithelial cell content was markedly lower than in spleen and whole small bowel; cardiac RNA was negative for both sequences. Administration of intraperitoneal interferon-gamma (IFN-gamma) (10(5) U daily for 2 days) to adult mice resulted in an increase in I-Abeta mRNA in epithelial cells, but did not alter levels of B7 mRNA. In addition, exposure of the IEC-6 rat cell line to the IFN-7 resulted in a dose-dependent increase in I-Abeta mRNA without altering levels of B7 mRNA. Thus, an apparent dichotomy exists in regulation of B7 and I-Abeta gene expression in rodent intestinal epithelial cells. Since maximal T-cell response to splenocytes depends on B7, the absence of B7 mRNA in intestinal epithelium may be a factor in determining why antigen-presenting enterocytes normally do not elicit damaging T-cell proliferative responses. C1 SHRINERS BURNS RES CTR,CAMBRIDGE,MA. RP SANDERSON, IR (reprint author), MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,MUCOSAL IMMUNOL LAB,13TH ST,BOSTON,MA 02129, USA. FU NICHD NIH HHS [HD12437]; NIDDK NIH HHS [DK33506, DK34854] NR 22 TC 66 Z9 68 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JUL PY 1993 VL 79 IS 3 BP 434 EP 438 PG 5 WC Immunology SC Immunology GA LP362 UT WOS:A1993LP36200015 PM 7691725 ER PT J AU GONZALEZ, A OBERLEY, TD SCHULTZ, JL OSTROM, J LI, JJ AF GONZALEZ, A OBERLEY, TD SCHULTZ, JL OSTROM, J LI, JJ TI IN-VITRO CHARACTERIZATION OF ESTROGEN-INDUCED SYRIAN-HAMSTER RENAL TUMORS - COMPARISON WITH AN IMMORTALIZED CELL-LINE DERIVED FROM DIETHYLSTILBESTROL-TREATED ADULT HAMSTER-KIDNEY SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE CELL CULTURE; HAMSTER; RENAL TUMOR ID PROXIMAL TUBULAR CELLS; MULTICELLULAR SPHEROIDS; COVALENT BINDING; GOLDEN-HAMSTER; DEFINED MEDIA; RECEPTOR; GROWTH; DIFFERENTIATION; PROLIFERATION; CARCINOMA AB Primary diethylstilbestrol-induced kidney tumors from Syrian hamsters were grown in vitro and maintained in culture for 6 mo. Combined immunohistochemical studies using antibodies to intermediate filaments and ultrastructural studies of tumor cells in culture exhibited characteristics similar to tumor cells in vivo. Furthermore, the cells manifested transformed properties in culture; they grew both as multilayered colonies attached to the tissue culture substrate and as floating multicellular colonies (spheroids). When cultured cells were injected into diethylstilbestrol-treated recipient hamsters, tumors developed at the injection sites. In contrast, renal tubules or whole kidney cortex from control hamsters cultured in the same medium underwent only short-term growth, with senescence developing after approximately 1 mo. However, cell cultures of kidney cortex from animals treated in vivo for 5 mo. with diethylstilbestrol formed a cell line. This diethylstilbestrol-induced cell line has been maintained in culture for 1.5 yr and has the following characteristics: a) it is anchorage-dependent, b) it is negative in in vivo tumorigenicity tests, and c) cultured cells are histochemically and ultrastructurally similar to cultured tumor cells. This culture system should prove to be of use in studying hormonal carcinogenesis in vitro. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,PATHOL SECT,OVERLOOK TERRACE,MADISON,WI 53705. UNIV UTAH,SCH MED,DEPT PATHOL,SALT LAKE CITY,UT 84148. WILLIAM S MIDDLETON MEM VET ADM MED CTR,PATHOL SECT,MADISON,WI 53705. WASHINGTON STATE UNIV,COLL PHARM,DEPT PHARMACEUT SCI,HORMONAL CARCINOGENESIS LAB,PULLMAN,WA 99164. VET AFFAIRS MED CTR,LAB SERV,SALT LAKE CITY,UT 84148. FU NCI NIH HHS [CA-22008] NR 34 TC 7 Z9 7 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI UPPER MARLBORO PA 9315 LARGO DR W #255, UPPER MARLBORO, MD 20774-4755 SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD JUL PY 1993 VL 29A IS 7 BP 562 EP 573 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA LR944 UT WOS:A1993LR94400009 PM 7689078 ER PT J AU SMITH, DJ TAUBMAN, MA HOLMBERG, CF EASTCOTT, J KING, WF ALISALAAM, P AF SMITH, DJ TAUBMAN, MA HOLMBERG, CF EASTCOTT, J KING, WF ALISALAAM, P TI ANTIGENICITY AND IMMUNOGENICITY OF A SYNTHETIC PEPTIDE DERIVED FROM A GLUCAN-BINDING DOMAIN OF MUTANS STREPTOCOCCAL GLUCOSYLTRANSFERASE SO INFECTION AND IMMUNITY LA English DT Article ID SEQUENCE-ANALYSIS; SOBRINUS GLUCOSYLTRANSFERASE; GENE; PROTEIN; SUCROSE; IMMUNIZATION; ANTIBODIES; INGBRITT; COMPLEX AB The immunogenicity and antigenicity of a multiply antigenic peptide construct containing four copies of the synthetic peptide TGAQTIKGQKLYFKANGQQVKG were measured in rodents and humans, respectively. The composition of this peptide construct (termed GLU) was derived from a major repeating sequence in the C-terminal region of mutans streptococcal glucosyltransferases that synthesize water-insoluble glucan (GTF-I). The GLU peptide elicited high levels of serum immunoglobulin G antibody to GLU after subcutaneous injection into Sprague-Dawley rats. These antisera also reacted with intact GTF isozymes from Streptococcus sobrinus and Streptococcus mutans (by enzyme-linked immunosorbent assay [ELISA] and Western blot [immunoblot] analyses) and with an 87-kDa glucan-binding protein from S. sobrinus (by Western blot). The synthesis of filter-retained glucan by GTF-Sd of S. sobrinus could be inhibited (30%) by preincubation with anti-GLU rat serum. Splenic and lymph node lymphocytes from rats injected once with S. sobrinus GTF isozymes demonstrated significant proliferation after 5 days of culture with GLU. The GLU peptide reacted with 4 of 29 human parotid saliva samples and 5 of 29 human serum samples (by ELISA). These results suggest that the GLU peptide contains B- and T-cell epitopes that are similar to those of intact mutans streptococcal GTFs and possibly certain other glucan-binding proteins as well. Furthermore, since antibody to this epitope(s) appears to inhibit GTF function, sequences within this peptide construct may have value for inclusion in a synthetic dental caries vaccine. RP SMITH, DJ (reprint author), FORSYTH DENT CTR,DEPT IMMUNOL,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-04733] NR 35 TC 40 Z9 42 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 JUL PY 1993 VL 61 IS 7 BP 2899 EP 2905 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LJ343 UT WOS:A1993LJ34300022 PM 8514393 ER PT J AU HONDALUS, MK DIAMOND, MS ROSENTHAL, LA SPRINGER, TA MOSSER, DM AF HONDALUS, MK DIAMOND, MS ROSENTHAL, LA SPRINGER, TA MOSSER, DM TI THE INTRACELLULAR BACTERIUM RHODOCOCCUS-EQUI REQUIRES MAC-1 TO BIND TO MAMMALIAN-CELLS SO INFECTION AND IMMUNITY LA English DT Article ID ENCAPSULATED STAPHYLOCOCCUS-AUREUS; MONOCYTE COMPLEMENT RECEPTORS; LISTERIA-MONOCYTOGENES; LEGIONELLA-PNEUMOPHILA; MONOCLONAL-ANTIBODIES; 3RD COMPONENT; LEISHMANIA PROMASTIGOTES; MEDIATED PHAGOCYTOSIS; LEUKOCYTE INTEGRINS; COUNTER-RECEPTOR AB Rhodococeus equi is a facultative intracellular bacterium of macrophages that causes disease in immunocompromised individuals, particularly those with AIDS. In this report, we demonstrate that R. equi binding to mammalian cells requires complement and is mediated primarily by the leukocyte complement receptor, Mac-1. Bacteria bind to macrophages poorly unless exogenous complement is added to the incubation medium. The addition of fresh nonimmune serum, which contains no detectable antibodies to R. equi, greatly enhances bacterial binding to macrophages, whereas heat inactivation of this serum or immunological depletion of C3 from the serum reduces binding to levels only slightly higher than those of binding under serum-free conditions. Human serum depleted of C2 or C4 is fully opsonic, indicating that complement activation and fixation occur by the alternative pathway. The serum-dependent binding of rhodococci to macrophages is mediated primarily by the macrophage complement receptor type 3, Mac-1 (CD11b/CD18). Bacteria do not bind to fibroblastoid or epithelial cells that lack this receptor. Most of the bacterial binding to macrophages is inhibited by a monoclonal antibody to Mac-1 but is unaffected by a monoclonal antibody to complement receptor type 1. Furthermore, opsonized, but not unopsonized, bacteria bind to purified Mac-1 immobilized on plastic. In addition, in the presence of opsonic complement, rhodococci bind efficiently to fibroblastoid cells transfected with cloned Mac-1 but relatively poorly to cells transfected with the complement receptor type 1. Hence, R. equi fixes complement by activating the alternative complement pathway, and this fixation is a requirement for bacterial adhesion and invasion. Furthermore, complement fixation defines rhodococcal host cell tropism, since R. equi binds specifically and exclusively to cells expressing Mac-1. C1 TEMPLE UNIV,HLTH SCI CTR,SCH MED,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19140. CTR BLOOD RES,COMM CELL & DEV BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Rosenthal, Louis/A-8868-2008; Mosser, David/I-6697-2016 OI Mosser, David/0000-0002-9503-4187 FU NCI NIH HHS [CA-31799]; NIAID NIH HHS [AI-O100101, AI-24313] NR 65 TC 58 Z9 59 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1993 VL 61 IS 7 BP 2919 EP 2929 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LJ343 UT WOS:A1993LJ34300025 PM 8514396 ER PT J AU RAMESH, N FULEIHAN, R RAMESH, V LEDERMAN, S YELLIN, MJ SHARMA, S CHESS, L ROSEN, FS GEHA, RS AF RAMESH, N FULEIHAN, R RAMESH, V LEDERMAN, S YELLIN, MJ SHARMA, S CHESS, L ROSEN, FS GEHA, RS TI DELETIONS IN THE LIGAND FOR CD40 IN X-LINKED IMMUNOGLOBULIN DEFICIENCY WITH NORMAL OR ELEVATED IGM (HIGMX-1) SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CD40 LIGAND; DELETIONS; HIGMX-1 ID B-CELL DIFFERENTIATION; T-CELLS; GENE; IMMUNODEFICIENCY; EXTRACTION; MUTATION; PROTEIN; RNA; DNA AB Patients with X-linked Ig deficiency with normal or elevated IgM (HIGMX-1) fail to switch from IgM/IgD to other Ig isotypes. Interaction between the B cell antigen CD40 and the CD40 ligand expressed on activated T cells is critical for T cell driven isotype switching. We have reported that T lymphocytes from three unrelated male patients with HIGMX-1 failed to express CD40 ligand on their surface, but the mRNA for CD40 ligand was of an apparently normal size and level. Analysis of CD40 ligand cDNA from two of the patients revealed deletions that alter the reading frame. Patient 1 displayed two mutations: a C --> A transversion at nucleotide 590 and the deletion of an adjacent C nucleotide. The second patient had a 58 bp deletion from nucleotides 289-346. Furthermore, neither patient expressed a protein product detectable by the CD40L mAb, 5c8. C1 MASSACHUSETTS GEN HOSP,NEUROGENET LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RP RAMESH, N (reprint author), CHILDRENS HOSP MED CTR,DIV IMMUNOL,ENDERS 8,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 23 TC 66 Z9 66 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 JUL PY 1993 VL 5 IS 7 BP 769 EP 773 DI 10.1093/intimm/5.7.769 PG 5 WC Immunology SC Immunology GA LP113 UT WOS:A1993LP11300009 PM 8103673 ER PT J AU BOTT, CM DOSHI, JB MORIMOTO, C ROMAIN, PL FOX, DA AF BOTT, CM DOSHI, JB MORIMOTO, C ROMAIN, PL FOX, DA TI ACTIVATION OF HUMAN T-CELLS THROUGH CD6 - FUNCTIONAL-EFFECTS OF A NOVEL ANTI-CD6 MONOCLONAL-ANTIBODY AND DEFINITION OF 4 EPITOPES OF THE CD6 GLYCOPROTEIN SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE PROTEIN KINASE-C; T-LYMPHOCYTE ACTIVATION ID PROTEIN-KINASE-C; HUMAN LYMPHOCYTES-T; CROSS-LINKING; DIFFERENTIATION ANTIGEN; INOSITOL PHOSPHATES; RECEPTOR COMPLEX; PHOSPHORYLATION; EXPRESSION; PATHWAY; PROLIFERATION AB The CD6 glycoprotein is expressed primarily on lymphocytes and conveys co-activating signals to T cells, but its exact function and ligand(s) are unknown. A novel mAb, termed UMCD6, was demonstrated to recognize CD6 by immunoprecipitation, Western blotting, and reactivity with COS cells transfected with CD6 cDNA. UMCD6 was mitogenic for T cells and was strongly synergistic with phorbol ester in inducing T cell activation. UMCD6 enhanced the autologous mixed lymphocyte reaction as previously observed with another anti-CD6 mAb, anti-T12. The activating effects of UMCD6 were more striking than those of other anti-CD6 mAbs and encompassed all of the diverse stimulatory properties previously reported for other anti-CD6 reagents. However, neither UMCD6 nor other anti-CD6 antibodies alone or in combination with phorbol ester or IL-2 were able to induce thymocytes to proliferate. Stimulation by UMCD6 is dependent on accessory cell function in a manner not accounted for simply by antibody cross-linking. UMCD6 did not induce an increase in cytoplasmic free Ca2+, but the CD6 activation pathway appears to involve protein kinase C. UMCD6 and a panel of seven other anti-CD6 mAbs were used in a series of experiments to define four discrete epitopes of CD6 using the criteria of antibody cross-blocking, reactivity on reduced Western blots, and resistance to controlled V8 protease digestion. The functional mAbs UMCD6, 2H1, and anti-T12 each recognized a different epitope. Taken together, the results of these studies strongly reinforce the hypothesis that CD6 plays a significant and distinct role in T cell activation, and suggest that multiple regions of CD6 may be functionally active. C1 UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,DIV RHEUMATOL,SPECIALIZED CTR RES RHEUMATOID ARTHRITIS,ANN ARBOR,MI 48109. UNIV MASSACHUSETTS,MED CTR,DEPT MED,DIV RHEUMATOL,WORCESTER,MA 01655. UNIV MICHIGAN,MED CTR,CTR MULTIPURPOSE ARTHRITIS,ANN ARBOR,MI 48109. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV TUMOR IMMUNOL,BOSTON,MA 02115. FU NIAMS NIH HHS [AR41703, AR 38477, AR20557] NR 47 TC 48 Z9 48 U1 1 U2 3 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 JUL PY 1993 VL 5 IS 7 BP 783 EP 792 DI 10.1093/intimm/5.7.783 PG 10 WC Immunology SC Immunology GA LP113 UT WOS:A1993LP11300011 PM 7690243 ER PT J AU RINALDI, MG AF RINALDI, MG TI IN-VITRO SUSCEPTIBILITY OF DERMATOPHYTES TO ANTIFUNGAL DRUGS SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Note C1 AUDIE L MURPHY MEM VET ADM MED CTR,DEPT VET AFFAIRS MYCOL REFERENCE LAB,SAN ANTONIO,TX. RP RINALDI, MG (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD JUL PY 1993 VL 32 IS 7 BP 502 EP 503 DI 10.1111/j.1365-4362.1993.tb02833.x PG 2 WC Dermatology SC Dermatology GA LK425 UT WOS:A1993LK42500005 PM 8340184 ER PT J AU WELCH, G THOMPSON, L HALL, A AF WELCH, G THOMPSON, L HALL, A TI THE BULIT-R - ITS RELIABILITY AND CLINICAL VALIDITY AS A SCREENING TOOL FOR DSM-III-R BULIMIA-NERVOSA IN A FEMALE TERTIARY EDUCATION POPULATION SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article ID ANOREXIA-NERVOSA; COLLEGE-STUDENTS; EATING DISORDERS; PREVALENCE; VALIDATION; INVENTORY AB The Bulimia Test (BULIT) has been updated to accommodate the DSM-III-R criteria for bulimia nervosa. Therefore, in this study, we evaluated the psychometric properties of the BULIT-R using a sample of young women at a tertiary educational institute. The results showed all 28 BULIT-R items correlated highly with the total test score (average = .59) and the internal reliability was high (.92). In terms of its concurrent validity, the BULIT-R correlated highly (.90) with the Bulimia Investigatory Test Edinburgh (BITE), a screening measure argued to detect bulimia nervosa. In terms of criterion-related validity, the optimal cutoff for the BULIT-R as a screening measure was 98 with this sample, using a semistructured DIS-III R interview administered by experienced clinicians who specialize in eating disorders. At this cutoff, the sensitivity was 100%, the specificity 99.0%, the negative predictive value 100%, and the positive predictive value 71.3%. (c) 1993 by John Wiley & Sons, Inc. C1 PORIRUA HOSP,WELLINGTON,NEW ZEALAND. WELLINGTON SCH MED,DEPT PSYCHOL MED,WELLINGTON,NEW ZEALAND. RP WELCH, G (reprint author), JOSLIN DIABET CTR,MENT HLTH UNIT,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 28 TC 34 Z9 35 U1 1 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD JUL PY 1993 VL 14 IS 1 BP 95 EP 105 DI 10.1002/1098-108X(199307)14:1<95::AID-EAT2260140113>3.0.CO;2-Z PG 11 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA LJ738 UT WOS:A1993LJ73800012 PM 8339105 ER PT J AU COLLINS, MD FACKLAM, RR RODRIGUES, UM RUOFF, KL AF COLLINS, MD FACKLAM, RR RODRIGUES, UM RUOFF, KL TI PHYLOGENETIC ANALYSIS OF SOME AEROCOCCUS-LIKE ORGANISMS FROM CLINICAL SOURCES - DESCRIPTION OF HELCOCOCCUS-KUNZII GEN-NOV, SP-NOV SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID 16S RIBOSOMAL-RNA; LACTIC-ACID BACTERIA; SEQUENCE-ANALYSIS; STREPTOCOCCUS; INFECTIONS AB 16S rRNA gene sequencing studies were performed on some unusual gram-positive catalase-negative cocci of unknown taxonomic position isolated from human clinical sources. Comparative analysis of the sequence data demonstrated that the clinical isolates represent a hitherto-unknown line of descent within the low-G+C-content gram-positive bacteria. On the basis of the phylogenetic findings and the phenotypic distinctiveness of the organisms, it is proposed that they be classified in a new genus, Helcococcus, as Helcococcus kunzii sp. nov. The type strain of H. kunzii is NCFB 2900. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. INST FOOD RES, READING LAB, READING RG6 2EF, ENGLAND. CTR DIS CONTROL, ATLANTA, GA 30333 USA. NR 26 TC 57 Z9 60 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1993 VL 43 IS 3 BP 425 EP 429 PG 5 WC Microbiology SC Microbiology GA LM382 UT WOS:A1993LM38200005 PM 8347503 ER PT J AU DEWHIRST, FE CHEN, CKC PASTER, BJ ZAMBON, JJ AF DEWHIRST, FE CHEN, CKC PASTER, BJ ZAMBON, JJ TI PHYLOGENY OF SPECIES IN THE FAMILY NEISSERIACEAE ISOLATED FROM HUMAN DENTAL PLAQUE AND DESCRIPTION OF KINGELLA-ORALE SP-NOV SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID RIBOSOMAL-RNA SEQUENCES; OLIGODEOXYNUCLEOTIDE PROBES; EIKENELLA-CORRODENS; PROTEOBACTERIA; STRAINS; CAVITY AB Fourteen human periodontal isolates recovered from a purported Eikenella corrodens-selective medium containing 1 mug of clindamycin per ml displayed biochemical traits which differed from those described for E. corrodens. These organisms were gram-negative rods which corroded agar. The isolates were oxidase positive and urease, indole, and esculin negative. They differed from E. corrodens in catalase, nitrate reduction, lysine decarboxylase, and ornithine decarboxylase activities. One isolate, strain UB-294, was presumptively identified as Kingella denitrificans. A second isolate, strain UB-204, differed from E. corrodens by being catalase positive and nitrate reduction negative. Twelve isolates, including strain UB-38 T (T = type strain), were phenotypically similar to Kingella kingae except that they did not produce acid from maltose and were not beta-hemolytic. Essentially complete (1,480-base) 16S rRNA sequences were determined for strains UB-38T, UB-204, and UB-294 and the type strains of Neisseria animalis, Neisseria canis, Neisseria denitrificans, Neisseria elongata, Neisseria flavescens, Neisseria macaca, and Neisseria polysaccharea. These sequences were compared with the previously published sequences of six other species belonging to the family Neisseriaceae. On the basis of the results of the comparative sequence analysis, UB-294 was confirmed as a K. denitrificans strain, UB-204 was identified as a member of a new species which may belong in the genus Eikenella, and UB-38T was identified as a member of a new species of the genus Kingella, for which we propose the name Kingella orale. Since strain UB-204 was the only representative of a new species, it was not named. DNA probes for identification of E. corrodens, K. denitrificans, and K. orale based on 16S rRNA sequence information are described. C1 SUNY Buffalo, SCH DENT MED, DEPT ORAL BIOL & PERIODONTOL, BUFFALO, NY 14214 USA. RP DEWHIRST, FE (reprint author), FORSYTH DENT CTR, DEPT MOLEC GENET, 140 FENWAY, BOSTON, MA 02115 USA. FU NIDCR NIH HHS [DE-04881, DE-08303, DE-04898] NR 25 TC 25 Z9 25 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1993 VL 43 IS 3 BP 490 EP 499 PG 10 WC Microbiology SC Microbiology GA LM382 UT WOS:A1993LM38200014 PM 8347509 ER PT J AU RHEA, JT SZTUCINSKI, K AF RHEA, JT SZTUCINSKI, K TI HOW TO IMPLEMENT A RADIOLOGY QUALITY IMPROVEMENT PROGRAM - PEARLS AND PITFALLS SO INVESTIGATIVE RADIOLOGY LA English DT Editorial Material RP RHEA, JT (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 6 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUL PY 1993 VL 28 IS 7 BP 639 EP 642 DI 10.1097/00004424-199307000-00016 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LK643 UT WOS:A1993LK64300012 PM 8344815 ER PT J AU BISWAS, DK DEZUBE, BJ AHLERS, CM PARDEE, AB AF BISWAS, DK DEZUBE, BJ AHLERS, CM PARDEE, AB TI PENTOXIFYLLINE INHIBITS HIV-1 LTR-DRIVEN GENE-EXPRESSION BY BLOCKING NF-KAPPA-B ACTION SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE PENTOXIFYLLINE; NF-KAPPA-B; HIV-1 LTR; STABLE TRANSFECTION; TRANSIENT TRANSFECTION ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR NECROSIS FACTOR; LONG TERMINAL REPEAT; BINDING PROTEIN; T-CELLS; TRANSCRIPTION; REPLICATION; ACTIVATION; INDUCTION; INVITRO AB The drug pentoxifylline (PTX) (1-(5'-oxohexyl) 3,7-dimethylxanthine) down-regulates human immunodeficiency virus (HIV-1) long terminal repeat (LTR)-directed gene expression in the human monocytic cell line U38. This effect of PTX has been tested in clinical trials. In this investigation, a similar inhibitory effect of PTX on HIV-1 LTR-driven gene expression was observed (a) in a stable transfectant of the human embryo kidney cell line 293-27-2 carrying an expression plasmid construct with the HIV-1 LTR fused to the bacterial lac Z gene, and also (b) by transient transfection of human embryo kidney cells 293 S with fusion plasmid constructs with wild-type [pHIV-LTR-chloramphenicol acetyltransferase (CAT)] or mutated (pHIV-LTR-mut-CAT) nuclear factor kappaB (NF-kappaB) motifs. In both stable and transient transfection studies, 4-beta-phorbol-12-beta-myristate-acetate (PMA)-induced or tumor necrosis factor-alpha (TNF-alpha)-induced activation of the HIV-1 LTR was correlated with a concomitant elevated level of NF-kappaB interaction with its motifs. The inducibility of HIV-1 LTR-driven gene expression by PMA or TNF-alpha in transiently transfected celts was completely eliminated by point mutations in the NF-KB motifs, suggesting that NF-KB plays a major role in the activation of the HIV-1 LTR by these agents in this cell system. Treatment of PMA-activated or TNF-alpha-activated cells with PFX, at concentrations that did not affect cell growth or other major cellular activities, strongly inhibited NF-KB interaction with its motifs and was followed by down-regulation of HIV-1 LTR-driven lac Z gene expression. PTX did not inhibit Rous sarcoma virus (RSV) LTR-driven CA T gene expression, suggesting a differential action of the drug on the NF-kappaB motif-carrying HIV-1 LTR. It is concluded that the antiviral action of the drug is, in a major part, mediated via interference with one or more of the steps of NF-kappaB activation and interaction with its motifs in the HIV-1 LTR sequence. These results implicate a role of the nuclear factor NF-KB in the mode of action of the drug PTX against HIV-1. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT MED,DIV HEMATOL & ONCOL,BOSTON,MA 02215. RP BISWAS, DK (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,ROOM 810A,44 BINNEY ST,BOSTON,MA 02115, USA. NR 30 TC 61 Z9 61 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 JUL PY 1993 VL 6 IS 7 BP 778 EP 786 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LH852 UT WOS:A1993LH85200004 PM 8509980 ER PT J AU DEZUBE, BJ PARDEE, AB CHAPMAN, B BECKETT, LA KORVICK, JA NOVICK, WJ CHIURCO, J KASDAN, P AHLERS, CM ECTO, LT CRUMPACKER, CS AF DEZUBE, BJ PARDEE, AB CHAPMAN, B BECKETT, LA KORVICK, JA NOVICK, WJ CHIURCO, J KASDAN, P AHLERS, CM ECTO, LT CRUMPACKER, CS TI PENTOXIFYLLINE DECREASES TUMOR-NECROSIS-FACTOR EXPRESSION AND SERUM TRIGLYCERIDES IN PEOPLE WITH AIDS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV; TUMOR NECROSIS FACTOR; PENTOXIFYLLINE; CYTOKINES; TRIGLYCERIDES ID IMMUNODEFICIENCY-VIRUS TYPE-1; BONE-MARROW TRANSPLANTATION; BLOOD MONONUCLEAR-CELLS; FACTOR-ALPHA; CANCER-PATIENTS; T-CELLS; CACHECTIN; INDUCTION; HYPERTRIGLYCERIDEMIA; REPLICATION AB Tumor necrosis factor-alpha (TNF)-cachectin increases the expression of the human immunodeficiency virus (HIV), reverses the therapeutic efficacy of zidovudine (ZDV), and may contribute to the wasting syndrome. Pentoxifylline (Trental) decreases TNF activity; in cell culture, it decreases HIV replication and down-regulates expression of the HIV long terminal repeat (LTR). Therefore, pentoxifylline was administered to 25 patients with advanced AIDS in this AIDS Clinical Trial Group study (ACTG # 160), the goal of which was to investigate the ability of the drug to decrease TNF expression and HIV replication in this patient population. One patient discontinued drug treatment because of toxicity. Data were analyzed on the 17 patients who completed the 8-week study treatment with pentoxifylline, 400 mg, thrice daily. The median pretreatment CD4+ lymphocyte count was 32 cells/mm3. Fasting serum triglycerides, which have previously been shown to correlate with levels of interferon-alpha and/or TNF, fell on average by 66 mg/dl (p = 0.06). TNF mRNA levels in peripheral blood mononuclear cells fell in 10 of 16 patients (p = 0.02). HIV load decreased and increased significantly in four and one patients, respectively, but did not change in the group as a whole. This study demonstrates the safety of pentoxifylline in AIDS patients and its ability to decrease triglycerides and TNF mRNA levels. C1 BETH ISRAEL HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,DIV INFECT DIS,BOSTON,MA 02215. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. NIAID,DIV AIDS,BETHESDA,MD 20892. ACTG OPERAT OFF,ROCKVILLE,MD. HOECHST ROUSSEL PHARMACEUT PROPRIETARY LTD,SOMERVILLE,NJ 08876. RP DEZUBE, BJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,D810A,BOSTON,MA 02115, USA. FU NIAID NIH HHS [N0-AI-62534, N0-AI-95030] NR 39 TC 101 Z9 101 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 JUL PY 1993 VL 6 IS 7 BP 787 EP 794 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LH852 UT WOS:A1993LH85200005 PM 8099612 ER PT J AU SHARKEYMATHIS, PK VELEZ, J FETCHICK, R GRAYBILL, JR AF SHARKEYMATHIS, PK VELEZ, J FETCHICK, R GRAYBILL, JR TI HISTOPLASMOSIS IN THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME (AIDS) - TREATMENT WITH ITRACONAZOLE AND FLUCONAZOLE SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HISTOPLASMOSIS; AZOLES; ITRACONAZOLE; FLUCONAZOLE; AMPHOTERICIN-B ID IMMUNE-DEFICIENCY-SYNDROME; PROGRESSIVE DISSEMINATED HISTOPLASMOSIS; OPPORTUNISTIC INFECTIONS; ADRENAL INSUFFICIENCY; KETOCONAZOLE THERAPY; SYSTEMIC MYCOSES; AMPHOTERICIN-B; PARACOCCIDIOIDOMYCOSIS; COMPLICATION; DIAGNOSIS AB The manifestations of histoplasmosis in 20 patients with the acquired immunodeficiency syndrome are presented. In this series, patients were treated with either itraconazole or fluconazole. Twelve patients received treatment with itraconazole at 400 mg/day, including two patients who had not responded to treatment with fluconazole at 100 mg/day. Of the responses, seven were classified as remissions (mean treatment duration of 24 months), two as improvements, and three as failures. Ten patients received fluconazole. Of the responses, three were classified as remissions (mean treatment duration of 12 months), one as improvement, and six as failures. Of the 10 patients treated with fluconazole, five received doses of 100 mg/day, and five were given doses of 400 or 800 mg/day. The differences in outcome among the five patients receiving the lower dose of fluconazole (one remission, one improvement, and three failures) and the five patients given the higher doses of fluconazole (two remissions and three failures) were negligible. One other patient showed signs of histoplasmosis while receiving fluconazole at 50 mg/day for treatment of thrush. Three failures (two treated with itraconazole and one with fluconazole) followed lapses in azole therapy because of associated conditions. Azole therapy was well tolerated. The treatment responses in this pilot series appear promising in comparison with those reported in the literature with amphotericin B or ketoconazole. C1 AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,SAN ANTONIO,TX 78284. RP SHARKEYMATHIS, PK (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV INFECT DIS,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NCRR NIH HHS [M01-RR-01346] NR 65 TC 40 Z9 40 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 JUL PY 1993 VL 6 IS 7 BP 809 EP 819 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LH852 UT WOS:A1993LH85200007 PM 8389850 ER PT J AU TSUZAKI, K HALES, CA STRIEDER, DJ VENEGAS, JG AF TSUZAKI, K HALES, CA STRIEDER, DJ VENEGAS, JG TI REGIONAL LUNG-MECHANICS AND GAS-TRANSPORT IN LUNGS WITH INHOMOGENEOUS COMPLIANCE SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE GAS TRANSPORT MECHANISMS; REGIONAL VENTILATION DISTRIBUTION; POSITRON IMAGING; DOGS ID HIGH-FREQUENCY VENTILATION; RESPIRATORY SYSTEM; TIDAL VOLUME; IMPEDANCE; DOGS; MODEL; OSCILLATION; RESISTANCE AB The effect of respiratory frequency (f) on the distributions of ventilation, regional gas transport, lung volume, and regional impedance was assessed with positron imaging in lungs with nonuniform lung mechanics after unilateral lung lavage. Supine dogs were studied during eucapnic oscillatory ventilation at f between 1 and 15 Hz and at a constant mean airway pressure of 5 cmH2O. Substantial differences in mean lung volume and tidal volume (VT) between lavaged and control lungs were found at all f values, but pendel-luft never exceeded 2% of mouth flow. For f less-than-or-equal-to 10 Hz, VT distributed in direct proportion to lung volume, whereas gas transport per unit of lung volume, measured from washout maneuvers, was reduced by 20% in the lavaged lung. At 15 Hz, however, the distributions Of VT and gas transport approached equality between both lungs. Regional impedance was analyzed with a model that included a Newtonian resistance, an inertance, and Hildebrandt's model of tissue viscoelasticity. The data obtained from this work provide useful insights with respect to the mechanisms of gas transport during high-frequency ventilation and suggest the impact of operating frequency in clinical situations where substantial interregional heterogeneity in lung compliance could be expected. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT BIOMED ENGN,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-38267] NR 30 TC 22 Z9 22 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 1993 VL 75 IS 1 BP 206 EP 216 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA LN649 UT WOS:A1993LN64900029 PM 8376266 ER PT J AU CHEN, TY ZAPOL, WM GREENE, E ROBINSON, DR RUBIN, RH AF CHEN, TY ZAPOL, WM GREENE, E ROBINSON, DR RUBIN, RH TI PROTECTIVE EFFECTS OF E5, AN ANTIENDOTOXIN MONOCLONAL-ANTIBODY, IN THE OVINE PULMONARY CIRCULATION SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE LIPOPOLYSACCHARIDE; ESCHERICHIA-COLI; SERRATIA-MARCESCENS ID GRAM-NEGATIVE BACTEREMIA; MUTANT ESCHERICHIA-COLI; CROSS-REACTIVITY; SEPTIC SHOCK; SALMONELLA-MINNESOTA; AWAKE SHEEP; LIPOPOLYSACCHARIDE; ENDOTOXIN; SEPSIS; CORE AB The cross-protective effects of a murine immunoglobulin M monoclonal antilipid A antibody (E5 MAb) were tested by challenging awake sheep with mixtures of in vitro incubated E5 MAb (0.02 mg/kg) with lipopolysaccharide (LPS, 0.02 mug/kg) derived from Escherichia coli O111:B4, E. coli 055:B5, or Serratia marcescens. Intravenous infusion of these LPS preparations without antibody into awake sheep produced a similar pattern of fever, leukopenia, plasma thromboxane B2 (TxB2) release, and acute pulmonary vasoconstriction with pulmonary hypertension. The addition of MAb E5 to LPS from E. coli O111:B4 reduced these responses to the LPS in a fashion comparable to that achieved with an MAb specific to the E. coli O111:B4 O-side chain. Incubation of LPS derived from E. coli 055:B5 with the E5 MAb only slightly diminished acute pulmonary hypertension, the delayed temperature increase, and the degree of leukopenia (all P = NS) but reduced the mean peak TxB, at 60 min (P < 0.05) compared with a control infusion of E. coli 055:B5 LPS. We were unable to demonstrate any protective effects on the pulmonary circulation from incubating E5 with LPS derived from S. marcescens. Preincubation of B55 MAb (a murine immunoglobulin M MAb directed against a human milk fat globulin), the control antibody, with LPS from E. coli O111:B4 decreased the mean peak TxB2 but had no effect on the other parameters. We conclude that incubating E5 with LPS protects the pulmonary circulation of sheep from challenge with LPS derived from the parent E. coli strain. There were trends toward protection by E5 against LPS from 055:B5 E. coli, but these did not reach statistical significance. There was no protection against a distantly related species of the enterobacteria S. marcescens. These observations suggest that E5 has different neutralizing efficacies against LPS-induced toxicity due to different gram-negative bacterial species and strains. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CLIN INVEST PROGRAM,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. NR 33 TC 9 Z9 9 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 1993 VL 75 IS 1 BP 233 EP 239 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA LN649 UT WOS:A1993LN64900032 PM 8376269 ER PT J AU QVIST, J HURFORD, WE PARK, YS RADERMACHER, P FALKE, KJ AHN, DW GUYTON, GP STANEK, KS HONG, SK WEBER, RE ZAPOL, WM AF QVIST, J HURFORD, WE PARK, YS RADERMACHER, P FALKE, KJ AHN, DW GUYTON, GP STANEK, KS HONG, SK WEBER, RE ZAPOL, WM TI ARTERIAL BLOOD-GAS TENSIONS DURING BREATH-HOLD DIVING IN THE KOREAN AMA SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE ARTERIAL CARBON DIOXIDE TENSION; ARTERIAL OXYGEN TENSION; BREATH HOLDING; BREATH-HOLD TIME; EXERCISE; HEMOGLOBIN; WATER IMMERSION ID HEMOGLOBIN; DIVERS; EXCHANGE; PIG AB Korean female unassisted divers (cachido ama) breath-hold dive >100 times to depths of 3-7 m during a work day. We sought to determine the extent of arterial hypoxemia during normal working dives and reasonable time limits for breath-hold diving by measuring radial artery blood gas tensions and pH in five cachido ama who dove to a fixed depth of 4-5 m and then continued to breath hold for various times after their return to the surface. Eighty-two blood samples were withdrawn from indwelling radial artery catheters during 37 ocean dives. We measured compression hyperoxia [arterial Po2 = 141 +/- 24 (SD) Torr] and hypercapnia (arterial Pco2 = 46.6 +/- 2.4 Torr) at depth. Mean arterial Po2 near the end of breath-hold dives lasting 32-95 s (62 +/- 14 s) was decreased (62.6 +/- 13.5 Torr). Mean arterial Pco2 reached 49.9 +/- 5.4 Torr. Complete return of these values to their baseline did not occur until 15-20 s after breathing was resumed. In dives of usual working duration (<30 s), blood gas tensions remained within normal ranges. Detailed analysis of hemoglobin components and intrinsic oxygenation properties revealed no evidence for adaptive changes that could increase the tolerance of the ama to hypoxic or hypothermic conditions associated with repetitive diving. C1 MASSACHUSETTS GEN HOSP, DEPT ANESTHESIA, BOSTON, MA 02114 USA. UNIV COPENHAGEN, HERLEV HOSP, DEPT ANESTHESIA, DK-2730 HERLEV, DENMARK. AARHUS UNIV, INST ZOOL & ZOOPHYSIOL, ZOOPHYSIOL LAB, DK-8000 AARHUS, DENMARK. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. KOSIN MED COLL, INST DIVING SCI, DEPT PHYSIOL, PUSAN, SOUTH KOREA. UNIV DUSSELDORF, DEPT ANESTHESIA, W-4000 DUSSELDORF 1, GERMANY. FREE UNIV BERLIN, DEPT ANESTHESIA, RUDOLPH VIRCHOW CLIN, W-1000 BERLIN 33, GERMANY. SUNY Buffalo, SCH MED, DEPT PHYSIOL, BUFFALO, NY 14214 USA. SUNY Buffalo, SCH MED, SCH BIOMED SCI, BUFFALO, NY 14214 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 31 TC 28 Z9 28 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 1993 VL 75 IS 1 BP 285 EP 293 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA LN649 UT WOS:A1993LN64900040 PM 8376276 ER PT J AU BRYAN, CL LEWIS, RE OWENS, SL EMANUEL, B JENKINSON, SG AF BRYAN, CL LEWIS, RE OWENS, SL EMANUEL, B JENKINSON, SG TI ALLOPURINOL INHIBITION OF NEUTROPHILIC ALVEOLAR RESPONSE DURING HYPEROXIA SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE OXYGEN TOXICITY; LUNG INFLAMMATION; RATS; BRONCHOALVEOLAR LAVAGE FLUID; FREE RADICALS ID RESPIRATORY-DISTRESS SYNDROME; PHORBOL-MYRISTATE ACETATE; LUNG INJURY; POLYMORPHONUCLEAR LEUKOCYTES; OXYGEN-TOXICITY; FREE-RADICALS; GRANULOCYTES; INFLAMMATION; ISCHEMIA; SHEEP AB Allopurinol is a potent xanthine oxidase inhibitor that has been administered to animals to protect tissues from oxidant injury. We hypothesized that allopurinol may protect against oxidant injury by inhibiting the inflammatory response. Male Sprague-Dawley rats were injected daily with vehicle or allopurinol and compared with noninjected controls. Animals were exposed to room air or 90% oxygen for 14 days. At the end of the exposure period, all animals were lavaged and bronchoalveolar lavage fluid (BALF) was examined for cell counts, lactate dehydrogenase (LDH), and protein. BALF neutrophils were significantly increased in oxygen-exposed noninjected controls (33 +/- 7 X 10(3)/mm3) and also in the vehicle-inoculated oxygen-exposed animals (43 +/- 6 X 10(3)/mm3). Allopurinol treatment resulted in a decrease in the neutrophilic alveolar response in oxygen-exposed animals (5.3 +/- 4 X 10(3)/mm3, P < 0.001). These data reveal that oxygen exposure produces a neutrophilic alveolar response that is attenuated by allopurinol treatment. BALF protein and LDH were significantly increased in all inoculated and noninoculated oxygen-exposed animals compared with air-exposed animals. Therefore, allopurinol decreases the neutrophilic alveolar response produced by a hyperoxic exposure in the rat but does not decrease lung injury as assessed by alveolar LDH and protein release. C1 WILFORD HALL USAF MED CTR,DEPT MED,SAN ANTONIO,TX 78284. WILFORD HALL USAF MED CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. RP BRYAN, CL (reprint author), UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY VET ADM HOSP,DEPT MED,PULM DIS SECT 111E,SAN ANTONIO,TX 78284, USA. FU NHLBI NIH HHS [HL-30556] NR 24 TC 8 Z9 9 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 1993 VL 75 IS 1 BP 357 EP 363 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA LN649 UT WOS:A1993LN64900049 PM 8376286 ER PT J AU HAAKE, DA CHAMPION, CI MARTINICH, C SHANG, ES BLANCO, DR MILLER, JN LOVETT, MA AF HAAKE, DA CHAMPION, CI MARTINICH, C SHANG, ES BLANCO, DR MILLER, JN LOVETT, MA TI MOLECULAR-CLONING AND SEQUENCE-ANALYSIS OF THE GENE ENCODING OMPL1, A TRANSMEMBRANE OUTER-MEMBRANE PROTEIN OF PATHOGENIC LEPTOSPIRA SPP SO JOURNAL OF BACTERIOLOGY LA English DT Article ID TREPONEMA-PALLIDUM; ESCHERICHIA-COLI; NEISSERIA-MENINGITIDIS; HEMOPHILUS-INFLUENZAE; BACTERIAL PORIN; ANTIBODY; INVASION; CELLS; ULTRASTRUCTURE; EXPRESSION AB Pathogenic Leptospira spp. are spirochetes that have a low transmembrane outer membrane protein content relative to that of enteric gram-negative bacteria. In a previous study we identified a 31-kDa surface Protein that was present in strains of Leptospira alstoni in amounts which correlated with the outer membrane particle density observed by freeze fracture electron microscopy (D. A. Haake, E. M. Walker, D. R. Blanco, C. A. Bolin, J. N. Miller, and M. A. Lovett, Infect. Immun. 59:1131-1140, 1991). The N-terminal amino acid sequence was used to design a pair of oligonucleotides which were utilized to screen a lambda ZAP II library containing EcoRI fragments of L. alstoni DNA. A 2.5-kb DNA fragment which contained the entire structural ompL1 gene was identified. The structural gene deduced from the sequence of this DNA fragment would encode a 320-amino-acid polypeptide with a 24-amino-acid leader peptide and a leader peptidase I cleavage site. Processing of OmpL1 results in a mature protein with a predicted molecular mass of 31,113 Da. Secondary-structure prediction identified repeated stretches of amphipathic beta-sheets typical of outer membrane protein membrane-spanning sequences. A topological model of OmpL1 containing 10 transmembrane segments is suggested. A recombinant OmpL1 fusion protein was expressed in Escherichia coli in order to immunize rabbits with the purified protein. Upon Triton X-114 extraction of L. alstoni and phase separation, anti-OmpL1 antiserum recognized a single band on immunoblots of the hydrophobic detergent fraction which was not present in the hydrophilic aqueous fraction. Immunoelectron microscopy with anti-Ompl1 antiserum demonstrates binding to the surface of intact L. alstoni. DNA hybridization studies indicate that the ompL1 gene is present in a single copy in all pathogenic Leptospira species that have been tested and is absent in nonpathogenic Leptospira species. OmpL1 may be the first spirochetal transmembrane outer membrane protein for which the structural gene has been cloned and sequenced. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT MICROBIOL & IMMUNOL, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, DIV INFECT DIS, LOS ANGELES, CA 90024 USA. RP HAAKE, DA (reprint author), W LOS ANGELES VET AFFAIRS MED CTR, DIV INFECT DIS, W111F, LOS ANGELES, CA 90073 USA. FU NIAID NIH HHS [AI-29733, 5-T32-AI07323, AI-21352] NR 48 TC 87 Z9 113 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 1993 VL 175 IS 13 BP 4225 EP 4234 PG 10 WC Microbiology SC Microbiology GA LL235 UT WOS:A1993LL23500036 PM 8320237 ER PT J AU BEHLAU, I MILLER, SI AF BEHLAU, I MILLER, SI TI A PHOP-REPRESSED GENE PROMOTES SALMONELLA-TYPHIMURIUM INVASION OF EPITHELIAL-CELLS SO JOURNAL OF BACTERIOLOGY LA English DT Article ID VIBRIO-CHOLERAE; VIRULENCE DETERMINANTS; ESCHERICHIA-COLI; DNA FRAGMENTS; MACROPHAGES; MUTATIONS; PROTEINS; PHOSPHATASES; CONSTRUCTION; RESISTANCE AB The Salmonella typhimurium transcriptional regulators, PhoP/PhoQ, induce phoP-activated gene (pag) expression to promote virulence and intracellular survival within macrophages. This response to the macrophage intracellular environment is simulated by phoP/phoQ constitutive mutations (phenotype PhoP(c)) that increase the expression of pag genes and repress the synthesis of approximately 20 proteins encoded by phoP-repressed genes (prg genes) (S. 1. Miller and J. J. Mekalanos, J. Bacteriol. 172:2485-2490, 1990). PhoP(c) bacteria are attenuated for mouse virulence, suggesting that prg genes are virulence genes. We now report the identification of five unlinked prg loci by use of the transposon TnphoA. In general, medium conditions (i.e., starvation) that activate pag expression repress prg expression. However, variable effects on the PhoP regulon were observed when bacteria were grown under different oxygen tensions (pag and prg genes) or exposed to low pH (prg genes), suggesting heterogenous control of the regulon. One prg locus, prgH, was demonstrated to contribute to mouse virulence by both the oral and the intraperitoneal routes. prgH was located at 59 min on the Salmonella chromosome, a region where other genes essential to invasion of epithelial cells are clustered. The prgH locus was highly linked to one invasion locus, hil (C. A. Lee, B. D. Jones, and S. Falkow, Proc. Natl. Acad. Sci. USA 89:1847-1851, 1992), although transcription of prgH was opposite that of the Tn5B50-encoded promoters that result in a hyperinvasive or hd phenotype. Both PrgH and PhoP(c) mutant S. typhimurium were found to be defective in induction of endocytosis by Madin-Darby canine kidney (MDCK) epithelial cells. The invasion defect of PrgH but not that of PhoP(c) mutant bacteria was complemented by plasmids containing prgH (hil) DNA. Therefore, two virulence properties of Salmonella species, induction of endocytosis by epithelial cells and survival within macrophages, are oppositely modulated by the PhoP/PhoQ virulence regulators. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP MILLER, SI (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114, USA. FU NIAID NIH HHS [AI08280, AI00917, AI30479] NR 52 TC 212 Z9 218 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 1993 VL 175 IS 14 BP 4475 EP 4484 PG 10 WC Microbiology SC Microbiology GA LM260 UT WOS:A1993LM26000024 PM 8392513 ER PT J AU LAURENCIN, CT NORMAN, ME ELGENDY, HM ELAMIN, SF ALLCOCK, HR PUCHER, SR AMBROSIO, AA AF LAURENCIN, CT NORMAN, ME ELGENDY, HM ELAMIN, SF ALLCOCK, HR PUCHER, SR AMBROSIO, AA TI USE OF POLYPHOSPHAZENES FOR SKELETAL TISSUE REGENERATION SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID BIOCOMPATIBILITY; ALLOGRAFTS; HYDROLYSIS; POLYMERS; SYSTEM; GLASS AB The hydrolytically unstable polyphosphazenes, poly [(imidazolyl) (methylphenoxy) phosphazenes] and poly [ethyl glycinato) (methylphenoxy) phosphazenes], were studied as potential polymeric supports for cells in tissue regeneration. For bone repair, their specific function would be to support osteoblast growth, forming a bone-polymer matrix. MC3T3-E1 cells (an osteogenic cell line) were seeded onto polymer matrices and cell adhesion and growth as well as polymer degradation were examined. Both imidazolyl- and ethyl glycinato-substituted polyphosphazenes supported the growth of MC3T3-E1 cells. An increase in the content of the imidazolyl side group resulted in a reduction in cell attachment and growth on the polymer surface and an increase in the rate of degradation of the polymer. In contrast, substitution with the ethyl glycinato group favored increased cell adhesion and growth and also an increase in the rate of degradation of the polymers. Thus, the polyphosphazenes represent a system whereby cell growth and degradation can be modulated by varying the nature of the hydrolytically unstable side chain. This in vitro evaluation suggests that the polyphosphazenes may be suitable candidate biomaterials for the construction of a cell-polymer matrix for tissue regeneration. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ORTHOPED SURG,BOSTON,MA 02114. PENN STATE UNIV,DEPT CHEM,UNIV PK,PA 16802. RP LAURENCIN, CT (reprint author), HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,ROOM 141,77 MASSACHUSETTS AVE,CAMBRIDGE,MA 02139, USA. OI Elgendy, Hoda/0000-0002-5573-7419; Marlow, Maria/0000-0002-0333-5290 NR 29 TC 105 Z9 110 U1 1 U2 7 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD JUL PY 1993 VL 27 IS 7 BP 963 EP 973 DI 10.1002/jbm.820270716 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA LG779 UT WOS:A1993LG77900015 PM 8360223 ER PT J AU SEILER, JG GELBERMAN, RH WILLIAMS, CS WOO, SLY DICKERSIN, GR SOFRANKO, R CHU, CR ROSENBERG, AE AF SEILER, JG GELBERMAN, RH WILLIAMS, CS WOO, SLY DICKERSIN, GR SOFRANKO, R CHU, CR ROSENBERG, AE TI AUTOGENOUS FLEXOR-TENDON GRAFTS - A BIOMECHANICAL AND MORPHOLOGICAL-STUDY IN DOGS SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article AB Intrasynovial and extrasynovial donor autogenous flexor-tendon grafts were placed in the synovial sheaths of the medial and lateral digits of the forepaw in twenty dogs (forty tendons). Postoperatively, the dogs were managed with early, controlled, passive mobilization. Histological and ultrastructural evaluations were carried out at ten days, three weeks, and six weeks, and biomechanical analyses were performed at three and six weeks. The intrasynovial and extrasynovial tendon grafts showed different healing processes histologically. The extrasynovial tendon grafts healed with early ingrowth of peripheral adhesions, which appeared to become larger and more dense over time. These grafts exhibited decreased cellularity and early neovascularization at ten days, and there was evidence of progressive revascularization and cellular repopulation at three and six weeks. In contrast, the intrasynovial tendon grafts demonstrated minimum adhesions, and both cellularity and collagen organization were normal at each time-interval. The intrasynovial grafts had significantly more angular rotation at the proximal interphalangeal joint at three and six weeks than did the extrasynovial grafts (p < 0.05). CLINICAL RELEVANCE: The intrasynovial donor tendon grafts had significantly improved morphological and functional characteristics compared with the extrasynovial tendon grafts at each interval of assessment (p < 0.05). These data provide the basis for an explanation of the variable results seen clinically when extrasynovial donor tendons have been used as autogenous grafts in the hand; they also support the concept that intrasynovial tendons may be especially suitable for survival in the environment of the digital sheath. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,WACC-527,BOSTON,MA 02114. EMORY CLIN,ORTHOPAED CLIN,ATLANTA,GA 30322. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. UNIV PITTSBURGH,DEPT ORTHOPAED SURG,MUSCULOSKELETAL RES LABS,PITTSBURGH,PA 15261. FU NIAMS NIH HHS [5R01-AR3309] NR 24 TC 46 Z9 49 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUL PY 1993 VL 75A IS 7 BP 1004 EP 1014 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA LP574 UT WOS:A1993LP57400006 PM 8335659 ER PT J AU SCHMALZRIED, TP HARRIS, WH AF SCHMALZRIED, TP HARRIS, WH TI HYBRID TOTAL HIP-REPLACEMENT - A 6.5-YEAR FOLLOW-UP-STUDY SO JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME LA English DT Article ID IMPROVED CEMENTING TECHNIQUES; ACETABULAR COMPONENT; ARTHROPLASTIES; MIGRATION; FIXATION; SOCKET AB We have reviewed 97 consecutive primary hip replacements with a cemented femoral component and a porous-ingrowth acetabular component at a minimum five-year follow-up (average 6.5 years). The average Harris hip score was 93, and 85 hips had no pain or only slight pain. There had been no deterioration in the results since the two-year follow-up. The hybrid hip is successful for up to eight years and appears to be suitable for many patients. Long-term femoral fixation has been shown to improve with second-generation cementing techniques and in this series was excellent with third-generation techniques, in that only one stem was revised for loosening. No cementless acetabular component was revised for loosening. C1 MASSACHUSETTS GEN HOSP, ORTHOPAED BIOMECH LAB, HIP & IMPLANT UNIT, 32 FRUIT ST, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. NR 39 TC 116 Z9 116 U1 0 U2 1 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON WC2N 6ET, ENGLAND SN 0301-620X EI 2044-5377 J9 J BONE JOINT SURG BR JI J. Bone Joint Surg.-Br. Vol. PD JUL PY 1993 VL 75 IS 4 BP 608 EP 615 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA LM943 UT WOS:A1993LM94300020 PM 8331118 ER PT J AU TOMASETTO, C NEVEU, MJ DALEY, J HORAN, PK SAGER, R AF TOMASETTO, C NEVEU, MJ DALEY, J HORAN, PK SAGER, R TI SPECIFICITY OF GAP JUNCTION COMMUNICATION AMONG HUMAN MAMMARY CELLS AND CONNEXIN TRANSFECTANTS IN CULTURE SO JOURNAL OF CELL BIOLOGY LA English DT Article ID INTER-CELLULAR COMMUNICATION; INTERCELLULAR COMMUNICATION; DYE TRANSFER; TUMOR-CELLS; GROWTH; PHOSPHORYLATION; PROTEIN; INHIBITION; CARCINOGENESIS; TRANSCRIPTION AB In a previous paper (Lee et al., 1992), it was shown that normal human mammary epithelial cells (NMEC) express two connexin genes, Cx26 and Cx43, whereas neither gene is transcribed in a series of mammary tumor cell lines (TMEC). In this paper it is shown that normal human mammary fibroblasts (NMF) communicate and express Cx43 mRNA and protein. Transfection of either Cx26 or Cx43 genes into a tumor line, 21MT-2, induced the expression of the corresponding mRNAs and proteins as well as communication via gap junctions (GJs), although immunofluorescence demonstrated that the majority of Cx26 and Cx43 proteins present in transfected TMEC was largely cytoplasmic. Immunoblotting demonstrated that NMEC, NMF, and transfected TMEC each displayed a unique pattern of posttranslationally modified forms of Cx43 protein. The role of different connexins in regulating gap junction intercellular communication (GJIC) was examined using a novel two-dye method to assess homologous and heterologous communication quantitatively. The recipient cell population was prestained with a permanent non-toxic lipophilic dye that binds to membranes irreversibly (PKH26, Zynaxis); and the donor population is treated with a GJ-permeable dye Calcein, a derivative of fluorescein diacetate (Molecular Probes). After mixing the two cell populations under conditions promoting GJ formation, cells were analyzed by flow cytometry to determine the percentage of cells containing both dyes. It is shown here that Cx26 and Cx43 transfectants display strong homologous communication, as do NMEC and NMF. Furthermore, NMEC mixed with NMF communicate efficiently, Cx26 transfectants communicate with NMEC but not with NMF, and Cx43 transfectants communicate with NMF. Communication between Cx26 TMEC transfectants and NMEC was asymetrical with preferential movement of calcein from TMEC to NMEC. Despite the presence of Cx43 as well as Cx26 encoded proteins in the GJs of NMEC, few Cx43 transfectants communicated with NMEC. No heterologous GJIC was observed between Cx26- and Cx43-transfected TMEC suggesting that heterotypic GJs do not form or that Cx26/Cx43 channels do not permit dye transfer. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. INSERM,U184,F-67085 STRASBOURG,FRANCE. CNRS,GENET MOLEC EUCARYOTES LAB,F-67085 STRASBOURG,FRANCE. RP TOMASETTO, C (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC GENET,BOSTON,MA 02115, USA. RI Tomasetto, Catherine/J-2783-2014 OI Tomasetto, Catherine/0000-0002-1811-5848 NR 47 TC 112 Z9 114 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL PY 1993 VL 122 IS 1 BP 157 EP 167 DI 10.1083/jcb.122.1.157 PG 11 WC Cell Biology SC Cell Biology GA LK410 UT WOS:A1993LK41000013 PM 8391000 ER PT J AU PEACH, RJ HOLLENBAUGH, D STAMENKOVIC, I ARUFFO, A AF PEACH, RJ HOLLENBAUGH, D STAMENKOVIC, I ARUFFO, A TI IDENTIFICATION OF HYALURONIC-ACID BINDING-SITES IN THE EXTRACELLULAR DOMAIN OF CD44 SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CARTILAGE PROTEOGLYCAN CORE; CELL-SURFACE GLYCOPROTEINS; LYMPHOCYTE HOMING RECEPTOR; LINK PROTEIN; HIGH ENDOTHELIUM; MOLECULAR-CLONING; CDNA CLONES; EXPRESSION; SEQUENCE; ANTIGEN AB CD44 is a polymorphic glycoprotein expressed on the surface of many tissues and cell lines which has been implicated in a number of cellular functions including lymphocyte homing to mucosal lymphoid tissue (Peyers patches), leukocyte activation, lymphopoiesis, and tumor metastasis. The predominant isoform found on human leukocytes, CD44H, is a receptor for hyaluronic acid. Because of the prominent role CD44 plays in diverse biological processes, we set out to identify the hyaluronic acid binding site(s) in the extracellular domain of CD44H. Using truncation and site-directed mutagenesis we identified two regions containing clusters of conserved basic residues which are important in hyaluronic acid binding. One of these regions is situated near the NH2 terminus and is homologous to other hyaluronic acid binding proteins including cartilage link protein. The other more membrane proximal region lies outside the link protein homologous domain. Mutagenesis of basic residues within these regions established their role as determinants in hyaluronic acid binding. Mutation of Arg 41, a position where a basic residue is conserved in all hyaluronic acid binding proteins, completely abolished binding suggesting that this residue plays a critical role in hyaluronic acid binding. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP PEACH, RJ (reprint author), BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121, USA. NR 51 TC 267 Z9 269 U1 0 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL PY 1993 VL 122 IS 1 BP 257 EP 264 DI 10.1083/jcb.122.1.257 PG 8 WC Cell Biology SC Cell Biology GA LK410 UT WOS:A1993LK41000022 PM 8314845 ER PT J AU RIEDEL, H HANSEN, H PARISSENTI, AM SU, LH SHIEH, HL ZHU, JW AF RIEDEL, H HANSEN, H PARISSENTI, AM SU, LH SHIEH, HL ZHU, JW TI PHORBOL ESTER ACTIVATION OF FUNCTIONAL-RAT PROTEIN-KINASE-C BETA-1 CAUSES PHENOTYPE IN YEAST SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE BAL31 DELETION; CALCIUM UPTAKE; CDNA EXPRESSION; SIGNAL TRANSDUCTION; TUMOR PROMOTER ID SACCHAROMYCES-CEREVISIAE; CA-2+ CHANNELS; FAMILY; CELLS; EXPRESSION; RECEPTOR; GENE; AUTOPHOSPHORYLATION; TRANSFORMATION; CONTAINS AB The phorbol ester receptor protein kinase C (PKC) gene family encodes essential mediators of various eukaryotic cellular signals. The molecular dissection of its mechanisms of action has been limited in part by the genetic inaccessibility and complexity of signaling in mammalian cells. Here we present a novel approach to study rat PKC beta-1 action in yeast, a simple lower eukaryotic genetic model. Expression of its cDNA in Saccharomyces cerevisiae introduces novel phorbol ester binding sites which stimulate a specific calcium- and phospholipid-dependent catalytic activity in vitro consistent with a fully functional protein which phosphorylates cellular yeast proteins in vivo. Phorbol ester activation of PKC beta-1 in vivo results in biological responses which include stimulation of extracellular calcium uptake, changes in cell morphology, and an increase in the cell doubling time. These PKC functions are not affected by truncation of 12 amino terminal amino acids; however, they are completely abolished by truncation of 15 or more carboxyl terminal amino acids which likely result in inactivation of the kinase. The increase in the yeast doubling time caused by PKC beta-1 activation provides a phenotype which can be exploited as a screen for the activity of random PKC cDNA mutations. Our findings indicate that rat PKC beta-1 is functional in yeast and leads to biological responses which suggest compatible aspects of higher and lower eukaryotic signaling pathways and the feasibility of dissecting parts of the action of common signaling mediators in a simple genetic model. (C) 1993 Wiley-Liss, Inc. C1 BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RP JOSLIN DIABET CTR, MOLEC BIOL SECT, 7 JOSLIN PL, BOSTON, MA 02215 USA. NR 50 TC 22 Z9 22 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 EI 1097-4644 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUL PY 1993 VL 52 IS 3 BP 320 EP 329 DI 10.1002/jcb.240520308 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LK265 UT WOS:A1993LK26500007 PM 8366143 ER PT J AU CALDERWOOD, SK STEVENSON, MA PRICE, BD AF CALDERWOOD, SK STEVENSON, MA PRICE, BD TI ACTIVATION OF PHOSPHOLIPASE-C BY HEAT-SHOCK REQUIRES GTP ANALOGS AND IS RESISTANT TO PERTUSSIS TOXIN SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID ARACHIDONIC-ACID RELEASE; LIVER PLASMA-MEMBRANES; INOSITOL TRISPHOSPHATE; GUANINE-NUCLEOTIDE; G-PROTEINS; MYOINOSITOL 1,4,5-TRISPHOSPHATE; PERMEABILIZED CELLS; 2ND MESSENGER; CYCLIC-AMP; PHOSPHORYLATION AB The heat shock response in mammals consists of a complex array of intracellular reactions initiated by stress, although its regulation is poorly understood. We have investigated the role of transmembrane signal transduction in the response, examining mechanisms involved in the activation of phospholipase C (PLC) by heat shock. In rodent fibroblasts permeabilized with digitonin, heat shock and receptor-mediated PLC activity exhibited a strict GTP analog dependency. This indicates that heat shock-mediated phopholipase activation, in common with receptor mediated stimulation, does not involve direct effects on the phospholipases and suggests the participation of GTP binding (G) proteins in the activation process. When cells were treated with the inhibitor pertussis toxin (PTX), the phospholipases retained their inducibility by heat shock, but became refractory to thrombin treatment, indicating that heat shock may influence PLC activity through a distinct population of G proteins compared to thrombin. The data seem to exclude a role for PTX sensitive G proteins in the production of IP3 after heating and suggest a pathway involving the direct thermal activation of the G(q) class of G proteins, which are coupled to the PLC(beta1) isoform. (C) 1993 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP CALDERWOOD, SK (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,STRESS PROT GRP,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA47407-01, CA44940-01] NR 34 TC 16 Z9 19 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 JUL PY 1993 VL 156 IS 1 BP 153 EP 159 DI 10.1002/jcp.1041560121 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA LK268 UT WOS:A1993LK26800020 PM 8314854 ER PT J AU LIBERFARB, RM JACKSON, AH EAVEY, RD ROBB, RM AF LIBERFARB, RM JACKSON, AH EAVEY, RD ROBB, RM TI UNIQUE HEREDITARY SENSORY AND AUTONOMIC NEUROPATHY WITH GROWTH-HORMONE DEFICIENCY SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID FIBERS AB The proband, a French-Canadian white boy, presented with congenital sensory polyneuropathy, moderate to severe sensorineural hearing loss, infantile cataracts, nystagmus, esotropia, unusual facies, hypotonia, bilateral congenital hip dysplasia, delayed ossification of the femoral heads, scoliosis, short stature secondary to growth hormone deficiency, and developmental delay. His parents are consanguineous. His maternal first cousin, a 16-year-old girl, has congenital sensory polyneuropathy, infantile cataracts, unusual facies, scoliosis, short stature secondary to growth hormone deficiency, late-childhood-onset arthritis, and hypoglycemia. Reportedly, she has no hearing difficulties and has normal intelligence. Her parents are third cousins. These children appear to have a distinct variant of hereditary sensory and autonomic neuropathy with infantile cataracts, unusual facies, skeletal dysplasia, short stature secondary to growth hormone deficiency, and other features, with probable autosomal recessive inheritance. C1 MASSACHUSETTS EYE & EAR INFIRM,SCHEPENS EYE RES INST,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,MED UNIT,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOL & LARYNGOL,BOSTON,MA 02114. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02115. TUFTS UNIV,SCH MED,BOSTON,MA 02111. BAYSTATE MED CTR,DEPT PEDIAT,PEDIAT NEUROL SECT,SPRINGFIELD,MA 01107. NR 15 TC 5 Z9 5 U1 0 U2 1 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD JUL PY 1993 VL 8 IS 3 BP 271 EP 276 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA LN492 UT WOS:A1993LN49200012 PM 8409271 ER PT J AU ROBERTS, JT ALI, HH SHORTEN, GD AF ROBERTS, JT ALI, HH SHORTEN, GD TI USING THE LARYNGEAL INDEXES CALIPER TO PREDICT DIFFICULTY OF LARYNGOSCOPY WITH A MACINTOSH-NUMBER-3 LARYNGOSCOPE SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE AIRWAY RESISTANCE; INTUBATION, INTRATRACHEAL; LARYNGOSCOPY AB Study Objective: (1) To evaluate a device of the authors' design, the laryngeal indices caliper, which quantitates the position of the anterior edges of the larynx relative to the upper teeth and the external auditory canals; (2) to determine how relative laryngeal position affects ease of direct laryngoscopy with a Macintosh #3 laryngoscope. Design: Randomized, double-blind study. Setting: Inpatient surgery center at a university medical center. Patients: 101 renal patients. Interventions: Patients were measured with the laryngeal indices caliper prior to induction of general endotracheal anesthesia. They were then given a sleep dose of thiopental sodium (4 mg/kg) and paralyzed with a bolus dose of succinylcholine (1 mg/kg). Measurements and Main Results: Of the measurements taken or calculated, only laryngeal tilt (LT) showed a significant correlation with grade of difficulty of laryngoscopy. When the anterior surface of the thyroid cartilage was tilted more than 20 degrees anteriorly to a line perpendicular to the laryngeal indices line, the vocal cords could not be seen in 83% of the patients. Conclusions: (1) Laryngeal tilt is a good predictor of difficulty of laryngoscopy with a Macintosh #3 laryngoscope; (2) the laryngeal indices caliper is a simple pocket device to measure LT indirectly. RP ROBERTS, JT (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD JUL-AUG PY 1993 VL 5 IS 4 BP 302 EP 305 DI 10.1016/0952-8180(93)90123-V PG 4 WC Anesthesiology SC Anesthesiology GA LR757 UT WOS:A1993LR75700009 PM 8373608 ER PT J AU ROBERTS, JT ALI, HH SHORTEN, GD AF ROBERTS, JT ALI, HH SHORTEN, GD TI USING THE BUBBLE INCLINOMETER TO MEASURE LARYNGEAL TILT AND PREDICT DIFFICULTY OF LARYNGOSCOPY SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE AIRWAY RESISTANCE; INTUBATION, INTRATRACHEAL; LARYNGOSCOPY AB Study Objective: To evaluate a simple device, the bubble inclinometer, to measure degrees of laryngeal tilt (LT) for predicting difficulty of direct laryngoscopy using a Macintosh #3 laryngoscope. Design: Randomized, double-blind study. Setting: Inpatient surgery center at a university medical center. Patients: 50 renal lithotripter patients. Interventions: Patients were measured with the bubble inclinometer and the laryngeal indices caliper. A sleep dose of thiopental sodium (4 mg/kg) and a muscle-relaxing dose of succinylcholine (1 mg/kg) were then given to each patient. Measurements and Main Results: LT was measured by both methods (directly and indirectly). Difficulty of laryngoscopy was graded as follows: Grade 1 = all of vocal cords seen; Grade 2 = part of vocal cords seen; Grade 3 = no part of vocal cords seen. Conclusions: The bubble inclinometer accurately and reproducibly measures relative LT, and the anterior tilt of the larynx directly correlates with the ability to see the laryngeal opening during direct laryngoscopy with a Macintosh #3 laryngoscope. RP ROBERTS, JT (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD JUL-AUG PY 1993 VL 5 IS 4 BP 306 EP 309 DI 10.1016/0952-8180(93)90124-W PG 4 WC Anesthesiology SC Anesthesiology GA LR757 UT WOS:A1993LR75700010 PM 8373609 ER PT J AU MARTIN, KA HALL, JE ADAMS, JM CROWLEY, WF AF MARTIN, KA HALL, JE ADAMS, JM CROWLEY, WF TI COMPARISON OF EXOGENOUS GONADOTROPINS AND PULSATILE GONADOTROPIN-RELEASING-HORMONE FOR INDUCTION OF OVULATION IN HYPOGONADOTROPIC AMENORRHEA SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID OVARIAN HYPERSTIMULATION SYNDROME; HYPOTHALAMIC AMENORRHEA; MENOTROPINS; SECRETION; ULTRASOUND; DISORDERS; DIAGNOSIS; PREGNANCY; THERAPY; WOMEN AB To compare the efficacy and safety of ovulation induction with exogenous gonadotropins vs. pulsatile GnRH in patients with hypogonadotropic amenorrhea, results from 30 patients in 111 cycles of gonadotropins and 41 patients in 118 cycles of pulsatile GnRH were analyzed retrospectively. Exogenous gonadotropins were administered using an individually adjusted protocol, using a starting dose of 150 IU. Pulsatile GnRH was delivered iv at a physiological frequency based upon our normative data. The doses administered ranged from 75-250 ng/kg. Preovulatory serum estradiol (E2) and luteal phase progesterone (P) levels were compared to those in normal cycling women (n = 87). The mean body mass index, age, and baseline gonadotropin levels were similar in the two groups. Overall ovulatory rates and conception rates per cycle and per patient were not significantly different between the two groups. However, the cumulative chance of conception after six cycles of treatment by life table analysis appeared to be higher with pulsatile GnRH treatment (96%) than with exogenous gonadotropins (72%). The risk of multiple gestation was also higher with exogenous gonadotropins (14.8% vs. 8.3%), although this was not statistically significant. All higher order multiple gestations (triplets or more) occurred in the gonadotropin-treated group. More than two dominant follicles were seen on ultrasound in 47.6% of gonadotropin-treated cycles compared to 18.9% of cycles with pulsatile GnRH treatment (P < 0.01). Three or more follicles were seen in 16.6% of the gonadotropin cycles compared to 5.4% with pulsatile GnRH (P < 0.05). No case of severe ovarian hyperstimulation was observed in either group, although the mean luteal phase ovarian size was significantly higher in the gonadotropin group (P < 0.05). Mean peak preovulatory E2 levels were significantly higher in the gonadotropin group (1684.5 +/- 124.4 vs. 1315.3 +/- 74.9 pmol/L; P < 0.05). The mean luteal phase P level 1 week after ovulation was significantly higher than normal in the gonadotropin group (84.9 +/- 10.8 vs. 61.1 +/- 3.2 nmol/L; P < 0.05), but was not significantly different from that in the pulsatile GnRH group (70.3 +/-6.0 nmol/L). We conclude that pulsatile GnRH, when compared to exogenous gonadotropins, results in high rates of ovulation and conception, but a decreased risk of multiple folliculogenesis, higher order multiple gestations, and ovarian enlargement. In addition, more physiological preovulatory E2 levels and luteal phase P levels are observed with pulsatile GnRH compared to exogenous gonadotropin treatment. Therefore, pulsatile GnRH would appear to be the treatment of choice for ovulation induction in hypogonadotropic amenorrhea. A prospective randomized trial of exogenous gonadotropins vs. pulsatile GnRH is necessary to further clarify this important issue. C1 MASSACHUSETTS GEN HOSP, DEPT MED, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. RP MARTIN, KA (reprint author), MASSACHUSETTS GEN HOSP, CTR REPROD ENDOCRINE SCI, REPROD ENDOCRINE UNIT, BOSTON, MA 02114 USA. FU FDA HHS [FDU-000477]; NICHD NIH HHS [HD-15080, HD-29164] NR 24 TC 69 Z9 71 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1993 VL 77 IS 1 BP 125 EP 129 DI 10.1210/jc.77.1.125 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LL828 UT WOS:A1993LL82800026 PM 8325934 ER PT J AU HIORT, O HUANG, Q SINNECKER, GHG SADEGHINEJAD, A KRUSE, K WOLFE, HJ YANDELL, DW AF HIORT, O HUANG, Q SINNECKER, GHG SADEGHINEJAD, A KRUSE, K WOLFE, HJ YANDELL, DW TI SINGLE-STRAND CONFORMATION POLYMORPHISM ANALYSIS OF ANDROGEN RECEPTOR GENE-MUTATIONS IN PATIENTS WITH ANDROGEN INSENSITIVITY SYNDROMES - APPLICATION FOR DIAGNOSIS, GENETIC-COUNSELING, AND THERAPY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ENZYMATIC AMPLIFICATION; STEROID-BINDING; DNA; RESISTANCE; PROTEIN; IDENTIFICATION; HETEROGENEITY; LOCALIZATION; CHROMOSOME; SEQUENCE AB Recent studies indicate that mutations in the androgen receptor gene are associated with androgen insensitivity syndromes, a heterogeneous group of related disorders involving defective sexual differentiation in karyotypic males. In this report, we address the possibility of rapid mutational analysis of the androgen receptor gene for initial diagnosis, genetic counseling, and molecular subclassification of affected patients and their families. DNA from peripheral blood leukocytes of six patients from five families with various degrees of androgen insensitivity was studied. Exons 2 to 8 of the androgen receptor gene were analyzed using a combination of single strand conformation polymorphism analysis and direct DNA sequencing. Female family members were also studied to identify heterozygote carriers. Point mutations in the AR gene were identified in all six patients, and all mutations caused amino acid substitutions. One patient with incomplete androgen insensitivity was a mosaic for the mutation. Four of the five mothers, as well as a young sister of one patient, were carriers of the mutation present in the affected child. Our data show that new mutations may occur in the androgen receptor gene leading to sporadic androgen insensitivity syndrome. Molecular genetic characterization of the variant allele can serve as a primary tool for diagnosis and subsequent therapy, and can provide a basis for distinguishing heterozygous carriers in familial androgen resistance. The identification of carriers is of substantial clinical importance for genetic counseling. C1 TUFTS UNIV, NEW ENGLAND MED CTR, DEPT PATHOL, BOSTON, MA 02111 USA. TUFTS UNIV, NEW ENGLAND MED CTR, DEPT PEDIAT, BOSTON, MA 02111 USA. MASSACHUSETTS EYE & EAR INFIRM, DEPT OPHTHALMOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT OPHTHALMOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH PUBL HLTH, DEPT CANC BIOL, BOSTON, MA 02115 USA. RP HIORT, O (reprint author), MED UNIV LUBECK, PADIATR KLIN, KAHLHORSTR 31-35, W-2400 LUBECK, GERMANY. NR 29 TC 61 Z9 63 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1993 VL 77 IS 1 BP 262 EP 266 DI 10.1210/jc.77.1.262 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LL828 UT WOS:A1993LL82800050 PM 8325950 ER PT J AU BERGELSON, JM CHAN, BMC FINBERG, RW HEMLER, ME AF BERGELSON, JM CHAN, BMC FINBERG, RW HEMLER, ME TI THE INTEGRIN VLA-2 BINDS ECHOVIRUS 1 AND EXTRACELLULAR-MATRIX LIGANDS BY DIFFERENT MECHANISMS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE VIRUS RECEPTOR; CELL ADHESION; INTEGRIN; DIVALENT CATIONS; COLLAGEN ID MOUTH-DISEASE VIRUS; ARG-GLY-ASP; CELL-ADHESION; MONOCLONAL-ANTIBODY; T-CELLS; ALPHA-2-BETA-1 INTEGRINS; VITRONECTIN RECEPTOR; DEPENDENT ADHESION; PLATELET INTEGRIN; LAMININ RECEPTOR AB The integrin VLA-2 mediates cell adhesion to collagen and laminin and also functions as a virus receptor, mediating cell surface attachment and infection by a human pathogen, echovirus 1. To determine whether extracellular matrix proteins and virus interact with VLA-2 in the same manner, we carried out a detailed comparison of these two functions and found that they differed markedly in six different respects. In contrast to the ECM/VLA-2 interaction, echovirus 1 binding did not discriminate between functional forms of VLA-2, showed a different pattern of inhibition by anti-beta1 and -alpha2 antibodies, was not stimulated by phorbol esters, was not activated by beta1 antibodies that stimulate ECM binding, was not inhibited by any particular divalent cation, and most notably was not inhibited by EDTA. These striking differences were found both with intact cells expressing VLA-2 and with solubilized VLA-2, suggesting that VLA-2 interacts with these different ligands by markedly different mechanisms, and probably at different functional sites. In addition, alterations in the alpha2 cytoplasmic domain that had marked effects on cellular responses to collagen and laminin had no effect on virus internalization and cell killing. Thus VLA-2-mediated events that occur after receptor occupancy by extracellular matrix proteins also appear to be distinct from those that occur after receptor interaction with virus. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. RI Finberg, Robert/E-3323-2010 FU NCI NIH HHS [CA42368]; NIAID NIH HHS [AI31628, AI89691] NR 60 TC 50 Z9 52 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1993 VL 92 IS 1 BP 232 EP 239 DI 10.1172/JCI116555 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LL773 UT WOS:A1993LL77300031 PM 7686920 ER PT J AU SCHNETZLER, B MURAKAWA, G ABALOS, D HALBAN, P SELDEN, R AF SCHNETZLER, B MURAKAWA, G ABALOS, D HALBAN, P SELDEN, R TI ADAPTATION TO SUPRAPHYSIOLOGICAL LEVELS OF INSULIN GENE-EXPRESSION IN TRANSGENIC MICE - EVIDENCE FOR THE IMPORTANCE OF POSTTRANSCRIPTIONAL REGULATION SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE TRANSGENIC MICE; INSULIN; TRANSCRIPTION; FASTING ID PANCREATIC BETA-CELLS; MESSENGER-RNA; TRANSLATIONAL CONTROL; RIN-5F CELLS; RAT; GLUCOSE; ISLETS; PROINSULIN; PREPROINSULIN; BIOSYNTHESIS AB Insulin production was studied in transgenic mice expressing the human insulin gene under the control of its own promoter. Glucose homeostasis during a 48-h fast was similar in control and transgenic mice, with comparable levels of serum immunoreactive insulin. Northern blot and primer extension analyses indicated that more than twice as much insulin mRNA is present in pancreata from transgenic mice. Primer extension analysis using oligonucleotides specific for mouse insulins I and II or for human insulin, showed that the excess insulin mRNA was due solely to expression of the foreign, human insulin gene. The ratio of mRNA for mouse insulin I and II was unaffected by coexpression of human insulin. There were coordinate changes in the levels of all three mRNA during the 48-h fast, or after a 24-h fast followed by 24-h refeed. Despite the supraphysiologic levels of insulin mRNA in the transgenic mice, their pancreatic content of immunoreactive insulin was not significantly different from controls. The comparison of the relative levels of human and mouse insulin mRNAs with their peptide counterparts (separated by HPLC) indicates that the efficiency of insulin production from mouse insulin mRNA is greater than that from human, stressing the importance of posttranscriptional regulatory events in the overall maintenance of pancreatic insulin content. C1 CTR MED UNIV GENEVA,RECH LOUIS JEANTET,1 RUE MICHEL SERVET,CH-1211 GENEVA 4,SWITZERLAND. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. FU NIDDK NIH HHS [DK-35292] NR 41 TC 11 Z9 11 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1993 VL 92 IS 1 BP 272 EP 280 DI 10.1172/JCI116561 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LL773 UT WOS:A1993LL77300036 PM 8325994 ER PT J AU KLEIN, BS HOGAN, LH JONES, JM AF KLEIN, BS HOGAN, LH JONES, JM TI IMMUNOLOGICAL RECOGNITION OF A 25-AMINO-ACID REPEAT ARRAYED IN TANDEM ON A MAJOR ANTIGEN OF BLASTOMYCES-DERMATITIDIS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE BLASTOMYCOSIS; TANDEM REPEAT; SERODIAGNOSIS; DIMORPHIC FUNGUS; CDNA ID MAMMALIAN-CELLS; PROTEIN; IDENTIFICATION; SEQUENCE; INVASIN; PURIFICATION; GLYCOPROTEIN; GENE AB A 120-kD glycoprotein antigen abundantly expressed on Blastomyces dermatitidis yeasts is a target of cellular and humoral immune responses in human infection. To investigate the antigen and immune response more carefully at the molecular level, we screened an expression library from B. dermatitidis to identify clones that encode this antigen, designated WI-1. A 942-bp cDNA was isolated by immunologic screening with polyclonal, rabbit anti-WI-1 antiserum. Northern hybridization analysis showed that the cDNA hybridized to yeast message congruent-to 3.9 kb. DNA and deduced protein sequence analysis of the clone demonstrated a 25-amino acid repeat arrayed in tandem, present in 4.5 copies near the 5' end, and rich in predicted antigenic epitopes. Further analysis showed strong homology in these tandem repeats with invasin, an adhesin of Yersiniae. Cloned cDNA was used to express a 30-kD fusion protein strongly recognized in western blots by rabbit anti-WI-1 antiserum, and by sera from all 35 blastomycosis patients studied. The fusion protein product of subcloned cDNA encoding only the tandem repeat also was strongly recognized in western blots by sera from the 35 blastomycosis patients, but not by sera from 10 histoplasmosis and 5 coccidioidomycosis patients. An antigen-inhibition radioimmunoassay showed that the tandem repeat alone completely eliminated rabbit and human anti-WI-1 antibody binding to radiolabeled native WI-1. From these results, we conclude that the 25-amino acid repeat of WI-1 displays an immunodominant B cell epitope, and that the carboxyl-terminus of the molecule exhibits an architecture that may promote adhesion of Blastomyces yeasts to host cells or extracellular matrix proteins and ultimately provide a clearer picture of the molecular pathogenesis of blastomycosis. C1 UNIV WISCONSIN,SCH MED,DEPT PEDIAT,MADISON,WI 53706. UNIV WISCONSIN,SCH MED,DEPT MED MICROBIOL & IMMUNOL,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,RES SERV,MADISON,WI 53705. RP KLEIN, BS (reprint author), UNIV WISCONSIN,HOSP & CLIN,600 HIGHLAND AVE,MADISON,WI 53792, USA. FU NIAID NIH HHS [AI-00905, AI-31479] NR 29 TC 51 Z9 51 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1993 VL 92 IS 1 BP 330 EP 337 DI 10.1172/JCI116571 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LL773 UT WOS:A1993LL77300044 PM 8326001 ER PT J AU PIETROPAOLO, M CASTANO, L BABU, S BUELOW, R KUO, YLS MARTIN, S MARTIN, A POWERS, AC PROCHAZKA, M NAGGERT, J LEITER, EH EISENBARTH, GS AF PIETROPAOLO, M CASTANO, L BABU, S BUELOW, R KUO, YLS MARTIN, S MARTIN, A POWERS, AC PROCHAZKA, M NAGGERT, J LEITER, EH EISENBARTH, GS TI ISLET-CELL AUTOANTIGEN 69-KD (ICA69) - MOLECULAR-CLONING AND CHARACTERIZATION OF A NOVEL DIABETES-ASSOCIATED AUTOANTIGEN SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE AUTOANTIGENS; PRECLINICAL DIABETES; MOLECULAR CLONING; AUTOIMMUNITY; ICA69 ID COMPLETE NUCLEOTIDE-SEQUENCE; GLUTAMIC-ACID DECARBOXYLASE; MALTOSE-BINDING PROTEIN; RIBOSOMAL-RNA GENE; ESCHERICHIA-COLI; INSULIN; EXPRESSION; MELLITUS; ANTIBODIES; AUTOANTIBODIES AB We have identified a novel 69-kD peptide autoantigen (ICA69) associated with insulin-dependent diabetes mellitus (IDDM) by screening a human islet lambdagt11 cDNA expression library with cytoplasmic islet cell antibody positive sera from relatives of IDDM patients who progressed to the overt disease. The deduced open reading frame of the ICA69 cDNA predicts a 483-amino acid protein. ICA69 shows no nucleotide or amino acid sequence relation to any known sequence in GenBank, except for two short regions of similarity with BSA. The ICA69 cDNA probe hybridizes with a 2-kb mRNA in poly(A+ ) RNA from human pancreas, brain, heart, thyroid, and kidney, but not with skeletal muscle, placenta, spleen, or ovary. Expression of ICA69 was also detected in beta cells and cell lines, as well as in tumoral tissue of islet cell origin. The native ICA69 molecule migrates to 69 kD in SDS-PAGE as detected with specific antibodies. Serum samples from relatives of IDDM patients specifically reacted with affinity-purified recombinant ICA69 on Western blotting. The structural gene for ICA69 was designated ICA]. A homologue in the mouse, designated Ica-1 was mapped to the proximal end of chromosome 6 (within 6 cM of the Met protooncogene). ICA69 adds a novel autoantigen to the family of identified islet target molecules. and by the manner of its identification and characterization large amounts of antigen are available for development of quantitative, convenient predictive assays for autoantibodies and analysis of the role of this molecule in diabetes autoimmunity, as well as its physiologic function. C1 UNIV COLORADO,HLTH SCI CTR,BARBARA DAVIS CTR CHILDHOOD DIABET,4200 E 9TH AVE,BOX B140,DENVER,CO 80262. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,ELLIOT P JOSLIN RES LAB,JOSLIN RES LAB,BOSTON,MA 02115. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,BOSTON,MA 02215. IMMULOG PHARMACEUT CORP,PALO ALTO,CA 94394. DIABET FORSCHUNGSINST,W-4000 DUSSELDORF,GERMANY. VANDERBILT UNIV,NASHVILLE VET AFFAIRS MED CTR,DIV ENDOCRINOL,NASHVILLE,TN 37232. JACKSON LAB,BAR HARBOR,ME 04609. RI Castano, Luis/C-3084-2009 FU NIDDK NIH HHS [DK 36175, DK 27722, DK 32083] NR 76 TC 222 Z9 224 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1993 VL 92 IS 1 BP 359 EP 371 DI 10.1172/JCI116574 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LL773 UT WOS:A1993LL77300047 PM 8326004 ER PT J AU PODOLSKY, DK LOBB, R KING, N BENJAMIN, CD PEPINSKY, B SEHGAL, P DEBEAUMONT, M AF PODOLSKY, DK LOBB, R KING, N BENJAMIN, CD PEPINSKY, B SEHGAL, P DEBEAUMONT, M TI ATTENUATION OF COLITIS IN THE COTTON-TOP TAMARIN BY ANTI-ALPHA-4 INTEGRIN MONOCLONAL-ANTIBODY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ADHESION; COLITIS; COTTON-TOP TAMARIN; INFLAMMATORY BOWEL DISEASE ID LEUKOCYTE ADHESION MOLECULE-1; DIRECT EXPRESSION CLONING; CELL-ADHESION; ENDOTHELIAL-CELLS; T-CELLS; FUNCTIONAL-CHARACTERIZATION; SOLUBLE FORM; ELAM-1; ACTIVATION; RECOGNITION AB Recent studies have demonstrated the induced expression of endothelial adhesion molecules including E-selectin (also called endothelial leukocyte adhesion molecule-1), vascular cell adhesion molecule and intercellular adhesion molecule in actively involved mucosa of patients with ulcerative colitis and Crohn's disease. Similar induction has been demonstrated in the colon of the Cotton-top tamarin (CTT), a New World primate that experiences a spontaneous acute and chronic colitis resembling ulcerative colitis. To assess the potential importance of leukocyte adhesion as a necessary step in acute colitis, the effect of parenteral mAb directed against adhesion molecules on CTT colitis was evaluated in placebo-controlled blinded trials. Serial administration of either of two anti-E-selectin mAb designated BB11 and EH8 effectively coated endothelial surfaces expressing this vascular adhesion molecule. Although colitis activity was slightly diminished after the 10-d treatment period in CTT receiving either BB1 1 or EH8, this reduction was not significantly different than that seen in animals given a placebo control when assessed by a previously validated standardized scale of inflammatory activity: mean histologic activity grade 2.2+/-0.2 pretreatment vs 1.5+/-0.5 posttreatment in group receiving mAb and 2.1+/-0.1 pretreatment vs 1.3+/-0.5 posttreatment in the placebo group (P > 0.2). In contrast, administration of an anti-alpha4 integrin mAb designated HP1/2 that binds VLA4 (alpha4beta1) and presumably alpha4beta7 integrins resulted in significant attenuation of acute colitis when compared to both pretreatment activity index (P = 0.005) and the placebo control group (P < 0.01):mean histologic activity grade 1.6+/-0.3 pretreatment vs 0.2+/-0.1 posttreatment in the group receiving HP1/2 and 1.8+/-0.5 pretreatment and 1.2+/-0.2 posttreatment in the placebo control group. These studies using a model of spontaneous colitis in the CTT demonstrate the feasibility of modulation of leukocyte-vascular adhesion and/or other integrin-mediated events possibly including T cell aggregation and T cell-stromal interactions, as well as lymphocyte homing. These results suggest both that these processes are important and possibly essential elements in sustaining acute colitis and that their disruption may result in therapeutic benefit. C1 MASSACHUSETTS GEN HOSP,NEW ENGLAND REG PRIMATE RES CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. BIOGEN INC,CAMBRIDGE,MA 02142. NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. RP PODOLSKY, DK (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,JACKSON 7,50 FRUIT ST,BOSTON,MA 02114, USA. FU NCRR NIH HHS [NERPRC 5P51RR00168]; NIDDK NIH HHS [R01DK36350, P30DK43351] NR 36 TC 262 Z9 267 U1 2 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1993 VL 92 IS 1 BP 372 EP 380 DI 10.1172/JCI116575 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LL773 UT WOS:A1993LL77300048 PM 7686922 ER PT J AU BONADONNA, RC DELPRATO, S SACCOMANI, MP BONORA, E GULLI, G FERRANNINI, E BIER, D COBELLI, C DEFRONZO, RA AF BONADONNA, RC DELPRATO, S SACCOMANI, MP BONORA, E GULLI, G FERRANNINI, E BIER, D COBELLI, C DEFRONZO, RA TI TRANSMEMBRANE GLUCOSE-TRANSPORT IN SKELETAL-MUSCLE OF PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE LIMB BALANCE; INSULIN RESISTANCE; HYPERGLYCEMIA ID GLYCOGEN-SYNTHASE ACTIVITY; RAT ADIPOSE-CELLS; POSTRECEPTOR DEFECT; RESPONSIVE TISSUES; PLASMA-MEMBRANE; SOLEUS MUSCLE; HUMAN FOREARM; PIMA-INDIANS; MELLITUS; RESISTANCE AB Insulin resistance for glucose metabolism in skeletal muscle is a key feature in non-insulin-dependent diabetes mellitus (NIDDM). Which cellular effectors of glucose metabolism are involved is still unknown. We investigated whether transmembrane glucose transport in vivo is impaired in skeletal muscle in nonobese NIDDM patients. We performed euglycemic insulin clamp studies in combination with the forearm balance technique (brachial artery and deep forearm vein catheterization) in six nonobese NIDDM patients and five age- and weight-matched controls. Unlabeled D-mannitol (a nontransportable molecule) and radioactive 3-0-methyl-D-glucose (the reference molecular probe to assess glucose transport activity) were simultaneously injected into the brachial artery, and the washout curves were measured in the deep venous effluent blood. In vivo transmembrane transport of 3-0-methyl-D-glucose in forearm muscle was determined by computerized analysis of the washout curves. At similar steady-state plasma concentrations of insulin (approximately 500 pmol/liter) and glucose (approximately 5.15 mmol/liter), transmembrane inward transport of 3-0-methyl-D-glucose in skeletal muscle was markedly reduced in the NIDDM patients (6.5 x 10(-2) +/- 0.56 x 10(-2) . min-1) compared with controls (12.5 x 10(-2) +/- 1.5 x 10(-2) - min-1, P < 0.005). Mean glucose uptake was also reduced in the diabetics both at the whole body level (9.25 +/- 1.84 vs. 28.3 +/- 2.44 mumol/min per kg, P < 0.02) and in the forearm tissues (5.84 +/- 1.51 vs. 37.5 +/- 7.95 mumol/min per kg, P < 0.02). When the latter rates were extrapolated to the whole body level, skeletal muscle accounted for - 80% of the defect in insulin action seen in NIDDM patients. We conclude that transmembrane glucose transport, when assessed in vivo in skeletal muscle, is insensitive to insulin in nonobese NIDDM patients, and plays a major role in determining whole body insulin resistance. C1 UNIV PADUA,DEPT ELECTR & INFORMAT,I-35100 PADUA,ITALY. WASHINGTON UNIV,SCH MED,DIV METAB,ST LOUIS,MO 63110. UNIV TEXAS,HLTH SCI CTR,DIV DIABET,SAN ANTONIO,TX 78284. UNIV TEXAS,AUDIE L MURPHY VET ADM HOSP,SAN ANTONIO,TX 78285. RP BONADONNA, RC (reprint author), UNIV PISA,CNR,INST CLIN PHYSIOL,METAB UNIT,VIA SAVI 8,I-56100 PISA,ITALY. RI Del Prato, Stefano/K-3405-2016; OI Del Prato, Stefano/0000-0002-5388-0270; BONORA, Enzo/0000-0003-1074-5164 FU NCRR NIH HHS [RR-00954]; NIDDK NIH HHS [DK-20579, DK-24092] NR 72 TC 126 Z9 128 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1993 VL 92 IS 1 BP 486 EP 494 DI 10.1172/JCI116592 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LL773 UT WOS:A1993LL77300063 PM 8326013 ER PT J AU CIACCI, C MAHIDA, YR DIGNASS, A KOIZUMI, M PODOLSKY, DK AF CIACCI, C MAHIDA, YR DIGNASS, A KOIZUMI, M PODOLSKY, DK TI FUNCTIONAL INTERLEUKIN-2 RECEPTORS ON INTESTINAL EPITHELIAL-CELLS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE CYTOKINE; RECEPTOR; TGF-BETA(1); MUCOSAL IMMUNITY; LYMPHOKINE ID BETA-CHAIN; GENE-EXPRESSION; LIGAND-BINDING; ALPHA-CHAIN; GROWTH; RAT; DIFFERENTIATION; LECTIN AB The presence of receptors for the cytokine IL-2 was assessed in the IEC-6 cell line established from normal rat crypt epithelium and primary intestinal epithelial cells. I-125-IL-2 was found to specifically bind to subconfluent IEC-6 cells. Maximal binding was observed within 30 min after addition of the ligand; binding could be inhibited by excess unlabeled IL-2 or addition of antibody to the IL-2 receptor. Both intermediate and low affinity receptors with approximate K(d) of 10 and 100 pM, respectively were present. Kinetic analysis were consistent with the results of Western blot analysis using an antisera to the 75-kD IL-2 receptor beta chain. IL-2 receptors appeared to be functional; addition of IL-2 led to modulation of proliferation with initial stimulation at 24 h followed by inhibition at 48 h. This effect could be blocked by addition of antibody to the IL-2 receptor beta chain. IL-2 treatment could be shown to enhance expression (range = 4- to 50-fold stimulation) of TGF-beta, as well as the lectin protein mac-2, in IEC-6 cells. The relevance of observations in the IEC-6 cell line to intestinal mucosa in vivo was supported by the demonstration of a gradient of expression of the IL-2 receptor in primary rat intestinal epithelial cells by Western blot analysis. In addition, mRNA for the IL-2 receptor-beta chain was demonstrated by Northern blot analysis using mRNA from primary rat intestinal epithelial cells depleted of detectable contaminating intraepithelial lymphocytes by two cycles of fractionation on Percoll gradients. Collectively, these observations suggest that the range of cellular targets of the putative lymphokine IL-2 is broader than appreciated, and IL-2 may serve to integrate epithelial and lymphocyte responses in the intestinal mucosa. C1 MASSACHUSETTS GEN HOSP,DEPT MED,CTR STUDY INFLAMMATORY BOWEL DIS,GASTROINTESTINAL UNIT,JACKSON 7,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI ciacci, carolina/A-2594-2012 OI ciacci, carolina/0000-0002-7426-1145 FU NIDDK NIH HHS [DK 41557, P30 DK43351] NR 28 TC 96 Z9 97 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1993 VL 92 IS 1 BP 527 EP 532 DI 10.1172/JCI116598 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LL773 UT WOS:A1993LL77300069 PM 8326018 ER PT J AU LIPSHULTZ, SE SALLAN, SE AF LIPSHULTZ, SE SALLAN, SE TI CARDIOVASCULAR-ABNORMALITIES IN LONG-TERM SURVIVORS OF CHILDHOOD MALIGNANCY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID HODGKINS-DISEASE; MEDIASTINAL IRRADIATION; THERAPY; RADIOTHERAPY; PERICARDITIS; RADIATION; CANCER RP LIPSHULTZ, SE (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 24 TC 72 Z9 74 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 JUL PY 1993 VL 11 IS 7 BP 1199 EP 1203 PG 5 WC Oncology SC Oncology GA LL233 UT WOS:A1993LL23300001 PM 8315417 ER PT J AU ANTMAN, K CROWLEY, J BALCERZAK, SP RIVKIN, SE WEISS, GR ELIAS, A NATALE, RB COOPER, RM BARLOGIE, B TRUMP, DL DOROSHOW, JH AISNER, J PUGH, RP WEISS, RB COOPER, BA CLAMOND, GH BAKER, LH AF ANTMAN, K CROWLEY, J BALCERZAK, SP RIVKIN, SE WEISS, GR ELIAS, A NATALE, RB COOPER, RM BARLOGIE, B TRUMP, DL DOROSHOW, JH AISNER, J PUGH, RP WEISS, RB COOPER, BA CLAMOND, GH BAKER, LH TI AN INTERGROUP PHASE-III RANDOMIZED STUDY OF DOXORUBICIN AND DACARBAZINE WITH OR WITHOUT IFOSFAMIDE AND MESNA IN ADVANCED SOFT-TISSUE AND BONE SARCOMAS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-DOSE IFOSFAMIDE; ONCOLOGY-GROUP; COMBINATION CHEMOTHERAPY; ADRIAMYCIN NSC-123127; UNRESECTABLE SARCOMA; PULMONARY METASTASES; HUMAN NEOPLASIA; ACTINOMYCIN-D; TRIAL; CYCLOPHOSPHAMIDE C1 WALTER REED ARMY INST RES,WASHINGTON,DC 20307. OHIO STATE UNIV,CTR HLTH,COLUMBUS,OH 43210. MCGILL UNIV,CTR CHEMOTHERAPY,MONTREAL H3A 2T5,QUEBEC,CANADA. PUGET SOUND ONCOL CONSORTIUM,SEATTLE,WA. CITY HOPE NATL MED CTR,DUARTE,CA 91010. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. UNIV MICHIGAN,MED CTR,ANN ARBOR,MI 48109. UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27103. UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. DUKE UNIV,DURHAM,NC 27706. ALLEGHENEY HLTH EDUC & RES,PITTSBURGH,PA. WAYNE STATE UNIV,MED CTR,DETROIT,MI 48202. SW ONCOL GRP,CTR STAT,SEATTLE,PA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV IOWA,IOWA CITY,IA 52242. FU NCI NIH HHS [CA-14028, CA-04920, CA-37429] NR 47 TC 280 Z9 290 U1 0 U2 8 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 JUL PY 1993 VL 11 IS 7 BP 1276 EP 1285 PG 10 WC Oncology SC Oncology GA LL233 UT WOS:A1993LL23300012 PM 8315425 ER PT J AU KIRN, D MAUCH, P SHAFFER, K PINKUS, G SHIPP, MA KAPLAN, WD TUNG, N WHEELER, C BEARD, CJ CANELLOS, GP SHULMAN, LN AF KIRN, D MAUCH, P SHAFFER, K PINKUS, G SHIPP, MA KAPLAN, WD TUNG, N WHEELER, C BEARD, CJ CANELLOS, GP SHULMAN, LN TI LARGE-CELL AND IMMUNOBLASTIC LYMPHOMA OF THE MEDIASTINUM - PROGNOSTIC FEATURES AND TREATMENT OUTCOME IN 57 PATIENTS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID UNDIFFERENTIATED LYMPHOMA; M-BACOD; SCLEROSIS; THERAPY C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV HEMATOL ONCOL,75 FRANCIS ST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,JOINT CTR RADIAT ONCOL,DIV MED ONCOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD LONGWOOD ONCOL GRP,BOSTON,MA. NR 19 TC 84 Z9 85 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 JUL PY 1993 VL 11 IS 7 BP 1336 EP 1343 PG 8 WC Oncology SC Oncology GA LL233 UT WOS:A1993LL23300021 PM 8315431 ER PT J AU SYKES, M HARTY, MW KARLHOFER, FM PEARSON, DA SZOT, G YOKOYAMA, W AF SYKES, M HARTY, MW KARLHOFER, FM PEARSON, DA SZOT, G YOKOYAMA, W TI HEMATOPOIETIC-CELLS AND RADIORESISTANT HOST ELEMENTS INFLUENCE NATURAL-KILLER-CELL DIFFERENTIATION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID BONE-MARROW CHIMERAS; NONLETHAL PREPARATIVE REGIMEN; GRAFT-REJECTION; ALLOGENEIC CHIMERISM; CLONAL DELETION; T-CELLS; TOLERANCE; MICE; POPULATIONS; DEPLETION AB Radioresistant host elements mediate positive selection of developing thymocytes, whereas bone marrow-derived cells induce clonal deletion of T cells with receptors that are strongly autoreactive. In contrast to T cell development, little is known about the elements governing the natural killer (NK) cell repertoire, which, similar to the T cell repertoire, differs between individuals bearing different major histocompatibility complex (MHC) phenotypes. We have used murine bone marrow transplantation models to analyze the influence of donor and host MHC on an NK cell subset. We examined the expression of Ly-49, which is strongly expressed on a subpopulation of NK cells of H-2b mice, but not by NK cells of H-2a mice, probably because of a negative effect induced by the interaction of Ly-49 with D(d). To evaluate the effect of hematopoietic cell H-2a expression on Ly-49 expression of H-2b NK cells, we prepared mixed allogeneic chimeras by administering T cell-depleted allogeneic (B10.A, H-2a) and host-type (B10, H-2b) marrow to lethally irradiated B10 mice, or by administering B10.A marrow to B10 recipients conditioned by a nonmyeloablative regimen. Expression of H-2a on bone marrow-derived cells was sufficient to downregulate Ly-49 expression on both H-2a and H-2b NK cells. This downregulation was thymus independent. To examine the effect of H-2a expressed only on radioresistant host elements, we prepared fully allogeneic chimeras by administering B10 bone marrow to lethally irradiated B10.A recipients. B10 NK cells of these fully allogeneic chimeras also showed downregulation of Ly-49 expression. The lower level of H-2a expressed on H-2b x H-2a F1 cells induced more marked downregulation of Ly-49 expression on B10 NK cells when presented on donor marrow in mixed chimeras than when expressed only on radioresistant host cells. Our studies show that differentiation of NK cells is determined by interactions with MHC molecules expressed on bone marrow-derived cells and, to a lesser extent, by MHC antigens expressed on radioresistant host elements. C1 MT SINAI MED CTR,BROOKDALE CTR MOLEC BIOL,NEW YORK,NY 10029. MT SINAI MED CTR,DEPT MED,NEW YORK,NY 10029. RP SYKES, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG SERV,CTR TRANSPLANTAT RES BIOL,MGH-E,BLDG 149,BOSTON,MA 02129, USA. FU PHS HHS [R01 31158] NR 32 TC 95 Z9 95 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1993 VL 178 IS 1 BP 223 EP 229 DI 10.1084/jem.178.1.223 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LH549 UT WOS:A1993LH54900019 PM 8315379 ER PT J AU SILVA, JA LEONG, GB WEINSTOCK, R WINE, DB AF SILVA, JA LEONG, GB WEINSTOCK, R WINE, DB TI DELUSIONAL MISIDENTIFICATION AND DANGEROUSNESS - A NEUROBIOLOGICAL HYPOTHESIS SO JOURNAL OF FORENSIC SCIENCES LA English DT Note DE FORENSIC PSYCHIATRY; DANGEROUSNESS; MENTAL DISORDER; SCHIZOPHRENIA; DELUSIONAL MISIDENTIFICATION SYNDROMES; FACE RECOGNITION ID CAPGRAS SYNDROME; FACIAL RECOGNITION; FREGOLI SYNDROME; KNOWLEDGE; TOMOGRAPHY; VIOLENCE; DEMENTIA; ATROPHY; SYSTEM AB Delusional misidentification syndromes have intrigued this century's psychiatric researchers. More recently, the dangerousness posed by individuals suffering from these syndromes has been a subject of scientific inquiry. A series of five individuals suffering from delusional misidentification syndromes was studied from a phenomenologic and neuropsy-chologic perspective. Using this information. a hypothesis involving the psychobiological contributions to the dangerousness of delusional misidentification can be generated. This may further our understanding of the dangerousness posed by psychotic individuals. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. RP SILVA, JA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PSYCHIAT SERV 116A,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 52 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD JUL PY 1993 VL 38 IS 4 BP 904 EP 913 PG 10 WC Medicine, Legal SC Legal Medicine GA LM756 UT WOS:A1993LM75600022 PM 8102637 ER PT J AU MULROW, CD LUCEY, CR FARNETT, LE AF MULROW, CD LUCEY, CR FARNETT, LE TI DISCRIMINATING CAUSES OF DYSPNEA THROUGH CLINICAL EXAMINATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review RP MULROW, CD (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 0 TC 46 Z9 49 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 1993 VL 8 IS 7 BP 383 EP 392 DI 10.1007/BF02600079 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA LN093 UT WOS:A1993LN09300008 PM 8410400 ER PT J AU CHERAYIL, BJ MACDONALD, K WANECK, GL PILLAI, S AF CHERAYIL, BJ MACDONALD, K WANECK, GL PILLAI, S TI SURFACE TRANSPORT AND INTERNALIZATION OF THE MEMBRANE IGM H-CHAIN IN THE ABSENCE OF THE MB-1 AND B29 PROTEINS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN RECEPTOR COMPLEX; IMMUNOGLOBULIN HEAVY-CHAIN; BINDING-PROTEIN; CELL-SURFACE; QA-2 ANTIGEN; LIGHT CHAIN; EXPRESSION; GENE; LINE; TRANSMEMBRANE AB The mum Ig H chain is one component of the membrane IgM complex, the endocytic and signal transducing receptor for Ag on the surface of B lymphocytes. It is transported to the cell surface in association with three other B cell-specific proteins, an L chain and the products of the mb-1 and B29 genes. The roles played by these various proteins in mediating the functions of the complex are unclear. To analyze mum function in the absence of other lymphoid-specific proteins, we first attempted to express mum on the surface of nonlymphoid cells. Deletion of the CH1 domain was sufficient to allow surface expression of this protein in transfected COS cells as well as in mouse L cells. To determine whether this extracellularly truncated mum was capable of endocytosis, we used an assay to detect the internalization of anti-mu antibody bound to the surface of transfected cells expressing the protein. Under both cross-linking and non cross-linking conditions, the CH1-deleted mum protein was internalized in endocytic vesicles. We conclude from these observations that a) the CH1 domain of mum contains a retention signal, the elimination of which allows surface transport of this protein, and b) mum by itself is capable of at least one of the functions of the membrane IgM complex. C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC IMMUNOL LAB,BLDG 149,13TH ST,CHARLESTOWN NAVY YARD,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CTR CANC,SURG SERV,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NIAID NIH HHS [AI-27835]; NIDDK NIH HHS [P30-DK43351]; NIGMS NIH HHS [GM-46467] NR 32 TC 25 Z9 25 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 1 PY 1993 VL 151 IS 1 BP 11 EP 19 PG 9 WC Immunology SC Immunology GA LM579 UT WOS:A1993LM57900002 PM 8326121 ER PT J AU BADEN, HP KVEDAR, JC AF BADEN, HP KVEDAR, JC TI EPITHELIAL CORNIFIED ENVELOPE PRECURSORS ARE IN THE HAIR FOLLICLE AND NAIL SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT 41ST ANNUAL SYMP ON THE BIOLOGY OF THE SKIN : FUNDAMENTALS OF HAIR BIOLOGY CY JUL 25-29, 1992 CL SNOWMASS VILLAGE, CO SP CUTANEOUS BIOL FDN ID MAMMALIAN EPIDERMIS; CROSS-LINKING; PROTEIN; KERATINOCYTES; PANCORNULINS AB Nail and certain layers of the hair follicle form cornified envelopes (CEs) that morphologically resemble those in epidermis. We have been studying two unique precursors of the CE in human epidermis, pancornulin an sciellin. Antibodies to these proteins stained the more central cells of the outer root sheath of the ostium and isthmus of the follicle where CEs are found. Staining was also observed with these antibodies in the inner root sheath, where CEs were thought not to be resent. Using immunoelectron microscopy, the staining by the sciellin antibody was at the cell periphery, but this technique did not work with the antibody to pancornulin. The antibody to pancornulin reacted to the nail fold and proximal matrix, whereas the one to sciellin reacted with the nail fold, matrix, and bed. Similar reactions were observed to monkey, sheep, and cow nail. These results suggest that envelope precursor may have an additional function in the hair follicle as well as contributing to the CE in hair and nail. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02114. NR 14 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1993 VL 101 IS 1 SU S BP S72 EP S74 DI 10.1111/1523-1747.ep12362869 PG 3 WC Dermatology SC Dermatology GA LN154 UT WOS:A1993LN15400013 PM 7686954 ER PT J AU ENOCHS, WS NILGES, MJ SWARTZ, HM AF ENOCHS, WS NILGES, MJ SWARTZ, HM TI PURIFIED HUMAN NEUROMELANIN, SYNTHETIC DOPAMINE MELANIN AS A POTENTIAL MODEL PIGMENT, AND THE NORMAL HUMAN SUBSTANTIA-NIGRA - CHARACTERIZATION BY ELECTRON-PARAMAGNETIC-RESONANCE SPECTROSCOPY SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE NEUROMELANIN; MELANINS; METAL IONS; SUBSTANTIA-NIGRA; ELECTRON PARAMAGNETIC RESONANCE SPECTROSCOPY; AGING; PARKINSONS DISEASE ID PARKINSONS-DISEASE; SPIN-RESONANCE; FREE-RADICALS; TRANSITION-METALS; NERVE-CELLS; BRAIN; IONS; MANGANESE; AFFINITY; IRON AB Neuromelanin is a poorly understood pigment that accumulates in catecholaminergic neurons during normal aging. Electron paramagnetic resonance spectroscopy, an especially effective technique for investigating melanins, is used in the present study to show unambiguously that neuromelanin is a melanin; however, it is not well modeled by synthetic dopamine melanin and thus is an atypical melanin. Some of the unusual features of neuromelanin can be explained by postulating two distinct sources for its free radicals, the dominant one possibly derived from a precursor containing sulfur. Examination of human substantia nigra by electron paramagnetic resonance spectroscopy during the purification of neuromelanin also demonstrates, contrary to some other studies, that a portion of the paramagnetic metal ions in this tissue are bound to the pigment in situ. Combined with previous histochemical data, these observations have implications for the mechanism through which neuromelanin accumulates in vivo and are consistent with its having a cytoprotective function under normal conditions, but a cytotoxic role at advanced ages and in patients with Parkinson's disease. Other results of this study show that homogenizing tissues during the purification of any natural pigment may cause contamination of the pigment by extraneous metal ions and that subsequent incubation in hot acid, though most effective in removing metal ions and hydrolyzing proteins, leads to degradation of melanin. A purification procedure using incubation in acid at room temperature, however, is well suited for identifying and characterizing unknown natural pigments by electron paramagnetic resonance spectroscopy. C1 UNIV ILLINOIS, COLL MED, URBANA, IL 61801 USA. MASSACHUSETTS GEN HOSP, MR PHARMACEUT PROGRAM, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CTR NMR, DEPT RADIOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. DARTMOUTH COLL, HITCHCOCK MED CTR, DARTMOUTH MED SCH, HANOVER, NH 03756 USA. FU NCRR NIH HHS [RR-01811] NR 77 TC 33 Z9 35 U1 0 U2 1 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 1993 VL 61 IS 1 BP 68 EP 79 DI 10.1111/j.1471-4159.1993.tb03538.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA LH227 UT WOS:A1993LH22700007 PM 8390568 ER PT J AU MILLER, A ZHANG, ZJ SOBEL, RA ALSABBAGH, A WEINER, HL AF MILLER, A ZHANG, ZJ SOBEL, RA ALSABBAGH, A WEINER, HL TI SUPPRESSION OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS BY ORAL-ADMINISTRATION OF MYELIN BASIC-PROTEIN .6. SUPPRESSION OF ADOPTIVELY TRANSFERRED DISEASE AND DIFFERENTIAL-EFFECTS OF ORAL VS INTRAVENOUS TOLERIZATION SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ORAL TOLERANCE; MYELIN BASIC PROTEIN ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; GROWTH-FACTOR-BETA; T-CELL; IMMUNE-RESPONSES; SELF-TOLERANCE; II COLLAGEN; ANTIGEN; MECHANISM; LYMPHOCYTES; SPECIFICITY AB Antigen-driven tolerance is an effective method of suppressing cell-mediated immune responses. We have previously shown that oral administration of myelin basic protein (MBP) suppresses experimental autoimmune encephalomyelitis (EAE) when it is actively induced by MBP emulsified in complete Freund's adjuvant. In order to further study antigen-driven tolerance in this model, we investigated the effect of oral tolerization on adoptively transferred EAE and compared oral tolerance to intravenously (i.v.) administered MBP in both actively induced EAE and adoptively transferred EAE. Although orally tolerized animals were not protected from adoptively transferred EAE, spleen cells from orally tolerized animals suppressed adoptively transferred EAE when co-transferred with encephalitogenic cells or when injected into recipient animals at a different site at the time encephalitogenic cells were transferred. This suppression was mediated by CD8+ T cells, correlated with suppression of DTH responses to MBP, and was associated with decreased inflammation in the spinal cord. Unlike oral tolerization, spleen cells from i.v. tolerized animals did not suppress adoptively transferred EAE when co-transferred with encephalitogenic cells although i.v. tolerized animals were protected from adoptively transferred EAE. MBP peptides were then utilized to further characterize differences between i.v. and oral tolerization in the actively induced disease model. Both orally and intravenously administered MBP suppressed actively induced EAE. However, EAE was only suppressed by prior i.v. tolerization with the encephalitogenic MBP peptide 71-90, but not with the non-encephalitogenic peptide 21-40, whereas prior tolerization with 21-40 did suppress actively induced EAE when administered orally. These results suggest a different mechanism of tolerance is initiated by oral vs. intravenous administered antigen. Specifically, oral tolerization suppresses primarily by the generation of active suppression whereas the dominant mechanism of suppression' associated with i.v. tolerization appears most consistent with the elicitation of clonal anergy. C1 BRIGHAM & WOMENS HOSP,DEPT MED,CTR NEUROL DIS,DIV NEUROL,221 LONGWOOD AVE,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. FU FIC NIH HHS [1F05TW04418]; NINDS NIH HHS [NS26773]; PHS HHS [N529352] NR 42 TC 48 Z9 49 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUL PY 1993 VL 46 IS 1-2 BP 73 EP 82 DI 10.1016/0165-5728(93)90235-Q PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA LZ487 UT WOS:A1993LZ48700010 PM 7689596 ER PT J AU FRIM, DM SIMPSON, J UHLER, TA SHORT, MP BOSSI, SR BREAKEFIELD, XO ISACSON, O AF FRIM, DM SIMPSON, J UHLER, TA SHORT, MP BOSSI, SR BREAKEFIELD, XO ISACSON, O TI STRIATAL DEGENERATION INDUCED BY MITOCHONDRIAL BLOCKADE IS PREVENTED BY BIOLOGICALLY DELIVERED NGF SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Note DE 3-NITROPROPIONIC ACID; NEUROPROTECTION; GENETICALLY ENGINEERED CELLS; NEURAL TRANSPLANTATION ID NERVE GROWTH-FACTOR; EXCITATORY AMINO-ACIDS; NEUROTROPHIC FACTOR; HUNTINGTONS-DISEASE; 3-NITROPROPIONIC ACID; NEURONAL DEGENERATION; PARKINSONS-DISEASE; FACTOR FAMILY; BRAIN; NEUROTOXICITY AB Consistent with the notion that a defect in cellular energy metabolism is a cause of human neurodegenerative disease, systemic treatment with the mitochondrial complex II inhibitor 3-nitropropionic acid (3-NPA) can model the striatal neurodegeneration seen in Huntington's disease. Previously, we have found that nerve growth factor (NGF), delivered biologically by the implantation of a genetically altered fibroblast cell-line, can protect locally against striatal degeneration induced by infusions of high doses of glutamate receptor agonists. We now report that implantation of NGF-secreting fibroblasts reduces the size of adjacent striatal 3-NPA lesions by an average of 64%. We conclude that biologically delivered NGF protects neurons against excitotoxicity and mitochondrial blockade both energy-depleting processes-implying that appropriate neurotrophic support in the adult brain could protect against neurodegenerative diseases caused in part by energy depletion. C1 MCLEAN HOSP, NEUROREGENERAT LAB, MRC-119, 115 MILL ST, BELMONT, MA 02178 USA. MASSACHUSETTS GEN HOSP, SERV NEUROSURG, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, SERV NEUROL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, NEUROGENET UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02115 USA. FU NINDS NIH HHS [NS 24279, NS 29178, NS 30064] NR 50 TC 65 Z9 66 U1 0 U2 0 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0360-4012 EI 1097-4547 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUL 1 PY 1993 VL 35 IS 4 BP 452 EP 458 DI 10.1002/jnr.490350413 PG 7 WC Neurosciences SC Neurosciences & Neurology GA LJ376 UT WOS:A1993LJ37600012 PM 8103116 ER PT J AU TAKAMIYA, Y SHORT, P MOOLTEN, FL FLEET, C MINETA, T BREAKEFIELD, XO MARTUZA, RL AF TAKAMIYA, Y SHORT, P MOOLTEN, FL FLEET, C MINETA, T BREAKEFIELD, XO MARTUZA, RL TI AN EXPERIMENTAL-MODEL OF RETROVIRUS GENE-THERAPY FOR MALIGNANT BRAIN-TUMORS SO JOURNAL OF NEUROSURGERY LA English DT Article DE GLIOMA; GENE THERAPY; RETROVIRUS; HERPES SIMPLEX VIRUS; THYMIDINE KINASE; GANCICLOVIR; MOUSE ID THYMIDINE KINASE GENES; NERVOUS-SYSTEM; GLIOMA-CELLS; RAT-BRAIN; HERPES; ASTROCYTOMAS; VECTORS; BEARING; MUTANT AB Recent research using rodent models of central nervous system gliomas indicates that a combination of gene transfer and drug treatment may be successful in killing tumor cells. In the present study, a mouse fibroblast-derived packaging cell line, psi 2, which releases a replication-defective retrovirus vector bearing the herpes simplex virus type 1 (HSV)-thymidine kinase (TK) gene, was grown with rat C6 tumor cells in the presence and absence of wild type Moloney murine leukemia virus (MoMLV). Consequently, tumor cells became sensitive to ganciclovir, which is selectively converted to a toxic nucleotide analog by HSV-TK. This killing effect was more effective in the presence than in the absence of wild type retrovirus both in culture and in subcutaneous tumors in nude mice. Tumors regressed in vivo and failed to regrow over a subsequent 10-day observation period after combined treatment with packaging cells, wild type MoMLV, and ganciclovir. This killing effect may be augmented by the ability of the helper retrovirus to package the vector in tumor cells and thus extend delivery of the HSV-TK gene to more tumor cells. This represents significant improvement in tumor therapy in this model system as compared with helper-free systems previously reported by the authors and others. Although additional improvements in the therapy can be envisioned, this approach may prove useful in combination with current modes of therapy for these insidious and lethal tumors. C1 GEORGETOWN UNIV,MED CTR,DEPT NEUROSURG,WASHINGTON,DC 20007. MASSACHUSETTS GEN HOSP,CTR NEUROSCI,NEUROSURG SERV,BOSTON,MA. MASSACHUSETTS GEN HOSP,NEUROL SERV,CAMBRIDGE,MA. EDITH NOURSE ROGERS MEM VET ADM HOSP,BEDFORD,MA 01730. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. BOSTON UNIV,SCH MED,DEPT MICROBIOL,BOSTON,MA 02118. FU NCPDCID CDC HHS [CIDA KO8012151]; NINDS NIH HHS [NS24279] NR 31 TC 130 Z9 131 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 JUL PY 1993 VL 79 IS 1 BP 104 EP 110 DI 10.3171/jns.1993.79.1.0104 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA LJ012 UT WOS:A1993LJ01200017 PM 8391069 ER PT J AU GOTTSCHALK, A JUNI, JE SOSTMAN, HD COLEMAN, RE THRALL, J MCKUSICK, KA FROELICH, JW ALAVI, A AF GOTTSCHALK, A JUNI, JE SOSTMAN, HD COLEMAN, RE THRALL, J MCKUSICK, KA FROELICH, JW ALAVI, A TI VENTILATION-PERFUSION SCINTIGRAPHY IN THE PIOPED STUDY .1. DATA-COLLECTION AND TABULATION SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article AB The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study of more than 700 patients is the largest existing study of the accuracy of lung scintigraphy in the diagnosis of acute pulmonary embolism. Perfusion scans were obtained in all patients and ventilation scans in almost all, using standardized techniques. Chest radiographs were obtained in all patients within 12 hr of the lung scan. Most patients underwent pulmonary arteriography. The images were interpreted according to a set of interpretive criteria which remained constant throughout the trial. A standardized, detailed description of each image set was derived by consensus of teams of two readers blinded to clinical and arteriographic findings. This communication reports the methods used to describe and categorize the ventilation-perfusion scintigrams obtained in patients who were enrolled in the PIOPED study. Scintigraphic technique is reviewed briefly, probability assessment is described and the scan description is reviewed in detail. The form used to describe the findings on ventilation-perfusion scans is reproduced. Use of this standardized description permits retrospective evaluation of the PIOPED interpretive criteria. In addition, it represents a rigorous approach to scan analysis which could facilitate application of formal interpretive schemes and enhance the reproducibility of lung scan interpretations in the clinical setting. C1 DUKE UNIV,MED CTR,DEPT RADIOL,BOX 3808,DURHAM,NC 27710. WILLIAM BEAUMONT HOSP,DEPT RADIOL,ROYAL OAK,MI 48072. SWEDISH MED CTR,RADIOL IMAGING ASSOCIATES,ENGLEWOOD,CO. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HOSP UNIV PENN,DEPT RADIOL,PHILADELPHIA,PA 19104. MICHIGAN STATE UNIV,DEPT RADIOL,E LANSING,MI 48824. FU NHLBI NIH HHS [N01-HR-34007, N01-HR-34009, N01-HR-34008] NR 1 TC 68 Z9 71 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 1993 VL 34 IS 7 BP 1109 EP 1118 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LL238 UT WOS:A1993LL23800019 PM 8315487 ER PT J AU GOTTSCHALK, A SOSTMAN, HD COLEMAN, RE JUNI, JE THRALL, J MCKUSICK, KA FROELICH, JW ALAVI, A AF GOTTSCHALK, A SOSTMAN, HD COLEMAN, RE JUNI, JE THRALL, J MCKUSICK, KA FROELICH, JW ALAVI, A TI VENTILATION-PERFUSION SCINTIGRAPHY IN THE PIOPED STUDY .2. EVALUATION OF THE SCINTIGRAPHIC CRITERIA AND INTERPRETATIONS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID PULMONARY-EMBOLISM; DIAGNOSIS; SCAN; DISEASE; DEFECTS AB This article presents an evaluation of the criteria used for categorical interpretation of the ventilation-perfusion (V/Q) scans performed in the PIOPED study. In addition, the correlation of percent probability estimates with the actual frequency of pulmonary embolism (PE) is presented. Cases which met the PIOPED criteria for various diagnostic categories were selected by computerized search of the detailed scan descriptions that had been done as part of the study. The process by which the scans were described was detailed in Part I of this report. Most of the criteria appropriately categorized V/Q scans which satisfied them. However, we recommend that three criteria should be reconsidered: 1. A single moderate perfusion defect is appropriately categorized as intermediate, rather than as low probability. 2. Extensive matched V/Q abnormalities are appropriate for low probability, provided that the chest radiograph is clear. On the other hand, single-matched defects may be better categorized as intermediate probability. Although due to the small number of cases with this finding, no definite, statistically founded recommendation can be made. 3. Two segmental mismatches may not be the optimum threshold for high probability, and in some cases should be considered for intermediate probability. However, due to the small number of cases with this finding, no definite, statistically founded recommendation can be made. We suggest that the revised criteria resulting from these adjustments should now be used for the interpretation of V/Q scans. C1 DUKE UNIV,MED CTR,DEPT RADIOL,BOX 3808,DURHAM,NC 27710. MICHIGAN STATE UNIV,DEPT RADIOL,E LANSING,MI 48824. HOSP UNIV PENN,DEPT RADIOL,PHILADELPHIA,PA 19104. WILLIAM BEAUMONT HOSP,DEPT RADIOL,ROYAL OAK,MI 48072. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. SWEDISH MED CTR,RADIOL IMAGING ASSOCIATES,ENGLEWOOD,CO. FU NHLBI NIH HHS [N01-HR-34009, N01-HR-34008, N01-HR-34007] NR 20 TC 237 Z9 244 U1 1 U2 4 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 1993 VL 34 IS 7 BP 1119 EP 1126 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LL238 UT WOS:A1993LL23800020 PM 8315488 ER PT J AU BARRIOS, C CASTRESANA, JS RUIZ, J KREICBERGS, A AF BARRIOS, C CASTRESANA, JS RUIZ, J KREICBERGS, A TI AMPLIFICATION OF C-MYC ONCOGENE AND ABSENCE OF C-HA-RAS POINT MUTATION IN HUMAN BONE SARCOMA SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID FACTOR RECEPTOR GENE; CELL LUNG-CANCER; ENHANCED EXPRESSION; PROTO-ONCOGENE; BREAST-CANCER; NUCLEOTIDE-SEQUENCE; GASTRIC-CANCER; N-MYC; TUMORS; PROTOONCOGENE AB The genomic organization of four oncogenes, c-myc, c-myb, c-Ha-ras, and v-fms, was analyzed in 21 patients with malignant bone tumors. Amplification of the c-myc proto-oncogene without rearrangement was the sole abnormality detected in four tumors: two chondrosarcomas, one osteosarcoma, and one lymphoma of bone. DNA hybridizations with c-myb, c-Ha-ras, and v-fms probes disclosed no structural gene abnormalities. Point mutations at the 12th codon of the c-Ha-ras gene were investigated with the polymerase chain reaction technique; no alterations were detected. The observed amplification of the c-myc there was not related to histologic type, grade, surgical stage, or ploidy level of the tumors. The results indicated that c-myc amplification, presumed to be involved in the development of malignancy in a variety of solid tumors, is encountered sporadically in malignant bone tumors; however, this occurs without relation to common histopathologic features. The clinical significance of oncogene amplification in bone sarcoma remains to be established. C1 KAROLINSKA HOSP,DEPT TUMOR PATHOL,S-10401 STOCKHOLM 60,SWEDEN. MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02114. KAROLINSKA HOSP,DEPT ORTHOPED,S-10401 STOCKHOLM 60,SWEDEN. OI Castresana, Javier S./0000-0002-2373-482X NR 52 TC 32 Z9 34 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD JUL PY 1993 VL 11 IS 4 BP 556 EP 563 DI 10.1002/jor.1100110410 PG 8 WC Orthopedics SC Orthopedics GA LQ688 UT WOS:A1993LQ68800009 PM 8101872 ER PT J AU NOGUCHI, M SEILER, JG GELBERMAN, RH SOFRANKO, RA WOO, SLY AF NOGUCHI, M SEILER, JG GELBERMAN, RH SOFRANKO, RA WOO, SLY TI IN-VITRO BIOMECHANICAL ANALYSIS OF SUTURE METHODS FOR FLEXOR TENDON REPAIR SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID CONTROLLED PASSIVE MOBILIZATION; MOTION AB This study was designed to compare five different suture methods that are used clinically for tendon repair. The flexor digitorum profundus tendons from the digits of adult mongrel dogs and adult human cadavers were used as models. The tendons in zone II of the hand, defined as the region from the distal palmar crease to the insertion of the flexor digitorum superficialis tendon at the middle phalanx, were transected and then were repaired by one of the suture methods developed by Kessler, Tsuge, Tajima, Savage, or Lee. The gliding function and tensile properties of the repaired tendons were evaluated biomechanically at time zero. The Tajima and Savage methods produced better gliding function than the other techniques. In the canine specimens that had been repaired by one of these two methods, the rotation of the distal interphalangeal joint was more than 60% of the rotation of the canine control specimens; only the Savage technique produced a rotation 124% that of the human control specimens. After the Tajima repair, the rotation of the proximal interphalangeal joint was 113% that of the canine control specimens and 157% that of the human controls. In the canine specimens that had had the Tajima or Savage repair, excursion of the tendon was greater than 55% that of the controls. The tendons repaired by the Savage method tolerated a significantly higher ultimate load to failure (14 and 25% that of the canine and human control specimens, respectively) than the other methods. Of the suture methods that were tested, the Savage technique provides sufficiently satisfactory gliding function and has enough initial stiffness and strength that it may be able to withstand early active mobilization following primary repair of flexor tendons. C1 UNIV PITTSBURGH,DEPT ORTHOPAED SURG,MUSCULOSKELETAL RES CTR,1010 KAUFMAN BLDG,3471 5TH AVE,PITTSBURGH,PA 15213. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. FU NIAMS NIH HHS [AR33097] NR 35 TC 64 Z9 64 U1 0 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD JUL PY 1993 VL 11 IS 4 BP 603 EP 611 DI 10.1002/jor.1100110415 PG 9 WC Orthopedics SC Orthopedics GA LQ688 UT WOS:A1993LQ68800014 PM 8340832 ER PT J AU CANNON, SC COREY, DP AF CANNON, SC COREY, DP TI LOSS OF NA+ CHANNEL INACTIVATION BY ANEMONE TOXIN (ATX II) MIMICS THE MYOTONIC STATE IN HYPERKALEMIC PERIODIC PARALYSIS SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID ADYNAMIA EPISODICA HEREDITARIA; SKELETAL-MUSCLE FIBERS; SINGLE SODIUM-CHANNELS; SEA-ANEMONE; PARAMYOTONIA-CONGENITA; ALPHA-SUBUNIT; SULCATA; GENE; POTASSIUM; CHLORIDE AB 1. Mutations that impair inactivation of the sodium channel in skeletal muscle have recently been postulated to cause several heritable forms of myotonia in man. A peptide toxin from Anemonia sulcata (ATX II) selectively disrupts the inactivation mechanism of sodium channels in a way that mimics these mutations. We applied ATX II to rat skeletal muscle to test the hypothesis that myotonia is inducible by altered sodium channel function. 2. Single-channel sodium currents were measured in blebs of surface membrane that arose from the mechanically disrupted fibres. ATX II impaired inactivation as demonstrated by persistent reopenings of sodium channels at strongly depolarized test potentials. A channel failed to inactivate, however, in only a small proportion of the depolarizing steps. With micromolar amounts of ATX II, the ensemble average open probability at the steady state was 0.01-0.02. 3. Ten micromolar ATX II slowed the relaxation of tension after a single twitch by an order of magnitude. Delayed relaxation is the in vitro analogue of the stiffness experienced by patients with myotonia. However, peak twitch force was not affected within the range of 0-10 mum ATX II. 4. Intracellular injection of a long-duration, constant current pulse elicited a train of action potentials in ATX II-treated fibres. After-depolarizations and repetitive firing often persisted beyond the duration of the stimulus. Trains of action potentials varied spontaneously in amplitude and firing frequency in a similar way to the electromyogram of a myotonic muscle. Both the after-depolarization and the post-stimulus firing were abolished by detubulating the fibres with glycerol. 5. We conclude that a loss of sodium channel inactivation alone, without changes in resting membrane conductance, is sufficient to produce the electrical and mechanical features of myotonia. Furthermore, in support of previous studies on myotonic muscle from patients, this model provides direct evidence that only a small proportion of sodium channels needs to function abnormally to cause myotonia. C1 HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02114. RP CANNON, SC (reprint author), MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,DEPT NEUROL,BOSTON,MA 02114, USA. NR 34 TC 52 Z9 52 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUL PY 1993 VL 466 BP 501 EP 520 PG 20 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA LM081 UT WOS:A1993LM08100027 PM 8105077 ER PT J AU KAMEI, K IDE, Y AF KAMEI, K IDE, Y TI THE PEDICLED ARTERIALIZED VENOUS FLAP SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Article AB The arterialized venous flap, in which arterial blood flowing through a vein returns to the venous system through the pedicle, was devised to solve the problems of increasing flap size and raising the overall success rate. This flap can obtain satisfactory blood inflow and pressure. The flap was clinically applied to reconstruct skin defects in three cases, with two complete successes and one partial superficial necrosis. This technique provides a flap to cover a relatively large defect, with no shunt formation, and a high success rate. RP KAMEI, K (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,50 BLOSSOM ST,BOSTON,MA 02114, USA. NR 0 TC 7 Z9 9 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0743-684X J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD JUL PY 1993 VL 9 IS 4 BP 287 EP 291 DI 10.1055/s-2007-1006669 PG 5 WC Surgery SC Surgery GA LL782 UT WOS:A1993LL78200008 PM 8410788 ER PT J AU ORTIZBRAVO, E SCHUMACHER, HR AF ORTIZBRAVO, E SCHUMACHER, HR TI COMPONENTS GENERATED LOCALLY AS WELL AS SERUM ALTER THE PHLOGISTIC EFFECT OF MONOSODIUM URATE CRYSTALS IN-VIVO SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE GOUT; SELF-LIMITED INFLAMMATION; IN-VIVO ID CALCIUM PYROPHOSPHATE DIHYDRATE; INDUCED INFLAMMATION; HUMAN-NEUTROPHILS; PROTEIN ADSORPTION; KNEE JOINTS; BINDING; GOUT; MONOHYDRATE; STIMULATION; MEDIATOR AB Proteins binding monosodium urate (MSU) crystals alter their phlogistic potential in vitro and in vivo. These proteins and other materials capable of interacting with crystals could enter the joint space from the circulation and/or could be produced locally. Using the rat subcutaneous air pouch synovium-like model, we observed different effects of collected pouch fluid supernatants from acute (6 h) and from subsiding (72 h) inflammation, and from autologous rat serum on MSU crystal induced inflammation in new air pouches. Plain crystals at 6 h produced a mean leukocyte count (WBC) of 18,156/mm3 with 12% of cells showing phagocytosis of MSU; reaction to plain crystals at 72 h had subsided to only 75 WBC/mm3 and 1% phagocytosis; new crystals preincubated in supernatant from acutely inflamed 6 h air pouches produced higher numbers of WBC in new pouches at 6 h (34,044/mm3); while crystals preincubated in 72 h supernatant gave only 9,825/mm3 and 7% phagocytosis; crystals preincubated in rat serum produced similar pouch WBC to plain crystals at 6 h, but resulted in only 2% phagocytosis. Our study provides evidence that components generated locally during subsiding inflammation as well as serum components could bind to MSU crystals and affect the generation of chemotactic factors and/or crystal phagocytosis contributing in the self-limited nature of acute gouty arthritis. C1 UNIV PENN,SCH MED,VET AFFAIRS MED CTR,CTR ARTHRITIS IMMUNOL 151K,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DIV RHEUMATOL,PHILADELPHIA,PA 19104. NR 45 TC 7 Z9 7 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 1993 VL 20 IS 7 BP 1162 EP 1166 PG 5 WC Rheumatology SC Rheumatology GA LM769 UT WOS:A1993LM76900014 PM 8371210 ER PT J AU WILENS, TE BIEDERMAN, J BALDESSARINI, RJ PUOPOLO, PR FLOOD, JG AF WILENS, TE BIEDERMAN, J BALDESSARINI, RJ PUOPOLO, PR FLOOD, JG TI ELECTROCARDIOGRAPHIC EFFECTS OF DESIPRAMINE AND 2-HYDROXYDESIPRAMINE IN CHILDREN, ADOLESCENTS, AND ADULTS TREATED WITH DESIPRAMINE SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE TRICYCLIC ANTIDEPRESSANTS; DESIPRAMINE; HYDROXYDESIPRAMINE; ELECTROCARDIOGRAM; PEDIATRICS ID ATTENTION DEFICIT DISORDER; PLASMA-LEVELS; TRICYCLIC ANTIDEPRESSANTS; HYPERACTIVE-CHILDREN; SUDDEN-DEATH; IMIPRAMINE; METABOLITES; 10-HYDROXYNORTRIPTYLINE; METHYLPHENIDATE; KINETICS AB Objective: To assess the developmental effects of desipramine (DMI) treatment on the electrocardiogram (ECG), we investigated serum concentrations of DMI ([DMI]), and its major active metabolite 2-hydroxy-desipramine ([OHDMI]) and ECG parameters. Methods: ECGs and [DMI] and [OHDMI] were analyzed from 50 children, 39 adolescents, and 30 adult psychiatric patients receiving DMI. Results: There were modest overall correlations between [DMI], [OHDMI], or [OHDMI+DMI], and the PR and QRS intervals when data from all 119 subjects were pooled. Within the pediatric age groups there were no significant associations between serum drug levels and heart rate or conduction intervals; and in all subjects with ECG abnormalities, there were some findings of higher [DMI], [OHDMI], and [OHDMI+DMI]. Conclusions: These findings indicate that only modest associations of [DMI] and [OHDMI] with ECG conduction intervals were found, and are not likely to be clinically significant in any of the age groups studied. Compared with adults, children and adolescents do not appear to be at increased risks for ECG changes related to DMI treatment or to circulating concentrations of [DMI] or [OHDMI]. C1 MCLEAN HOSP,MAILMAN RES CTR,BELMONT,MA 02178. HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CLIN CHEM LAB,BOSTON,MA 02114. RP WILENS, TE (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,PEDIAT PSYCHOPHARMACOL UNIT,ACC 725,BOSTON,MA 02114, USA. FU NIMH NIH HHS [NIMH MH-31154, NIMH MH-41314, NIMH MH-47370] NR 42 TC 35 Z9 35 U1 0 U2 1 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 JUL PY 1993 VL 32 IS 4 BP 798 EP 804 DI 10.1097/00004583-199307000-00014 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA LH947 UT WOS:A1993LH94700014 PM 8340301 ER PT J AU BIEDERMAN, J BALDESSARINI, RJ GOLDBLATT, A LAPEY, KA DOYLE, A HESSLEIN, PS AF BIEDERMAN, J BALDESSARINI, RJ GOLDBLATT, A LAPEY, KA DOYLE, A HESSLEIN, PS TI A NATURALISTIC STUDY OF 24-HOUR ELECTROCARDIOGRAPHIC RECORDINGS AND ECHOCARDIOGRAPHIC FINDINGS IN CHILDREN AND ADOLESCENTS TREATED WITH DESIPRAMINE SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE CARDIAC; CHILDREN; DESIPRAMINE; DRUG LEVELS; ADVERSE EFFECTS ID ATTENTION DEFICIT DISORDER; DEPRESSED-PATIENTS; IMIPRAMINE; DISEASE; PLASMA; BOYS; ADD AB Objective: Recent studies assessing cardiovascular effects of desipramine (DMI) in pediatric patients consistently have found small, clinically benign, but statistically significant, increases in heart rate and electrocardiographic (ECG) conduction parameters. However, single, routine ECG recordings cannot fully assess potential infrequent rhythm disturbances. Method: We analyzed data from 24-hour ECG monitoring, two-dimensional Doppler echocardiography, and expert clinical cardiac examination of DMI-treated patients. Subjects were 71 children (N = 35) and adolescents (N = 36) receiving long-term treatment (XBAR +/- SD = 1.5 +/- 1.2 years, median = 1.0 year) with DMI (XBAR +/- SD = 3.5 +/- 1.6 mg/kg). Results: Compared with previous observations in untreated healthy children, DMI-treated patients had significantly lower rates of sinus pauses and junctional rhythm, but significantly higher rates of single or paired premature atrial contractions and runs of supraventricular tachycardia. There was an association between DMI serum levels and paired premature atrial contractions, but no other associations were detected. Conclusions: These findings support the impression from previous ECG studies that DMI-associated cardiac effects in pediatric patients are quite benign. Nevertheless, it remains to be ascertained whether even minor cardiac abnormalities may predict later, evidently rare, adverse cardiovascular effects that may include sudden death. C1 MCLEAN HOSP,MAILMAN RES CTR,PSYCHIAT RES LABS,BELMONT,MA 02178. HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA 02115. CHILDRENS HOSP,ST PAUL,MN. UNIV MINNESOTA,VARIETY CLUB CHILDRENS HOSP,SCH MED,MINNEAPOLIS,MN 55455. RP BIEDERMAN, J (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,ACC-725,15 PARKMAN ST,BOSTON,MA 02114, USA. FU NIMH NIH HHS [NIMH R01 MH-41314-01A2, NIMH MH-31154, NIMH-47370] NR 28 TC 49 Z9 49 U1 1 U2 2 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 JUL PY 1993 VL 32 IS 4 BP 805 EP 813 DI 10.1097/00004583-199307000-00015 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA LH947 UT WOS:A1993LH94700015 PM 8340302 ER PT J AU BIEDERMAN, J ROSENBAUM, JF BOLDUCMURPHY, EA FARAONE, SV CHALOFF, J HIRSHFELD, DR KAGAN, J AF BIEDERMAN, J ROSENBAUM, JF BOLDUCMURPHY, EA FARAONE, SV CHALOFF, J HIRSHFELD, DR KAGAN, J TI A 3-YEAR FOLLOW-UP OF CHILDREN WITH AND WITHOUT BEHAVIORAL-INHIBITION SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE BEHAVIORAL INHIBITION; TEMPERAMENT; LONGITUDINAL; CHILDREN; ANXIETY ID PANIC DISORDER; ANXIETY DISORDERS; SEPARATION ANXIETY; SEMISTRUCTURED INTERVIEW; YOUNG-CHILDREN; AGORAPHOBIA; ADOLESCENTS; PARENTS; FAMILY; RELIABILITY AB Objective: Previous work suggested that children of parents with panic disorder and agoraphobia were likely to be classified as behaviorally inhibited and that behaviorally inhibited children were likely to develop anxiety disorders. Although these findings suggested that ''behavioral inhibition to the unfamiliar'' may be associated with risk for anxiety disorders in children, longitudinal data were needed to confirm the initial impressions. Method: Using DSM-III structured interviews, the authors examined psychiatric disorders at 3-year follow-up in children of two independently ascertained, previously described, and preexisting samples of children. One sample was cross sectional and clinically derived (Massachusetts General Hospital at-risk sample), and the other was epidemiologically derived and longitudinal (Kagan et al. Longitudinal Cohort). Results: Analyses of follow-up findings revealed significant differences between inhibited and not inhibited children in the rates of multiple greater-than-or-equal-to 4 psychiatric disorders, multiple greater-than-or-equal-to 2 anxiety disorders, avoidant disorder, separation anxiety disorder, and agoraphobia. Among inhibited children, the rates of anxiety disorders increased markedly from baseline to follow-up assessments, attaining statistical significance for multiple greater-than-or-equal-to 2 anxiety disorders and avoidant disorder. Our findings also show there were significant differences between inhibited and not inhibited children in the emergence of multiple greater-than-or-equal-to 2 anxiety disorders, avoidant disorder, and separation anxiety disorder in children who did not have these diagnoses at baseline. Conclusions: These findings indicate that inhibited children are at high fisk for developing childhood-onset anxiety disorders and provide additional support for the hypothesis that behavioral inhibition is a predictor of later anxiety disorder. C1 MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BEHAV THERAPY UNIT,BOSTON,MA 02114. HARVARD UNIV,BROCKTON W ROXBURY VET ADM MED CTR,SCH MED,BOSTON,MA 02115. UNIV MASSACHUSETTS,CTR MENTAL HLTH,DEPT PSYCHIAT,BOSTON,MA 02125. BOSTON UNIV,DOCTORAL PROGRAM CLIN PSYCHOL,BOSTON,MA 02215. HARVARD UNIV,DEPT PSYCHOL & SOCIAL RELAT,CAMBRIDGE,MA 02138. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-40619] NR 32 TC 295 Z9 298 U1 4 U2 27 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 JUL PY 1993 VL 32 IS 4 BP 814 EP 821 DI 10.1097/00004583-199307000-00016 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA LH947 UT WOS:A1993LH94700016 PM 8340303 ER PT J AU HERZOG, DB SACKS, NR KELLER, MB LAVORI, PW VONRANSON, KB GRAY, HM AF HERZOG, DB SACKS, NR KELLER, MB LAVORI, PW VONRANSON, KB GRAY, HM TI PATTERNS AND PREDICTORS OF RECOVERY IN ANOREXIA-NERVOSA AND BULIMIA-NERVOSA SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ANOREXIA NERVOSA; BULIMIA NERVOSA; RECOVERY; PREDICTORS ID LONG-TERM FOLLOW; ADOLESCENTS; INTERVIEW; RELAPSE AB Objective: The purpose of this study was to assess the course and outcome of anorexia nervosa and bulimia nervosa at 1 year in a large cohort of women with eating disorders. Method: A prospective, naturalistic, longitudinal design was used to map the course of 225 women with anorexia nervosa, bulimia nervosa, and mixed anorexia and bulimia nervosa. Structured interviews were conducted quarterly. Follow-up data are presented in terms of patterns of recovery, clinical features predictive of time to recovery, and the role of comorbid disorders as fixed predictors. Results: The recovery rate of bulimics was significantly better than that of anorexic or mixed subjects, yet nearly half the anorexic and mixed subjects no longer met full DSM-III-R criteria for at least 8 consecutive weeks during the first year of follow-up. Percent ideal body weight and type of eating disorder were significantly associated with outcome. Conclusions: Our findings suggest that the diagnosis of anorexia nervosa has severe implications. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. BROWN UNIV,DEPT PSYCHIAT & HUMAN BEHAV,PROVIDENCE,RI 02912. STANFORD UNIV,MED CTR,SCH MED,DIV BIOSTAT,STANFORD,CA 94305. RP HERZOG, DB (reprint author), MASSACHUSETTS GEN HOSP,EATING DISORDERS UNIT,ACC 725,15 PARKMAN ST,BOSTON,MA 02114, USA. RI von Ranson, Kristin/C-1447-2014 OI von Ranson, Kristin/0000-0001-6023-7948 FU NIMH NIH HHS [R01 MH38333-01A5] NR 39 TC 106 Z9 108 U1 1 U2 9 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 JUL PY 1993 VL 32 IS 4 BP 835 EP 842 DI 10.1097/00004583-199307000-00020 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA LH947 UT WOS:A1993LH94700020 PM 8340307 ER PT J AU ANDERSON, EJ RICHARDSON, M CASTLE, G CERCONE, S DELAHANTY, L LYON, R MUELLER, D SNETSELAAR, L AF ANDERSON, EJ RICHARDSON, M CASTLE, G CERCONE, S DELAHANTY, L LYON, R MUELLER, D SNETSELAAR, L TI NUTRITION INTERVENTIONS FOR INTENSIVE THERAPY IN THE DIABETES CONTROL AND COMPLICATIONS TRIAL SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID METABOLIC CONTROL; INSULIN; MELLITUS; DIET AB As part of an intensive treatment regimen that had as its goal achieving and maintaining blood glucose levels in the normal range in individuals with insulin-dependent diabetes mellitus, dietitians in the Diabetes Control and Complications Trial implemented varying nutrition intervention strategies to counsel patients to attain normoglycemia. Dietary management encompassed recommendations on altering insulin dosages for varying food intake. Nutrition intervention was tailored to best meet a participant's life-style, motivation, ability to grasp information, diet history, and specific intensive insulin therapy. Dietitians were integral participants in the team management of individuals in the intensive treatment group. Selected nutrition interventions-Healthy Food Choices, exchange systems, carbohydrate counting, and total available glucose-and behavior management approaches were coupled with intensive insulin therapy. Case presentations illustrate each nutrition intervention in the attainment of normoglycemia. C1 CORNELL UNIV, MED CTR, NEW YORK HOSP, COLL MED, NEW YORK, NY 10021 USA. UNIV CALIF SAN DIEGO, CLIN RES FACIL, LA JOLLA, CA 92093 USA. MASSACHUSETTS GEN HOSP, DEPT DIETET DIABET CONTROL & COMPLICAT TRIAL, BOSTON, MA 02114 USA. INT DIABET CTR, MINNEAPOLIS, MN 55416 USA. UNIV IOWA, GEN HOSP, DEPT INTERNAL MED, IOWA CITY, IA 52242 USA. UNIV TEXAS, SW MED CTR, DEPT INTERNAL MED, DALLAS, TX 75235 USA. RI Zinman, Bernard/E-7266-2013 NR 20 TC 64 Z9 70 U1 1 U2 5 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUL PY 1993 VL 93 IS 7 BP 768 EP 772 DI 10.1016/0002-8223(93)91750-K PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LT801 UT WOS:A1993LT80100005 PM 8320402 ER PT J AU MALMROSE, LC GRAY, SL PIEPER, CF BLAZER, DG ROWE, JW SEEMAN, TE ALBERT, MS AF MALMROSE, LC GRAY, SL PIEPER, CF BLAZER, DG ROWE, JW SEEMAN, TE ALBERT, MS TI MEASURED VERSUS ESTIMATED CREATININE CLEARANCE IN A HIGH-FUNCTIONING ELDERLY SAMPLE - MACARTHUR-FOUNDATION STUDY OF SUCCESSFUL AGING SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID RENAL-FUNCTION; SERUM CREATININE; AGE; PREDICTION; INDEX AB Objective: To assess the validity of several equations for estimating creatinine clearance in a large sample of high-functioning, community-dwelling elderly. Design: Serum and 12-hour urine samples were collected and assayed for creatinine using the Jaffe total chromagen method. Fifteen clearance-estimating equations were evaluated for bias, accuracy, correlation with measured clearance values, and frequency of erroneous placement into renal function categories. Stepwise regression modeling and reliability testing were performed on a split sample to construct and assess a novel creatinine-clearance-estimating equation. Setting: New Haven, Connecticut, East Boston, Massachusetts, and a five-county region in and around Durham, North Carolina. Participants: A subsample of community-dwelling men and women (age range 70-79 years) from the Established Populations for Epidemiological Studies of the Elderly was screened for physical and cognitive functioning and placed into high-, medium-, and low-functioning groups (n = 1354). High-functioning respondents who provided blood and complete urine samples (n = 762) were included in the present study. Results: In general, estimated creatinine clearance was more closely correlated to measured values in males than in females. Most equations underestimated creatinine clearance, with average bias ranging from -33.1 mL/min to +19.6 mL/min. Predictive accuracy ranged from 18.2 mL/min to 38.0 mL/min. Equations were variable in their erroneous placement of individuals into renal function categories. Regression modeling yielded an equation which contained novel components but failed to provide better estimates of creatinine clearance than those already available. Conclusions: The equations evaluated here provide unacceptable predictions of creatinine clearance in normally aging individuals. We advocate the use of serum drug concentration measurements when available and encourage investigation into timed urine collections of short duration as alternatives to clearance-estimating equations in the elderly. C1 DUKE UNIV MED CTR,CTR STUDY AGING,DURHAM,NC. DUKE UNIV,MED CTR,DEPT COMMUNITY & FAMILY MED,DURHAM,NC 27710. UNIV WISCONSIN,MADISON,WI 53706. MT SINAI MED CTR,NEW YORK,NY 10029. YALE UNIV,NEW HAVEN,CT 06520. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP MALMROSE, LC (reprint author), DUKE UNIV,MED CTR,DEPT PSYCHIAT,BOX 3875,DURHAM,NC 27710, USA. FU NIA NIH HHS [NIA N01-AG-2110] NR 42 TC 31 Z9 31 U1 0 U2 1 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 JUL PY 1993 VL 41 IS 7 BP 715 EP 721 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA LL111 UT WOS:A1993LL11100004 PM 8315180 ER PT J AU YU, YM BURKE, JF YOUNG, VR AF YU, YM BURKE, JF YOUNG, VR TI A KINETIC-STUDY OF L-2H3-METHYL-1-13C-METHIONINE IN PATIENTS WITH SEVERE BURN INJURY SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID AMINO-ACID METABOLISM; BODY PROTEIN-SYNTHESIS; METHIONINE METABOLISM; PARENTERAL-NUTRITION; URINARY-EXCRETION; HUMANS; TRANSSULFURATION; TRANSAMINATION; BREAKDOWN; LEUCINE AB To explore the consequences of severe burn injury on methionine metabolism we carried out tracer studies, using [1-C-13, H-2(3)-methyl] methionine, given by continuous intravenous infusion, in 12 adult patients. Each was studied in the ''fasted'' and in the fed state while receiving parenteral nutrition. Compared with findings obtained in our previous studies in healthy adults using a similar protocol, the rates of transmethylation (Tm), homocysteine remethylation (Rm), and methionine oxidation (C) were all substantially increased in burn patients. From the relationships between these systems, it appears that there is a relative increase in the recycling of methionine carbon via Rm during the fasted state. This implies active methyl group transfer and utilization in burn patients. Parenteral feeding increased methyl-methionine flux (Qm) and the rates of Tm, Rm, and C. However, the Tm/Qm ratio did not change with feeding in the patients, whereas it increased in healthy young adults. This may not necessarily reflect the consequences of burn injury, but may be due to differences in the route of methionine intake or its level relative to requirement, compared with the conditions of study in healthy adults. Further studies on methionine-cysteine interrelationships, using an isotopic approach, in burned patients are needed to evaluate these possibilities. C1 MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,51 BLOSSOM ST,BOSTON,MA 02114. MIT,SCH SCI,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. FU NIDDK NIH HHS [DK 15856]; NIGMS NIH HHS [GM 02700] NR 41 TC 29 Z9 29 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JUL PY 1993 VL 35 IS 1 BP 1 EP 7 DI 10.1097/00005373-199307000-00001 PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA LP571 UT WOS:A1993LP57100001 PM 8331698 ER PT J AU RIPPLE, M MULCAHY, RT WILDING, G AF RIPPLE, M MULCAHY, RT WILDING, G TI CHARACTERISTICS OF THE GLUTATHIONE GLUTATHIONE-S-TRANSFERASE DETOXIFICATION SYSTEM IN MELPHALAN RESISTANT HUMAN PROSTATE-CANCER CELLS SO JOURNAL OF UROLOGY LA English DT Article DE PROSTATE NEOPLASMS; GLUTATHIONE; GLUTATHIONE TRANSFERASES; MELPHALAN ID CYTO-TOXICITY; RAT-LIVER; BUTHIONINE SULFOXIMINE; CARCINOMA; LINE; ASSAY; ESTABLISHMENT; INHIBITION; DEPLETION; SURVIVAL AB Glutathione (GSH) and glutathione-S-transferases (GST) have been implicated in resistance of tumor cells to certain alkylating agents, including melphalan. Glutathione levels and GST activities were determined in melphalan-resistant sublines of the human prostate carcinoma cell lines DU 145, PC-3 and LNCaP produced by serial treatment with melphalan at progressively increasing concentrations. The resistant sublines M4.5DU145, M5DU145, M6DU145, M6PC-3 and M6LNCaP were 27-, 7-, 3-, 6- and 2-fold more resistant to melphalan than the parental lines. The melphalan-resistant DU 145 and PC-3 lines showed cross-resistance to cisplatin and tetraplatin, but retained sensitivity to vinblastine, colchicine and etoposide. Interestingly, both sublines were also resistant to methotrexate and adriamycin. The melphalan-resistant LNCaP line showed slight resistance to cisplatin and adriamycin, but remained sensitive to tetraplatin and methotrexate. This line also retained sensitivity to vinblastine while developing resistance to colchicine. Intracellular GSH levels were increased 2.8 fold for M5DU145, 1.7 fold for M6PC-3 and 2.1 fold for M6LNCaP compared to the parental lines, whereas GST activity using chlorodinitro-benzene as a substrate was comparable for all lines. When cumene hydroperoxide was used as a substrate, an increase in GST activity was noted only in the M6PC-3 line as compared with the parent line. Western blot analysis showed no change in GST isozyme profile between parent and resistant DU 145 lines; however a mu class isoenzyme was detected in the resistant, but not in the parent PC-3 line, using a Y(b1) antibody. M5DU145 cells maintained in the absence of melphalan for seven months maintained their resistance to melphalan. Depletion of GSH, with buthionine sulfoximine, to control levels reversed melphalan resistance to control levels. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. RP RIPPLE, M (reprint author), UNIV WISCONSIN,CTR COMPREHENS CANC,DEPT HUMAN ONCOL,K4-666 CSC,600 HIGHLAND AVE,MADISON,WI 53792, USA. FU NCI NIH HHS [CA 50590] 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 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 1993 VL 150 IS 1 BP 209 EP 214 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA LH013 UT WOS:A1993LH01300072 PM 8510259 ER PT J AU COOKE, JC CAMBRIA, RP AF COOKE, JC CAMBRIA, RP TI SIMULTANEOUS TRACHEOBRONCHIAL AND ESOPHAGEAL OBSTRUCTION CAUSED BY A DESCENDING THORACIC ANEURYSM SO JOURNAL OF VASCULAR SURGERY LA English DT Note ID TRACHEAL COMPRESSION; RESPIRATORY INSUFFICIENCY; AORTA; MANAGEMENT AB Descending thoracic aortic aneurysms are a rare cause of symptomatic airway or esophageal obstruction. We report the case of a patient with simultaneous severe dyspnea and dysphagia from the thoracic portion of a thoracoabdominal aortic aneurysm. Perioperative management of the airway obstruction was an essential component of successful treatment. Repair of the aneurysm resulted in resolution of the patient's symptoms. C1 MASSACHUSETTS GEN HOSP,DIV VASC SURG,ACC-4 SUITE 458,15 PARKMAN ST,BOSTON,MA 02114. NR 19 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 1993 VL 18 IS 1 BP 90 EP 94 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA LM777 UT WOS:A1993LM77700012 PM 8326664 ER PT J AU THALI, M MOORE, JP FURMAN, C CHARLES, M HO, DD ROBINSON, J SODROSKI, J AF THALI, M MOORE, JP FURMAN, C CHARLES, M HO, DD ROBINSON, J SODROSKI, J TI CHARACTERIZATION OF CONSERVED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120 NEUTRALIZATION EPITOPES EXPOSED UPON GP120-CD4 BINDING SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; RECEPTOR-MEDIATED ACTIVATION; ENVELOPE GLYCOPROTEIN; SOLUBLE CD4; VIRAL FUSION; HIV-1 INFECTIVITY; HTLV-III/LAV; T4 MOLECULE; PROTEIN; CELLS AB Interaction with the CD4 receptor enhances the exposure on the human immunodeficiency type 1 gp120 exterior envelope glycoprotein of conserved, conformation-dependent epitopes recognized by the 17b and 48d neutralizing monoclonal antibodies. The 17b and 48d antibodies compete with anti-CD4 binding antibodies such as 15e or 21h, which recognize discontinuous gp120 sequences near the CD4 binding region. To characterize the 17b and 48d epitopes, a panel of human immunodeficiency virus type 1 gp120 mutants was tested for recognition by these antibodies in the absence or presence of soluble CD4. Single amino acid changes in five discontinuous, conserved, and generally hydrophobic regions of the gp120 glycoprotein resulted in decreased recognition and neutralization by the 17b and 48d antibodies. Some of these regions overlap those previously shown to be important for binding of the 15e and 21h antibodies or for CD4 binding. These results suggest that discontinuous, conserved epitopes proximal to the binding sites for both CD4 and anti-CD4 binding antibodies become better exposed upon CD4 binding and can serve as targets for neutralizing antibodies. C1 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,HLTH SCI CTR,FARMINGTON,CT 06030. RP THALI, M (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIROL,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI 31783, AI 24030, AI22541] NR 91 TC 487 Z9 494 U1 2 U2 8 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 JUL PY 1993 VL 67 IS 7 BP 3978 EP 3988 PG 11 WC Virology SC Virology GA LH124 UT WOS:A1993LH12400033 PM 7685405 ER PT J AU INOUYE, SK ALBERT, MS MOHS, R SUN, K BERKMAN, LF AF INOUYE, SK ALBERT, MS MOHS, R SUN, K BERKMAN, LF TI COGNITIVE PERFORMANCE IN A HIGH-FUNCTIONING COMMUNITY-DWELLING ELDERLY POPULATION SO JOURNALS OF GERONTOLOGY LA English DT Article ID MINI-MENTAL STATE; ALZHEIMERS-DISEASE; RISK; DEMENTIA; INDEX AB Background. The purpose of this study was to examine the role of demographic factors as predictors of cognitive performance in a high-functioning, community-dwelling elderly population. Methods. The study cohort consisted of 1,192 community-dwelling subjects, who were selected to represent the highest third of an elderly population with respect to physical and cognitive functioning. A neuropsychological battery, including 5 cognitive performance subtests (confrontation naming, delayed recognition span, similarities, figure-copying, and incidental delayed recall) was administered to the subjects in their homes. Results. A summary measure of the 5 neuropsychological subtest scores, the total cognitive score, arrayed the study group across a broad range of difficulty, creating a near-normal distribution. Education, income, and race had statistically significant associations with the total score and the individual subtests. The effect of education was the most striking finding, explaining 30% of the variance in the total score. Education was most strongly related to the abstraction (partial R2 = .11) subtest, and least related to the memory subtests, delayed recognition (R2 = .02) and delayed recall (R2 = .01). Conclusions. Demographic factors are important predictors of cognitive performance in this high-functioning cohort. Education had the strongest influence on overall cognitive performance, and particularly notable associations with subtests that depended upon the use of previously learned materials. Longitudinal follow-up, now underway, will help to determine whether high levels of education help to maintain cognitive performance with age. C1 YALE UNIV,SCH MED,DEPT INTERNAL MED,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. CUNY MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. VET ADM MED CTR,BRONX,NY 10468. FU NIA NIH HHS [1K08AG00524-01] NR 31 TC 54 Z9 54 U1 1 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD JUL PY 1993 VL 48 IS 4 BP M146 EP M151 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA LL261 UT WOS:A1993LL26100030 PM 8315227 ER PT J AU PEI, Y HERCZ, G GREENWOOD, C SEGRE, G MANUEL, A SAIPHOO, C FENTON, S SHERRARD, D AF PEI, Y HERCZ, G GREENWOOD, C SEGRE, G MANUEL, A SAIPHOO, C FENTON, S SHERRARD, D TI RENAL OSTEODYSTROPHY IN DIABETIC-PATIENTS SO KIDNEY INTERNATIONAL LA English DT Article ID BONE HISTOMORPHOMETRY; DIALYSIS; UREMIA; TRANSPLANTATION; OSTEOMALACIA; HEMODIALYSIS; MELLITUS; ALUMINUM; DISEASE AB To assess the effects of diabetes mellitus on renal osteodystrophy, we examined the database of 256 patients (45% on hemodialysis and 55% on peritoneal dialysis) who were prospectively studied in three Toronto dialysis centers between October of 1987 and 1989. All patients had serial documentation of their clinical, laboratory and risk parameters of bone disease, and completed a series of investigations that included the deferoxamine test, measurement of intact 1-84 PTH levels, and an iliac crest bone biopsy. Twenty-five percent of these patients were diabetic. When compared to non-diabetic patients, they were on dialysis for a shorter duration (2.4 +/- 0.3 vs. 4.7 +/- 0.3 years; P < 0.0002), used calcium carbonate as the only phosphate binder more frequently (40 vs. 25%; P < 0.007), and had lower parathyroid hormone levels (12 +/- 1.4 vs. 24 +/- 2.3 pmol/liter; P < 0.002). High-turnover bone disorders (that is, osteitis fibrosa and mixed disorder) were distinctly uncommon (8 vs. 33%; P < 0.01 by Fisher's exact test), while the mild (19 vs. 9%; P = NS) and the aplastic disorders (with mean stainable bone surface aluminum of 6.5 +/- 0.7%) (46 vs. 31%; P = NS) tended to be more common in diabetic patients. The prevalence of aluminum bone disease was the same in both groups (27%). Diabetic patients ingested a smaller cumulative dose of aluminum gels (3.7 +/- 0.6 vs. 9.3 +/- 1. 1 kg; P < 0.005), yet had a higher rate of aluminum accumulation on bone surfaces than non-diabetic patients (1.5 +/- 0.19 vs. 0.96 +/- 0.10% per month on dialysis; P < 0.015). Although the cumulative exposure to aluminum gels remained the major risk factor for aluminum bone disease (P < 0.0001), a positive interaction was noted for diabetic mellitus to increase this risk (P < 0.05). Thus, diabetes mellitus appears to predispose dialysis patients to low bone-turnover states. In addition, it appears to increase aluminum accumulation on bone surfaces and predisposes to aluminum bone disease. The clinical significance of the aplastic disorder remains to be defined. C1 VET ADM MED CTR,SEATTLE,WA 98108. UNIV TORONTO,MOUNT SINAI RES INST,CLIN EPIDEMIOL,TORONTO M5S 1A1,ONTARIO,CANADA. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. RP PEI, Y (reprint author), TORONTO HOSP,DEPT MED,13 EN 228,TORONTO GEN SITE,200 ELIZABETH ST,TORONTO M5G 2C4,ON,CANADA. NR 33 TC 90 Z9 92 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 1993 VL 44 IS 1 BP 159 EP 164 DI 10.1038/ki.1993.226 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA LG816 UT WOS:A1993LG81600022 PM 8355457 ER PT J AU RUBIN, RH SNYDMAN, D HARRINGTON, JT MADIAS, NE KING, A MYER, K SINGH, A AF RUBIN, RH SNYDMAN, D HARRINGTON, JT MADIAS, NE KING, A MYER, K SINGH, A TI INFECTIOUS-DISEASE COMPLICATIONS OF RENAL-TRANSPLANTATION SO KIDNEY INTERNATIONAL LA English DT Discussion ID CYTOMEGALO-VIRUS INFECTION; B LIVER-DISEASE; HERPES-SIMPLEX INFECTION; HEPATITIS-B; TRIMETHOPRIM-SULFAMETHOXAZOLE; LYMPHOPROLIFERATIVE LESIONS; ORGAN-TRANSPLANTATION; ALLOGRAFT RECIPIENTS; MONOCLONAL-ANTIBODY; GLOMERULOPATHY C1 TUFTS UNIV NEW ENGLAND MED CTR, DIV NEPHROL, BOSTON, MA 02111 USA. NEWTON WELLESLEY HOSP, NEWTON LOWER FALLS, MA 02162 USA. RP RUBIN, RH (reprint author), MASSACHUSETTS GEN HOSP, INFECT DIS UNIT, BOSTON, MA 02114 USA. NR 84 TC 236 Z9 242 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD JUL PY 1993 VL 44 IS 1 BP 221 EP 236 DI 10.1038/ki.1993.234 PG 16 WC Urology & Nephrology SC Urology & Nephrology GA LG816 UT WOS:A1993LG81600030 PM 8394951 ER PT J AU MARTI, HP LOVETT, DH AF MARTI, HP LOVETT, DH TI MESANGIAL MATRIX METALLOPROTEINASES AND THEIR ROLE IN GLOMERULONEPHRITIS SO KIDNEY INTERNATIONAL LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO VET ADM MED CTR,DEPT MED,SAN FRANCISCO,CA 94143. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 1993 VL 44 IS 1 BP 258 EP 258 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA LG816 UT WOS:A1993LG81600131 ER PT J AU ELLOZY, M AF ELLOZY, M TI INTERACTIVE DIETARY INTERVIEWING FOR PATIENTS SO M D COMPUTING LA English DT Editorial Material ID FOOD FREQUENCY QUESTIONNAIRE; RECORDS RP ELLOZY, M (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0724-6811 J9 M D COMPUT JI M D Comput. PD JUL-AUG PY 1993 VL 10 IS 4 BP 206 EP 207 PG 2 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA LL176 UT WOS:A1993LL17600002 PM 8366773 ER PT J AU BURN, PR POTTS, MS MOORE, RH FISCHMAN, AJ STRAUSS, HW AF BURN, PR POTTS, MS MOORE, RH FISCHMAN, AJ STRAUSS, HW TI TISSUE DISTRIBUTION AND EXCRETION OF TC-99M-DISOFENIN IN 3 MARINE SPECIES - PLEURONECTES-AMERICANUS (WINTER FLOUNDER), HOMARUS-AMERICANUS (LOBSTER), AND MYA-ARENARIA (SOFT-SHELL CLAM) SO MARINE BIOLOGY LA English DT Article ID LESIONS; NEOPLASMS; CHEMICALS; EXPOSURE; HARBOR AB To determine the pharmacokinetics of a small lipophilic molecule in vivo, the distribution and accumulation of Tc-99m-radiolabelled disofenin (diisopropylacetanilide iminodiacetic acid) were traced during 19911992 by scintigraphy and gamma well counting in winter flounder (Pleuronectes americanus collected from Boston Harbor and Long Island Sound in 1992), lobsters (Homarus americanus collected from Massachusetts Bay in 1991), and soft-shell clams (Mya arenaria purchased in 1991). The agent was distributed throughout the bodies of lobsters within 12 s, throughout flounder within 40 s, and throughout clams within 2 min. It was concentrated most strongly by the liver of flounder, which contained 61.2 +/- 7.8 % of the injected dose within 1 h of injection, and by the lobster hepatopancreas. Accumulation also occurred in the flounder kidney, lobster antennal glands, and the kidney and pericardial glands of clams. The compound was rapidly excreted from the flounder liver into the gall bladder, and from the lobster hepatopancreas into the stomach. The data suggest its excretion from the lobster antennal glands and clam kidneys. The rate of clearance of disofenin from the body varied among species: 99 +/- 2.1 % of the initial dose remained in flounder sampled 16 to 24 h after injection, compared to 80.5 +/- 7 % remaining in the lobster after 15 h, and 87.4 +/- 5.9 % remaining in clams after 27 h. The clearance rates in flounder and lobster are considered to be minimum values because of the lack of gut activity in unfed individuals. Overall, these in vivo tracer studies establish the utility of scintigraphy for assessing the uptake and excretion of a lipid soluble compound in different taxa, and may be applicable for evaluating disease and/or environmental effects on organ function in marine animals. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV NEW HAMPSHIRE,DURHAM,NH 03824. RP BURN, PR (reprint author), SUFFOLK UNIV,BEACON HILL,BOSTON,MA 02114, USA. NR 22 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0025-3162 J9 MAR BIOL JI Mar. Biol. PD JUL PY 1993 VL 116 IS 3 BP 355 EP 361 DI 10.1007/BF00350052 PG 7 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA LN998 UT WOS:A1993LN99800002 ER PT J AU SAX, HC SOUBA, WW AF SAX, HC SOUBA, WW TI ENTERAL AND PARENTERAL FEEDINGS - GUIDELINES AND RECOMMENDATIONS SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE-RENAL-FAILURE; CHAIN AMINO-ACIDS; ACUTE-PANCREATITIS; DOUBLE-BLIND; NUTRITION; COMPLICATIONS; INFECTION; CATHETER; GUT; PREVENTION C1 MASSACHUSETTS GEN HOSP,DIV SURG ONCOL,BOSTON,MA 02114. RP SAX, HC (reprint author), UNIV ROCHESTER,SCH MED,DEPT SURG,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. FU NCI NIH HHS [CA 45327]; NHLBI NIH HHS [HL 44986] NR 45 TC 20 Z9 20 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JUL PY 1993 VL 77 IS 4 BP 863 EP 880 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA LM797 UT WOS:A1993LM79700012 PM 8321074 ER PT J AU GALL, KP VERHEY, LJ WAGNER, M AF GALL, KP VERHEY, LJ WAGNER, M TI COMPUTER-ASSISTED POSITIONING OF RADIOTHERAPY PATIENTS USING IMPLANTED RADIOPAQUE FIDUCIALS SO MEDICAL PHYSICS LA English DT Article DE PATIENT ALIGNMENT; STEREOSCOPIC LOCALIZATION; FIDUCIAL MARKERS; RADIOTHERAPY ID RADIATION-THERAPY; RADIOSURGERY AB For certain external beam radiotherapy procedures, precise alignment of patients with the treatment beam is essential for good treatment outcome. A method has been developed for quickly achieving precise Patient alignment with the aid of stereoscopically located fiducial markers. The alignment algorithm is developed from standard rigid body mechanics using closed form solutions, obviating the need for iterative fitting methods. The technique is implemented with a digitizing tablet and plane film radiographs. The accuracy of alignment with this method in phantom studies is better than 1 mm and 1 deg relative to CT data. The repeatability of positioning is 0.5 mm (standard deviation) and 0.36 deg (standard deviation). C1 HARVARD UNIV,CYCLOTRON LAB,CAMBRIDGE,MA 02138. RP GALL, KP (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 21239] NR 10 TC 69 Z9 70 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL-AUG PY 1993 VL 20 IS 4 BP 1153 EP 1159 DI 10.1118/1.596969 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LU093 UT WOS:A1993LU09300024 PM 8413025 ER PT J AU TOMERA, JF LILFORD, K AF TOMERA, JF LILFORD, K TI THE ALPHA-STUDY - MULTIPLE-REGRESSION OF THE INOSITOL 1,4,5-TRIPHOSPHATE SIGNAL-TRANSDUCTION MECHANISM IN BURN TRAUMA SO METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY LA English DT Article DE ADENOSINE 3'/5'CYCLIC MONOPHOSPHATE; BURN TRAUMA; CALCIUM; INOSITOL TRIPHOSPHATE; MULTIVARIATE ANALYSES; SKELETAL MUSCLE AB The novelty of applying 3-dimensional graphic capabilities, involving area and vector changes was used to understand variations in inositol derivatives due to the systemic effects of large body surface area (BSA) bums. This report is an attempt to broaden current perspectives on how such changes in inositol forms impact on the disposition of IP3 within skeletal muscle cells. Because it is the first of its type to evaluate systemic effects in this way, it is called the alpha study. Consideration of multiple factors (viz., 5 orders of magnitude) involved in burn trauma in this manner provides new insight into the pharmacologic changes which utilize the IP3 signal transducing system that underlie burn trauma. Such insight would prove beneficial in improving the quality of rehabilitative burn care with respect to skeletal muscle physiology. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. SHRINERS BURNS RES CTR,ANESTHESIA SERV,CLIN PHARMACOL LAB,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT ANESTHESIOL,BOSTON,MA 02115. NR 13 TC 15 Z9 15 U1 0 U2 0 PU J R PROUS SA PI BARCELONA PA APARTADO DE CORREOS 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0379-0355 J9 METHOD FIND EXP CLIN JI Methods Find. Exp. Clin. Pharmacol. PD JUL-AUG PY 1993 VL 15 IS 6 BP 395 EP 406 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LX453 UT WOS:A1993LX45300008 PM 8231459 ER PT J AU FLOTTE, TJ AF FLOTTE, TJ TI RESEARCH BY PATHOLOGISTS IN THE UNITED-STATES - ANALYSIS OF PUBLICATIONS SO MODERN PATHOLOGY LA English DT Article DE CITATION; RESEARCH SUPPORT; PATHOLOGY AB Academic pathology is a unique profession in which the ability to pursue almost any type of academic or scholarly endeavor can be supported. Although it is difficult to define methods of comparing individual achievements in medicine, for investigative activity, common measures of academic productivity are numbers of peer-reviewed publications and National Institute of Health support. Articles from pathology departments were randomly selected from MEDLINE. One hundred and five articles were examined for the following features: financial support, human subjects, the presence of a photomicrograph, molecular biology techniques, and the number of times each article was cited as determined using the Science Citation Index. The articles were assigned to one of the following categories: anatomical pathology, clinical pathology, or research. The following percentages of articles were federally funded: total, 43.8; anatomical pathology, 33.3; clinical pathology, 9.5 and research, 74.4. The citations per article for federally funded and not federally funded articles, respectively, for each as these categories was as follows: total, 18.7 and 5.3; anatomical pathology, 15.7 and 5.5; clinical pathology, 2.0 and 4.9; and research, 21.4 and 5.7. It can be concluded from the data presented that federally funded articles from departments of pathology are cited more often than articles that are not federally funded. The most impressive finding in reviewing the articles is the wide diversity of research conducted in pathology departments. The use of federal funding or citation analysis to evaluate the performance of an individual pathologist would be a mistake. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02114. RP FLOTTE, TJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,50 BLOSSOM ST,BOSTON,MA 02114, USA. FU NIAMS NIH HHS [AR40352] NR 3 TC 6 Z9 6 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 JUL PY 1993 VL 6 IS 4 BP 484 EP 486 PG 3 WC Pathology SC Pathology GA LM088 UT WOS:A1993LM08800018 PM 8415596 ER PT J AU CHITTENDEN, T LIVINGSTON, DM DECAPRIO, JA AF CHITTENDEN, T LIVINGSTON, DM DECAPRIO, JA TI CELL-CYCLE ANALYSIS OF E2F IN PRIMARY HUMAN T-CELLS REVEALS NOVEL E2F COMPLEXES AND BIOCHEMICALLY DISTINCT FORMS OF FREE E2F SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR E2F; ADENOVIRUS E1A PROTEINS; DNA-BINDING ACTIVITY; HUMAN MYC PROMOTER; TRANS-ACTIVATION; PRODUCT; GENE; SEQUENCES; TRANSACTIVATION; EXPRESSION AB The transcription factor E2F activates the expression of multiple genes involved in cell proliferation, such as c-myc and the dihydrofolate reductase gene. Regulation of E2F involves its interactions with other cellular proteins, including the retinoblastoma protein (Rb), the Rb-related protein p107, cyclin A, and cdk2. We undertook a detailed analysis of E2F DNA-binding activities and their cell cycle behavior in primary human T cells. Three E2F DNA-binding activities were identified in resting (G0) T cells with mobilities in gel shift assays distinct from those of previously defined E2F complexes. One of these activities was found to be a novel, less abundant, Rb-E2F complex. The most prominent E2F activity in resting T cells (termed complex X) was abundant in both G0 and G1 but disappeared as cells entered S phase, suggesting a possible role in negatively regulating E2F function. Complex X could be dissociated by adenovirus EIA with a requirement for an intact ElA conserved region 2. However, X failed to react with a variety of antibodies against Rb or p107, implicating the involvement of an ElA-binding protein other than Rb or p107. In addition to these novel E2F complexes, three distinct forms of unbound (free) E2F were resolved in gel shift experiments. These species showed different cell cycle kinetics. UV cross-linking experiments suggested that a distinct E2F DNA-binding protein is uniquely associated with the S-phase p107 complex and is not associated with Rb. Together, these results suggest that E2F consists of multiple, biochemically distinct DNA-binding proteins which function at different points in the cell cycle. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 49 TC 112 Z9 112 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 JUL PY 1993 VL 13 IS 7 BP 3975 EP 3983 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LJ362 UT WOS:A1993LJ36200014 PM 8321204 ER PT J AU MERIKA, M ORKIN, SH AF MERIKA, M ORKIN, SH TI DNA-BINDING SPECIFICITY OF GATA FAMILY TRANSCRIPTION FACTORS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NITROGEN REGULATORY GENE; PUTATIVE ZINC FINGER; NEUROSPORA-CRASSA; SACCHAROMYCES-CEREVISIAE; ENDOTHELIAL-CELLS; GLOBIN PROMOTER; MAMMALIAN-CELLS; EXPRESSION; PROTEIN; SEQUENCE AB GATA-binding proteins constitute a family of transcription factors that recognize a target site conforming to the consensus WGATAR (W = A or T and R = A or G). Here we have used the method of polymerase chain reaction-mediated random site selection to assess in an unbiased manner the DNA-binding specificity of GATA proteins. Contrary to our expectations, we show that GATA proteins bind a variety of motifs that deviate from the previously assigned consensus. Many of the nonconsensus sequences bind protein with high affinity, equivalent to that of conventional GATA motifs. By using the selected sequences as probes in the electrophoretic mobility shift assay, we demonstrate overlapping, but distinct, sequence preferences for GATA family members, specified by their respective DNA-binding domains. Furthermore, we provide additional evidence for interaction of amino and carboxy fingers of GATA-1 in defining its binding site. By performing cotransfection experiments, we also show that transactivation parallels DNA binding. A chimeric protein containing the finger domain of areA and the activation domains of GATA-1 is capable of activating transcription in mammalian cells through GATA motifs. Our findings suggest a mechanism by which GATA proteins might selectively regulate gene expression in cells in which they are coexpressed. C1 CHILDRENS HOSP MED CTR,DANA FARBER CANC INST,DIV HEMATOL ONCOL,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. NR 47 TC 530 Z9 535 U1 1 U2 5 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 JUL PY 1993 VL 13 IS 7 BP 3999 EP 4010 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LJ362 UT WOS:A1993LJ36200017 PM 8321207 ER PT J AU MADISON, LD AHLQUIST, JAO ROGERS, SD JAMESON, JL AF MADISON, LD AHLQUIST, JAO ROGERS, SD JAMESON, JL TI NEGATIVE REGULATION OF THE GLYCOPROTEIN HORMONE ALPHA-GENE PROMOTER BY THYROID-HORMONE - MUTAGENESIS OF A PROXIMAL RECEPTOR-BINDING SITE PRESERVES TRANSCRIPTIONAL REPRESSION SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE GLYCOPROTEIN HORMONE; THYROID HORMONE RECEPTOR; GENE EXPRESSION ID BETA-SUBUNIT GENE; RETINOIC ACID RECEPTORS; INHIBITORY ELEMENT; MAMMALIAN-CELLS; DNA-BINDING; TATA BOX; EXPRESSION; ADJACENT; JUN AB Transcription of the glycoprotein hormone alpha gene is repressed by the thyroid hormone receptor (TR) in a hormone dependent manner. Previous studies identified a TR binding site immediately downstream of the TATA box. Site directed mutagenesis and transient gene expression studies were used to evaluate the role of this TR binding site as a negative thyroid response element (nTRE). Mutagenesis of the putative negative thyroid response element (nTRE) site eliminated TR binding but failed to eliminate negative regulation by T3. A mutation which converted the putative nTRE to a higher affinity palindromic element did not enhance repression, but rather eliminated thyroid hormone dependent negative regulation. Proximal a promoter sequences between -100 and +44 were replaced with a heterologous thymidine kinase promoter resulting in a construct that was not repressed by T3 treatment. This finding confirmed that repression required proximal a promoter sequences and also indicated that repression did not occur by interference with the function of upstream the a gene enhancers. These studies indicate that TR binding adjacent to the TATA box is not required for T3 mediated repression of the alpha promoter and suggest that negative regulation may involve protein-protein interactions with promoter-specific transcription factors. C1 MASSACHUSETTS GEN HOSP,THYROID UNIT,JACKSON 1021,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [HD 28138]; NIDDK NIH HHS [DK 42144] NR 35 TC 26 Z9 26 U1 0 U2 1 PU ELSEVIER SCI 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 JUL PY 1993 VL 94 IS 1 BP 129 EP 136 DI 10.1016/0303-7207(93)90060-W PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA LL157 UT WOS:A1993LL15700016 PM 7690722 ER PT J AU DEULOFEUT, H IGLESIAS, A MIKAEL, N BING, DH AWDEH, Z YUNIS, J MARCUSBAGLEY, D KRUSKALL, MS ALPER, CA YUNIS, EJ AF DEULOFEUT, H IGLESIAS, A MIKAEL, N BING, DH AWDEH, Z YUNIS, J MARCUSBAGLEY, D KRUSKALL, MS ALPER, CA YUNIS, EJ TI CELLULAR RECOGNITION AND HLA RESTRICTION OF A MIDSEQUENCE HBSAG PEPTIDE IN HEPATITIS-B VACCINATED INDIVIDUALS SO MOLECULAR IMMUNOLOGY LA English DT Article ID SURFACE-ANTIGEN HBSAG; HAPLOTYPE CONTROLS NONRESPONSIVENESS; HUMORAL IMMUNE-RESPONSE; SUPPRESSOR T-CELLS; GENETIC-REGULATION; SYNTHETIC PEPTIDES; ANTIBODY-RESPONSES; LYMPHOCYTES-T; DETERMINANTS; HUMANS AB Vaccination with native HBsAg results in both a humoral and a cellular immune response in humans. In individuals who responded to vaccination, the HBsAg (S region) specific response, as measured by cell proliferation, diminished significantly after 12 weeks, a time when the antibody response was still vigorous. Reduced and nonreduced HBsAg were equivalent in eliciting lymphocyte proliferation. Anti-MHC class II monoclonal antibodies were used in blocking studies to demonstrate that anti-HLA-DR but not anti-HLA-DQ or anti-HLA-DP inhibited specific lymphocyte proliferation to HBsAg. Both the monomer (reduced) and dimer (nonreduced) forms of an immunodominant midsequence HBsAg peptide (amino acid residues 139-146) produced lymphocyte proliferation roughly comparable to that induced by whole HBsAg in 6 of 7 responders immunized with whole HBsAg and the peptide-induced proliferation was blocked by anti-HLA-DR but not by anti-HLA-DP antibodies. These results suggest that HBsAg p 139-146 is a major immunodominant peptide of HBsAg and is restricted by HLA-DR. C1 BETH ISRAEL HOSP,CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. AMER RED CROSS,NE REG,DEDHAM,MA 02026. FU NHLBI NIH HHS [HL-29583]; NIAID NIH HHS [AI-14157]; NICHD NIH HHS [HD-17461] NR 32 TC 29 Z9 29 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 JUL PY 1993 VL 30 IS 10 BP 941 EP 948 DI 10.1016/0161-5890(93)90019-8 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA LP878 UT WOS:A1993LP87800011 PM 8341285 ER PT J AU YU, GL KATAGIRI, F AUSUBEL, FM AF YU, GL KATAGIRI, F AUSUBEL, FM TI ARABIDOPSIS MUTATIONS AT THE RPS2 LOCUS RESULT IN LOSS OF RESISTANCE TO PSEUDOMONAS-SYRINGAE STRAINS EXPRESSING THE AVIRULENCE GENE AVRRPT2 SO MOLECULAR PLANT-MICROBE INTERACTIONS LA English DT Article DE DEFENSE RESPONSE; GENE-FOR-GENE; HYPERSENSITIVE RESPONSE ID DISEASE RESISTANCE; PV GLYCINEA; THALIANA; PATHOGENS; ELICITOR; HOST; IDENTIFICATION AB We isolated and characterized two Arabidopsis thaliana mutants that fail to mount a hypersensitive defense response (HR) when infiltrated with phytopathogenic Pseudomonas strains carrying the avirulence (avr) gene avrRpt2 but still mount an HR when infiltrated with strains carrying other avr genes. One of these mutants was isolated using a method we developed that enriches for Arabidopsis seedlings that survive vacuum-infiltration with a bacterial strain carrying an avr gene. Genetic analysis showed that the phenotypes of both mutants resulted from mutations at a single locus, RPS2. In contrast to the wild type, both rps2 mutants failed to limit the growth of Pseudomonas strains carrying avrRpt2. Heterozygous RPS2/rps2 plants displayed a phenotype intermediate between those of RPS2/RPS2 and rps2/rps2 homozygotes. These experiments show that the wild-type allele at the rps2 locus, RPS2, encodes a component of a signal transduction pathway that responds to a signal generated by avrRpt2 and that RPS2 is required for the elicitation of an HR. RPS2 was mapped near the restriction fragment length polymorphism marker PG11 on chromosome IV. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. FU NIGMS NIH HHS [GM48707] NR 34 TC 91 Z9 93 U1 1 U2 6 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 SN 0894-0282 J9 MOL PLANT MICROBE IN JI Mol. Plant-Microbe Interact. PD JUL-AUG PY 1993 VL 6 IS 4 BP 434 EP 443 DI 10.1094/MPMI-6-434 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Plant Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Plant Sciences GA LY143 UT WOS:A1993LY14300005 PM 8400373 ER PT J AU SRIVASTAVA, R BROUILLET, E BEAL, MF STOREY, E HYMAN, BT AF SRIVASTAVA, R BROUILLET, E BEAL, MF STOREY, E HYMAN, BT TI BLOCKADE OF 1-METHYL-4-PHENYLPYRIDINIUM ION (MPP+) NIGRAL TOXICITY IN THE RAT BY PRIOR DECORTICATION OR MK-801 TREATMENT - A STEREOLOGICAL ESTIMATE OF NEURONAL LOSS SO NEUROBIOLOGY OF AGING LA English DT Article DE MPP+; MK-801; SUBSTANTIA-NIGRA; STEREOLOGY; RAT; DECORTICATION; EXCITOTOXICITY ID PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; MOUSE-BRAIN; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; METABOLITE; MPTP; ABNORMALITIES; NEUROTOXICITY; PROTECTION; TRANSPORT AB 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, (MPTP), produces a parkinsonian syndrome both in man and in experimental animals. Its toxicity is mediated by a metabolite, the 1-methyl-4-phenylpyridinium ion (MPP+). When injected into the striatum, MPP+ is accumulated by dopaminergic nerve terminals and retrogradely transported to the substantia nigra pars compacta (SNc) where it causes neuronal degeneration. MPP + accumulates in mitochondria and blocks complex I of the electron transport chain. A proposed mechanism of neurotoxicity is excitotoxic neuronal degeneration induced by this energy depletion. We examined whether either prior decortication or administration of the N-methyl-D-aspartate (NMDA) receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) could prevent or diminish the selective nigral neuronal degeneration that follows unilateral intrastriatal injection of MPP+. We quantified the extent of neuronal death in the SNc ipsilateral and contralateral to the injections on Nissl-stained sections with unbiased stereological techniques. One week after injection of MPP+, approximately 75% of the SNc neurons were lost on the side of the injection. The loss was a consequence of the reduction in both SNc volume and neuronal density. Both prior decortication or the administration of MK-801 for 2 days nearly completely prevented MPP+-induced neuronal loss in the ipsilateral SNc. These results are consistent with an NMDA receptor mediated excitotoxic mechanism for MPP+-induced nigral toxicity. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,32 FRUIT ST,BOSTON,MA 02114. RI Storey, Elsdon/A-9889-2013; Brouillet, Emmanuel/B-4784-2014 OI Brouillet, Emmanuel/0000-0001-6322-7403 FU NINDS NIH HHS [NS16367, NS10828] NR 31 TC 82 Z9 83 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 1993 VL 14 IS 4 BP 295 EP 301 DI 10.1016/0197-4580(93)90114-Q PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA LL571 UT WOS:A1993LL57100003 PM 8103573 ER PT J AU MARKESBERY, WR WANG, HZ KOWALL, NW KOSIK, KS MCKEE, AC AF MARKESBERY, WR WANG, HZ KOWALL, NW KOSIK, KS MCKEE, AC TI MORPHOMETRIC IMAGE-ANALYSIS OF NEUROPIL THREADS IN ALZHEIMERS-DISEASE SO NEUROBIOLOGY OF AGING LA English DT Article DE ALZHEIMERS DISEASE; NEUROPIL THREADS; COMPUTERIZED MORPHOMETRIC IMAGE ANALYSIS; TAU IMMUNOCYTOCHEMISTRY ID PAIRED HELICAL FILAMENTS; MICROTUBULE-ASSOCIATED PROTEIN; SENILE PLAQUE NEURITES; NEUROFIBRILLARY TANGLES; FRONTAL-CORTEX; TAU; DEMENTIA; PATHOLOGY; BRAIN; ABNORMALITIES AB Neuropil threads were quantitated in the neuropil (excluding senile plaques) of the superior frontal gyrus of 6 late stage patients with Alzheimer's disease (AD) and 6 age-matched control subjects using tau immunocytochemistry and computerized morphometric image analysis. The mean percent of the area of the neuropil occupied by neuropil threads was 10.6 for AD and 0. 19 for controls (p < 1 x 10(-10)). The mean length of neuropil threads in AD was 21.9mu compared with 19.7mu for controls (p < 1 x 10(-10)). The mean area of neuropil threads was 25.3mu2 for AD and 21.3mu2 for controls (p < 1 x 10(-10)). In AD, the threads were most prominent in mid cortex (lamina 2 and 3) and least prominent in the lower cortex (lamina 5 and 6). Neuropil threads appear to lead to severe disorganization of intracortical and corticocortical connectivity and probably play a role in the cognitive failure in AD. C1 UNIV KENTUCKY,MED CTR,DEPT PATHOL NEUROPATHOL,LEXINGTON,KY 40536. UNIV KENTUCKY,MED CTR,DEPT NEUROL,LEXINGTON,KY 40536. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL & NEUROL,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,CTR NEUROL DIS,BOSTON,MA 02115. RP MARKESBERY, WR (reprint author), UNIV KENTUCKY,MED CTR,SANDERS BROWN CTR AGING 101,LEXINGTON,KY 40536, USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NIA NIH HHS [5 P50-AG05144, 1 PO1-AG05119] NR 36 TC 12 Z9 13 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 1993 VL 14 IS 4 BP 303 EP 307 DI 10.1016/0197-4580(93)90115-R PG 5 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA LL571 UT WOS:A1993LL57100004 PM 8367011 ER PT J AU CARLSON, MD PENNEY, JB YOUNG, AB AF CARLSON, MD PENNEY, JB YOUNG, AB TI NMDA, AMPA, AND BENZODIAZEPINE BINDING-SITE CHANGES IN ALZHEIMERS-DISEASE VISUAL-CORTEX SO NEUROBIOLOGY OF AGING LA English DT Article DE GLYCINE; NMDA; BENZODIAZEPINE; ALZHEIMERS DISEASE; VISUAL CORTEX; OCCIPITAL LOBE; TEMPORAL LOBE; AREA-17; AREA-18; AREA-21 ID METHYL-D-ASPARTATE; AMINO-ACID RECEPTORS; HUMAN CEREBRAL-CORTEX; NEUROFIBRILLARY TANGLES; GLUTAMATE BINDING; NERVOUS-SYSTEM; H-3 GLYCINE; NEURONS; NEUROTRANSMITTER; LAMINAR AB Quantitative receptor autoradiography was used to measure the laminar distribution of [H-3]glycine and [H-3]glutamate binding to the N-methyl-D-aspartate (NMDA) receptor complex, [H-3]D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) binding to the AMPA receptor, and [H-3]flunitrazepam binding to the benzodiazepine (BDZ) receptor in three areas of visual cortex in control and Alzheimer's disease (AD) postmortem human brains (primary or striate visual cortex, visual association cortex, and higher-order visual association cortex, corresponding to Brodmann Areas 17, 18, and 21, respectively). In Area 17, binding to the NMDA, AMPA, and BDZ receptors was not significantly altered in the AD brains (except in layer VI for [H-3]glycine and layer III for [H-3]AMPA, where binding was reduced in the AD brains). Ligand binding to the two EAA receptors in Area 18 was, however, significantly reduced in the AD brains (layers I through III for [H-3]glycine and layers III through VI for [H-3]AMPA). In Area 2 1, binding to both the NMDA and BDZ receptors but not to the AMPA receptor, was significantly reduced in almost all laminae of the AD brains (layers I through VI for [H-3]glycine and layers I through V for [H-3]flunitrazepam). This hierarchical pattern of laminar binding loss with increasing complexity of association visual cortices is consistent with the increasing numbers of neurofibrillary tangles found in those areas, implicating NMDA and BDZ receptor bearing cells in AD neuropathology. AMPA receptor losses do not parallel the pathology, suggesting that AMPA receptors are not directly correlated with the pathology. C1 UNIV MICHIGAN, DEPT NEUROL, ANN ARBOR, MI 48109 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. FU NIA NIH HHS [AG08671] NR 75 TC 40 Z9 40 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 1993 VL 14 IS 4 BP 343 EP 352 DI 10.1016/0197-4580(93)90120-Z PG 10 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA LL571 UT WOS:A1993LL57100009 PM 7690114 ER PT J AU PRICE, RH ALBIN, RL SAKURAI, SY POLINSKY, RJ PENNEY, JB YOUNG, AB AF PRICE, RH ALBIN, RL SAKURAI, SY POLINSKY, RJ PENNEY, JB YOUNG, AB TI CEREBELLAR EXCITATORY AND INHIBITORY AMINO-ACID RECEPTORS IN MULTIPLE SYSTEM ATROPHY SO NEUROLOGY LA English DT Article ID GLUTAMATE BINDING-SITES; SHY-DRAGER SYNDROME; OLIVOPONTOCEREBELLAR ATROPHY; RAT-BRAIN; AUTORADIOGRAPHIC LOCALIZATION; NEUROTRANSMITTER RECEPTORS; REGIONAL DISTRIBUTION; AMPA RECEPTORS; H-3 GLYCINE; D-ASPARTATE AB We studied excitatory and inhibitory amino acid binding sites autoradiographically in control and multiple system atrophy (MSA) cerebella. Within the dentate nucleus (DN) of MSA specimens, we found a significant increase in the level of GABA(A), benzodiazepine, and metabotropic binding sites compared with controls. In the granule cell layer, kainate, N-methyl-D-aspartate, and GABA(A) binding sites were all decreased significantly in MSA specimens compared with controls. In the molecular layer of MSA cerebellum, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate binding sites were decreased significantly compared with controls. Cerebellar cortical binding site decreases are likely due to Purkinje and granule cell loss. The increase of binding site levels in DN of MSA specimens may represent receptor up-regulation reflecting loss of descending inhibitory Purkinje cell and ascending excitatory afferents to the DN. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,FRUIT ST,BOSTON,MA 02114. UNIV MICHIGAN,DEPT NEUROL,ANN ARBOR,MI 48109. NINCDS,NEUROPHARMACOL SECT,BETHESDA,MD 20892. FU NINDS NIH HHS [NS15655, NS01300, NS19613] NR 45 TC 10 Z9 11 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 1993 VL 43 IS 7 BP 1323 EP 1328 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA LM104 UT WOS:A1993LM10400011 PM 8392149 ER PT J AU HARDIMAN, O SKLAR, RM BROWN, RH AF HARDIMAN, O SKLAR, RM BROWN, RH TI DIRECT EFFECTS OF CYCLOSPORINE-A AND CYCLOPHOSPHAMIDE ON DIFFERENTIATION OF NORMAL HUMAN MYOBLASTS IN CULTURE SO NEUROLOGY LA English DT Note AB We examined the direct effects of the commonly used immunosuppressive agents cyclosporin A and cyclophosphamide on cultures of clonally derived aneural human myoblasts. When applied to cultures in doses reflecting the therapeutic dose in vivo, both cyclosporin A and cyclophosphamide had dose-related reproducible effects on myoblast fusion: fusion was enhanced by cyclophosphamide and inhibited by cyclosporin A. These findings indicate that immunosuppressive agents may have effects on muscle that are independent of their ability to regulate the immune system. C1 MASSACHUSETTS GEN HOSP,CECIL B DAY NEUROMUSCULAR RES LABS,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP HARDIMAN, O (reprint author), NATL UNIV IRELAND UNIV COLL DUBLIN,SCH MED,DEPT PHYSIOL,EARLSFORT TERRACE,DUBLIN 2,IRELAND. FU PHS HHS [R01 00787-05] NR 10 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 1993 VL 43 IS 7 BP 1432 EP 1434 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA LM104 UT WOS:A1993LM10400035 PM 8093118 ER PT J AU SPIRO, IJ YANDELL, DW LI, C SAINI, S FERRY, J POWELSON, J KATKOV, WN COSIMI, AB AF SPIRO, IJ YANDELL, DW LI, C SAINI, S FERRY, J POWELSON, J KATKOV, WN COSIMI, AB TI LYMPHOMA OF DONOR ORIGIN OCCURRING IN THE PORTA-HEPATIS OF A TRANSPLANTED LIVER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note ID POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; BONE-MARROW TRANSPLANTATION; RENAL-ALLOGRAFT RECIPIENT; EPSTEIN-BARR VIRUS; IMMUNOBLASTIC SARCOMA; CELLS; DNA; POLYMORPHISMS; LEUKEMIA C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP SPIRO, IJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. RI Li, Chuan-Yuan/H-4148-2013 NR 21 TC 60 Z9 61 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 1 PY 1993 VL 329 IS 1 BP 27 EP 29 DI 10.1056/NEJM199307013290105 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA LJ338 UT WOS:A1993LJ33800005 PM 8505941 ER PT J AU OSSWALD, S TROUTON, TG AF OSSWALD, S TROUTON, TG TI NEUROCARDIOGENIC (VASODEPRESSOR) SYNCOPE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note RP OSSWALD, S (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 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 1 PY 1993 VL 329 IS 1 BP 30 EP 30 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LJ338 UT WOS:A1993LJ33800006 PM 8110215 ER PT J AU CASTRONOVO, FP MCKUSICK, KA DOPPELT, SH BARTON, NW AF CASTRONOVO, FP MCKUSICK, KA DOPPELT, SH BARTON, NW TI RADIOPHARMACOLOGY OF INHALED XE-133 IN SKELETAL SITES CONTAINING DEPOSITS OF GAUCHER CELLS SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article ID DISEASE; VENTILATION AB Gaucher's disease is a lysosomal storage disease in which cells of the reticuloendothelial system accumulate the lipid glucocerebroside. It is characterized by slowly progressive visceral and osseous involvement. One of the latter manifestations includes lipid infiltration of bone marrow. We monitored the rate of inhaled Xe-133 uptake and wash-out over diseased and normal metaphyseal and epiphyseal areas of the knee. Twenty-two patients (15 adults, 7 children) with various degrees of previously diagnosed Gaucher's disease were positioned supine under a gamma-camera interfaced to a computer system. All patients rebreathed Xe-133 gas from a closed system for 10 min followed by 14 min of wash-out. Digitized images of the lung, liver, spleen, bony sites and soft tissue were obtained at 1 min intervals during the wash-in and wash-out phases. Counts for each ROI were normalized per 100 pixels and plotted as a function (time). Maximum uptake was also calculated by relating the counts/ROI/100 pixels to the 10 min integrated lung count during equilibrium (the administered ''dose''). There was essentially no Xe-133 uptake in liver and spleen involved with Gaucher's disease. Monophasic uptake and biphasic wash-out curves were observed in the limited investigative population. Skeletal Gaucher deposits released the Xe-133 at a greater rate relative to soft tissue. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NIH,BETHESDA,MD 20892. RP CASTRONOVO, FP (reprint author), BRIGHAM & WOMENS HOSP,DEPT RADIOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 25 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JUL PY 1993 VL 20 IS 5 BP 707 EP 714 DI 10.1016/0969-8051(93)90042-S PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LK303 UT WOS:A1993LK30300019 PM 8358357 ER PT J AU CUNNINGHAM, JJ LEFFELL, M HARMATZ, P AF CUNNINGHAM, JJ LEFFELL, M HARMATZ, P TI BURN SEVERITY, COPPER DOSE, AND PLASMA CERULOPLASMIN IN BURNED CHILDREN DURING TOTAL PARENTERAL-NUTRITION SO NUTRITION LA English DT Article ID INFANTS; ZINC; SERUM; RATS AB Copper (Cu) is an essential nutrient with known metabolic roles in wound healing. Ceruloplasmin (CP), the primary Cu-transport protein, responds as an acute-phase reactive protein after trauma. However, for severe burn trauma, this response is absent in the early catabolic phase despite Cu provision. We report data for 14 severely burned children receiving Cu in total parenteral nutrition (TPN-Cu) ranging from 7 to 26 mug Cu . kg-1 . day-1. All patients manifested low plasma levels of CP. The reduction in CP reflected burn severity but also appeared to be dependent on the Cu dose. Increasing Cu supplementation to improve CP raises a concern for hepatotoxicity, which is accompanied by an elevation in the plasma nonceruloplasmin Cu (nonCP-Cu). The calculated plasma nonCP-Cu in our series is consistent with a lack of increased risk and suggests that TPN-Cu at the general pediatric guideline of 20 mug kg-1 . day-1 is safe and reasonable for severely burned children. Cu supplementation >20 mug/kg may be beneficial; however, monitoring of both CP and total Cu should continue as standard practice in the management of these patients. C1 MASSACHUSETTS GEN HOSP, SURG SERV, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CHILDRENS SERV, BOSTON, MA 02114 USA. UNIV MASSACHUSETTS, DEPT NUTR, AMHERST, MA 01003 USA. RP CUNNINGHAM, JJ (reprint author), SHRINERS BURNS INST, NUTR SUPPORT UNIT, 51 BLOSSOM ST, BOSTON, MA 02114 USA. NR 19 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD JUL-AUG PY 1993 VL 9 IS 4 BP 329 EP 332 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LT895 UT WOS:A1993LT89500004 PM 8400588 ER PT J AU DSOUZA, B BERDICHEVSKY, F KYPRIANOU, N TAYLORPAPADIMITRIOU, J AF DSOUZA, B BERDICHEVSKY, F KYPRIANOU, N TAYLORPAPADIMITRIOU, J TI COLLAGEN-INDUCED MORPHOGENESIS AND EXPRESSION OF THE ALPHA-2-INTEGRIN SUBUNIT IS INHIBITED IN C-ERBB2-TRANSFECTED HUMAN MAMMARY EPITHELIAL-CELLS SO ONCOGENE LA English DT Article ID MONOCLONAL-ANTIBODIES; C-ERBB-2 PROTEIN; BREAST; TUMORS; GLAND; GENE; ADENOCARCINOMA; AMPLIFICATION; KERATIN-19; DISTINCT AB The c-erbB2 (or Her2) oncogene is amplified and/or overexpressed in a significant proportion of breast cancers. To assess the role of the c-erbB2 oncogene in mammary tumorigenesis, we have transfected the corresponding human c-erbB2 cDNA into an immortalized human mammary epithelial cell line, MTSV1-7, that was derived from luminal epithelial cells cultured from milk. Three transfectants expressing different levels of the c-erbB2 gene product have been isolated which form colonies in agar and produce tumours in nude mice with high efficiency. We have observed that MTSV1-7 cells form three-dimensional structures in collagen gels and that alpha2beta1-integrin plays a crucial role in the process of morphogenesis. We now find that the c-erbB2 transfectants exhibit an impaired ability to undergo morphogenesis in collagen gets as compared with the parental cell line or the control neomycin transfectant, and that the degree of impairment is related to the level of c-erbB2 expression. Moreover, overexpression of the c-erbB2 product was found to be correlated with a specific decrease in the expression of alpha2beta1-integrin subunit and in the alpha2-mRNA. The breast cancer cell line SKBr3, which carries multiple copies of the c-erbB2 gene and overexpresses the 185-kDa product, was also found to express very low levels of the alpha2-integrin protein and mRNA. Our results confirm the involvement of the alpha2beta1-integrin in collagen-induced morphogenesis of mammary epithelial cells and suggest that the c-erbB2 gene product may inhibit this morphogenesis by inhibiting the expression of the alpha2-integrin subunit. C1 IMPERIAL CANC RES FUND,POB 123,44 LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND. UNIV MARYLAND HOSP,DEPT SURG,DIV UROL,BALTIMORE,MD 21205. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 33 TC 75 Z9 76 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 1993 VL 8 IS 7 BP 1797 EP 1806 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LG682 UT WOS:A1993LG68200011 PM 8099725 ER PT J AU MACKLIS, RM MAUCH, PM THOMPSON, L BURAKOFF, SJ SMITH, BR AF MACKLIS, RM MAUCH, PM THOMPSON, L BURAKOFF, SJ SMITH, BR TI PHENOTYPIC AND FUNCTIONAL-ANALYSIS OF EXPANDED NATURAL-KILLER-CELL SUBPOPULATIONS IN HODGKINS-DISEASE PATIENTS TREATED WITH LYMPHOID IRRADIATION SO ONCOLOGY LA English DT Article DE HODGKINS DISEASE; NK CELLS; LYMPHOID IRRADIATION ID PERIPHERAL-BLOOD; FLOW-CYTOMETRY; LYMPHOCYTES; LEU-7; POPULATIONS; EXPRESSION; REMISSION; ANTIGENS AB We have evaluated the immunophenotype and function of presumptive NK cells taken from Hodgkin's disease patients before and after mantle/paraaortic lymphoid irradiation. We find that the lymphoid irradiation appears to induce a relatively stable, generalized expansion of the entire NK cell compartment rather than an increase in any specific NK cell subset. Flow cytometric cell sorting and functional NK cell assays based on immunophenotype demonstrate no significant changes in the phenotypic proportions of individual NK cell subsets and no significant changes in the lytic activity or cytotoxicity spectrum of these NK cells. These changes in the NK cell compartment may play a role in the long-term immunosuppression of these patients. C1 BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. RP MACKLIS, RM (reprint author), HARVARD UNIV,JOINT CTR RADIAT THERAPY,50 BINNEY ST,BOSTON,MA 02215, USA. NR 25 TC 7 Z9 7 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY JI Oncology PD JUL-AUG PY 1993 VL 50 IS 4 BP 323 EP 328 PG 6 WC Oncology SC Oncology GA LJ043 UT WOS:A1993LJ04300026 PM 8497384 ER PT J AU SHIMAZAKI, J TSUBOTA, K HAYASHI, K KENYON, KR LAING, RA AF SHIMAZAKI, J TSUBOTA, K HAYASHI, K KENYON, KR LAING, RA TI DISTRIBUTION OF AUTOFLUORESCENCE IN THE RABBIT CORNEAL EPITHELIUM SO OPHTHALMIC RESEARCH LA English DT Article DE OCULAR REDOX FLUOROMETRY; CORNEAL EPITHELIUM; AUTOFLUORESCENCE; PYRIDINE NUCLEOTIDE; FLAVOPROTEINS ID PYRIDINE-NUCLEOTIDE; FLUORESCENCE AB Autofluorescence from reduced pyridine nucleotides (PN) and oxidized flavoproteins (Fp) was measured in order to detect the difference in redox states in rabbit corneal epithelium. The enucleated rabbit eye was mounted in an eye bank eye container with McCarey-Kaufman medium, and the autofluorescence was measured using ocular redox fluorometry as a function of depth. The PN signal distributed evenly whereas the Fp signal was greater in the posterior epithelial region than in the anterior region (p < 0.05). The PN/Fp ratio, a sensitive indicator of tissue redox state, was less in the posterior region. After the application of 1 mM of potassium cyanide in the medium, the ratio increased significantly in each layer (p < 0.001), and the difference between anterior and posterior region diminished. These results indicate that ocular redox fluorometry has the potential to resolve the redox states of the various layers of the corneal epithelium. The posterior region of the epithelium is more active in mitochondrial respiration than the anterior region. C1 HAYASHI EYE HOSP,FUKUOKA,JAPAN. TOKYO DENT COLL,DEPT OPHTHALMOL,TOKYO 101,JAPAN. BOSTON UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02118. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,RETINA FDN,INST EYE RES,CAMBRIDGE,MA 02138. OI HAYASHI, KEN/0000-0002-7297-1477 FU NEI NIH HHS [1 R01 EY 01227, EY 01990] NR 15 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 J9 OPHTHALMIC RES JI Ophthalmic Res. PD JUL-AUG PY 1993 VL 25 IS 4 BP 220 EP 225 PG 6 WC Ophthalmology SC Ophthalmology GA LW113 UT WOS:A1993LW11300004 PM 8233347 ER PT J AU SANDBERG, MA TOLENTINO, MJ MILLER, S BERSON, EL GAUDIO, AR AF SANDBERG, MA TOLENTINO, MJ MILLER, S BERSON, EL GAUDIO, AR TI HYPEROPIA AND NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION SO OPHTHALMOLOGY LA English DT Article ID MEMBRANES; FEATURES AB Purpose: Refractive errors for phakic eyes of patients referred with age-related macular degeneration were reviewed to determine whether some range of refractive error might be a risk factor for the neovascular form. Methods: The authors compared refractive errors of 198 patients with unilateral neovascular disease with refractive errors of 129 patients with bilateral dry disease. These groups had comparable distributions with respect to age, sex, and visual acuity of their better eyes. Student's t tests and multiple linear regression analyses were performed to assess group differences in mean refractive error. Contingency table and multiple logistic regression analyses were performed to determine odds ratios for having the neovascular form based on a stratification of refractive error. Results: By comparing better eyes of the two groups, patients with the unilateral neovascular form had an average spherical equivalent that was 1.0 diopter (D) more hyperopic than that of patients with the bilateral dry form (P < 0.001). Patients with a refractive error of +0.75 D or greater were more likely to have the neovascular form compared with patients with other refractive errors (odds ratio, 2.40; 95% confidence interval, 1.53-3.78; P < 0.001). Similar relationships between the two groups of patients were found by comparing worse eyes. Conclusion: These findings suggest that hyperopia is a risk factor for choroidal neovascularization among patients referred with age-related macular degeneration. RP SANDBERG, MA (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY08398] NR 20 TC 32 Z9 32 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 1993 VL 100 IS 7 BP 1009 EP 1013 PG 5 WC Ophthalmology SC Ophthalmology GA LK967 UT WOS:A1993LK96700013 PM 7686644 ER PT J AU LILGE, L FLOTTE, TJ KOCHEVAR, IE JACQUES, SL HILLENKAMP, F AF LILGE, L FLOTTE, TJ KOCHEVAR, IE JACQUES, SL HILLENKAMP, F TI PHOTOACTIVABLE FLUOROPHORES FOR THE MEASUREMENT OF FLUENCE IN TURBID MEDIA SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID TISSUE; PHANTOMS; LIGHT; FLUX AB Knowledge of the fluence distribution in biological tissue is essential for applications of lasers and light in medicine. A method using a photoactivable fluorophore as a chemical actinometer is presented to investigate the fluence (J/cm2) distribution in tissue-simulating phantoms. Such a chemical actinometer provides high spatial resolution (less-than-or-equal-to 20 mum) while minimizing the disturbance of the fluence distribution. The actinometer substance, nonfluorescent in its native state, is incorporated into an acrylamide gel. Upon absorption of 351 nm radiation (lambda(act)), the actinometer substance becomes a fluorophore, which is excited at lambda(ex) less-than-or-equal-to 485 nm. Thus the spatial distribution of the emitted fluorescence (lambda(ex) greater-than-or-equal-to 515 nm) in the actinometer represents the fluence distribution of the activating radiation. Using histological techniques, 20 mum sections are cut from gel-like optical phantoms containing the actinometric substance. The fluorescence intensity in the section is recorded under a standard fluorescence microscope equipped with a sensitive video camera. To simulate different biological tissues, the scattering and absorption properties of the gel phantoms are varied over a wide range. The experimentally obtained fluence distributions are compared with theoretical models of light distribution in turbid media. C1 UNIV MUNSTER,INST MED PHYS,W-4400 MUNSTER,GERMANY. MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. UNIV TEXAS,M D ANDERSON CANC CTR,HOUSTON,TX 77030. RI Lilge, lothar/J-6434-2013 NR 23 TC 12 Z9 12 U1 1 U2 4 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUL PY 1993 VL 58 IS 1 BP 37 EP 44 DI 10.1111/j.1751-1097.1993.tb04900.x PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LR037 UT WOS:A1993LR03700006 ER PT J AU LIN, CW SHULOK, JR KIRLEY, SD BACHELDER, CM FLOTTE, TJ SHERWOOD, ME CINCOTTA, L FOLEY, JW AF LIN, CW SHULOK, JR KIRLEY, SD BACHELDER, CM FLOTTE, TJ SHERWOOD, ME CINCOTTA, L FOLEY, JW TI PHOTODYNAMIC DESTRUCTION OF LYSOSOMES MEDIATED BY NILE BLUE PHOTOSENSITIZERS SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID BLADDER-CARCINOMA CELLS; ASPARTYL CHLORIN E6; ADRIAMYCIN-RESISTANT; INTRACELLULAR-PH; LIVING CELLS; PHOTOFRIN-II; INVITRO; RHODAMINE-123; LOCALIZATION; AGENTS AB Previous studies have established that a number of Nile blue derivatives arc potent photosensitizers and that they are localized primarily in the lysosomes. The present study examines whether the lysosome is a main target of the photocytotoxic action mediated by these sensitizers. Chosen for this study were NBS-61 and sat-NBS, which represented, respectively, derivatives with high and moderate degrees of lysosomal selectivity. Overall results indicated that both derivatives are very effective in mediating a photodestruction of lysosomes. This is indicated by the light- and drug-dose-dependent losses of acid phosphatase staining particles, reduction of hexosaminidase in the lysosome-containing subcellular fraction, and impairment of the lysosomes to take up and sequester acridine orange. Ultrastructurally, swollen and ruptured lysosomes were seen as one of the first evidences of cell damage mediated by these photosensitizers. However, the study also showed that sat-NBS, which is less lysosomal selective, was less effective in mediating lysosomal destruction. Also, the degree of lysosomal destruction mediated by sat-NBS did not parallel the degree of cytotoxicity generated. This implies that for derivatives that are not exclusively localized in the lysosome, other subcellular sites may also be damaged by the photodynamic action and may play a role in the photocytotoxic process. C1 MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. ROWLAND INST SCI INC,CAMBRIDGE,MA 02142. RP LIN, CW (reprint author), MASSACHUSETTS GEN HOSP,UROL RES LAB,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 32259] NR 44 TC 45 Z9 46 U1 0 U2 2 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUL PY 1993 VL 58 IS 1 BP 81 EP 91 DI 10.1111/j.1751-1097.1993.tb04907.x PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LR037 UT WOS:A1993LR03700013 PM 8378436 ER PT J AU STOHR, C TISCHNER, R WARD, MR AF STOHR, C TISCHNER, R WARD, MR TI CHARACTERIZATION OF THE PLASMA-MEMBRANE-BOUND NITRATE REDUCTASE IN CHLORELLA-SACCHAROPHILA (KRUGER) NADSON SO PLANTA LA English DT Article DE CHLORELLA; NITRATE REDUCTASE (PLASMA-MEMBRANE BOUND); PLASMA MEMBRANE ID TRITON X-114; SEPARATION; PROTEINS; VESICLES; PURIFICATION; ENZYME AB The plasma membranes of Chlorella saccharophila (Kruger) Nadson cells contained a membrane-bound nitrate reductase. This form of nitrate reductase was purified and characterized. Several differences from the soluble form of nitrate reductase were apparent, the most important being: (i) the greater hydrophobicity, as proven using Triton X-114 phase separation, hydrophobic interaction chromatography and stimulation by phosphilipids; (ii) the differences in the native molecular mass compared with Chlorella sorokiniana (Kruger) Nadson; and (iii) the different polypeptide pattern obtained by two-dimensional polyacrylamide gel electrophoresis. Only the plasma-membrane-bound nitrate reductase could be found in both inside-out and right-side-out plasma-membrane vesicles. C1 UNIV GOTTINGEN, INST PFLANZENPHYSIOL, UNTERE KARSPULE 2, D-37073 GOTTINGEN, GERMANY. MASSACHUSETTS GEN HOSP, DEPT MOLEC BIOL, BOSTON, MA 02129 USA. NR 23 TC 32 Z9 32 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0032-0935 EI 1432-2048 J9 PLANTA JI Planta PD JUL PY 1993 VL 191 IS 1 BP 79 EP 85 PG 7 WC Plant Sciences SC Plant Sciences GA LN218 UT WOS:A1993LN21800010 ER PT J AU ROSENWALD, IB RHOADS, DB CALLANAN, LD ISSELBACHER, KJ SCHMIDT, EV AF ROSENWALD, IB RHOADS, DB CALLANAN, LD ISSELBACHER, KJ SCHMIDT, EV TI INCREASED EXPRESSION OF EUKARYOTIC TRANSLATION INITIATION-FACTORS EIF-4E AND EIF-2-ALPHA IN RESPONSE TO GROWTH INDUCTION BY C-MYC SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DELAYED EARLY GENES; GENE EXPRESSION; PROTEIN SYNTHESIS ID PROTEIN-SYNTHESIS; GENE; TRANSCRIPTION; CELLS; TRANSFORMATION; SEQUENCES; BINDING; CAP AB Although activation of c-myc is a critical step in the development of lymphomas and other tumors, its normal function(s) in cell growth remain obscure because few myc-regulated genes are known. myc expression normally increases in response to mitogens and peaks in G1 when additional protein synthesis is required for cell-cycle progression. Protein synthesis is controlled by the availability of translation initiation factors, including the mRNA cap binding protein (eIF-4E) and the alpha subunit of the eIF-2 complex that binds the initiator Met-tRNA. Consequently we examined eIF-4E and eIF-2alpha for evidence of regulation by c-myc. Expression of eIF-4E and eIF-2alpha correlated with c-myc expression in fibroblasts after growth stimulation. In addition, expression of eIF-4E and eIF-2alpha was increased in myc-transformed rat embryo fibroblasts but was not increased in ras-transformed cells. Transcription rates of eIF-4E and eIF-2alpha mRNAs were regulated by c-myc in cells expressing an estrogen receptor-Myc fusion protein. Finally, electrophoretic mobility-shift assays identified a sequence element in the eIF-2alpha promoter, TCCGCATGCGCG, which was specifically retarded by extracts of myc-expressing cells. c-myc is thought to deregulate the growth of cancer cells by activating transcription, suggesting that specific genes regulated by c-myc should also function as oncogenes. In previous studies these translation initiation factors could induce neoplastic growth because overexpression of eIF-4E-transformed cells and inhibition of a suppressor of eIF-2alpha (eIF-2alpha kinase) also caused malignant transformation. Our studies suggest that one important biological function of c-myc may be to increase cell growth by increasing expression of eIF-4E and eIF-2alpha. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BLDG 149,13TH ST,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. FU NIDDK NIH HHS [DK 01392] NR 31 TC 214 Z9 219 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 1 PY 1993 VL 90 IS 13 BP 6175 EP 6178 DI 10.1073/pnas.90.13.6175 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM035 UT WOS:A1993LM03500062 PM 8327497 ER PT J AU KLIMM, JL KLOCZEWIAK, MA LINDON, J AF KLIMM, JL KLOCZEWIAK, MA LINDON, J TI EFFECTS OF FREE AND MACROMOLECULAR-BOUND TXA(2)-RECEPTOR ANTAGONIST BM-13.505 ON U46619-INDUCED PLATELET-AGGREGATION SO PROSTAGLANDINS LA English DT Article ID THROMBOXANE-A2 RECEPTOR; BLOOD-PLATELETS; BINDING-SITE; ACTIVATION; PROSTAGLANDIN-H2; DISTINCT; PROTEINS; INVIVO AB The goal of this study was to synthesize a macromolecular probe of the TXA2 receptor antagonist BM13.505 which is unable to penetrate the platelet membrane for localization and characterization of the TXA2 receptor. The active NHS-ester of BM13.505 was synthesized and purified. It was used for covalent coupling of BM13.505 to bovine serum albumin, a macromolecular carrier. Inhibitory effects of free and macromolecular bound BM13.505 on aggregatory properties of U46619-stimulated platelets were measured and compared to TXA2 generation in platelets, as determined by TXB2 radioimmuno assay. No inhibitory effects of free and macromolecular-bound BM13.505 on ADP- or thrombin-induced platelet aggregation were observed. Equimolar concentrations of free or macromolecular bound BM13.505 inhibited U46619-induced platelet aggregation and TXA2 generation with equal potency. IC50-values for platelet aggregation inhibition by free and macromolecular bound BM13.505 were 64 nM and 96 nM respectively. It appears that the TXA2 receptor ligand binding site is located close to the outer membrane surface of platelets. Interaction of macromolecular bound BM13.505 with the platelet thromboxane receptor does not depend on the availability of the free carboxyl residue in BM13.505. The method for coupling a TXA2 receptor antagonist to a macromolecule will aid in constructing probes for the localization and characterization of the TXA2 receptor. C1 SHRINERS BURNS INST,BOSTON,MA. GEN HOSP,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. RP KLIMM, JL (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. NR 24 TC 1 Z9 1 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0090-6980 J9 PROSTAGLANDINS JI Prostaglandins PD JUL PY 1993 VL 46 IS 1 BP 27 EP 36 DI 10.1016/0090-6980(93)90060-K PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LP952 UT WOS:A1993LP95200003 PM 8378540 ER PT J AU FAVA, M ANDERSON, K ROSENBAUM, JF AF FAVA, M ANDERSON, K ROSENBAUM, JF TI ARE THYMOLEPTIC-RESPONSIVE ANGER ATTACKS A DISCRETE CLINICAL SYNDROME SO PSYCHOSOMATICS LA English DT Note ID PANIC ATTACKS; DEPRESSION; HOSTILITY; AGGRESSION; DISORDERS; BEHAVIOR; SYMPTOM C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. RP FAVA, M (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,15 PARKMAN ST,ACC815,BOSTON,MA 02114, USA. NR 23 TC 14 Z9 14 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 1993 VL 34 IS 4 BP 350 EP 355 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA LJ932 UT WOS:A1993LJ93200009 PM 8351310 ER PT J AU LEVITTE, SS AF LEVITTE, SS TI COEXISTENT HYPOMANIA AND SEVERE HYPOTHYROIDISM - IN REPLY SO PSYCHOSOMATICS LA English DT Letter RP LEVITTE, SS (reprint author), PORTLAND VET AFFAIRS MED CTR,PORTLAND,OR 97207, USA. NR 4 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 JUL-AUG PY 1993 VL 34 IS 4 BP 374 EP 375 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA LJ932 UT WOS:A1993LJ93200019 ER PT J AU GERWECK, LE SENEVIRATNE, T GERWECK, KK AF GERWECK, LE SENEVIRATNE, T GERWECK, KK TI ENERGY STATUS AND RADIOBIOLOGICAL HYPOXIA AT SPECIFIED OXYGEN CONCENTRATIONS SO RADIATION RESEARCH LA English DT Article ID P-31 NMR-SPECTROSCOPY; MURINE FIBRO-SARCOMA; INDUCED DAMAGE; CELL FRACTION; X-IRRADIATION; TUMOR SIZE; INVIVO; SENSITIVITY; DEPENDENCE; TENSION RP GERWECK, LE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-22860] NR 19 TC 18 Z9 18 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 1993 VL 135 IS 1 BP 69 EP 74 DI 10.2307/3578398 PG 6 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA LM856 UT WOS:A1993LM85600009 PM 8327663 ER PT J AU ROSEN, BR ARONEN, HJ KWONG, KK BELLIVEAU, JW HAMBERG, LM FORDHAM, JA AF ROSEN, BR ARONEN, HJ KWONG, KK BELLIVEAU, JW HAMBERG, LM FORDHAM, JA TI ADVANCES IN CLINICAL NEUROIMAGING - FUNCTIONAL MR-IMAGING TECHNIQUES SO RADIOGRAPHICS LA English DT Article DE BRAIN, MR; MAGNETIC RESONANCE (MR), VASCULAR STUDIES; MAGNETIC RESONANCE (MR), TECHNOLOGY ID POSITRON EMISSION TOMOGRAPHY; MAGNETIC-SUSCEPTIBILITY; RADIATION NECROSIS; CONTRAST AGENTS; BRAIN; DIFFUSION; TIME; PET; DIFFERENTIATION; PERFUSION RP ROSEN, BR (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR MGH NMR,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 49 TC 24 Z9 24 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JUL PY 1993 VL 13 IS 4 BP 889 EP 896 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LM860 UT WOS:A1993LM86000013 PM 8356274 ER PT J AU CONNELLY, A JACKSON, GD FRACKOWIAK, RSJ BELLIVEAU, JW VARGHAKHADEM, F GADIAN, DG AF CONNELLY, A JACKSON, GD FRACKOWIAK, RSJ BELLIVEAU, JW VARGHAKHADEM, F GADIAN, DG TI FUNCTIONAL MAPPING OF ACTIVATED HUMAN PRIMARY CORTEX WITH A CLINICAL MR-IMAGING SYSTEM SO RADIOLOGY LA English DT Article DE BLOOD, FLOW DYNAMICS; BRAIN, BLOOD FLOW; BRAIN, FUNCTION; MAGNETIC RESONANCE (MR), VASCULAR STUDIES ID MAGNETIC-RESONANCE; BLOOD AB Functional activation of the human brain can be visualized with magnetic resonance (MR) imaging, but most studies so far have used echo-planar imaging or magnetic fields of 2 T and above, neither of which are at present widely available. The authors used a standard 1.5-T MR imaging system to map regions of the brain that are activated with visual and motor tasks, using a long echo time (60 msec) fast low-angle shot sequence. Eleven visual and 14 motor studies were performed, and activation was seen in all cases. Up to 15% signal intensity change was apparent in gray matter but not in white matter. The precise anatomic location and extent of activation were defined by reference to T1-weighted images acquired during the same examination. This method of relating brain structure to function uses equipment that is widely available, which has considerable implications for the investigation of many neurologic and neurosurgical diseases and for our understanding of brain function and dysfunction. C1 INST CHILD HLTH, RADIOL & PHYS UNIT, GREAT ORMOND ST, LONDON WC1N 3JH, ENGLAND. MASSACHUSETTS GEN HOSP, DEPT RADIOL, BOSTON, MA USA. HOSP SICK CHILDREN, LONDON WC1N 3JH, ENGLAND. MRC, CYCLOTRON UNIT, LONDON WC1E 6AS, ENGLAND. INST NEUROL, LONDON WC1N 3BG, ENGLAND. INST CHILD HLTH, NEUROSCI UNIT, LONDON WC1N 3JH, ENGLAND. RI Gadian, David/C-4961-2008; Vargha-Khadem, Faraneh/C-2558-2008; Connelly, Alan/A-9065-2013; Frackowiak, Richard/I-1809-2013; Frackowiak, Richard/H-4383-2011; Jackson, Graeme/A-9064-2013 OI Frackowiak, Richard/0000-0002-3151-822X; Jackson, Graeme/0000-0002-7917-5326 NR 21 TC 134 Z9 134 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 1993 VL 188 IS 1 BP 125 EP 130 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LH284 UT WOS:A1993LH28400025 PM 8511285 ER PT J AU HUNCHAREK, M KLASSEN, H AF HUNCHAREK, M KLASSEN, H TI ACYCLOVIR IN VARICELLA PNEUMONIA IN HEALTHY-ADULTS SO RESPIRATION LA English DT Letter RP HUNCHAREK, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT MED,BOSTON,MA 02114, USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0025-7931 J9 RESPIRATION JI Respiration PD JUL-AUG PY 1993 VL 60 IS 4 BP 254 EP 255 PG 2 WC Respiratory System SC Respiratory System GA MG466 UT WOS:A1993MG46600013 PM 8265885 ER PT J AU KACMAREK, RM AF KACMAREK, RM TI NEWEST GENERATION OF MECHANICAL VENTILATORS - IMPROVING PATIENT-VENTILATOR INTERFACE SO SEMINARS IN RESPIRATORY MEDICINE LA English DT Article ID END-EXPIRATORY PRESSURE; RESPIRATORY-FAILURE C1 HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115. RP KACMAREK, RM (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 36 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 0192-9755 J9 SEMIN RESPIR MED PD JUL PY 1993 VL 14 IS 4 BP 251 EP 261 DI 10.1055/s-2007-1006325 PG 11 WC Respiratory System SC Respiratory System GA LP264 UT WOS:A1993LP26400002 ER PT J AU STAFFORD, RS AF STAFFORD, RS TI TOOLS FOR PRIMARY-CARE RESEARCH - RESEARCH METHODS FOR PRIMARY-CARE, VOL 2 - STEWART,M, TUDIVER,F, BASS,MJ, DUNN,EV, NORTON,PG SO SOCIAL SCIENCE & MEDICINE LA English DT Book Review RP STAFFORD, RS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD JUL PY 1993 VL 37 IS 2 BP 279 EP 280 DI 10.1016/0277-9536(93)90467-I PG 2 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA LK329 UT WOS:A1993LK32900020 ER PT J AU VANEENENAAM, DP ELKHOURY, GY AF VANEENENAAM, DP ELKHOURY, GY TI DELAYED POSTTRAUMATIC VERTEBRAL COLLAPSE (KUMMELLS-DISEASE) - CASE-REPORT WITH SERIAL RADIOGRAPHS, COMPUTED TOMOGRAPHIC SCANS, AND BONE SCANS SO SPINE LA English DT Article DE KUMMELL DISEASE; VERTEBRAL COLLAPSE AB A case of delayed posttraumatic vertebral collapse (Kummell's disease) is described and documented with serial radiographs, computed tomographic scans, and bone scans. The bone scan was normal before the back injury occurred and showed increased radionuclide uptake 3 weeks after injury and before vertebral collapse. Plain radiographs and computed tomographic scans taken during the interval between injury and collapse revealed no evidence of fracture or bone destruction. The authors believe this represents the first example of Kummell's phenomenon documented with serial computed tomographic and bone scans, and provides further support to the ischemic necrosis theory as the underlying process. RP VANEENENAAM, DP (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,HARVARD COMBINED ORTHOPAED SURG RESIDENCY PROGRAM,BOSTON,MA 02114, USA. NR 0 TC 24 Z9 24 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-2436 J9 SPINE JI SPINE PD JUL PY 1993 VL 18 IS 9 BP 1236 EP 1241 DI 10.1097/00007632-199307000-00019 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA LN354 UT WOS:A1993LN35400019 PM 8362333 ER PT J AU SIEFF, C GUINAN, E AF SIEFF, C GUINAN, E TI IN-VITRO ENHANCEMENT OF ERYTHROPOIESIS BY STEEL FACTOR IN DIAMOND-BLACKFAN ANEMIA AND TREATMENT OF OTHER CONGENITAL CYTOPENIAS WITH RECOMBINANT INTERLEUKIN-3/GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR SO STEM CELLS LA English DT Article DE DIAMOND-BLACKFAN ANEMIA; FANCONIS ANEMIA; AMEGAKARYOCYTIC THROMBOCYTOPENIA; STEEL FACTOR; INTERLEUKIN-3; GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR; CONGENITAL BONE MARROW FAILURE ID BONE-MARROW TRANSPLANTATION; C-KIT PROTOONCOGENE; CELL GROWTH-FACTOR; MYELODYSPLASTIC SYNDROMES; FANCONIS ANEMIA; APLASTIC-ANEMIA; GM-CSF; PROGENITOR CELLS; PHASE-I/II; HEMATOPOIESIS AB Recombinant cytokines were used to investigate the pathophysiology of Diamond-Blackfan anemia (DBA) and to treat patients with Fanconi's anemia (FA) and amegakaryocytic thrombocytopenic purpura (AMT). We compared the erythroid burst forming units (BFU-E) colony growth of six DBA patients with four normal controls. BFU-E showed erythropoietin (Epo) dose dependence in all patients, although colony numbers were reduced in comparison with normals. The number and size of BFU-E were increased with the addition to Epo of interleukin 3 (IL-3) or Steel factor (SF), but IL-3 + SF was not synergistic. SF increased the nonadherent cell production in DBA long-term bone marrow cultures, and stromal cells from DBA patients showed normal SF mRNA transcripts. These data suggest that SF is not involved in the pathogenesis of DBA, although it may be useful in treatment. A small group of patients with FA and bone marrow failure were treated with daily s.c. granulocyte-macrophage colony stimulating factor (GM-CSF). Toxicity was minimal, and the majority of the patients responded with significant, sustained increase in neutrophils. Multilineage response was rare. GM-CSF may thus be palliative in patients with FA. Five patients with AMT were treated with IL-3 or IL-3 followed by GM-CSF in a Phase I/II study. There was minimal toxicity, and IL-3, but not GM-CSF, resulted in improved platelet counts in two patients and decreased platelet transfusion requirements in the other three. Prolonged IL-3 treatment resulted in platelet increases in two of the latter patients. Thus, IL-3 may contribute to the treatment of patients with AMT. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL IMMUNOL,BOSTON,MA 02115. RP SIEFF, C (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,44 BINNEY ST,ROOM DANA 1630B,BOSTON,MA 02115, USA. NR 37 TC 4 Z9 4 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 JUL PY 1993 VL 11 SU 2 BP 113 EP 122 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA LP542 UT WOS:A1993LP54200019 PM 7691316 ER PT J AU MOSCOWITZ, MA AF MOSCOWITZ, MA TI ENDOTHELIUM-DEPENDENT EFFECTS OF SUBSTANCE-P AND CALCITONIN-GENE-RELATED PEPTIDE ON MOUSE PIAL ARTERIOLES - COMMENT SO STROKE LA English DT Note RP MOSCOWITZ, MA (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL & NEUROSURG,BOSTON,MA 02114, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 1993 VL 24 IS 7 BP 1047 EP 1048 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA LK328 UT WOS:A1993LK32800019 ER PT J AU OGILVY, CS PAKZABAN, P LEE, JM AF OGILVY, CS PAKZABAN, P LEE, JM TI OCULOMOTOR NERVE CAVERNOUS ANGIOMA IN A PATIENT WITH ROBERTS-SYNDROME SO SURGICAL NEUROLOGY LA English DT Article DE CAVERNOUS ANGIOMA; ROBERTS SYNDROME; SC-PHOCOMYELIA; 3RD NERVE PALSY ID VASCULAR MALFORMATION; OPTIC CHIASM; CAUDA-EQUINA; HEMANGIOMA; HEMORRHAGE AB A 25-year-old man with Roberts Syndrome (SC-phocomyelia) is described who presented with an acute onset of a complete right third nerve palsy. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated an enhancing lesion in the region of the right third nerve with bony erosion of the posterior clinoid process. At exploration, the lesion proved to be a cavernous angioma arising from the substance of the third nerve. Three other cases of third nerve cavernous angioma have been reported. One of these lesions also occurred in a patient with this unusual genetic syndrome. The surgical management and possible role of the genetic defect in the pathogenesis of this lesion are discussed. C1 HARVARD UNIV,SCH MED,DEPT PATHOL NEUROPATHOL,BOSTON,MA 02115. RP OGILVY, CS (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,FRUIT ST,BOSTON,MA 02114, USA. NR 14 TC 30 Z9 30 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD JUL PY 1993 VL 40 IS 1 BP 39 EP 42 DI 10.1016/0090-3019(93)90168-Z PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA LM923 UT WOS:A1993LM92300011 PM 8322177 ER PT J AU BURTON, B DESPOSITO, F FROSTER, U HOLMES, LB HOLZGREVE, W JACKSON, L LAGE, J MAHONEY, MJ MENNUTI, M MILNER, R OLNEY, R WILSON, RD ZACHARY, JM DELACRUZ, F KAMINETZKY, H AF BURTON, B DESPOSITO, F FROSTER, U HOLMES, LB HOLZGREVE, W JACKSON, L LAGE, J MAHONEY, MJ MENNUTI, M MILNER, R OLNEY, R WILSON, RD ZACHARY, JM DELACRUZ, F KAMINETZKY, H TI REPORT OF NATIONAL-INSTITUTE-OF-CHILD-HEALTH AND HUMAN-DEVELOPMENT-WORKSHOP-ON-CHORIONIC-VILLUS-SAMPLING AND LIMB AND OTHER DEFECTS, OCTOBER 20, 1992 SO TERATOLOGY LA English DT Editorial Material ID PRENATAL-DIAGNOSIS; MINOR ANOMALIES; MALFORMATIONS; ABNORMALITIES; REDUCTION; CVS AB A Workshop on Chorionic Villus Sampling (CVS) was convened by the National Institute of Child Health and Human Development (NICHD) and the American College of Obstetricians and Gynecologists at the National Institutes of Health on April 17, 1992, to discuss recent reports of an increased occurrence of malformations of the upper and lower limbs and oral structures among CVS-exposed infants. We summarize here the defects described in the CVS-exposed infants, the retrospective reassessments of published studies of the safety of CVS, the prevalence of limb deficiencies in infants not exposed to CVS, the status of the 7-9 week (conception or fertilization age) embryo, and the relevant human and animal experimental models of how CVS might be harmful to the embryo or fetus. C1 UNIV HOSP BRITISH COLUMBIA,DEPT MED GENET,VANCOUVER,BC,CANADA. GEORGETOWN UNIV,CTR BIOSTAT,WASHINGTON,DC 20057. HUMANA HOSP MICHAEL REESE,CTR MED GENET,CHICAGO,IL. AMER ACAD PEDIAT,COMM GENET,EVANSTON,IL 60204. LUBECK MED UNIV,DEPT OBSTET & GYNECOL,LUBECK,GERMANY. MASSACHUSETTS GEN HOSP,EMBRYOL TERATOL UNIT,BOSTON,MA 02114. UNIV MUNSTER,ZENTRUM FRAUENHEILKUNDE,W-4400 MUNSTER,GERMANY. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DIV MED GENET,PHILADELPHIA,PA 19107. GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20057. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. UNIV PENN,DEPT OBSTET & GYNECOL,PHILADELPHIA,PA 19104. UNIV BRITISH COLUMBIA,DEPT AIME COTTON,VANCOUVER V6T 1W5,BC,CANADA. CTR ENVIRONM HLTH,DIV BIRTH DEFECTS & DEV DISABIL,ATLANTA,GA. NICHHD,MENTAL RETARDAT & DEV DISABIL BRANCH,BETHESDA,MD 20892. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC. NR 29 TC 13 Z9 13 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 0040-3709 J9 TERATOLOGY JI Teratology PD JUL PY 1993 VL 48 IS 1 BP 7 EP 13 PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA LH937 UT WOS:A1993LH93700003 ER PT J AU GRILLO, HC AF GRILLO, HC TI PRIMARY TRACHEAL TUMORS SO THORAX LA English DT Editorial Material RP GRILLO, HC (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 3 TC 7 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 0040-6376 J9 THORAX JI Thorax PD JUL PY 1993 VL 48 IS 7 BP 681 EP 682 DI 10.1136/thx.48.7.681 PG 2 WC Respiratory System SC Respiratory System GA LQ060 UT WOS:A1993LQ06000001 PM 8153911 ER PT J AU BADIMON, L BADIMON, JJ CHESEBRO, JH FUSTER, V AF BADIMON, L BADIMON, JJ CHESEBRO, JH FUSTER, V TI VON-WILLEBRAND-FACTOR AND CARDIOVASCULAR-DISEASE SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID CORONARY-ARTERY DISEASE; DAMAGED VESSEL WALL; COLLAGEN TYPE-I; PLATELET DEPOSITION; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; SHEAR RATE; ATHEROSCLEROSIS; PIGS; THROMBOSIS C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,BOSTON,MA 02114. CSIC SANT PAU,CARDIOVASC RES UNIT & FDN,BARCELONA,SPAIN. RI BADIMON, LINA/O-4711-2014; Fuster, Valentin/H-4319-2015 OI BADIMON, LINA/0000-0002-9162-2459; Fuster, Valentin/0000-0002-9043-9986 FU NHLBI NIH HHS [HL-38933, HL-38393, HL-39840] NR 55 TC 69 Z9 69 U1 0 U2 2 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUL 1 PY 1993 VL 70 IS 1 BP 111 EP 118 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LT064 UT WOS:A1993LT06400020 PM 8236085 ER PT J AU GUO, ZZ WEINSTEIN, MJ PHILLIPS, MD KROLL, MH AF GUO, ZZ WEINSTEIN, MJ PHILLIPS, MD KROLL, MH TI MR 6,400 AURIN TRICARBOXYLIC-ACID DIRECTLY ACTIVATES PLATELETS SO THROMBOSIS RESEARCH LA English DT Article DE THROMBOSIS; PROTEIN KINASES; PHOSPHOLIPASE; CYCLIC NUCLEOTIDES; AURIN TRICARBOXYLIC ACID ID MURINE MONOCLONAL-ANTIBODY; VONWILLEBRAND-FACTOR; AURINTRICARBOXYLIC ACID; FIBRINOGEN; BINDING; AGGREGATION; RECEPTOR; HEPARIN; GPIB; IIIA AB ATA is a novel anticoagulant polymeric anionic aromatic compound that inhibits von Willebrand factor binding to platelet glycoprotein Ib and thereby prevents ristocetin- and shear stress-induced platelet aggregation. To investigate its mechanism of action, ATA fractions of homogeneous M(r) have been prepared by size exclusion chromatography. ATA fractions of M(r) greater-than-or-equal-to 2,500 are most effective at inhibiting vWF-mediated platelet aggregation, and ATA of M(r) = 2,500 also inhibits thrombin-induced platelet activation. Paradoxical results were observed in studies of ATA with M(r) = 6,400. This fraction of ATA stimulates aggregation of washed platelets or platelet-rich-plasma. The dose/response of aggregation shows a bell-shaped curve with maximal aggregation at approximately 2 mug/ml. Platelet aggregation is associated with phosphoinositide turnover and protein kinase C- and calcium-dependent protein phosphorylation. Platelet signalling responses to ATA are inhibited by platelet pretreatment with PGI2 or dibutyryl-cyclic AMP, but are unaffected by inhibiting platelet cyclooxygenase with aspirin. These results suggest that M(r) 6,400 ATA directly activates platelet phospholipase C to initiate platelet aggregation. This effect, unique to M(r) 6,400 ATA, could potentially mitigate ATA's beneficial anti-thrombotic effect on vWF-mediated platelet responses, and should be considered when analyzing results of experiments that utilize unfractionated ATA. C1 BAYLOR COLL MED,VA MED CTR,HEMATOL SECT,MS 902 6565,HOUSTON,TX 77030. RICE UNIV,HOUSTON,TX 77251. BOSTON UNIV,SCH MED,BOSTON,MA 02118. FU NHLBI NIH HHS [HL02311, HL46981, HL22355] NR 24 TC 17 Z9 17 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD JUL 1 PY 1993 VL 71 IS 1 BP 77 EP 88 DI 10.1016/0049-3848(93)90207-5 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LJ163 UT WOS:A1993LJ16300005 PM 8367837 ER PT J AU TOMFORD, WW FORTINI, B AF TOMFORD, WW FORTINI, B TI MUSCULOSKELETAL ALLOGRAFTS IN 1990 AND 1991 - A SURVEY OF UNITED-STATES TISSUE-BANKS SO TRANSFUSION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 1993 VL 33 IS 7 BP 620 EP 620 PG 1 WC Hematology SC Hematology GA LM691 UT WOS:A1993LM69100049 ER PT J AU LEPOR, H MACHI, G BARRY, MJ AF LEPOR, H MACHI, G BARRY, MJ TI COMPARISON OF AUA SYMPTOM INDEX IN UNSELECTED MALES AND FEMALES BETWEEN 55 AND 79 YEARS OF AGE SO UROLOGY LA English DT Article ID BENIGN PROSTATIC HYPERPLASIA; PROSTATECTOMY AB A symptom index for benign prostatic hyperplasia (BPH) was recently developed and validated by the Multidisciplinary Measurements Committee of the American Urologic Association, Inc. (AUA). The AUA symptom index ascertains the severity of seven nonspecific urinary symptoms associated with clinical BPH. The objective of the present study was to determine the influence of aging and gender on the AUA symptom index. Approximately 750 individuals attended a health fair at Froedtert Memorial Lutheran Hospital which included exhibits related to surgical and medical disease processes affecting the aging population. A nurse specialist randomly invited male and female attendees to complete the self-administered AUA symptom index and two additional inquiries related to age and gender. A total of 101 males and 96 females between fifty-five and seventy-nine years of age completed the AUA symptom index. The mean age of the males and females completing the AUA symptom index was 69.3 +/- 0.5 years and 68.2 +/- 0.6 years, respectively (p = 0.14). The mean AUA symptom scores in the male and female groups were 6.7 +/- 0.5 and 7.5 +/- 0.6, respectively. The difference between the mean AUA symptom scores in the male and female groups was not statistically significant (p - 0.35). The differences between AUA symptom scores were also not significantly different between males and females in five consecutive advancing-age groups between fifty-five and seventy-nine years of age. The percentage of males with mild, moderate, and severe symptoms was 64 percent, 32 percent, and 4 percent, respectively. The percentage of females with mild, moderate, and severe symptoms was 61 percent, 35 percent, and 4 percent, respectively. The present study suggests that prostatism-like symptoms are a manifestation of aging, and that the AUA symptom index is not BPH-specific. C1 MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,BOSTON,MA 02114. RP LEPOR, H (reprint author), MED COLL WISCONSIN,DEPT UROL,9200 W WISCONSIN AVE,MILWAUKEE,WI 53226, USA. NR 13 TC 227 Z9 232 U1 1 U2 3 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD JUL PY 1993 VL 42 IS 1 BP 36 EP 41 DI 10.1016/0090-4295(93)90332-5 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA LR144 UT WOS:A1993LR14400006 PM 7687078 ER PT J AU BARNETT, ML LAMB, KA COSTELLO, KM PIKE, MC AF BARNETT, ML LAMB, KA COSTELLO, KM PIKE, MC TI CHARACTERIZATION OF INTERLEUKIN-8 RECEPTORS IN HUMAN NEUTROPHIL MEMBRANES - REGULATION BY GUANINE-NUCLEOTIDES SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE INTERLEUKIN-8; RECEPTOR; G-PROTEIN; SIGNAL TRANSDUCTION; NEUTROPHIL; CHEMOTAXIS ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; CHEMOTACTIC FACTOR MDNCF; TUMOR NECROSIS FACTOR; 2 AFFINITY STATES; ACTIVATING FACTOR; CHEMOATTRACTANT RECEPTOR; BETA-THROMBOGLOBULIN; GENE-EXPRESSION; MESSENGER-RNA; CYTOKINE AB Interleukin-8 (IL-8) is a polymorphonuclear leukocyte (PMN) chemoattractant and activator which mediates its effects through specific cell-surface receptors. Indirect evidence indicates that guanine nucleotide regulatory proteins (G proteins) are necessary for transmembrane signaling. The present study characterizes IL-8 receptors in isolated PMN membrane fractions and shows direct regulation of these receptors by guanine nucleotides. The binding of [I-125]IL-8 to subcellular fractions of PMNs showed specific binding in a low-density membrane fraction containing, alkaline phosphatase, but not in primary or secondary granules. The binding of [I-125]IL-8 was rapid and reversible. The equilibrium dissociation constant (K(d)) of the receptor ranged from 5.0-12.4 nM and there were 1.58-5.90 . 10(10) receptors/mg protein. The dose-response curves for the competitive binding of three different forms of IL-8 to the receptor labeled by [I-125]IL-8 corresponded with their ability to produce chemotaxis and granule exocytosis in PMNs. Treatment of membranes with the nonhydrolyzable analogs of GTP, GMP-PNP and GTPgammaS. inhibited the binding of [I-125]IL-8. GMP-PNP decreased the affinity of the IL-8 receptor by approx. 2-fold without altering the total receptor number. These findings demonstrate that IL-8 receptors in PMN membranes arc of high affinity and are convertible to a low-affinity state in the presence of guanine nucleotides, suggesting a direct role for G proteins in transmembrane signaling by this cytokine. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ARTHRITIS UNIT,FRUIT ST,BOSTON,MA 02114. FU NIAID NIH HHS [R01 AI28386, F32 AI108484, P01 AI28465] NR 43 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD JUN 30 PY 1993 VL 1177 IS 3 BP 275 EP 282 DI 10.1016/0167-4889(93)90123-7 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LK264 UT WOS:A1993LK26400006 PM 8323978 ER PT J AU LEEHUANG, S LIN, JJ KUNG, H HUANG, PL LEE, L HUANG, PL AF LEEHUANG, S LIN, JJ KUNG, H HUANG, PL LEE, L HUANG, PL TI THE HUMAN ERYTHROPOIETIN-ENCODING GENE CONTAINS A CAAT BOX, TATA BOXES AND OTHER TRANSCRIPTIONAL REGULATORY ELEMENTS IN ITS 5' FLANKING REGION SO GENE LA English DT Article DE GENE EXPRESSION; TRANSCRIPTION SIGNALS; GROWTH FACTORS; HORMONE; HEMATOPOIESIS ID TRANSGENIC MICE; STIMULATING FACTOR; NUCLEAR FACTORS; EXPRESSION; PROTEIN; INTERLEUKIN-6; SEQUENCES; PROMOTER; INVITRO; LIVER AB We have reported the cloning and expression of a human erythropoietin (hEp)-encoding cDNA [Lee-Huang, Proc. Natl. Acad. Sci. USA 81 (1984) 2708-2712]. Using this hEp cDNA as a probe, we isolated a 9.3-kb BamHI genomic Ep clone from a human leukocyte library soon thereafter. The size and restriction map of this clone is in agreement with restriction analysis of human genomic DNA probed with the hEp cDNA, demonstrating that this clone is representative of the single hEp gene. This clone is unique in that it extends beyond any reported hEp genomic clone by 3.9 kb on the 5' side and by 1.8 kb on the 3' side. The promoter function of the newly described 5' flanking region has been demonstrated by the expression of biologically active hEp in transfected cells. We find that, despite reports to the contrary, hEp does contain classic canonical TATA boxes and a CAAT box. The 5'-flanking region also contains cytokine-responsive consensus sequences, tissue-specific and metal-responsive elements, CRE and GRE sites, and binding sites for transcription factors, including AP1, NF-kappabeta and Spl. These regulatory elements have not been found in the hEp genomic clones thus far reported. The identification of these elements and their precise localization in hEp should be useful in studying the regulation of hEp expression, as well as in gene therapy and physiologic modulation of this hormone. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP LEEHUANG, S (reprint author), NYU,SCH MED,DEPT BIOCHEM,NEW YORK,NY 10016, USA. FU NHLBI NIH HHS [HL 30862, HL21683] NR 45 TC 29 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 30 PY 1993 VL 128 IS 2 BP 227 EP 236 DI 10.1016/0378-1119(93)90567-M PG 10 WC Genetics & Heredity SC Genetics & Heredity GA LK345 UT WOS:A1993LK34500011 PM 8514189 ER PT J AU LAPOSATA, M MUSZBEK, L AF LAPOSATA, M MUSZBEK, L TI COVALENT MODIFICATION OF PROTEINS BY ARACHIDONATE AND EICOSAPENTAENOATE IN PLATELETS SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. LAJOS KOSSUTH UNIV,SCH MED,DEPT CLIN CHEM,H-4010 DEBRECEN,HUNGARY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN 30 PY 1993 VL 69 IS 6 BP 550 EP 550 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LT577 UT WOS:A1993LT57700034 ER PT J AU GRABOWSKI, EF ZUCKERMAN, DB GRABOWSKI, AC NEMERSON, Y GUHA, A AF GRABOWSKI, EF ZUCKERMAN, DB GRABOWSKI, AC NEMERSON, Y GUHA, A TI FUNCTIONAL EXPRESSION OF TISSUE FACTOR (TF) BY ACTIVATED ENDOTHELIAL-CELLS IS ENHANCED DRAMATICALLY BY ANTITISSUE FACTOR PATHWAY INHIBITOR (ANTI-TFPI) UNDER FLOW CONDITIONS SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. MT SINAI MED CTR,NEW YORK,NY 10029. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN 30 PY 1993 VL 69 IS 6 BP 581 EP 581 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LT577 UT WOS:A1993LT57700132 ER PT J AU ODA, A DRUKER, BJ ARIYOSHI, H SMITH, M SALZMAN, EW AF ODA, A DRUKER, BJ ARIYOSHI, H SMITH, M SALZMAN, EW TI PP60SRC IS AN ENDOGENOUS SUBSTRATE FOR CALPAIN IN HUMAN BLOOD-PLATELETS SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 BETH ISRAEL HOSP,DEPT SURG,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR MOLEC BIOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN 30 PY 1993 VL 69 IS 6 BP 698 EP 698 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LT577 UT WOS:A1993LT57700566 ER PT J AU MUSZBEK, L LAPOSATA, M AF MUSZBEK, L LAPOSATA, M TI MYRISTOYLATION OF PROTEINS IN PLATELETS SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 LAJOS KOSSUTH UNIV,SCH MED,DEPT CLIN CHEM,H-4010 DEBRECEN,HUNGARY. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN 30 PY 1993 VL 69 IS 6 BP 699 EP 699 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LT577 UT WOS:A1993LT57700571 ER PT J AU BADIMON, JJ FUSTER, V CHESEBRO, JH BADIMON, L AF BADIMON, JJ FUSTER, V CHESEBRO, JH BADIMON, L TI EFFECT OF DEPTH OF ARTERIAL INJURY ON KINETICS OF FIBRINOGEN DEPOSITION IN ARTERIAL THROMBOSIS SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. CSIC,CID,CARDIOVASC RES UNIT & FDN,BARCELONA,SPAIN. RI BADIMON, LINA/O-4711-2014 OI BADIMON, LINA/0000-0002-9162-2459 NR 0 TC 0 Z9 0 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 JUN 30 PY 1993 VL 69 IS 6 BP 796 EP 796 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LT577 UT WOS:A1993LT57700905 ER PT J AU BADIMON, L FUSTER, EV CHESEBRO, JH BADIMON, JJ AF BADIMON, L FUSTER, EV CHESEBRO, JH BADIMON, JJ TI KINETICS OF FIBRINOGEN DEPOSITION ON STENOTIC DAMAGED VESSEL WALL IN ARTERIAL THROMBOSIS SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. CSIC & FDN,CARDIOVASC RES UNIT,BARCELONA,SPAIN. RI BADIMON, LINA/O-4711-2014 OI BADIMON, LINA/0000-0002-9162-2459 NR 0 TC 1 Z9 1 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN 30 PY 1993 VL 69 IS 6 BP 813 EP 813 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LT577 UT WOS:A1993LT57700966 ER PT J AU COLLEN, D STASSEN, JM REFINO, CJ PAONI, WF KEYT, BA ROSKAMS, T JANG, IK LIJNEN, HR GOLD, HK BENNETT, W AF COLLEN, D STASSEN, JM REFINO, CJ PAONI, WF KEYT, BA ROSKAMS, T JANG, IK LIJNEN, HR GOLD, HK BENNETT, W TI COMPARATIVE THROMBOLYTIC PROPERTIES OF RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR (RT-PA) AND OF 2 PLASMINOGEN-ACTIVATOR INHIBITOR-1 (PAI-1) RESISTANT GLYCOSYLATION VARIANTS IN A COMBINED ARTERIAL AND VENOUS THROMBOSIS MODEL IN THE DOG SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 CATHOLIC UNIV LEUVEN,CTR THROMBOSIS & VASC RES,B-3000 LOUVAIN,BELGIUM. CATHOLIC UNIV LEUVEN,DEPT PATHOL,B-3000 LOUVAIN,BELGIUM. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. GENENTECH INC,DEPT CARDIOVASC PHARMACOL,S SAN FRANCISCO,CA 94080. NR 0 TC 4 Z9 4 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN 30 PY 1993 VL 69 IS 6 BP 841 EP 841 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LT577 UT WOS:A1993LT57701072 ER PT J AU MCBANE, RD HASSINGER, NL GRILL, DE BADIMON, JJ FUSTER, V CHESEBRO, JH AF MCBANE, RD HASSINGER, NL GRILL, DE BADIMON, JJ FUSTER, V CHESEBRO, JH TI INHIBITION OF ACUTE THROMBUS BY WARFARIN DURING ANGIOPLASTY IN PIGS SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MAYO CLIN & MAYO FDN,DEPT BIOCHEM & MOLEC BIOL,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,HEMATOL RES SECT,ROCHESTER,MN 55905. NR 0 TC 2 Z9 2 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 JUN 30 PY 1993 VL 69 IS 6 BP 981 EP 981 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LT577 UT WOS:A1993LT57701578 ER PT J AU JAHROUDI, N LYNCH, DC AF JAHROUDI, N LYNCH, DC TI ENDOTHELIAL SPECIFIC EXPRESSION OF VON-WILLEBRAND-FACTOR GENE SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN 30 PY 1993 VL 69 IS 6 BP 1212 EP 1212 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LT577 UT WOS:A1993LT57702381 ER PT J AU GARABEDIAN, HD DOHERTY, JM GOLD, HK SHATOS, MA AF GARABEDIAN, HD DOHERTY, JM GOLD, HK SHATOS, MA TI PROTECTIVE EFFECT OF SPECIFIC THROMBIN INHIBITION ON THE FIBRINOLYTIC POTENTIAL OF CULTURED HUMAN ENDOTHELIAL-CELLS DURING ANOXIA FOLLOWED BY REOXYGENATION SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 UNIV VERMONT,COLL MED,DEPT SURG,BURLINGTON,VT 05405. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN 30 PY 1993 VL 69 IS 6 BP 1234 EP 1234 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LT577 UT WOS:A1993LT57702460 ER PT J AU KISS, RG COLLEN, D LU, HR JANG, IK ROSKAMS, T PLOW, EF GOLD, HK AF KISS, RG COLLEN, D LU, HR JANG, IK ROSKAMS, T PLOW, EF GOLD, HK TI TIME-COURSE OF THE EFFECTS OF A SINGLE BOLUS INJECTION OF F(AB')2 FRAGMENTS OF THE ANTIPLATELET GLYCOPROTEIN-IIB/IIIA (GPIIB/IIIA) ANTIBODY-7E3, 7E3-F(AB')2, ON ARTERIAL EVERSION GRAFT OCCLUSION, PLATELET-AGGREGATION AND BLEEDING-TIME IN DOGS SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 CTR THROMBOSIS & VASC RES,LOUVAIN,BELGIUM. DEPT HISTOPATHOL,LOUVAIN,BELGIUM. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. CLEVELAND CLIN,CLEVELAND,OH 44106. NR 0 TC 0 Z9 0 U1 0 U2 2 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN 30 PY 1993 VL 69 IS 6 BP 1322 EP 1322 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LT577 UT WOS:A1993LT57702791 ER PT J AU FATTAEY, A HELIN, K HARLOW, E AF FATTAEY, A HELIN, K HARLOW, E TI TRANSCRIPTIONAL INHIBITION BY THE RETINOBLASTOMA PROTEIN SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Article ID HUMAN MYC PROMOTER; GENE-PRODUCT; FACTOR E2F; TRANS-ACTIVATION; E1A; BIND AB The retinoblastoma protein, pRB, appears to play a key role in coordinating the regulation of cell cycle position and transcriptional events. pRB undergoes specific cell-cycle-dependent phosphorylation, being underphosphorylated in G1 and heavily phosphorylated in S, G2, and M. The underphosphorylated form is able to interact with the E2F transcription factor. Recently, we have cloned a cDNA for E2F-1. By using this clone and a series of non-pRB binding mutants, we have been able to show that the binding of pRB to E2F-1 causes inhibition of E2F-mediated transactivation. pRB's inhibition of E2F-mediated transcription would be lost by mutation in the retinoblastoma gene in human tumours, by pRB's interaction with DNA tumour virus oncoproteins, or by phosphorylation during the cell cycle. RP FATTAEY, A (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 23 TC 9 Z9 9 U1 0 U2 0 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON, ENGLAND SW1Y 5AG SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD JUN 29 PY 1993 VL 340 IS 1293 BP 333 EP 336 DI 10.1098/rstb.1993.0075 PG 4 WC Biology SC Life Sciences & Biomedicine - Other Topics GA LL729 UT WOS:A1993LL72900010 PM 8103936 ER PT J AU GANZINI, L CASEY, DE HOFFMAN, WF MCCALL, AL AF GANZINI, L CASEY, DE HOFFMAN, WF MCCALL, AL TI THE PREVALENCE OF METOCLOPRAMIDE-INDUCED TARDIVE-DYSKINESIA AND ACUTE EXTRAPYRAMIDAL MOVEMENT-DISORDERS SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article AB Background: Metoclopramide hydrochloride, a neuroleptic dopamine receptor antagonist used to treat gastric ailments, is reported to cause extrapyramidal movement disorders. The goals of this study were (1) to determine the prevalence and severity of tardive dyskinesia and acute extrapyramidal movement syndromes including akathisia, acute dystonia, and drug-induced parkinsonism in metoclopramide-treated patients and (2) to compare the prevalence and severity of tardive dyskinesia in metoclopramide-treated diabetics and nondiabetics. Methods: From a list of metoclopramide-treated patients received from the Portland (Ore) Veterans Affairs Medical Center pharmacy, 53 patients met inclusion criteria and 51 (96%) agreed to participate. Controls consisted of a convenience sample drawn from the Portland Veterans Affairs Medical Center Outpatient Clinic who were matched to subjects on age (+/-10 years), gender, and presence or absence of diabetes. Of 61 potential controls contacted, 51 (84%) agreed to participate. Metoclopramide-treated subjects and controls were seen by a rater who was ''blind'' to all diagnoses and treatments. The rater performed a standardized examination used to elicit signs and symptoms of tardive dyskinesia and acute extrapyramidal movement syndromes. Results: The relative risk for tardive dyskinesia was 1.67 (95% confidence interval, 0.93 to 2.97), and the relative risk for drug-induced parkinsonism was 4.0 (95% confidence interval, 1.5 to 10.5). Metoclopramide-treated patients had significantly greater severity of tardive dyskinesia, drug-induced parkinsonism, and subjective akathisia than controls. Use of metoclopramide was associated with impairment in ambulation and increased use of benzodiazepines. Metoclopramide-treated diabetics had significantly greater severity of tardive dyskinesia than metoclopramide-treated nondiabetics. Conclusions: Metoclopramide use is associated with a significantly increased prevalence and severity of several extrapyramidal movement disorders. C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. RP GANZINI, L (reprint author), PORTLAND VET AFFAIRS MED CTR,PSYCHIAT SERV,116A-P,POB 1034,PORTLAND,OR 97207, USA. FU NINDS NIH HHS [NS22213]; PHS HHS [36657, 43586] NR 30 TC 127 Z9 127 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 28 PY 1993 VL 153 IS 12 BP 1469 EP 1475 DI 10.1001/archinte.153.12.1469 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA LJ892 UT WOS:A1993LJ89200007 PM 8512437 ER PT J AU ONUNAIN, S RUSKIN, J AF ONUNAIN, S RUSKIN, J TI CARDIAC-ARREST SO LANCET LA English DT Article ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; SUSTAINED VENTRICULAR TACHYARRHYTHMIAS; CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; ARRHYTHMIAS; PREDICTION; SURVIVORS; DEATH; RISK C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA 02114. NR 35 TC 13 Z9 13 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 26 PY 1993 VL 341 IS 8861 BP 1641 EP 1647 DI 10.1016/0140-6736(93)90770-H PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA LJ727 UT WOS:A1993LJ72700016 PM 8100002 ER PT J AU HUANG, ZD CHEN, YN MENON, K TEICHER, BA AF HUANG, ZD CHEN, YN MENON, K TEICHER, BA TI SYNTHESIS AND EVALUATION OF THE ANTITUMOR-ACTIVITY OF 4,5-DIAMINO-SUBSTITUTED 1,2-BENZOQUINONES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTICANCER AGENTS; TUMOR-CELLS; QUINONES; OXIDATION; CATECHOLS; SPECTROSCOPY; MECHANISMS; CHEMISTRY; COMPLEXES; INVITRO AB A series of 4,5-diamino-substituted-1,2-benzoquinones were prepared from catechol and the corresponding secondary amines in high yield in a single step using copper complex formation to stabilize the intermediate. The cytotoxicity of the products under various conditions was evaluated using the EMT-6 mammary carcinoma cell line, and antitumor activity was tested in the L1210 murine leukemia. The 4,5-diaziridinyl-1,2-benzoquinone was a more potent cytotoxic agent than diaziquone (AZQ) and was very effective against the L1210 leukemia. The azetidine, pyrrolidine, and diethylamine derivatives were not effective antitumor agents. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115. FU NCI NIH HHS [R01-CA50174, R01-CA47379-06] NR 43 TC 18 Z9 18 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 25 PY 1993 VL 36 IS 13 BP 1797 EP 1801 DI 10.1021/jm00065a001 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA LJ878 UT WOS:A1993LJ87800001 PM 8515418 ER PT J AU MANSFIELD, FL OCONNELL, JX ROSENTHAL, DI SCULLY, RE BOYD, RJ ZUSMAN, RM GOODMAN, TA AF MANSFIELD, FL OCONNELL, JX ROSENTHAL, DI SCULLY, RE BOYD, RJ ZUSMAN, RM GOODMAN, TA TI A 67-YEAR-OLD MAN WITH OSTEOLYTIC LESIONS OF T11 AND T12 - PAGETS-DISEASE, ACTIVE, OF 2 VERTEBRAS, WITH PATHOLOGICAL FRACTURE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID BONE C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP MANSFIELD, FL (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 24 PY 1993 VL 328 IS 25 BP 1836 EP 1841 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA LH210 UT WOS:A1993LH21000009 ER PT J AU BYRNE, MC OHARA, RM KUCHROO, VK JAYARAMAN, S RAO, A DORF, ME COLLINS, M AF BYRNE, MC OHARA, RM KUCHROO, VK JAYARAMAN, S RAO, A DORF, ME COLLINS, M TI THE ROLE OF THE T-CELL RECEPTOR-ALPHA CHAIN IN ANTIGEN-SPECIFIC IMMUNE SUPPRESSION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. RP BYRNE, MC (reprint author), GENET INST INC,87 CAMBRIDGE PK DR,CAMBRIDGE,MA 02140, USA. NR 2 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 23 PY 1993 VL 685 BP 611 EP 613 DI 10.1111/j.1749-6632.1993.tb35924.x PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LL567 UT WOS:A1993LL56700077 PM 8363270 ER PT J AU RIDKER, PM HEBERT, PR FUSTER, V HENNEKENS, CH AF RIDKER, PM HEBERT, PR FUSTER, V HENNEKENS, CH TI ARE BOTH ASPIRIN AND HEPARIN JUSTIFIED AS ADJUNCTS TO THROMBOLYTIC THERAPY FOR ACUTE MYOCARDIAL-INFARCTION SO LANCET LA English DT Review ID TISSUE PLASMINOGEN-ACTIVATOR; ENTERIC-COATED ASPIRIN; LOW-DOSE ASPIRIN; INTRAVENOUS HEPARIN; INHIBITION C1 BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PREVENT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 21 TC 47 Z9 47 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 19 PY 1993 VL 341 IS 8860 BP 1574 EP 1577 DI 10.1016/0140-6736(93)90707-N PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA LH550 UT WOS:A1993LH55000014 PM 8099650 ER PT J AU COTTLERFOX, M SPITZER, TR AF COTTLERFOX, M SPITZER, TR TI IMMUNOGLOBULIN PREPARATIONS, ACUTE GRAFT-VERSUS-HOST DISEASE, AND INFECTION AFTER MARROW TRANSPLANT SO LANCET LA English DT Letter C1 MASSACHUSETTS GEN HOSP,BONE MARROW TRANSPLANT UNIT,BOSTON,MA 02114. RP COTTLERFOX, M (reprint author), NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892, USA. NR 4 TC 2 Z9 3 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 19 PY 1993 VL 341 IS 8860 BP 1592 EP 1592 DI 10.1016/0140-6736(93)90726-W PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LH550 UT WOS:A1993LH55000026 PM 8099659 ER PT J AU DEWHIRST, MW GRIFFIN, TW SMITH, AR PARKER, RG HANKS, GE BRADY, LW AF DEWHIRST, MW GRIFFIN, TW SMITH, AR PARKER, RG HANKS, GE BRADY, LW TI INTERSOCIETY COUNCIL ON RADIATION ONCOLOGY ESSAY ON THE INTRODUCTION OF NEW MEDICAL TREATMENTS INTO PRACTICE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID FAST-NEUTRON RADIOTHERAPY; SOFT-TISSUE SARCOMAS; PROGNOSTIC FACTORS; FINAL REPORT; HYPERTHERMIA; IRRADIATION; TUMORS; CANCER; TRIAL; HEAD C1 UNIV WASHINGTON,MED CTR,DEPT RADIAT ONCOL,SEATTLE,WA 98195. HAHNEMANN UNIV,DEPT RADIAT ONCOL,PHILADELPHIA,PA 19102. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT MED,BOSTON,MA 02114. UNIV CALIF LOS ANGELES,DEPT RADIAT ONCOL,LOS ANGELES,CA 90024. RP DEWHIRST, MW (reprint author), DUKE UNIV,MED CTR,DEPT RADIAT ONCOL,BOX 3455,DURHAM,NC 27710, USA. NR 23 TC 16 Z9 17 U1 1 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 16 PY 1993 VL 85 IS 12 BP 951 EP 957 DI 10.1093/jnci/85.12.951 PG 7 WC Oncology SC Oncology GA LF842 UT WOS:A1993LF84200010 PM 8496981 ER PT J AU BUDACH, W TAGHIAN, A FREEMAN, J GIOIOSO, D SUIT, HD AF BUDACH, W TAGHIAN, A FREEMAN, J GIOIOSO, D SUIT, HD TI IMPACT OF STROMAL SENSITIVITY ON RADIATION RESPONSE OF TUMORS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FLAVONE ACETIC-ACID; SCID MUTATION; MICE; VASCULATURE; INDUCTION; REPAIR; GROWTH; TISSUE; MECHANISM AB Background: Irradiation of tumors causes the death of both parenchymal tumor cells as well as normal tissue stromal cells (e. g., endothelium, connective tissue). However, it has been difficult to distinguish the contributions to overall tumor response after irradiation from the two compartments. The development of the severe combined immunodeficient (SCID) mouse provides a model in which the contribution of stromal cell responses to ionizing radiation to overall tumor response can be defined, because its normal tissue cells are extremely radiosensitive. Therefore, the results of irradiation of tumors in radiation-sensitive (SCID) and radiation-resistant hosts can be compared, and the contribution of the normal tissue stroma clarified. Purpose: Our purpose was to investigate the effects of radiation-induced stromal cell damage on tumor cell death, using tumor growth delay (GD) and local control (complete and permanent regression of the irradiated tumor) as end points. Methods: Tumor GD and local control experiments were performed in SCID, athymic, and C3H mice. Sixty SCID and 60 nude mice for each of three human tumor cell lines (HGL9, HSTS26, HCT15) and for each of five murine cell lines (FSC1, FSC2, FSM1, FSM2, E01) and 60 SCID and 60 C3H mice for the FSa2 spontaneous C3H sarcoma were studied. Neoplasms were produced by injection of 10(6) cells from in vitro tissue cultures into the flanks of donor mice; after tumors had grown, experimental neoplasms were produced by transplanting 2- to 3-mm fragments into recipient mice. Animals were randomly assigned to various groups when tumors reached average volumes of 120 mm3. Graded, single-dose x irradiations (15-115 Gy, dose rate about 7 Gy/min) were given under acutely hypoxic conditions. Tumors were scored one to two times per week until recurrence. Results: The x-ray doses needed to achieve local control in 50% of the animals (tumor control doses, TCD50) ranged from 45.1 to 58.0 Gy for human tumors and from 36.3 to 114.0 Gy for murine tumors. On average, the TCD50 values in SCID mice were only about 3.5% lower than values in nude or C3H mice. The amount of GD defined at 66% of the TCD50 for the various groups was, however, 27% longer in the SCID mice (P = .004). Conclusions: While the three-fold higher radiation sensitivity of the normal tissue stromal cells in the SCID mice did not alter the percentage of tumors controlled by x irradiation in the SCID mouse hosts as compared with other hosts, there appear to be significant differences in GD. Radiation-induced stromal cell damage does not significantly contribute to tumor cell death; however, it can prolong the interval of tumor regression. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114. FU NCI NIH HHS [CA-13311] NR 16 TC 51 Z9 51 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 JUN 16 PY 1993 VL 85 IS 12 BP 988 EP 993 DI 10.1093/jnci/85.12.988 PG 6 WC Oncology SC Oncology GA LF842 UT WOS:A1993LF84200015 PM 8496984 ER PT J AU RODRIGUEZ, A SANTAERA, O LARRIBEAU, M SOSA, MI PALACIOS, IF AF RODRIGUEZ, A SANTAERA, O LARRIBEAU, M SOSA, MI PALACIOS, IF TI EARLY DECREASE IN MINIMAL LUMINAL DIAMETER AFTER SUCCESSFUL PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY PREDICTS LATE RESTENOSIS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ANGIOGRAPHIC FOLLOW-UP; SCINTIGRAPHY; STENOSIS AB Eighty-eight patients underwent serial coronary arteriography before, immediately after, 24 hours after and 7 +/- 2 months after successful percutaneous transluminal coronary angioplasty (PTCA) of 102 lesions. Severity of coronary obstruction was measured using quantitative digital angiography. Three groups of lesions were defined when comparing angiograms recorded immediately after and 24 hours after PTCA: group I - lesions with either no change or less-than-or-equal-to 10% increase in arterial diameter stenosis after PTCA (n = 71); group II - lesions with >10% increase in diameter stenosis after PTCA (n = 19); and group III - patients with total occlusion (n = 12). There were no significant differences in the severity of stenosis before or immediately after PTCA among the 3 groups of lesions. Twenty-four hours after PTCA the diameter stenosis was 14.2 +/- 6.3% in group I, 34.7 +/- 8.1% in group II and 100 in group III (p<0.0001) At 7.1 +/- 2 months after PTCA the diameter stenosis was 21.2 +/- 16.8% in group I, 61.3 +/- 1.1% in group II, and 98.5 +/- 1.3% in group III (p<0.0001). Restenosis (greater-than-or-equal-to 50% stenosis diameter) at follow-up per lesion was significantly greater in group II than in group I (73.6 vs 9.8%) (p<0.0001). Thus, early aw giographic study after successful PTCA stratifies lesions into angiographic subsets with low (group I) and high (group II) risk of coronary restenosis. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,FRUIT ST,BOSTON,MA 02114. ANCHORENA HOSP,DIV CARDIOL,BUENOS AIRES,ARGENTINA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 24 TC 44 Z9 45 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 15 PY 1993 VL 71 IS 16 BP 1391 EP 1395 DI 10.1016/0002-9149(93)90598-7 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LF823 UT WOS:A1993LF82300003 PM 8517382 ER PT J AU FILATOV, V STEINERT, RF TALAMO, JH AF FILATOV, V STEINERT, RF TALAMO, JH TI POSTKERATOPLASTY ASTIGMATISM WITH SINGLE RUNNING SUTURE OR INTERRUPTED SUTURES SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID REMOVAL AB In a prospective randomized clinical trial we compared astigmatism after penetrating keratoplasty with two different suture techniques between two groups of patients (38 patients). The first group (18 patients) had a 24-bite single running 10-0 nylon suture (single running suture) with postoperative suture adjustment to decrease astigmatism. The second group (20 patients) had a combination of a 16-bite running 10-0 nylon suture and eight interrupted 10-0 nylon sutures (combined running and interrupted sutures) with selective postoperative removal of interrupted sutures to decrease astigmatism. The single running suture resulted in a lower postoperative astigmatism than a combined running and interrupted suture technique (single running suture, 2.7 +/- 2.2 diopters; combined running and interrupted sutures, 3.9 +/- 2.5 diopters; P < .02). Average length of follow-up was similar in both groups (single running suture, 9.0 +/- 2.2 months and combined running and interrupted sutures, 8.4 +/- 2.2 months). Minimal length of follow-up was six months in both groups. No running sutures were broken. The adjustable single running suture technique provided greater control of astigmatism after penetrating keratoplasty than a technique using a combination of a 16-bite running suture and eight interrupted sutures. C1 YALE UNIV,DEPT OPHTHALMOL & VISUAL SCI,NEW HAVEN,CT 06520. CTR EYE RES,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 11 TC 37 Z9 37 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN 15 PY 1993 VL 115 IS 6 BP 715 EP 721 PG 7 WC Ophthalmology SC Ophthalmology GA LE993 UT WOS:A1993LE99300003 PM 8506906 ER PT J AU SAORNIL, MA MARCUS, DM DOEPNER, D APOLONE, G TORRE, V ALBERT, DM AF SAORNIL, MA MARCUS, DM DOEPNER, D APOLONE, G TORRE, V ALBERT, DM TI NUCLEOLAR ORGANIZER REGIONS IN DETERMINING MALIGNANCY OF PIGMENTED CONJUNCTIVAL LESIONS SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PRIMARY ACQUIRED MELANOSIS; MELANOCYTIC LESIONS; PROTEINS; DYSPLASIA AB We assessed the usefulness of silver staining of nucleolar organizer regions in the diagnosis of pigmented conjunctival tumors. Fifty-one biopsy specimens were silver stained to identify the nucleolar organizer regions. Nineteen nevi without atypia, three nevi with atypia, eight primary acquired melanosis lesions, and 14 melanomas were studied. In each specimen, silver staining of the nucleolar organizer regions was counted in 100 cells to yield an average of the silver staining of the nucleolar organizer region count. The mean silver staining of the nucleolar organizer region counts per cell was correlated with the degree of malignancy of pigmented conjunctival lesions as follows: nevi, 3.0; primary acquired melanosis, 3.2; nevi with atypia, 3.9; primary acquired melanosis with atypia, 5.0; and melanoma, 5.7 (Spearman correlation [rS] = .83, P = .0001; analysis of variance [ANOVA] F test = 20.9, P = .0001). A cutoff value of 4.0 (mean silver staining of nucleolar organizer regions per cell) will differentiate melanoma and primary acquired melanosis with atypia from other lesions (sensitivity, 100%; specificity, 96%). The silver staining of nucleolar organizer regions is a useful adjunct in determining the malignancy of pigmented conjunctival tumors. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,EYE PATHOL LAB,BOSTON,MA 02114. MARIO NEGRI INST PHARMACOL RES,EPIDEMIOL CLIN LAB,I-20157 MILAN,ITALY. FU NEI NIH HHS [EY01917] NR 23 TC 8 Z9 8 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN 15 PY 1993 VL 115 IS 6 BP 800 EP 805 PG 6 WC Ophthalmology SC Ophthalmology GA LE993 UT WOS:A1993LE99300017 PM 8506916 ER PT J AU ADAMIS, AP SHIMA, DT YEO, KT YEO, TK BROWN, LF BERSE, B DAMORE, PA FOLKMAN, J AF ADAMIS, AP SHIMA, DT YEO, KT YEO, TK BROWN, LF BERSE, B DAMORE, PA FOLKMAN, J TI SYNTHESIS AND SECRETION OF VASCULAR-PERMEABILITY FACTOR VASCULAR ENDOTHELIAL GROWTH-FACTOR BY HUMAN RETINAL-PIGMENT EPITHELIAL-CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CHORIOCAPILLARIS; PROTEINS; MITOGEN C1 CHILDRENS HOSP MED CTR,DEPT SURG,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT ANAT,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT CELLULAR BIOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT PATHOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM CELL & DEV BIOL,BOSTON,MA 02115. RP ADAMIS, AP (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02115, USA. FU NEI NIH HHS [NEI EY00325] NR 26 TC 284 Z9 293 U1 0 U2 10 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 15 PY 1993 VL 193 IS 2 BP 631 EP 638 DI 10.1006/bbrc.1993.1671 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LG153 UT WOS:A1993LG15300025 PM 8512562 ER PT J AU HAMMOND, TG MAJEWSKI, RR ONORATO, JJ BRAZY, PC MORRE, DJ AF HAMMOND, TG MAJEWSKI, RR ONORATO, JJ BRAZY, PC MORRE, DJ TI ISOLATION AND CHARACTERIZATION OF RENAL CORTICAL MEMBRANES USING AN AQUEOUS 2-PHASE PARTITION TECHNIQUE SO BIOCHEMICAL JOURNAL LA English DT Article ID BRUSH-BORDER MEMBRANE; TRANSPORT; PROTEIN; ENDOSOMES; VESICLES; ASSAY AB The aqueous two-phase partition technique is a simple, rapid and inexpensive method for the fractionation of membrane preparations. Aqueous two-phase partitioning separates according to surface properties such as charge and hydrophobicity, making it complementary to established centrifugation techniques, which separate on the basis of density. Although aqueous two-phase partitioning has been successfully applied to animal tissues, there are limited data on the functional properties of the isolated membranes. We have applied the aqueous two-phase partition technique to rat renal brush-border membrane vesicles and sheets. Our aim was to remove organelle contamination while maintaining the functional properties of the membranes. Evidence from marker enzyme analysis and electron microscopy supports the conclusion that renal brush-border membranes are fractionated separate from the mitochondria and endoplasmic reticulum. This separation procedure did not alter the Na+-dependent transport of brush-border membrane vesicles. Na+-D-glucose symporter and Na+-H+ antiporter activity in the fractionated preparation increased to the same extent as did the enrichment of enzyme markers for brush-border membranes. C1 PURDUE UNIV,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. RP HAMMOND, TG (reprint author), UNIV WISCONSIN,DEPT MED,NEPHROL SECT,CTR CLIN SCI H4-510,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 28 TC 3 Z9 3 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 JUN 15 PY 1993 VL 292 BP 743 EP 748 PN 3 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LJ401 UT WOS:A1993LJ40100020 PM 7686365 ER PT J AU ZON, LI YAMAGUCHI, Y YEE, K ALBEE, EA KIMURA, A BENNETT, JC ORKIN, SH ACKERMAN, SJ AF ZON, LI YAMAGUCHI, Y YEE, K ALBEE, EA KIMURA, A BENNETT, JC ORKIN, SH ACKERMAN, SJ TI EXPRESSION OF MESSENGER-RNA FOR THE GATA-BINDING PROTEINS IN HUMAN EOSINOPHILS AND BASOPHILS - POTENTIAL ROLE IN GENE-TRANSCRIPTION SO BLOOD LA English DT Article ID LEYDEN CRYSTAL PROTEIN; MAJOR BASIC-PROTEIN; PORPHOBILINOGEN DEAMINASE GENE; PROMYELOCYTIC LEUKEMIA-CELLS; MATURE HUMAN EOSINOPHILS; DOMINANT CONTROL REGION; DIFFERENTIATION FACTOR; MOLECULAR-CLONING; CATIONIC PROTEIN; HL-60 CELLS C1 HOWARD HUGHES MED INST,BOSTON,MA. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,DIV INFECT DIS,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PEDIAT,DANA FARBER CANC INST,BOSTON,MA 02115. FU NHLBI NIH HHS [HL02347]; NIAID NIH HHS [AI22660, AI25230] NR 74 TC 148 Z9 155 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1993 VL 81 IS 12 BP 3234 EP 3241 PG 8 WC Hematology SC Hematology GA LG659 UT WOS:A1993LG65900010 PM 8507862 ER PT J AU GRABOWSKI, EF ZUCKERMAN, DB NEMERSON, Y AF GRABOWSKI, EF ZUCKERMAN, DB NEMERSON, Y TI THE FUNCTIONAL EXPRESSION OF TISSUE FACTOR BY FIBROBLASTS AND ENDOTHELIAL-CELLS UNDER FLOW CONDITIONS SO BLOOD LA English DT Article ID FACTOR-XA; MONOCLONAL-ANTIBODY; SHEAR-STRESS; INTERLEUKIN-1; SURFACE; BIOSYNTHESIS; PROCOAGULANT; LOCALIZATION; ANTIGEN; SITE C1 CUNY,SCH MED,DEPT MED,NEW YORK,NY 10021. CUNY,SCH MED,DEPT BIOCHEM,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP GRABOWSKI, EF (reprint author), MASSACHUSETTS GEN HOSP,DEPT PEDIAT,PEDIAT HEMATOL ONCOL UNIT,15 PARKMAN ST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL 33095] NR 28 TC 80 Z9 80 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1993 VL 81 IS 12 BP 3265 EP 3270 PG 6 WC Hematology SC Hematology GA LG659 UT WOS:A1993LG65900014 PM 8507863 ER PT J AU GRIBBEN, JG NEUBERG, D FREEDMAN, AS GIMMI, CD PESEK, KW BARBER, M SAPORITO, L WOO, SD CORAL, F SPECTOR, N RABINOWE, SN GROSSBARD, ML RITZ, J NADLER, LM AF GRIBBEN, JG NEUBERG, D FREEDMAN, AS GIMMI, CD PESEK, KW BARBER, M SAPORITO, L WOO, SD CORAL, F SPECTOR, N RABINOWE, SN GROSSBARD, ML RITZ, J NADLER, LM TI DETECTION BY POLYMERASE CHAIN-REACTION OF RESIDUAL CELLS WITH THE BCL-2 TRANSLOCATION IS ASSOCIATED WITH INCREASED RISK OF RELAPSE AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR B-CELL LYMPHOMA SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; NON-HODGKINS LYMPHOMA; FOLLICULAR LYMPHOMAS; CHROMOSOMAL TRANSLOCATION; GENE REARRANGEMENT; ANTIGEN RECEPTOR; CLUSTER REGION; MESSENGER-RNA; T(14-18) C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV BIOSTAT,BOSTON,MA 02115. RP GRIBBEN, JG (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU FIC NIH HHS [FO5-TWO4496]; NCI NIH HHS [CA-34183, CA-55207] NR 41 TC 300 Z9 300 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1993 VL 81 IS 12 BP 3449 EP 3457 PG 9 WC Hematology SC Hematology GA LG659 UT WOS:A1993LG65900039 PM 8507880 ER PT J AU DUNBAR, SF ROSENBERG, A MANKIN, H ROSENTHAL, D SUIT, HD AF DUNBAR, SF ROSENBERG, A MANKIN, H ROSENTHAL, D SUIT, HD TI GORHAM MASSIVE OSTEOLYSIS - THE ROLE OF RADIATION-THERAPY AND A REVIEW OF THE LITERATURE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Note DE GORHAM DISEASE; OSTEOLYSIS; SPONTANEOUS REGRESSION; SURGERY; RADIATION THERAPY; REOSSIFICATION ID DISEASE AB Purpose: This paper reviews the natural history and management of patients with Gorham's disease and presents four cases treated at The Massachusetts General Hospital since 1965. Gorham's disease is characterized by localized endothelial proliferation which results in destruction and resorption of bone. The etiology is undefined. There is no evidence of a malignant, neuropathic, or infectious component. This disease is progressive in most patients, but in occasional instances the process has been noted to be self-limited. The principal treatment modalities are surgery and radiation therapy. Methods and Material: Since 1965, four patients with Gorham's Disease have been treated at the Massachusetts Gene al Hospital. Three received definitive radiation therapy in doses ranging from 31.5 to 45 Gy. The fourth patient underwent surgery primarily. Results: Three patients are currently alive and fully functional with no evidence of disease at last follow-up. The fourth patient died of progressive disease despite treatment with both radiation therapy and surgery. Conclusion: The prognosis for patients with Gorham's disease is generally good unless vital structures are involved. due to the rarity of this entity, there is no standard therapy. Definitive radiation, therapy in moderate doses (40-45 Gy in 2 Gy fractions) appears to result in a good outcome and few long-term complications. C1 BRIGHAM & WOMENS HOSP, DEPT RADIAT ONCOL, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, DEPT PATHOL, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, DEPT ORTHOPAED, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, DEPT RADIOL, BOSTON, MA 02115 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, BOSTON, MA 02114 USA. NR 41 TC 74 Z9 79 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 15 PY 1993 VL 26 IS 3 BP 491 EP 497 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA LH910 UT WOS:A1993LH91000015 PM 8514544 ER PT J AU BENK, VA ADAMS, JA SHIPLEY, WU URIE, MM MCMANUS, PL EFIRD, JT WILLETT, CG GOITEIN, M AF BENK, VA ADAMS, JA SHIPLEY, WU URIE, MM MCMANUS, PL EFIRD, JT WILLETT, CG GOITEIN, M TI LATE RECTAL BLEEDING FOLLOWING COMBINED X-RAY AND PROTON HIGH-DOSE IRRADIATION FOR PATIENTS WITH STAGES T3-T4 PROSTATE CARCINOMA SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Note DE PROSTATE CANCER; RECTAL RADIATION TOLERANCE; DOSE VOLUME HISTOGRAM; PROTON IRRADIATION; CONFORMAL THERAPY ID EXTERNAL BEAM IRRADIATION; RADIATION-THERAPY; BOOST THERAPY; ADENOCARCINOMA; CANCER; BIOPSY AB Purpose: Dose escalation for prostate cancer by external beam irradiation is feasible by a 160 MeV perineal proton beam that reduces the volume of rectum irradiated. We correlated the total doses received to portions of the anterior rectum to study the possible relationship of the volume irradiated to the incidence of late rectal toxicity. Methods: We have randomized 191 patients with stages T3 and T4 prostatic carcinoma to one of two treatment dose arms. These were: 1) 75.6 Cobalt-Gy-equivalent (CGE), 50.4 Gy delivered by 107-25 MV photons followed by 25.2 CGE delivered perineally by protons (Arm 1) or 2) 67.2 CGE delivered by 10-25 MV photons (Arm 2). Results: With a median follow-up of 3.7 years, post-irradiation rectal bleeding (grades 1 and 2 only, none requiring surgery or hospitalization) from telangietatic rectal mucosal vessels has occurred in 34% of 99 Arm-1 patients and 16% of 92 Arm-2 patients (p = 0.013). Dose-volume histograms (DVHs) for the anterior rectal wall, the posterior rectal wall and the total rectum in 41 patients treated on Arm 1 were calculated from the three dimensional dose distributions. Rectal bleeding has occurred in 14 or 34% of the 41 DVH-analyzed subset of Arm-1 patients. Both the fractional volume of the anterior rectum and the total dose received by fractional volumes of the anterior rectum significantly correlate with the actuarial probability of bleeding. Conclusions: Clinicians planning dose escalation to men with localized prostate cancer should approve with caution treatment plans raising more than 40% of the anterior rectum to more than 75 CGE without additional effort to protect the rectal mucosa because this late sequela data indicate that more than half of these men will otherwise have rectal bleeding. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,GU ONCOL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR CANC,SCH MED,BOSTON,MA 02114. FU NCI NIH HHS [CA 221239] NR 26 TC 121 Z9 124 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 15 PY 1993 VL 26 IS 3 BP 551 EP 557 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA LH910 UT WOS:A1993LH91000025 PM 8514551 ER PT J AU SLAPAK, CA KHARBANDA, S SALEEM, A KUFE, DW AF SLAPAK, CA KHARBANDA, S SALEEM, A KUFE, DW TI DEFECTIVE TRANSLOCATION OF PROTEIN-KINASE-C IN MULTIDRUG-RESISTANT HL-60 CELLS CONFERS A REVERSIBLE LOSS OF PHORBOL ESTER-INDUCED MONOCYTIC DIFFERENTIATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROMYELOCYTIC LEUKEMIA-CELLS; TRANSCRIPTION FACTOR AP-1; COLONY-STIMULATING FACTOR; TUMOR NECROSIS FACTOR; FOS GENE-EXPRESSION; MOLECULAR-CLONING; P-GLYCOPROTEIN; HL60 CELLS; TERMINAL DIFFERENTIATION; ERYTHROLEUKEMIA-CELLS AB Previous studies have demonstrated that human HL-60 myeloid leukemia cells differentiate in response to phorbol esters. This event is associated with induction of the c-jun early response gene and appearance of a monocytic phenotype. The present studies have examined the effects of vincristine-selected, multidrug resistance on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced HL-60 cell differentiation. The results demonstrate that multidrug-resistant HL-60 cells, designated HL-60/vinc, fail to respond to TPA with an increase in c-jun transcripts or other phenotypic characteristics of monocytic differentiation. By contrast, treatment of HL-60/vinc cells with okadaic acid, an inhibitor of serine/threonine protein phosphatases, induces c-jun transcription, growth arrest, and expression of the c-fms gene. Studies were also performed with an HL-60/vinc revertant (HL-60/vinc/R) line that has regained partial sensitivity to vincristine. The finding that HL-60/vinc/R cells respond to TPA with induction of a monocytic phenotype, but not c-jun expression, suggests that c-jun induction is not obligatory for monocytic differentiation. Other studies further demonstrate that the jun-B and fra-1 genes are induced by TPA in both HL-60/vinc and HL-60/vinc/R cells, whereas c-fos expression is attenuated in the HL-60/vinc line. Since TPA activates protein kinase C (PKC), we examined translocation of PKC from the cytosol to the membrane fraction. Although HL-60 and HL-60/vinc/R cells demonstrated translocation of PKC activity, this subcellular redistribution was undetectable in HL-60/vinc cells. Activity of the mitogen-activated protein kinase family with associated phosphorylation of c-Jun Y-peptide was markedly diminished in TPA-treated HL-60/vinc cells, but not in response to okadaic acid. Taken together, these findings suggest that vincristine resistance confers insensitivity to TPA-induced differentiation and can include defects in PKC-mediated signaling events and induction of jun/fos early response gene expression. RP SLAPAK, CA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-01613, CA42802] NR 70 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 15 PY 1993 VL 268 IS 17 BP 12267 EP 12273 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LG658 UT WOS:A1993LG65800010 PM 8389757 ER PT J AU ROSENBERG, IM IYER, R CHERAYIL, B CHIODINO, C PILLAI, S AF ROSENBERG, IM IYER, R CHERAYIL, B CHIODINO, C PILLAI, S TI STRUCTURE OF THE MURINE MAC-2 GENE - SPLICE VARIANTS ENCODE PROTEINS LACKING FUNCTIONAL SIGNAL PEPTIDES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GALACTOSIDE-BINDING LECTIN; MONOCLONAL-ANTIBODIES; ENDOGENOUS LECTINS; INITIATION; ANTIGEN; CELLS; SEQUENCE; PATHWAY; IGE; EXPRESSION AB The murine Mac-2 gene is composed of six exons dispersed over 10.5 kilobases. Sl nuclease mapping showed multiple transcription initiation sites, clustered within a 30-base pair region. Sequence analysis revealed that a consensus initiator sequence is located in this area which lacks a TATA motif. The untranslated first exon contains an alternative splice donor site, confirming the existence of two cDNA species with the potential to encode proteins differing at their NH2 termini. In vitro expression and translocation experiments demonstrate that both of the alternatively spliced variants of Mac-2 encode proteins which lack a functional signal peptide. Subcellular fractionation studies indicate that most of the Mac-2 protein is present in the cytosol. These results support the view that Mac-2 is exported from the cell by an unusual mechanism which does not depend on the presence of a signal peptide. C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC GENET GRP,MOLEC IMMUNOL LAB,BLDG 149,13TH ST,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NIAID NIH HHS [AI-27835] NR 34 TC 24 Z9 25 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 15 PY 1993 VL 268 IS 17 BP 12393 EP 12400 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LG658 UT WOS:A1993LG65800029 PM 8509379 ER PT J AU ODA, A DRUKER, BJ ARIYOSHI, H SMITH, M SALZMAN, EW AF ODA, A DRUKER, BJ ARIYOSHI, H SMITH, M SALZMAN, EW TI PP60SRC IS AN ENDOGENOUS SUBSTRATE FOR CALPAIN IN HUMAN BLOOD-PLATELETS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIN-BINDING PROTEIN; CA-2+-DEPENDENT PROTEASE; STIMULATED PLATELETS; INHIBITOR CALPEPTIN; PLASMA-MEMBRANE; ACTIVATION; THROMBIN; AGGREGATION; PHOSPHORYLATION; PP60C-SRC AB Calpain is distributed ubiquitously in virtually every tissue (Croall, D. E., and DeMartino, G. N. (1991) Physiol. Rev. 71, 813-846), but its physiological role remains to be determined. The identification of its natural endogenous substrates would be of great interest. Since pp60src, a major tyrosine kinase in platelets, is known to be easily cleaved during purification from cells (Feder, D., and Bishop, J. M. (1990) J. Biol. Chem. 265, 8205-8211), we examined the possibility that it is an endogenous substrate of calpain. In the whole cell lysate from resting platelets, which was analyzed by Western blotting with monoclonal antibody 327, we found pp60src almost exclusively in a 60-kDa form, with a trace of 52-kDa form. Addition of A23187 (a calcium ionophore) or dibucaine, which are known to be activators of platelet calpain (Croall and DeMartino, 1991; Fox, J. E., Reynolds, C., Morrow, J. S., and Phillips, D. R. (1987) Blood 76, 2510-2519; Fox, J. E., Austin, C. D., Boyles, J. K., and Steffen, P. K. (1990b) J. Cell Biol. 111, 483-493), caused dose- and time-dependent cleavage of actin-binding protein and p235 protein (talin). At the same time, loss of the 60-kDa species of pp60src and generation of the 52-kDa (occasionally seen as doublets) and 47-kDa species were detected by the Western blotting. In platelets aggregated by 1 unit/ml thrombin, apparently identical cleavage products were found. The cleavage of pp60src was inhibited by calpeptin (20 muM), an inhibitor of calpain (Tsujinaka, T., Kajiwara, Y., Kambayashi, J., Sakon, M., Higuchi, N., Tanaka, T., and Mori, T. (1988) Biochem. Biophys. Res. Commun. 153,1201-1208; Tsujinaka, T., Ariyoshi, H., Uemura, Y., Sakon, M., Kambayashi, J., and Mori, T. (1990) Life Sci. 46, 1059-1066; Fox, J. E., Clifford, C. C., and Austin, C. D. (1990) Blood 76, 2510-2519; Fox, J. E., Austin, C. D., Boyles, J. K., and Steffen, P. K. (1990) J. Cell. Biol. 111, 483-493; Fox, J. E., Austin, C. D., Clifford, C. C., and Steffen, P. K. (1991) J. Biol. Chem. 266, 13289-13295). Addition of EGTA (3 mM) to the extracellular media completely inhibited the cleavage of actin-binding protein, talin, and pp60src in response to A23187 (1 muM). Intact pp60src was distributed in both cytosolic and particulate (membrane) fractions. Cleaved species were found exclusively in the cytosolic fraction. pp60src-associated enolase kinase activity was reduced. Thus, pp60src is an endogenous substrate for calpain, the cleavage of which may have regulatory effects on the kinase. C1 BETH ISRAEL HOSP,DEPT SURG,330 BROOKLINE AVE,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR MOLEC BIOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-33014] NR 33 TC 113 Z9 113 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 15 PY 1993 VL 268 IS 17 BP 12603 EP 12608 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LG658 UT WOS:A1993LG65800057 PM 7685344 ER PT J AU JONES, M CORDELL, JL BEYERS, AD TSE, AGD MASON, DY AF JONES, M CORDELL, JL BEYERS, AD TSE, AGD MASON, DY TI DETECTION OF T-CELL AND B-CELL IN MANY ANIMAL SPECIES USING CROSS-REACTIVE ANTIPEPTIDE ANTIBODIES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BOVINE LYMPHOCYTES-T; LEUKOCYTE-COMMON ANTIGEN; MONOCLONAL-ANTIBODIES; DIFFERENTIATION ANTIGEN; SURFACE-ANTIGENS; GENE SUPERFAMILY; RAT LYMPHOCYTES; IDENTIFICATION; MOLECULE; HOMOLOG AB A wide range of lineage-specific Ag are detectable in the human lymphoid system using mAb, but only a few such markers are detectable in animal species. In this paper, we have investigated the interspecies reactivity of antibodies raised against intracytoplasmic peptide sequences from two T cell Ag (CD3 and CD5) and two B cell markers (the Ig-associated polypeptides encoded by the mb-1 and B29 genes). Immunocytochemical labeling of tissue sections showed that these antibodies cross-react widely between different species (including ungulates, rodents, and marsupials), staining B or T cell areas selectively in lymphoid tissue. The specificity of these antibodies for the animal homologues of the human T and B cell markers was confirmed for the rat by Western blotting analysis. The broad cross-reactivity of these antibodies appears to be due to the fact that they were raised against intra-cytoplasmic peptide sequences that are highly conserved between humans and rodents, i.e., 80% for mb-1, 85% for CD5, and 100% for CD3 and B29. This strategy should, in the future, widen the range of lineage-associated markers detectable in experimental animals. C1 UNIV OXFORD SIR WILLIAM DUNN SCH PATHOL,MRC,CELLULAR IMMUNOL UNIT,OXFORD OX1 3RE,ENGLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. RP JONES, M (reprint author), JOHN RADCLIFFE HOSP,NUFFIELD DEPT PATHOL,LEUKAEMIA RES FUND IMMUNODIAGNOST UNIT,LEVEL 1,OXFORD OX3 9DU,ENGLAND. RI Cordell, Jacqueline/B-3430-2009; Jones, Margaret/B-4083-2009 NR 47 TC 193 Z9 196 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1993 VL 150 IS 12 BP 5429 EP 5435 PG 7 WC Immunology SC Immunology GA LH978 UT WOS:A1993LH97800023 PM 8515069 ER PT J AU YUZAWA, Y BRENTJENS Jr BRETT, J CALDWELL, PRB ESPOSITO, C FUKATSU, A GODMAN, G STERN, D ANDRES, G AF YUZAWA, Y BRENTJENS, JR BRETT, J CALDWELL, PRB ESPOSITO, C FUKATSU, A GODMAN, G STERN, D ANDRES, G TI ANTIBODY-MEDIATED REDISTRIBUTION AND SHEDDING OF ENDOTHELIAL ANTIGENS IN THE RABBIT SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANGIOTENSIN-CONVERTING ENZYME; CELL-SURFACE-ANTIGENS; IMMUNE-COMPLEXES; HEPARAN-SULFATE; C3B RECEPTOR; PROTEIN-C; COMPLEMENT; INJURY; LUNG; RELEASE AB We report the results of studies performed in vitro and in vivo that were designed to explore individual, sequential, and concurrent Ag-antibody interactions at the surface of rabbit endothelial cells. Divalent heterologous antibodies to rabbit lung angiotensin-converting enzyme and to rabbit lung thrombomodulin were employed. In cultured monolayers, both antibodies redistributed the specific Ag and co-redistributed the immunologically unrelated Ag inducing partial or complete disappearance of the Ag from the cell surface (antigenic modulation) in 15 to 60 min. When injected into living rabbits, each antibody induced a rapid (1 to 3 min) redistribution and subsequent modulation of the specific and of the unrelated Ag at the surface of alveolar endothelial cells. Immune complexes, and the unrelated Ag, were shed in the circulation, attaining peak levels 3 to 4 min after the injection; were rapidly bound by platelets, E, and polymorphonuclear leukocytes; and were subsequently found in phagocytic cells in the spleen and in the liver. Thrombomodulin co-shed by angiotensin-converting enzyme antibody and, to a lesser degree, angiotensin-converting enzyme co-shed by thrombomodulin antibody, crossed the glomerular capillary walls and were reabsorbed by the epithelial cells of the proximal tubules within 2 to 3 min. The results show that immunologically unrelated Ag can be passively entrapped during formation of immune complexes at the cell surface, and provide new information on the kinetics of clearance of immune complexes containing endogenous, structural Ag. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP E,SCH MED,7TH FLOOR, 149 13TH ST, BOSTON, MA 02129 USA. SUNY Buffalo, DEPT MICROBIOL PATHOL & MED, BUFFALO, NY 14214 USA. BUFFALO GEN HOSP, RENAL IMMUNOPATHOL LAB, BUFFALO, NY 14203 USA. COLUMBIA UNIV COLL PHYS & SURG, DEPT PATHOL & PHYSIOL, NEW YORK, NY 10032 USA. COLUMBIA UNIV COLL PHYS & SURG, DEPT MED, NEW YORK, NY 10032 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02129 USA. RI Caldwell, Peter/E-2968-2015 OI Caldwell, Peter/0000-0001-8227-3771 FU NHLBI NIH HHS [HL-34625, HL-42588]; NIDDK NIH HHS [DK36807] NR 57 TC 22 Z9 22 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1993 VL 150 IS 12 BP 5633 EP 5646 PG 14 WC Immunology SC Immunology GA LH978 UT WOS:A1993LH97800045 PM 7685798 ER PT J AU BASKAR, S OSTRANDROSENBERG, S NABAVI, N NADLER, LM FREEMAN, GJ GLIMCHER, LH AF BASKAR, S OSTRANDROSENBERG, S NABAVI, N NADLER, LM FREEMAN, GJ GLIMCHER, LH TI CONSTITUTIVE EXPRESSION OF B7 RESTORES IMMUNOGENICITY OF TUMOR-CELLS EXPRESSING TRUNCATED MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CD28; TUMOR IMMUNITY ID INVARIANT CHAIN; MONOCLONAL-ANTIBODIES; COSTIMULATORY SIGNAL; T-CELLS; BINDING; INTERLEUKIN-2; PROLIFERATION; COMPARTMENTS; ANTIGEN-B7; REJECTION AB The inability of the autologous host to reject resident tumor cells is frequently the result of inadequate generation of tumor-specific T cells. Specific activation of T cells occurs after delivery of two signals by the antigen-presenting cell. The first signal is antigen-specific and is the engagement of the T-cell antigen receptor by a specific major histocompatibility complex antigen-peptide complex. For some T cells, the second or costimulatory signal is the interaction of the T-cell CD28 receptor with the B7 activation molecule of the antigen-presenting cell. In the present study, we demonstrate that mouse sarcoma cells genetically engineered to provide both T-cell activation signals stimulate potent tumor-specific CD4+ T cells that cause rejection of both engineered and wild-type neoplastic cells. Two other recent studies have also demonstrated that costimulation via B7 can improve tumor immunity. However, our study differs from these reports by two important observations. (i) One of these studies utilized mouse tumor cells expressing xenogeneic viral antigens, and hence, the results are not applicable to wild-type resident tumors. Our study, however, demonstrates that coexpression of B7 by major histocompatibility complex class H+ tumor cells induces immunity in the autologous host that is specific for naturally occurring tumor antigens of poorly immunogenic tumors. (ii) In both earlier studies, only CD8+ T cells were activated after coexpression of B7, whereas in the present report, tumor-specific CD4+ T cells are generated. This report therefore illustrates the role of the B7 activation molecule in stimulating potent tumor-specific CD4+ T cells that mediate rejection of wild-type tumors and provides a theoretical basis for immunotherapy of established tumors. C1 ROCHE RES CTR,DEPT IMMUNOPHARMACOL,NUTLEY,NJ 07110. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP OSTRANDROSENBERG, S (reprint author), UNIV MARYLAND,DEPT BIOL SCI,CATONSVILLE,MD 21228, USA. FU NCI NIH HHS [R01CA52527]; NIAID NIH HHS [R01AI21569] NR 28 TC 300 Z9 301 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 15 PY 1993 VL 90 IS 12 BP 5687 EP 5690 DI 10.1073/pnas.90.12.5687 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LH129 UT WOS:A1993LH12900065 PM 7685909 ER PT J AU GONCALVES, E YAMADA, K THATTE, HS BACKER, JM GOLAN, DE KAHN, CR SHOELSON, SE AF GONCALVES, E YAMADA, K THATTE, HS BACKER, JM GOLAN, DE KAHN, CR SHOELSON, SE TI OPTIMIZING TRANSMEMBRANE DOMAIN HELICITY ACCELERATES INSULIN-RECEPTOR INTERNALIZATION AND LATERAL MOBILITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SCHISTOSOMA-MANSONI; PROLINE RESIDUES; TYROSINE KINASE; MEMBRANE; PROTEINS; CELLS; AUTOPHOSPHORYLATION; COMPONENTS; REGION AB Transmembrane (TM) domains of integral membrane proteins are generally thought to be helical. However, a Gly-Pro sequence within the TM domain of the insulin receptor is predicted to act as a helix breaker. CD analyses of model TM peptides in a lipid-like environment show that substitution of Gly and Pro by Ala enhances helicity. On this basis, Gly933 and Pro934 within the TM domain of the intact human insulin receptor were mutated to Ala (G --> A, P --> A, GP --> AA) to assess effects of altered helicity on receptor functions. Mutated and wild-type receptors, expressed stably in cultured CHO cells at equivalent levels, were properly assembled, biosynthetically processed, and exhibited similar affinities for insulin. Receptor autophosphorylation and substrate kinase activity in intact cells and soluble receptor preparations were indistinguishable. In contrast, insulin-stimulated receptor internalization was accelerated 2-fold for the GP --> AA mutant, compared to a wild-type control or the G --> A and P --> A mutants. Insulin degradation, which occurs during receptor endocytosis and recycling, was similarly elevated in cells transfected with GP --> AA mutant receptors. Fluorescence photobleaching recovery measurements showed that the lateral mobility of GP --> AA mutant receptors was also increased 2- to 3-fold. These results suggest that lateral mobility directly influences rates of insulin-mediated receptor endocytosis and that rates of endocytosis and lateral mobility are retarded by a kinked TM domain in the wild-type receptor. Invariance of Gly-Pro within insulin receptor TM domain sequences suggests a physiologic advantage for submaximal rates of receptor internalization. C1 JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MOLEC PHARMACOL,BOSTON,MA 02115. NR 40 TC 30 Z9 30 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 15 PY 1993 VL 90 IS 12 BP 5762 EP 5766 DI 10.1073/pnas.90.12.5762 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LH129 UT WOS:A1993LH12900081 PM 8390680 ER PT J AU WILLIAMS, NG PARADIS, H AGARWAL, S CHAREST, DL PELECH, SL ROBERTS, TM AF WILLIAMS, NG PARADIS, H AGARWAL, S CHAREST, DL PELECH, SL ROBERTS, TM TI RAF-1 AND P21(V-RAS) COOPERATE IN THE ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BACULOVIRUS; SF9 INSECT CELLS; ERK1 PROTEIN KINASE ID SIGNAL-REGULATED KINASES; SERINE THREONINE KINASES; MAP KINASES; GROWTH; IDENTIFICATION; FAMILY; ERKS; PHOSPHORYLATION; TRANSDUCTION; ANTIBODIES AB Mitogen-activated protein (MAP) kinases Raf-1, pp60src, and p21ras all play important roles in the transfer of signals from the cell surface to the nucleus. We have used the baculovirus/Sf9 insect cell system to elucidate the regulatory relationships between pp60v-src, p21v-ras, MAP kinase (p44erk1/mapk), and Raf-1. In Sf9 cells, p44erk1/mapk is activated by coexpression with either v-Raf or a constitutively activated form of Raf-1 (Raf 22W). In contrast, p44erk1/mapk is activated to only a limited extent by coexpression with either Raf-1 or p21v-ras alone. This activation of p44erk1/mapk is greatly enhanced by coexpression with both p21v-ras and Raf-1. Since we have previously shown that p21v-ras stimulates Raf-1 activity, the activation of p44erk1/mapk by p21v-ras may occur exclusively via a Raf-1-dependent pathway. However, a dominant-inhibitory mutant of Raf-1 (Raf301) does not block the activation of p44erk1/mapk by p21v-ras. Further, pp60v-src, which activates Raf-1 at least as effectively as p21v-ras, fails to enhance p44erk1/mapk activity greatly when coexpressed with Raf-1. These data suggest that activation of p44erk1/mapk by p21v-ras may occur via both Raf-1-dependent and Raf-1-independent pathways. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV BRITISH COLUMBIA,BIOMED RES CTR,DEPT MED,VANCOUVER V6T 1Z3,BC,CANADA. KINETEK BIOTECHNOL CORP,RICHMOND V7C 1T6,BC,CANADA. FU NCI NIH HHS [CA43803]; NICHD NIH HHS [HD24926] NR 38 TC 110 Z9 111 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 15 PY 1993 VL 90 IS 12 BP 5772 EP 5776 DI 10.1073/pnas.90.12.5772 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LH129 UT WOS:A1993LH12900083 PM 8390681 ER PT J AU POLAK, M SCHARFMANN, R SEILHEIMER, B EISENBARTH, G DRESSLER, D VERMA, IM POTTER, H AF POLAK, M SCHARFMANN, R SEILHEIMER, B EISENBARTH, G DRESSLER, D VERMA, IM POTTER, H TI NERVE GROWTH-FACTOR INDUCES NEURON-LIKE DIFFERENTIATION OF AN INSULIN-SECRETING PANCREATIC BETA-CELL LINE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PANCREAS; NEURAL CREST; ENDODERM; DEVELOPMENT; TRK ONCOGENE ID ENDOCRINE-CELLS; NGF RECEPTOR; PC12 CELLS; EXPRESSION; GENE; ONCOGENE; PROTEIN; ENCODES; MIGRATION; GLUCAGON AB Nerve growth factor (NGF) is the best understood of a class of trophic proteins that are important for the survival of neurons and the elaboration of their characteristic processes. Here we demonstrate that RINm5F, a rat insulinoma cell line representing an early stage in pancreatic beta cell differentiation, expresses both the Trk and p75 NGF receptors and responds to NGF by extending neurite-like (neurofilament-containing) processes. NGF treatment of RINm5F cells also induces the expression of genes normally responsive to NGF in neurons, including the NGF-1A gene. Inasmuch as pancreatic beta cells arise from the embryonic endoderm, these results suggest that NGF may play a wider role during development than previously thought-a role not restricted to cells of neuroectodermal origin-and that endocrine and neuronal cells share a developmental pathway. The specific effect of NGF on an early pancreatic beta cell line also suggests that this neurotrophic factor might form the basis of a therapeutic treatment for some types of diabetes by inducing the proliferative differentiation of islet cells. C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,220 LONGWOOD AVE,BOSTON,MA 02115. SALK INST BIOL STUDIES,SAN DIEGO,CA 92138. JOSLIN DIABET CTR,BOSTON,MA 02215. NR 48 TC 103 Z9 108 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 15 PY 1993 VL 90 IS 12 BP 5781 EP 5785 DI 10.1073/pnas.90.12.5781 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LH129 UT WOS:A1993LH12900085 PM 8516328 ER PT J AU HODGSON, JM JOHNSON, G AF HODGSON, JM JOHNSON, G TI VISUAL WORD RECOGNITION IN DEVELOPMENTAL DYSGRAPHIA - ONE LEXICON OR 2 SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article RP HODGSON, JM (reprint author), MASSACHUSETTS GEN HOSP, INST HLTH PROFESS, GRAD PROGRAM COMMUN SCI & DISORDERS, BOSTON, MA 02114 USA. NR 2 TC 2 Z9 2 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD JUN 14 PY 1993 VL 682 BP 354 EP 356 DI 10.1111/j.1749-6632.1993.tb22992.x PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LK214 UT WOS:A1993LK21400039 PM 8323134 ER PT J AU MICHALEK, MT GRANT, EP GRAMM, C GOLDBERG, AL ROCK, KL AF MICHALEK, MT GRANT, EP GRAMM, C GOLDBERG, AL ROCK, KL TI A ROLE FOR THE UBIQUITIN-DEPENDENT PROTEOLYTIC PATHWAY IN MHC CLASS I-RESTRICTED ANTIGEN PRESENTATION SO NATURE LA English DT Article ID TOXIC LYMPHOCYTES-T; ACTIVATING ENZYME; MOLECULES; EXPRESSION; DEGRADATION; PROTEIN; ICAM-1; CELLS; GENE; E1 AB THE degradation of most cellular proteins starts with their covalent conjugation with ubiquitin1,2. This labels the proteins for rapid hydrolysis to oligopeptides by a (26S) proteolytic complex containing a (20S) degradative particle called the proteasome3,4. Some system in the cytosol also generates antigenic peptides from endogenously synthesized cellular and viral proteins5-10. These peptides bind to newly synthesized class I major histocompatibility complex molecules in the endoplasmic reticulum and peptide/class I complexes are then transported to the cell surface for presentation to cytotoxic T cells11,12. How these peptides are produced is unknown, although a modification that promotes ubiquitin-dependent degradation of a viral protein enhances its presentation with class I13 and indirect evidence suggests a role for proteolytic particles closely resembling and perhaps identical to the proteasome4,12,14,15. Using cells that exhibit a temperature-sensitive defect in ubiquitin conjugation, we report here that nonpermissive temperature inhibited class I-restricted presentation of ovalbumin introduced into the cytosol, but did not affect presentation of an ovalbumin peptide synthesized from a minigene. These results implicate the ubiquitin-dependent proteolytic pathway in the production of antigenic peptides. C1 HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT CELLULAR & MOLEC PHYSIOL, BOSTON, MA 02115 USA. RP MICHALEK, MT (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV LYMPHOCYTE BIOL, BOSTON, MA 02115 USA. NR 37 TC 284 Z9 287 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 10 PY 1993 VL 363 IS 6429 BP 552 EP 554 DI 10.1038/363552a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF939 UT WOS:A1993LF93900053 PM 8389422 ER PT J AU NATHAN, DM AF NATHAN, DM TI LONG-TERM COMPLICATIONS OF DIABETES-MELLITUS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID INSULIN-DEPENDENT DIABETICS; CORONARY HEART-DISEASE; METABOLIC CONTROL; NATURAL-HISTORY; KIDNEY-FUNCTION; MYOCARDIAL-INFARCTION; BLOOD-PRESSURE; RISK-FACTORS; MICROVASCULAR COMPLICATIONS; ANTIHYPERTENSIVE TREATMENT C1 HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, DEPT MED, BOSTON, MA 02114 USA. RP NATHAN, DM (reprint author), MASSACHUSETTS GEN HOSP, DIABET UNIT, BOSTON, MA 02114 USA. FU AHRQ HHS [1-R01 HSO6665]; NIDDK NIH HHS [5UO1 DK30643] NR 126 TC 693 Z9 726 U1 6 U2 40 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 10 PY 1993 VL 328 IS 23 BP 1676 EP 1685 DI 10.1056/NEJM199306103282306 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA LF054 UT WOS:A1993LF05400006 PM 8487827 ER PT J AU HIRSCH, MS DAQUILA, RT AF HIRSCH, MS DAQUILA, RT TI THERAPY FOR HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID AIDS-RELATED COMPLEX; RECOMBINANT SOLUBLE CD4; COLONY-STIMULATING FACTOR; REVERSE-TRANSCRIPTASE INHIBITORS; SYNTHETIC HIV-1 PROTEASE; PLACEBO-CONTROLLED TRIAL; TERM ZIDOVUDINE THERAPY; HERPES-SIMPLEX VIRUS; PHASE-I TRIAL; INTERFERON-ALPHA RP MASSACHUSETTS GEN HOSP, DEPT MED, INFECT DIS UNIT, BOSTON, MA 02114 USA. NR 133 TC 154 Z9 155 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 10 PY 1993 VL 328 IS 23 BP 1686 EP 1695 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA LF054 UT WOS:A1993LF05400007 PM 8387640 ER PT J AU DURAND, ML CALDERWOOD, SB SWARTZ, MN AF DURAND, ML CALDERWOOD, SB SWARTZ, MN TI ACUTE BACTERIAL-MENINGITIS IN ADULTS - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP DURAND, ML (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 10 PY 1993 VL 328 IS 23 BP 1713 EP 1713 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LF054 UT WOS:A1993LF05400019 ER PT J AU DEC, GW NARULA, J YASUDA, T AF DEC, GW NARULA, J YASUDA, T TI ACUTE BACTERIAL-MENINGITIS IN ADULTS - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP DEC, GW (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 10 PY 1993 VL 328 IS 23 BP 1714 EP 1715 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA LF054 UT WOS:A1993LF05400023 ER PT J AU ADAMS, RD AF ADAMS, RD TI IMPACT OF CHARCOT,JEAN,MARTIN ON NEUROLOGY, MEDICAL-EDUCATION AND PSYCHOLOGY IN THE UNITED-STATES SO BULLETIN DE L ACADEMIE NATIONALE DE MEDECINE LA French DT Article RP ADAMS, RD (reprint author), MASSACHUSETS GEN HOSP,DEPT NEUROL,BOSTON,MA, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIE NATL DE MEDECINE PI PARIS 06 PA 16 RUE BONAPARTE, 75272 PARIS 06, FRANCE SN 0001-4079 J9 B ACAD NAT MED PARIS JI Bull. Acad. Natl. Med. PD JUN 8 PY 1993 VL 177 IS 6 BP 877 EP 881 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA MA058 UT WOS:A1993MA05800004 PM 8221187 ER PT J AU BARLETBAS, C ARYSTARKHOVA, E CHEVAL, L MARSY, S SWEADNER, K MODYANOV, N DOUCET, A AF BARLETBAS, C ARYSTARKHOVA, E CHEVAL, L MARSY, S SWEADNER, K MODYANOV, N DOUCET, A TI ARE THERE SEVERAL ISOFORMS OF NA,K-ATPASE ALPHA-SUBUNIT IN THE RABBIT KIDNEY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID NA-K-ATPASE; CATALYTIC SUBUNIT; MESSENGER-RNAS; RAT-BRAIN; NA+,K+-ATPASE; NEPHRON; IDENTIFICATION; EXPRESSION; SEGMENTS; SEQUENCE AB Previous pharmacologic and kinetic studies have demonstrated the axial heterogeneity of the rabbit kidney tubule with regard to Na,K-ATPase. To evaluate whether this heterogeneity might reflect the presence of distinct isoforms of the alpha subunit of Na,K-ATPase, we used two monoclonal antibodies, IIC9 and IIE2 (G8), specific for the alpha1 and alpha3 isoforms, respectively, as probes for changes in the specific activity of Na,K-ATPase at the level of successive segments of the rabbit nephron. Single, well defined nephron segments were obtained by microdissection of collagenase-treated kidney. Results indicate that IIC9 antibody inhibited Na,K-ATPase activity by >90% in all the segments of the nephron except the collecting duct. Conversely, IIE2 (G8) antibody abolished Na,K-ATPase activity in the collecting duct, whereas it had no effect in other nephron segments. These findings suggest that the rabbit collecting duct preferentially expresses a distinct isoform of Na,K-ATPase catalytic subunit, which is presumably alpha3-like, in agreement with previous pharmacologic and kinetic observations, whereas other nephron segments would express the alpha1 isoform. C1 CNRS,PHYSIOL LAB,UNITE RECH ASSOCIEE 219,11 PL M BERTHELOT,F-75231 PARIS 05,FRANCE. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MM SHEMYAKIN INST BIOORGAN CHEM,MOSCOW 117871,RUSSIA. NR 24 TC 31 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 5 PY 1993 VL 268 IS 16 BP 11512 EP 11515 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LF284 UT WOS:A1993LF28400011 PM 8389354 ER PT J AU TARBELL, NJ GELBER, RD WEINSTEIN, HJ MAUCH, P AF TARBELL, NJ GELBER, RD WEINSTEIN, HJ MAUCH, P TI SEX-DIFFERENCES IN RISK OF 2ND MALIGNANT-TUMORS AFTER HODGKINS-DISEASE IN CHILDHOOD SO LANCET LA English DT Article ID CANCER; COMPLICATIONS; IRRADIATION; THERAPY; CHEMOTHERAPY; CHILDREN; LEUKEMIA; LYMPHOMA AB There have been reports of a high incidence of second malignant disorders in survivors of Hodgkin's disease. We studied the cumulative incidence of second tumours in 191 children, who were 16 years or younger at diagnosis, with stage IA-IVB Hodgkin's disease, treated at the Joint Center for Radiation Therapy, Boston, between 1969 and 1988. The 10-year actuarial survival was 89 (SE 2)%. The median follow-up time was 11 (range 3-21) years from diagnosis. 109 children were initially treated with radiotherapy alone, 61 received chemotherapy and radiotherapy, and 21 received chemotherapy alone. Second tumours arose in 15 patients 6-20 years after the diagnosis of Hodgkin's disease. The estimated cumulative incidence of second malignant disorders at 1 5 years was 12 (4)% overall. 10 of the second tumours arose among 66 female patients, compared with 5 among 125 male patients (cumulative incidence 24 [9] vs 5 [3]%). The relative risk of a second tumour for female compared with male patients was 4.5 (95% CI 1.4-15.1; p=0.013). For male patients, the observed incidence of second tumours was 18 times that expected for the normal population (95% CI 6-42), whereas for female patients it was 57 times that expected (27-105). 13 of the second malignant disorders were solid tumours, including 4 breast cancers. Thus, the risk of a child treated for Hodgkin's disease developing a second tumour is higher for girls than for boys. The cumulative incidence of second cancers increases from 10 years after treatment. These findings emphasise the importance of continued surveillance in patients treated for Hodgkin's disease. C1 HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,DEPT BIOSTAT,DIV BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP TARBELL, NJ (reprint author), JOINT CTR RADIAT THERAPY,DEPT RADIAT ONCOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 06516] NR 30 TC 53 Z9 54 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 5 PY 1993 VL 341 IS 8858 BP 1428 EP 1430 DI 10.1016/0140-6736(93)90880-P PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA LF841 UT WOS:A1993LF84100002 PM 8099139 ER PT J AU MARGOSSIAN, SS SLAYTER, HS KACZMAREK, E MCDONAGH, J AF MARGOSSIAN, SS SLAYTER, HS KACZMAREK, E MCDONAGH, J TI PHYSICAL CHARACTERIZATION OF RECOMBINANT TISSUE-PLASMINOGEN ACTIVATOR SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE PLASMINOGEN ACTIVATOR; TISSUE-TYPE PLASMINOGEN ACTIVATOR; PROTEIN CHARACTERIZATION; ELECTRON MICROSCOPY; MOLECULAR WEIGHT ID ONE-CHAIN; BLOOD; CLEAVAGE; SITE; THROMBOSPONDIN; CELLS; FORM AB Electron microscopic and physical-chemical properties of one- and two-chain tissue plasminogen activator (t-PA) were studied. The molecular weight of one-chain t-PA obtained by both sedimentation equilibrium and SDS-PAGE was estimated to be about 65000, while both chains in the reduced two-chain form were in the range of 35000-40000. Sedimentation coefficients were identical for both forms of t-PA (S20,w0 = 4.12). The two forms of t-PA were indistinguishable by electron microscopic analysis, which confirmed the sedimentation results, and showed that they were ellipsoidal end relatively compact. The major and minor axes were approx. 13 nm and approx. 10 nm and f/f0 was 1.36. The individual domains of t-PA are relatively small and are folded within the molecule, so that the overall appearance is globular. C1 BETH ISRAEL HOSP,DEPT PATHOL,330 BROOKLINE AVE,BOSTON,MA 02215. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT BIOCHEM,BRONX,NY 10461. MONTEFIORE MED CTR,BRONX,NY 10467. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT ORTHOPED RES,BRONX,NY 10461. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-2659, HL-33014] NR 34 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD JUN 4 PY 1993 VL 1163 IS 3 BP 250 EP 256 DI 10.1016/0167-4838(93)90159-O PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LG890 UT WOS:A1993LG89000004 PM 8507663 ER PT J AU CIGARROA, JE EAGLE, KA ISSELBACHER, EM AF CIGARROA, JE EAGLE, KA ISSELBACHER, EM TI THE DIAGNOSIS OF THORACIC AORTIC DISSECTION BY NONINVASIVE IMAGING PROCEDURES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP CIGARROA, JE (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 3 PY 1993 VL 328 IS 22 BP 1638 EP 1638 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LE289 UT WOS:A1993LE28900016 ER PT J AU GREENE, R AF GREENE, R TI CASE 46-1992 - CORRECTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID SABER-SHEATH TRACHEA RP GREENE, R (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 3 PY 1993 VL 328 IS 22 BP 1642 EP 1643 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA LE289 UT WOS:A1993LE28900032 PM 8487817 ER PT J AU MARK, EJ GRILLO, HC AF MARK, EJ GRILLO, HC TI A 48-YEAR-OLD WOMAN WITH A NARROWED TRACHEA - TRACHEOPATHIA-OSTEOPLASTICA - (SABER-SHEATH TRACHEA) (VOL 327, PG 1512, 1992) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Correction, Addition RP MARK, EJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 3 PY 1993 VL 328 IS 22 BP 1643 EP 1643 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LE289 UT WOS:A1993LE28900033 ER PT J AU BLUMENTHAL, D AF BLUMENTHAL, D TI TOTAL QUALITY MANAGEMENT AND PHYSICIANS CLINICAL DECISIONS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HEALTH-CARE C1 MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED & HLTH CARE POLICY,BOSTON,MA 02115. RP BLUMENTHAL, D (reprint author), MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,MPEC,50 STANIFORD ST,BOSTON,MA 02114, USA. NR 25 TC 59 Z9 59 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 2 PY 1993 VL 269 IS 21 BP 2775 EP 2778 DI 10.1001/jama.269.21.2775 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA LD671 UT WOS:A1993LD67100029 PM 8492405 ER PT J AU NIHEI, K MCKEE, AC KOWALL, NW AF NIHEI, K MCKEE, AC KOWALL, NW TI PATTERNS OF NEURONAL DEGENERATION IN THE MOTOR CORTEX OF AMYOTROPHIC-LATERAL-SCLEROSIS PATIENTS SO ACTA NEUROPATHOLOGICA LA English DT Article DE AMYOTROPHIC LATERAL SCLEROSIS; MOTOR CORTEX; CYTOSKELETAL PROTEINS; PARVALBUMIN; NADPH-DIAPHORASE ID PARVALBUMIN-IMMUNOREACTIVE NEURONS; CENTRAL-NERVOUS-SYSTEM; RAT SPINAL-CORD; ALZHEIMERS-DISEASE; HUNTINGTONS-DISEASE; PYRAMIDAL NEURONS; QUANTITATIVE-ANALYSIS; VULNERABLE SUBSET; AXONAL SWELLINGS; CORTICAL-NEURONS AB We examined patterns of neuronal degeneration in the motor cortex of amyotrophic lateral sclerosis (ALS) patients using traditional cell stains and several histochemical markers including neurofilament, parvalbumin, NADPH-diaphorase, ubiquitin. Alz-50 and tau. Three grades of ALS (mild, moderate, severe) were defined based on the extent of Betz cell depletion. Non-phosphorylated neurofilament immunoreactive cortical pyramidal neurons and non-pyramidal parvalbumin local circuit neurons were significantly depleted in all grades of ALS. In contrast, NADPH-diaphorase neurons and Alz-50-positive neurons were quantitatively preserved despite reduced NADPH-diaphorase cellular staining and dendritic pruning. The density of ubiquitin-positive structures in the middle and deep layers of the motor cortex was increased in all cases. Axonal tau immunoreactivity was not altered. These histochemical results suggest that cortical degeneration in ALS is distinctive from other neurodegenerative diseases affecting cerebral cortex. Unlike Huntington's disease, both pyramidal and local cortical neurons are affected in ALS; unlike Alzheimer's disease, alteration of the neuronal cytoskeleton is not prominent. The unique pattern of neuronal degeneration found in ALS motor cortex is consistent with non-N-methyl-D-aspartate glutamate receptor-mediated cytotoxicity. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. YAMAGATA UNIV,DEPT INTERNAL MED 3,YAMAGATA 99023,JAPAN. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02118. BEDFORD VA MED CTR,CTR GERIATR RES EDUC CLIN,BEDFORD,MA 01730. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 NR 64 TC 107 Z9 107 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JUN PY 1993 VL 86 IS 1 BP 55 EP 64 PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA LJ873 UT WOS:A1993LJ87300009 PM 8396837 ER PT J AU VONDEIMLING, A LOUIS, DN MENON, AG VONAMMON, K PETERSEN, I ELLISON, D WIESTLER, OD SEIZINGER, BR AF VONDEIMLING, A LOUIS, DN MENON, AG VONAMMON, K PETERSEN, I ELLISON, D WIESTLER, OD SEIZINGER, BR TI DELETIONS ON THE LONG ARM OF CHROMOSOME-17 IN PILOCYTIC ASTROCYTOMA SO ACTA NEUROPATHOLOGICA LA English DT Note DE PILOCYTIC ASTROCYTOMA; LOSS OF HETEROZYGOSITY; CHROMOSOME-17; TUMOR SUPPRESSOR GENE; NEUROFIBROMATOSIS TYPE-1 ID NEUROFIBROMATOSIS TYPE-1 GENE; HUMAN GLIOMAS; TUMORIGENESIS; MUTATIONS; CANCER; NM23; GAP AB Pilocytic astrocytomas are the most common astrocytic tumors of childhood and differ clinically and histopathologically from those astrocytomas that affect adults. Studies of adult astrocytic tumors have revealed allelic losses on chromosomes 10, 17p, 19q and alterations in the epidermal growth factor receptor (EGFR) gene. We have previously examined pilocytic astrocytomas for allelic losses on chromosomes 10 and 19q and for amplification of the EGFR gene, but did not detect genomic alterations at these loci. In the present study we assayed 20 pilocytic astrocytomas for loss of allelic heterozygosity of chromosome 17p, including one locus in the p53 tumor suppressor gene. In addition. because pilocytic astrocytomas frequently affect patients with neurofibromatosis type 1 (NF1) and the NF1 gene has been mapped to 17q11.2, we also examined multiple loci on the long arm of chromosome 17. Allelic loss was observed on chromosome 17 in four cases (three sporadic, one NF1); all lost portions of the long arm in chromosome 17, and one tumor lost the short arm as well. One tumor showed an interstitial deletion on the long arm that included the region of the NF1 gene. These data suggest the presence of a tumor suppressor gene on 17q that is associated with pilocytic astrocytomas. A potentiel candidate for this gene is the NF1 tumor suppressor gene. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. UNIV BONN,MED CTR,DEPT NEUROPATHOL,W-5300 BONN 1,GERMANY. MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV ZURICH,DEPT NEUROSURG,CH-8091 ZURICH,SWITZERLAND. UNIV ZURICH,DEPT PATHOL,NEUROSURG LAB,CH-8091 ZURICH,SWITZERLAND. SOUTHAMPTON GEN HOSP,DEPT NEUROSURG,SOUTHAMPTON SO9 4XY,HANTS,ENGLAND. RP VONDEIMLING, A (reprint author), MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02129, USA. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X FU NCI NIH HHS [NRSA CA 09144] NR 34 TC 67 Z9 68 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JUN PY 1993 VL 86 IS 1 BP 81 EP 85 PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA LJ873 UT WOS:A1993LJ87300013 PM 8103960 ER PT J AU HUNG, L RICHARDSON, A AF HUNG, L RICHARDSON, A TI THE EFFECT OF AGING ON THE GENETIC EXPRESSION OF RENIN BY MOUSE KIDNEY SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE AGING; MOUSE KIDNEY; RENIN MESSENGER RNA AB The effect of aging on the genetic expression of renin was studied in kidney tissue by measuring renin mRNA levels. RNA was isolated from the kidneys of 5- to 37-month-old male C57BL/6J mice. The relative levels of the renin mRNA were measured by dot blot hybridization using a cDNA probe to renin. The size of renin mRNA as determined by northern blot analysis was found to be 1.6 Kb. The size of renin mRNA did not change with increasing age. However, the levels of renin mRNA in kidney RNA decreased 70% after 12 months of age. C1 AUDIE L MURPHY MEM VET ADM MED CTR,GRECC 182,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284. FU NIA NIH HHS [AG 01548] NR 0 TC 1 Z9 1 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 JUN PY 1993 VL 5 IS 3 BP 193 EP 198 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA LH825 UT WOS:A1993LH82500005 PM 8399464 ER PT J AU MARGALITH, M MEDINA, DJ HSIUNG, GD SMITH, BR DAQUILA, RT KAPLAN, JC BECHTEL, L WANG, MZ SKOLNIK, PR HIRSCH, MS AF MARGALITH, M MEDINA, DJ HSIUNG, GD SMITH, BR DAQUILA, RT KAPLAN, JC BECHTEL, L WANG, MZ SKOLNIK, PR HIRSCH, MS TI INTERACTIONS BETWEEN HIV-1 AND CYTOMEGALOVIRUS IN HUMAN OSTEOSARCOMA CELLS CARRYING BOTH VIRUSES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HOMOSEXUAL MEN; HTLV-III; INFECTION; AIDS; TYPE-1; GENE; REPLICATION; EXPRESSION; INCREASES AB Cytomegalovirus (CMV) and the human immunodeficiency virus type 1 (HIV-1) may interact in the pathogenesis of AIDS. We compared CMV replication in human osteosarcoma (HOS) cells to that in HOS cells genetically engineered to contain an envelope-deficient HIV-1 proviral construct (designated HOS-HXG). Following acute CMV infection of each cell line, HOS-HXG cells contained higher numbers of intranuclear CMV nucleocapsids than did HOS cells. Infectious CMV could be persistently detected in culture supernatant fluids of the CMV-infected HOS-HXG cells, whereas CMV was lost over several weeks from HOS cells infected with CMV in parallel. HIV-1 CMV pseudotypes were not detected in supernatant fluids from CMV-infected HOS-HXG cells. On day 119 after CMV infection, these cultures were superinfected with HIV-1. These dually infected HOS-HXG cells produced infectious HIV-1 and exhibited markedly enhanced CMV replication compared to parental CMV-infected HOS-HXG cells. Two different HIV-1 tat gene function antagonists, Ro24-7429 and chemically modified antibodies to the Tat protein, did not inhibit the replication of CMV in either acute or persistent infections of HOS-HXG cells at concentrations that inhibited HIV-1 replication. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,INFECT DIS UNIT,BOSTON,MA 02114. TUFTS UNIV,SCH MED,BOSTON,MA 02111. VET ADM MED CTR,W HAVEN,CT 06516. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. RI Medina, Daniel/B-8196-2013 OI Medina, Daniel/0000-0003-4830-6941 FU NCI NIH HHS [CA35020, CA54741]; NIAID NIH HHS [AI28241] NR 41 TC 5 Z9 5 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 JUN PY 1993 VL 9 IS 6 BP 519 EP 527 DI 10.1089/aid.1993.9.519 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LJ320 UT WOS:A1993LJ32000006 PM 8394095 ER PT J AU SCHENKER, S HU, ZQ JOHNSON, RF YANG, YQ FROSTO, T ELLIOTT, BD HENDERSON, GI MOCK, DM AF SCHENKER, S HU, ZQ JOHNSON, RF YANG, YQ FROSTO, T ELLIOTT, BD HENDERSON, GI MOCK, DM TI HUMAN PLACENTAL BIOTIN TRANSPORT - NORMAL CHARACTERISTICS AND EFFECT OF ETHANOL SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE BIOTIN; PLACENTA; ALCOHOL ID THIAMINE TRANSPORT; MEMBRANE-VESICLES; RAT; DEFICIENCY; INVITRO; DIFFERENTIATION; ANTIPYRINE; EXPOSURE; GLUCOSE; MICE AB Biotin, a vitamin essential for many metabolic reactions, is supplied to the fetus exclusively from the mother. Deficiency of biotin in pregnancy leads to impaired fetal growth and development. Alcohol taken in pregnancy likewise may cause fetal growth abnormalities. Normal biotin transport via the placenta and the effects of ethanol on this transport apparently have not been studied. Our aims were to characterize these phenomena for the normal human-term placenta. Using maternal-facing placental membrane vesicles, biotin uptake was sodium- and temperature-dependent, saturable, and inhibited by structural analogs of biotin (desthiobiotin, biocytin, and biotin methyl ester), as well as by 4 and 10 hr exposure to 3 g/liter ethanol. Using the isolated perfused single cotyiedon method to measure placental transport of biotin at a perfusion concentration of 1 nm, the overall rate of biotin transport was found to be only 30% that of antipyrine, a freely diffusible marker. Clearance of biotin was approximately 2 ml/hr.g placenta, which was equal to the clearance of passively transferred L-glucose; biotin clearance was similar in both maternal to fetal and fetal to maternal directions. Overall transfer of biotin from maternal to fetal compartments was not inhibited by 500-fold greater concentrations of the three analogs, did not proceed against a biotin concentration gradient, and was not inhibited by 90-240 min exposure to an initial concentration of 4 g/liter ethanol. Concentration of biotin in the fetal compartment at the end of the study was not higher than on the maternal side (after maternal to fetal infusion), but placental concentration was 2- to 3-fold greater. No significant metabolism of biotin was detected. Exposing human placental cultured trophoblast on day 3 to 24 hr of ethanol (2 g/liter) had no effect on the net uptake of biotin by these cells. These studies provide evidence that maternal-facing placental membranes take up biotin by a mediated, carrier-dependent process that is inhibited by ethanol; however, based on the perfusion studies, we conclude that the overall (maternal-fetal) rate-limiting transfer of biotin by the human placenta is most consistent with a passive process, which is not inhibited by short-term exposure to ethanol. C1 UNIV TEXAS,HLTH SCI CTR,DEPT OBSTET & GYNECOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PHARMACOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV IOWA,COLL MED,DEPT PEDIAT,DIV GASTROENTEROL & HEPATOL,IOWA CITY,IA 52242. RP SCHENKER, S (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GASTROENTEROL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIAAA NIH HHS [KO2 AA00121, R01 AA07541]; NIDDK NIH HHS [DK36823] NR 44 TC 23 Z9 24 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1993 VL 17 IS 3 BP 566 EP 575 DI 10.1111/j.1530-0277.1993.tb00801.x PG 10 WC Substance Abuse SC Substance Abuse GA LH409 UT WOS:A1993LH40900008 PM 8333586 ER PT J AU NANJI, AA ZHAO, SP LAMB, RG SADRZADEH, SMH DANNENBERG, AJ WAXMAN, DJ AF NANJI, AA ZHAO, SP LAMB, RG SADRZADEH, SMH DANNENBERG, AJ WAXMAN, DJ TI CHANGES IN MICROSOMAL PHOSPHOLIPASES AND ARACHIDONIC-ACID IN EXPERIMENTAL ALCOHOLIC LIVER-INJURY - RELATIONSHIP TO CYTOCHROME-P-450 2E1 INDUCTION AND CONJUGATED DIENE FORMATION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ETHANOL; PHOSPHOLIPASE; CYTOCHROME-P-450 2E1; LIPID PEROXIDATION; ARACHIDONIC ACID ID HEPATIC LIPID-PEROXIDATION; UNSATURATED FATTY-ACIDS; RAT-LIVER; INDUCIBLE CYTOCHROME-P-450; ETHANOL OXIDATION; RADICAL FORMATION; OXIDASE ACTIVITY; DIETARY-FAT; ACTIVATION; CYTOCHROMES-P-450 AB We evaluated the role of changes in microsomal phospholipases (A and C) and arachidonic acid in the intragastric rat feeding model. The experimental animals (male Wistar rats), divided into 4-5 rats/group, were fed the following diets: corn oil and ethanol and corn oil plus dextrose. One set of groups was killed after 2 weeks of feeding, and the second set was killed after 1 month. For each animal, microsomal analysis of cytochrome P-450 2E1 (CYP 2E1) and fatty acids was done. Fourteen animals had analyses of phospholipase C (PLC) and phospholipase A (PLA), and 10 animals had measurements of conjugated dienes. A significant correlation was obtained between the level of CYP 2E1 and the decrease in arachidonic acid (AA) from baseline levels (r = 0.69, p < 0.01). The decrease in AA also correlated with the increase in conjugated dienes (r = 0.70, p < 0.05). PLA and PLC activities were both significantly increased in the corn oil and ethanol groups. The activity of PLC correlated with the decline in AA (r = 0.69, p < 0.01). The correlations noted between the decrease in microsomal AA and CYP 2E1 induction and conjugated diene formation suggest that these processes may be interlinked especially in regard to generation of lipid peroxides that may play a role in alcoholic liver injury. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL,RICHMOND,VA 23298. CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV DIGEST DIS & NUTR,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP NANJI, AA (reprint author), NEW ENGLAND DEACONESS HOSP,DEPT PATHOL,185 PILGRIM RD M323,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK33765, IK08 DK1992] NR 49 TC 55 Z9 55 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1993 VL 17 IS 3 BP 598 EP 603 DI 10.1111/j.1530-0277.1993.tb00806.x PG 6 WC Substance Abuse SC Substance Abuse GA LH409 UT WOS:A1993LH40900013 PM 8333590 ER PT J AU DELUCA, SA AF DELUCA, SA TI HYPERTROPHIC PYLORIC-STENOSIS SO AMERICAN FAMILY PHYSICIAN LA English DT Article AB Hypertrophic pyloric stenosis is a gastrointestinal tract disorder common in infancy. The disorder causes projectile vomiting, weight loss, and fluid and electrolyte abnormalities. The problem can usually be diagnosed by clinical symptoms and manual detection of an enlarged pylorus. When the diagnosis cannot be confirmed by these methods, however, imaging studies are relevant. Until recently, plain radiographs and upper gastrointestinal contrast studies have been used to make the diagnosis, but ultrasonography is becoming the method of choice because it is highly accurate and lacks the ionizing radiation inherent in a radiologic procedure. Surgery provides a safe an effective treatment. RP DELUCA, SA (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD JUN PY 1993 VL 47 IS 8 BP 1771 EP 1773 PG 3 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA LF546 UT WOS:A1993LF54600014 PM 8498286 ER PT J AU BROOKS, R RUSKIN, JN POWELL, AC NEWELL, J GARAN, H MCGOVERN, BA AF BROOKS, R RUSKIN, JN POWELL, AC NEWELL, J GARAN, H MCGOVERN, BA TI PROSPECTIVE EVALUATION OF DAY-TO-DAY REPRODUCIBILITY OF UPRIGHT TILT-TABLE TESTING IN UNEXPLAINED SYNCOPE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HEAD-UP TILT; INDUCED HYPOTENSION-BRADYCARDIA; NEURALLY MEDIATED SYNCOPE; UNKNOWN ORIGIN; ISOPROTERENOL; DISOPYRAMIDE AB To evaluate the day-to-day reproducibility of upright tilt-table testing, 109 patients with unexplained syncope prospectively underwent testing on 2 consecutive days using a uniform protocol. Results of testing on 2 separate days were concordant in 69 of 109 patients (63%), and discordant in 40 of 109 patients (37%). Thirty-six of 109 patients (33%) had vasodepressor syncope on 1 or both days of testing. Nineteen of 30 patients (63%) with vasodepressor responses on the first day did not response this response during the second day of testing. An additional 6 patients with an initial negative tilt test had a vasodepressor response on the second day. Only 11 of 36 patients (31%) had reproducible vasodepressor responses on both days of testing. Patients with reproducible vasodepressor responses had a significantly higher mean number of preceding clinical syncopal events than patients with 2 normal tests (p < 0.02) or nonreproducible results (p < 0.04). In addition, these patients had a significantly longer duration of clinical symptoms relative to patients with 2 tests that yielded negative results (p < 0.008) and nonreproducible results (p < 0.01). The elapsed time between the most recent clinical event and the performance of tilt-table testing was not significantly different among the 3 groups, and did not appear to influence the outcome of testing. These data show that vasodepressor responses elicited by upright tilt-table testing show day-to-day variability in many patients, a finding that may limit the interpretation of initial and follow-up test results. RP BROOKS, R (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC ARRHYTHMIA SERV,CARDIAC UNIT,BOSTON,MA 02114, USA. NR 17 TC 67 Z9 70 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 1993 VL 71 IS 15 BP 1289 EP 1292 DI 10.1016/0002-9149(93)90542-K PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LD402 UT WOS:A1993LD40200007 PM 8498368 ER PT J AU BROWN, FR VOIGT, R SINGH, AK SINGH, I AF BROWN, FR VOIGT, R SINGH, AK SINGH, I TI PEROXISOMAL DISORDERS - NEURODEVELOPMENTAL AND BIOCHEMICAL ASPECTS SO AMERICAN JOURNAL OF DISEASES OF CHILDREN LA English DT Article ID RAT-LIVER PEROXISOMES; RHIZOMELIC CHONDRODYSPLASIA PUNCTATA; INFANTILE REFSUMS DISEASE; RENAL ZELLWEGER SYNDROME; ACID STORAGE DISEASE; CHAIN FATTY-ACIDS; X-LINKED ADRENOLEUKODYSTROPHY; CULTURED SKIN FIBROBLASTS; NEONATAL ADRENOLEUKODYSTROPHY; PHYTANIC ACID AB The peroxisomal disorders represent a group of inherited metabolic disorders that derive from defects of peroxisomal biogenesis and/or from dysfunction of single or multiple peroxisomal enzymes. Because peroxisomes are involved in the metabolism of lipids critical to the functioning of the nervous system, many of the peroxisomal disorders manifest with significant degrees of progressive psychomotor dysfunction. These disorders should be considered in the differential diagnosis of the infant with hypotonia and psychomotor delay (especially if accompanied by facial dysmorphisms, hepatomegaly, cataracts and/or retinitis, calcific stippling, short limbs, or combinations of these features), in the school-aged child with progressive neurologic dysfunction, and in adults with slowly progressive motor dysfunction. Current knowledge of peroxisomal biochemical and enzymatic processes permits precise identification of particular disorders within the peroxisomal disorder grouping. An effort should be made to identify the specific peroxisomal disorder to provide a precise explanation for neurodevelopmental deficits, to potentially prevent recurrence through genetic counseling, and to provide appropriate therapies when available. C1 MED UNIV S CAROLINA,DEPT PATHOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT PEDIAT,CHARLESTON,SC 29425. RALPH JOHNSON VET ADM MED CTR,CHARLESTON,SC. RP BROWN, FR (reprint author), TEXAS CHILDRENS HOSP,CTR CLIN CARE,MEYER CTR DEV PEDIAT,1102 BATES ST,SUITE 530,HOUSTON,TX 77030, USA. FU NINDS NIH HHS [NS-22576] NR 83 TC 57 Z9 57 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0002-922X J9 AM J DIS CHILD JI Am. J. Dis. Child. PD JUN PY 1993 VL 147 IS 6 BP 617 EP 626 PG 10 WC Pediatrics SC Pediatrics GA LF301 UT WOS:A1993LF30100014 PM 7685145 ER PT J AU ROBERTSON, MJ TANTRAVAHI, R GRIFFIN, JD CANELLOS, GP CANNISTRA, SA AF ROBERTSON, MJ TANTRAVAHI, R GRIFFIN, JD CANELLOS, GP CANNISTRA, SA TI HEMATOLOGIC REMISSION AND CYTOGENETIC IMPROVEMENT AFTER TREATMENT OF STABLE-PHASE CHRONIC MYELOGENOUS LEUKEMIA WITH CONTINUOUS-INFUSION OF LOW-DOSE CYTARABINE SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE CML; PHILADELPHIA CHROMOSOME; CYTOGENETIC REMISSION ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; INTENSIVE COMBINATION CHEMOTHERAPY; CHRONIC GRANULOCYTIC-LEUKEMIA; PHILADELPHIA-CHROMOSOME; CYTOSINE-ARABINOSIDE; PROGENITOR CELLS; INTERFERON; ABL; INHIBITION AB Prolonged exposure to low concentrations of cytarabine preferentially inhibits in vitro growth of neoplastic myeloid progenitors from patients with chronic myelogenous leukemia (CML) compared to that of normal myeloid progenitors. Continuous infusions of cytarabine in doses of 15-30 mg/m2/day were therefore administered for extended periods to patients with CML in stable phase to determine if this treatment could achieve selective cytoreduction of Philadelphia chromosome (Ph)-positive cells. Five patients demonstrating > 90% Ph-positive metaphases before treatment received a total of 43 cycles of cytarabine infusional therapy. Cytarabine was administered on an outpatient basis using a portable, battery-operated syringe pump until the total leukocyte count reached 2500/mul or the platelet count reached 75,000/mul. A new cycle was begun when the total leukocyte count exceeded 4,000/mul and the platelet count exceeded 100,000/mul. The median duration of cytarabine administration per cycle was 29 days (range 15-72 days). Leukocytosis was readily controlled by low-dose cytarabine therapy in all patients. All five patients experienced complete hematologic responses during cytarabine therapy. The fraction of Ph-positive metaphases in the marrow of the five patients was reduced to 0, 10%, 43%, 72%, and 84%, respectively, during therapy. The median time to achieve optimal cytogenetic response was 4.8 months (range 2.8-8.6 months). One patient demonstrated a complete cytogenetic response after three cycles of cytarabine. Another patient demonstrated persistent cytogenetic improvement during 20 cycles of cytarabine, with a median 38% Ph-positive marrow metaphases (range 10-53%) over 32 months. Cytarabine therapy was generally well-tolerated, but was discontinued in one patient because of persistent asymptomatic elevations in hepatic enzymes, which resolved within 2 months after discontinuing therapy. There were no episodes of fever during neutropenia, and platelet transfusions were not required. However, symptomatic anemia requiring transfusion of red cells occurred during most cycles of treatment. In summary, treatment of CML with low-dose cytarabine can induce prolonged cytogenetic improvement in some patients with acceptable toxicity. Further evaluation is needed to ascertain the effects of this treatment on duration of stable phase and overall survival. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. NR 35 TC 26 Z9 27 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 1993 VL 43 IS 2 BP 95 EP 102 DI 10.1002/ajh.2830430205 PG 8 WC Hematology SC Hematology GA LA006 UT WOS:A1993LA00600004 PM 8342558 ER PT J AU DRYJA, TP RAPAPORT, J MCGEE, TL NORK, TM SCHWARTZ, TL AF DRYJA, TP RAPAPORT, J MCGEE, TL NORK, TM SCHWARTZ, TL TI MOLECULAR ETIOLOGY OF LOW-PENETRANCE RETINOBLASTOMA IN 2 PEDIGREES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HEREDITARY RETINOBLASTOMA; SUSCEPTIBILITY GENE; WILSON DISEASE; MUTATIONS; CHROMOSOME-13; POLYMORPHISMS; ASSIGNMENT; SEQUENCE AB In one family with low-penetrance retinoblastoma, a germ-line deletion is shared by affected and unaffected, obligate carriers. The deletion encompasses exon 4 of the retinoblastoma gene and corresponds to a mutant protein without residues 127-166. In a second family, RFLP analysis shows that two distant relatives have independently derived mutations. These families, together with others reported elsewhere, indicate that attributes of alleles at the retinoblastoma locus specify penetrance. C1 W VIRGINIA UNIV,HLTH SCI CTR,UNIV EYE CTR,DEPT OPHTHALMOL,MORGANTOWN,WV 26506. RP DRYJA, TP (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY08724, EY05321] NR 36 TC 81 Z9 81 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 JUN PY 1993 VL 52 IS 6 BP 1122 EP 1128 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA LG133 UT WOS:A1993LG13300013 PM 8099255 ER PT J AU TENNERRACZ, K RACZ, P THOME, C MEYER, CG ANDERSON, PJ SCHLOSSMAN, SF LETVIN, NL AF TENNERRACZ, K RACZ, P THOME, C MEYER, CG ANDERSON, PJ SCHLOSSMAN, SF LETVIN, NL TI CYTOTOXIC EFFECTOR CELL GRANULES RECOGNIZED BY THE MONOCLONAL-ANTIBODY TIA-1 ARE PRESENT IN CD8+ LYMPHOCYTES IN LYMPH-NODES OF HUMAN IMMUNODEFICIENCY VIRUS-1-INFECTED PATIENTS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PERSISTENT GENERALIZED LYMPHADENOPATHY; VIRUS-REPLICATION; AIDS; HIV; PROTEIN; SUPPRESSION; EXPRESSION; COMPLEXES; RELEVANCE; ANTIGENS AB A novel monoclonal antibody (mAB) TIA-1, which recognizes a 15-kd granule-associated protein of cytotoxic T lymphocytes and natural killer cells, has been applied to sections of lymph nodes with human immunodeficiency virus (HIV)-induced lymphadenopathy (follicular hyperplasia and lymphocyte depletion). The protein recognized by this mAB induces apoptosis in permeabilized lymphocytes in vitro. While this mAB reacted with approximately 46% of paracortical CD8+ cells in control nodes. It reacted with 75% of such cells in HIV-induced follicular hyperplasia. Germinal centers of the control nodes contained few TIA-1+ cells; in follicular hyperplasia caused by HIV-1, almost all germinal center CD8+ cells were TIA-1+. Both in the control nodes and in HIV-induced follicular hyperplasia the majority of TIA-1+ cells coexpressed CD45R0. A marked loss of CD8+TIA-1+ cells was seen in lymphocyte-depleted nodes of patients with AIDS. The loss of these cytotoxic T lymphocytes may have a significant impact on the progression of the disease. C1 HARVARD UNIV,SCH MED,NEW ENGLAND REG PRIMATE RES CTR,1 PINE HILL DR,SOUTHBOROUGH,MA 01772. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. BERNHARD NOCHT INST TROP MED,DEPT PATHOL,W-2000 HAMBURG 4,GERMANY. BERNHARD NOCHT INST TROP MED,MOLEC BIOL SECT,W-2000 HAMBURG 4,GERMANY. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. BERNHARD NOCHT INST TROP MED,KORBER LAB AIDS RES,W-2000 HAMBURG 4,GERMANY. ALLGEMEINES KRANKENHAUS ST GEORG,DEPT HEMATOL,HAMBURG,GERMANY. NR 43 TC 56 Z9 56 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 1993 VL 142 IS 6 BP 1750 EP 1758 PG 9 WC Pathology SC Pathology GA LF978 UT WOS:A1993LF97800010 PM 8506945 ER PT J AU LAMURAGLIA, GM ORTU, P FLOTTE, TJ ROBERTS, WG SCHOMACKER, KT CHANDRASEKAR, NR HASAN, T AF LAMURAGLIA, GM ORTU, P FLOTTE, TJ ROBERTS, WG SCHOMACKER, KT CHANDRASEKAR, NR HASAN, T TI CHLOROALUMINUM SULFONATED PHTHALOCYANINE PARTITIONING IN NORMAL AND INTIMAL HYPERPLASTIC ARTERY IN THE RAT - IMPLICATIONS FOR PHOTODYNAMIC THERAPY SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; PHOTOSENSITIZATION; INJURY AB Photodynamic therapy, the light activation of photosensitizers into cytotoxic mediators, has been a successful treatment for experimental intimal hyperplasia (IH). To understand the basis of the photosensitizer chloroaluminum sulfonated phthalocyanine (CASPc)-mediated photoinhibition of intimal hyperplasia in the rat common carotid artery model, we studied photo-sensitizer partitioning in hyperplastic as compared to normal arterial tissue. Serum clearance of CASPc is exponential with, a half-life of 300 minutes. Laser-induced fluorescence and spectrofluorimetric analyses of artery tissue demonstrated an approximately 60% lower uptake and retention of CASPc by normal arterial tissue as compared to arteries with IH, the differences become more pronounced at 24 h. Fluorescent microscopy of arterial tissue demonstrated increased uptake of the CASPc by the artery with IH. However, by 24 h it is primary the IH tissue that has retained the CASPc, with clearance of the dye from the media of normal or hyperplastic arteries. These data demonstrate that IH, like neoplastic tissue, has an increased accumulation of CASPc compared to normal artery. The preferential partitioning into hyperplastic tissue has implications for therapeutic targeting of this cellular population with photodynamic therapy. C1 MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP LAMURAGLIA, GM (reprint author), MASSACHUSETTS GEN HOSP,GEN SURG SERV,DIV VASC SURG,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [K-08HL02563-01] NR 16 TC 18 Z9 20 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 1993 VL 142 IS 6 BP 1898 EP 1905 PG 8 WC Pathology SC Pathology GA LF978 UT WOS:A1993LF97800025 PM 8506957 ER PT J AU HARMATZ, PR CARRINGTON, PW GIOVINOBARRY, V HATZ, RA BLOCH, KJ AF HARMATZ, PR CARRINGTON, PW GIOVINOBARRY, V HATZ, RA BLOCH, KJ TI INTESTINAL ADAPTATION DURING LACTATION IN THE MOUSE .2. ALTERED INTESTINAL PROCESSING OF A DIETARY-PROTEIN SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE MICE; DIETARY ANTIGEN UPTAKE ID PEYERS PATCHES; MICE; OVALBUMIN; TRANSPORT; RESPONSES; ANTIGEN; RAT AB We previously demonstrated in lactating mice a six- to eightfold increase in the intestinal uptake of the dietary protein, ovalbumin (OVA), administered by gavage. In this study, we tested the possibility that alterations in intestinal morphology, transit time, reduced luminal proteolysis, and enhanced association with the intestinal surface might account for the increased uptake of the protein observed in lactating mice. We found that these animals had a significant increase in length, wet weight, and surface area of the small intestine. No change in the number of Peyer's patches was noted. Intestinal transit was assessed by gavage administration of I-125-OVA and 10 mg OVA and localization of the peak of radioactivity 15, 30, and 60 min after feeding. Although motility (distance traveled per unit time) was not different in lactating and control mice at 15 and 30 min, the fraction of the small intestine traversed by the peak of radioactivity was less in lactating mice. Digestion of I-125-OVA administered by gavage with 10 mg unlabeled OVA was examined by trichloroacetic acid precipitation and gel permeation of the resulting fragments. Lactating and control mice did not show differences in digestion of I-125-OVA by either measurement. The association of I-125-OVA with small intestinal segments, however, was enhanced in lactating mice, especially in the second and third segments of the small intestine. Thus several factors including an increase in length and surface area of the small intestine, prolonged contact of protein with the small intestinal absorptive surface, and enhanced association of the protein with the intestinal surface contribute to increased uptake. Neither differences in number of Peyer's patches nor in the rate of digestion of OVA were found, making it unlikely that these variables contribute to the enhanced uptake of protein observed in lactating mice. C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,CLIN IMMUNOL UNIT,BOSTON,MA 02114. UNIV MUNICH,DEPT SURG,W-8000 MUNICH 2,GERMANY. MASSACHUSETTS GEN HOSP,ALLERGY UNIT,BOSTON,MA 02114. VET ADM W SIDE MED CTR,CHICAGO,IL 60680. HARVARD UNIV,SCH MED,DEPT PEDIAT & MED,BOSTON,MA 02115. NR 23 TC 4 Z9 4 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUN PY 1993 VL 264 IS 6 BP G1126 EP G1132 PN 1 PG 7 WC Physiology SC Physiology GA LL132 UT WOS:A1993LL13200072 ER PT J AU FARAONE, SV BIEDERMAN, J LEHMAN, BK KEENAN, K NORMAN, D SEIDMAN, LJ KOLODNY, R KRAUS, I PERRIN, J CHEN, WJ AF FARAONE, SV BIEDERMAN, J LEHMAN, BK KEENAN, K NORMAN, D SEIDMAN, LJ KOLODNY, R KRAUS, I PERRIN, J CHEN, WJ TI EVIDENCE FOR THE INDEPENDENT FAMILIAL TRANSMISSION OF ATTENTION-DEFICIT HYPERACTIVITY DISORDER AND LEARNING-DISABILITIES - RESULTS FROM A FAMILY GENETIC-STUDY SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID LA-TOURETTES SYNDROME; MULTIPLE THRESHOLDS; CHILDREN; TRAITS AB Objective: The purpose of the study was to clarify the relationship between attention deficit hyperactivity disorder and learning disabilities. Method: The authors assessed learning disabilities in a sample of 140 children with attention deficit hyperactivity disorder and in 120 normal comparison children. They also assessed a sample of the probands' 822 first-degree relatives. Results: The risk for learning disabilities was highest among relatives of probands with both attention deficit hyperactivity disorder and learning disabilities. The two disorders did not cosegregate in families. There was nonrandom mating between spouses with attention deficit hyperactivity disorder and learning disabilities. Conclusions: The two disorders are transmitted independently in families, and their co-occurrence may be due to nonrandom mating. Attention deficit hyperactivity disorder is likely to be etiologically independent from learning disabilities. C1 MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,ACC-725,FRUIT ST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PEDIAT SERV,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PSYCHIAT EPIDEMIOL & GENET SECT,BOSTON,MA 02115. VET ADM MED CTR,PSYCHIAT SERV,BROCKTON,MA 02401. HARVARD COMMUNITY HLTH PLAN,DEPT PEDIAT,BOSTON,MA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-41314] NR 21 TC 132 Z9 134 U1 2 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 1993 VL 150 IS 6 BP 891 EP 895 PG 5 WC Psychiatry SC Psychiatry GA LD843 UT WOS:A1993LD84300007 PM 8494064 ER PT J AU BROWN, JH CHEW, FS AF BROWN, JH CHEW, FS TI PLEOMORPHIC XANTHOASTROCYTOMA SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 4 TC 5 Z9 5 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 1993 VL 160 IS 6 BP 1272 EP 1272 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LW013 UT WOS:A1993LW01300026 PM 8498232 ER PT J AU MATTIA, AR FERRY, JA HARRIS, NL AF MATTIA, AR FERRY, JA HARRIS, NL TI BREAST LYMPHOMA - A B-CELL SPECTRUM INCLUDING THE LOW-GRADE B-CELL LYMPHOMA OF MUCOSA-ASSOCIATED LYMPHOID-TISSUE SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE BREAST LYMPHOMA; MALT-TYPE LYMPHOMA; EXTRANODAL; IMMUNOPHENOTYPING ID PRIMARY MALIGNANT-LYMPHOMA; MYOEPITHELIAL SIALADENITIS; PSEUDOLYMPHOMA; MASTOPATHY; MIGRATION; DISEASE; SYSTEM; ORGAN; MALT; LUNG AB We studied the morphologic, immunologic, and clinical features of 31 cases of malignant lymphoma involving the breast. Primary breast lymphoma occurred in nine women with a median age of 69 years (range, 51-87 years); median follow-up was 31 months (range, 9-67 months). Eight cases were low grade, one was high grade, and all expressed B-lineage antigens. Four cases had features of lymphoma of mucosa-associated lymphoid tissue (MALT); three were free of disease after excision alone at 10, 12, and 48 months, whereas the fourth relapsed with transition to immunoblastic lymphoma and died at 25 months. Four patients had follicular lymphomas, three of which relapsed, causing death from active disease at a median of 55 months (range, 25-67 months). One case of small noncleaved cell lymphoma relapsed, causing death at 31 months. Lymphoma secondarily involved the breast in 22 patients (21 women, one man) with a median age of 60 years (range, 39-83 years) at breast relapse; these patients were followed for a median of 88 months (range, 2-271 months) from primary diagnosis and 4 months (range, 0-116 months) from breast relapse. Nineteen patients had prior documented lymphomas (10 nodal or splenic, nine extranodal), and breast involvement most commonly occurred as part of widespread, predominantly nodal disease. Three patients had breast involvement by lymphomas that were generalized at diagnosis or staging. Thirteen cases were low grade (nine follicular), seven intermediate grade, and one high grade; 19 of 20 cases expressed B-lineage antigens, and one expressed T-lineage antigens. Four cases had features of MALT-type lymphoma; in these patients, isolated breast relapses were interspersed with other extranodal relapses, with interim resolution of disease after local or systemic therapy; two were free of disease and two were alive with localized disease on treatment at median follow-up of 60 months (range, 9-91 months). In contrast, 15 of 18 non-MALT lymphomas had widespread disease at breast relapse (median, 29 months; range, 0-259 months); 16 of 18 received systemic therapy, 10 died with active disease, and five of eight had disseminated active disease at last follow-up. Primary breast lymphomas were commonly low grade. The follicular lymphomas had clinical behavior similar to nodal follicular lymphoma. Primary MALT-type lymphomas were a distinct subset with a potential for disease-free survival after local therapy. Secondary breast lymphomas were heterogeneous and more commonly higher grade, although follicular lymphoma was the most common subtype. Non-MALT secondary breast lymphoma occurred in a setting of widespread disease in most cases. However, MALT-type lymphomas occurred as isolated relapses from other extranodal sites, with a potential for disease free survival after local therapy. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP MATTIA, AR (reprint author), MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,DEPT PATHOL,WARREN 2,BOSTON,MA 02114, USA. NR 70 TC 124 Z9 129 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 JUN PY 1993 VL 17 IS 6 BP 574 EP 587 DI 10.1097/00000478-199306000-00005 PG 14 WC Pathology; Surgery SC Pathology; Surgery GA LD355 UT WOS:A1993LD35500005 PM 8333556 ER PT J AU OCONNELL, JX KATTAPURAM, SV MANKIN, HJ BHAN, AK ROSENBERG, AE AF OCONNELL, JX KATTAPURAM, SV MANKIN, HJ BHAN, AK ROSENBERG, AE TI EPITHELIOID HEMANGIOMA OF BONE - A TUMOR OFTEN MISTAKEN FOR LOW-GRADE ANGIOSARCOMA OR MALIGNANT HEMANGIOENDOTHELIOMA SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE BONE; HEMANGIOMA; EPITHELIOID HEMANGIOMA ID ANGIOLYMPHOID HYPERPLASIA; HISTIOCYTOID HEMANGIOMA; EOSINOPHILIA; LESION AB Epithelioid hemangiomas are benign vascular tumors that usually occur in the skin and subcutis. They have been infrequently recognized in bone. Because of their unusual cytologic appearance and growth patterns, they are commonly confused with malignant tumors. We report a series of 12 epithelioid hemangiomas of bone occurring in adult patients, including five males and seven females whose ages at presentation ranged from 24 to 74 years, with a mean of 46 years. Five tumors were associated with involvement of the adjacent soft tissue. A single patient had multifocal bone disease. The most common presenting symptom was localized pain. Treatment of the patients varied widely; however, none of the tumors behaved aggressively. In 11 cases, adequate tissue was available for immunohistochemical analysis, which revealed positive staining for the epithelial markers cytokeratin and epithelial membrane antigen in nine cases. All 11 tumors stained for factor VIII-related antigen and Ulex europeus agglutinin. We believe that many of the vascular tumors of bone that have been reported as low-grade malignant hemangioendotheliomas probably represent examples of epithelioid hemangiomas. We recommend that the criteria for diagnosing vascular tumors of bone conform to those used for morphologically similar tumors that arise in the soft tissues. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114. NR 28 TC 74 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 JUN PY 1993 VL 17 IS 6 BP 610 EP 617 DI 10.1097/00000478-199306000-00009 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA LD355 UT WOS:A1993LD35500009 PM 8333560 ER PT J AU NIVEN, RW KACMAREK, RM BRAIN, JD PETERFREUND, RA AF NIVEN, RW KACMAREK, RM BRAIN, JD PETERFREUND, RA TI SMALL-BORE NOZZLE EXTENSIONS TO IMPROVE THE DELIVERY EFFICIENCY OF DRUGS FROM METERED-DOSE INHALERS - LABORATORY EVALUATION SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Note ID MECHANICALLY VENTILATED PATIENTS; AEROSOL DELIVERY; ENDOTRACHEAL-TUBES AB Metered dose inhalers (MDIs) are frequently used to supply aerosolized drugs, particularly bronchodilators, to the tracheobronchial tree of patients with endotracheal tubes in the intensive care unit or in the operating room. The efficiency of delivery to the lungs of agents such as the beta2-adrenergic agonists is known to be low. In an in vitro model, we evaluated a means of improving the delivery of drug released from an MDI beyond the distal tip of the endotracheal tube. Extensions of the MDI nozzle were fashioned from modified intravenous catheters or sections of small bore polyethylene tubing. A model trachea/carina was constructed and suspended above a collecting device. An albuterol MDI was actuated through the nozzle extension and into the model airway. We measured the quantity of albuterol deposited in the nozzle extension, in the trachea/carina and in the distal collecting device. Particle size distribution was determined with a cascade impactor. The results indicate an inverse relationship between the quantity of drug delivered distally and the inner diameter of the nozzle extension, with a marked increase in delivery for an inner diameter < 1 mm. Ninety percent of the actuated dose from the MDI exited a 0.76-mm inner diameter nozzle extension. From 20 to 30% of the nominal MDI dose was recovered from the distal collector, 70% of which deposited in the particle size range of 1 to 5 mum. Deposition in the trachea/carina was high, but this was reduced by introducing a flare in the tip of the nozzle extension, which did not affect the dose reaching the distal collector. The data suggest that nozzle extensions for MDIs can substantially improve distal delivery of aerosolized drugs. This strategy may have clinical utility in the therapy of bronchospasm or other conditions in patients with endotracheal tubes. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,CAMBRIDGE,MA 02138. RP NIVEN, RW (reprint author), HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL-019170] NR 15 TC 12 Z9 12 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD JUN PY 1993 VL 147 IS 6 BP 1590 EP 1594 PG 5 WC Respiratory System SC Respiratory System GA LJ667 UT WOS:A1993LJ66700045 PM 8503573 ER PT J AU SHORTEN, GD ALI, HA AF SHORTEN, GD ALI, HA TI ATRACURIUM AFTER AN ANTICHOLINESTERASE - DOES PRIOR REVERSAL WITH EDROPHONIUM OR NEOSTIGMINE INFLUENCE THE RESPONSE TO ATRACURIUM SO ANAESTHESIA LA English DT Note DE NEUROMUSCULAR RELAXANTS; ATRACURIUM; PANCURONIUM; TUBOCURARINE ID COMPETITIVE NEUROMUSCULAR BLOCK; RECEPTOR OCCLUSION C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 12 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0003-2409 J9 ANAESTHESIA JI Anaesthesia PD JUN PY 1993 VL 48 IS 6 BP 524 EP 526 DI 10.1111/j.1365-2044.1993.tb07077.x PG 3 WC Anesthesiology SC Anesthesiology GA LE080 UT WOS:A1993LE08000016 PM 8322995 ER PT J AU ELSON, CE KUFE, D JOHNSTON, WW AF ELSON, CE KUFE, D JOHNSTON, WW TI IMMUNOHISTOCHEMICAL DETECTION AND SIGNIFICANCE OF AXILLARY LYMPH-NODE MICROMETASTASES IN BREAST-CARCINOMA - A STUDY OF 97 CASES SO ANALYTICAL AND QUANTITATIVE CYTOLOGY AND HISTOLOGY LA English DT Article ID EPITHELIAL MEMBRANE ANTIGEN; MONOCLONAL-ANTIBODY DF3; MICRO-METASTESES; PROGNOSTIC-SIGNIFICANCE; CANCER; METASTASES; TUMOR; MACROMETASTASES; CELLS; REACTIVITY AB Paraffin blocks of all axillary lymph nodes from 97 patients with an initial histologic diagnosis of infiltrating ductal carcinoma and negative axillary nodes were recut and stained with two monoclonal antibodies, AE/AE3 (antikeratin) and DF3 (developed against breast cancer cells and reactive with a glycoprotein tumor-associated antigen). Immunohistochemical staining detected occult micrometastases in 20 patients (20.6%). No patient had more than three lymph nodes involved by tumor. Review of the original hematoxylin and eosin-stained sections revealed that foci of tumor were initially overlooked in nine of these cases (9.3%). In the remaining 11 cases (11.3%) the metastatic foci were encountered in the process of recutting the paraffin blocks for immunohistochemical studies. AE1/AE3 proved to be the more effective of the two antibodies in staining micrometastases. After a mean follow-up period of 5.7 years, no significant decrease in survival or increase in tumor recurrence was detected for patients with occult micrometastases as compared to those patients without micrometastases. C1 DUKE UNIV,MED CTR,DEPT PATHOL,BOX 3712,DURHAM,NC 27710. RES MED CTR,DEPT PATHOL,KANSAS CITY,MO. HARVARD UNIV,DANA FARBER CANC INST,CLIN PHARMACOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 34 TC 34 Z9 34 U1 0 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0884-6812 J9 ANAL QUANT CYTOL JI Anal. Quant. Cytol. Histol. PD JUN PY 1993 VL 15 IS 3 BP 171 EP 178 PG 8 WC Cell Biology SC Cell Biology GA LH824 UT WOS:A1993LH82400004 PM 7688511 ER PT J AU CHIONG, CM GLYNN, RJ XU, WZ NADOL, JB AF CHIONG, CM GLYNN, RJ XU, WZ NADOL, JB TI SURVIVAL OF SCARPA GANGLION IN THE PROFOUNDLY DEAF HUMAN SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE COCHLEAR IMPLANTATION; SCARPAS GANGLION; SENSORINEURAL HEARING LOSS; SPIRAL GANGLION AB The electrically evoked auditory brain stem response in some cochlear implant patients may be confounded by evoked potentials generated by vestibular neurons. The magnitude of this contribution to the response from the vestibular system is unknown, in part because the survival of cells within Scarpa's ganglion in profoundly deaf humans is unknown. Therefore, we undertook a quantitative study of Scarpa's ganglion in 48 deaf subjects who in life would have been candidates for cochlear implantation and in 5 subjects with normal hearing. The numbers of residual cells in both Scarpa's ganglion and the spiral ganglion in deaf subjects were significantly less than in individuals with normal hearing. Bivariate analysis demonstrated a highly significant positive correlation between cell counts of Scarpa's ganglion and the spiral ganglion. The durations of hearing loss and of profound deafness were negatively correlated with Scarpa's ganglion cell counts. However, in contrast to spiral ganglion cell survival, the cause of profound deafness did not predict the number of Scarpa's ganglion cells. Multiple linear regression analysis using a variety of clinical parameters demonstrated that the best predictor of the number of Scarpa's ganglion cells in profoundly deaf humans was the number of remaining spiral ganglion cells. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,CHANNING LAB,DEPT MED,BOSTON,MA 02115. FU NIDCD NIH HHS [P01 DC00361] NR 15 TC 13 Z9 13 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 JUN PY 1993 VL 102 IS 6 BP 425 EP 428 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA LG412 UT WOS:A1993LG41200003 PM 8512267 ER PT J AU FIALA, TGS LEE, WPA MAY, JW AF FIALA, TGS LEE, WPA MAY, JW TI AUGMENTATION MAMMAPALSTY - RESULTS OF A PATIENT SURVEY SO ANNALS OF PLASTIC SURGERY LA English DT Article ID HUMAN ADJUVANT DISEASE; BREAST AUGMENTATION; MAMMAPLASTY; CANCER; IMPLANTS AB A detailed survey on aesthetic augmentation mammoplasty was sent to patients who had undergone this procedure at the Massachusetts General Hospital between July 1973 and July 1991 to determine the incidence of postoperative complications after augmentation mammoplasty, and to qualify the factors related to patient satisfaction (n = 304). Surgical records of respondents were examined. After a mean follow-up of 8.2 years, there were no patients with known breast cancer or autoimmune disease after augmentation. Five implants (2.5%) were replaced due to leakage. Other complications were rare. Overall satisfaction was high and correlated inversely with capsular contracture ratings and elapsed time. Contracture ratings increased with time for silicone implants. Gel implants in the submuscular position were softer than subglandular ones after 5 years elapsed time. Most women are satisfied after augmentation mammoplasty, despite a significant incidence of capsular contracture. The incidence of other adverse effects after augmentation is low. Augmentation mammoplasty does not appear to be an inducer of autoimmune disease or of breast cancer. C1 MASSACHUSETTS GEN HOSP,DIV PLAST SURG,BOSTON,MA 02114. NR 15 TC 27 Z9 27 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD JUN PY 1993 VL 30 IS 6 BP 503 EP 509 DI 10.1097/00000637-199306000-00005 PG 7 WC Surgery SC Surgery GA LH469 UT WOS:A1993LH46900005 PM 8368775 ER PT J AU FIALA, TGS LEE, WPA HONG, HZ MAY, JW AF FIALA, TGS LEE, WPA HONG, HZ MAY, JW TI BACTERIAL CLEARANCE CAPABILITY OF LIVING SKIN EQUIVALENT, LIVING DERMAL EQUIVALENT, SALINE DRESSING, AND XENOGRAFT DRESSING IN THE RABBIT SO ANNALS OF PLASTIC SURGERY LA English DT Article ID INVITRO AB Two new skin substitutes, Living Skin Equivalent (LSE) and Living Dermal Equivalent (DE), have recently been developed. In this experiment, the ability of the LSE and DE preparations to function as biological dressings in an acute wound model was tested. Forty full-thickness wounds were made in New Zealand White rabbits. Each wound was inoculated with 5 x 10(5) Staphylococcus aureus organisms. Twenty-four hours later, one of the following four dressings was applied: saline gauze, porcine-derived xenograft, LSE, or DE. Daily dressing changes and wound biopsies for bacterial counts were performed. At 96 hours after inoculation, split-thickness autograft was applied to all wounds. Skin graft take was assessed 5 days later. In all treatment groups, bacterial counts decreased over time (p = 0.02). At 72 and 96 hours after inoculation, wounds dressed with LSE or DE had significantly lower mean bacterial counts than wounds treated with xenograft dressing (p < 0.01). No significant differences were found among the LSE-, DE-, or saline-treated groups. Skin grafts took well in LSE- and DE-treated wounds. In conclusion, the LSE and DE were more effective than xenograft in reducing bacterial wound contamination in this model, thereby demonstrating their potential application as biological dressing materials. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,DIV PLAST SURG,BOSTON,MA 02114. NR 8 TC 1 Z9 1 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD JUN PY 1993 VL 30 IS 6 BP 516 EP 519 DI 10.1097/00000637-199306000-00008 PG 4 WC Surgery SC Surgery GA LH469 UT WOS:A1993LH46900008 PM 8368778 ER PT J AU BEALL, AC JONES, JW GUINN, GA SVENSSON, LG NAHAS, C AF BEALL, AC JONES, JW GUINN, GA SVENSSON, LG NAHAS, C TI CARDIOPULMONARY BYPASS IN PATIENTS WITH PREVIOUSLY COMPLETED STROKE SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 29TH Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 25-27, 1993 CL SAN ANTONIO, TX SP SOC THORAC SURGEONS ID ASCENDING AORTA; SURGERY AB It has been assumed that patients with neurological residua after a completed stroke are at increased risk of neurological complications associated with cardiac operations requiring cardiopulmonary bypass. To evaluate these assumptions, we reviewed retrospectively 1,163 consecutive patients undergoing cardiac operations with cardiopulmonary bypass. Among these 1,163 patients were 43 patients having a previously completed stroke with neurological residua, but without clinically significant extracranial carotid artery disease. Forty-one underwent coronary artery bypass grafting; of these, 1 required concomitant aortic valve replacement, 1 had mitral valve replacement, and 1 had aortic valve replacement. There was one death in this group of 43 patients, due to massive pulmonary embolism. Only 1 of these 43 patients experienced new neurological symptoms after operation, which would appear to indicate that patients with a previous, completed stroke may not be at increased risk of neurological complications from cardiac operations requiring cardiopulmonary bypass. C1 BAYLOR COLL MED,CORA & WEBB MADING DEPT SURG,HOUSTON,TX 77030. HOUSTON VET AFFAIRS MED CTR,HOUSTON,TX. NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 1993 VL 55 IS 6 BP 1382 EP 1385 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA LH441 UT WOS:A1993LH44100007 ER PT J AU FISCHMAN, AJ ALPERT, NM LIVNI, E RAY, S SINCLAIR, I CALLAHAN, RJ CORREIA, JA WEBB, D STRAUSS, HW RUBIN, RH AF FISCHMAN, AJ ALPERT, NM LIVNI, E RAY, S SINCLAIR, I CALLAHAN, RJ CORREIA, JA WEBB, D STRAUSS, HW RUBIN, RH TI PHARMACOKINETICS OF F-18 LABELED FLUCONAZOLE IN HEALTHY-HUMAN SUBJECTS BY POSITRON EMISSION TOMOGRAPHY SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CEREBROSPINAL-FLUID; CANDIDA-ALBICANS; KETOCONAZOLE; PENETRATION; HYPOTHESIS; UK-49,858; TRIAZOLES; PROFILE; INVITRO; INVIVO AB The distribution of fluconazole in tissue of human volunteers was determined by positron emission tomographic scanning over a 2-h period following the infusion of a tracer dose of F-18-fluconazole (5 to 7 mCi) plus 400 mg of unlabeled drug (the standard daily dose of fluconazole). Previous studies have validated this approach for animals. From serial positron emission tomographic imaging and blood sampling, pharmacokinetics of fluconazole in tissue were determined. There was significant distribution of the radiolabeled drug in all organs studied, with nearly constant levels achieved by 1 h. Plateau concentrations of fluconazole in key organs (micrograms per gram) included the following: whole brain, 4.92 +/- 0.17; heart, 6.98 +/- 0.20; lung, 7.81 +/- 0.46; liver, 12.94 +/- 0.24; spleen, 22.96 +/- 2.5; kidney, 11.23 +/- 0.61; prostate, 8.24 +/- 0.58; and blood, 3.76 +/- 0.30. Since levels of fluconazole of >6 mug/g are needed to treat infection with most strains of Candida and levels of > 10 mug/g are needed for Cryptococcus neoformans, Coccidioides immitis, and Histoplasma capsulatum, the following predictions can be made. The current standard dose of 400 mg/day should be more than adequate in the treatment of urinary tract and hepatosplenic candidiasis but problematic in the treatment of candidal osteomyelitis, even with the higher levels that develop after multiple doses. Similarly, higher doses should be considered, particularly in immunocompromised patients, with infection with C. neoformans, H. capsulatum, and C. immitis that involves the central nervous and musculoskeletal systems. C1 MASSACHUSETTS GEN HOSP,MED SERV,CLIN INVEST PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. PFIZER LTD,CENT RES,SANDWICH CT13 9NJ,KENT,ENGLAND. PFIZER INC,ROERIG MED DEPT,NEW YORK,NY. RP FISCHMAN, AJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114, USA. NR 35 TC 58 Z9 59 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1993 VL 37 IS 6 BP 1270 EP 1277 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA LF135 UT WOS:A1993LF13500012 PM 8328777 ER PT J AU MARTIN, S MARTIN, A STAUNTON, DE SPRINGER, TA AF MARTIN, S MARTIN, A STAUNTON, DE SPRINGER, TA TI FUNCTIONAL-STUDIES OF TRUNCATED SOLUBLE INTERCELLULAR-ADHESION MOLECULE-1 EXPRESSED IN ESCHERICHIA-COLI SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IMMUNOGLOBULIN-LIKE DOMAINS; RHINOVIRUS RECEPTOR; RNA-POLYMERASE; BETA-SUBUNIT; ICAM-1; BINDING; LFA-1; NEUTRALIZATION; ANTIBODIES; EPITOPES AB We have expressed in Escherichia coli the two N-terminal immunoglobulin (Ig)-like domains of the intercellular adhesion molecule 1 (ICAM-1). The first 188 residues of ICAM-1 were expressed with an N-terminal methionine (MP188) or as a maltose-binding fusion protein which was cleaved with factor Xa (XP188). After refolding, both MP188 and XP188 were active in binding to the leukocyte integrin lymphocyte function-associated antigen 1, which has previously been shown to bind to the N-terminal Ig domain of ICAM-1. The major group of rhinoviruses and malaria-infected erythrocytes bind to distinct sites within the first Ig-like domain of ICAM-1. Both MP188 and XP188 bound to malaria-infected erythrocytes; however, only XP188 inhibited human rhinovirus plaque formation. A product (MdQ1P188) with the initiation methionine fused to residue 2, i.e., with glutamine 1 deleted, inhibited plaque formation. MdQ1P188 was able to induce a conformational change of the virus capsid as shown by conversion of 149S particles to 85S particles, whereas MP188 had no effect. These results show that functionally active fragments of ICAM-1 can be produced in E. coli, that glycosylation is not required for ligand binding, and that the N-terminal residue of ICAM-1 is proximal to or part of the human rhinovirus-binding site. C1 CTR BLOOD RES,200 LONGWOOD AVE,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NIAID NIH HHS [AI31921] NR 35 TC 17 Z9 17 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 JUN PY 1993 VL 37 IS 6 BP 1278 EP 1285 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA LF135 UT WOS:A1993LF13500013 PM 8101071 ER PT J AU WALSH, TJ STANDIFORD, HC REBOLI, AC JOHN, JF MULLIGAN, ME RIBNER, BS MONTGOMERIE, JZ GOETZ, MB MAYHALL, CG RIMLAND, D STEVENS, DA HANSEN, SL GERARD, GC RAGUAL, RJ AF WALSH, TJ STANDIFORD, HC REBOLI, AC JOHN, JF MULLIGAN, ME RIBNER, BS MONTGOMERIE, JZ GOETZ, MB MAYHALL, CG RIMLAND, D STEVENS, DA HANSEN, SL GERARD, GC RAGUAL, RJ TI RANDOMIZED DOUBLE-BLINDED TRIAL OF RIFAMPIN WITH EITHER NOVOBIOCIN OR TRIMETHOPRIM-SULFAMETHOXAZOLE AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCUS-AUREUS COLONIZATION - PREVENTION OF ANTIMICROBIAL RESISTANCE AND EFFECT OF HOST FACTORS ON OUTCOME SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID NASAL CARRIAGE; HOSPITAL OUTBREAK; UNITED-STATES; INFECTIONS; MUPIROCIN; ERADICATION; EFFICACY; THERAPY; HEMODIALYSIS; PROPHYLAXIS AB Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen in hospitals. Current antimicrobial regimens for eradicating colonizing strains are not well defined and are often complicated by the emergence of resistance. The combination of novobiocin plus rifampin in vitro and in vivo was found to prevent the emergence of resistant populations of initially susceptible strains of MRSA, particularly resistance to rifampin. We therefore studied, in a randomized, double-blind, multicenter comparative trial, the combination of novobiocin plus rifampin versus trimethoprim-sulfamethoxazole (T/S) plus rifampin in order to determine the efficacy of each regimen in eradicating MRSA colonization and to further characterize the host factors involved in the response to this antimicrobial therapy. Among the 126 individuals enrolled in the study, 94 (80 patients; 14 hospital personnel) were evaluable. Among the 94 evaluable subjects, no significant demographic or medical differences existed between the two treatment groups. Successful clearance of the colonizing MRSA strains was achieved in 30 of 45 (67%) subjects receiving novobiocin plus rifampin, whereas successful clearance was achieved in 26 of 49 (53%) subjects treated with T/S plus rifampin (P = 0.18). The emergence of resistance to rifampin developed more frequently in 14% (7 of 49) of subjects treated with T/S plus rifampin than in 2% (1 of 45) of subjects treated with novobiocin plus rifampin (P = 0.04). Restriction endonuclease studies of large plasmid DNA demonstrated that the same strain was present at pretherapy and posttherapy in most refractory cases (24 of 29 [83%] subjects). Among the 56 successfully treated subjects, clearance of MRSA was age dependent: 29 of 36 (80%) subjects in the 18- to 49-year-old age group, 19 of 35 (54%) subjects in the 50- to 69-year-old age group, and 8 of 23 (35%) in the 70- to 94-year-old age group (P < 0.01). Clearance was also site dependent; culture-positive samples from wounds were related to a successful outcome in only 22 (48%) of 46 subjects, whereas culture-positive samples from sites other than wounds (e.g., nares, rectum, and sputum) were associated with a success rate of 34 of 48 (71%) subjects (P = 0.02). Foreign bodies in wounds did not prevent the eradication of MRSA by either regimen. T/S plus rifampin was less effective in clearing pressure wounds compared with other wounds, whereas novobiocin plus rifampin was equally effective in clearing both pressure and other wounds. There were no significant differences in toxicity between the two regimens. Thus, the combination of novobiocin plus rifampin, in comparison with T/S plus rifampin, was more effective in preventing the emergence of resistance to rifampin and demonstrated a trend toward greater activity in clearing the MRSA carrier state. The response to either combination depended on host factors, particularly age and the site of MRSA colonization. C1 BALTIMORE VET AFFAIRS MED CTR,INFECT DIS SECT,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. MED UNIV S CAROLINA,CHARLESTON,SC 29425. NCI,BETHESDA,MD 20892. VET AFFAIRS MED CTR,CHARLESTON,SC 29425. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. ASHEVILLE VET AFFAIRS MED CTR,ASHEVILLE,NC 28805. DUKE UNIV,MED CTR,DURHAM,NC 27710. RANCHO LOS AMIGOS MED CTR,DOWNEY,CA 90242. UNIV CALIF LOS ANGELES,SEPULVEDA VET AFFAIRS MED CTR,LOS ANGELES,CA 90024. VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,RICHMOND,VA 23219. VET AFFAIRS MED CTR,DECATUR,GA 30033. EMORY UNIV,SCH MED,ATLANTA,GA 30322. SANTA CLARA VALLEY MED CTR,SAN JOSE,CA 95128. STANFORD UNIV,SCH MED,CALIF INST MED RES,SAN JOSE,CA 94305. UPJOHN CO,KALAMAZOO,MI 49001. OI Goetz, Matthew/0000-0003-4542-992X NR 56 TC 88 Z9 89 U1 3 U2 7 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 JUN PY 1993 VL 37 IS 6 BP 1334 EP 1342 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA LF135 UT WOS:A1993LF13500022 PM 8328783 ER PT J AU COLLINS, LA ELIOPOULOS, GM WENNERSTEN, CB FERRARO, MJ MOELLERING, RC AF COLLINS, LA ELIOPOULOS, GM WENNERSTEN, CB FERRARO, MJ MOELLERING, RC TI INVITRO ACTIVITY OF RAMOPLANIN AGAINST VANCOMYCIN-RESISTANT GRAM-POSITIVE ORGANISMS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID ENTEROCOCCI AB In vitro activity of ramoplanin, a cyclic lipoglycopeptide, against 92 vancomycin-resistant gram-positive organisms was evaluated. Ramoplanin demonstrated potent activity against many highly vancomycin-resistant organisms including enterococci (MICs for 90% of strains tested of 0.5 mug/ml) and against Lactobacillus spp., Leuconostoc spp., and Pediococcus spp., all of which were inhibited at concentrations of less-than-or-equal-to 0.25 mug/ml. This drug or a derivative compound merits further investigation as a potential therapeutic agent for infections due to vancomycin-resistant enterococci. C1 NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 14 TC 39 Z9 39 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1993 VL 37 IS 6 BP 1364 EP 1366 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA LF135 UT WOS:A1993LF13500027 PM 8328787 ER PT J AU FAEDDA, GL TONDO, L BALDESSARINI, RJ SUPPES, T TOHEN, M AF FAEDDA, GL TONDO, L BALDESSARINI, RJ SUPPES, T TOHEN, M TI OUTCOME AFTER RAPID VS GRADUAL DISCONTINUATION OF LITHIUM TREATMENT IN BIPOLAR DISORDERS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MANIC-DEPRESSIVE PATIENTS; MAINTENANCE THERAPY; PROPHYLACTIC LITHIUM; AFFECTIVE-ILLNESS; LIFE TABLE; FOLLOW-UP; WITHDRAWAL; RECURRENCE; PSYCHIATRY; RELAPSE AB Objectives: Withdrawal of bipolar mood disorder (BP-I) patients from prolonged, stable lithium maintenance has a high risk of early recurrence, particularly of mania. We thus compared risks of stopping lithium rapidly vs gradually. Design: Outpatients undergoing clinically determined discontinuation of lithium treatment at different rates were followed up prospectively to 5 years. Risks and timing of new episodes were analyzed. Patients: Subjects (N=64) with a DSM-III-R BP disorder, previously stable on lithium monotherapy for 18 to 120 months (mean, 3.6 years) were followed up clinically after discontinuing lithium (elected in prolonged well-being in 67%). None was unavailable for follow-up, and subtyping (BP-I or BP-II) remained stable. Results: Within 5 years, 75% had a recurrent episode; BP-I patients were 1.5-times less likely than BP-II to remain in remission. Polarity of first-recurrent and onset episodes was 80.8% concordant. Overall risk of a new episode of mania was significantly greater after rapid (<2) than gradual (2 to 4 weeks discontinuation (5-year hazard ratio=2.8); the difference in risk of depression was even greater hazard ratio=5.4). Recurrence rate was more elevated within months of rapid discontinuation (12-month hazard ratio=5.4). Recurrence rate was more elevated within months of rapid discontinuation (12-month hazard ratio=4.3) than at later times (2 to 5 years), when courses of ''survival' over time were nearly parallel in both discontinuation groups. Conclusions: Risk of early recurrence of BP disorder following discontinuation of lithium maintenance is elevated, but may be both predictable (timing and polarity) and modifiable by gradual discontinuation. C1 HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MCLEAN DIV,MAILMAN RES CTR,PSYCHOT DISORDERS PROGRAM,PSYCHIAT RES LABS,BELMONT,MA. MCLEAN HOSP,BIPOLAR DISORDER RES PROGRAM,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CTR LUCIO BINI,CAGLIARI,ITALY. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. OI Faedda, Gianni/0000-0001-6197-0543 FU NIMH NIH HHS [MH-47370, MH-31154] NR 48 TC 189 Z9 190 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 1993 VL 50 IS 6 BP 448 EP 455 PG 8 WC Psychiatry SC Psychiatry GA LF796 UT WOS:A1993LF79600004 PM 8498879 ER PT J AU BERSON, EL ROSNER, B SANDBERG, MA HAYES, KC NICHOLSON, BW WEIGELDIFRANCO, C WILLETT, W AF BERSON, EL ROSNER, B SANDBERG, MA HAYES, KC NICHOLSON, BW WEIGELDIFRANCO, C WILLETT, W TI A RANDOMIZED TRIAL OF VITAMIN-A AND VITAMIN-E SUPPLEMENTATION FOR RETINITIS-PIGMENTOSA SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID LIQUID-CHROMATOGRAPHY; ALPHA-TOCOPHEROL; RHODOPSIN GENE; ONE FORM; QUESTIONNAIRE; MUTATIONS; CAROTENE; TOXICITY; PLASMA; DESIGN AB Objective.-To determine whether supplements of vitamin A or vitamin E alone or in combination affect the course of retinitis pigmentosa. Design.-Randomized, controlled, double-masked trial with 2x2 factorial design and duration of 4 to 6 years. Electroretinograms, visual field area, and visual acuity were measured annually. Setting.-Clinical research facility. Patients.-601 patients aged 18 through 49 years with retinitis pigmentosa meeting preset eligibility criteria. Ninety-five percent of the patients completed the study. There were no adverse reactions. Intervention.-Patients were assigned to one of four treatment groups receiving 15 000 IU/d of vitamin A, 15 000 IU/d of vitamin A plus 400 IU/d of vitamin E, trace amounts of both vitamins, or 400 IU/d of vitamin E. Main Outcome Measure.-Cone electroretinogram amplitude. Results.-The two groups receiving 15 000 IU/d of vitamin A had on average a slower rate of decline of retinal function than the two groups not receiving this dosage (P=.01). Among 354 patients with higher initial amplitudes, the two groups receiving 15000 IU/d of vitamin A were 32% less likely to have a decline in amplitude of 50% or more from baseline in a given year than those not receiving this dosage (P=.01), while the two groups receiving 400 IU/d of vitamin E were 42% more likely to have a decline in amplitude of 50% or more from baseline than those not receiving this dosage (P=.03). While not statistically significant, similar trends were observed for rates of decline of visual field area. Visual acuity declined about 1 letter per year in all groups. Conclusions.-These results support a beneficial effect of 15 000 IU/d of vitamin A and suggest an adverse effect of 400 IU/d of vitamin E on the course of retinitis pigmentosa. RP BERSON, EL (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114, USA. FU NEI NIH HHS [U10-EY02014] NR 67 TC 315 Z9 325 U1 0 U2 12 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 JUN PY 1993 VL 111 IS 6 BP 761 EP 772 PG 12 WC Ophthalmology SC Ophthalmology GA LF543 UT WOS:A1993LF54300018 PM 8512476 ER PT J AU CHENEY, ML VARVARES, MA NADOL, JB AF CHENEY, ML VARVARES, MA NADOL, JB TI THE TEMPOROPARIETAL FASCIAL FLAP IN HEAD AND NECK RECONSTRUCTION SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID EAR RECONSTRUCTION; SURGICAL ANATOMY; SCALP AB The technique for using the temporoparietal fascial flap in head and neck reconstruction is described. The advantages and applications of this flap are discussed and illustrated with case reports. Donor site morbidity is discussed, and the details of flap harvesting are reviewed. We have found the flap to be useful in the reconstruction of a variety of defects that require thin, vascular, and durable coverage. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP CHENEY, ML (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,DIV FACIAL PLAST & RECONSTRUCT SURG,BOSTON,MA 02114, USA. NR 25 TC 47 Z9 48 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUN PY 1993 VL 119 IS 6 BP 618 EP 623 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA LF783 UT WOS:A1993LF78300004 PM 8388696 ER PT J AU FAUSTI, SA HENRY, JA SCHAFFER, HI OLSON, DJ FREY, RH BAGBY, GC AF FAUSTI, SA HENRY, JA SCHAFFER, HI OLSON, DJ FREY, RH BAGBY, GC TI HIGH-FREQUENCY MONITORING FOR EARLY DETECTION OF CISPLATIN OTOTOXICITY SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID HIGH-DOSE CISPLATIN; CIS-DICHLORODIAMMINEPLATINUM-II; CANCER-PATIENTS; HEARING-LOSS; PLATINUM; CHEMOTHERAPY; THERAPY; DIAMMINEDICHLOROPLATINUM; AUDIOMETRY; TOXICITY AB Cisplatin can cause irreversible hearing loss initially detectable as impairment of high-frequency hearing with progression to lower frequencies. Many patients receiving cisplatin are too ill to tolerate lengthy audiometric testing. Therefore, a rapid and sensitive high-frequency monitoring strategy to detect cisplatin-induced ototoxicity is needed. Serial conventional (0.25 to 8 kHz) and high-frequency (greater-than-or-equal-to 8 kHz) threshold monitoring was performed in patients receiving cisplatin, resulting in 84% of ears showing hearing loss, of which 71% were detected first in frequencies of 8 kHz or greater. By analysis according to an individualized, specific high-frequency range, early identification of hearing loss occurred in 94% of ears showing change. This five-frequency procedure is a sensitive detector of ototoxicity and is proposed as an alternative monitoring protocol for patients receiving cisplatin who cannot tolerate extended testing. C1 PORTLAND VET AFFAIRS MED CTR,AUDITORY RES LAB,PORTLAND,OR. PORTLAND VET AFFAIRS MED CTR,HEMATOL ONCOL SERV,PORTLAND,OR. OREGON HLTH SCI UNIV,MED ONCOL SERV,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT OTOLARYNGOL,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DIV HEMATOL,PORTLAND,OR 97201. RP FAUSTI, SA (reprint author), PORTLAND VET AFFAIRS MED CTR,DEPT VET AFFAIRS,POB 1034,PORTLAND,OR 97207, USA. NR 33 TC 48 Z9 52 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUN PY 1993 VL 119 IS 6 BP 661 EP 666 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA LF783 UT WOS:A1993LF78300014 PM 8499098 ER PT J AU GLIKLICH, RE CUNNINGHAM, MJ EAVEY, RD AF GLIKLICH, RE CUNNINGHAM, MJ EAVEY, RD TI THE CAUSE OF AURAL POLYPS IN CHILDREN SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID CHOLESTEATOMA AB This 20-year retrospective review identifies 35 pediatric patients with aural polyps in an attempt to assess for clinical predictors of significant otopathologic conditions. Chronic otitis media (43%), cholesteatoma (29%), and retained tympanostomy tubes (23%) were the common causes. Unusual causes included mycobacterial infection and Langerhans' cell histiocytosis. Multivariate analysis revealed the co-occurrence of conductive hearing loss at presentation to be a significant clinical predictor (P=.03) of cholesteatoma; the histopathologic finding of keratin-induced giant cell reaction was nonspecific in this respect. Cholesteatoma was also prevalent in recurrent polyp cases, suggesting the need for prolonged follow-up in those children whose initial clinicopathologic evaluation does not yield a definitive diagnosis. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. NR 5 TC 13 Z9 13 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUN PY 1993 VL 119 IS 6 BP 669 EP 671 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA LF783 UT WOS:A1993LF78300015 PM 8499099 ER PT J AU WELCH, JP WELCH, CE AF WELCH, JP WELCH, CE TI CANCER OF THE RECTUM - WHERE ARE WE - WHERE ARE WE GOING SO ARCHIVES OF SURGERY LA English DT Article ID LOCAL EXCISION; PREOPERATIVE IRRADIATION; RECTOSIGMOID CARCINOMA; COLORECTAL-CANCER; RANDOMIZED TRIAL; ADJUVANT THERAPY; RADIATION; MANAGEMENT; 5-FLUOROURACIL; RADIOTHERAPY C1 HARTFORD HOSP,HARTFORD,CT 06115. UNIV CONNECTICUT,CTR HLTH,FARMINGTON,CT 06032. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. AMER COLL SURGEONS,CHICAGO,IL 60611. RP WELCH, JP (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 27 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUN PY 1993 VL 128 IS 6 BP 697 EP 702 PG 6 WC Surgery SC Surgery GA LF305 UT WOS:A1993LF30500017 PM 8503775 ER PT J AU EVANS, JE GHOSH, A EVANS, BA NATOWICZ, MR AF EVANS, JE GHOSH, A EVANS, BA NATOWICZ, MR TI SCREENING TECHNIQUES FOR THE DETECTION OF INBORN-ERRORS OF BILE-ACID METABOLISM BY DIRECT INJECTION AND MICRO-HIGH PERFORMANCE LIQUID-CHROMATOGRAPHY CONTINUOUS-FLOW FAST-ATOM-BOMBARDMENT MASS-SPECTROMETRY SO BIOLOGICAL MASS SPECTROMETRY LA English DT Article ID URINE AB Two methods, direct injection-continuous flow fast atom bombardment (DI-CF/FAB) mass spectrometry and micro-high-performance liquid chromatography (muHPLC)-CF/FAB) mass spectrometry were developed for the clinical analysis of urinary bile acids and their conjugates, specifically for the diagnosis of disorders of bile acid metabolism. The method based upon DI of urine extracts into the CF/FAB flow stream was developed for the rapid screening of large numbers of patient samples. It allows injections to be made at 4 min intervals for high sample throughput. Analyses of standard mixtures of bile salts demonstrate that linear response curves are obtained over more than a hundred-fold concentration range with a minimum detectable amount in the picogram range. Oxo bile salts are identified by reduction with sodium borodeuteride followed by reanalysis for detection of any reduction products. This methodology has been used for the analysis of over 1000 specimens. A reverse-phase muHPLC-CF/FAB mass spectrometric method was also developed for use in the confirmation or further investigation of screening results. With no additional sample preparation this method permits the separation, identification and quantitation of urinary bile salt isomers within a 45 min analysis time. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV MED GENET,WALTHAM,MA 02154. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP EVANS, JE (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DEPT BIOMED SCI,200 TRAPELO RD,WALTHAM,MA 02154, USA. FU NINDS NIH HHS [NS16447] NR 16 TC 28 Z9 28 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1052-9306 J9 BIOL MASS SPECTROM JI Biol. Mass Spectrom. PD JUN PY 1993 VL 22 IS 6 BP 331 EP 337 DI 10.1002/bms.1200220604 PG 7 WC Biophysics; Spectroscopy SC Biophysics; Spectroscopy GA LE994 UT WOS:A1993LE99400003 PM 8329462 ER PT J AU MEYERSWALLEN, VN LEE, MM MANGANARO, TF KURODA, T MACLAUGHLIN, D DONAHOE, PK AF MEYERSWALLEN, VN LEE, MM MANGANARO, TF KURODA, T MACLAUGHLIN, D DONAHOE, PK TI MULLERIAN-INHIBITING SUBSTANCE IS PRESENT IN EMBRYONIC TESTES OF DOGS WITH PERSISTENT MULLERIAN DUCT SYNDROME SO BIOLOGY OF REPRODUCTION LA English DT Article ID GROWTH FACTOR-BETA; XY SEX REVERSAL; RIBONUCLEIC-ACID; GRANULOSA-CELLS; SERTOLI CELLS; FETAL TESTIS; HORMONE; BOVINE; EXPRESSION; ONTOGENY AB Mullerian Inhibiting Substance (MIS) causes regression of the Mullerian ducts during a critical period in embryonic development in male mammals. In Persistent Mullerian Duct Syndrome (PMDS), an autosomal recessive trait in humans and dogs, the Mullerian ducts fail to regress in otherwise normal males. Previously we reported that PMDS-affected dogs produce bioactive testicular MIS postnatally. The purpose of the present study was to determine whether PMDS-affected canine embryos appropriately express MIS mRNA and protein during the critical period for Mullerian duct regression. Homozygous (PMDS-affected) and normal canine embryos were removed from timed pregnancies. Gonadal sex and the degree of Mullerian duct regression were determined from histologic sections. Positive immunohistochemical staining for MIS was found in testis sections of PMDS-affected and normal male embryos. A 1.8-kb MIS mRNA transcript was detected in testes of PMDS-affected males and normal male embryos and neonates. Furthermore, equal amounts of MIS mRNA transcript were detected in testes of PMDS-affected embryos and normal male littermates during the critical period for Mullerian duct regression. These data support a hypothesis of target organ resistance, such as an abnormality in the putative MIS receptor, as the etiology of the defect in this dog model. C1 CORNELL UNIV,COLL VET MED,JA BAKER INST,ITHACA,NY 14853. CORNELL UNIV,COLL VET MED,DEPT CLIN SCI,ITHACA,NY 14853. MASSACHUSETTS GEN HOSP,DEPT PEDIAT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. OI Lee, Mary/0000-0002-7204-4884 FU NCI NIH HHS [CA 17393]; NICHD NIH HHS [HD 19393, T32 HD07396] NR 55 TC 23 Z9 23 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUN PY 1993 VL 48 IS 6 BP 1410 EP 1418 DI 10.1095/biolreprod48.6.1410 PG 9 WC Reproductive Biology SC Reproductive Biology GA LE757 UT WOS:A1993LE75700027 PM 8318594 ER PT J AU ZELEN, M AF ZELEN, M TI OPTIMAL SCHEDULING OF EXAMINATIONS FOR THE EARLY DETECTION OF DISEASE SO BIOMETRIKA LA English DT Article DE FORWARD RECURRENCE TIME; LENGTH BIASED SAMPLING; PERIODIC SCREENING; POINT PROCESS ID BREAST-CANCER; LEAD TIME; MAMMOGRAPHY; MORTALITY AB The general theory of scheduling examinations for the diagnosis of disease is formulated with respect to the optimal spacing between examinations. This same theory is also applicable, with a change in language, to the inspection of equipment and the scheduling of patients under surveillance with disease. Optimal scheduling programmes are investigated using a weighted utility function which is linear in the probabilities both of finding a case at examination and of being clinically incident between examinations. If disease incidence is independent of time, then a necessary and sufficient condition for the intervals to be equally spaced is that the sensitivity of the examination be unity. The equations for finding the optimal intervals are derived and depend on the distribution of the pre-clinical sojourn times and the sensitivity of the test. If the sojourn distribution is exponential, the optimal intervals are equal except for the first and last intervals. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP ZELEN, M (reprint author), HARVARD UNIV,SCH PUBL HLTH,44 BINNEY ST,BOSTON,MA 02115, USA. NR 23 TC 53 Z9 53 U1 2 U2 4 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD JUN PY 1993 VL 80 IS 2 BP 279 EP 293 PG 15 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA LZ065 UT WOS:A1993LZ06500003 ER PT J AU TONER, M CRAVALHO, EG STACHECKI, J FITZGERALD, T TOMPKINS, RG YARMUSH, ML ARMANT, DR AF TONER, M CRAVALHO, EG STACHECKI, J FITZGERALD, T TOMPKINS, RG YARMUSH, ML ARMANT, DR TI NONEQUILIBRIUM FREEZING OF ONE-CELL MOUSE EMBRYOS - MEMBRANE INTEGRITY AND DEVELOPMENT POTENTIAL SO BIOPHYSICAL JOURNAL LA English DT Article ID INTRACELLULAR ICE FORMATION; DROSOPHILA-MELANOGASTER EMBRYOS; WATER PERMEABILITY; HUMAN-GRANULOCYTES; DIMETHYLSULFOXIDE; SURVIVAL; OOCYTES; CRYOPRESERVATION; TEMPERATURE; FROZEN AB A thermodynamic model was used to evaluate and optimize a rapid three-step rapid three-step nonequilibrium freezing protocol for one-cell mouse embryos in the absence of cryoprotectants (CPAs) that avoided lethal intracellular ice formation (IIF). Biophysical parameters of one-cell mouse embryos were determined at subzero temperatures using cryomicroscopic investigations (i.e., the water permeability of the plasma membrane, its temperature dependence, and the parameters for heterogeneous IIF). The parameters were then incorporated into the thermodynamic model, which predicted the likelihood of IIF. Model predictions showed that IIF could be prevented at a cooling rate of 120-degrees-C/min when a 5-min holding period was inserted at -10-degrees-C to assure cellular dehydration. This predicted freezing protocol, which avoided IIF in the absence of CPAs, was two orders of magnitude faster than conventional embryo cryopreservation cooling rates of between 0.5 and 1-degrees-C/min. At slow cooling rates, embryos predominantly follow the equilibrium phase diagram and do not undergo IIF, but mechanisms other that IIF (e.g., high electrolyte concentrations, mechanical effects, and others) cause cellular damage. We tested the predictions of our thermodynamic model using a programmable freezer and confirmed the theoretical predictions. The membrane integrity of one-cell mouse embryos, as assessed by fluorescein diacetate retention, was approximately 80% after freezing down to -45-degrees-C by the rapid nonequilibrium protocol derived from our model. The fact that embryos could be rapidly frozen in the absence of CPAs without damage to the plasma membrane as assessed by fluorescein diacetate retention is a new and exciting finding. Further refinements of this protocol is necessary to retain the developmental competence of the embryos. C1 SHRINERS BURNS INST,BOSTON,MA 02114. RUTGERS UNIV,DEPT CHEM & BIOCHEM ENGN,NEW BRUNSWICK,NJ 08903. WAYNE STATE UNIV,CS MOTT CTR HUMAN GROWTH & DEV,SCH MED,DEPT OBSTET & GYNECOL,DETROIT,MI 48202. RP TONER, M (reprint author), MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114, USA. FU NICHD NIH HHS [HD-25795] NR 36 TC 51 Z9 55 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 1993 VL 64 IS 6 BP 1908 EP 1921 PG 14 WC Biophysics SC Biophysics GA LJ216 UT WOS:A1993LJ21600028 PM 8369414 ER PT J AU RESTREPO, D OKADA, Y TEETER, JH LOWRY, LD COWART, B BRAND, JG AF RESTREPO, D OKADA, Y TEETER, JH LOWRY, LD COWART, B BRAND, JG TI HUMAN OLFACTORY NEURONS RESPOND TO ODOR STIMULI WITH AN INCREASE IN CYTOPLASMIC CA2+ SO BIOPHYSICAL JOURNAL LA English DT Note ID RECEPTOR NEURONS; CALCIUM; CONDUCTANCE; MEMBRANE; CATFISH; CILIA; CELL AB The sense of smell allows terrestrial animals to collect information about the chemical nature of their environment through the detection of airborne molecules (7). In humans smell is believed to play an important role in protecting the organism from environmental hazards such as fire, gas leaks and spoiled food, in determining the flavor of foods, and perhaps in infant-parent bonding (8). In addition, the study of human olfaction is relevant to a number of medical problems that result in olfactory dysfunction, which can affect nutritional state, and to the study of the etiology of neurodegenerative diseases which manifest themselves in the olfactory epithelium (8, 26). Although much is known about behavioral aspects of human olfaction (8), little is understood about the underlying cellular mechanisms in humans. Here we report that viable human olfactory neurons (HON) can be isolated from olfactory tissue biopsies, and we find that HON respond to odorants with an increase in intracellular calcium concentration ([Ca(i)]). C1 UNIV PENN,SCH MED,DEPT PHYSIOL,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. NAGASAKI UNIV,DEPT PHYSIOL,NAGASAKI 852,JAPAN. THOMAS JEFFERSON UNIV,DEPT OTOLARYNGOL,PHILADELPHIA,PA 19107. UNIV PENN,SCH DENT MED,DEPT BIOCHEM,PHILADELPHIA,PA 19104. RP RESTREPO, D (reprint author), MONELL CHEM SENSES CTR,3500 MARKET ST,PHILADELPHIA,PA 19104, USA. FU NIDCD NIH HHS [DC-01434, DC-00566, DC-00214] NR 27 TC 52 Z9 53 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 JUN PY 1993 VL 64 IS 6 BP 1961 EP 1966 PG 6 WC Biophysics SC Biophysics GA LJ216 UT WOS:A1993LJ21600031 PM 8369416 ER PT J AU OGAWA, M AF OGAWA, M TI DIFFERENTIATION AND PROLIFERATION OF HEMATOPOIETIC STEM-CELLS SO BLOOD LA English DT Review ID COLONY-STIMULATING FACTOR; TRANSFORMING GROWTH FACTOR-BETA-1; RECOMBINANT GIBBON INTERLEUKIN-3; TUMOR NECROSIS FACTOR; PROGENITOR CELLS; GM-CSF; C-KIT; PAIRED PROGENITORS; FORMING-UNITS; SELF-RENEWAL C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. RP OGAWA, M (reprint author), RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,109 BEE ST,CHARLESTON,SC 29401, USA. FU NIDDK NIH HHS [DK 32294] NR 126 TC 1076 Z9 1094 U1 3 U2 44 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1993 VL 81 IS 11 BP 2844 EP 2853 PG 10 WC Hematology SC Hematology GA LF065 UT WOS:A1993LF06500002 PM 8499622 ER PT J AU RAVID, K KUTER, DJ BEELER, DL DOI, T ROSENBERG, RD AF RAVID, K KUTER, DJ BEELER, DL DOI, T ROSENBERG, RD TI SELECTION OF AN HEL-DERIVED CELL-LINE EXPRESSING HIGH-LEVELS OF PLATELET FACTOR-IV SO BLOOD LA English DT Article ID LEUKEMIA; GENE; ESTABLISHMENT; MEMBRANE; MARROW C1 MASSACHUSETTS GEN HOSP,HEMATOL UNIT,BOSTON,MA 02114. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP RAVID, K (reprint author), MIT,DEPT BIOL,77 MASSACHUSETTS AVE,E25-229,CAMBRIDGE,MA 02139, USA. FU NHLBI NIH HHS [HL42443, HL39753] NR 16 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1993 VL 81 IS 11 BP 2885 EP 2890 PG 6 WC Hematology SC Hematology GA LF065 UT WOS:A1993LF06500008 PM 8499627 ER PT J AU REIS, BE AF REIS, BE TI TOWARD A PSYCHOANALYTIC UNDERSTANDING OF MULTIPLE PERSONALITY-DISORDER SO BULLETIN OF THE MENNINGER CLINIC LA English DT Article; Proceedings Paper CT MENNINGER CONTINUING EDUCATION CONF ON DISSOCIATIVE STATES : MULTIPLE PERSONALITY AND OTHER TRAUMA-RELATED DISORDERS CY FEB 14-16, 1992 CL TOPEKA, KS ID PERSPECTIVE; OBJECT AB The author suggests a developmental psychoanalytic frame from which to understand the clinical phenomenology of multiple personality disorder (MPD). Annihilation anxiety and fears of nonbeing are understood as central, they are seen as resulting from actual early traumatic impingements at key developmental periods. Alter ''personalities '' are conceptualized as functional delusional processes that serve to maintain self-cohesion. The alters are brought about through the subject's lack of capacity for illusion. Some therapeutic implications regarding a psychoanalytic stance are discussed. C1 MASSACHUSETTS GEN HOSP,TRAUMA CLIN,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP REIS, BE (reprint author), ERICH LINDEMANN MENTAL HLTH CTR,TRAUMA CLIN,25 STANIFORD ST,BOSTON,MA 02114, USA. NR 48 TC 6 Z9 6 U1 0 U2 1 PU MENNINGER FOUNDATION PI TOPEKA PA BOX 829, TOPEKA, KS 66601 SN 0025-9284 J9 B MENNINGER CLIN JI Bull. Menninger Clin. PD SUM PY 1993 VL 57 IS 3 BP 309 EP 318 PG 10 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA LP570 UT WOS:A1993LP57000004 PM 8401383 ER PT J AU LOVICH, MA SIMON, BA VENEGAS, JG SIMS, NM COOPER, JB AF LOVICH, MA SIMON, BA VENEGAS, JG SIMS, NM COOPER, JB TI A MASS-BALANCE MODEL FOR THE MAPLESON-D ANESTHESIA BREATHING SYSTEM SO CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Article DE EQUIPMENT, ANESTHESIA CIRCUITS; NON-REBREATHING; MAPLESON-D ID CONTROLLED VENTILATION; T-PIECE; FLOW REQUIREMENTS; ANESTHETIC SYSTEM; BAIN CIRCUIT; CHILDREN AB A mathematical model is described which calculates the alveolar concentration of CO2(F(ACO2) in a patient breathing through a Mapleson D anaesthesia system. The model is derived using a series of mass balances for CO2 in the alveolar space, dead space, breathing system limb volume and reservoir. The variables included in the model are tidal volume (V(T)), respiratory rate, fresh gas flow rate (V(f), dead space volume, I:E ratios, and expiratory limb volume (V(l)), time constant of lung expiration, and carbon dioxide production rate. The model predictions are compared with measurements made using a mechanical lung simulator in both spontaneous and controlled ventilation. Both the model and the experimental data predict that at high fresh gas flow rates and low respiratory rates, F(ACO2) is independent of V(f); at low fresh gas flow rates and high respiratory rates, F(ACO2) is independent of respiratory rate. The model and the data show that the V(T) influences F(ACO2), independent of minute ventilation alone, during both partial rebreathing and non-rebreathing operation. Therefore, describing the operation in terms of minute ventilation is ambiguous. It is also shown that V(l) influences F(ACO2) such that, for any combination of patient and breathing-system variables, there is a V(l) that minimizes the V(f) required to maintain F(ACO2). In addition, expiratory resistance can increase the fresh gas flow rate required to maintain a given F(ACO2). The respiratory patterns observed with spontaneous and controlled ventilation are responsible for the difference in V(f) required with each mode of ventilation. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,ANESTHESIA BIOENGN UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115. NR 28 TC 1 Z9 1 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 JUN PY 1993 VL 40 IS 6 BP 554 EP 567 PG 14 WC Anesthesiology SC Anesthesiology GA LT362 UT WOS:A1993LT36200016 PM 8403123 ER PT J AU TAHAN, SR NEUBERG, DS DIEFFENBACH, A YACOUB, L AF TAHAN, SR NEUBERG, DS DIEFFENBACH, A YACOUB, L TI PREDICTION OF EARLY RELAPSE AND SHORTENED SURVIVAL IN PATIENTS WITH BREAST-CANCER BY PROLIFERATING CELL NUCLEAR ANTIGEN SCORE SO CANCER LA English DT Article DE PROLIFERATING CELL NUCLEAR ANTIGEN; CELL CYCLE; BREAST CANCER; IMMUNOHISTOCHEMISTRY ID FLOW CYTOMETRIC ANALYSIS; DNA POLYMERASE-DELTA; CYCLIN PCNA; S-PHASE; PROTEIN CYCLIN; MONOCLONAL-ANTIBODIES; PROGNOSTIC FACTORS; PARAFFIN SECTIONS; AUXILIARY PROTEIN; MITOTIC COUNT AB Background. Cell cycle kinetic measures have been shown to have prognostic significance in breast cancer. Methods that have been used to assess the proliferating fraction of tumors include measurements of DNA content with S-phase calculation by flow cytometric analysis, radioisotope-labeled nucleotide incorporation, and cell cycle-associated protein expression. The recent discovery of the S-phase-specific nuclear protein proliferating cell nuclear antigen (PCNA) opens the door for a novel approach to cell kinetic measurement with an immunocytochemical assay. Methods. A quantitative immunocytochemical assay for PCNA was performed on 82 primary invasive breast carcinomas fixed in formaldehyde solution and embedded in paraffin and 18 corresponding axillary metastases. The percentage of tumor cells with strong nuclear staining was determined by visual count. This PCNA score was correlated with histologic parameters, age, relapse intervals, and long-term survival. Results. PCNA scores were distributed normally among primary carcinomas (range, 5-54; mean, 22.5). Carcinomas had much higher scores than adjacent normal epithelium (means, 22.5 and 4.1, respectively; P < 0.0001), and axillary node metastases had slightly higher scores than corresponding primary breast tumors (means, 26.4 and 22.5, respectively; P = 0.05). The PCNA score did not correlate with age, tumor size, axillary node status, intramammary lymphatic-vascular invasion, or estrogen and progesterone binding capacities. Furthermore, its variability could not be explained by grade. PCNA values increased as the mitotic rate increased. Cancers with high PCNA scores (greater-than-or-equal-to 25) were associated with shorter disease-free (P = 0.007) and overall survival times (P = 0.01) than tumors with low PCNA scores (< 25) (median follow-up, 166 months). Conclusions. PCNA score has potential value as a prognostic indicator in breast cancer. This method of assessing the proliferating pool offers advantages over other assays in terms of relative simplicity of the method. applicability to paraffin-embedded fixed tissue, and low cost. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. RP TAHAN, SR (reprint author), NEW ENGLAND DEACONESS HOSP,DEPT PATHOL,MEISSNER 201,BOSTON,MA 02215, USA. NR 51 TC 78 Z9 84 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 JUN 1 PY 1993 VL 71 IS 11 BP 3552 EP 3559 DI 10.1002/1097-0142(19930601)71:11<3552::AID-CNCR2820711115>3.0.CO;2-N PG 8 WC Oncology SC Oncology GA LE419 UT WOS:A1993LE41900014 PM 8098267 ER PT J AU ZLOTECKI, RA BOUCHER, Y LEE, I BAXTER, LT JAIN, RK AF ZLOTECKI, RA BOUCHER, Y LEE, I BAXTER, LT JAIN, RK TI EFFECT OF ANGIOTENSIN-II-INDUCED HYPERTENSION ON TUMOR BLOOD-FLOW AND INTERSTITIAL FLUID PRESSURE SO CANCER RESEARCH LA English DT Note ID MAMMARY-CARCINOMA; CHEMOTHERAPY AB The effect of angiotensin II-induced hypertension on tumor interstitial fluid pressure (TIFP) and tumor blood flow (TBF) was investigated to examine blood flow and pressure regulation in solid tumors. TIFP measurements were made before and after administration of angiotensin II using the wick-in-needle method in s.c. tumor implants. Relative TBF was continuously monitored by laser doppler velocimetry. The effect or host strain on TIFP was evaluated in MCA-IV mammary carcinoma, transplanted in C3H and SCID mice, and showed no significant difference. The effects of tumor types were evaluated by comparing two murine tumors, MCA-IV mammary carcinoma and FSaII fibrosarcoma, and a human tumor xenograft, LS174T adenocarcinoma, transplanted in SCID mice. Baseline TIFP was elevated in all three tumor lines to significantly different pressures. AII-induced hypertension (approximately 150 mm Hg) had a variable but tumor line-specific effect on TIFP and TBF. The increase in TIFP was correlated with the baseline TIFP (r2 = 0.853) (increasing from 6.9 to 8.7 mm Hg, 10.5 to 15.8 mm Hg, and 21.7 to 29.4 mm Hg in FSaII, MCA-IV, and LS174T, respectively). These data suggest that in addition to blood now redistribution due to the steal phenomenon, arterial control of TBF and TIFP exists within these solid tumors; however, the extent of control is tumor line dependent and less than that in normal tissues. Moreover, parallel increases in TIFP and TBF do not support the hypothesis that elevated TIFP causes vascular collapse and thus decreases TBF. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP ZLOTECKI, RA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,STEELE LAB,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-49792, CA-37239] NR 23 TC 58 Z9 59 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1993 VL 53 IS 11 BP 2466 EP 2468 PG 3 WC Oncology SC Oncology GA LE026 UT WOS:A1993LE02600003 PM 8495405 ER PT J AU CHANG, TKH WAXMAN, DJ AF CHANG, TKH WAXMAN, DJ TI CYCLOPHOSPHAMIDE MODULATES RAT HEPATIC CYTOCHROME-P450 2C11 AND STEROID 5-ALPHA-REDUCTASE ACTIVITY AND MESSENGER-RNA LEVELS THROUGH THE COMBINED ACTION OF ACROLEIN AND PHOSPHORAMIDE MUSTARD SO CANCER RESEARCH LA English DT Article ID ISOPHOSPHAMIDE NSC-109724; HORMONAL-REGULATION; METABOLISM; TOXICITY; EXPRESSION; PHARMACOKINETICS; IDENTIFICATION; PHARMACOLOGY; DENATURATION; GLUTATHIONE AB Cyclophosphamide treatment of adult male rats leads to sustained decreases in several liver microsomal cytochrome P450 (CYP) activities, including CYP 2C11-catalyzed cyclophosphamide activation, via a process that is associated with a feminization of the overall pattern of liver enzyme expression (G. A. LeBlanc and D. J. Waxman, Cancer Res., 50: 5720-5726, 1990). The present study compares the effects of cyclophosphamide and its isomeric analogue ifosphamide on the gender-dependent expression of hepatic CYP 2C11 and steroid 5alpha-reductase in adult male rats and also examines the role of the cyclophosphamide metabolites acrolein and phosphoramide mustard in feminizing the expression of these liver enzymes. Ifosphamide (a) suppressed the male-specific CYP 2C11 mRNA and CYP 2C11-catalyzed liver microsomal testosterone 2alpha-hydroxylation and cyclophosphamide and ifosphamide 4-hydroxylation and (b) elevated the female-dominant liver enzyme steroid 5alpha-reductase and its mRNA 7-9 days after drug treatment, both occurring in a manner similar to that of cyclophosphamide, but requiring a 50% higher dose (180 mg/kg, single i.p. injection) to achieve these effects. This pattern of response could not be achieved by treatment of rats with acrolein or with cyclophosphamide analogues that decompose to acrolein without formation of phosphoramide mustard. In contrast, phosphoramide mustard treatment (100 mg/kg) did modulate microsomal CYP 2C11 and steroid 5alpha-reductase activities. Treatment with a lower dose (50 mg/kg) of phosphoramide mustard or with the acrolein precursor 4-hydroperoxydechlorocyclophosphamide (200 mg/kg) alone did not affect liver enzyme expression, whereas the combination of these agents produced an overall pattern of response that was similar to that conferred by cyclophosphamide. These studies establish that ifosphamide is less potent than cyclophosphamide in modulating the pattern of cytochrome P450 and steroid 5alpha-reductase expression and that phosphoramide mustard is responsible for the modulation of liver enzyme expression by cyclophosphamide, with acrolein potentiating the modulating activity of the mustard. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,ROOM JF-525,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA-49248] NR 48 TC 27 Z9 27 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1993 VL 53 IS 11 BP 2490 EP 2497 PG 8 WC Oncology SC Oncology GA LE026 UT WOS:A1993LE02600009 PM 8495410 ER PT J AU CINCOTTA, L FOLEY, JW CINCOTTA, AH AF CINCOTTA, L FOLEY, JW CINCOTTA, AH TI PHOTOTOXICITY, REDOX BEHAVIOR, AND PHARMACOKINETICS OF BENZOPHENOXAZINE ANALOGS IN EMT-6 MURINE SARCOMA-CELLS SO CANCER RESEARCH LA English DT Article ID PHOTODYNAMIC THERAPY; INVITRO EVALUATION; SINGLET OXYGEN; ACRIDINE-DYES; LIVING CELLS; NILE RED; PHOTOSENSITIZERS; HEMATOPORPHYRIN; TUMOR; DERIVATIVES AB Structural modifications to the photoinactive benzophenoxazine Nile blue A have led to three novel derivatives which include 5-ethylamino-9-diethylaminobenzo[a]phenoxazinium (EtNBA), 5-ethylamino-9-diethyl-aminobenzo[a]phenothiazinium (EtNBS), and 5-ethylamino-9-diethyl-aminobenzo[a]phenoselenazinium (EtNBSe) chlorides. The incorporation of sulfur and selenium into the benzophenoxazine moiety results in lipophilic, red-absorbing (650-660 nm) chromophores which possess significantly increased singlet oxygen yields (0.025 and 0.65, respectively, compared to 0.005 for EtNBA). This study examines the photosensitizing efficacies and pharmacokinetics in vitro in the EMT-6 murine mammary sarcoma cell line as well as the physicochemical, photochemical, and redox properties of these new analogues. Comparisons with Photofrin II, the only photosensitizer available clinically, were made in an attempt to high-light their different pharmacological characteristics. The photodynamic activity of the benzophenoxazine dyes correlates with their ability to generate the phototoxin singlet oxygen and increases in the following order: EtNBA < EtNBS << EtNBSe. At an extracellular dye concentration of 0.5 pm, the light dose required to kill approximately 50% of the cells was 2.0 and < 0.5 J/cm2 for the sulfur and selenium dyes, respectively. The light dose required to kill approximately 50% of the cells for both EtNBA and Photofrin II could not be determined because of their weak phototoxic effect under these conditions. At a light dose of 3.3 J/cm2, EtNBSe is approximately 1000 times more phototoxic than Photofrin II. All three benzophenoxazine derivatives are characterized by a similar uptake/efflux pattern in vitro consisting of a rapid and extensive cellular accumulation followed by a slow efflux rate. Contrary to their rapid uptake, 50% of the accumulated EtNBS and EtNBSe is retained intracellularly after a 6-h period in dye-free medium. Video-enhanced fluorescence microscopy corroborates the rapid uptake measurements as well as indicating the intracellular localization of the dyes in both living and thermally inactivated cells. Low extracellular dye concentrations (0.05 muM) result in a punctate fluorescence pattern in the perinuclear region, while higher dye concentrations (> 0.1 muM) lead to additional fluorescence in the cytoplasm, cytomembranes, and other organelles but apparently not the nucleus. Absorption spectrometry revealed that living cells rapidly reduce the dyes to their colorless leuko form (photoinactive) if oxygen is not readily available in the environment. It is shown that the cellular reduction is an enzymatic process and that an oxygen-free and cell-free medium containing both the coenzyme NADH and the hydride transfer enzyme diaphorase is capable of reducing the dyes to the colorless leuko form. EtNBSe exhibited the fastest rate of reduction under these conditions. In addition, the benzophenoxazine derivatives also undergo a light-induced reduction under anaerobic conditions in the presence of NADH; the rates increase in the following order: EtNBA < EtNBS << EtNBSe. Reoxidation of the leuko form occurs upon introduction of oxygen. This investigation demonstrates that the benzophenoxazine chalcogen analogues are a unique class of photochemotherapeutic agents. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. RP CINCOTTA, L (reprint author), ROWLAND INST SCI INC,100 EDWIN LAND BLVD,CAMBRIDGE,MA 02142, USA. NR 67 TC 49 Z9 49 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1993 VL 53 IS 11 BP 2571 EP 2580 PG 10 WC Oncology SC Oncology GA LE026 UT WOS:A1993LE02600023 PM 8495421 ER PT J AU RABIN, EM GORDON, K KNOPPERS, MH LUTHER, MA NEIDHARDT, EA FLYNN, JF SARDONINI, CA SAMPO, TM CONCINO, MF RECNY, MA REINHERZ, EL DWYER, DS AF RABIN, EM GORDON, K KNOPPERS, MH LUTHER, MA NEIDHARDT, EA FLYNN, JF SARDONINI, CA SAMPO, TM CONCINO, MF RECNY, MA REINHERZ, EL DWYER, DS TI INHIBITION OF T-CELL ACTIVATION AND ADHESION FUNCTIONS BY SOLUBLE CD2 PROTEIN SO CELLULAR IMMUNOLOGY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-3; RED BLOOD-CELLS; MHC CLASS-II; LYMPHOCYTE-T; MONOCLONAL-ANTIBODIES; ERYTHROCYTE RECEPTOR; MOLECULE-1 ICAM-1; LARGE POPULATION; BINDING; RECOGNITION C1 PROCEPT INC,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 44 TC 6 Z9 7 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUN PY 1993 VL 149 IS 1 BP 24 EP 38 DI 10.1006/cimm.1993.1133 PG 15 WC Cell Biology; Immunology SC Cell Biology; Immunology GA LJ146 UT WOS:A1993LJ14600003 PM 7685660 ER PT J AU ANZUETO, A MUNOZ, J GLENN, ME WISE, D DUNCAN, C JENKINSON, S AF ANZUETO, A MUNOZ, J GLENN, ME WISE, D DUNCAN, C JENKINSON, S TI LEFT UPPER EXTREMITY EDEMA, RASH, AND VENOUS VARICOSITIES IN A 52-YEAR-OLD MAN SO CHEST LA English DT Article C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV PULM DIS CRIT,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT RADIOL,SAN ANTONIO,TX 78284. RP ANZUETO, A (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PULM DIS SECT 111E,SAN ANTONIO,TX 78284, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1993 VL 103 IS 6 BP 1849 EP 1850 DI 10.1378/chest.103.6.1849 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA LF719 UT WOS:A1993LF71900039 PM 8404111 ER PT J AU RECTOR, TS JOHNSON, G DUNKMAN, WB DANIELS, G FARRELL, L HENRICK, A SMITH, B COHN, JN AF RECTOR, TS JOHNSON, G DUNKMAN, WB DANIELS, G FARRELL, L HENRICK, A SMITH, B COHN, JN TI EVALUATION BY PATIENTS WITH HEART-FAILURE OF THE EFFECTS OF ENALAPRIL COMPARED WITH HYDRALAZINE PLUS ISOSORBIDE DINITRATE ON QUALITY-OF-LIFE - V-HEFT-II SO CIRCULATION LA English DT Article DE CLINICAL TRIALS; QUALITY OF LIFE; HEART FAILURE; QUESTIONNAIRES AB Background. Two new questionnaires concerning the quality of life of patients with heart failure were used in a randomized, controlled trial to determine if the patients' perceptions of the effects of enalapril on their daily activities and sense of well-being were different from those of a group treated with hydralazine and isosorbide dinitrate. Methods and Results. The questionnaires were completed at baseline and at 3 months, 6 months, and subsequently every 6 months during follow-up, which averaged 2.5 years (range, 0.5-5.7 years). Data from the questionnaires were reliable as indicated by correlation coefficients between repeated baseline scores of 0.88 and 0.87. Both treatment groups showed a progressive deterioration in quality of life as measured by both questionnaires. The questionnaire scores of the two treatment groups were not significantly different at any follow-up visit. Furthermore, there were no differences between treatments among subgroups defined by baseline questionnaire scores, peak oxygen consumption, ejection fraction, previous vasodilator use, and plasma norepinephrine concentration. Conclusions. Although several factors may limit the generalization of these results, the lack of a difference with regard to patients' quality of life is an important consideration for the evaluation of the relative therapeutic efficacy of these vasodilators. C1 UNIV MINNESOTA,SCH MED,DIV CARDIOVASC,BOX 488 UMHC,420 DELAWARE ST SE,MINNEAPOLIS,MN 55455. VET AFFAIRS MED CTR,W HAVEN,CT. VET AFFAIRS MED CTR,PHILADELPHIA,PA. VET AFFAIRS MED CTR,MILWAUKEE,WI. VET AFFAIRS MED CTR,HINES,IL. VET AFFAIRS MED CTR,NASHVILLE,TN. NR 5 TC 73 Z9 72 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 JUN PY 1993 VL 87 IS 6 SU 6 BP 71 EP 77 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LG179 UT WOS:A1993LG17900010 ER PT J AU DUNKMAN, WB JOHNSON, GR CARSON, PE BHAT, G FARRELL, L COHN, JN AF DUNKMAN, WB JOHNSON, GR CARSON, PE BHAT, G FARRELL, L COHN, JN TI INCIDENCE OF THROMBOEMBOLIC EVENTS IN CONGESTIVE-HEART-FAILURE SO CIRCULATION LA English DT Article DE THROMBOEMBOLISM; STROKE; ANTICOAGULATION; ANTIPLATELETS ID IDIOPATHIC DILATED CARDIOMYOPATHY; CHRONIC ATRIAL-FIBRILLATION; ANTITHROMBOTIC THERAPY; NATURAL-HISTORY; ANTICOAGULANT-THERAPY; MYOCARDIAL-DISEASE; SYSTEMIC EMBOLISM; CARDIAC DISEASE; STROKE; RISK AB Background. The incidence of thromboembolism and the benefit of anticoagulation in congestive heart failure are controversial. Mdhods and Results. The data base provided by the Veterans Affairs Vasodilator-Heart Failure Trials (V-HeFT I and II) was examined retrospectively to address these issues. In V-HeFT I, 642 men with heart failure were followed an average of 2.28 years, providing 1,464 patient-years of follow-up. In V-HeFT II, 804 men were followed an average of 2.56 years, with 2,061 patient-years of follow-up. Mean left ventricular ejection fraction was 30% in V-HeFT I and 29% in V-HeFT II. Functional capacity was at the interface of classes II and III with a peak exercise oxygen consumption of 14.7 mL . kg-1 . min-1 in V-HeFT I and 13.7 mL . kg-1 . min-1 in V-HeFT II. Warfarin and antiplatelet agents were administered at the discretion of individual investigators. The incidence of all thromboembolic events during 1,068 patient-years without warfarin in V-HeFT I was 2.7/100 patient-years and during 1,188 patient-years in V-HeFT II was 2.1/100 patient-years and was not reduced in patients treated with warfarin. Patients experiencing events had a lower peak exercise oxygen consumption (p < 0.03 in V-HeFT I and p < 0.001 in V-HeFT II) and a lower mean ejection fraction (p=0.10 in V-HeFT I and p=0.07 in V-HeFT II). Atrial fibrillation was not associated with an increased risk of thromboembolic events. Conclusions. The incidence of thromboembolism and stroke in class II or III congestive heart failure is not high and may not be significantly reduced with warfarin treatment. Routine use of anticoagulants in patients with heart failure may not be justified. C1 VET AFFAIRS MED CTR,CINCINNATI,OH. VET AFFAIRS MED CTR,WASHINGTON,DC. VET AFFAIRS MED CTR,CTR COORDINATING,COOPERAT STUDIES PROGRAM,W HAVEN,CT. VET AFFAIRS MED CTR,MINNEAPOLIS,MN. UNIV PENN,SCH MED,DIV CARDIOVASC,PHILADELPHIA,PA 19104. GEORGETOWN UNIV,SCH MED,DIV CARDIOVASC,WASHINGTON,DC 20057. UNIV CINCINNATI,COLL MED,DIV CARDIOVASC,CINCINNATI,OH 45221. UNIV MINNESOTA,SCH MED,DIV CARDIOVASC,MINNEAPOLIS,MN 55455. RP DUNKMAN, WB (reprint author), VET AFFAIRS MED CTR,CARDIOL SECT 111C,PHILADELPHIA,PA 19104, USA. NR 59 TC 152 Z9 156 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 JUN PY 1993 VL 87 IS 6 SU 6 BP 94 EP 101 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LG179 UT WOS:A1993LG17900013 ER PT J AU CARSON, PE JOHNSON, GR DUNKMAN, WB FLETCHER, RD FARRELL, L COHN, JN AF CARSON, PE JOHNSON, GR DUNKMAN, WB FLETCHER, RD FARRELL, L COHN, JN TI THE INFLUENCE OF ATRIAL-FIBRILLATION ON PROGNOSIS IN MILD-TO-MODERATE HEART-FAILURE - THE V-HEFT STUDIES SO CIRCULATION LA English DT Article DE ENALAPRIL; PRAZOSIN; HYDRALAZINE ISOSORBIDE DINITRATE; VASODILATORS ID IDIOPATHIC DILATED CARDIOMYOPATHY; CONGESTIVE CARDIOMYOPATHY; MORTALITY; SURVIVAL; PREDICTION; EXERCISE AB Background. Atrial fibrillation occurs commonly in heart failure; however, its importance in terms of prognosis is controversial. Methods and Results. We assessed the relation of atrial fibrillation on first Holter monitor to morbidity and mortality in mild to moderate heart failure in 632 patients in the Veterans Affairs Vasodilator-Heart Failure Trial (V-HeFT) I and 795 patients in V-HeFT II. Ninety-nine patients in atrial fibrillation and 533 patients in sinus rhythm were followed for a mean of 2.5 years (range, 6 months to 5.7 years) in V-HeFT I; 107 patients in atrial fibrillation and 688 patients in sinus rhythm in V-HeFT II were followed for a mean of 2.5 years (range, 6 months to 5.0 years). V-HeFT I compared treatment with prazosin, hydralazine-isosorbide dinitrate, and placebo, whereas V-HeFT II compared hydralazine-isosorbide dinitrate with enalapril. Follow-up evaluations included serial Holter monitors, serial metabolic exercise testing, hospitalization data, and clinical examinations. In V-HeFT I, cumulative mortality at 2 years was 0.34 for patients with atrial fibrillation and 0.30 for patients in sinus rhythm (p=0.25). Overall cumulative mortality was 0.54 for atrial fibrillation patients and 0.64 for sinus rhythm patients (p=0.86). In V-HeFT II, cumulative mortality at 2 years was 0.20 for patients with atrial fibrillation and 0.21 for patients with sinus rhythm (p=0.68), and overall cumulative mortality was 0.46 for atrial fibrillation patients and 0.52 for those in sinus rhythm (p<0.46). Sudden death was not increased with atrial fibrillation in V-HeFT I patients (p=0.64) or in V-HeFT II (p=0.68). By multivariate analysis, the relative mortality risk for atrial fibrillation was 0.95 in V-HeFT I and 0.76 in V-HeFT II. Metabolic exercise testing, showed no significant difference in mean change in peak oxygen consumption between patients with atrial fibrillation and those with sinus rhythm in V-HeFT I and a slight decrease late in V-HeFT II. Hospitalization rate for heart failure was not increased in either study. The embolic event rate was not increased for atrial fibrillation patients: 3% versus 4.9% of patients in sinus rhythm (p=0.41) in V-HeFT I and 4.0% versus 6.0% in V-HeFT II patients (p=0.44). A secondary analysis compared mortality of patients in atrial fibrillation with that of patients in sinus rhythm on all Holters: Mortality was not increased overall (p=0.72 in V-HeFT I and p=0.35 in V-HeFT II). Conclusions. Atrial fibrillation does not increase major morbidity or mortality in mild to moderate heart failure. C1 VET AFFAIRS MED CTR, CTR COOPERAT STUDIES COORDINATING, West Haven, CT USA. VET AFFAIRS MED CTR, MINNEAPOLIS, MN USA. UNIV PENN, VET AFFAIRS MED CTR, PHILADELPHIA, PA 19104 USA. UNIV PENN, DIV CARDIOVASC, PHILADELPHIA, PA 19104 USA. RP CARSON, PE (reprint author), VET AFFAIRS MED CTR, DEPT CARDIOL, 50 IRVING ST NW, WASHINGTON, DC 20422 USA. NR 31 TC 224 Z9 227 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JUN PY 1993 VL 87 IS 6 SU 6 BP 102 EP 110 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LG179 UT WOS:A1993LG17900014 ER PT J AU DANG, H LAZARIDIS, K TALAL, N FISCHBACH, M SANZ, I AF DANG, H LAZARIDIS, K TALAL, N FISCHBACH, M SANZ, I TI CLONING OF A HUMAN-IGM AUTOANTIBODY BEARING A CROSS-REACTIVE IDIOTYPE IN A LAMBDA-EXPRESSION VECTOR - A NEW APPROACH TO STUDYING AUTOANTIBODIES SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTI-SM AUTOANTIBODY; INTERSPECIES IDIOTYPE; ESCHERICHIA-COLI; REPERTOIRE; DNA; ANTIBODIES; MICE; GENERATION; DIVERSITY C1 UNIV TEXAS,HLTH SCI CTR,RHEUMATOL SECT,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP DANG, H (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CLIN IMMUNOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIAID NIH HHS [AI 29003]; NIDCR NIH HHS [DE09311] NR 34 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD JUN PY 1993 VL 67 IS 3 BP 249 EP 256 DI 10.1006/clin.1993.1072 PN 1 PG 8 WC Immunology; Pathology SC Immunology; Pathology GA LF995 UT WOS:A1993LF99500010 PM 8500272 ER PT J AU JOHNSON, CC AF JOHNSON, CC TI SUSCEPTIBILITY OF ANAEROBIC-BACTERIA TO BETA-LACTAM ANTIBIOTICS IN THE UNITED-STATES SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 1ST NORTH AMERICAN CONGRESS ON ANAEROBIC BACTERIA AND ANAEROBIC INFECTIONS CY JUL 24-26, 1992 CL MARINA DEL REY, CA SP ABBOTT LABS ID BACTEROIDES-FRAGILIS GROUP; ANTIMICROBIAL AGENTS; INVITRO ACTIVITY; TICARCILLIN-CLAVULANATE; CEFOPERAZONE SULBACTAM; RESISTANCE; IMIPENEM; PIPERACILLIN; INHIBITORS; CEFOXITIN AB Beta-lactam antibiotics are critical agents in the treatment of anaerobic infections. Susceptibility to these agents, however, varies widely, depending on the specific drug and organism; has not been constant over time; and differs in various geographic locations within the United States for many species. For the organisms in the Bacteroides fragilis group, the beta-lactam antibiotics with the most consistent activity are imipenem and combinations of a beta-lactam drug plus a beta-lactamase inhibitor, such as ticarcillin/clavulanate and ampicillin/sulbactam. Antibiotics with less activity include cefoxitin, piperacillin, cefotetan, and ceftizoxime. In other species of anaerobic gram-negative bacilli, beta-lactamase production is seen with increasing frequency. In vitro susceptibility of these strains is now similar to that of the B. fragilis group, with imipenem, ticarcillin/clavulanate, ampicillin/sulbactam, and cefoxitin being the most active drugs. The anaerobic gram-positive cocci and bacilli remain, for the most part, highly susceptible to penicillins and imipenem. C1 DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA. RP JOHNSON, CC (reprint author), MED COLL PENN,3300 HENRY AVE,PHILADELPHIA,PA 19129, USA. NR 37 TC 16 Z9 16 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN PY 1993 VL 16 SU 4 BP S371 EP S376 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LE919 UT WOS:A1993LE91900045 PM 8324150 ER PT J AU TANNER, A STILLMAN, N AF TANNER, A STILLMAN, N TI ORAL AND DENTAL INFECTIONS WITH ANAEROBIC-BACTERIA - CLINICAL-FEATURES, PREDOMINANT PATHOGENS, AND TREATMENT SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 1ST NORTH AMERICAN CONGRESS ON ANAEROBIC BACTERIA AND ANAEROBIC INFECTIONS CY JUL 24-26, 1992 CL MARINA DEL REY, CA SP ABBOTT LABS ID NECROTIZING ULCERATIVE GINGIVITIS; TETRACYCLINE FIBER THERAPY; DNA PROBE DETECTION; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PERIODONTAL-DISEASE; EIKENELLA-CORRODENS; SUBGINGIVAL PLAQUE; LESIONS; PERICORONITIS; PROGRESSION AB Microbial populations colonizing the teeth are a major source of pathogens responsible for oral and dental infections, including periodontal diseases, gingivitis, pericoronitis, endodontitis, peri-implantitis, and postextraction infections. Each entity has distinct clinical and microbial features. Bacterial species associated with oral infections include Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus, Campylobacter rectus, Eubacterium species, Fusobacterium nucleatum, Eikenella corrodens, and Peptostreptococcus micros. Treponema pallidum-related spirochetes have been associated with acute necrotizing ulcerative gingivitis. Porphyronionas endodontalis appears to be specifically related to endodontic infections. Oral infections in medically compromised patients, including those with AIDS, are associated with similar species and are usually complicated by superinfection with enteric and Candida species. Isolation of species causing oral infections requires the collection of appropriate samples and the use of strictly anacrotic techniques. Rapid selective culture, immunofluorescence, and DNA probe methods have been developed for the identification of these oral species. The varied measures required in the management of oral and dental infections may include antimicrobial therapy. Accurate microbiological diagnosis, including antibiotic susceptibility testing, is indicated for cases that do not respond to therapy. C1 HARVARD UNIV,SCH DENT MED,BOSTON,MA 02115. RP TANNER, A (reprint author), FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE 04881, DE 10160, DE 09513] NR 54 TC 22 Z9 23 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN PY 1993 VL 16 SU 4 BP S304 EP S309 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LE919 UT WOS:A1993LE91900027 PM 8324136 ER PT J AU ZARINS, B MCMAHON, MS ROWE, CR AF ZARINS, B MCMAHON, MS ROWE, CR TI DIAGNOSIS AND TREATMENT OF TRAUMATIC ANTERIOR INSTABILITY OF THE SHOULDER SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PUTTI-PLATT; DISLOCATION; BANKART AB Traumatic anterior glenohumeral joint dislocation is the most common type of shoulder instability. Lesions that usually result are avulsion of the anterior capsule and glenoid labrum from the glenoid rim (Bankart lesion), compression fracture of the posterosuperior humeral head (Hill-Sachs lesion), and laxity of the joint capsule. Another common lesion is a lengthwise disruption of the rotator cuff at the interval between the subscapularis and supraspinatus tendons. The shoulder that dislocates repeatedly after trauma has an excellent success rate when treated by surgical repair. The aim of the Bankart procedure is to restore stability to the shoulder by repairing the traumatic lesion of the anterior glenoid rim without altering normal anatomy. RP ZARINS, B (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPAED SURG SERV,BOSTON,MA 02214, USA. NR 45 TC 35 Z9 35 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUN PY 1993 IS 291 BP 75 EP 84 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA LF224 UT WOS:A1993LF22400009 PM 8504617 ER PT J AU RAAFAT, NA LEE, MJ DAWSON, SL MUELLER, PR AF RAAFAT, NA LEE, MJ DAWSON, SL MUELLER, PR TI CASE-REPORT - COMBINED CONSERVATIVE AND PERCUTANEOUS MANAGEMENT OF A PERFORATED DUODENAL-ULCER SO CLINICAL RADIOLOGY LA English DT Article ID NONOPERATIVE TREATMENT; PEPTIC-ULCER; DRAINAGE; DISEASE AB A case is presented of perforated duodenal ulcer with associated abscesses treated by percutaneous drainage in a patient with markedly impaired respiratory function. The potential role of conservative management in such patients is discussed. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 10 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD JUN PY 1993 VL 47 IS 6 BP 426 EP 428 DI 10.1016/S0009-9260(05)81066-9 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LF346 UT WOS:A1993LF34600011 PM 8519152 ER PT J AU REYNOLDS, EM RYAN, DP DOODY, DP AF REYNOLDS, EM RYAN, DP DOODY, DP TI PERMISSIVE HYPERCAPNIA AND PRESSURE-CONTROLLED VENTILATION AS TREATMENT OF SEVERE ADULT RESPIRATORY-DISTRESS SYNDROME IN A PEDIATRIC BURN PATIENT SO CRITICAL CARE MEDICINE LA English DT Note DE ADULT RESPIRATORY DISTRESS SYNDROME; INTERMITTENT POSITIVE-PRESSURE VENTILATION; HYPERCAPNIA; ANOXEMIA; PEDIATRICS; BURNS; CRITICAL CARE; PULMONARY EMERGENCIES; MECHANICAL VENTILATION ID LUNG-FUNCTION; FAILURE; MORTALITY; INJURY; CHILDREN; SURVIVAL; ECMO C1 MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 18 TC 8 Z9 8 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 1993 VL 21 IS 6 BP 944 EP 947 DI 10.1097/00003246-199306000-00027 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA LG494 UT WOS:A1993LG49400027 PM 8504665 ER PT J AU MUDHAR, HS POLLOCK, RA WANG, CY STILES, CD RICHARDSON, WD AF MUDHAR, HS POLLOCK, RA WANG, CY STILES, CD RICHARDSON, WD TI PDGF AND ITS RECEPTORS IN THE DEVELOPING RODENT RETINA AND OPTIC-NERVE SO DEVELOPMENT LA English DT Article DE PDGF; PDGF RECEPTORS; RETINA; OPTIC NERVE; NEURONS; GLIAL CELLS; BLOOD VESSELS; INSITU HYBRIDIZATION; IMMUNOHISTOCHEMISTRY; RAT; MOUSE ID GROWTH-FACTOR; OLIGODENDROCYTE DEVELOPMENT; PROGENITOR CELLS; GENE-EXPRESSION; GANGLION-CELLS; DIFFERENTIATION; NEURONS; CHAIN; CEREBELLUM; ASTROCYTES AB We have used in situ hybridization to visualize cells in the developing rat retina and optic nerve that express mRNAs encoding the A and B chains of platelet-derived growth factor (PDGF-A and PDGF-B), and the alpha and beta subunits of the PDGF receptor (PDGF-alphaR and PDGF-betaR). We have also visualized PDGF-A protein in these tissues by immunohistochemistry. In the retina, PDGF-A mRNA is present in pigment epithelial cells, ganglion neurons and a subset of amacrine neurons. PDGF-A transcripts accumulate in ganglion neurons during target innervation and in amacrine neurons around the time of eye opening, suggesting that PDGF-A expression in these cells may be regulated by target-derived signals or by electrical activity. In the mouse retina, PDGF-A immunoreactivity is present in the cell bodies, dendrites and proximal axons of ganglion neurons, and throughout the inner nuclear layer. PDGF-alphaR mRNA is expressed in the retina by astrocytes in the optic fibre layer and by a subset of cells in the inner nuclear layer that might be Muller glia or bipolar neurons. Taken together, our data suggest short-range paracrine interactions between PDGF-A and PDGF-alphaR, the ligand and its receptor being expressed in neighbouring layers of cells in the retina. In the optic nerve, PDGF-A immunoreactivity is present in astrocytes but apparently not in the retinal ganglion cell axons. PDGF-alphaR+ cells in the optic nerve first appear near the optic chiasm and subsequently spread to the retinal end of the nerve; these PDGF-alphaR+ cells are probably oligodendrocyte precursors (Pringle et al., 1992). RNA transcripts encoding PDGF-B and PDGF-betaR are expressed by cells of the hyaloid and mature vascular systems in the eye and optic nerve. C1 UNIV LONDON UNIV COLL,DEPT BIOL,MEDAWAR BLDG,LONDON WC1E 6BT,ENGLAND. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RI Richardson, William/C-1762-2008 OI Richardson, William/0000-0001-7261-2485 FU Wellcome Trust NR 51 TC 124 Z9 127 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 1993 VL 118 IS 2 BP 539 EP 552 PG 14 WC Developmental Biology SC Developmental Biology GA LH327 UT WOS:A1993LH32700021 PM 8223278 ER PT J AU PUGH, JA JACOBSON, JM VANHEUVEN, WAJ WATTERS, JA TULEY, MR LAIRSON, DR LORIMOR, RJ KAPADIA, AS VELEZ, R AF PUGH, JA JACOBSON, JM VANHEUVEN, WAJ WATTERS, JA TULEY, MR LAIRSON, DR LORIMOR, RJ KAPADIA, AS VELEZ, R TI SCREENING FOR DIABETIC-RETINOPATHY - THE WIDE-ANGLE RETINAL CAMERA SO DIABETES CARE LA English DT Article ID MYDRIATIC FUNDUS PHOTOGRAPHY AB OBJECTIVE- To define the test characteristics of four methods of screening for diabetic retinopathy. RESEARCH DESIGN AND METHODS - Four screening methods (an exam by an ophthalmologist through dilated pupils using direct and indirect ophthalmoscopy, an exam by a physician's assistant through dilated pupils using direct ophthalmoscopy, a single 45-degrees retinal photograph without pharmacological dilation, and a set of three dilated 45-degrees retinal photographs) were compared with a reference standard of stereoscopic 30-degrees retinal photographs of seven standard fields read by a central reading center. Sensitivity, specificity, and positive and negative likelihood ratios were calculated after dichotomizing the retinopathy levels into none and mild nonproliferative versus moderate to severe nonproliferative and proliferative. Two sites were used. All patients with diabetes in a VA hospital outpatient clinic between June 1988 and May 1989 were asked to participate. Patients with diabetes identified from a laboratory list of elevated serum glucose values were recruited from a DOD medical center. RESULTS- The subjects (352) had complete exams excluding the exam by the physician's assistant that was added later. The sensitivities, specificities, and positive and negative likelihood ratios are as follows: ophthalmologist 0.33, 0.99, 72, 0.67; photographs without pharmacological dilation 0.61, 0.85, 4.1, 0.46; dilated photographs 0.81, 0.97, 24, 0.19; and physician's assistant 0.14, 0.99, 12, 0.87. CONCLUSIONS- Fundus photographs taken by the 45-degrees camera through pharmacologically dilated pupils and read by trained readers perform as well as ophthalmologists for detecting diabetic retinopathy. Physician extenders can effectively perform the photography with minimal training but would require more training to perform adequate eye exams. In this older population, many patients did not obtain adequate nonpharmacological dilation for use of the 45-degrees camera. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GEN MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT OPHTHALMOL,SAN ANTONIO,TX 78284. USAF,WILFORD HALL MED CTR,LACKLAND AFB,TX 78236. RP PUGH, JA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. OI Pugh, Jacqueline/0000-0003-4933-141X NR 28 TC 91 Z9 93 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 1993 VL 16 IS 6 BP 889 EP 895 DI 10.2337/diacare.16.6.889 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LD942 UT WOS:A1993LD94200004 PM 8100761 ER PT J AU MEYER, TE HABENER, JF AF MEYER, TE HABENER, JF TI CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE RESPONSE ELEMENT-BINDING PROTEIN (CREB) AND RELATED TRANSCRIPTION-ACTIVATING DEOXYRIBONUCLEIC ACID-BINDING PROTEINS SO ENDOCRINE REVIEWS LA English DT Review ID LEUCINE ZIPPER PROTEINS; NUCLEAR FACTOR CREB; STEROID-RECEPTOR SUPERFAMILY; SIGNAL-TRANSDUCTION PATHWAYS; INDUCIBLE ENHANCER ELEMENTS; ATF CDNA CLONES; DNA-BINDING; SOMATOSTATIN GENE; KINASE-C; REPRESSES TRANSCRIPTION C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC ENDOCRINOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. FU NIDDK NIH HHS [DK-30457, R01 DK-25532] NR 169 TC 467 Z9 471 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 1993 VL 14 IS 3 BP 269 EP 290 DI 10.1210/er.14.3.269 PG 22 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LF282 UT WOS:A1993LF28200002 PM 8319595 ER PT J AU WEISS, J CROWLEY, WF HALVORSON, LM JAMESON, JL AF WEISS, J CROWLEY, WF HALVORSON, LM JAMESON, JL TI PERIFUSION OF RAT PITUITARY-CELLS WITH GONADOTROPIN-RELEASING-HORMONE, ACTIVIN, AND INHIBIN REVEALS DISTINCT EFFECTS ON GONADOTROPIN GENE-EXPRESSION AND SECRETION SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; RIBONUCLEIC-ACID LEVELS; LUTEINIZING-HORMONE; ALPHA; TRANSCRIPTION; RESPONSES; FREQUENCY; PROTEINS; SUBUNITS; RECEPTOR AB Gonadotropin biosynthesis and secretion are influenced by pulsatile GnRH derived from the hypothalamus as well as by paracrine factors. In the current studies, we compared the effects of inhibin, activin, and GnRH, alone and in combination, on gonadotropin subunit messenger RNA (mRNA) levels and gonadotropin secretion. A pituitary perifusion system was used to allow GnRH to be administered as pulses and to minimize paracrine effects. FSHbeta mRNA levels were increased 25-fold by a maximal concentration of activin (3 ng/ml) and suppressed 83% by a maximal concentration of inhibin (30 ng/ml). When activin and inhibin were perifused together, inhibin attenuated the effects of maximal activin stimulation in a concentration-dependent manner, with a 10-fold excess of inhibin required to block the effects of activin entirely. Whole cell receptor assays using I-125-labeled activin confirmed that the inhibin used in the perifusion experiments competed for activin binding sites, although with a lower affinity. Direct competition at the activin receptor may thus account for part of the activin/inhibin antagonism observed at the level of FSHbeta mRNA. Neither activin nor inhibin had a significant effect on levels of LHbeta or a mRNAs. Hourly pulses of 10 nM GnRH elicited a 2- to 5-fold increase in FSHbeta mRNA. This increment was maintained in the presence of activin and inhibin, suggesting separate, but dependent, mechanisms of action for GnRH vs. inhibin and activin. In studies of secretion, continuous activin stimulation (3 ng/ml) elicited only a small (approximately 30%) increase in basal FSH secretion. However, the response of FSH to pulses of GnRH was amplified 3-fold in the presence of activin. A similar enhancement of GnRH-induced, but not basal, LH release was also observed. Inhibin, in contrast, elicited no changes in basal or GnRH-stimulated release of FSH or LH. We conclude that activin and inhibin are the primary regulators of FSHbeta mRNA levels, whereas GnRH appears to be the major effector for gonadotropin secretion. There is significant functional overlap, however, and the combined actions of activin, inhibin, and GnRH determine the final level of FSHbeta mRNA and the pattern of gonadotropin secretion. C1 MASSACHUSETTS GEN HOSP, DEPT MED, THYROID UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RP WEISS, J (reprint author), MASSACHUSETTS GEN HOSP, DEPT MED, REPROD ENDOCRINE UNIT, BHX-5, BOSTON, MA 02114 USA. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [R01 HD015788, P30 HD-28138, U54 HD-29164] NR 33 TC 87 Z9 88 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1993 VL 132 IS 6 BP 2307 EP 2311 DI 10.1210/en.132.6.2307 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LE170 UT WOS:A1993LE17000006 PM 8504735 ER PT J AU ELLIOTT, ME GOODFRIEND, TL AF ELLIOTT, ME GOODFRIEND, TL TI MECHANISM OF FATTY-ACID INHIBITION OF ALDOSTERONE SYNTHESIS BY BOVINE ADRENAL GLOMERULOSA CELLS SO ENDOCRINOLOGY LA English DT Article ID GLUCOCORTICOID RECEPTORS; BINDING; SECRETION; RAT AB Previous work from this laboratory has suggested that the adrenal glomerulosa is under tonic inhibition by fatty acids. The purpose of the present work was to define the mechanism by which fatty acids inhibit aldosterone synthesis. Experiments with isolated bovine adrenocortical cells showed the following. 1) Fatty acids inhibited angiotensin-II-stimulated and (Bu)2cAMP-stimulated aldosterone synthesis with similar potencies. 2) Inhibition of aldosterone synthesis was highly dependent on fatty acid chain length and degree of unsaturation as well as on configuration of double bonds. Oleic acid was the most potent inhibitor among fatty acids prominent in plasma. 3) Cortisol synthesis was less sensitive to oleic acid inhibition than was aldosterone synthesis. 4) Pregnenolone synthesis by angiotensin-II-stimulated adrenal glomerulosa cells was relatively insensitive to oleic acid. 5) For both glomerulosa and fasciculata cells, cortisol synthesis from 21-deoxycortisol, which requires the participation of P450(21), was relatively insensitive to fatty acids. Cortisol synthesis from corticosterone by fasciculata cells, which requires the participation of P450(17alpha), was also insensitive to oleic acid. These are microsomal enzymes. 6) In glomerulosa cells, aldosterone synthesis from added corticosterone, which requires the 18-oxidase function of P450(11beta), a mitochondrial enzyme, was potently inhibited by fatty acids; cortisol synthesis from 11-deoxycortisol by glomerulosa cells, which requires P450(11beta), was less sensitive to inhibition, and cortisol synthesis from 11-deoxycortisol by fasciculata cells was even less sensitive. 7) Aldosterone synthesis from exogenous 18-hydroxycorticosterone was potently inhibited by oleic acid. Thus, fatty acids are potent inhibitors of the 18-oxidase function of the mitochondrial enzyme P450(11beta), whereas nonmitochondrial steroidogenic enzymes and the 11-hydroxylase function of P450(11beta) are relatively insensitive to fatty acids. The special sensitivity of aldosterone synthesis to fatty acid inhibition appears to result from the unusual susceptibility of the 18-oxidase function of the mitochondrial steroidogenic enzyme P450(11beta). This mechanism would allow differential regulation of aldosterone vs. cortisol production by unesterified fatty acids. C1 UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,SCH MED,DEPT PHARMACOL,MADISON,WI 53706. RP ELLIOTT, ME (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,HYPERTENS RES LAB,ROOM C4114,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 16 TC 14 Z9 14 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 JUN PY 1993 VL 132 IS 6 BP 2453 EP 2460 DI 10.1210/en.132.6.2453 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LE170 UT WOS:A1993LE17000024 PM 8504749 ER PT J AU NUSSBAUM, SR AF NUSSBAUM, SR TI PATHOPHYSIOLOGY AND MANAGEMENT OF SEVERE HYPERCALCEMIA SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID HORMONE-RELATED PROTEIN; CANCER-ASSOCIATED HYPERCALCEMIA; BONE-RESORPTION INVITRO; MALIGNANCY-ASSOCIATED HYPERCALCEMIA; INTRAVENOUS ETIDRONATE DISODIUM; PARATHYROID-HORMONE; HUMORAL HYPERCALCEMIA; AMINOHYDROXYPROPYLIDENE DIPHOSPHONATE; HUMAN-TUMOR; PRIMARY HYPERPARATHYROIDISM C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP NUSSBAUM, SR (reprint author), MASSACHUSETTS GEN HOSP,MED SERV,ENDOCRINE UNIT,BOSTON,MA 02114, USA. NR 93 TC 30 Z9 30 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD JUN PY 1993 VL 22 IS 2 BP 343 EP 362 PG 20 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LH883 UT WOS:A1993LH88300011 PM 8325291 ER PT J AU ABBATE, M BACHINSKY, D ZHENG, G STAMENKOVIC, I MCLAUGHLIN, M NILES, JL MCCLUSKEY, RT BROWN, D AF ABBATE, M BACHINSKY, D ZHENG, G STAMENKOVIC, I MCLAUGHLIN, M NILES, JL MCCLUSKEY, RT BROWN, D TI LOCATION OF GP330/ALPHA-2-M RECEPTOR-ASSOCIATED PROTEIN (ALPHA-2-MRAP) AND ITS BINDING-SITES IN KIDNEY - DISTRIBUTION OF ENDOGENOUS ALPHA-2-MRAP IS MODIFIED BY TISSUE PROCESSING SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE IMMUNOCYTOCHEMISTRY; GP330; ALPHA-2-MACROGLOBULIN RECEPTOR-ASSOCIATED PROTEIN; REDISTRIBUTION; KIDNEY ID DENSITY-LIPOPROTEIN RECEPTOR; HEYMANN NEPHRITIS ANTIGEN; BRUSH-BORDER ANTIGENS; ALPHA-2-MACROGLOBULIN RECEPTOR; MONOCLONAL-ANTIBODIES; MEMBRANE GLYCOPROTEIN; EPITHELIAL-CELLS; PROXIMAL TUBULES; INVARIANT CHAIN; LDL RECEPTOR AB The alpha2-macroglobulin receptor-associated protein (alpha2-MRAP) is a 39 to 44 kDa protein that copurifies with the alpha2-macroglobulin receptor (alpha2-MR/LRP) and also with gp330, a highly glycosylated protein located within kidney proximal tubules and glomerular podocytes. Both gp330 and the alpha2-macroglobulin receptor are members of the low density lipoprotein receptor family but the physiological ligands for gp330 are unknown. In order to understand potential functions of the alpha2-MRAP, specific anti-alpha2-MRAP antibodies were used for immunocytochemical studies on paraformaldehyde lysine periodate (PLP)-fixed rat kidneys and on snap-frozen/acetone-fixed tissue. Conflicting results were obtained. After PLP fixation, alpha2-MRAP was detected almost exclusively in rough endoplasmic reticulum (RER) cisternae; cell surface staining was virtually absent. In snap-frozen tissue, intense staining of the proximal tubule brush border was found, with little or no cytoplasmic staining. A series of experiments showed that during incubation of snap-frozen tissues, endogenous alpha2-MRAP is released in soluble form from its intracellular location (i.e., the RER) and binds to gp330 on the brush border of proximal tubules. The location of binding sites for alpha2-MRAP in rat kidney was also examined, using an alpha2-MRAP-IgG fusion protein. In both snap-frozen and PLP-fixed tissues, this probe bound exclusively to brush borders, and not to intracellular sites. Our results demonstrate: a) that in renal proximal tubule cells, alpha2-MRAP is located predominantly in the RER, b) that alpha2-MRAP-binding sites are present on gp330, which is on the proximal tubule brush border, and c) that the apparent brush border localization of alpha2-MRAP detected in snap-frozen sections is due to an artifactual redistribution of endogenous alpha2-MRAP that occurs during tissue processing. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,149 13TH ST,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL & GENET,BOSTON,MA 02129. FU NIDDK NIH HHS [DK42956, DK 37807-22] NR 37 TC 55 Z9 55 U1 0 U2 0 PU WISSENSCHAFTLICHE VERLAG MBH PI STUTTGART PA BIRKENWALDSTRASSE 44, POSTFACH 10 10 61, 70009 STUTTGART, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD JUN PY 1993 VL 61 IS 1 BP 139 EP 149 PG 11 WC Cell Biology SC Cell Biology GA LM961 UT WOS:A1993LM96100016 PM 8223699 ER PT J AU JONDAL, M OKRET, S MCCONKEY, D AF JONDAL, M OKRET, S MCCONKEY, D TI KILLING OF IMMATURE CD4+CD8+ THYMOCYTES INVIVO BY ANTI-CD3 OR 5'-(N-ETHYL)-CARBOXAMIDO-ADENOSINE IS BLOCKED BY GLUCOCORTICOID RECEPTOR ANTAGONIST RU-486 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE THYMOCYTE; APOPTOSIS; GLUCOCORTICOID; CAMP; T-CELL RECEPTOR ID PROTEIN KINASE-C; DNA FRAGMENTATION; DEATH APOPTOSIS; T-CELLS; STIMULATION; ACTIVATION; SELECTION; COMPLEX; INVITRO; CULTURE AB Negative selection in thymus occurs by apoptosis in CD4+CD8+ cells. These immature thymocytes are readily killed, both in vitro and in vivo, by glucocorticoid treatment. Increased levels of intracellular cAMP in vitro also induce apoptosis of thymocytes and T cell receptor (TcR) stimulation potentiate cAMP responses through receptors linked to adenylic cyclase. Presently, we have tested the possibility that TcR-mediated apoptosis in vivo may require the glucocorticoid receptor (GR) as a downstream, intracellular mediator. Use of the GR antagonist RU-486, 24 h before and simultaneous with, anti-CD3 or 5'-(N-ethyl)-carboxamide-adenosine (NECA) treatment, resulted in a selective inhibition of CD4+CD8+ thymocyte death. In addition, a low dose of glucocorticoid potentiated thymocyte death induced by anti-CD3 monoclonal antibodies. These data support a model in which thymic negative selection depends on a defined set of transduction signals which potentiate the GR to become responsive to endogenous levels of glucocorticoid. C1 KAROLINSKA INST,DEPT MED NUTR,S-10401 STOCKHOLM 60,SWEDEN. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP JONDAL, M (reprint author), KAROLINSKA INST,DEPT IMMUNOL,S-10401 STOCKHOLM 60,SWEDEN. NR 31 TC 81 Z9 82 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 1993 VL 23 IS 6 BP 1246 EP 1250 DI 10.1002/eji.1830230608 PG 5 WC Immunology SC Immunology GA LG517 UT WOS:A1993LG51700007 PM 8099013 ER PT J AU CUFF, CF CEBRA, CK RUBIN, DH CEBRA, JJ AF CUFF, CF CEBRA, CK RUBIN, DH CEBRA, JJ TI DEVELOPMENTAL RELATIONSHIP BETWEEN CYTOTOXIC ALPHA/BETA T-CELL RECEPTOR-POSITIVE INTRAEPITHELIAL LYMPHOCYTES AND PEYER PATCH LYMPHOCYTES SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE REOVIRUS; INTRAEPITHELIAL LYMPHOCYTES; PEYER PATCH LYMPHOCYTES; CYTOTOXIC T-CELLS ID MURINE INTESTINAL EPITHELIUM; NATURAL-KILLER CELLS; MONOCLONAL-ANTIBODY; LAMINA PROPRIA; GAMMA-DELTA; REOVIRUS; DIFFERENTIATION; POPULATIONS; FREQUENCIES; PRECURSORS AB Following intraduodenal priming of mice with reovirus, precursor cytotoxic T lymphocytes (pCTL) rapidly appear in intraepithelial lymphocytes (IEL) and Peyer's patches. These cells express CTL activity after secondary in vitro stimulation with reovirus-infected cells. Adoptive transfer of Peyer's patch lymphocytes from normal BALB/c mice into reovirus-infected CB. 17 severe combined immunodeficiency mice results in the infection-dependent appearance of large numbers of both CD8+Thy-l+ and CD8-Thy-l+, IEL that express the alpha/beta T cell receptor (TcR). Phenotypic and functional characterization of IEL derived from conventionally reared, reovirus-infected mice also points to extensive similarities in the pCTL derived from Peyer's patches and IEL. As in the Peyer's patches, pCTL are persistent in the IEL compartment for up to 4 weeks after infection. A large percentage of IEL that are recovered from reovirus-primed mice after in vitro culture are CD8+Thy-1+ cells that express alpha/beta TcR. Furthermore, depletion experiments demonstrate that the CD8+Thy-1+ population mediates the virus-specific CTL activity. Using limiting dilution analyses, it was estimated that 7 days after intraduodenal infection the average frequency of virus-specific pCTL was 197/10(6) CD8+Thy-l+ IEL and 190/10(6) CD8+Thy-l+ Peyer's patch lymphocytes. Taken together, these observations provide evidence that specific cellular immunity to reovirus in IEL is mediated, at least in part, by conventional cytotoxic T lymphocytes and that these cells are functionally and phenotypically similar to the pCTL derived from the Peyer's patches. C1 UNIV PENN,DEPT BIOL,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. UNIV PENN,DEPT MICROBIOL,PHILADELPHIA,PA 19104. FU NCI NIH HHS [T-32-CA-09140]; NIAID NIH HHS [AI-17997, AI-23970] NR 36 TC 62 Z9 62 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 1993 VL 23 IS 6 BP 1333 EP 1339 DI 10.1002/eji.1830230622 PG 7 WC Immunology SC Immunology GA LG517 UT WOS:A1993LG51700021 PM 8388798 ER PT J AU PASCUAL, M CATANA, E WHITE, T SPIEGELMAN, BM SCHIFFERLI, JA AF PASCUAL, M CATANA, E WHITE, T SPIEGELMAN, BM SCHIFFERLI, JA TI INHIBITION OF COMPLEMENT ALTERNATIVE PATHWAY IN MICE WITH FAB ANTIBODY TO RECOMBINANT ADIPSIN FACTOR-D SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Note DE COMPLEMENT; ALTERNATIVE PATHWAY; ADIPSIN; FACTOR-D ID IMMUNE ADHERENCE; INVIVO; COMPLEXES; PROTEINS AB Mouse adipsin is a serine protease secreted mainly by adipocytes. Similarly to factor D of human complement, it cleaves factor B. That adipsin is the equivalent of human factor D in the mouse is further suggested by their structural homology. Specific antisera against recombinant mouse adipsin (r-adipsin) were produced in rabbits. Anti-r-adipsin IgG was shown to bind to radiolabeled r-adipsin and to inhibit its hemolytic activity. In vitro, these antibodies Ab and Fab fragments thereof inhibited the adipsin/factor D hemolytic activity of mouse serum. They also blocked C3 activation induced by cobra venom factor (CVF), but did not interfere with classical pathway function. After intravenous injection of anti-r-adipsin Fab into BALB/c mice, the adipsin/factor D hemolytic activity of serum was abolished during a 4-h period. The C3 depleting effect of CVF injected intravenously was significantly delayed in BALB/c mice which had been pretreated with anti-r-adipsin Fab. These experiments demonstrate that mouse adipsin is the only form of mouse factor D and that anti-r-adipsin antibody can be used to produce a specific inhibition of the alternative pathway in vivo. C1 SCIOS NOVA INC,MT VIEW,CA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP PASCUAL, M (reprint author), CTR MED UNIV GENEVA,IMMUNONEPHROL LAB 5222,1 RUE MICHEL SERVET,CH-1211 GENEVA 4,SWITZERLAND. NR 19 TC 10 Z9 11 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 1993 VL 23 IS 6 BP 1389 EP 1392 DI 10.1002/eji.1830230632 PG 4 WC Immunology SC Immunology GA LG517 UT WOS:A1993LG51700031 PM 8500532 ER PT J AU YEE, WM FRIM, DM ISACSON, O AF YEE, WM FRIM, DM ISACSON, O TI RELATIONSHIPS BETWEEN STRESS PROTEIN INDUCTION AND NMDA-MEDIATED NEURONAL DEATH IN THE ENTORHINAL CORTEX SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE UBIQUITIN; HEAT SHOCK PROTEIN 72KD; C-FOS; ENTORHINAL CORTEX; NMDA; NEURONAL LOSS; ALZHEIMERS DISEASE; STRESS PROTEIN; NEURODEGENERATION; NEUROTOXICITY; RAT ID HEAT-SHOCK PROTEIN; C-FOS EXPRESSION; PAIRED HELICAL FILAMENTS; EXCITATORY AMINO-ACIDS; ALZHEIMERS-DISEASE; GROWTH-FACTOR; NEUROFIBRILLARY TANGLES; TAU-IMMUNOREACTIVITY; GEL-ELECTROPHORESIS; TRANSIENT ISCHEMIA AB The entorhinal cortex (EC) appears to be one of the earliest regions to express cellular pathology in aging and Alzheimer's disease. The relationships between cellular stress protein responses and the temporal and spatial aspects of cell death induced by N-methyl-D-aspartate (NMDA) was investigated in this anatomical region. Low doses of NMDA were infused stereotactically into the medial EC of the rat. At intervals starting from 0.5 h up to 7 days after a 1.25-mul EC infusion of 15 mM NMDA, 30 mM NMDA, or saline, the expression of ubiquitin (Ub), 72-kDa heat shock protein (HSP 72), and c-Fos was determined in relation to neuronal death. Volumes of entorhinal Ub- and HSP 72-like immunoreactivity peaked between 18 and 48 h after either 15 or 30 mM NMDA infusions. After 15 mM NMDA infusions, maximal volumes of HSP 72- and Ub-like immunoreactivity in the EC at 48 h were similar to the subsequent maximal volume of neuronal loss in the EC seen after 96 hours. After infusion of 30 mM NMDA, the final EC volume of neuronal loss seen at 7 days after NMDA corresponded to 70-80% of the maximal HSP-Ub stress protein response seen at 2 days, implying that a population of HSP 72- and Ub-immunopositive cells survived the NMDA insult. C-Fos expression as determined by immunoreactivity for the nuclear phosphoprotein (Fos) indicated neuronal activation at NMDA infusion sites, in the perirhinal cortex, hippocampus, and other sites throughout the injected hemisphere. In the EC, c-Fos immunoreactivity returned to baseline levels by 8 h, well before the dramatic increases in HSP 72 and Ub volumes. Our results demonstrate that HSP 72 and Ub expression in vivo precedes and correlates with, but does not necessarily lead to, neuronal death following glutamate receptor-mediated toxicity in the EC. C1 MCLEAN HOSP, NEUROREGENERAT LAB, BELMONT, MA 02178 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROSURG, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, NEUROSCI PROGRAM, BOSTON, MA 02115 USA. FU NINDS NIH HHS [NINDS 5T32 NS07340-02, NS29178] NR 66 TC 25 Z9 27 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 EI 1432-1106 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUN PY 1993 VL 94 IS 2 BP 193 EP 202 PG 10 WC Neurosciences SC Neurosciences & Neurology GA LH572 UT WOS:A1993LH57200002 PM 8395405 ER PT J AU DALEY, GQ GOLDMAN, JM AF DALEY, GQ GOLDMAN, JM TI AUTOLOGOUS TRANSPLANT FOR CML REVISITED SO EXPERIMENTAL HEMATOLOGY LA English DT Review DE CMG; STEM CELLS; AUTOGRAFTING ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; CHRONIC GRANULOCYTIC-LEUKEMIA; PHILADELPHIA-CHROMOSOME; HEMATOPOIETIC-CELLS; PROGENITOR CELLS; MARROW TRANSPLANTATION; INTERFERON-ALPHA; CHRONIC PHASE; BLAST CRISIS AB A chronic myelogenous leukemia (CML)-Like disease can be induced in mice by infecting hematopoietic stem cells with a BCR/ABL-containing retrovirus; serial transplantation produces either normal or leukemic animals. In many patients with CML, autografting produces transient Philadelphia chromosome (Ph)-negativity, but Ph-negative hematopoiesis is prolonged in some cases. These and other observations suggest that at diagnosis, CML patients may have substantial numbers of normal stem cells in their marrow, which may in certain circumstances regain a proliferative advantage if leukemic hematopoiesis can be suppressed by intensive chemotherapy. Thus autografting may have the capacity to restore normal hematopoiesis for long periods in patients not eligible for treatment by allogeneic bone marrow transplantation. C1 ROYAL POSTGRAD MED SCH,DEPT HAEMATOL,LONDON W12 0NN,ENGLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 36 TC 38 Z9 38 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUN PY 1993 VL 21 IS 6 BP 734 EP 737 PG 4 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW611 UT WOS:A1993MW61100002 PM 8500574 ER PT J AU WULLNER, U BROUILLET, E ISACSON, O YOUNG, AB PENNEY, JB AF WULLNER, U BROUILLET, E ISACSON, O YOUNG, AB PENNEY, JB TI GLUTAMATE-RECEPTOR BINDING-SITES IN MPTP-TREATED MICE SO EXPERIMENTAL NEUROLOGY LA English DT Note ID EXCITATORY AMINO-ACID; SUBTHALAMIC NUCLEUS; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; BASAL GANGLIA; GLOBUS-PALLIDUS; RAT; STRIATUM; NEURONS; N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,WARREN 408,FRUIT ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MCLEAN HOSP,NEUROREGENERAT LAB,BELMONT,MA 02178. RI Brouillet, Emmanuel/B-4784-2014 OI Brouillet, Emmanuel/0000-0001-6322-7403 FU NIA NIH HHS [AG08671]; NINDS NIH HHS [NS19613, NS30064] NR 25 TC 28 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUN PY 1993 VL 121 IS 2 BP 284 EP 287 DI 10.1006/exnr.1993.1098 PG 4 WC Neurosciences SC Neurosciences & Neurology GA LP257 UT WOS:A1993LP25700018 PM 8393409 ER PT J AU RAPOLD, HJ GOLD, HK WU, Z NAPIER, M BUNTING, S COLLEN, D AF RAPOLD, HJ GOLD, HK WU, Z NAPIER, M BUNTING, S COLLEN, D TI EFFECTS OF G4120, A ARG-GLY-ASP-CONTAINING SYNTHETIC PLATELET GLYCOPROTEIN IIB/IIIA-RECEPTOR ANTAGONIST, ON ARTERIAL AND VENOUS THROMBOLYSIS WITH RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR IN DOGS SO FIBRINOLYSIS LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; STREPTOKINASE-INDUCED THROMBOLYSIS; ANTIPLATELET GPIIB/IIIA ANTIBODY; CORONARY THROMBOLYSIS; MONOCLONAL-ANTIBODY; CANINE MODEL; INTRACORONARY STREPTOKINASE; F(AB')2 FRAGMENTS; RANDOMIZED TRIAL; THROMBOSIS AB The effects of G4120, L-cysteine, N-(mercaptoacetyl)-D-tyrosyl-L-arginylglycyl-L-alpha-aspartyl-cyclic(1->5)-sulfide, 5-oxide, a novel synthetic cyclic RGD-containing pentapeptide, on thrombolysis with rt-PA were investigated in a combined arterial and venous thrombosis model in the dog. In a blinded study, design dogs were randomly assigned to 0.5 mg/kg rt-PA+0.1 mg/kg G4120 (group I, n=5), 0.5 mg/kg rt-PA+placebo (II, n=5), 0.25 mg/kg rt-PA+0.1 mg/kg G4120 (III, n=5) or 0.25 mg/kg rt-PA+placebo (IV, n=5). Cyclic reflow and reocclusion occurred in 8 out of 10 animals given rt-PA alone versus 2 out of 10 dogs given rt-PA+G4120 (p<0.05). The patency status, classified as persistent patency, cyclic reflow with final patency and final occlusion was 51010, 2/3/0,3/1/1 and 0/1/4 for groups I to IV, respectively (p=0.006). Venous clot lysis was not altered by G4120. ADP-induced ex vivo platelet aggregation was completely inhibited during the infusion of G4120, and partially recovered 30 min (22+/-9% of baseline) and 90 min (38+/-15%) later. Bleeding times increased from 2.1+/-0.1 min at baseline to 26+/-2 min during G4120 infusion, and returned to 2.8+/-4 min within 90 min. Thus, G4120, a potent short-lived reversible platelet GPIIb/IIIa receptor antagonist, maintains arterial patency following recanalization with rt-PA. It may be useful for the prevention of reocclusion following thrombolytic therapy in patients with acute myocardial infarction. C1 CATHOLIC UNIV LEUVEN,CTR THROMBOSIS & VASC RES,CAMPUS GASTHUISBERG,O&N HERESTR 49,B-3000 LOUVAIN,BELGIUM. CATHOLIC UNIV LEUVEN,EXPTL CARDIOL LAB,B-3000 LOUVAIN,BELGIUM. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,BOSTON,MA 02114. GENENTECH INC,DEPT CARDIOVASC RES,S SAN FRANCISCO,CA 94080. NR 55 TC 12 Z9 12 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0268-9499 J9 FIBRINOLYSIS JI Fibrinolysis PD JUN PY 1993 VL 7 IS 4 BP 248 EP 256 DI 10.1016/0268-9499(93)90133-G PG 9 WC Hematology SC Hematology GA LL664 UT WOS:A1993LL66400006 ER PT J AU GRAHAM, DY LEW, GM LECHAGO, J AF GRAHAM, DY LEW, GM LECHAGO, J TI ANTRAL G-CELL AND D-CELL NUMBERS IN HELICOBACTER-PYLORI INFECTION - EFFECT OF HELICOBACTER-PYLORI ERADICATION SO GASTROENTEROLOGY LA English DT Article ID DUODENAL-ULCER PATIENTS; GASTRIC-ACID SECRETION; PEPTIC-ULCER; CAMPYLOBACTER-PYLORI; RESECTED STOMACHS; PLASMA GASTRIN; PARIETAL-CELLS; DISEASE; SERUM; HYPERGASTRINEMIA C1 VET AFFAIRS MED CTR,DEPT PATHOL,HOUSTON,TX. VET AFFAIRS MED CTR,DIV MOLEC VIROL,HOUSTON,TX. BAYLOR COLL MED,HOUSTON,TX 77030. RP GRAHAM, DY (reprint author), VET AFFAIRS MED CTR 111D,DEPT MED,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. FU NIDDK NIH HHS [DK 39919] NR 47 TC 77 Z9 79 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 1993 VL 104 IS 6 BP 1655 EP 1660 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LE468 UT WOS:A1993LE46800010 PM 8500723 ER PT J AU MOTOKURA, T ARNOLD, A AF MOTOKURA, T ARNOLD, A TI PRAD-1 CYCLIN-D1 PROTOONCOGENE - GENOMIC ORGANIZATION, 5' DNA-SEQUENCE, AND SEQUENCE OF A TUMOR-SPECIFIC REARRANGEMENT BREAKPOINT SO GENES CHROMOSOMES & CANCER LA English DT Article ID PARATHYROID-HORMONE GENE; ILLEGITIMATE RECOMBINATION EVENTS; CHROMOSOMAL TRANSLOCATION; CANDIDATE ONCOGENE; MOLECULAR ANALYSIS; CELL-CYCLE; B-CELL; EXPRESSION; DELETIONS; CLONING AB PRADI (previously D11S287) is a putative proto-oncogene at 11q13, activated by overexpression through gene rearrangement or gene amplification in several types of human tumors including parathyroid adenomas, centrocytic lymphomas and other B-cell tumors with t(11;14), and breast cancers. PRADI (also CCNDI) encodes cyclin DI, which may regulate the G1-S phase transition in the cell cycle. Here, we report the cloning and characterization of the chromosomal PRADI/cyclin D1 gene and the sequence of its promoter region. The gene spans about 15 kb and has 5 exons; its promoter region has Sp1 binding sites and no obvious TATA box, characteristics of housekeeping genes and growth-regulating genes. Furthermore, an E2F binding motif present close to the major transcription start site may be involved in cell cycle-dependent expression of this gene. We also report the sequence of DNAs spanning joining regions of a reciprocal parathyroid hormone/PRADI gene rearrangement in a parathyroid adenoma. Comparison with normal sequences suggests that the rearrangement was not a simple break-and-ligate event, but rather involved multiple steps, including two microdeletions and a microinversion. Very short sequences conserved near the breakpoints and symmetrical elements in the eventually inverted DNA segment might have played a role in this illegitimate complex recombination, which may have similarities with a constitutional translocation in Duchenne muscular dystrophy. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,WELLMAN 5,FRUIT ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02114. FU NCI NIH HHS [CA55909]; NIDDK NIH HHS [DK11794] NR 45 TC 148 Z9 150 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUN PY 1993 VL 7 IS 2 BP 89 EP 95 DI 10.1002/gcc.2870070205 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA LE460 UT WOS:A1993LE46000004 PM 7687458 ER PT J AU BARDEN, RC KINSCHERFF, R GEORGE, W FLYER, R SEIDEL, JS HENDERSON, DP AF BARDEN, RC KINSCHERFF, R GEORGE, W FLYER, R SEIDEL, JS HENDERSON, DP TI EMERGENCY MEDICAL-CARE AND INJURY ILLNESS PREVENTION SYSTEMS FOR CHILDREN SO HARVARD JOURNAL ON LEGISLATION LA English DT Article ID CHILDHOOD INJURIES; PEDIATRIC-PATIENT; TRISS METHOD; TRAUMA; SERVICES; NEEDS AB Each year, thousands of children suffer accidental deaths because they do not receive appropriate emergency care. The authors of this Article present evidence that a concerted effort by state and federal legislators to implement emergency medical care systems and injury prevention programs would greatly reduce these needless deaths. C1 UNIV UTAH,SCH MED,SALT LAKE CITY,UT 84112. HAMLINE UNIV,SCH LAW,ST PAUL,MN 55104. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. ROPES & GRAY,BOSTON,MA. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,EMSC PROJECT,TORRANCE,CA 90509. HARVARD UNIV,SCH LAW & MED SOC,CAMBRIDGE,MA 02138. RP BARDEN, RC (reprint author), LINDQUIST & VENNUM,MINNEAPOLIS,MN, USA. NR 56 TC 2 Z9 2 U1 1 U2 1 PU HARVARD LAW SCHOOL PI CAMBRIDGE PA PUBLICATIONS CTR, CAMBRIDGE, MA 02138 SN 0017-808X J9 HARVARD J LEGIS JI Harv. J. Legis. PD SUM PY 1993 VL 30 IS 2 BP 461 EP 497 PG 37 WC Law SC Government & Law GA LK680 UT WOS:A1993LK68000006 ER PT J AU LEVINE, RA GARDNER, JC STUFFLEBEAM, SM FULLERTON, BC CARLISLE, EW FURST, M ROSEN, BR KIANG, NYS AF LEVINE, RA GARDNER, JC STUFFLEBEAM, SM FULLERTON, BC CARLISLE, EW FURST, M ROSEN, BR KIANG, NYS TI BINAURAL AUDITORY PROCESSING IN MULTIPLE-SCLEROSIS SUBJECTS SO HEARING RESEARCH LA English DT Article DE BRAIN-STEM AUDITORY EVOKED POTENTIALS; SOUND LATERALIZATION; MULTIPLE SCLEROSIS; MAGNETIC RESONANCE IMAGING; INTERAURAL DISCRIMINATION ID CENTRAL-NERVOUS-SYSTEM; EVOKED-POTENTIALS; CLICK LATERALIZATION; BRAIN; CAT; FIBERS AB In order to relate human auditory processing to physiological and anatomical experimental animal data, we have examined the interrelation-ships between behavioral, elecirophysiological and anatomical data obtained from human subjects with focal brainstem lesions. Thirty-eight subjects with multiple sclerosis were studied with tests of interaural time and level discrimination (just noticeable differences or jnds), brainstem auditory evoked potentials and magnetic resonance (MR) imaging. Interaural testing used two types of stimuli, high-pass ( > 4000 Hz) and low-pass ( < 1000 Hz) noise bursts. Abnormal time jnds (Tjnd) were far more common than abnormal level jnds (70% vs 11%); especially for the high-pass (Hp) noise (70% abnormal vs 40% abnormal for low-pass (Lp) noise). The HpTjnd could be abnormal with no other abnormalities; however, whenever the BAEPs, LpTjnd and/or level jnds were abnormal HpTjnd was always abnormal. Abnormal wave III amplitude was associated with abnormalities in both time jnds, but abnormal wave III latency with only abnormal HpTjnds. Abnormal wave V amplitude, when unilateral, was associated with a major HpTjnd abnormality, and, when bilateral, with both HpTjnd and LpTjnd major abnormalities. Sixteen of the subjects had their MR scans obtained with a uniform protocol and could be analyzed with objective criteria. In all four subjects with lesions involving the pontine auditory pathway, the BAEPs and both time jnds were abnormal. Of the twelve subjects with no lesions involving the pontine auditory pathway, all had normal BAEPs and level jnds, ten had normal LpTjnds, but only five had normal HpTjnds. We conclude that interaural time discrimination is closely related to the BAEPs and is dependent upon the stimulus spectrum. Redundant encoding of low-frequency sounds in the discharge patterns of auditory neurons, may explain why the HpTjnd is a better indicator of neural desynchrony than the LpTjnd. Encroachment of MS lesions upon the pontine auditory pathway always is associated with abnormal BAEPs and abnormal interaural time discrimination but may have normal interaural level discrimination. Our data provide one of the most direct demonstrations in humans of relationships among auditory performance, evoked potentials and anatomy. We present a model showing that many of these interrelationships can be readily interpreted using ideas developed from work on animals, even though these relationships could not have been predicted with confidence beforehand. This work provides a clear advance in our understanding of human auditory processing and should serve as a basis for future studies. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MIT,CAMBRIDGE,MA 02139. TEL AVIV UNIV,IL-69978 TEL AVIV,ISRAEL. RP LEVINE, RA (reprint author), MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [T32 DC00006, P01 DC00119] NR 38 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUN PY 1993 VL 68 IS 1 BP 59 EP 72 DI 10.1016/0378-5955(93)90065-9 PG 14 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA LL524 UT WOS:A1993LL52400007 PM 8376216 ER PT J AU LEVINE, RA GARDNER, JC FULLERTON, BC STUFFLEBEAM, SM CARLISLE, EW FURST, M ROSEN, BR KIANG, NYS AF LEVINE, RA GARDNER, JC FULLERTON, BC STUFFLEBEAM, SM CARLISLE, EW FURST, M ROSEN, BR KIANG, NYS TI EFFECTS OF MULTIPLE-SCLEROSIS BRAIN-STEM LESIONS ON SOUND LATERALIZATION AND BRAIN-STEM AUDITORY-EVOKED POTENTIALS SO HEARING RESEARCH LA English DT Article DE BRAIN-STEM AUDITORY EVOKED POTENTIALS; SOUND LATERALIZATION; MULTIPLE SCLEROSIS; MAGNETIC RESONANCE IMAGING; INTERAURAL DISCRIMINATION ID STEM RESPONSES ABRS; COCHLEAR NUCLEUS; CAT; GENERATION; SYSTEM AB Magnetic resonance (MR) imaging, brainstem auditory evoked potentials (BAEPs), and tests of interaural time and level discrimination were performed on sixteen subjects with multiple sclerosis (MS). Objective criteria were used to define MR lesions. Of the eleven subjects in whom no pontine lesions were detected and the one subject who had pontine lesions that did not encroach upon the auditory pathways, all had normal BAEPs and interaural level discrimination, although a few had abnormal interaural time discrimination. Of four subjects with lesions involving the pontine auditory pathway, all had both abnormal BAEPs and abnormal interaural time discrimination; one also had abnormal interaural level discrimination. Analysis of the data suggest the following: waves I and II are generated peripheral to the middle of the ventral acoustic stria (VAS); wave III is generated ipsilaterally in the region of the rostral VAS, caudal superior olivary complex (SOC) and trapezoid body (TB); and waves V and L are generated contralaterally, rostral to the SOC-TB. The region of the ipsilateral rostral SOC-TB is implicated as part of the pathway involved in the generation of waves V and L. Interaural time discrimination of both high and low frequency stimuli were affected by all brainstem lesions that encroached on auditory pathways. A unilateral lesion in the region of the LL affected interaural time discrimination for low-frequency stimuli less severely than bilateral lesions of the LL or a unilateral lesion of the VAS. The only interaural level discrimination abnormality occurred for a subject with a unilateral lesion involving the entire rostral VAS. It appears that detailed analysis of lesion locations coupled with electrophysiological and psychophysical data holds promise for testing hypotheses concerning the function of various human auditory brainstem structures. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MIT,CAMBRIDGE,MA 02139. TEL AVIV UNIV,IL-69978 TEL AVIV,ISRAEL. RP LEVINE, RA (reprint author), MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [P01 DC 00119, T32 DC00006] NR 37 TC 38 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUN PY 1993 VL 68 IS 1 BP 73 EP 88 DI 10.1016/0378-5955(93)90066-A PG 16 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA LL524 UT WOS:A1993LL52400008 PM 8376217 ER PT J AU FREEDMAN, AS NADLER, LM AF FREEDMAN, AS NADLER, LM TI DEVELOPMENTS IN PURGING IN AUTOTRANSPLANTATION SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID BONE-MARROW TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; NEURO-BLASTOMA CELLS; ACUTE MYELOBLASTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMAS; HUMAN LYMPHOCYTES-B; BREAST-CANCER CELLS; ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; ACUTE MYELOCYTIC-LEUKEMIA C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP FREEDMAN, AS (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA40216, CA55207] NR 211 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1993 VL 7 IS 3 BP 687 EP 715 PG 29 WC Oncology; Hematology SC Oncology; Hematology GA LF894 UT WOS:A1993LF89400011 PM 8344886 ER PT J AU LEO, MA ROSMAN, AS LIEBER, CS AF LEO, MA ROSMAN, AS LIEBER, CS TI DIFFERENTIAL DEPLETION OF CAROTENOIDS AND TOCOPHEROL IN LIVER-DISEASE SO HEPATOLOGY LA English DT Article ID HEPATIC VITAMIN-A; BETA-CAROTENE; RETINOIC ACID; RAT; ETHANOL; METABOLISM; TISSUE; DEHYDROGENASE; CONVERSION; MICROSOMES AB Carotenoids and tocopherols are major natural protective agents against free radical-mediated liver damage, but their levels in diseased liver are largely uncharted. Therefore we carried out measurements with high-pressure liquid chromatography of alpha- and beta-carotene, lycopene, cryptoxanthin, lutein and zeaxanthin, total retinoids and alpha- and gamma-tocopherol. Liver tissue was obtained from percutaneous needle biopsies, livers of transplant recipients or a donor bank. Compared with controls (transplant donors; n = 13), levels of all carotenoids and retinoids were extremely low at all stages of liver disease. Patients with alcoholic cirrhosis (n = 11) had 20- and 25-fold decreases of levels of lycopene (p < 0.001) and alpha- and beta-carotene (p < 0.005), respectively. Even in subjects with less severe alcoholic liver disease (steatosis, perivenular fibrosis, portal fibrosis; n = 14) and in patients with nonalcoholic liver disease (n = 13), levels were four to six times lower than those in normal subjects. By contrast, levels of alpha-tocopherol were decreased significantly only in patients with cirrhosis, who displayed a threefold reduction. In the serum of most patients, lycopene and tocopherol concentrations were not depressed, whereas one third of alpha- and beta-carotene levels were low, probably reflecting poor dietary intake. A significant correlation was observed between serum and liver alpha- and beta-carotene levels (p < 0.0001; r = 0.715). However, of the patients with extremely low liver alpha- and beta-carotene concentrations, more than half had blood levels in the normal range, suggesting that liver disease interferes with the uptake, excretion or, perhaps, metabolism of alpha- and beta-carotene. In the cirrhotic livers of eight candidates for liver transplantation, the ratios of alpha- and beta-carotene to total retinoids and of beta-carotene to retinoids were much higher than those in normal livers, suggesting some impairment in the conversion of alpha- and beta-carotene to retinoids. In most cases, even with high ratios, absolute levels of hepatic alpha- and beta-carotene and retinoids were severely depressed. We concluded that, even in the presence of normal serum levels alpha- and beta-carotene, tocopherol and lycopene, patients with cirrhosis have extremely low hepatic levels. C1 MT SINAI SCH MED,NEW YORK,NY 10468. BRONX VET AFFAIRS MED CTR,LIVER DIS & NUTR SECT,BRONX,NY 10468. BRONX VET AFFAIRS MED CTR,ALCOHOL RES & TREATMENT CTR 151-G,130 W KINGSBRIDGE RD,BRONX,NY 10468. FU NIAAA NIH HHS [AA03508]; NIDDK NIH HHS [DK32810] NR 38 TC 103 Z9 105 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 1993 VL 17 IS 6 BP 977 EP 986 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LJ985 UT WOS:A1993LJ98500005 PM 8514270 ER PT J AU WONG, TY REED, JA SUSTER, S FLYNN, SD MIHM, MC AF WONG, TY REED, JA SUSTER, S FLYNN, SD MIHM, MC TI BENIGN TRICHOGENIC TUMORS - A REPORT OF 2 CASES SUPPORTING A SIMPLIFIED NOMENCLATURE SO HISTOPATHOLOGY LA English DT Article DE SKIN; TRICHOGENIC TUMOR; HAIR FOLLICLE NEOPLASM ID GIANT SOLITARY TRICHOEPITHELIOMA; ADENOID CYSTIC CARCINOMA; HAIR GERM; NEOPLASMS AB We report two cases of a rare benign tumour of hair germ. Clinically, both were solitary, well-circumscribed, subcutaneous nodules located in the extremities. Histologically, the tumours were characterized by nests and thin cords of basaloid epithelial cells intimately associated with a cellular stroma. The basaloid cells exhibited peripheral palisading, keratinization in the form of keratotic cysts and squamoid transformation, and pilar differentiation. An unusual, but distinctive, cribriform pattern of growth was observed. There was no communication with the overlying epidermis. Abundant primitive hair germinal buds and rare more advanced abortive hair follicles were identified. These histological appearances encompass features of both trichoblastic fibroma and trichogenic trichoblastoma, thus distinguishing these neoplasms from other skin tumours and reinforcing the hypothesis that these tumours are closely related from a histogenetic point of view. The presence of overlapping histological features can be problematic for practising histopathologists who rarely encounter these conditions. With this in mind, the term benign trichogenic tumour may be more appropriate to encompass these two tumours and related neoplasms that appear to lie within the spectrum of hair follicle development. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. NEW YORK HOSP,DIV DERMATOPATHOL,NEW YORK,NY 10021. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. MT SINAI MED CTR,DEPT PATHOL,MIAMI BEACH,FL 33140. UNIV MIAMI,SCH MED,MIAMI,FL 33152. YALE NEW HAVEN MED CTR,DEPT PATHOL,NEW HAVEN,CT 06504. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. RP WONG, TY (reprint author), MASSACHUSETTS GEN HOSP,DIV DERMATOPATHOL,WARREN BLDG SUITE 227,FRUIT ST,BOSTON,MA 02114, USA. NR 16 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD JUN PY 1993 VL 22 IS 6 BP 575 EP 580 DI 10.1111/j.1365-2559.1993.tb00179.x PG 6 WC Cell Biology; Pathology SC Cell Biology; Pathology GA LH541 UT WOS:A1993LH54100009 PM 8354489 ER PT J AU HAMNER, MB AF HAMNER, MB TI PTSD AND COCAINE ABUSE SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Letter ID STRESS DISORDER RP HAMNER, MB (reprint author), RALPH HENRY JOHNSON VET AFFAIRS MED CTR,CHARLESTON,SC, USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD JUN PY 1993 VL 44 IS 6 BP 591 EP 592 PG 2 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA LC960 UT WOS:A1993LC96000021 PM 8514313 ER PT J AU BERNARDS, A SNIJDERS, AJ HANNIGAN, GE MURTHY, AE GUSELLA, JF AF BERNARDS, A SNIJDERS, AJ HANNIGAN, GE MURTHY, AE GUSELLA, JF TI MOUSE NEUROFIBROMATOSIS TYPE-1 CDNA SEQUENCE REVEALS HIGH-DEGREE OF CONSERVATION OF BOTH CODING AND NONCODING MESSENGER-RNA SEGMENTS SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENE-PRODUCT; POINT MUTATIONS; POLY(A); GAP; POLYADENYLATION; ENCODES; DOMAIN; TAIL AB To identify evolutionary conserved domains and facilitate the recognition of potentially significant mutations in NF1 patients or tumors, we have determined the complete approximately 12 kb sequence of mouse neurofibromatosis type 1 mRNA. The sequence predicts a 2841 amino acid protein that is more than 98% identical to human neurofibromin. All but 9 of the 45 amino acid differences between mouse and human neurofibromin occur in the N-terminal half of the protein, with 16 changes clustered just upstream of the IRA-related segment. Given the high degree of sequence identity, virtually any sequence alteration in NF1 patients or tumors is potentially significant. We have also found that the 3' untranslated segment of NF1 mRNA is highly conserved, suggesting that this region may also be a target for mutations in NF1 patients. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,CHARLESTOWN NAVY YARD,149 13TH ST,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. RI Hannigan, Greg/A-5092-2009 FU NINDS NIH HHS [NS22224] NR 26 TC 53 Z9 55 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 JUN PY 1993 VL 2 IS 6 BP 645 EP 650 DI 10.1093/hmg/2.6.645 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA LH892 UT WOS:A1993LH89200005 PM 8353485 ER PT J AU DUYAO, MP TAYLOR, SAM BUCKLER, AJ AMBROSE, CM LIN, C GROOT, N CHURCH, D BARNES, G WASMUTH, JJ HOUSMAN, DE MACDONALD, ME GUSELLA, JF AF DUYAO, MP TAYLOR, SAM BUCKLER, AJ AMBROSE, CM LIN, C GROOT, N CHURCH, D BARNES, G WASMUTH, JJ HOUSMAN, DE MACDONALD, ME GUSELLA, JF TI A GENE FROM CHROMOSOME-4P16.3 WITH SIMILARITY TO A SUPERFAMILY OF TRANSPORTER PROTEINS SO HUMAN MOLECULAR GENETICS LA English DT Article ID DNA AB We have previously used exon amplification to identify the ADD1 gene in cosmid Y24 from the Huntington's disease (HD) region of 4p16.3. The same technique has now yielded a second gene from this cosmid. This gene appears to encode a novel member of a superfamily of transporter proteins that includes active and passive transporters in a number of species. The predicted protein of 455 amino acids displays sequence similarity with the E.coli tetracycline resistance efflux protein encoded by cloning vector pBR322, and with a number of related transporters. This gene should open a route to isolating additional mammalian members of this growing superfamily. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. UNIV CALIF IRVINE,DEPT BIOL CHEM,IRVINE,CA 92717. FU NHGRI NIH HHS [HG00169]; NINDS NIH HHS [NS16367] NR 17 TC 18 Z9 19 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN PY 1993 VL 2 IS 6 BP 673 EP 676 DI 10.1093/hmg/2.6.673 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA LH892 UT WOS:A1993LH89200009 PM 8353488 ER PT J AU MCCLATCHEY, AI CANNON, SC SLAUGENHAUPT, SA GUSELLA, JF AF MCCLATCHEY, AI CANNON, SC SLAUGENHAUPT, SA GUSELLA, JF TI THE CLONING AND EXPRESSION OF A SODIUM-CHANNEL BETA-1-SUBUNIT CDNA FROM HUMAN BRAIN SO HUMAN MOLECULAR GENETICS LA English DT Article ID RAT-BRAIN; XENOPUS-OOCYTES; SKELETAL-MUSCLE; ALPHA-SUBUNIT AB Electrical excitability of neurons and muscle cells is mediated largely through the actions of the voltage-gated sodium channel. Initiation and propagation of the action potential is a direct result of the precisely controlled inward flux of sodium through these channels. Much attention has been paid to the sodium channel alpha-subunit, the major, pore-forming component. However, alpha-subunits are associated with one or more smaller beta-subunits, which have been implicated in the critical fine tuning of the gating properties of the channel. To investigate the properties of the beta-subunit, we have isolated a cDNA encoding the human brain beta1-subunit and assigned the corresponding gene to chromosome 19. We have also examined the effects of expressing the brain beta1-subunit on the kinetics of a coexpressed muscle sodium channel alpha-subunit. Our results underscore the functional importance of the beta1-subunit and imply a conserved mechanism for the interaction of the beta1-subunit with different alpha-subunits. C1 MASSACHUSETTS GEN HOSP E,MOLEC NEUROGENET UNIT,BLDG 149,13TH ST,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. FU NINDS NIH HHS [NS22224] NR 28 TC 71 Z9 73 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN PY 1993 VL 2 IS 6 BP 745 EP 749 DI 10.1093/hmg/2.6.745 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA LH892 UT WOS:A1993LH89200021 PM 8394762 ER PT J AU CUALING, H SIEGEL, R SCHWARTING, GA SUCHY, SF MCCLUER, RH BERNAL, S AF CUALING, H SIEGEL, R SCHWARTING, GA SUCHY, SF MCCLUER, RH BERNAL, S TI THE EXPRESSION OF H-LIKE BLOOD-GROUP GLYCOLIPIDS IN SMALL-CELL CARCINOMA OF THE LUNG SO HYBRIDOMA LA English DT Article ID MONOCLONAL-ANTIBODIES; ANTIGEN; GLYCOSPHINGOLIPIDS; GANGLIOSIDE; CANCER AB Monoclonal antibody SM1 has been shown to be preferentially reactive with small cell carcinoma of the lung (SCCL) cell lines by fluorescent and radioimmunoassay membrane staining (1). Using solid phase indirect radioimmunoassay, the antigen is not detected in non-SCCL lung carcinomas histologically classified as squamous carcinoma, adenocarcinoma or large cell carcinoma , and other tumors,viz; pheochromocytoma, a mesoderm derived lymphoblastic leukemia cell line or in normal human brain, heart, liver, colon, endothelial tissues of the aorta and blood vessels, skin, omentum, muscle, lung parenchyma and is weakly reactive with bronchial mucosa, pancreas, and kidney. The membrane antigens detected by SM1 were isolated from small cell carcinoma of the lung (SCCL) cell line, SW2, using anion exchange chromatography and thin layer chromatography, and were further analysed by exoglycosidase and endoglycosidase treatments followed by chemical staining and immunostaining with SM1 and other antibodies. We show here that SM1 antibody reacts with a group of fucose-containing neutral glycolipids and gangliosides many of which are cross-reactive with antibodies to H antigens. C1 UNIV CINCINNATI, SCH MED, DEPT PATHOL, CINCINNATI, OH 45267 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV MED, BOSTON, MA 02115 USA. E K SHRIVER CTR, DEPT BIOCHEM, WALTHAM, MA 02254 USA. FU NCI NIH HHS [NCI PO1-CA38493]; NICHD NIH HHS [HD-05515] NR 27 TC 1 Z9 1 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1993 VL 12 IS 3 BP 239 EP 247 DI 10.1089/hyb.1993.12.239 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA LH387 UT WOS:A1993LH38700002 PM 8395464 ER PT J AU GIANELLO, P FISHBEIN, JM SACHS, DH AF GIANELLO, P FISHBEIN, JM SACHS, DH TI TOLERANCE TO PRIMARILY VASCULARIZED ALLOGRAFTS IN MINIATURE SWINE SO IMMUNOLOGICAL REVIEWS LA English DT Review ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II GENES; DISPARATE RENAL-ALLOGRAFTS; CYCLOSPORIN-A TREATMENT; SUPPRESSOR T CELLS; CLONAL ANERGY; TRANSPLANTATION TOLERANCE; CARDIAC ALLOGRAFT; MONOCLONAL-ANTIBODIES; PERIPHERAL TOLERANCE C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP GIANELLO, P (reprint author), MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NHLBI NIH HHS [HL18646]; NIAID NIH HHS [AI31046] NR 91 TC 49 Z9 50 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 1993 VL 133 BP 19 EP 44 DI 10.1111/j.1600-065X.1993.tb01508.x PG 26 WC Immunology SC Immunology GA LR370 UT WOS:A1993LR37000002 PM 8225367 ER PT J AU LEI, MG QURESHI, N MORRISON, DC AF LEI, MG QURESHI, N MORRISON, DC TI LIPOPOLYSACCHARIDE (LPS) BINDING TO 73-KDA AND 38-KDA SURFACE-PROTEINS ON LYMPHORETICULAR CELLS - PREFERENTIAL INHIBITION OF LPS BINDING TO THE FORMER BY RHODOPSEUDOMONAS-SPHAEROIDES LIPID-A SO IMMUNOLOGY LETTERS LA English DT Article DE LPS-BINDING PROTEIN; KDO DETERMINANT; LIPID-A; RS-DPLA ID MURINE SPLENOCYTES; ENDOTOXIN; MACROPHAGES; RECEPTOR; IDENTIFICATION; REQUIREMENTS; ASSOCIATION; INDUCTION; MICE AB Using a photoactivable, radioiodinated lipopolysaccharide probe, [I-125]ASD-LPS (derivatized from purified E. coli 0111:B4 S-LPS), we earlier reported the presence of a 73-kDa (p73) predominant LPS-binding protein on mouse lymphocytes and macrophages with specificity for the lipid A region of LPS. Both Re-LPS from Salmonella minnesota and purified lipid A will inhibit the binding of LPS to the p73 LPS receptor. In the studies reported here, we have found that nontoxic diphosphoryl lipid A purified from Rhodopseudomonas sphaeroides has the capability to inhibit the binding of [I-125]ASD-LPS to the p73 protein. However, using the same LPS probe and photoaffinity cross-linking techniques, our data suggest that a less dominant 38-kDa (p38) LPS-specific binding protein identified on mouse splenocytes, J774.1 macrophage-like cell line, and 70Z/3 pre B-cell line by SDS-PAGE is not inhibited by purified lipid A, even at a concentration in 50-fold excess of that of [I-125]ASD-LPS. The binding of the LPS probe to the p38 protein could be inhibited in a dose-dependent manner by underivatized native S. minnesota Re-LPS (composed only of Kdo and lipid A). We speculate that this p38 LPS-binding protein may manifest a specificity for inner core oligosaccharide determinants on LPS. C1 UNIV KANSAS,MED CTR,CTR CANC,KANSAS CITY,KS 66160. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MYCOBACTERIOL LAB,MADISON,WI 53705. UNIV WISCONSIN,COLL AGR & LIFE SCI,DEPT BACTERIOL,MADISON,WI 53706. RP LEI, MG (reprint author), UNIV KANSAS,MED CTR,DEPT MICROBIOL MOLEC GENET & IMMUNOL,KANSAS CITY,KS 66160, USA. FU NCI NIH HHS [P01-CA54474]; NIAID NIH HHS [R37-AI-23447]; NIGMS NIH HHS [GM-36054] NR 26 TC 20 Z9 20 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JUN PY 1993 VL 36 IS 3 BP 245 EP 250 DI 10.1016/0165-2478(93)90096-K PG 6 WC Immunology SC Immunology GA LM836 UT WOS:A1993LM83600003 PM 7690343 ER PT J AU BHATIA, E JACKSON, RA AF BHATIA, E JACKSON, RA TI T-CELL ANTIGEN RECEPTOR-GAMMA CHAIN POLYMORPHISMS IN TYPE-1 DIABETES SO INDIAN JOURNAL OF MEDICAL RESEARCH SECTION B-BIOMEDICAL RESEARCH OTHER THAN INFECTIOUS DISEASES LA English DT Article ID FRAGMENT LENGTH POLYMORPHISM; BETA-CHAIN; GRAVES-DISEASE; ALPHA-CHAIN; MULTIPLE-SCLEROSIS; GENE; LOCUS; ASSOCIATION; FAMILIES; COMPLEX AB The T-cell antigen receptor gamma chain, in conjunction with the delta chain, forms a functional receptor on a small percentage of circulating T-cells. Using restriction enzymes Msp 1 and Stu 1, and a human gamma chain cDNA probe, pT gamma 1, frequent restriction fragment length polymorphisms (RFLPs; 8 kb Msp 1 band; 7.6, 5.0, and 4.3/4.0 kb Stu 1 bands) were detected using DNA from healthy controls. These RFLPs allowed determination of parental alleles at the gamma chain locus, and follow up of their inheritance within families. Since Type 1 diabetes is an organ-specific autoimmune disease thought to be mediated by T-cells, the association of gamma chain polymorphisms with Type 1 diabetes was studied in a population study. No significant association was found with any of the polymorphic bands. The segregation of the gamma chain alleles among diabetic sibs in 6 multiplex families with Type 1 diabetes was also studied but linkage with diabetes could not be demonstrated. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. NR 31 TC 0 Z9 0 U1 0 U2 0 PU INDIAN COUNCIL MEDICAL RES PI NEW DELHI PA PO BOX 4508 ANSARI NAGAR, NEW DELHI 110029, INDIA SN 0019-5340 J9 INDIAN J MED RES-B PD JUN PY 1993 VL 98 BP 107 EP 113 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LL077 UT WOS:A1993LL07700001 PM 7901158 ER PT J AU PFALLER, MA RINALDI, MG AF PFALLER, MA RINALDI, MG TI ANTIFUNGAL SUSCEPTIBILITY TESTING - CURRENT STATE OF TECHNOLOGY, LIMITATIONS, AND STANDARDIZATION SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID FUNGAL-INFECTIONS; AMPHOTERICIN-B; UNITED-STATES; INVITRO; AGENTS; FLUCONAZOLE; INVIVO; THERAPY; YEASTS; KETOCONAZOLE C1 UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. OREGON HLTH SCI UNIV,DEPT MED,PORTLAND,OR 97201. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP PFALLER, MA (reprint author), OREGON HLTH SCI UNIV,DEPT PATHOL,3181 SW SAM JACKSON PK RD,PORTLAND,OR 97201, USA. NR 55 TC 46 Z9 46 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 1993 VL 7 IS 2 BP 435 EP 444 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LK347 UT WOS:A1993LK34700016 PM 8345178 ER PT J AU CHEN, JZ TROUNSTINE, M ALT, FW YOUNG, F KURAHARA, C LORING, JF HUSZAR, D AF CHEN, JZ TROUNSTINE, M ALT, FW YOUNG, F KURAHARA, C LORING, JF HUSZAR, D TI IMMUNOGLOBULIN GENE REARRANGEMENT IN B-CELL DEFICIENT MICE GENERATED BY TARGETED DELETION OF THE J(H) LOCUS SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE B-CELL DEFICIENT MICE; B-CELL DEVELOPMENT; IG GENE REARRANGEMENT; J(H) LOCUS; TARGETED MUTATION ID MURINE LEUKEMIA-VIRUS; LIGHT CHAIN GENES; PRE-B; BONE-MARROW; ALLELIC EXCLUSION; STEM-CELLS; MOUSE; LINES; DIFFERENTIATION; EXPRESSION AB B lymphocyte differentiation is characterized by an ordered series of Ig gene assembly and expression events. In the majority of normal B cells, assembly and expression of Ig heavy (H) chain genes precedes that of light (L) chain genes. To determine the role of the Ig heavy chain protein in B cell development and L chain gene rearrangement, we have generated mice that cannot assemble Ig H chain genes as a result of targeted deletion of the J(H) gene segments in embryonic stem cells. Mice homozygous for this deletion are devoid of slg+ B cells in the bone marrow and periphery. B cell differentiation in these mice is blocked at the large, CD43+ precursor stage. However, these precursor B cells do assemble kappa L chain genes at a low level in the absence of mu H chain proteins. These data demonstrate that rearrangement and expression of the mu H chain gene is not absolutely required for kappa L chain gene rearrangement in vivo. Expression of mu chains may facilitate either efficient L chain gene rearrangement or the survival of cells that have rearranged light chain genes by promoting the differentiation of large, CD43+ to small, CD43- pre-B cells. C1 GENPHARM INT INC,297 N BERNADO AVE,MT VIEW,CA 94043. CTR BLOOD RES,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. FU NIAID NIH HHS [SSS-4 (B) 1 R43 AI32268-01]; PHS HHS [A.I.20047] NR 57 TC 303 Z9 304 U1 0 U2 5 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 JUN PY 1993 VL 5 IS 6 BP 647 EP 656 DI 10.1093/intimm/5.6.647 PG 10 WC Immunology SC Immunology GA LJ998 UT WOS:A1993LJ99800011 PM 8347558 ER PT J AU SOPARKER, CN OBRIEN, JM ALBERT, DM AF SOPARKER, CN OBRIEN, JM ALBERT, DM TI INVESTIGATION OF THE ROLE OF THE RAS PROTOONCOGENE POINT MUTATION IN HUMAN UVEAL MELANOMAS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE RAS; ONCOGENE; UVEA; MELANOMA; MUTATION ID N-RAS; GENE FAMILY; HUMAN-LUNG; ACTIVATION; ONCOGENE; TUMORS; NEUROBLASTOMAS; AMPLIFICATION; CARCINOMAS; PHENOTYPE AB Purpose. Genetic alterations have been observed in a wide variety of neoplastic processes, including Burkitt's lymphoma, chronic myelogenous leukemia, promyelocytic leukemia, and solid tumors of the colon, skin, and breast. The polymerase chain reaction (PCR), dot blotting, and direct double-stranded DNA sequencing were used to assess ras gene activation in human uveal melanomas for three candidate genes: c-Ha-ras1, c-Ki-ras2, and N-ras at codons 12, 13, and 61. Methods. Samples of 49 human uveal melanomas were obtained. Amplifiable high molecular weight DNA was obtained from 39 of these. PCR amplification of regions centering on three candidate ras genes was performed. PCR-amplified DNA was evaluated by dot blot and double-stranded DNA sequencing utilizing standard methods. Results. No point mutations were identified in screening the c-Ha-ras gene nor were any genetic alterations found in the c-Ki-ras2 gene at codons 12 and 13. Only wild-type sequences were found at codon 61. No ras mutations were detected in any uveal melanomas studied. Conclusions. This study provides no evidence to support an association between ras protooncogene mutations and human uveal melanomas at codons 12, 13, or 61. C1 UNIV MASSACHUSETTS,MED CTR,DEPT PATHOL,WORCESTER,MA 01605. MASSACHUSETTS EYE & EAR INFIRM,DAVID G COGAN EYE PATHOL LAB,BOSTON,MA 02114. FU NEI NIH HHS [EY01917] NR 32 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1993 VL 34 IS 7 BP 2203 EP 2209 PG 7 WC Ophthalmology SC Ophthalmology GA LF867 UT WOS:A1993LF86700007 PM 8505202 ER PT J AU PARK, CH LATINA, MA AF PARK, CH LATINA, MA TI EFFECTS OF GAMMA-INTERFERON ON HUMAN TRABECULAR MESHWORK CELL PHAGOCYTOSIS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE TRABECULAR MESHWORK; GAMMA-INTERFERON; PHAGOCYTOSIS; FLOW CYTOMETRY; UVEITIS ID ENDOTOXIN-INDUCED UVEITIS; MYELIN BASIC-PROTEIN; CLASS-II ANTIGENS; AQUEOUS-HUMOR; EPITHELIAL-CELLS; IFN-GAMMA; T-CELL; EXPRESSION; LYMPHOKINE; INDUCTION AB Purpose. Gamma-interferon (G-IFN) regulates a variety of immune responses including the modulation of the phagocytic response and induction of class II major histocompatibility complex antigens. Because human trabecular meshwork (HTM) cells in culture are known to be actively phagocytic and have been shown to express class II major histocompatibility complex antigens, the effects of G-IFN on HTM cells were examined. Methods. Confluent HTM cells were incubated in media (Dulbecco's modified Eagle's medium + 10% fetal bovine serum) containing 0, 10, 50, 100, 500, 1 000, or 5000 units/ml of recombinant human G-IFN for 72 hr. After incubation, the cultured HTM cells were challenged with 5 ml of media containing 1 X 10(8) fluorescein labeled microspheres/ml. Phagocytic uptake was determined by flow cytometry. Results. Flow cytometric analysis of microsphere uptake shows that G-IFN inhibited HTM cell phagocytosis of microspheres in a dose-dependent fashion. At 5000 units/ml of G-IFN, phagocytosis of microspheres was inhibited by 64.5 +/- 2.4% compared to control (P < 0.007). The half maximal dose of phagocytic inhibition is <10 units/ml. Increasing the time of G-IFN exposure from 24 to 72 hr at 10 units/ml increased the level of phagocytic inhibition from 39 to 49%, respectively. The rate of microsphere uptake was also reduced in a dose-dependent fashion. Morphologic examination after G-IFN incubation showed that HTM cells became enlarged and flattened compared to the control. Actin cytoskeletal immunofluorescence staining showed that parallel actin beams of the control cells were changed to a radial, spokelike arrangement when incubated in G-IFN. Conclusions. G-IFN is a potent inhibitor of HTM cell phagocytosis in vitro. G-IFN's effect on the actin cytoskeleton suggests that G-IFN may be disturbing the cytoskeletal organization necessary for phagocytosis. C1 MASSACHUSETTS GEN HOSP,WELLMAN LABS,BOSTON,MA 02114. EYE RES INST,BOSTON,MA. NR 31 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1993 VL 34 IS 7 BP 2228 EP 2236 PG 9 WC Ophthalmology SC Ophthalmology GA LF867 UT WOS:A1993LF86700010 PM 8505204 ER PT J AU WATANABE, M KONDO, I NISSATO, S WAKISAKA, A TODA, T IKEDA, J WASMUTH, JJ GUSELLA, JF KANAZAWA, I AF WATANABE, M KONDO, I NISSATO, S WAKISAKA, A TODA, T IKEDA, J WASMUTH, JJ GUSELLA, JF KANAZAWA, I TI A LINKAGE STUDY WITH DNA MARKERS (D4S95, D4S115, AND D4S111) IN JAPANESE HUNTINGTON DISEASE FAMILIES SO JAPANESE JOURNAL OF HUMAN GENETICS LA English DT Article DE HUNTINGTON DISEASE; LINKAGE ANALYSIS; D4S95; D4S115; D4S111 ID GENE; REGION; CHROMOSOME-4; LOCUS; DISEQUILIBRIUM; CONSTRUCTION; LOCALIZATION; TELOMERE AB Attempts to isolate the Huntington disease (HD) gene based on its position have been frustrated by apparently contradictory recombination events in HD pedigrees that have predicted two non-overlapping candidate regions: 100 kb at the telomere of the short arm of chromosome 4, and a 2.2 Mb region located internally at 4p16.3. The proximal location is also supported by the detection of a linkage disequilibrium between HD and some restriction fragment length polymorphisms (RFLPs) at the D4S95, D4S98, and D4S127 loci. In the present study, a proximal marker D4S95 showed tight linkage to the disease locus in Japanese pedigrees (Z(max)=3.31, theta(max)=0.00), while distal markers D4S115 and D4S111 did not. Particularly, a two point linkage analysis between D4S111 and HD yielded a lod score - 2.01 for theta = 0.015. This result leads to the exclusion, as a possible region of localization of the HD gene, of more than 3 cM of the genome around D4S111 locus. At the same ti me our results favor aforementioned proximal location as a candidate location for the HD gene. C1 UNIV TOKYO,INST BRAIN RES,DEPT NEUROL,BUNKYO KU,TOKYO 113,JAPAN. EHIME UNIV,SCH MED,DEPT HYG,SHIGENOBU,EHIME 79102,JAPAN. HOKKAIDO UNIV,SCH MED,DEPT PATHOL,SAPPORO,HOKKAIDO 060,JAPAN. UNIV CALIF IRVINE,DEPT BIOL CHEM,IRVINE,CA 92717. UNIV TSUKUBA,INST CLIN MED,DEPT NEUROL,TSUKUBA 305,JAPAN. TOKAI UNIV,SCH MED,IKEDA GENOSPHERE PROJECT,ERATO,JRDC,ISEHARA,KANAGAWA 25911,JAPAN. MASSACHUSETTS GEN HOSP,NEUROGENET LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. NR 35 TC 2 Z9 2 U1 0 U2 1 PU TOKYO MEDICAL DENTAL UNIV PI TOKYO PA MED RES INST-DEPT CYTOGENETICS YUSHIMA 1 BUNKYO-KU, TOKYO 113, JAPAN SN 0916-8478 J9 JPN J HUM GENET JI Jpn. J. Hum. Genet. PD JUN PY 1993 VL 38 IS 2 BP 193 EP 201 DI 10.1007/BF01883710 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA LK587 UT WOS:A1993LK58700005 PM 8102909 ER PT J AU GODFREY, E STANLEY, K AF GODFREY, E STANLEY, K TI CLINICAL RESEARCH UNITS FOR THE TREATMENT OF PATIENTS WITH HIV DISEASE - OPERATIONAL ISSUES AND COMPONENTS NEEDED TO CONDUCT CLINICAL-TRIALS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV; CLINICAL TRIALS; PRIMARY CARE; CLINICAL RESEARCH ID AIDS-RELATED COMPLEX; AZT AB Clinical trials are of paramount importance for the development and evaluation of new therapies for patients with human immunodeficiency virus (HIV) disease. The objective of an HIV clinical research unit is to conduct high quality clinical research with patients who have HIV disease. The conduct of these research studies requires accurate and complete data collection. Coordination of the patients' primary care must be complemented by a working knowledge of the relevant ethical issues. In addition, technical, managerial, and clinical expertise is needed for conducting the trials and collecting data. To accurately plan the research, personnel and resource allocation should be periodically assessed. Clinicians, particularly those who have not previously conducted clinical trials or who are considering the incorporation of a research program into a primary care setting, must be familiar with these issues in order to create and supervise this type of clinical research unit. A smoothly running clinic observing a defined cohort of patients is attractive to government agencies and pharmaceutical sponsors for funding of clinical trials and research projects. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,AIDS CLIN TRIALS GRP,STAT & DATA ANAL CTR,BOSTON,MA 02115. RP GODFREY, E (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV INFECT DIS,INFECT DIS UNIT,GRAY 5,55 FRUIT ST,BOSTON,MA 02114, USA. FU NIAID NIH HHS [01-AI-27659, 01-AI-95030] NR 22 TC 3 Z9 3 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 JUN PY 1993 VL 6 IS 6 BP 567 EP 574 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LC751 UT WOS:A1993LC75100004 PM 8496789 ER PT J AU FRATAZZI, C SHARMA, PL FAZELY, F GREENE, MF WYAND, MS PENNINCK, D RUPRECHT, RM AF FRATAZZI, C SHARMA, PL FAZELY, F GREENE, MF WYAND, MS PENNINCK, D RUPRECHT, RM TI HIGH-RATE OF SIMIAN IMMUNODEFICIENCY VIRUS-INFECTION OF RHESUS-MONKEY FETUSES VIA AMNIOTIC-FLUID - A MODEL TO STUDY IMMUNOPATHOGENESIS AND PROPHYLAXIS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,VIRAL PATHOGENESIS LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. TUFTS UNIV,SCH VET MED,MEDFORD,MA 02155. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD JUN PY 1993 VL 6 IS 6 BP 678 EP 678 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LC751 UT WOS:A1993LC75100060 ER PT J AU DELWART, EL SHPAER, EG WALKER, BD HIRSCH, MS MCCUTCHAN, F GOUDSMIT, J MULLINS, JI AF DELWART, EL SHPAER, EG WALKER, BD HIRSCH, MS MCCUTCHAN, F GOUDSMIT, J MULLINS, JI TI ENVIRONMENTAL ADAPTATION OF HIV GENOMES SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 STANFORD UNIV,MED CTR,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV AMSTERDAM,HENRY M JACKSON FDN,AMSTERDAM,NETHERLANDS. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD JUN PY 1993 VL 6 IS 6 BP 684 EP 684 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LC751 UT WOS:A1993LC75100086 ER PT J AU FLECKENSTEIN, B BIESINGER, B FICKENSCHER, H ENSSER, A GRASSMANN, R RAMSTEDT, U HASELTINE, WA JUNG, JU DESROSIERS, RC AF FLECKENSTEIN, B BIESINGER, B FICKENSCHER, H ENSSER, A GRASSMANN, R RAMSTEDT, U HASELTINE, WA JUNG, JU DESROSIERS, RC TI A HERPESVIRUS VECTOR FOR T-CELL TRANSFORMING ONCOGENES SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 UNIV ERLANGEN NURNBERG,INST KLIN & MOLEK VIROL,W-8520 ERLANGEN,GERMANY. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,NEW ENGLAND PRIMATE RES CTR,BOSTON,MA 02115. RI Fickenscher, Helmut/A-3004-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD JUN PY 1993 VL 6 IS 6 BP 696 EP 696 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LC751 UT WOS:A1993LC75100132 ER PT J AU GABUZDA, D LAWRENCE, K LANGHOFF, E TERWILLIGER, E DORFMAN, T SODROSKI, J HASELTINE, W AF GABUZDA, D LAWRENCE, K LANGHOFF, E TERWILLIGER, E DORFMAN, T SODROSKI, J HASELTINE, W TI THE ROLE OF VIF IN REPLICATION OF HIV-1 IN CD4+ T-LYMPHOCYTES SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 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 JUN PY 1993 VL 6 IS 6 BP 700 EP 700 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LC751 UT WOS:A1993LC75100147 ER PT J AU MIRIAM, M DAQUILA, RT BECHTEL, LJ SMITH, BR KAPLAN, JC HIRSCH, MS AF MIRIAM, M DAQUILA, RT BECHTEL, LJ SMITH, BR KAPLAN, JC HIRSCH, MS TI HIV-1 DNA IN FIBROBLAST-CULTURES INFECTED WITH URINE FROM HIV-SEROPOSITIVE CYTOMEGALOVIRUS (CMV) EXCRETORS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MORPHOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD JUN PY 1993 VL 6 IS 6 BP 717 EP 717 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LC751 UT WOS:A1993LC75100216 ER PT J AU LAMPE, MA PATARCA, R CANTOR, H AF LAMPE, MA PATARCA, R CANTOR, H TI DEFINITION OF INTERACTIONS BETWEEN RETROVIRUSES AND THE RPT-1 GENE THAT MAY REGULATE T-CELL DIFFERENTIATION SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOPATHOL LAB,BOSTON,MA 02115. UNIV MIAMI,SCH MED,E M PAPPER LAB CLIN IMMUNOL,MIAMI,FL 33101. NR 0 TC 0 Z9 0 U1 0 U2 4 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 JUN PY 1993 VL 6 IS 6 BP 730 EP 730 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LC751 UT WOS:A1993LC75100270 ER PT J AU MOEBIUS, U CLAYTON, LK ABRAHAM, S HARRISON, SC REINHERZ, EL AF MOEBIUS, U CLAYTON, LK ABRAHAM, S HARRISON, SC REINHERZ, EL TI THE HIV GP120 BINDING-SITE ON CD4 - DELINEATION BY QUANTITATIVE EQUILIBRIUM AND KINETIC BINDING-STUDIES OF MUTANTS IN CONJUNCTION WITH A HIGH-RESOLUTION CD4 ATOMIC-STRUCTURE SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 HOWARD HUGHES MED INST,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,PSYCHOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,CAMBRIDGE,MA 02138. NR 0 TC 0 Z9 0 U1 0 U2 3 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 JUN PY 1993 VL 6 IS 6 BP 731 EP 731 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LC751 UT WOS:A1993LC75100271 ER PT J AU SCHMALZRIED, TP JASTY, M ROSENBERG, A HARRIS, WH AF SCHMALZRIED, TP JASTY, M ROSENBERG, A HARRIS, WH TI HISTOLOGIC IDENTIFICATION OF POLYETHYLENE WEAR DEBRIS USING OIL RED-O STAIN SO JOURNAL OF APPLIED BIOMATERIALS LA English DT Article AB Ultra high molecular weight polyethylene (UHMWPE) wear particles are frequently implicated in causing failure of total joint arthroplasties by eliciting a foreign body reaction. The majority of these particles are subcellular and many are submicron in size. Identification of these small particles of UHMWPE by conventional histologic techniques is difficult. We have therefore investigated the utility of Oil Red 0 (ORO) stain to identify UHMWPE on histologic sections. A wide variety of specimens was studied including an experimental rabbit model with subcutaneous implantation of polyethylene particles as well as specimens from clinical cases with joint arthroplasties. The sensitivity and specificity of ORO stain was compared to conventional polarized light microscopy for the identification of particulate UHMWPE debris. The ORO stain was found to be as sensitive in identifying particulate UHMWPE debris as polarized light microscopy. However, ORO stain was less specific: two specimens that did not contain any UHMWPE also stained with ORO. Careful examination of standard hematoxylin and eosin stained sections with polarized light was therefore more specific for the identification of particulate UHMWPE. As a single test, the ORO stain does not appear to offer any clear advantage specifically for the identification of UHMWPE. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 7 TC 52 Z9 52 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-4861 J9 J APPL BIOMATER JI J. Appl. Biomater. PD SUM PY 1993 VL 4 IS 2 BP 119 EP 125 DI 10.1002/jab.770040202 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA LD056 UT WOS:A1993LD05600001 PM 10150994 ER PT J AU STEIN, JA SMITH, GM GUY, SM BENTLER, PM AF STEIN, JA SMITH, GM GUY, SM BENTLER, PM TI CONSEQUENCES OF ADOLESCENT DRUG-USE ON YOUNG-ADULT JOB BEHAVIOR AND JOB-SATISFACTION SO JOURNAL OF APPLIED PSYCHOLOGY LA English DT Article ID SUBSTANCE USE; HIGH-SCHOOL; COUNTERPRODUCTIVE BEHAVIOR; GENDER DIFFERENCES; DRINKING BEHAVIOR; FOLLOW-UP; ALCOHOL; WORK; MODELS; INVOLVEMENT AB Longitudinal data (N=785) collected during Ss high school years(1971-1973) and in 1981 were used to assess the influence of adolescent drug use on adult job behaviors, job satisfaction, and adverse terminations while accounting for concurrent adult drug use, years of drug use, and adolescent achievement motivation. Relationships were minimal between adolescent drug use and adult work-related indicators in confirmatory factor analyses (CFAs) and predictive path models. Although significantly related in the CFAs, higher adolescent achievement motivation did not predict less adult drug use when adolescent drug use was included as a control. Less achievement motivation in adolescence significantly predicted more negative job behaviors and less job satisfaction, but not terminations. Correlations were significant between more adolescent drug use and less adolescent achievement motivation and between adult job problems and adult drug use. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP STEIN, JA (reprint author), UNIV CALIF LOS ANGELES,DEPT PSYCHOL,405 HILGARD AVE,LOS ANGELES,CA 90024, USA. FU NIDA NIH HHS [DA00017, DA01070] NR 62 TC 28 Z9 28 U1 3 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0021-9010 J9 J APPL PSYCHOL JI J. Appl. Psychol. PD JUN PY 1993 VL 78 IS 3 BP 463 EP 474 PG 12 WC Psychology, Applied; Management SC Psychology; Business & Economics GA LH161 UT WOS:A1993LH16100013 PM 8331025 ER PT J AU ENGH, CA ZETTLSCHAFFER, KF KUKITA, Y SWEET, D VIRGINIA, A JASTY, M BRAGDON, C AF ENGH, CA ZETTLSCHAFFER, KF KUKITA, Y SWEET, D VIRGINIA, A JASTY, M BRAGDON, C TI HISTOLOGICAL AND RADIOGRAPHIC ASSESSMENT OF WELL-FUNCTIONING POROUS-COATED ACETABULAR COMPONENTS - A HUMAN POSTMORTEM RETRIEVAL STUDY SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID BONE AB Nine porous-coated acetabular components were retrieved post mortem. All components had been inserted at our institution and had been in situ for a mean of fifty months (range, seventeen to eighty-seven months). Clinical records revealed that all had been functioning well at the time of death, and clinical radiographs showed signs that all had been stable. Standard backscattered scanning electron microscopy was used to quantitate the amount of bone ingrowth into the porous coating. For each component, the histological appearance of the bone-metal interface was compared with the appearance on clinical radiographs. Light microscopy was used to study the non-ossified areas. Every component had growth of bone into the porous coating, with the ingrowth occupying a mean of 32 per cent (range, 3 to 84 per cent) of the fields that were examined. In areas where bone ingrowth had occurred, the mean area density was 48 per cent (range, 26 to 65 per cent). Use of radiographs consistently led to an underestimation of the presence of gap areas and an overestimation of the occurrence of bone apposition. When fibrous tissue was present in non-ossified areas, it was extremely dense and well organized. Within the limits of light microscopic examination, there was no evidence of granulomatous formation in the non-ossified regions. This is particularly encouraging since the fibrous tissue-bone interfaces seem to prohibit the deposit of particulate debris. C1 SAPPORO MED COLL,DEPT ORTHOPAED SURG,CHUO KU,SAPPORO,HOKKAIDO 060,JAPAN. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP ENGH, CA (reprint author), ANDERSON ORTHOPAED RES INST,2445 ARMY NAVY DR,ARLINGTON,VA 22206, USA. NR 29 TC 85 Z9 86 U1 0 U2 2 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUN PY 1993 VL 75A IS 6 BP 814 EP 824 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA LK828 UT WOS:A1993LK82800003 PM 8314822 ER PT J AU JIRANEK, WA MACHADO, M JASTY, M JEVSEVAR, D WOLFE, HJ GOLDRING, SR GOLDBERG, MJ HARRIS, WH AF JIRANEK, WA MACHADO, M JASTY, M JEVSEVAR, D WOLFE, HJ GOLDRING, SR GOLDBERG, MJ HARRIS, WH TI PRODUCTION OF CYTOKINES AROUND LOOSENED CEMENTED ACETABULAR COMPONENTS - ANALYSIS WITH IMMUNOHISTOCHEMICAL TECHNIQUES AND IN-SITU HYBRIDIZATION SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID OSTEOCLAST-ACTIVATING FACTOR; STIMULATES BONE-RESORPTION; RHEUMATOID SYNOVIAL-CELLS; PROSTAGLANDIN PRODUCTION; MONOCLONAL-ANTIBODY; INTERFERON-GAMMA; GENE-EXPRESSION; GROWTH-FACTORS; RAT CALVARIAE; INTERLEUKIN-1 AB The chronic inflammatory response to wear particles from orthopaedic joint implants is believed to cause osteolysis and to contribute to prosthetic loosening. Previous in vitro experiments have demonstrated that particulate debris from joint implants causes cells in culture to release products that have been implicated in this pathological bone resorption. The purpose of the current study was to investigate the in vivo features of this complex process in patients who had had a total hip replacement. Membranous tissue was obtained from the cement-bone interface of ten polyethylene acetabular components that had been revised for aseptic loosening in ten patients. The immunoperoxidase technique, which involves the use of specific antibodies for each cell type, showed that macrophages were the predominant cellular constituents but also that fibroblasts, many of which were not identified on plain histological study, were present and were actively producing collagen. T lymphocytes were present variably, but they generally composed less than 10 per cent of the cells. Particulate debris (polyethylene, methylmethacrylate, and metal) was present in all membrane specimens but was intracellular only in macrophages and multi-nucleated giant cells. S-35-labeled nucleic-acid probes, complementary to human interleukin-1-beta and to platelet-derived growth-factor-2 messenger RNA (mRNA), were hybridized with serial tissue sections. Hybridization demonstrated interleukin-1-beta mRNA predominantly in macrophages, and not in fibroblasts or in T lymphocytes to any major extent. In contrast, immunolocalization demonstrated interleukin-1-beta protein on both macrophages and fibroblasts, suggesting that macrophages release interleukin-1-beta, which then binds to both fibroblasts and macrophages. Platelet-derived growth-factor transcripts were found in both macrophages and fibroblasts. CLINICAL RELEVANCE: These data demonstrate that interleukin-1-beta and platelet-derived growth factor, two potent cytokines that have been implicated in many disease states, are produced at the cement-bone interface of failed joint prostheses. These cytokines are probably involved in bone resorption, fibrous proliferation, and, ultimately, loosening of prostheses. Even with technological advances, it is unlikely that particulate wear debris from total joint replacements will be eliminated. However, an understanding of which cytokines cause bone resorption and which cells produce the cytokines will enhance the ability to block the deleterious effects of particulate wear debris and will lead to an increase in the longevity of reconstructed joints. C1 TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,DEPT ORTHOPAED,BOSTON,MA 02116. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,DEPT PATHOL,BOSTON,MA 02116. MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ARTHRIT RES LABS,BOSTON,MA 02118. RP JIRANEK, WA (reprint author), TUCKAHOE ORTHOPAED ASSOCIATES,8919 3 CHOPT RD,RICHMOND,VA 23229, USA. NR 71 TC 384 Z9 391 U1 1 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUN PY 1993 VL 75A IS 6 BP 863 EP 879 PG 17 WC Orthopedics; Surgery SC Orthopedics; Surgery GA LK828 UT WOS:A1993LK82800007 PM 8314826 ER PT J AU PAIEMENT, GD WESSINGER, SJ HUGHES, R HARRIS, WH AF PAIEMENT, GD WESSINGER, SJ HUGHES, R HARRIS, WH TI ROUTINE USE OF ADJUSTED LOW-DOSE WARFARIN TO PREVENT VENOUS THROMBOEMBOLISM AFTER TOTAL HIP-REPLACEMENT SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID VEIN THROMBOSIS; PROPHYLAXIS; HEPARIN; ARTHROPLASTY AB The efficacy and safety of routine use of adjusted low-dose warfarin for twelve weeks - without sonography or venography - for the prophylaxis of deep-vein thrombosis after total hip replacement was assessed in 268 patients (134 men and 134 women) who were between the ages of forty and eighty-five years (average, sixty-one years). The patients were given warfarin orally both before and after the operation. The initial dose was usually ten milligrams on the night before the operation and five milligrams on the night after the operation. Thereafter, the dose was adjusted to keep the prothrombin time between fourteen and sixteen seconds. The control time was ten to twelve seconds. The partial thromboplastin time was also measured, and the dose of warfarin was reduced if the value was more than fifty seconds. All 268 patients continued to take low-dose warfarin for twelve weeks after the operation. There were 170 primary and ninety-eight revisional total hip-replacement operations. Thirty-four patients (13 per cent) had a history of thromboembolic disease or venous stasis in a lower limb. Neither phlebography nor sonography was done routinely. All of the patients were followed for six months after the operation. There were no fatal pulmonary emboli during the period of the study and no known pulmonary emboli after any patient was discharged from the hospital. Two non-fatal pulmonary emboli were identified, both during hospitalization. Ten patients (4 per cent) had an episode of major bleeding - a wound hematoma in nine and a gastrointestinal hemorrhage in one - during hospitalization. After discharge, sixteen patients had a minor episode of bleeding but no episode led to treatment. No major bleeding episode occurred after discharge from the hospital. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. SAN FRANCISCO GEN HOSP,DEPT ORTHOPAED SURG,SAN FRANCISCO,CA 94110. NR 16 TC 51 Z9 51 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUN PY 1993 VL 75A IS 6 BP 893 EP 898 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA LK828 UT WOS:A1993LK82800010 PM 8314829 ER PT J AU ORWOLL, ES OVIATT, SK BIDDLE, JA AF ORWOLL, ES OVIATT, SK BIDDLE, JA TI PRECISION OF DUAL-ENERGY X-RAY ABSORPTIOMETRY - DEVELOPMENT OF QUALITY-CONTROL RULES AND THEIR APPLICATION IN LONGITUDINAL-STUDIES SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID BONE MASS; FRACTURE; DENSITY; WOMEN; AGE AB In research settings, longitudinal measurements of bone mineral density have become an integral part of the assessment of patients with metabolic skeletal disorders. To adequately utilize longitudinal measures, confidence in the long-term precision of the measurement technique must be very high. Dual-energy x-ray absorptiometry (DXA) has become commonly utilized in this context, and to better understand its long-term precision and to develop quality assurance protocols for its use, we examined the performance of eight DXA machines over a 3 year period. Anthropomorphic spine phantoms were measured frequently on each machine during the period of observation, and precision was estimated from the consistency of these determinations. Overall precision was excellent (mean longitudinal coefficient of variation, 0.4%). Nevertheless, by using a series of objective quality control criteria, small alterations in the performance of each machine were identified (mean number of changes, 4.6 in 3 years; mean magnitude, 0.0039 g/cm2, or 0.4%). The cumulative effects of those changes were sufficient to cause a significant (albeit minor) change in the regression slopes (phantom mineral density versus time) of most machines. The same quality control rules were also used to quantitate the magnitude of change and to adjust retrospectively machine performance during the period of observation, such that alterations were minimal and regression slopes were not significantly different from zero. Although the precision of DXA is excellent, alterations in machine function must be anticipated during longitudinal use. The development of quality control protocols provides the means to detect change objectively and to adjust for alterations in performance during the course of longitudinal evaluations. C1 PORTLAND VA MED CTR,BONE & MINERAL RES UNIT,PORTLAND,OR. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. OI Orwoll, Eric/0000-0002-8520-7355 NR 12 TC 85 Z9 85 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 1993 VL 8 IS 6 BP 693 EP 699 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LE193 UT WOS:A1993LE19300006 PM 8328311 ER PT J AU BUBIEN, JK ZHOU, LJ BELL, PD FRIZZELL, RA TEDDER, TF AF BUBIEN, JK ZHOU, LJ BELL, PD FRIZZELL, RA TEDDER, TF TI TRANSFECTION OF THE CD20 CELL-SURFACE MOLECULE INTO ECTOPIC CELL-TYPES GENERATES A CA2+ CONDUCTANCE FOUND CONSTITUTIVELY IN B-LYMPHOCYTES SO JOURNAL OF CELL BIOLOGY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; MONOCLONAL-ANTIBODIES; DIFFERENTIATION ANTIGEN; COMPLEMENTARY-DNA; ION CHANNELS; ACTIVATION; CALCIUM; RAT; EXPRESSION; RECEPTOR AB CD20 is a plasma membrane phosphoprotein expressed exclusively by B lymphocytes. mAb binding to CD20 alters cell cycle progression and differentiation, indicating that CD20 plays an essential role in B lymphocyte function. Whole-cell patch clamp and fluorescence microscopy measurements of plasma membrane ionic conductance and cytosolic-free Ca2+ activity, respectively, were used to directly examine CD20 function. Transfection of human T and mouse pre-B lymphoblastoid cell lines with CD20 cDNA and subsequent stable expression of CD20 specifically increased transmembrane Ca2+ conductance. Transfection of CD20 cDNA and subsequent expression of CD20 in nonlymphoid cells (human K562 erythroleukemia cells and mouse NIH-3T3 fibroblasts) also induced the expression of an identical transmembrane Ca2+ conductance. The binding of a CD20-specific mAb to CD20+ lymphoblastoid cells also enhanced the transmembrane Ca2+ conductance. The mAb-enhanced Ca2+ currents had the same conductance characteristics as the CD20-associated Ca2+ currents in CD20 cDNA-transfected cells. C20 is structurally similar to several ion channels; each CD20 monomer possesses four membrane spanning domains, and both the amino and carboxy termini reside within the cytoplasm. Biochemical cross-linking of cell-surface molecules with subsequent immunoprecipitation analysis of CD20 suggests that CD20 may be present as a multimeric oligomer within the membrane, as occurs with several known membrane channels. Taken together, these findings indicate that CD20 directly regulates transmembrane Ca2+ conductance in B lymphocytes, and suggest that multimeric complexes of CD20 may form Ca2+ conductive ion channels in the plasma membrane of B lymphoid cells. C1 UNIV ALABAMA,DEPT PHYSIOL & BIOPHYS,BIRMINGHAM,AL 35294. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP BUBIEN, JK (reprint author), UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294, USA. FU NCI NIH HHS [CA-34183]; NIAID NIH HHS [AI-26872]; NIDDK NIH HHS [DK-31091] NR 60 TC 214 Z9 222 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN PY 1993 VL 121 IS 5 BP 1121 EP 1132 DI 10.1083/jcb.121.5.1121 PG 12 WC Cell Biology SC Cell Biology GA LE291 UT WOS:A1993LE29100015 PM 7684739 ER PT J AU RAMIREZ, JA GOODMAN, WG GORNBEIN, J MENEZES, C MOULTON, L SEGRE, GV SALUSKY, IB AF RAMIREZ, JA GOODMAN, WG GORNBEIN, J MENEZES, C MOULTON, L SEGRE, GV SALUSKY, IB TI DIRECT INVIVO COMPARISON OF CALCIUM-REGULATED PARATHYROID-HORMONE SECRETION IN NORMAL VOLUNTEERS AND PATIENTS WITH SECONDARY HYPERPARATHYROIDISM SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HEMODIALYSIS-PATIENTS; RENAL OSTEODYSTROPHY; BONE-DISEASE; RELEASE; SUPPRESSION; TISSUE; 1,25-DIHYDROXYVITAMIN-D; HYPERCALCEMIA; DIALYSATE; ALUMINUM AB The regulation of PTH secretion by calcium is altered in patients with primary hyperparathyroidism. A similar disturbance may occur in secondary hyperparathyroidism, but direct in vivo comparisons of PTH secretion in normal subjects and those with secondary hyperparathyroidism have not been made. Thus, 13 patients with end-stage renal failure and secondary hyperparathyroidism and 20 healthy volunteers underwent dynamic tests of PTH secretion. Changes in ionized calcium were induced by 2-h iv infusions of calcium gluconate or sodium citrate on consecutive days, and the sigmoidal relationship between serum ionized calcium and PTH levels was examined. During sodium citrate infusions, serum ionized calcium levels decreased by 0.21 +/- 0.04 and 0.20 +/- 0.05 mmol/L, respectively (mean +/- SD), in normal volunteers and dialyzed patients (P = NS). Serum PTH levels rose from 27 +/- 7 to 107 +/- 33 pg/mL in controls and from 480 +/- 238 to 859 +/- 412 pg/mL in dialyzed subjects; thus, maximum PTH levels were 396% of preinfusion values in normal subjects, but only 79% greater than baseline values in dialyzed patients (P < 0.001). During the first 30 min of calcium infusions, the increase in serum ionized calcium did not differ between groups, but PTH levels fell more rapidly in normal volunteers; values were 24% of preinfusion levels in controls, but only 56% of the baseline in dialyzed patients (P < 0.01) after 30 min. Minimum PTH levels were attained after 50 min of calcium infusion in normal volunteers and after 70 min in dialyzed patients. The derived values for set-point were 1.21 +/- 0.04 and 1.24 +/- 0.06 mmol/L, respectively, in control and dialyzed subjects (P = NS). These results do not support the contention that the set-point for calcium-regulated PTH secretion is greater than normal in patients with secondary hyperparathyroidism due to end-stage renal disease. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT PEDIAT, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT RADIOL, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT PEDIAT, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT BIOMATH, LOS ANGELES, CA 90024 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, ENDOCRINE UNIT, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-00865]; NIDDK NIH HHS [DK-35423] NR 29 TC 104 Z9 105 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1993 VL 76 IS 6 BP 1489 EP 1494 DI 10.1210/jc.76.6.1489 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LF088 UT WOS:A1993LF08800018 PM 8501155 ER EF