FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Arany, Z Huang, LE Eckner, R Bhattacharya, S Jiang, C Goldberg, MA Bunn, HF Livingston, DM AF Arany, Z Huang, LE Eckner, R Bhattacharya, S Jiang, C Goldberg, MA Bunn, HF Livingston, DM TI An essential role for p300/CBP in the cellular response to hypoxia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; E1A-ASSOCIATED PROTEIN P300; HUMAN ERYTHROPOIETIN GENE; ADENOVIRUS E1A; INDUCIBLE FACTOR-1; TRANSCRIPTIONAL ADAPTER; NUCLEAR FACTOR; CBP; REPRESSION; EXPRESSION AB p300 and CBP are homologous transcription adapters targeted by the EIA oncoprotein. They participate in numerous biological processes, including cell cycle arrest, differentiation, and transcription activation. p300 and/or CBP (p300/CBP) also coactivate CREB, How they participate in these processes is not yet known, In a search for specific p300 binding proteins, we have cloned the intact cDNA for HIF-1 alpha, This transcription factor mediates hypoxic induction of genes encoding certain glycolytic enzymes, erythropoietin (Epo), and vascular endothelial growth factor. Hypoxic conditions lead to the formation of a DNA binding complex containing both HIF-1 alpha and p300/CBP, Hypoxia-induced transcription from the Epo promoter was specifically enhanced by ectopic p300 and inhibited by E1A binding to p300/CBP, Hypoxia-induced VEGF and Epo mRNA synthesis were similarly inhibited by E1A. Hence, p300/CBP-HIF complexes participate in the induction of hypoxia-responsive genes, including one (vascular endothelial growth factor) that plays a major role in tumor angiogenesis. Paradoxically, these data, to our knowledge for the first time, suggest that p300/CBP are active in both transformation suppression and tumor development. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL,BOSTON,MA 02115. RI Bhattacharya, Shoumo/F-4127-2010 NR 41 TC 478 Z9 498 U1 2 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 12 PY 1996 VL 93 IS 23 BP 12969 EP 12973 DI 10.1073/pnas.93.23.12969 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VT054 UT WOS:A1996VT05400055 PM 8917528 ER PT J AU Cheng, T Shen, HM Giokas, D Gere, J Tenen, DG Scadden, DT AF Cheng, T Shen, HM Giokas, D Gere, J Tenen, DG Scadden, DT TI Temporal mapping of gene expression levels during the differentiation of individual primary hematopoietic cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE differentiation; hematopoiesis; hematopoietic stem cells; transcription factors; gene expression ID COLONY-STIMULATING FACTOR; POLYMERASE CHAIN-REACTION; TRANSCRIPTION FACTOR PU.1; MESSENGER-RNA; FACTOR-RECEPTOR; STEM-CELLS; MYELOID DIFFERENTIATION; CD11B PROMOTER; MICE LACKING; C-FMS AB A hierarchical order of gene expression has been proposed to control developmental events in hematopoiesis, but direct demonstration of the temporal relationships between regulatory gene expression and differentiation has been difficult to achieve. We modified a single-cell PCR method to detect 2-fold changes in mRNA copies per cell (dynamic range, 250-250,000 copies/cell) and used it to sequentially quantitate gene expression levels as single primitive (CD34(+),CD38(-)) progenitor cells underwent differentiation to become erythrocytes, granulocytes, or monocyte/macrophages. Markers of differentiation such as CD34 or cytokine receptor mRNAs and transcription factors associated with their regulation were assessed, All transcription factors tested were expressed in multipotent progenitors. During lineage-specific differentiation, however, distinct patterns of expression emerged, SCL, GATA-2, and GATA-1 expression sequentially extinguished during erythroid differentiation. PU.1, AML1B, and C/EBP alpha expression profiles and their relationship to cytokine receptor expression in maturing granulocytes could be distinguished from similar profiles in monocytic cells, These data characterize the dynamics of gene expression accompanying blood cell development and define a signature gene expression pattern for specific stages of hematopoietic differentiation. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CTR AIDS RES,CHARLESTOWN,MA 02129. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02215. FU NHLBI NIH HHS [HL 44851, R01 HL044851]; NIDDK NIH HHS [DK 50234, R01 DK050234] NR 31 TC 142 Z9 145 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 NOV 12 PY 1996 VL 93 IS 23 BP 13158 EP 13163 DI 10.1073/pnas.93.23.13158 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VT054 UT WOS:A1996VT05400088 PM 8917561 ER PT J AU Baukrowitz, T Yellen, G AF Baukrowitz, T Yellen, G TI Two functionally distinct subsites for the binding of internal blockers to the pore of voltage-activated K+ channels SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE potassium channels; quaternary ammonium blockers; use-dependent blockade ID SHAKER POTASSIUM CHANNELS; 2 INACTIVATION MECHANISMS; MOLECULAR MECHANISMS; LOCAL-ANESTHETICS; SODIUM-CHANNELS; BLOCKADE; AXONS; CELLS AB Many blockers of Na+ and K+ channels act by blocking the pore from the intracellular side. For Shaker K+ channels, such intracellular blockers vary in their functional effect on slow (C-type) inactivation: Some blockers interfere with C-type inactivation, whereas others do not. These functional differences can be explained by supposing that there are two overlapping ''subsites'' for blocker binding, only one of which inhibits C-type inactivation through an allosteric effect. We find that the ability to bind to these subsites depends on specific structural characteristics of the blockers, and correlates with the effect of mutations in two distinct regions of the channel protein. These interactions are important because they affect the ability of blockers to produce use-dependent inhibition. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Baukrowitz, T (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,50 BLOSSOM ST,WEL340A,BOSTON,MA 02114, USA. OI Yellen, Gary/0000-0003-4228-7866 FU NINDS NIH HHS [R01 NS029693, NS29693] NR 21 TC 47 Z9 47 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 12 PY 1996 VL 93 IS 23 BP 13357 EP 13361 DI 10.1073/pnas.93.23.13357 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VT054 UT WOS:A1996VT05400122 PM 8917595 ER PT J AU HirtArmon, K Pober, BR Holmes, LB AF HirtArmon, K Pober, BR Holmes, LB TI Type III tracheal agenesis with familial tetralogy of Fallot and absent pulmonary valve syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE tracheal agenesis (TA); tetralogy of Fallot (TOF); congenital absence of pulmonary valve syndrome (CAPV); ventricular septal defect (VSD); fluorescent in situ hybridization (FISH) ID MALFORMATIONS AB We describe a female infant born at 33 weeks gestation diagnosed postnatally with a previously unreported phenotype consisting of Type III tracheal agenesis plus tetralogy of Fallot with absent pulmonary valve. She was delivered to a mother who had the same congenital heart malformation, but no detectable tracheal abnormality. We discuss possible etiologies of these malformations. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,GENET & TERATOL UNIT,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT NEWBORN MED,BOSTON,MA 02115. YALE UNIV,DEPT HUMAN GENET,NEW HAVEN,CT 06520. NR 19 TC 5 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 11 PY 1996 VL 65 IS 4 BP 266 EP 268 DI 10.1002/(SICI)1096-8628(19961111)65:4<266::AID-AJMG3>3.0.CO;2-N PG 3 WC Genetics & Heredity SC Genetics & Heredity GA VQ484 UT WOS:A1996VQ48400003 PM 8923932 ER PT J AU Prence, EM Zalewski, I Natowicz, MR AF Prence, EM Zalewski, I Natowicz, MR TI Unusual thermolability properties of beta-hexosaminidase: Studies of enzyme from cultured cells and clinical implications SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE beta-hexosaminidase; Tay-Sachs disease; prenatal diagnosis ID TAY-SACHS-DISEASE; CARRIER DETECTION; PSEUDODEFICIENCY; DIAGNOSIS AB Tay Sachs disease (TSD) is a neurodegenerative genetic disorder caused by a deficiency of beta-hexosaminidase A (Hex A) activity, To diagnose TSD and to screen for TSD heterozygosity, laboratories use an assay that exploits the differential thermolability of the major beta-hexosaminidase isoenzymes, Hex A and Hex B. At 50-52 degrees C Hex A is labile, and Hex B is stable. We previously noted that the stability of leukocyte Hex B at 52 degrees C varied significantly, depending on the sample concentration in the incubation mixture. We have now examined this phenomenon in enzyme from cultured cells used for prenatal and postnatal diagnostic testing. We found that fibroblast Hex A and Hex B behave similarly to the leukocyte isoenzymes, in control and TSD fibroblasts there was a linear correlation between Hex B thermostability and sample concentration; at lower sample concentrations Hex B was less stable than at higher concentrations, Dialysis of the samples prior to heat treatment did not change the thermostability properties of Hex B, indicating that the change in stability is not due to a soluble low molecular weight substance, Cultured amniotic fluid cell and chorionic villus cell Hex B had a similar, but less pronounced, instability at low sample concentrations, Therefore, the unusual thermolability properties of Hex B, first detected for leukocyte Hex B, were noted in multiple tissues, Based on these data, we suggest that the concentration of cell extract be stringently controlled when the heat-inactivation method is used for the pre- or postnatal diagnosis of TSD, and that supplementation with non-thermolability-based beta-hexosaminidase assays should be employed as needed. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Prence, EM (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV MED GENET,200 TRAPELO RD,WALTHAM,MA 02254, 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 11 PY 1996 VL 65 IS 4 BP 320 EP 324 DI 10.1002/(SICI)1096-8628(19961111)65:4<320::AID-AJMG14>3.0.CO;2-W PG 5 WC Genetics & Heredity SC Genetics & Heredity GA VQ484 UT WOS:A1996VQ48400014 PM 8923943 ER PT J AU Johnson, J Chen, TK Rickman, DW Evans, C Brecha, NC AF Johnson, J Chen, TK Rickman, DW Evans, C Brecha, NC TI Multiple gamma-aminobutyric acid plasma membrane transporters (GAT-1, GAT-2, GAT-3) in the rat retina SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE neurotransmitter transporter; amacrine cells; retina pigment epithelium; nonpigmented ciliary epithelium; glia cells ID GABA-LIKE IMMUNOREACTIVITY; CARRIER-MEDIATED RELEASE; MACAQUE MONKEY RETINA; HORIZONTAL CELLS; RABBIT RETINA; GLUTAMATE-DECARBOXYLASE; AMACRINE CELLS; GLIAL-CELLS; IMMUNOCYTOCHEMICAL LOCALIZATION; NEUROTRANSMITTER TRANSPORTERS AB gamma-Aminobutyric acid (GABA) plasma membrane transporters (GATs) influence synaptic neurotransmission by high-affinity uptake and release of GABA. The distribution and cellular localization of GAT-1, GAT-2, and GAT-3 in the rat retina have been evaluated by using affinity-purified polyclonal antibodies directed to the C terminus of each of these GAT subtypes. Small GAT-1-immunoreactive cell bodies were located in the proximal inner nuclear layer (INL) and ganglion cell layer (GCL), and processes were distributed to all laminae of the interplexiform layer (IPL). Varicose processes were in the optic fiber layer (OFL) and the outer plexiform layer (OPL). Weak GAT-1 immunostaining surrounded cells in the INL and GCL, and it was found in the OFL and OPL and in numerous processes in the outer nuclear layer (ONL) that ended at the outer limiting membrane. GAT-1 is therefore strongly expressed by amacrine, displaced amacrine, and interplexiform cells and weakly expressed by Muller cells. GAT-2 immunostaining was observed in the retina pigment epithelium and the nonpigmented ciliary epithelium. GAT-3 immunoreactivity was distributed to the OFL, to all laminae of the IPL, GCL and INL, and to processes in the ONL that ended at the outer limiting membrane. Small GAT-3-immunoreactive cell bodies were in the proximal INL and GCL. GAT-3 is therefore strongly expressed by Muller cells, and by some amacrine and displaced amacrine cells. Together, these observations demonstrate a heterologous distribution of GATs in the retina. These transporters are likely to take up GABA from, and perhaps release GABA into, the synaptic cleft and extracellular space. This suggests that GATs regulate GABA levels in these areas and thus influence synaptic neurotransmission. (C) 1996 Wiley-Liss, Inc. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROBIOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,DIGEST DIS RES CTR,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,JULES STEIN EYE INST,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,INST NEUROPSYCHIAT,LOS ANGELES,CA 90095. ST LOUIS UNIV,DEPT OPHTHALMOL,ST LOUIS,MO 63104. ST LOUIS UNIV,ANHEUSER BUSCH EYE INST,ST LOUIS,MO 63104. RP Johnson, J (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CURE,11301 WILSHIRE BLVD,BLDG 115,ROOM 221,LOS ANGELES,CA 90073, USA. FU NEI NIH HHS [R01 EY004067, R56 EY004067, R01 EY004067-15, EY 04067] NR 86 TC 96 Z9 97 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD NOV 11 PY 1996 VL 375 IS 2 BP 212 EP 224 PG 13 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VR073 UT WOS:A1996VR07300003 PM 8915826 ER PT J AU Inoue, G Cheatham, B Kahn, CR AF Inoue, G Cheatham, B Kahn, CR TI Different pathways of postreceptor desensitization following chronic insulin treatment and in cells overexpressing constitutively active insulin receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; GROWTH-FACTOR-I; DOWN-REGULATION; TRANSMEMBRANE DOMAIN; SOS-GRB2 COMPLEX; RAS ACTIVATION; S6 KINASE; SIGNAL; SHC; DISASSOCIATION AB We have reported previously that substitution of the transmembrane domain of the insulin receptor with that of the erbB-2 oncogene (IR(erbV-->E)) results in constitutive activation of the insulin receptor kinase. Compared to NIH3T3 cells overexpressing wild-type insulin receptors (IR(wt)), cells overexpressing IR(erbV-->E) displayed a decrease in IRS-1 protein content by 55%, but basal tyrosine phosphorylation of IRS-1 was increased. This resulted in an increased association of IRS-1 with the p85 subunit of phosphatidylinositol 3-kinase, increased phosphatidylinositol 3-kinase activity in anti-IRS-1 immunoprecipitates, constitutive activation of p70 S6 protein kinase, and an increased association of Grb2 with She in the absence of Ligand. However, Grb2 association with IRS-1 could not be detected in the basal or insulin-stimulated states, and mitogen-activated protein kinase (MAPK) activity could not be stimulated by insulin, epidermal growth factor, or platelet-derived growth factor. In contrast to IR(erbV-->E), the insulin receptor content and its tyrosine phosphorylation were significantly decreased in IR(wt) cells chronically stimulated (>24 h) with insulin, With decreased IRS-1 content, tyrosine phosphorylation of IRS-1 was decreased by over 75%, leading to decreased IRS-1-associated PI 3-kinase and Grb2. In addition, Grb2 association with She and activation of MAPK and the p70 S6 kinase were insensitive to insulin stimulation, By contrast, association of Grb2 with She and activation of MAPK; but not the p70 S6 kinase, could be stimulated by epidermal growth factor or platelet-derived growth factor. These data suggest that there are multiple levels of postreceptor desensitization to insulin action. These are used somewhat differently in these two different models, probably due in part to the difference in receptor down-regulation. C1 BRIGHAM & WOMENS HOSP,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. FU NIDDK NIH HHS [DK 36836, DK 31036] NR 35 TC 19 Z9 19 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 NOV 8 PY 1996 VL 271 IS 45 BP 28206 EP 28211 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VU033 UT WOS:A1996VU03300037 PM 8910437 ER PT J AU Krane, SM Byrne, MH Lemaitre, V Henriet, P Jeffrey, JJ Witter, JP Liu, X Wu, H Jaenisch, R Eeckhout, Y AF Krane, SM Byrne, MH Lemaitre, V Henriet, P Jeffrey, JJ Witter, JP Liu, X Wu, H Jaenisch, R Eeckhout, Y TI Different collagenase gene products have different roles in degradation of type I collagen SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MATRIX METALLOPROTEINASES; INTERSTITIAL COLLAGENASE; FIBROBLAST COLLAGENASE; SEQUENCE-ANALYSIS; HUMAN STROMELYSIN; CLEAVAGE SITE; MESSENGER-RNA; CELLS; PURIFICATION; CLONING AB Vertebrate collagenases, matrix metalloproteinases (MMPs), cleave type I collagen at a single helical locus. We show here that rodent interstitial collagenases (MMP-13), but not human fibroblast collagenase (MMP-1), cleave type I collagen at an additional aminoitelopeptide locus. Collagenase cDNAs and chimeric constructs in pET-3d, juxtaposing MMP-13 sequences amino-terminal to the active site in the catalytic domain and MMP-1 sequences carboxyl-terminal and vice versa, were expressed in Escherichia coli. Assays utilized collagen from wild type (+/+) mice or mice that carry a targeted mutation (r/r) that encodes substitutions in alpha 1(I) chains that prevent collagenase cleavage at the helical locus, MMP-13 and chimeric molecules that contained the MMP-13 sequences amino-terminal to the active site cleaved (+/+) collagen at the helical locus and cleaved cross-linked (r/r) collagen in the aminotelopeptide (beta components converted to ct chains), Human MMP-1 and chimeric MMP-1/MMP-13 with MMP-1 sequences aminoterminal to the active site cleaved collagen at the helical locus but not in the aminotelopeptide. All activities were inhibited by TIMP-1, 1,10-phenanthroline, and EDTA. Sequences in the distal two-thirds of the catalytic domain determine the aminotelopeptide-degrading capacity of MMP-13. C1 MASSACHUSETTS GEN HOSP, ARTHRIT UNIT, BOSTON, MA 02114 USA. UNIV LOUVAIN, CONNECT TISSUE GRP, B-1200 BRUSSELS, BELGIUM. INT INST CELLULAR & MOL PATHOL, B-1200 BRUSSELS, BELGIUM. ALBANY MED COLL, DEPT MED, DIV HEMATOL, ALBANY, NY 12208 USA. WHITEHEAD INST BIOMED RES, CAMBRIDGE, MA 02142 USA. MIT, DEPT BIOL, CAMBRIDGE, MA 02142 USA. RP HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02114 USA. FU NIAMS NIH HHS [AR-03564, TR-AR-07258]; NICHD NIH HHS [HD-05291] NR 36 TC 93 Z9 97 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 8 PY 1996 VL 271 IS 45 BP 28509 EP 28515 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VU033 UT WOS:A1996VU03300079 PM 8910479 ER PT J AU Rubin, SC Benjamin, I Behbakht, K Takahashi, H Morgan, MA LiVolsi, VA Berchuck, A Muto, MG Garber, JE Weber, BL Lynch, HT Boyd, J AF Rubin, SC Benjamin, I Behbakht, K Takahashi, H Morgan, MA LiVolsi, VA Berchuck, A Muto, MG Garber, JE Weber, BL Lynch, HT Boyd, J TI Clinical and pathological features of ovarian cancer in women with germ-line mutations of BRCA1 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FAMILIES; BREAST; GENE; MANAGEMENT AB Background We tested the hypothesis that ovarian cancers associated with germ-line mutations of BRCA1 have distinct clinical and pathological features as compared with sporadic ovarian cancers. Methods We reviewed clinical and pathological data on patients with primary epithelial ovarian cancer found to have germ-fine mutations of BRCA1. Survival among patients with advanced-stage cancer and such mutations was compared with that in control patients matched for age and stage, grade, and histologic subtype of the tumors. A combination of single-strand conformation and sequencing analyses was used to examine the 22 coding exons and intronic splice-donor and splice-acceptor regions of BRCA1 for mutations in pathological specimens. Alternatively, some patients were known to be obligate carriers of the mutant BRCA1 gene because of their parental relationships with documented mutant-gene carriers. Results We identified 53 patients with germ-line mutations of BRCA1. The average age at diagnosis was 48 years (range, 28 to 78). Histologic examination in 43 of the 53 patients showed serous adenocarcinoma. Thirty-seven tumors were of grade 3, 11 were of grade 2, 2 were of grade 1, and 3 were of low malignant potential. In 38 patients, the tumors were of stage III; 9 patients (including those with tumors of low malignant potential) had stage I disease, 5 had stage IV, and 1 had stage II. As of June 1996, with a median follow-up among survivors of 71 months from diagnosis, 20 patients had died of ovarian cancer, 27 had no evidence of the disease, 4 were alive with the disease, and 2 had died of other diseases. Actuarial median survival for the 43 patients with advanced-stage disease was 77 months, as compared with 29 months for the matched controls (P<0.001). Conclusions As compared with sporadic ovarian cancers, cancers associated with BRCA1 mutations appear to have a significantly more favorable clinical course. (C)1996, Massachusetts Medical Society. C1 UNIV PENN,MED CTR,DEPT LAB MED & PATHOL,DIV ANAT PATHOL,PHILADELPHIA,PA 19104. UNIV PENN,MED CTR,DIV HEMATOL & ONCOL,DEPT MED,PHILADELPHIA,PA 19104. BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. CREIGHTON UNIV,SCH MED,DEPT PREVENT MED & PUBL HLTH,OMAHA,NE. RP Rubin, SC (reprint author), UNIV PENN,MED CTR,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,3400 SPRUCE ST,PHILADELPHIA,PA 19104, USA. OI Behbakht, Kian/0000-0003-4793-9958 NR 20 TC 325 Z9 331 U1 1 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 7 PY 1996 VL 335 IS 19 BP 1413 EP 1416 DI 10.1056/NEJM199611073351901 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA VT339 UT WOS:A1996VT33900001 PM 8875917 ER PT J AU Nathan, DM AF Nathan, DM TI Lifetime benefits and costs of intensive therapy as practiced in the diabetes control and complications trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LOWER-EXTREMITY AMPUTATION; NEPHROPATHY; RETINOPATHY; PREVALENCE; MELLITUS; PEOPLE; CARE; POPULATION; TECHNOLOGY; IDDM AB Objective.-To examine the cost-effectiveness of alternative approaches to the management of insulin-dependent diabetes mellitus (IDDM). Design.-A Monte Carlo simulation model was developed to estimate the lifetime benefits and costs of conventional and intensive insulin therapy. Data were collected as part of the Diabetes Control and Complications Trial (DCCT) and supplemented with data from other clinical trials and epidemiologic studies. Setting.-Twenty-nine academic medical centers. Patients.-Persons with IDDM in the United States who meet demographic and clinical eligibility criteria for enrollment in the DCCT. Interventions.-Conventional vs intensive diabetes management. Results.-Approximately 120 000 persons with IDDM in the United States meet DCCT eligibility criteria. implementing intensive rather than conventional therapy in this population would result in a gain of 920 000 years of sight, 691 000 years free from end-stage renal disease, 678 000 years free from lower extremity amputation, and 611 000 years of life at an additional cost of $4.0 billion over the lifetime of the population. The incremental cost per year of life gained is $28 661. Conclusions.-Over a lifetime, DCCT-defined intensive therapy reduces complications, improves quality of life, and can be expected to increase length of life. From a health care system perspective, intensive therapy is well within the range of cost-effectiveness considered to represent a good value. RP Nathan, DM (reprint author), MASSACHUSETTS GEN HOSP, DIABET UNIT BULFINCH 408, 32 FRUIT ST, BUL 405, BOSTON, MA 02114 USA. RI Zinman, Bernard/E-7266-2013 NR 49 TC 298 Z9 301 U1 2 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 6 PY 1996 VL 276 IS 17 BP 1409 EP 1415 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA VQ464 UT WOS:A1996VQ46400027 ER PT J AU Lohi, J Tani, T Leivo, I Linnala, A Kangas, L Burgeson, RE Lehto, VP Virtanen, I AF Lohi, J Tani, T Leivo, I Linnala, A Kangas, L Burgeson, RE Lehto, VP Virtanen, I TI Expression of laminin in renal-cell carcinomas, renal-cell carcinoma cell lines and xenografts in nude mice SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; DIFFERENTIAL EXPRESSION; CLONING; KIDNEY; CHAIN; RECEPTORS; KALININ; TUMORS AB We studied the expression of laminin (Ln) chains (alpha 1-alpha 3 beta 1-beta 3, gamma 1) in human renal-cell carcinomas (RCC), papillary renal neoplasms (PRN) and oncocytomas, in RCC cell lines and their xenografts. In RCCs the basement membranes (BM) showed immunoreactivity for chains of Ln-1 (alpha 1-beta 1-gamma 1). Only in well-differentiated RCCs could vessel BMs be distinguished from those of carcinoma cell islets. RCCs and oncocytomas also exhibited an abundant immunoreactivity for Ln beta 2 chain in both vessel and tumor cell BMs, while Ln alpha 2 chain was not seen in any renal tumors. In distinction from RCCs, PRNs presented a strong BM immunoreactivity for Ln alpha 3 and beta 3 chains and for Ln-5, as well as lack of Ln beta 2 chain. A more variable reactivity for Ln-5 was seen in oncocytomas. As PRNs and oncocytomas have been suggested to originate from collecting ducts, it is notable that in normal human kidney, we could detect immunoreactivity for Ln-5 and its chains only in BM of the tubules of the loop of Henle. In immunoprecipitation experiments, an abundant production of Ln-l, but not of Ln-5, was seen in cultured RCC cells, while in xenografts of the same cells BM-confined immunoreactivity for both Ln-1 and Ln-5 was seen. Ln beta 2 chain was produced by 2 of the 4 RCC cell lines in culture but was found only in 1 of the xenografted tumors. (C) 1996 Wiley-Liss, Inc. C1 UNIV HELSINKI,CENT HOSP,DEPT PATHOL,TURKU,FINLAND. ORION CORP FARMOS,FARMOS RES,SF-20101 TURKU,FINLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA. UNIV OULU,BIOCTR,OULU,FINLAND. UNIV OULU,DEPT PATHOL,OULU,FINLAND. RP Lohi, J (reprint author), UNIV HELSINKI,DEPT ANAT,INST BIOMED,POB 9,SILTAVUORENPENGER 20A,FIN-00014 HELSINKI,FINLAND. NR 24 TC 16 Z9 16 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 4 PY 1996 VL 68 IS 3 BP 364 EP 371 DI 10.1002/(SICI)1097-0215(19961104)68:3<364::AID-IJC15>3.0.CO;2-8 PG 8 WC Oncology SC Oncology GA VR176 UT WOS:A1996VR17600015 PM 8903479 ER PT J AU Galpern, WR Matthews, RT Beal, MF Isacson, O AF Galpern, WR Matthews, RT Beal, MF Isacson, O TI NGF attenuates 3-nitrotyrosine formation in a 3-NP model of Huntington's disease SO NEUROREPORT LA English DT Article DE free radicals; neuroprotection; neurotrophic factor; nitric oxide; 3-nitrotyrosine; peroxynitrite; superoxide ID NERVE GROWTH-FACTOR; SUPEROXIDE-DISMUTASE; NEURODEGENERATIVE DISEASES; 3-NITROPROPIONIC ACID; STRIATAL DEGENERATION; AGED RATS; IMPAIRMENT; ENERGY; GLUTAMATE; RECEPTOR AB NERVE growth factor (NGF)-secreting fibroblasts are able to protect against the Huntington-like striatal neurodegeneration induced by the mitochondrial toxin 3-nitropropionic acid (3-NP). In the present study, we investigated whether the neuroprotective effects of NGF are mediated through antioxidative mechanisms. Rats were grafted in the corpus callosum with NGF[+] or NGF[-] fibroblasts 7 days before administration of 3-NP. The generation of peroxynitrite was evaluated by measuring the striatal levels of 3-nitrotyrosine. NGF significantly decreased the 3-NP induced generation of S-nitrotyrosine, presumably by decreasing peroxynitrite formation. These findings suggest that NGF might protect against neuronal death by inhibiting the production of nitric oxide or decreasing the levels of superoxide radicals, thereby decreasing the generation of oxidative agents such as peroxynitrite. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA 01655. RP Galpern, WR (reprint author), HARVARD UNIV,SCH MED,MCLEAN HOSP,NEUROGENERAT LAB,PROGRAM NEUROSCI,MCR 119,115 MILL ST,BELMONT,MA 02178, USA. FU NINDS NIH HHS [NS 16367, NS 31579, NS 30064] NR 26 TC 44 Z9 44 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 4 PY 1996 VL 7 IS 15-17 BP 2639 EP 2642 DI 10.1097/00001756-199611040-00046 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WB711 UT WOS:A1996WB71100046 PM 8981438 ER PT J AU Clarke, M Collins, R Davies, C Godwin, J Gray, R Peto, R Abe, O Abe, R Enomoto, K Kikuchi, K Koyama, H Nomura, Y Sakai, K Sugimachi, K Tominaga, T Uchino, J Yoshida, M vandeVelde, AO vanDongen, JA Vermorken, JB Arvelakis, A Giokas, G Lissaios, B Harvey, VJ Holdaway, TM Kay, RG Mason, BH Coates, A Forbes, JF Focan, C Lobelle, JP Peek, U Oates, GD Powell, J Bastert, G Rauschecker, H Sauer, R Sauerbrei, W Schauer, A Schumacher, M Durand, M Mauriac, L Bartholomeus, S Piccart, MJ Gelman, RS Henderson, IC Shapiro, CL Hancock, AK Masood, MB Parker, D Price, JJ Jackson, S Ragaz, J Delozier, T MaceLesech, J Haybittle, JL Cirrincione, C Korzun, A Weiss, RB Wood, WC Baum, M Houghton, J Riley, D Dent, DM Gudgeon, CA Hacking, A Horgan, K Hughes, L Stewart, HJ Gordon, NH Davis, HL Lehingue, Y Owen, JR Meier, P Howell, A Ribeiro, GC Swindell, R Albano, J deOliveira, CF Gervasio, H Gordilho, J Carstensen, B Palshof, T Johansen, H Korzeniowski, S Skolyszewski, J Andersen, KW Axelsson, CK BlichertToft, M Mouridsen, HT Overgaard, M Rose, C Corcoran, N Trampisch, HJ Abeloff, MD Carbone, PC Glick, J Tormey, DC Rossbach, J Scanlon, EF Schurman, S deSchryver, A Yosef, HMA McArdle, CS Smith, DC Lara, PC Boccardo, F Erazo, A Medina, JY Izuo, M Morishita, Y Bentley, A Doran, Z Fentiman, IS Hayward, JL Rubens, RD Kaufmann, M Jonat, W Scheurlen, H vonFournier, D Fountzilas, G Klefstrom, P Blomqvist, C Cuzick, J Margreiter, R Castiglione, M Cavalli, F Collins, J Forbes, J Gelber, RD Goldhirsch, A Lindtner, J Price, KN Rudenstam, CM Senn, HJ Bliss, JM Chilvers, CED Coombes, RC Marty, M Borovik, R Brufman, G Hayat, H Robinson, E Wigler, N Pannuti, F Takashima, S Tasutomi, T Sonoo, H Yamashita, J Ogawa, M Hupperets, PSGJ Bonte, J Tengrup, I TennvallNittby, L Martin, P Romain, S Ahmann, D Schaid, DJ Buzdar, AU Smith, T Hakes, T Norton, L Wittes, R delaHuerta, R Sainz, MG Bonadonna, G delVecchio, M Valagussa, P Veronesi, U Dubois, JB Bianco, AR Lippman, ME Pierce, LJ Simon, R Steinberg, SM Brown, A Fisher, B Redmond, C Wolmark, N Jackson, IM Palmer, MK Ingle, JN Suman, VJ Bengtsson, NO Larsson, LG Lythgoe, JP Kissin, M Hannisdal, E Varhaug, JE NissenMeyer, R Blamey, RW Mitchell, AK Robertson, JFR Nakamura, Y Mathe, G Misset, JL AbuZahra, HT Clarke, EA McLaughlin, JR Clark, RM Levine, M Myles, JD Pater, JL Pritchard, KI Morimoto, K Sawa, K Takatsuka, Y Gundersen, S HauerJensen, M Host, A Crossley, E Durrant, K Harris, A Beighton, A Collins, R Evans, V Greaves, E Harwood, C James, S Lau, E Mead, G Muldal, A Naughton, A Tooth, A Wheatley, K Rambert, P Asselain, B Salmon, RJ Vilcoq, JR Arriagada, R Hill, C Laplanche, A Le, MG Speilmann, M Cocconi, G diBlasio, B Catalano, R Creech, RH Brockschmidt, J Cooper, MR Andrysek, O Barkmanova, J Falkson, CJ Abraham, M Klijn, JGM TreurnietDonker, AD vanPutten, WLJ Easton, D Powles, TJ Gazet, JC Semiglazov, V Deshpande, N diMartino, L Douglas, P Host, H Bryant, AJS Ewing, GH KrushenKosloski, JL Forrest, APM Jack, W McDonald, C Moller, TR Ryden, S Carstensen, J Hatschek, T Soderberg, M Carpenter, JT Albain, K Crowley, J Green, S Martino, S Osborne, CK Ravdin, PM Rutqvist, LE Wallgren, A Holm, LE Yoshimoto, M DeBoer, G Paterson, AHG Meakin, JW Panzarella, T Naja, A Bahi, J Reid, M Spittle, M Senanayake, F Bergh, J Holmberg, L Sevelda, P Zielinsky, CC Jakesz, R Gnant, M Buchanan, RB Cross, M Dunn, JA Gillespie, WM Kelly, K Morrison, JM Litton, A Chlebowski, RT Bezwoda, WR Caffier, H AF Clarke, M Collins, R Davies, C Godwin, J Gray, R Peto, R Abe, O Abe, R Enomoto, K Kikuchi, K Koyama, H Nomura, Y Sakai, K Sugimachi, K Tominaga, T Uchino, J Yoshida, M vandeVelde, AO vanDongen, JA Vermorken, JB Arvelakis, A Giokas, G Lissaios, B Harvey, VJ Holdaway, TM Kay, RG Mason, BH Coates, A Forbes, JF Focan, C Lobelle, JP Peek, U Oates, GD Powell, J Bastert, G Rauschecker, H Sauer, R Sauerbrei, W Schauer, A Schumacher, M Durand, M Mauriac, L Bartholomeus, S Piccart, MJ Gelman, RS Henderson, IC Shapiro, CL Hancock, AK Masood, MB Parker, D Price, JJ Jackson, S Ragaz, J Delozier, T MaceLesech, J Haybittle, JL Cirrincione, C Korzun, A Weiss, RB Wood, WC Baum, M Houghton, J Riley, D Dent, DM Gudgeon, CA Hacking, A Horgan, K Hughes, L Stewart, HJ Gordon, NH Davis, HL Lehingue, Y Owen, JR Meier, P Howell, A Ribeiro, GC Swindell, R Albano, J deOliveira, CF Gervasio, H Gordilho, J Carstensen, B Palshof, T Johansen, H Korzeniowski, S Skolyszewski, J Andersen, KW Axelsson, CK BlichertToft, M Mouridsen, HT Overgaard, M Rose, C Corcoran, N Trampisch, HJ Abeloff, MD Carbone, PC Glick, J Tormey, DC Rossbach, J Scanlon, EF Schurman, S deSchryver, A Yosef, HMA McArdle, CS Smith, DC Lara, PC Boccardo, F Erazo, A Medina, JY Izuo, M Morishita, Y Bentley, A Doran, Z Fentiman, IS Hayward, JL Rubens, RD Kaufmann, M Jonat, W Scheurlen, H vonFournier, D Fountzilas, G Klefstrom, P Blomqvist, C Cuzick, J Margreiter, R Castiglione, M Cavalli, F Collins, J Forbes, J Gelber, RD Goldhirsch, A Lindtner, J Price, KN Rudenstam, CM Senn, HJ Bliss, JM Chilvers, CED Coombes, RC Marty, M Borovik, R Brufman, G Hayat, H Robinson, E Wigler, N Pannuti, F Takashima, S Tasutomi, T Sonoo, H Yamashita, J Ogawa, M Hupperets, PSGJ Bonte, J Tengrup, I TennvallNittby, L Martin, P Romain, S Ahmann, D Schaid, DJ Buzdar, AU Smith, T Hakes, T Norton, L Wittes, R delaHuerta, R Sainz, MG Bonadonna, G delVecchio, M Valagussa, P Veronesi, U Dubois, JB Bianco, AR Lippman, ME Pierce, LJ Simon, R Steinberg, SM Brown, A Fisher, B Redmond, C Wolmark, N Jackson, IM Palmer, MK Ingle, JN Suman, VJ Bengtsson, NO Larsson, LG Lythgoe, JP Kissin, M Hannisdal, E Varhaug, JE NissenMeyer, R Blamey, RW Mitchell, AK Robertson, JFR Nakamura, Y Mathe, G Misset, JL AbuZahra, HT Clarke, EA McLaughlin, JR Clark, RM Levine, M Myles, JD Pater, JL Pritchard, KI Morimoto, K Sawa, K Takatsuka, Y Gundersen, S HauerJensen, M Host, A Crossley, E Durrant, K Harris, A Beighton, A Collins, R Evans, V Greaves, E Harwood, C James, S Lau, E Mead, G Muldal, A Naughton, A Tooth, A Wheatley, K Rambert, P Asselain, B Salmon, RJ Vilcoq, JR Arriagada, R Hill, C Laplanche, A Le, MG Speilmann, M Cocconi, G diBlasio, B Catalano, R Creech, RH Brockschmidt, J Cooper, MR Andrysek, O Barkmanova, J Falkson, CJ Abraham, M Klijn, JGM TreurnietDonker, AD vanPutten, WLJ Easton, D Powles, TJ Gazet, JC Semiglazov, V Deshpande, N diMartino, L Douglas, P Host, H Bryant, AJS Ewing, GH KrushenKosloski, JL Forrest, APM Jack, W McDonald, C Moller, TR Ryden, S Carstensen, J Hatschek, T Soderberg, M Carpenter, JT Albain, K Crowley, J Green, S Martino, S Osborne, CK Ravdin, PM Rutqvist, LE Wallgren, A Holm, LE Yoshimoto, M DeBoer, G Paterson, AHG Meakin, JW Panzarella, T Naja, A Bahi, J Reid, M Spittle, M Senanayake, F Bergh, J Holmberg, L Sevelda, P Zielinsky, CC Jakesz, R Gnant, M Buchanan, RB Cross, M Dunn, JA Gillespie, WM Kelly, K Morrison, JM Litton, A Chlebowski, RT Bezwoda, WR Caffier, H TI Ovarian ablation in early breast cancer: Overview of the randomised trials SO LANCET LA English DT Article AB Background Among women with early breast cancer, the effects of ovarian ablation on recurrence and death have been assessed by several randomised trials that now have long follow-up. In this report, the Early Breast Cancer Trialists' Collaborative Group present their third 5-yearly systematic overview (meta-analysis), now with 15 years' follow-up. Methods in 1995, information was sought on each patient in any randomised trial of ovarian ablation or suppression versus control that began before 1990. Data were obtained for 12 of the 13 studies that assessed ovarian ablation by irradiation or surgery, all of which began before 1980, but not for the four studies that assessed ovarian suppression by drugs, all of which began after 1985. Menopausal status was not consistently defined across trials; therefore, the main analyses are limited to women aged under 50 (rather than ''premenopausal'') when randomised. Oestrogen receptors were measured only in the trials of ablation plus cytotoxic chemotherapy versus the same chemotherapy alone. Findings Among 2102 women aged under 50 when randomised, most of whom would have been premenopausal at diagnosis, 1130 deaths and an additional 153 recurrences were reported. 15-year survival was highly significantly improved among those allocated ovarian ablation (52 . 4 vs 46 . 1%, 6 . 3 [SD 2 . 3] fewer deaths per 100 women, logrank 2p=0 . 001), as was recurrence-free survival (45 . 0 vs 39 . 0%, 2p=0 . 0007). The numbers of events were too small for any subgroup analyses to be reliable. The benefit was, however, significant both for those with (''node positive'') and for those without (''node negative'') axillary spread when diagnosed. In the trials of ablation plus cytotoxic chemotherapy versus the same chemotherapy alone, the benefit appeared smaller (even for women with oestrogen receptors detected on the primary tumour) than in the trials of ablation in the absence of chemotherapy (where the observed survival improvements were about six per 100 node-negative women and 12 per 100 node-positive women). Among 1354 women aged 50 or over when randomised, most of whom would have been perimenopausal or postmenopausal, there was only a non-significant improvement in survival and recurrence-free survival. Interpretation In women aged under 50 with early breast cancer, ablation of functioning ovaries significantly improves long-term survival, at least in the absence of chemotherapy. Further randomised evidence is needed on the additional effects of ovarian ablation in the presence of other adjuvant treatments, and to assess the relevance of hormone-receptor measurements. C1 AMSTERDAM INTEGRAAL KANKERCTR, AMSTERDAM, NETHERLANDS. ATHENS METAXAS MEM CANC HOSP, ATHENS, GREECE. AUCKLAND BREAST CANC STUDY GRP, AUCKLAND, NEW ZEALAND. CARDIFF SURG TRIALISTS, CARDIFF, S GLAM, WALES. BERLIN BUCH AKAD WISSENSCH, BERLIN, GERMANY. BIRMINGHAM GEN HOSP, BIRMINGHAM, W MIDLANDS, ENGLAND. BMFT FREIBERG, FREIBERG, GERMANY. BORDEAUX INST BERGONIE, BORDEAUX, FRANCE. DANA FARBER CANC INST, BOSTON, MA 02115 USA. BRADFORD ROYAL INFIRM, BRADFORD BD9 6RJ, W YORKSHIRE, ENGLAND. BRITISH COLUMBIA CANC AGCY, VANCOUVER, BC V5Z 4E6, CANADA. CAEN CTR REG FRANCOIS BACLESSE, CAEN, FRANCE. ADDENBROOKES HOSP, CAMBRIDGE, ENGLAND. CANC & LEUKEMIA GRP B, DURHAM, NC USA. CANC RES CAMPAIGN, LONDON SW1Y 5AR, ENGLAND. GROOTE SCHUUR HOSP, ZA-7925 CAPE TOWN, SOUTH AFRICA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. CTR LEON BERARD, F-69373 LYON, FRANCE. CHELTENHAM GEN HOSP, CHELTENHAM, GLOS, ENGLAND. UNIV CHICAGO, CHICAGO, IL 60637 USA. CHRISTIE HOSP & HOLT RADIUM INST, MANCHESTER M20 9BX, LANCS, ENGLAND. COIMBRA INST ONCOL, COIMBRA, PORTUGAL. DANISH CANC REGISTRY, COPENHAGEN, DENMARK. COPENHAGEN RADIUM CTR, COPENHAGEN, DENMARK. CRACOW INST ONCOL, KRAKOW, POLAND. ST LUKES HOSP, DUBLIN, IRELAND. UNIV DUSSELDORF, D-4000 DUSSELDORF, GERMANY. EASTERN COOPERAT ONCOL GRP, BOSTON, MA USA. EUROPEAN ORG RES TREATMENT CANC, BRUSSELS, BELGIUM. NORTHWESTERN UNIV, EVANSTON HOSP, EVANSTON, IL 60201 USA. STATE UNIV GHENT HOSP, B-9000 GHENT, BELGIUM. WESTERN INFIRM & ASSOCIATED HOSP, BEATSON ONCOL CTR, GLASGOW G11 6NT, LANARK, SCOTLAND. GLASGOW VICTORIA INFIRM, GLASGOW, LANARK, SCOTLAND. GRANADA UNIV HOSP, GRANADA, SPAIN. GUADALAJARA HOSP 20 NOVIEMBRE, GUADALAJARA, JALISCO, MEXICO. GUNMA UNIV, MAEBASHI, GUMMA 371, JAPAN. GUYS HOSP, LONDON SE1 9RT, ENGLAND. HEIDELBERG UNIV 1, HEIDELBERG, GERMANY. HEIDELBERG UNIV 2, HEIDELBERG, GERMANY. HELLENIC COOPERAT ONCOL GRP, ATHENS, GREECE. HELSINKI DEACONESS MED CTR, HELSINKI, FINLAND. UNIV HELSINKI, FIN-00014 HELSINKI, FINLAND. IMPERIAL CANC RES FUND, LONDON WC2A 3PX, ENGLAND. UNIV INNSBRUCK, A-6020 INNSBRUCK, AUSTRIA. LUDWIG INT BREAST CANC STUDY GRP, EPALINGES, SWITZERLAND. INT COLLABORAT CANC GRP, LONDON, ENGLAND. ISRAEL NSABC, JERUSALEM, ISRAEL. KAWASAKI MED UNIV, KAWASAKI, KANAGAWA, JAPAN. KUMAMOTO UNIV GRP, KUMAMOTO, JAPAN. KYUSHU NATL CANC CTR, FUKUOKA, JAPAN. BREAST CANC STUDY GRP COMPREHENS CANC CTR, LIMBURG, NETHERLANDS. ACAD ZIEKENHUIS ST RAFAEL, LOUVAIN, BELGIUM. MARSEILLE LAB CANCEROL BIOL APM, MARSEILLE, FRANCE. MAYO CLIN, ROCHESTER, MN 55905 USA. UNIV TEXAS, MD ANDERSON CANC CTR, HOUSTON, TX USA. MEXICAN NATL MED CTR, MEXICO CITY, DF, MEXICO. IST NAZL STUDIO & CURA TUMORI, I-20133 MILAN, ITALY. CTR PAUL LAMARQUE, MONTPELLIER, FRANCE. UNIV NAPLES, I-80138 NAPLES, ITALY. NCI, BETHESDA, MD 20892 USA. NORTHWICK PK HOSP & CLIN RES CTR, HARROW HA1 3UJ, MIDDX, ENGLAND. NORWEGIAN RADIUM HOSP, OSLO, NORWAY. CITY HOSP NOTTINGHAM, NOTTINGHAM, ENGLAND. OITA PREFECTURAL HOSP, OITA, JAPAN. ONTARIO CANC TREATMENT & RES FDN, TORONTO, ON, CANADA. ONTARIO CLIN ONCOL GRP, HAMILTON, ON, CANADA. CANADA CLIN TRIALS GRP, ONTARIO NATL CANC INST, KINGSTON, ON, CANADA. OSAKA CITY UNIV, OSAKA 558, JAPAN. OSAKA NATL HOSP, OSAKA, JAPAN. OSLO RADIUM HOSP, OSLO, NORWAY. OXFORD CHURCHILL HOSP, OXFORD, ENGLAND. OXFORD ICRF MRC CLIN TRIAL SERV UNIT, OXFORD, ENGLAND. CTR RENE HUGUENIN, PARIS, FRANCE. INST CURIE, PARIS, FRANCE. INST GUSTAVE ROUSSY, PARIS, FRANCE. PARMA HOSP, PARMA, ITALY. FOX CHASE CANC CTR, PHILADELPHIA, PA 19111 USA. PIEDMONT ONCOL ASSOC, WINSTON SALEM, NC USA. CHARLES UNIV, PRAGUE, CZECH REPUBLIC. UNIV PRETORIA, ZA-0002 PRETORIA, SOUTH AFRICA. INST CARDIOVASC ROSARIO, ROSARIO, ARGENTINA. DR DANIEL DEN HOED CANC CTR, NL-3008 AE ROTTERDAM, NETHERLANDS. ROYAL MARSDEN HOSP, CANC RES INST, LONDON, ENGLAND. UNIV LONDON ST GEORGES HOSP, LONDON SW17 0RE, ENGLAND. ST PETERSBURG PETROV RES INST ONCOL, ST PETERSBURG, RUSSIA. SARDINIA ONCOL HOSP A BUSINICO, SARDINIA, ITALY. SASKATCHEWAN CANC FDN, SASKATOON, SK, CANADA. SCOTTISH CANC TRIALS OFF, EDINBURGH, MIDLOTHIAN, SCOTLAND. SW ONCOL GRP, KANSAS CITY, KS USA. STOCKHOLM BREAST CANC STUDY GRP, STOCKHOLM, SWEDEN. KAROLINSKA HOSP, S-10401 STOCKHOLM, SWEDEN. SAKK & OSAKO, SWISS GRP CLIN CANC RES, BERN, SWITZERLAND. TEL AVIV UNIV, IL-69978 TEL AVIV, ISRAEL. CANC INST HOSP, TOKYO, JAPAN. TORONTO EDMONTON BREAST CANC STUDY GRP, TORONTO, ON, CANADA. PRINCESS MARGARET HOSP, TORONTO, ON M4X 1K9, CANADA. CTR CLAUDIUS REGAUD, TOULOUSE, FRANCE. INST SALAH AZAIZ, TUNIS, TUNISIA. UPPSALA OREBRO CANC STUDY GRP, UPPSALA, SWEDEN. UNIV HOSP VIENNA, DEPT GYNAECOL 1, VIENNA, AUSTRIA. UNIV HOSP VIENNA, DEPT SURG, VIENNA, AUSTRIA. UNIV WITWATERSRAND, ZA-2050 WITWATERSRAND, SOUTH AFRICA. UNIV WURZBURG, D-97070 WURZBURG, GERMANY. RP Clarke, M (reprint author), RADCLIFFE INFIRM, CLIN TRIAL SERV UNIT, OXFORD OX2 6HE, ENGLAND. RI Jonat, Walter/E-3024-2010; McLaughlin, John/E-4577-2013; Barkmanova, Jaroslava/A-1411-2017 OI Barkmanova, Jaroslava/0000-0003-1406-7292 NR 17 TC 352 Z9 357 U1 1 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD NOV 2 PY 1996 VL 348 IS 9036 BP 1189 EP 1196 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VQ467 UT WOS:A1996VQ46700009 ER PT J AU Crowley, WF Thier, SO AF Crowley, WF Thier, SO TI The continuing dilemma in clinical investigation and the future of American health care: A system-wide problem requiring collaborative solutions SO ACADEMIC MEDICINE LA English DT Article AB American medicine faces a paradox: on the one hand, decades of basic science research have produced fundamental insights into disease mechanisms. On the other, there has rarely been a more difficult environment for the training and employment of clinical investigators, who perform the research that translates basic biomedical knowledge into practical advances in patient cart. The authors explain the historical roots of this crisis and the lack of data about specific workforce needs for clinical investigators, discuss long-standing difficulties of recruiting, training, and retaining these scientists (e.g., time-consuming training, inadequate emphasis on clinical research in medical school, fewer role models) and why these processes are becoming more difficult (e.g., a coming flattening of federal support for research; the impact of managed care on academic health centers). In confronting this problem, the authors stress the importance of (1) carefully defining the major subtypes of clinical investigation (i.e., physiologic investigation, outcomes research, and clinical trials) and noting which are and which are not endangered; (2) understanding the potential solutions to the problem that have been offered in the past; and (3) defining and hopefully marshaling a coalition of those institutions whose resources are currently available to address the problem and that have an important stake in its solution: academic health centers, the National Institutes of Hearth, health care providers, foundations and educational societies, medical schools, and industry. The authors stress that finding solutions to the current problem are a shared responsibility that must be carried out, for without well-trained and innovative clinical investigators, the social contract of biomedical research - to keep society well - cannot be fulfilled. C1 PARTNERS HEALTHCARE SYST,BOSTON,MA 02114. RP Crowley, WF (reprint author), MASSACHUSETTS GEN HOSP,CLIN RES PROGRAM,32 FRUIT ST,BOSTON,MA 02114, USA. NR 16 TC 21 Z9 21 U1 1 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD NOV PY 1996 VL 71 IS 11 BP 1154 EP 1163 DI 10.1097/00001888-199611000-00013 PG 10 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA VT717 UT WOS:A1996VT71700016 PM 9217505 ER PT J AU Dupuy, DE Spillane, RM Rosol, MS Rosenthal, DI Palmer, WE Burke, DW Rosenberg, AE AF Dupuy, DE Spillane, RM Rosol, MS Rosenthal, DI Palmer, WE Burke, DW Rosenberg, AE TI Quantification of articular cartilage in the knee with three-dimensional MR imaging SO ACADEMIC RADIOLOGY LA English DT Article DE articular cartilage; knee; magnetic resonance imaging ID CHONDROMALACIA PATELLAE; COMPUTED-TOMOGRAPHY AB Rationale and Objectives. To determine the volume of articular cartilage in cadavers, patients, and healthy volunteers by using a volumetric, fat-suppressed spoiled gradient-recalled signal acquisition in the steady state (SPGR) magnetic resonance (MR) sequence. Methods. Sagittal MR images were obtained with a fat-suppressed SPGR sequence (repetition time, 52 msec; echo time, 10 msec; 60 degrees flip angle; 3.0-3.5-mm partitions, 256 x 192 matrix, two signals acquired). The cartilaginous surfaces of the tibia, femur, and patella were planimetrically defined with a three-dimensional workstation. A three-dimensional model volume was created by threshold segmenting the cartilage from the adjacent tissues. The volume as calculated by using MR imaging was compared with the actual volume of the cartilage specimens. Result. Observed measurements correlated with actual weight and volume displacement measurements with an accuracy of 82%-99% and linear correlation coefficients of 0.99 (P = 2.5(e-15)) and 0.99 (P = 4.4(e-15)). Precision of segmentation in healthy volunteers yielded a coefficient of variation of 0.4% for interobserver variability and 0.3% for intraobserver variability. Conclusion. This pilot study suggests that accurate volumetric calculations of knee articular cartilage are possible with currently available MR imaging pulse sequences and a commercially available work station. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Dupuy, DE (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,15 PARKMAN ST ACC 515,BOSTON,MA 02114, USA. OI Dupuy, Damian/0000-0003-0524-5982 NR 14 TC 28 Z9 28 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 1996 VL 3 IS 11 BP 919 EP 924 DI 10.1016/S1076-6332(96)80299-6 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VW753 UT WOS:A1996VW75300004 PM 8959181 ER PT J AU Goldberg, SN Gazelle, GS Compton, CC Mueller, PR McLoud, TC AF Goldberg, SN Gazelle, GS Compton, CC Mueller, PR McLoud, TC TI Radio-frequency tissue ablation of VX2 tumor nodules in the rabbit lung SO ACADEMIC RADIOLOGY LA English DT Article DE radiofrequency; tumor ablation; tissue ablation; pulmonary neoplasms ID LIVER METASTASES; RADIOFREQUENCY AB Rationale and Objectives. The authors investigated whether small pulmonary malignancies could be treated with computed tomography (CT)-guided, percutaneously placed radio-frequency (RF) electrodes. Methods. Pulmonary tumors were created in 11 New Zealand white rabbits by using CT-guided injection of a VX2 sarcoma cell suspension into the lower portion of the right lung. Tumors were allowed to grow 14-21 days to achieve a diameter of 6-12 mm. Electrodes were placed coaxially into the tumors via insulated 19-gauge Turner needles. Seven tumors were treated with RF for 6 minutes at 90 degrees C. Four tumors served as controls and were not treated. Follow-up CT and histopathologic analysis were performed on days 0-28. Specimens from treated rabbits were examined histopathologically on days 0 and 3 (n = 2 each), and days 1, 5, and 28 (n = 1 each). Results. Immediately following treatment, CT images showed rounded opacities enveloping the tumor. This corresponded histologically to coagulation necrosis of tumor and surrounding alveoli. In all cases, at least 95% of treated tumor nodules were necrotic at histopathologic analysis. Peripheral residual nests of histologically viable tumor were seen in three rabbits (43%). Control rabbits showed growing tumor nodules without necrosis at autopsy (mean survival, 23 days after inoculation). Two RE-treated rabbits (29%) and one control rabbit (25%) had pneumothoraces. Conclusion. Percutaneous RF tissue ablation can be used to successfully treat small parenchymal tumor nodules within the lung in an animal model. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. RP Goldberg, SN (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114, USA. NR 17 TC 97 Z9 107 U1 0 U2 7 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 1996 VL 3 IS 11 BP 929 EP 935 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VW753 UT WOS:A1996VW75300006 PM 8959183 ER PT J AU Halavaara, JT Hamberg, LM Leong, FS Hunter, GJ Gazelle, GS Wolf, GL AF Halavaara, JT Hamberg, LM Leong, FS Hunter, GJ Gazelle, GS Wolf, GL TI Functional CT with an experimental intravascular contrast agent in the assessment of liver vascular physiology SO ACADEMIC RADIOLOGY LA English DT Article DE liver; CT; liver; blood supply; liver; contrast agents; liver; perfusion ID COMPUTED-TOMOGRAPHY; DYNAMIC CT; PERFUSION; INJECTION AB Rationale and Objectives, We evaluated liver vascular physiology with a functional spiral computed tomography (CT) technique and an intravascular contrast agent. Methods. Eleven rabbits were studied by means of continuous 40-second single-section data acquisition after bolus injection of an experimental contrast agent. Sequential images were reconstructed at 200-msec intervals. Aortic, portal and hepatic venous, and liver time- HU curves were obtained. From these, hepatic blood volume and flow, tissue transit times, and arterial and portal contributions to total liver blood supply were assessed. Results. The following measures were obtained: hepatic blood volume fraction, 0.33 +/- 0.03 (mean +/- standard error), total flow, 241.1 mL/min +/- 33.6 per 100 g of tissue (arterial component, 11.3 mL/min +/- 3.0 per 100 g of tissue; portal component. 226.4 mL/min +/- 30.7 per 100 g of tissue); arterial transit time, 5.7 seconds +/- 1.6: portal transit time, 8.7 seconds +/- 1.3; arterial to portal perfusion ratio, 0.06 +/- 0.01; and calculated arterial and portal perfusion indexes, 0.05 +/- 0.01 and 0.95 +/- 0.01, respectively. Conclusion. Functional CT is a promising, high-resolution tomographic imaging technique for evaluating liver perfusion. C1 MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. UNIV HELSINKI,CENT HOSP,DEPT RADIOL,HELSINKI,FINLAND. NR 18 TC 13 Z9 13 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 1996 VL 3 IS 11 BP 946 EP 952 DI 10.1016/S1076-6332(96)80307-2 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VW753 UT WOS:A1996VW75300008 PM 8959185 ER PT J AU Centeno, BA Szyfelbein, WM Daniels, GH Vickery, AL AF Centeno, BA Szyfelbein, WM Daniels, GH Vickery, AL TI Fine needle aspiration biopsy of the thyroid gland in patients with prior Graves' disease treated with radioactive iodine - Morphologic findings and potential pitfalls SO ACTA CYTOLOGICA LA English DT Article DE Graves' disease; thyroid diseases; iodine radioisotopes; aspiration biopsy ID IRRADIATION; MANAGEMENT AB OBJECTIVE: To evaluate the morphologic findings and their potential pitfalls in fine needle aspiration biopsies (FNAB) of thyroid glands obtained following radioactive iodine (RaI) (131I) treatment for Graves' disease. STUDY DESIGN: Study of thyroid FNAB specimens from six patients with prior Graves' disease treated with RaI who developed palpable nodules and had subsequent thyroid resections. RESULTS: The cytologic changes attributed to radiation were quite variable among the six cases and were so pronounced in one case that a false positive diagnosis of papillary carcinoma was made even though a history of RaI had been provided. The FNAB specimen from the second case, submitted without a history of RaI treatment, was diagnosed as suspicious for papillary carcinoma. The smears from patient 3 were signed out descriptively because the pertinent clinical history had not been provided. The FNAB specimens from the last three patients were correctly interpreted because of the history of RaI therapy provided. All six thyroid surgical specimens showed changes consistent with radiation injury, and none contained evidence of malignancy. CONCLUSION: The study's findings demonstrate that the atypia produced by RaI may be severe, leading to an erroneous diagnosis of malignancy. Provision of the appropriate clinical history of Graves' disease treated with RaI may prevent this pitfall. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Centeno, BA (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,WARREN 219,FRUIT ST,BOSTON,MA 02114, USA. NR 15 TC 28 Z9 29 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD NOV-DEC PY 1996 VL 40 IS 6 BP 1189 EP 1197 PG 9 WC Pathology SC Pathology GA VY541 UT WOS:A1996VY54100012 PM 8960027 ER PT J AU Hirsch, MS AF Hirsch, MS TI Strategies for combination therapy in HIV infection SO AIDS LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD NOV PY 1996 VL 10 SU 2 BP 101 EP 101 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VU963 UT WOS:A1996VU96300022 ER PT J AU Steiner, JC Halloran, MM Jabamoni, K Emanuele, NV Emanuele, MA AF Steiner, JC Halloran, MM Jabamoni, K Emanuele, NV Emanuele, MA TI Sustained effects of a single injection of ethanol on the hypothalamic-pituitary-gonadal axis in the male rat SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ethanol; LH; testosterone; LHRH ID LUTEINIZING-HORMONE; MESSENGER-RNA; BONE MASS; GONADOTROPIN; SECRETION; MEN; LH; OSTEOPOROSIS; EXPRESSION; GENES AB The hormones responsible for regulating the hypothalamic-pituitary-gonadal axis are essential for proper reproductive function, Ethanol (EtOH) has been shown to exert its effects at all three levels of this axis. The present study defines striking differences in the time course of recovery of luteinizing hormone (LH) in gonadally intact, compared with, castrated male rats after acute EtOH administration, Serum levels of LH and testosterone were measured at various time points up to 2 weeks (1.5, 3, 24, 48, 72, 96, 168, and 336 hr) after a single intraperitoneal injection of either saline or 3 g/kg of EtOH in intact adult male rats, One EtOH injection significantly suppressed testosterone levels to as low as 20% (p < 0.01) of saline-injected intact rats, This occurred as early as 1.5 hr after EtOH administration (the first measured time point), and statistically significant suppression was sustained for 96 hr, Similarly, LH levels showed a significant decrease, However, this significant fall in LH did not begin until 3 hr (p < 0.05) and continued up to 96 hr (p < 0.01), with a gradual return to control levels at 168 and 336 hr after treatment, Despite the significant and prolonged fail in testosterone levels in the EtOH-treated intact rats, beta-LH mRNA levels were inappropriately not elevated, as would be expected in the context of low circulating testosterone. However, at 168 and 336 hr, steady-state levels of beta-LH mRNA were significantly higher than seen in saline-injected controls (p < 0.05 and p < 0.01, respectively), temporally correlating with the return of serum LH to control. LH levels in the castrated animals were significantly suppressed at 1.5 hr (p < 0.05) and 3 hr (p < 0.01) after EtOH treatment, compared with controls, yet they returned much more quickly by 24 hr after treatment, beta-LH mRNA levels of castrated animals also showed a significant depression at 1.5 and 3 hr, and returned to control levels by 24 hr. In these rats, the hypothalamic LH-releasing hormone mRNA levels were not altered by a single EtOH injection at anytime point, However, in the intact animals, there was a transient increase in LH-releasing hormone mRNA at 72 and 96 hr (p < 0.01 and p < 0.05, respectively) that may lead to the upregulation of beta-LH mRNA expression, These studies indicate that EtOH causes prolonged decreases in important serum hormones that are essential to the reproductive axis of the adult male rat. C1 LOYOLA UNIV,STRITCH SCH MED,DEPT MED,MAYWOOD,IL 60153. LOYOLA UNIV,STRITCH SCH MED,PROGRAM MOL BIOL,MAYWOOD,IL 60153. LOYOLA UNIV,STRITCH SCH MED,DIV RES DRUGS ABUSSE,MAYWOOD,IL 60153. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,RES SERV,HINES,IL 60141. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,MED SERV,HINES,IL 60141. RP Steiner, JC (reprint author), LOYOLA UNIV,STRITCH SCH MED,DEPT MOL & CELLULAR BIOCHEM,2160 S 1ST AVE,MAYWOOD,IL 60153, USA. NR 31 TC 15 Z9 16 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 NOV PY 1996 VL 20 IS 8 BP 1368 EP 1374 DI 10.1111/j.1530-0277.1996.tb01136.x PG 7 WC Substance Abuse SC Substance Abuse GA VU644 UT WOS:A1996VU64400008 PM 8947312 ER PT J AU Grauer, SE Pantely, GA Xu, JP Ge, SP Giraud, GD Shiota, T Sahn, DJ AF Grauer, SE Pantely, GA Xu, JP Ge, SP Giraud, GD Shiota, T Sahn, DJ TI Myocardial imaging with a new transpulmonary lipid-fluorocarbon echo contrast agent: Experimental studies in pigs SO AMERICAN HEART JOURNAL LA English DT Article ID PULMONARY INTRAVASCULAR MACROPHAGES; PERIPHERAL VENOUS INJECTION; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; SONICATED DEXTROSE ALBUMIN; COLLATERAL BLOOD-FLOW; CORONARY-OCCLUSION; RISK AREA; 2-DIMENSIONAL ECHOCARDIOGRAPHY; INTRAVENOUS-INJECTION; INFARCT SIZE AB The development of echo contrast agents that can provide reliable opacification of the myocardium after intravenous injection is an important advancement for the clinical application of contrast echocardiography. In this study, the hemodynamic effects and echocardiographic characteristics of a new lipid-fluorocarbon echo contrast agent, Aerosomes MRX 115 (ImaRx Pharmaceutical Corp., Tucson, Ariz.) were studied in six anesthetized ventilated pigs. Intravenous injection of this new agent in doses ranging from 0.0005 to 0.01 ml/kg produced significant measurable and visible myocardial opacification without any effect on heart rate, systemic pressure, partial pressure of oxygen, or left ventricular systolic function. The two largest doses (0.005 and 0.01 ml/kg), however, resulted in mild reversible increases in mean pulmonary artery pressure of 12 and 16 mm Hg, respectively. In four animals, epicardial images were obtained before and during coronary artery occlusion. Intravenous contrast injection during coronary occlusion permitted delineation of the hypoperfused myocardial segment. This capability may further expand the utility of contrast echocardiography. C1 OREGON HLTH SCI UNIV,DEPT MED,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,CLIN CARE CTR CONGENITAL HEART DIS,PORTLAND,OR 97201. PORTLAND VET AFFAIRS MED CTR,PORTLAND,OR. FU NCI NIH HHS [CA-62659-03] NR 47 TC 22 Z9 23 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 1996 VL 132 IS 5 BP 938 EP 945 DI 10.1016/S0002-8703(96)90002-2 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VQ034 UT WOS:A1996VQ03400003 PM 8892764 ER PT J AU Ansell, JE Hughes, R AF Ansell, JE Hughes, R TI Evolving models of warfarin management: Anticoagulation clinics, patient self-monitoring, and patient self-management SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID ATRIAL-FIBRILLATION; PROTHROMBIN TIME; ORAL ANTICOAGULATION; THERAPY; COMPLICATIONS; PREVENTION; ATTITUDES C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Ansell, JE (reprint author), BOSTON UNIV,MED CTR,DEPT MED,BOSTON,MA 02118, USA. NR 42 TC 96 Z9 100 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 NOV PY 1996 VL 132 IS 5 BP 1095 EP 1100 DI 10.1016/S0002-8703(96)90040-X PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VQ034 UT WOS:A1996VQ03400041 PM 8892802 ER PT J AU Gold, MR OGara, PT Buckley, MJ DeSanctis, RW AF Gold, MR OGara, PT Buckley, MJ DeSanctis, RW TI Efficacy and safely of Procainamide in preventing arrhythmias after coronary artery bypass surgery SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SUPRA-VENTRICULAR TACHYARRHYTHMIAS; SUPRAVENTRICULAR TACHYARRHYTHMIAS; ATRIAL-FIBRILLATION; DOUBLE-BLIND; PROPRANOLOL; PROPHYLAXIS; OPERATIONS; DIGOXIN; FLECAINIDE; FLUTTER AB Arrhythmias are common after cardiac surgery and are associated with hemodynamic compromise, stroke, and prolonged hospitalization. Beta blockers prevent atrial fibrillation postoperatively, but there are few data regarding the prophylactic use of type I antiarrhythmic agents or the prevention of ventricular arrhythmias, Accordingly, we performed a randomized, double-blind, placebo-controlled study of the effects of oral procainamide on 100 patients undergoing elective coronary artery bypass surgery, Procainamide was received for 4 days; the dosage was adjusted for body weight Patients receiving procainamide had a significant reduction in atrial fibrillation (16 vs 29 patient-days, p < 0,05) and ventricular tachycardia (2% vs 20%, p < 0.01). However, the incidence of atrial fibrillation was not significantly reduced (38% vs 26%), In the group achieving therapeutic serum procainamide levels, there was a reduction in all measured postoperative arrhythmias. No serious cardiac or noncardiac adverse events were noted during procainamide therapy, although there was a significant increase in the incidence of nausea, We conclude that procainamide reduces arrhythmias in the early postoperative period after coronary artery bypass surgery, most prominently in patients who achieve therapeutic serum levels. This was associated with no serious cardiac adverse reactions. (C) 1996 by Excerpta Medica, Inc. C1 UNIV MARYLAND,MED SYST,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21201. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIAC SURG UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 27 TC 38 Z9 39 U1 0 U2 1 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 NOV 1 PY 1996 VL 78 IS 9 BP 975 EP 979 DI 10.1016/S0002-9149(96)00519-X PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VQ229 UT WOS:A1996VQ22900001 PM 8916473 ER PT J AU Laposata, M AF Laposata, M TI What many of us are doing or should be doing in clinical pathology - A list of the activities of the pathologist in the clinical laboratory SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE laboratory medicine; clinical laboratory; laboratory director; residency training AB Mr. Paul Mango, Chief Operating Officer of a hospital-based clinical laboratory network in Pittsburgh, recently performed a survey of patients presenting for phlebotomy, The survey included the question, ''What does a pathologist do?'' The results were that 50% of the patients had no idea what a pathologist did, and 30% of the patients stated that pathologists examined dead bodies. It is not surprising that there is a limited understanding by patients of the activities of pathologists because patients do not usually see pathologists. However, beyond autopsy and surgical pathology, the activities of pathologists are also not well known to nonpathologist physicians and hospital administrators. A poor understanding of activities in clinical pathology have placed these clinical responsibilities of the pathologist under particular scrutiny for cost reduction. The quantitation of output from anatomic pathology, in number of slides reviewed or number of autopsies performed, is objective and easily understood, As noted in the list of clinical pathology acitivities that follows, the responsibilities within the clinical laboratory are highly diverse and, if the pathologist handles them successfully, highly contributory to patient care, Thus, it is timely that a compilation of activities in clinical pathology be issued for review by the pathologist community, I would hope that this list will serve as a starting point for a universally accepted group of activities that describes clinical pathology today and that it will be useful for pathologists to make their significant contributions in the clinical laboratory apparent to administrators, fellow physicians, and patients, The clinical laboratory responsibilities should also be valuable to directors of residency training programs to focus training in clinical pathology toward the development of currently desirable expertise. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP Laposata, M (reprint author), MASSACHUSETTS GEN HOSP,CLIN LABS,DEPT PATHOL,DIV CLIN LABS,BOSTON,MA 02114, USA. NR 0 TC 22 Z9 22 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD NOV PY 1996 VL 106 IS 5 BP 571 EP 573 PG 3 WC Pathology SC Pathology GA VU645 UT WOS:A1996VU64500005 PM 8929464 ER PT J AU vonTitte, SN McCabe, CJ Ottinger, LW AF vonTitte, SN McCabe, CJ Ottinger, LW TI Delayed appendectomy for appendicitis: Causes and consequences SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE appendicitis; complication; delay ID DIAGNOSIS; CT; ULTRASONOGRAPHY AB This study was undertaken to describe the causes and consequences of delayed diagnosis and intervention in cases of appendicitis, The hospital records of adult patients undergoing appendectomy during a I-year period (November 1989 to November 1993) were reviewed, with concentration on 40 patients who had a delay of 72 hours or more from initial symptoms to operation, The initial medical contact points for patients were walk-in clinics and community emergency departments, Definitive care was provided in a general hospital, Patients were adults with appendicitis who underwent an operation for definitive management 72 or more hours after the onset of symptoms, Length of hospital stay, reasons for delay in diagnosis, incidence of perforation, and complications were recorded, Delay in diagnosis and treatment was attributed to factors controlled by the patient in 15 cases (27.5%) and by the physician in 25 cases (62.5%), Perforation, postoperative complications, and hospital length of stay were related to the delay in diagnosis; with delay, the mean hospital length of stay was 9 days, the incidence of perforation was 90%, and major complications were recorded in 60% of the patients, Early diagnosis and surgical management for appendicitis remains an important and, at times, elusive goal, Delays of 72 hours or more have serious consequences, Patient education and the experience, intuitiveness, and persistence of the physician are important elements to improving these findings. Copyright (C) 1996 by W.B. Saunders Company C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. NR 18 TC 41 Z9 41 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 1996 VL 14 IS 7 BP 620 EP 622 DI 10.1016/S0735-6757(96)90074-1 PG 3 WC Emergency Medicine SC Emergency Medicine GA VT355 UT WOS:A1996VT35500002 PM 8906756 ER PT J AU Weston, MD Kelley, PM Overbeck, LD Wagenaar, M Orten, DJ Hasson, T Chen, ZY Corey, D Mooseker, M Sumegi, J Cremers, C Moller, C Jacobson, SG Gorin, MB Kimberling, WJ AF Weston, MD Kelley, PM Overbeck, LD Wagenaar, M Orten, DJ Hasson, T Chen, ZY Corey, D Mooseker, M Sumegi, J Cremers, C Moller, C Jacobson, SG Gorin, MB Kimberling, WJ TI Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SYNDROME TYPE-I; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; GENE; CHROMOSOME-11; DEAFNESS; MUSCLE AB Usher syndrome type 1b (USH1B) is an autosomal recessive disorder characterized by congenital profound hearing loss, vestibular abnormalities, and retinitis pigmentosa, The disorder has recently been shown to be caused by mutations in the myosin VIIa gene (MYO7A) located on 11q14, In the current study, a panel of 189 genetically independent Usher I cases were screened for the presence of mutations in the N-terminal coding portion of the motor domain of MYO7A by heteroduplex analysis of 14 exons, Twenty-three mutations were found segregating with the disease in 20 families, Of the 23 mutations, 13 were unique, and 2 of the 13 unique mutations (Arg212His and Arg212Cys) accounted for the greatest percentage of observed mutant alleles (8/23, 31%), Six of the 13 mutations caused premature stop codons, 6 caused changes in the amino acid sequence of the myosin VIIa protein, and 1 resulted in a splicing defect, Three patients were homozygotes or compound heterozygotes for mutant alleles; these three cases were Tyr333Stop/Tyr333Stop, Arg212His-Arg302His/Arg212His-Arg302His, and IVS13nt-8c-->g/Glu450Gln. All the other USH1B mutations observed were simple heterozygotes, and it is presumed that the mutation on the other allele is present in the unscreened regions of the gene, None of the mutations reported here were observed in 96 unrelated control samples, although several polymorphisms were detected, These results add three patients to single case reported previously where mutations have been found in both alleles and raises the total number of unique mutations in MYO7A to 16. C1 BOYS TOWN NATL RES HOSP,CTR HEREDITARY COMMUN DISORDERS,DEPT GENET,OMAHA,NE 68131. UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE. UNIV NIJMEGEN HOSP,DEPT OTORHINOLARYNGOL,NL-6500 HB NIJMEGEN,NETHERLANDS. YALE UNIV,DEPT BIOL,NEW HAVEN,CT. YALE UNIV,DEPT PATHOL,NEW HAVEN,CT. YALE UNIV,DEPT CELL BIOL,NEW HAVEN,CT. MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. LINKOPING UNIV,DEPT OTOLARYNGOL,LINKOPING,SWEDEN. UNIV PENN,SCHEIE EYE INST,PHILADELPHIA,PA 19104. UNIV PITTSBURGH,DEPT OPHTHALMOL,PITTSBURGH,PA 15260. UNIV PITTSBURGH,DEPT HUMAN GENET,PITTSBURGH,PA. RI Cremers, C.W.R.J./L-4254-2015; OI Corey, David/0000-0003-4497-6016 FU NEI NIH HHS [R01 EY05627]; NIDCD NIH HHS [P01 DC01813-01]; NIDDK NIH HHS [P01 DK38979] NR 22 TC 81 Z9 83 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 NOV PY 1996 VL 59 IS 5 BP 1074 EP 1083 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA VN900 UT WOS:A1996VN90000015 PM 8900236 ER PT J AU Marrie, TJ Peeling, RW Fine, MJ Singer, DE Coley, CM Kapoor, WN AF Marrie, TJ Peeling, RW Fine, MJ Singer, DE Coley, CM Kapoor, WN TI Ambulatory patients with community-acquired pneumonia: The frequency of atypical agents and clinical course SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID REQUIRING HOSPITALIZATION; PROSPECTIVE MULTICENTER; TWAR STRAIN; ETIOLOGY; CHLAMYDIA; INFECTIONS; DIAGNOSIS; THERAPY AB OBJECTIVES: TO determine the etiology of community-acquired pneumonia in patients treated in an ambulatory setting, using serological methods, and to compare presenting symptoms, radiographic manifestations, and clinical outcomes of patients with pneumonia of ''atypical'' and undetermined etiology. PATIENTS AND METHODS: This prospective cohort study was conducted in emergency room and outpatient facilities of Victoria General Hospital, Halifax, Nova Scotia, and in offices of participating family doctors based in Halifax. One hundred forty-nine adults with acute onset of one or more symptoms or signs suggestive of pneumonia and radiographic evidence of pneumonia who provided informed consent were enrolled. Patients known to be HIV positive or who had been discharged from a hospital within the previous 10 days were ineligible for enrollment. Demographic features and clinical data were collected by direct patient interview and chart review by trained research nurses. Outcome measures included quantitative evaluation of pneumonia-specific symptoms, and responses to the Short Form 36 Health Survey at presentation and at 30 days after presentation. Information was also collected on each patient's health prior to pneumonia, as well as the time until each patient's self-reported return to work and to usual activities. The etiology of pneumonia was determined by testing acute and convalescent serum samples for antibodies to Legionella pneumophila serogroup 1, Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci, Coxiella burnetii, adenovirus, respiratory syncytial virus, influenza viruses A and B, and parainfluenza viruses 1, 2, 3. RESULTS: The study population consisted of 149 patients, 54 (36%) of whom were men, with a mean age (+/- SD) of 41 +/- 15 years. An etiological diagnosis was made in 74 (49.7%) patients using serological methods. Etiological agents included M pneumoniae 34 (22.8%); C pneumoniae 16 (10.7%); M pneumoniae and C pneumoniae 5 (3.4%); C burnetii 4 (2.7%); influenza A virus 4 (2.7%); and other agents 6% (7.4%). Three patients (2%) had a conventional bacterial etiology, and 72 patients (48.3%) had pneumonia of undetermined etiology. Patients with pneumonia of known (atypical) and undetermined etiology were similar in terms of age, gender, race, education, employment, and comorbidity. Despite a higher proportion of patients with pneumonia of known etiology reporting sweats, chills, and headache at presentation, the two groups were similar for symptom severity and bother. The patients with pneumonia of undetermined etiology were more likely to have multilobar pneumonia (P <0.02). Both patients with atypical pneumonia and those with pneumonia of undetermined etiology suffered severe deterioration of physical functioning with a marked but incomplete recovery at 30 days. Those with atypical pneumonia had higher physical functioning and general mental health scores at 30 days. CONCLUSIONS: Nearly half the cases of ambulatory community-acquired pneumonia are due to ''atypical'' agents. It is not possible to reliably distinguish patients with atypical pneumonia from those with pneumonia of undetermined etiology by clinical features at baseline. The outcomes in terms of resolution of symptoms, functional status, return to work, and return to usual activities are essentially similar in the two groups. (C) 1996 Excerpta Medica, Inc. C1 DALHOUSIE UNIV,DEPT MED,HALIFAX,NS,CANADA. DALHOUSIE UNIV,DEPT MICROBIOL,HALIFAX,NS,CANADA. VICTORIA GEN HOSP,HALIFAX,NS B3H 2Y9,CANADA. HLTH CANADA,LAB CTR DIS CONTROL,WINNIPEG,MB,CANADA. UNIV PITTSBURGH,DEPT MED,DIV GEN INTERNAL MED,PITTSBURGH,PA. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU AHRQ HHS [R01-HS-06468] NR 27 TC 203 Z9 209 U1 1 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD NOV PY 1996 VL 101 IS 5 BP 508 EP 515 DI 10.1016/S0002-9343(96)00255-0 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VV792 UT WOS:A1996VV79200010 PM 8948274 ER PT J AU Hamberg, LM Hunter, GJ Kierstead, D Lo, EH Gonzalez, RG Wolf, GL AF Hamberg, LM Hunter, GJ Kierstead, D Lo, EH Gonzalez, RG Wolf, GL TI Measurement of cerebral blood volume with subtraction three-dimensional functional CT SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE animal studies; blood volume; computed tomography, three-dimensional ID MAXIMUM-INTENSITY-PROJECTION; EMISSION COMPUTED-TOMOGRAPHY; X-RAY-FLUORESCENCE; SPIRAL CT; ACUTE STROKE; ISCHEMIA; ANGIOGRAPHY; CATS; DIAGNOSIS; TISSUE AB PURPOSE: To implement a three-dimensional subtraction functional CT technique to permit rapid quantitative mapping of regional cerebral blood volume (CBV). METHODS: The 3-D functional CT technique was implemented in a rabbit model using normal and ischemic animals, Two spiral data acquisitions were performed, one before and one during biphasic administration of contrast material. CBV maps were then produced on a voxel-by-voxel basis through the whole brain. RESULTS: The average normal CBV was 3.3+/-0.4 mL/100 g (n=7), and the regional values were 4.5+/-0.6 mL/100 g for cortical gray matter, 2.5+/-0.6 mL/100 g for white matter, and 3.7+/-0.4 mL/100 g for the basal ganglia. The CBVs in ischemic regions were 1.5+/-0.4 mL/100 g, 0.7+/-0.7 mL/100 g, and 1.8+/-0.9 mL/100 g, respectively. CONCLUSION: Subtraction 3-D functional CT is a fast, potentially cost-effective method with which to assess whole-brain CBV. Because the data collected in 3-D functional CT imaging also can be used to produce large-vessel angiograms, its use in a clinical setting can provide a multiparametric study of cerebrovascular abnormalities that encompasses both large and small vessel circulations for patients being examined for stroke. RP Hamberg, LM (reprint author), MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,DEPT RADIOL,2ND FLOOR,ROOM 2329,BLDG 149,CHARLESTOWN,MA 02129, USA. NR 42 TC 76 Z9 80 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 1996 VL 17 IS 10 BP 1861 EP 1869 PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA VU080 UT WOS:A1996VU08000010 PM 8933870 ER PT J AU Filatov, V Alexandrakis, G Talamo, JH Steinert, RF AF Filatov, V Alexandrakis, G Talamo, JH Steinert, RF TI Comparison of suture-in and suture-out postkeratoplasty astigmatism with single running suture or combined running and interrupted sutures SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PENETRATING KERATOPLASTY; MERSILENE AB PURPOSE: To evaluate postkeratoplasty astigmatism between two suture techniques 2 to 4 years postoperatively in a group of patients previously studied 9 months postoperatively. METHODS: Thirty-two patients who underwent penetrating keratoplasty were randomly assigned to; one of two groups. Group 1 (16 patients) had a 24-bite single running 10-0 nylon suture with postoperative suture tension adjustment; group 2 (16 patients) had combined 16-bite running and eight interrupted 10-0 nylon sutures with selective postoperative removal of interrupted sutures. During long-term follow-up, the running suture was removed in 19 patients (59%). RESULTS: Postoperative astigmatism was slightly lower in patients with the single running suture technique when sutures were in place and was slightly greater after the sutures were removed compared with the combined running and interrupted suture technique (sutures in: single running suture +/- SD, 2.6 +/- 1.2 diopters [five patients, 31%]; combined running and interrupted sutures, 3.8 +/- 1.1 diopters [eight patients, 50%]; sutures out: single running suture, 3.3 +/- 1.3 diopters [11 patients, 69%]; combined running and interrupted sutures, 2.8 +/- 1.5 diopters [eight patients, 50%]). These differences were not statistically significant (sutures in, P <.13; sutures out, P <.46). Averages of follow-up were group 1, 48.3 +/- 10.6 months and group 2, 46.3 +/- 13.0 months. Follow-up ranged from 23 to 60 months. CONCLUSIONS: Postoperative astigmatism 4 years after penetrating keratoplasty is similar for these two suturing techniques, with or without residual sutures. A single running suture results in more rapid visual rehabilitation and less early astigmatism compared with the combined interrupted and running suture technique. C1 CTR EYE RES,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. GREENWICH EYE CTR,GREENWICH,CT. UNIV VERMONT,COLL MED,BURLINGTON,VT. NR 8 TC 42 Z9 42 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 1996 VL 122 IS 5 BP 696 EP 700 PG 5 WC Ophthalmology SC Ophthalmology GA VQ701 UT WOS:A1996VQ70100011 PM 8909210 ER PT J AU Ciulla, TA Frederick, AR Kelly, C Amrein, R AF Ciulla, TA Frederick, AR Kelly, C Amrein, R TI Postvitrectomy positioning complicated by ulnar nerve palsy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: Ulnar nerve palsy is an unusual complication of postvitrectomy positioning. METHOD: We report two such cases. RESULTS: Both patients developed ulnar nerve palsy after maintaining a face-down position for 2 to 4 weeks after vitrectomy with intraocular perfluoro-octane. The neuropathy resolved in one patient after he was instructed to avoid prolonged pressure on his flexed elbows, whereas the other patient ultimately required surgical decompression of the nerve at the elbow. CONCLUSION: Ulnar nerve palsy can result from postvitrectomy positioning associated with prolonged direct pressure on the ulnar nerve or compression of the ulnar nerve via flexion of the elbow. C1 OPHTHALM CONSULTANTS BOSTON,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. INDIANA UNIV,SCH MED,DEPT OPHTHALMOL,BLOOMINGTON,IN 47405. HARVARD UNIV,SCH MED,BOSTON,MA. CTR EYE RES,BOSTON,MA. HARVARD UNIV,SCH MED,DEACONESS HOSP,DEPT ANESTHESIOL,BOSTON,MA. NR 5 TC 14 Z9 16 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 1996 VL 122 IS 5 BP 739 EP 740 PG 2 WC Ophthalmology SC Ophthalmology GA VQ701 UT WOS:A1996VQ70100022 PM 8909221 ER PT J AU McKenna, MJ Kristiansen, AG Haines, J AF McKenna, MJ Kristiansen, AG Haines, J TI Polymerase chain reaction amplification of a measles virus sequence from human temporal bone sections with active otosclerosis SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article DE otosclerosis; measles virus; polymerase chain reaction ID EPSTEIN-BARR-VIRUS; HODGKINS-DISEASE; DNA AB Investigation of a possible viral etiology for otosclerosis was initiated because of the clinical and histopathologic similarities between otosclerosis and Paget's disease of bone and the mounting evidence of a viral etiology in Paget's disease. Thus far, ultrastructural and immunohistochemical studies have revealed measles-like structures and antigens in active otosclerotic lesions. A method for isolation and identification of both DNA and RNA sequences in archival human temporal bone specimens using the polymerase chain reaction technique has been developed. With use of this technique, a 115-base pair sequence of the measles nucleocapsid gene has been identified in 8 of 11 different temporal bone specimens with histologic evidence of otosclerosis. Zero of nine control specimens without histologic evidence of otosclerosis were positive. The association between the presence of the measles nucleocapsid gene sequence and histologic otosclerosis was significant (p < 0.01). This study provides further evidence for a possible measles virus etiology in otosclerosis. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,BOSTON,MA 02114. RP McKenna, MJ (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. RI Haines, Jonathan/C-3374-2012 FU NIDCD NIH HHS [5 K08DC00065-04] NR 20 TC 60 Z9 62 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD NOV PY 1996 VL 17 IS 6 BP 827 EP 830 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA VQ203 UT WOS:A1996VQ20300004 PM 8915408 ER PT J AU Loda, M Capodieci, P Mishra, R Yao, H Corless, C Grigioni, W Wang, YB MagiGalluzzi, C Stork, PJS AF Loda, M Capodieci, P Mishra, R Yao, H Corless, C Grigioni, W Wang, YB MagiGalluzzi, C Stork, PJS TI Expression of mitogen-activated protein kinase phosphatase-1 in the early phases of human epithelial carcinogenesis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID IMMEDIATE-EARLY GENE; EPIDERMAL GROWTH-FACTOR; NEU-ONCOGENE PROTEIN; HUMAN-BREAST-CANCER; MAP KINASE; TYROSINE-PHOSPHATASE; PC12 CELLS; MOLECULAR-GENETICS; VACCINIA VIRUS; BLADDER-CANCER AB Many mitogens and human oncogenes activate extracellular regulated kinases (ERKs), which in turn convey proliferation signals, ERKs or mitogen-activated protein (MAP) kinases are inactivated in vitro by MAP kinase phosphatases (MKPs), The gene encoding one of these MKPs, MKP-1, is a serum-inducible gene and is transcriptionally activated by mitogenic signals in cultured cells, As MKP-1 has been shown to block DNA synthesis by inhibiting ERKs tt,ben expressed at elevated levels in cultured cells, it has been suggested that it may act as a tumor suppressor. MKP-1 mRNA and MAP kinase (ERK-1 and -2) protein expression was assessed in 164 human epithelial tumors of diverse tissue origin by in situ hybridization and immunohistochemistry. MKP-1 was overexpressed in the early phases of prostate, colon, and bladder carcinogenesis, with progressive loss of expression with higher histological grade and in metastases. In contrast, breast carcinomas showed significant MKP-1 expression even when poorly differentiated or in late stages of the disease, MKP-1, ERK-1, and ERK-2 were co-expressed in most tumors examined. In a subset of 15 tumors, ERK-1 enzymatic activity as well as structural alterations that might be responsible for loss of function of MKP-1 during tumor progression, were examined. ERK-1 enzymatic activity was found to be elevated despite MKP-1 overexpression, No loss of 5q35-ter (containing the MKP-1 locus) was detected by polymerase chain reaction in metastases compared with primary tumors. Finally, no mutations were found in the catalytic domain of MKP-1. These data indicate that MKP-1 is an early marker for a wide range of human epithelial tumors and suggest that MKP-1 does not behave as a tumor suppressor in epithelial tumors. C1 OREGON HLTH SCI UNIV,VOLLUM INST ADV BIOMED RES,PORTLAND,OR 97201. DEACONESS HOSP,DEPT PATHOL,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115. UNIV BOLOGNA,DEPT PATHOL,BOLOGNA,ITALY. OREGON HLTH SCI UNIV,DEPT PATHOL,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT MICROBIOL,PORTLAND,OR 97201. NR 70 TC 144 Z9 150 U1 1 U2 6 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1996 VL 149 IS 5 BP 1553 EP 1564 PG 12 WC Pathology SC Pathology GA VQ237 UT WOS:A1996VQ23700016 PM 8909245 ER PT J AU Huang, SF Xiao, S Renshaw, AA Loughlin, KR Hudson, TJ Fletcher, JA AF Huang, SF Xiao, S Renshaw, AA Loughlin, KR Hudson, TJ Fletcher, JA TI Fluorescence in situ hybridization evaluation of chromosome deletion patterns in prostate cancer SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; TUMOR-SUPPRESSOR GENE; ALLELIC LOSS; INSITU HYBRIDIZATION; MALIGNANT MESOTHELIOMA; INTERPHASE CYTOGENETICS; HOMOZYGOUS DELETION; LUNG-CANCER; LONG ARM; CARCINOMA AB Various nonrandom chromosomal aberations have been identified in prostate carcinoma. These aberrations include deletions of several chromosome regions, particularly the chromosome 8 short arm. Large-scale numerical aberrations, reflected in aberrant DNA ploidy, are also found in a minority of cases. However, it is unclear whether prostate carcinomas contain aberrations of certain chromosome regions that are deleted frequently in other common types of cancer. In this study, we performed dual-color fluorescence in situ hybridization on intact nuclei from touch preparations of 16 prostate cancers. Chromosome copy number was determined using pericentromeric probes, whereas potential chromosome arm deletions were evaluated using yeast artificial chomosome (YAC) and P1 probes. Two YAC probes targeted chromosome 8 short arm regions known to be deleted frequently in prostate cancer. Other YACs and P1s were for chromosome regions, including 1p22, 3p14, 6q21, 9p21, and 22q12, that are deletion targets in a variety of cancers although not extensively studied ill prostate cancer. Hybridization efficiencies and signal intensities were excellent for both repeat sequence (alpha-satellite) and single-copy copy (YAC and P1) fluorescence in situ hybridization probes. Of 16 prostate cancers, 11 had clonal abet-rations of 1 or more of the 13 chromosome regions evaluated and 10 cases (62.5%) had 8p deletions, including 4 cases with 8p deletion in virtually all cells and aneuploidy in only a subset of those deleted cells. Deletions at 3p14, 6q21, and 22q12 were identified in 2, 1, and 1 case, respectively, and each of those cases had a similarly sized cell population with 8p deletion. These studies confirm 8p deletion in the majority of prostate carcinomas. 8p deletions appear to be early events in prostate tumorigenesis, often antedating aneuploidy. Fluorescence in situ hybridization strategies incorporating pericentromeric and single-copy regional chromosome probes offer a powerful and efficient means for determining frequency progression of oncogenetic events in prostate cancer. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. MIT,WHITEHEAD INST BIOL SCI,CAMBRIDGE,MA 02139. DANA FARBER CANC INST,BOSTON,MA 02115. RI Huang, Shiu-Feng/E-3977-2010 NR 54 TC 29 Z9 29 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 NOV PY 1996 VL 149 IS 5 BP 1565 EP 1573 PG 9 WC Pathology SC Pathology GA VQ237 UT WOS:A1996VQ23700017 PM 8909246 ER PT J AU Burton, MP Schneider, BG Brown, R Gulley, ML AF Burton, MP Schneider, BG Brown, R Gulley, ML TI The effect of histologic strains on PCR analysis of microdissected, paraffin-embedded tissues SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. WILFORD HALL USAF MED CTR,SAN ANTONIO,TX 78236. NR 0 TC 0 Z9 0 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 NOV PY 1996 VL 149 IS 5 BP ST18 EP ST18 PG 1 WC Pathology SC Pathology GA VQ237 UT WOS:A1996VQ23700104 ER PT J AU Rajagopalan, S Li, P Fryetes, C AF Rajagopalan, S Li, P Fryetes, C TI Presence of breast cancer cells in peripheral blood stem cell harvests used in autotransplantation SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Meeting Abstract C1 METHODIST HOSP,HOUSTON,TX 77030. BAYLOR COLL MED,HOUSTON,TX 77030. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1996 VL 149 IS 5 BP ST6 EP ST6 PG 1 WC Pathology SC Pathology GA VQ237 UT WOS:A1996VQ23700092 ER PT J AU Bosch, I Jackson, GR Croop, JM Cantiello, HF AF Bosch, I Jackson, GR Croop, JM Cantiello, HF TI Expression of Drosophila melanogaster P-glycoproteins is associated with ATP channel activity SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE Sf9 cells; baculovirus; multidrug-resistance gene products; adenosine 5'-triphosphate release ID TRANSMEMBRANE CONDUCTANCE REGULATOR; MULTIDRUG-RESISTANCE; CHLORIDE CHANNELS; DRUG TRANSPORT; INSECT CELLS; GENE; MEMBRANE; CURRENTS; PHOSPHORYLATION; BACULOVIRUS AB Two distinct Drosophila melanogaster P-glycoprotein (Pgp) gene homologues of different chromosomal origin, MDR49 and MDR65, have been previously identified (38). Most Pgps are implicated in the development of the multidrug-resistance phenotype. Despite intense efforts to identify the molecular mechanism(s) associated with Pgp function, the endogenous substrate(s) of these transport molecules is largely unknown. Recent studies from our laboratory indicate that a murine Pgp homologue (E. H. Abraham, A. G. Prat, L. Gerweck, T. Seneveratne, R. J. Arceci, R. Kramer, G. Guidotti, and H. F. Cantiello. Proc. Natl. Acad. Sci. USA 90: 312-316, 1993) and a related protein, the cystic fibrosis transmembrane conductance regulator (CFTR; I. L. Reisin, A. Prat, E. H. Abraham, J. F. Amara, R. J. Gregory, D. A. Ausiello, and H. F. Cantiello. J. Biol. Chem. 269: 20584-20591, 1994), are novel ATP-permeable ion channels. The common feature of these two proteins is the conserved ATP-binding cassettes (ABC); thus molecules structurally linked to the ABC transporter family may be also functionally associated with ATP channel activity. In this study, MDR65 and MDR49 Pgps were functionally expressed in Sig cells, and patch-clamp techniques were applied to assess the role of these proteins in the electrodiffusional movement of ATP. In the presence of intracellular ATP and external NaCl, expression of MDR65 was associated with a linear electrodiffusional pathway that was permeable to both ATP and Cl-. Under symmetrical ATP conditions, only voltage depolarization activated a MDR65-mediated ATP-conductive pathway. Expression of MDR49 was also associated with a voltage-activated ATP conductance in symmetrical ATP, but no apparent permeability to either Cl- or ATP was observed under asymmetrical conditions. The different functional properties of MDR65 and MDR49 may be indicative of distinct physiological roles in this organism. The study indicates, however, that the two Drosophila Pgp homologues share strong functional similarities with their mammalian relatives Pgp and CFTR. C1 MASSACHUSETTS GEN HOSP EAST, RENAL UNIT, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV PEDIAT HEMATOL ONCOL, BOSTON, MA 02115 USA. CHILDRENS HOSP, BOSTON, MA 02115 USA. NR 39 TC 32 Z9 32 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD NOV PY 1996 VL 271 IS 5 BP C1527 EP C1538 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA VT088 UT WOS:A1996VT08800014 ER PT J AU CoupayeGerard, B Bookstein, C Duncan, P Chen, XY Smith, PR Musch, M Ernst, SA Chang, EB Kleyman, TR AF CoupayeGerard, B Bookstein, C Duncan, P Chen, XY Smith, PR Musch, M Ernst, SA Chang, EB Kleyman, TR TI Biosynthesis and cell surface delivery of the NHE1 isoform of Na+/H+ exchanger in A6 cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE protein sorting; intracellular trafficking; anti-sodium proton exchanger-1 antibody; biotinylation; sodium/proton exchanger ID RAT NA/H EXCHANGER; MOLECULAR-CLONING; GROWTH-FACTOR; EXTRACELLULAR DOMAIN; CYTOPLASMIC DOMAIN; EPITHELIAL-CELLS; H+ EXCHANGER; CDNA CLONING; EXPRESSION; RECEPTOR AB The Na+/H+ exchanger isoform NHE1 is localized to the basolateral membrane of renal and intestinal epithelia. We examined the plasma membrane distribution, biosynthesis, and cell surface delivery of NHE1 in A6 epithelia. NHE1 was localized to the basolateral membrane. Studies of NHE1 biosynthesis with a pulse-chase protocol demonstrated that a core glycosylated, endoglycosidase H-sensitive, 90-kDa NHE1 was present 0-5 h into the chase period and that mature 110-kDa NHE1 was present 1-24 h into the chase period. Studies of plasma membrane delivery of newly synthesized NHE1 demonstrated that the 90-kDa NHE1 was detected at both apical and basolateral membranes 2-5 h into the chase period. The 110-kDa NHE1 was observed at the basolateral membrane 5-24 h into the chase period. These results suggest that NHE1 is expressed primarily at the basolateral membrane of A6 cells, that core glycosylated NHE1 is delivered to the plasma membrane in a nonpolarized manner, and that mature 110-kDa NHE1 is delivered to the basolateral membrane. C1 VET AFFAIRS MED CTR, MED RES 151, PHILADELPHIA, PA 19104 USA. UNIV PENN, DEPT MED, PHILADELPHIA, PA 19104 USA. UNIV PENN, DEPT PHYSIOL, PHILADELPHIA, PA 19104 USA. MED COLL PENN & HAHNEMANN UNIV, DEPT PHYSIOL, PHILADELPHIA, PA 19102 USA. UNIV CHICAGO, DEPT MED, CHICAGO, IL 60637 USA. UNIV MICHIGAN, DEPT ANAT & CELL BIOL, ANN ARBOR, MI 48109 USA. NR 30 TC 32 Z9 32 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD NOV PY 1996 VL 271 IS 5 BP C1639 EP C1645 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA VT088 UT WOS:A1996VT08800025 ER PT J AU Levine, S Tikunov, B Henson, D LaManca, J Sweeney, HL AF Levine, S Tikunov, B Henson, D LaManca, J Sweeney, HL TI Creatine depletion elicits structural, biochemical, and physiological adaptations in rat costal diaphragm SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE guanidinopropionic acid; myosin heavy chain isoforms; cross-sectional area of fiber types; fatigability ID HEAVY-CHAIN ISOFORMS; SKELETAL-MUSCLE; FIBER TYPES; PHOSPHOCREATINE; FATIGUE; KINASE; UNDERNUTRITION; CONTRACTILITY; TRANSITIONS; DEFICIENT AB To elucidate adaptations elicited by creatine (Cr) depletion in the costal diaphragm (Dia), 16 12-wk-old male Fisher 344 rats had 2% beta-guanidinopropionic acid (beta-GPA), a competitive inhibitor of Cr transport into muscle, added to their food; a control group (Con) of 16 rats ate normal rat chow. After 18 wk, beta-GPA and Con Dia did not differ histochemically with respect to fiber-type distribution; however, the cross-sectional area of type II(b + x) fibers was 33% less in beta-GPA than Con Dia. Biochemically, the proportion of myosin heavy chain IIb in beta-GPA Dia was decreased 42% from Con Dia, whereas the proportions of myosin heavy chains I and IIa were increased. Physiologically, both peak twitch tension and tetanic tension in beta-GPA Dia were decreased 40% from Con. To assess fatigability, we used the protocol of Kelsen and Nochomovitz (J. Appl. Physiol. 53: 440-447, 1982) for 2-6 min duration; the percentage of initial force exhibited by beta-GPA Dia was approximately twice that of Con Dia. We conclude that these structural, biochemical, and physiological adaptations elicited by Cr depletion can all be explained by selective atrophy of IIb muscle fibers in the Dia. C1 VET AFFAIRS MED CTR, PULM & CRIT CARE SECT, PHILADELPHIA, PA 19104 USA. MED COLL PENN & HAHNEMANN UNIV, PHILADELPHIA, PA 19104 USA. RI Sweeney, H Lee/F-1862-2010 NR 30 TC 8 Z9 8 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD NOV PY 1996 VL 271 IS 5 BP C1480 EP C1486 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA VT088 UT WOS:A1996VT08800008 ER PT J AU Carlberg, KA Alvin, BL Gwosdow, AR AF Carlberg, KA Alvin, BL Gwosdow, AR TI Exercise during pregnancy and maternal and fetal plasma corticosterone and androstenedione in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE blood sampling; cardiac puncture; fetal blood; halothane; prenatal stress ID PITUITARY-ADRENAL AXIS; SEXUAL-BEHAVIOR; PRENATAL STRESS; IMMOBILIZATION STRESS; ACTH INJECTIONS; FEMALE RATS; ANDROGENS; SECRETION AB Adrenocortical glucocorticoid and androgen secretion is stimulated by exercise. Excesses of thee hormones in fetuses can cause abnormalities in development. We measured maternal and fetal plasma corticosterone and androstenedione concentrations in Sprague-Dawley rats immediately after maternal exercise in exercise-trained mothers and at rest in sedentary mothers. To do this, we developed a technique for fetal blood sampling and assessed its effect on maternal and fetal plasma corticosterone concentrations. Under halothane anesthesia. maternal blood was collected by cardiac puncture and fetal blood was collected from carotid and jugular vessels. Corticosterone was not affected by the blood collection procedure. Corticosterone was significantly higher in exercised mothers and their fetuses after 30 min of running than in sedentary mothers and their fetuses at rest. Androstenedione was significantly higher in exercised mothers after 30 min of running than in sedentary mothers at rest, but fetal androstenedione was not different between groups. We conclude that this maternal exercise protocol elevates plasma corticosterone but not androstenedione concentrations in fetal rats. C1 EASTERN WASHINGTON UNIV, DEPT MATH, CHENEY, WA 99004 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, ENDOCRINE UNIT, BOSTON, MA 02114 USA. RP Carlberg, KA (reprint author), EASTERN WASHINGTON UNIV, DEPT BIOL, 526 5TH ST, MS-72, CHENEY, WA 99004 USA. FU NICHD NIH HHS [HD-28228]; NIDDK NIH HHS [DK-41419] NR 30 TC 9 Z9 9 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV PY 1996 VL 271 IS 5 BP E896 EP E902 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA VT346 UT WOS:A1996VT34600015 PM 8944678 ER PT J AU Goke, M Zuk, A Podolsky, DK AF Goke, M Zuk, A Podolsky, DK TI Regulation and function of extracellular matrix in intestinal epithelial restitution in vitro SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE intestinal crypt cells; cell migration; basement membrane; mucosal injury ID GROWTH-FACTOR-BETA; BASEMENT-MEMBRANE COMPONENTS; RAT SMALL-INTESTINE; IV COLLAGEN; MESSENGER-RNA; A-CHAIN; GLOBULAR DOMAIN; INVITRO MODEL; LAMININ-A; CELLS AB Repair of epithelial injury in the gastrointestinal tract is initially accomplished by migration of epithelial cells from the wound edge (''restitution''). To assess expression and function of the extracellular matrix (ECM) in the restitution phase after epithelial injury, in vitro studies using wounded monolayers of a rat intestinal epithelium-derived cell Line (IEC-B) were undertaken. IEC-6 cells expressed fibronectin (FN) mRNA and protein in large amounts and lesser quantities of laminin-beta(1) (LN beta(1)) and LN gamma(1). Collagen IV (Col IV) was weakly expressed, and LN alpha(1) was not detected. After wounding, a significant decrease in FN, LN beta(1), LN gamma(1), and Col IV alpha(1) mRNA steady-state levels was observed; mean content 24 h after wounding was reduced by 75-90%. FN, LN, and Col IV proteins were also reduced. The downregulation of these ECM transcripts and proteins could be substantially prevented by transforming growth factor-beta(1), a restitution-promoting growth factor. In addition to changes of expression, the distribution of FN and LN was also altered in migrating cells after wounding, as assessed by immunofluorescence. Arg-Gly-Asp peptides that recognize the major cell attachment Bite on FN and antibodies recognizing the main noncollagenous domain of Col IV inhibited cell migration, but immunoneutralizing anti-LN antisera did not affect restitution. In conclusion, although paradoxically downregulated after wounding, ECM proteins, in particular FN and Col IV molecules, are able to enhance intestinal epithelial restitution. C1 MASSACHUSETTS GEN HOSP, GASTROINTESTINAL UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CTR STUDY INFLAMMATORY BOWEL DIS, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, RENAL UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-46768, DK-43351, DK-41557] NR 73 TC 60 Z9 61 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 1996 VL 271 IS 5 BP G729 EP G740 PG 12 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA VT747 UT WOS:A1996VT74700001 PM 8944685 ER PT J AU Takehara, Y Sumii, K Tari, A Yoshihara, M Sumii, M Haruma, K Kajiyama, G Wu, SV Walsh, JH AF Takehara, Y Sumii, K Tari, A Yoshihara, M Sumii, M Haruma, K Kajiyama, G Wu, SV Walsh, JH TI Evidence that endogenous GRP in rat stomach mediates omeprazole-induced hypergastrinemia SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE gastrin-releasing peptide; gastrin; bombesin antagonist ID GASTRIN-RELEASING PEPTIDE; BOMBESIN; SECRETION; IMMUNOREACTIVITY; EXTRACTION; TISSUE; GENE; RNA AB To investigate the physiological role of endogenous gastrin-releasing peptide (GRP) in regulating the release of gastrin, we evaluated the response of intragastric pH, gastrin, and GRP after omeprazole treatment in rats. A significant elevation of the plasma level of GRP (P < 0.01) and a significant reduction of the antral content of GRP (P < 0.05) were observed after the administration of 100 mg/kg omeprazole. The antral content of GRP was significantly decreased 12 h after omeprazole administration and thereafter gradually returned to control levels. Peak values for intragastric pH and plasma GRP were observed 3 h after omeprazole administration and before the peak of serum gastrin. The bombesin antagonist [D-Phe(6)]-bombesin-(6,13)-methyl ester significantly inhibited gastrin release after omeprazole treatment (P < 0.05). These observations indicate that omeprazole-induced inhibition of acid secretion stimulates the release of GRP and suggest that the secretion of GRP induced by omeprazole may stimulate the secretion of gastrin, at least in the early phase. C1 HIROSHIMA UNIV, SCH MED, DEPT INTERNAL MED 1, MINAMI KU, HIROSHIMA 734, JAPAN. W LOS ANGELES VET AFFAIRS MED CTR, CTR ULCER RES & EDUC, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA 90024 USA. NR 26 TC 9 Z9 10 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 1996 VL 271 IS 5 BP G799 EP G804 PG 6 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA VT747 UT WOS:A1996VT74700009 PM 8944693 ER PT J AU Ziegler, TR Mantell, MP Chow, JC Rombeau, JL Smith, RJ AF Ziegler, TR Mantell, MP Chow, JC Rombeau, JL Smith, RJ TI Gut adaptation and the insulin-like growth factor system: Regulation by glutamine and IGF-I administration SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE glutamine; insulin-like growth factor-I; insulin-like growth factor binding proteins; small intestine ID DEXAMETHASONE-TREATED RATS; TOTAL PARENTERAL-NUTRITION; SMALL-BOWEL RESECTION; BINDING-PROTEINS; GENE-EXPRESSION; RECEPTORS AB Intestinal adaptation after extensive small bowel resection in rats is augmented by the provision of diets supplemented with the amino acid glutamine (Gin) or by administration of insulinlike growth factor-I (IGF-I). The goal of this study was to investigate potential synergistic effects of Gin and IGF-I on postresection ileal hyperplasia. Rats underwent 80% small bowel resection (SBR) and then were fed low-Gin or L-Gln-enriched diets and subcutaneously given recombinant human IGF-I or vehicle for 7 days. Gin and IGF-I each significantly enhanced adaptive ileal hyperplasia (DNA content) compared with rats receiving vehicle and low-Gin diet. Ileal DNA content was highest when IGF-I was administered together with Gin supplementation. Combined IGF-I plus Gin synergistically increased ileal weight and protein content. This was associated with higher plasma concentrations of IGF-I and Gin than observed when IGF-I or Gin was given individually. Ileal IGF-I mRNA expression rose nearly twofold during gut adaptation after SBR; this response was augmented with IGF-I administration but was unaltered by Gin feeding. In contrast, dietary Gin, but not IGF-I therapy, prevented a decrease in hepatic IGF-I mRNA induced by SBR. We conclude that parenteral IGF-I and enteral Gin have both individual and synergistic effects on ileal adaptation after massive small intestinal resection. These findings support the concept that specific gut-trophic nutrients and growth factors may be combined to enhance intestinal adaptation and possibly reduce the severity of short bowel syndrome after intestinal resection. C1 HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, JOSLIN RES LAB, BOSTON, MA 02215 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DEPT MED, BOSTON, MA 02215 USA. HOSP UNIV PENN, DEPT SURG, PHILADELPHIA, PA 19104 USA. FU NIDDK NIH HHS [DK-48503, DK-43038]; NIGMS NIH HHS [GM-36428] NR 30 TC 83 Z9 91 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 1996 VL 271 IS 5 BP G866 EP G875 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA VT747 UT WOS:A1996VT74700018 PM 8944702 ER PT J AU Herlihy, JP Vermeulen, HW Hales, CA AF Herlihy, JP Vermeulen, HW Hales, CA TI Human alveolar macrophages prevent apoptosis in polymorphonuclear leukocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE programmed cell death; tumor necrosis factor; granulocyte/macrophage colony-stimulating factor; allergic reaction ID COLONY-STIMULATING FACTOR; PROGRAMMED CELL-DEATH; AGING NEUTROPHILS; MONOCYTES; SMOKE; PHAGOCYTOSIS; ACTIVATION; CYTOKINES; SURVIVAL; INJURY AB Polymorphonuclear leukocytes (PMN) are recruited to the lungs to defend against injury and infection. However, PMN undergo apoptosis, thereby losing functional ability within hours, and die with lysis soon thereafter unless they receive specific signals preventing this phenomenon. We hypothesized that alveolar macrophages (AM) could provide these signals. Therefore AM, obtained through bronchoalveolar lavage of healthy volunteers (n = 9), were cultured for 24 h, after which the AM conditioned media (AM-CM) were removed. Freshly isolated PMN, which showed no apoptosis, were suspended in AM-CM, as well as in unconditioned media (UM), and followed over 48 h for apoptosis and survival. In eight of nine patients, AM-CM contained tumor necrosis factor (TNF), which modestly delayed AM apoptosis so that the percentage of PMN apoptotic at 24 h was 77 +/- 6% in AM-CM compared with 91 +/- 2% in UM (P < 0.05). In one patient, urticaria developed early in the lavage, and this subject's AM-CM profoundly prevented apoptosis of PMN (to 10% at 24 h). PMN survival in this patient was similarly enhanced, so that at 48 h of culture it was 60%, compared with 45 +/- 8% in AM-CM and 30 +/- 6% in UM (P < 0.05 UM vs. AM-CM). Granulocyte/macrophage colony-stimulating factor (GM-CSF), in addition to TNF-alpha, partly accounted for this medium's activity. Thus AM can delay apoptosis in PMN through production of TNF-alpha and in some cases by GM-CSF. When activated in vivo by conditions such as an allergic reaction, AM can rapidly and profoundly suppress PMN apoptosis. C1 MASSACHUSETTS GEN HOSP, PULM & CRIT CARE UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. FU NHLBI NIH HHS [HL-36829, 1-F32-HL-09017-01, R29-HL-46966] NR 24 TC 6 Z9 6 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD NOV PY 1996 VL 271 IS 5 BP L681 EP L687 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA VR965 UT WOS:A1996VR96500001 PM 8944710 ER PT J AU Kelly, KJ TolkoffRubin, NE Rubin, RH Williams, WW Meehan, SM Meschter, CL Christenson, JG Bonventre, JV AF Kelly, KJ TolkoffRubin, NE Rubin, RH Williams, WW Meehan, SM Meschter, CL Christenson, JG Bonventre, JV TI An oral platelet-activating factor antagonist, Ro-24-4736, protects the rat kidney from ischemic injury SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE acute renal failure; ischemia-reperfusion injury; phospholipid mediators; leukocyte adhesion; animal models ID ACUTE-RENAL-FAILURE; INDUCED LEUKOCYTE ADHERENCE; ENDOTHELIAL-CELLS; FACTOR PAF; REPERFUSION; ICAM-1; ACCUMULATION; DYSFUNCTION; INVOLVEMENT; NEUTROPHILS AB The role of platelet-activating factor (PAF) in ischemic acute renal failure was evaluated by administering an oral PAF antagonist (Re-24-4736) to rats prior to or after interruption of blood flow to both kidneys for 30 min. In animals treated with the PAF antagonist prior to ischemia, renal function was less impaired and histological abnormalities was less pronounced when compared with postischemic kidneys from vehicle-treated animals. Serum creatinine (mg/dl) 24 h following renal ischemia was 1.58 +/- 0.17 in the PAF antagonist-treated rats compared with 2.19 +/- 0.15 in rats given placebo (P < 0.01). There was less necrosis in the outer medulla of kidneys of PAF antagonist-treated animals (P < 0.01). Tissue myeloperoxidase activity at 48 and 72 h postisch emia was lower in kidneys of PAF antagonist-treated rats (P < 0.05). The PAF antagonist was also protective when administered 30 min but not 2 h following the ischemic insult. The coincident use of anti-intercellular adhesion molecule-1 monoclonal antibody did not confer additional protection over that observed with the oral PAF antagonist alone. These data suggest that PAF contributes to the pathophysiology of renal ischemic injury, perhaps by its effects on leukocyte-endothelial interactions. An orally active PAF antagonist can protect against the development of ischemic acute renal failure. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,MED SERV, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED, PATHOL SERV, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL, PATHOL SERV, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL, MED SERV, BOSTON, MA 02114 USA. HARVARD UNIV, MIT, CTR EXPT PHARMACOL & THERAPEUT, DIV HLTH SCI & TECHNOL, CAMBRIDGE, MA 02139 USA. HOFFMANN LA ROCHE INC, ROCHE RES CTR, NUTLEY, NJ 07110 USA. NR 36 TC 31 Z9 31 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD NOV PY 1996 VL 271 IS 5 BP F1061 EP F1067 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA VT083 UT WOS:A1996VT08300015 ER PT J AU Levy, ML Cummings, JL Fairbanks, LA Bravi, D Calvani, M Carta, A AF Levy, ML Cummings, JL Fairbanks, LA Bravi, D Calvani, M Carta, A TI Longitudinal assessment of symptoms of depression, agitation, and psychosis in 181 patients with Alzheimer's disease SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry CY FEB 14-17, 1996 CL TUCSON, AZ SP Amer Assoc Geriatr Psychiat ID PSYCHIATRIC-SYMPTOMS; NURSING-HOME; DEMENTIA; SCALE AB Objective: The goal of this study was to define the recurrence or continuation of neuropsychiatric symptoms in patients with Alzheimer's disease who were observed serially for a 1-year period. Method: One hundred eighty-one patients with probable Alzheimer's disease were assessed five time at 3-month intervals with a standardized neuropsychiatric rating instrument. Results: Recurrence rates of neuropsychiatric symptoms during the 1-year period were 85% for depression, 93% for agitation, and 95% for psychosis. Symptom frequency at any point in time underestimated the cumulative 1-year frequency. Recurrence rates were significantly greater among patients who had multiply symptoms. Women exhibited more symptoms than men. Patients in the oldest age group (76-87 years) had more psychosis, less depression and agitation, and slower cognitive decline. Psychosis was associated with more rapid cognitive decline, and agitation was associated with more rapid functional deterioration. Conclusions: These results indicate that once psychiatric symptoms are present in patients with Alzheimer's disease, they frequently recur. These symptoms vary with age, sex, and rate of illness progression. C1 UNIV CALIF LOS ANGELES,SCH MED,INST NEUROPSYCHIAT,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,LOS ANGELES,CA 90073. SIGMA TAU PHARMACEUT,GAITHERSBURG,MD. FU NIA NIH HHS [AG-10123] NR 23 TC 185 Z9 188 U1 1 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1996 VL 153 IS 11 BP 1438 EP 1443 PG 6 WC Psychiatry SC Psychiatry GA VP754 UT WOS:A1996VP75400010 PM 8890677 ER PT J AU Teoh, SK Whitman, GJ Chew, FS AF Teoh, SK Whitman, GJ Chew, FS TI Villous adenoma of the colon SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MD ANDERSON HOSP & TUMOR INST,DIV DIAGNOST IMAGING,HOUSTON,TX 77030. NR 4 TC 4 Z9 4 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 1996 VL 167 IS 5 BP 1146 EP 1146 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VR329 UT WOS:A1996VR32900015 PM 8911168 ER PT J AU Kaufman, JA Kazanjian, SA Rivitz, SM Geller, SC Waltman, AC AF Kaufman, JA Kazanjian, SA Rivitz, SM Geller, SC Waltman, AC TI Long-term central venous catheterization in patients with limited access SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PERCUTANEOUS PLACEMENT; HICKMAN CATHETER; INTERCOSTAL VEIN; INSERTION RP Kaufman, JA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,GRB 290,FRUIT ST,BOSTON,MA 02114, USA. NR 11 TC 10 Z9 10 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 1996 VL 167 IS 5 BP 1327 EP 1333 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VR329 UT WOS:A1996VR32900054 PM 8911206 ER PT J AU Jones, MA Young, RH AF Jones, MA Young, RH TI Endocervical type A (noncystic) tunnel clusters with cytologic atypia - A report of 14 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE cervix; pseudoneoplastic glandular lesion; tunnel cluster ID UTERINE CERVIX; MICROGLANDULAR HYPERPLASIA; ADENOMATOUS HYPERPLASIA; ADENOCARCINOMA INSITU; LESIONS AB Tunnel clusters (TCs) are benign, pseudoneoplastic glandular lesions of the cervix that may be divided into type A (noncystic) and type B (cystic). We report 14 examples of type A TC characterized by a florid proliferation of glands with greater cytologic atypia than normally encountered in this lesion. The Majority had been sent for consultation to exclude adenoma malignum (minimal deviation adenocarcinoma). The patients ranged in age from 32 to 54 (mean 44.8) years. Mean gravidity was 2.5 and parity 2.1; all but one patient were multigravid. A history of recent exogenous hormone intake was present in 4 (33%) patients, An of the lesions were incidental findings, and none was associated with a gross abnormality. Microscopically, all were characterized by a lobulated proliferation of predominantly small-caliber, nondilated, closely packed glands frequently arranged around a central primary or secondary endocervical cleft. Most were well circumscribed, but irregular borders created a pseudoinvasive appearance in four cases. The lesions ranged from 2.5 to 7 (mean 3.5 mm) and were frequently associated with type B TC. The glands were lined by either mucinous columnar cells or low cuboidal cells. Cellular crowding with pseudostratification was common, bur true stratification or cribriforming was absent. All cases had foci of cytologic atypia including nuclear enlargement, hyperchromasia, prominent nucleoli, and vesicular chromatin. Mitotic activity was absent or inconspicuous. Follow-up in 9 patients (7 treated with hysterectomy, one each with cone biopsy and biopsy only) ranged from 1 to 6 (mean 2.7) years and tvas uneventful in all of them, Follow-up Nas unavailable in one, and four were recent cases, Endocervical type A TC with cytologic atypia is a common benign glandular lesion that must be distinguished from adenoma malignum. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA. RP Jones, MA (reprint author), MAINE MED CTR,DEPT PATHOL,22 BRAMBALL ST,PORTLAND,ME 04102, USA. NR 15 TC 17 Z9 18 U1 0 U2 2 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 NOV PY 1996 VL 20 IS 11 BP 1312 EP 1318 DI 10.1097/00000478-199611000-00002 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA VQ503 UT WOS:A1996VQ50300002 PM 8898835 ER PT J AU Kosower, E Berman, N AF Kosower, E Berman, N TI Comparison of pediatric resident and faculty learning styles: Implications for medical education SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE residents; faculty; learning styles; teaching; inventory; medical education ID CAREER CHOICE AB This article compares resident and faculty learning strategies and styles and considers implications for teaching. The Kolb Learning Style Inventory was administered to 17 pediatric residents and 22 faculty in a pediatric department of an urban university-affiliated public medical center in 1991. Four scales-concrete experience (CE), reflective observation (RO), abstract conceptualization (AC), and active experimentation (AE)-are derived from self-ranking groups of words. Combining strategies leads to one of four styles: accommodator, diverger, converger, or assimilator, Analysis of variance and chi-square statistics were used to analyze strongest strategies and styles and to compare groups. It was found that resident and faculty preferred learning strategies and styles were significantly different. Resident strategies were spread primarily between concrete experience (40.5%) and active experimentation (40.5%), whereas faculty clearly preferred abstract conceptualization (77%). Most residents had either an accommodator or diverger learning style (81%), whereas most faculty were either assimilators or convergers (73%), This knowledge of learning strategy preferences and styles may have implications for design and delivery of instruction to residents. C1 UNIV CALIF LOS ANGELES,SCH MED,W LOS ANGELES VET AFFAIRS,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,HARBOR MED CTR,TORRANCE,CA 90509. NR 18 TC 13 Z9 13 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD NOV PY 1996 VL 312 IS 5 BP 214 EP 218 DI 10.1097/00000441-199611000-00004 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA VR279 UT WOS:A1996VR27900004 PM 8900383 ER PT J AU Cooper, JB AF Cooper, JB TI Is voluntary reporting of critical events effective for quality assurance? SO ANESTHESIOLOGY LA English DT Editorial Material DE complications; monitoring; quality assurance ID ANESTHESIA; ERROR RP Cooper, JB (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA & CRIT CARE,55 FRUIT ST,BOSTON,MA 02114, USA. NR 16 TC 28 Z9 30 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 1996 VL 85 IS 5 BP 961 EP 964 DI 10.1097/00000542-199611000-00002 PG 4 WC Anesthesiology SC Anesthesiology GA VT350 UT WOS:A1996VT35000004 PM 8916811 ER PT J AU Fishman, SM Catarau, EM Sachs, G Stojanovic, M Borsook, D AF Fishman, SM Catarau, EM Sachs, G Stojanovic, M Borsook, D TI Corticosteroid-induced mania after single regional application at the celiac plexus SO ANESTHESIOLOGY LA English DT Article DE psychosis, mania; hormones, corticosteroids; anesthetic techniques, regional, nerve blockade ID STEROID-INDUCED PSYCHOSIS; LITHIUM PROPHYLAXIS; BIPOLAR DISORDER RP Fishman, SM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,MGH PAIN CTR,ACC 324,32 FRUIT ST,BOSTON,MA 02114, USA. NR 25 TC 6 Z9 6 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 NOV PY 1996 VL 85 IS 5 BP 1194 EP 1196 DI 10.1097/00000542-199611000-00030 PG 3 WC Anesthesiology SC Anesthesiology GA VT350 UT WOS:A1996VT35000032 PM 8916839 ER PT J AU Heinrich, RS Fontaine, AA Grimes, RY Sidhaye, A Yang, S Moore, KE Levine, RA Yoganathan, AP AF Heinrich, RS Fontaine, AA Grimes, RY Sidhaye, A Yang, S Moore, KE Levine, RA Yoganathan, AP TI Experimental analysis of fluid mechanical energy losses in aortic valve stenosis: Importance of pressure recovery SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE aortic valve stenosis; control volume; conservation of energy; Medtronic-Hall; St Jude ID PROSTHETIC HEART-VALVES; PULSATILE FLOW; DOPPLER ECHOCARDIOGRAPHY; GORLIN FORMULA; INVITRO; GRADIENTS; SEVERITY; HEMODYNAMICS; VALIDATION; DYNAMICS AB Current methods for assessing the severity of aortic stenosis depend primarily on measures of maximum systolic pressure drop at the aortic valve orifice and related calculations such as valve area. It is becoming increasingly obvious, however, that the impact of the obstruction on the left ventricle is equally important in assessing its severity and could potentially be influenced by geometric factors of the valve, causing variable degrees of downstream pressure recovery. The goal of this study was to develop a method for measuring fluid mechanical energy losses in aortic stenosis that could then be directly related to the hemodynamic load placed on the left ventricle. A control volume form of conservation of energy was theoretically analyzed and modified for application to aortic valve stenosis measurements. In vitro physiological pulsatile flow experiments were conducted with different types of aortic stenosis models, including a venturi meter, a nozzle, and 21-mm Medtronic-Hall tilting disc and St. Jude bileaflet mechanical valves. The energy loss created by each model was measured for a wide range of experimental conditions, simulating physiological variation. In all cases, there was more energy lost for the nozzle (mean = 0.27 J) than for any other model for a given stroke volume. The two prosthetic valves generated approximately the same energy losses (mean = 0.18 J), which were not statistically different, whereas the venturi meter had the lowest energy loss for all conditions (mean = 0.037 J). Energy loss correlated poorly with orifice pressure drop (r(2) = 0.34) but correlated well with recovered pressure drop (r(2) = 0.94). However, when the valves were considered separately, orifice and recovered pressure drop were both strongly correlated with energy loss (r(2) = 0.99, 0.96). The results show that recovered pressure drop, not orifice pressure drop, is directly related to the energy loss that determines pump work and therefore is a more accurate measure of the hemodynamic significance of aortic stenosis. C1 GEORGIA INST TECHNOL,SCH CHEM ENGN,CARDIOVASC FLUID MECH LAB,ATLANTA,GA 30332. GEORGIA INST TECHNOL,SCH MECH ENGN,ATLANTA,GA 30332. GEORGIA INST TECHNOL,INST BIOENGN & BIOSCI,ATLANTA,GA 30332. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,NONINVAS CARDIAC LAB,BOSTON,MA. NR 40 TC 32 Z9 32 U1 1 U2 5 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD NOV-DEC PY 1996 VL 24 IS 6 BP 685 EP 694 DI 10.1007/BF02684181 PG 10 WC Engineering, Biomedical SC Engineering GA VR212 UT WOS:A1996VR21200006 PM 8923988 ER PT J AU Shea, JA Healey, MJ Berlin, JA Clarke, JR Malet, PF Staroscik, RN Schwartz, JS Williams, SV AF Shea, JA Healey, MJ Berlin, JA Clarke, JR Malet, PF Staroscik, RN Schwartz, JS Williams, SV TI Mortality and complications associated with laparoscopic cholecystectomy - A meta-analysis SO ANNALS OF SURGERY LA English DT Review ID BILE-DUCT STONES; INTRAOPERATIVE CHOLANGIOGRAPHY; CONSECUTIVE PATIENTS; SYMPTOMATIC CHOLELITHIASIS; OPERATIVE CHOLANGIOGRAPHY; PROSPECTIVE MULTICENTER; LASER CHOLECYSTECTOMY; COMMUNITY EXPERIENCE; INITIAL EXPERIENCE; SURGICAL-TREATMENT AB Objective The purpose of this study was to perform a meta-analysis of targe laparoscopic cholecystectomy case-series and compare results concerning complications, particularly bile duct injury, to those reported in open cholecystectomy case-series. Summary Background Data Since the introduction of laparoscopic cholecystectomy in the United States, hundreds of reports about the technique have been published, many including statements about the advantages of laparoscopic cholecystectomy compared with those of open cholecystectomy. There is an unevenness in scope and quality of the studies. Nevertheless, enough data have accumulated from large series to permit analyses of data regarding some of the most important issues. Methods Articles identified via a MEDLINE (the National Library of Medicine's computerized database) search were evaluated according to standard criteria. Data regarding the patient sample, study methods, and outcomes of cholecystectomy were abstracted and summarized across studies. Results Outcomes of laparoscopic cholecystectomy are examined for 78,747 patients reported on in 98 studies and compared with outcomes of open cholecystectomy for 12,973 patients reported on in 28 studies. Laparoscopic cholecystectomy appears to have a higher common bile duct injury rate and a lower mortality rate. Estimated rates of other types of complications after laparoscopic cholecystectomy generally were low. Most conversions followed operative discoveries (e.g., dense adhesions) and were not the result of injury. Conclusions There is wide variability in the amount and type of data reported within any single study, and patient populations may not be comparable across studies. Except for a higher common bile duct injury rate, laparoscopic cholecystectomy appears to be at least as safe a procedure as that of open cholecystectomy. C1 UNIV PENN,DIV GASTROENTEROL,PHILADELPHIA,PA 19104. UNIV PENN,DEPT SURG,CTR CLIN EPIDEMIOL & BIOSTAT,PHILADELPHIA,PA 19104. UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. ALLEGHANY UNIV,DEPT SURG,PHILADELPHIA,PA. RP Shea, JA (reprint author), UNIV PENN,DEPT MED,DIV GEN INTERNAL MED,RALSTON HOUSE 318,615 CHESTNUT ST,PHILADELPHIA,PA 19104, USA. FU AHRQ HHS [HS06481] NR 140 TC 244 Z9 264 U1 1 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD NOV PY 1996 VL 224 IS 5 BP 609 EP 620 DI 10.1097/00000658-199611000-00005 PG 12 WC Surgery SC Surgery GA VR939 UT WOS:A1996VR93900005 PM 8916876 ER PT J AU Li, XQ Parkekh, SG Rosenberg, AE Mankin, HJ AF Li, XQ Parkekh, SG Rosenberg, AE Mankin, HJ TI Assessing prognosis for high-grade soft-tissue sarcomas: Search for a marker SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE soft tissue; sarcoma; prognosis; flow cytometry ID MUSCULOSKELETAL TUMORS; STATIC CYTOFLUOROMETRY; DNA-PLOIDY; MRI; CLASSIFICATION; RADIATION; EXTREMITY; CYTOMETRY AB Background: Although improved staging technology, limb-sparing surgery, and adjunctive radiation and chemotherapy have improved the outlook for patients with malignant soft-tissue tumors of the trunk and extremities, it is evident that we cannot predict which patients will develop distant metastases. Although local control is now frequently achieved, most series of high-grade soft-tissue sarcomas carry a mortality rate of >50%. Methods: In a retrospective study of 93 patients with high-grade sarcomas treated between 1986 and 1992, for whom complete studies including size and Volume measurements and DNA ploidy determinations as assessed by now cytometry were available, a search for a marker for increased risk of metastasis or death was performed. Results: Grade of the lesion, sex, diagnosis, anatomical site, ploidic data (including mean DNA index and presence of an aneuploid peak), and treatment factors (including type of surgery, local recurrence, or radiation protocol) did not correlate with outcome. Age (younger patients did better), size (greatest diameter) and volume, and positive margins at surgery correlated with total survival. Conclusions: The results of the study, although negative, point out that using anatomical site, diagnosis, or ploidic analysis offers little toward anticipating outcome, whereas the size of the tumor is important. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ORTHOPAED SERV G606,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ORTHOPAED ONCOL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CONNECT TISSUE ONCOL CTR,BOSTON,MA 02114. NR 42 TC 15 Z9 16 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD NOV PY 1996 VL 3 IS 6 BP 550 EP 557 DI 10.1007/BF02306088 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA VQ160 UT WOS:A1996VQ16000008 PM 8915487 ER PT J AU Chen, G Teicher, BA Frei, E AF Chen, G Teicher, BA Frei, E TI Differential interactions of Pgp inhibitor thaliblastine with adriamycin, etoposide, taxol and anthrapyrazole CI941 in sensitive and multidrug-resistant human MCF-7 breast cancer cells SO ANTICANCER RESEARCH LA English DT Article ID HIGH-DOSE VERAPAMIL; P-GLYCOPROTEIN; DRUG-RESISTANCE; BIOCHEMICAL-CHANGES; TOPOISOMERASE-II; PACLITAXEL TAXOL; CYTO-TOXICITY; TUMOR-CELLS; PHASE-II; EXPRESSION AB The reversing effect of p-glycoprotein (Pgp) inhibitors on the multidrug resistance (MDR) phenotype is well established in a variety of MDR cell lines. The interactions of these inhibitors with individual MDR drugs in the respective parental lines, however, is less documented. This kind of information is not only essential for understanding of the outcome of clinical trials for MDR modulation in heterogeneous tumor populations but also important for evaluating of new Pgp blockers. Interaction of the Pgp inhibitor, thaliblastine (TBL), with several MDR drugs was therefore investigated in sensitive human breast cancer cell line (MCF-7) as well as adriamycin (AdR) selected MDR subline MCF/AdR. While the resistance to anthrapyrazole CI941 was completely overcome by simutaneous exposure to TBL (8 mu M) in a 45 h exposure MTT assay compared with MCF-7 cells exposed to the same combination, only partial reversal was achieved in the case of AdR and etoposide (VP-16), but 240-fold hypersensitivity (or collateral al sensitivity) was obtained in the MCF/AdR cells treated with taxol plus TBL, with IC50s of 0.10 +/- 0.03 mu M and 24.6 +/- 5.0 mu M in the resistant and sensitive cell lines, respectively In the parental MCF-7 cells, on the other hand no change of AdR cytotoxicity by simultaneous exposure to TBL was observed. There was an enhancement of CI941 cytotoxicity but an antagonism against taxol and VP-16 obtained upon addition of TBL to the treatment with the drugs in the MCF-7 par ental cell line. Our results demonstrate that while TBL can overcome the resistance to each of the MDR drugs studied in MCF/AdR cells, albeit to a different extent varying from the partial reversal to the hypersensitivity, TBL co-exposure does not uniformely increase the cytotoxicity of these drugs in the par ental MCF-7 cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. NR 44 TC 9 Z9 9 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 1996 VL 16 IS 6B BP 3499 EP 3505 PG 7 WC Oncology SC Oncology GA WB836 UT WOS:A1996WB83600021 PM 9042212 ER PT J AU Gall, K Desrosiers, M Bensen, D Serago, C AF Gall, K Desrosiers, M Bensen, D Serago, C TI Alanine EPR dosimeter response in proton therapy beams SO APPLIED RADIATION AND ISOTOPES LA English DT Article; Proceedings Paper CT 4th International Symposium on ESR Dosimetry and Applications CY MAY 15-19, 1995 CL MUNICH, GERMANY SP GSF, IAEA, WHO, Russian Acad Sci ID RADIATION AB We report a series of measurements directed to assess the suitability of alanine as a mailable dosimeter for dosimetry quality assurance of proton radiation therapy beams. These measurements include dose-response of alanine at 140 MeV, and comparison of response vs energy with a parallel plate ionization chamber. All irradiations were made at the Harvard Cyclotron Laboratory, and the dosimeters were read at NIST. The results encourage us that alanine could be expected to serve as a mailable dosimeter with Systematic error due to differential energy response no greater than 3% when doses of 25 Gy are used. Copyright (C) 1996 Published by Elsevier Science Ltd C1 NIST,IONIZING RADIAT DIV,US DEPT COMMERCE,GAITHERSBURG,MD 20899. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. FU NCI NIH HHS [CA 21239] NR 3 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 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD NOV-DEC PY 1996 VL 47 IS 11-12 BP 1197 EP 1199 DI 10.1016/S0969-8043(96)00201-1 PG 3 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA WD715 UT WOS:A1996WD71500012 PM 9022180 ER PT J AU Copeland, JF Gall, KP Lee, SY Chabot, GE AF Copeland, JF Gall, KP Lee, SY Chabot, GE TI Proton dosimetry in bone using electron spin resonance SO APPLIED RADIATION AND ISOTOPES LA English DT Article; Proceedings Paper CT 4th International Symposium on ESR Dosimetry and Applications CY MAY 15-19, 1995 CL MUNICH, GERMANY SP GSF, IAEA, WHO, Russian Acad Sci ID RADIATION-THERAPY; EPR DOSIMETRY; BEAM; DEPENDENCE AB We have studied the ESR response of proton-irradiated (in vitro) bone. The ESR response as a function of proton (E = 105 MeV) dose to bone was linear from 0 to 50 Gy and similar to the photon (E = 6 MV) dose response. The ESR depth response (Bragg) curve was depressed as compared to a depth-response curve determined with a parallel plate ionization chamber (PPIC). There was a short-term ESR signal fade in the Bragg peak region, likely attributable to the organic component in bone. We are continuing to investigate these latter two effects. Copyright (C) 1996 Elsevier Science Ltd C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. RP Copeland, JF (reprint author), UNIV LOWELL,DEPT PHYS,RADIOL SCI PROGRAM,LOWELL,MA 01854, USA. FU NCI NIH HHS [CA-21239] NR 23 TC 9 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD NOV-DEC PY 1996 VL 47 IS 11-12 BP 1533 EP 1538 DI 10.1016/S0969-8043(96)00246-1 PG 6 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA WD715 UT WOS:A1996WD71500069 PM 9022199 ER PT J AU Craig, AH Cummings, JL Fairbanks, L Itti, L Miller, BL Li, J Mena, I AF Craig, AH Cummings, JL Fairbanks, L Itti, L Miller, BL Li, J Mena, I TI Cerebral blood flow correlates of apathy in Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID FRONTAL-SUBCORTICAL CIRCUITS; SENILE DEMENTIA; PERSONALITY CHANGES; SYNAPSE LOSS; CORTEX; PATTERNS; SPECT AB Background: Apathy is a pervasive noncognitive neuropsychiatric disturbance in Alzheimer disease, which causes significant caregiver distress. The neuroanatomical substrate of apathy is not well understood. Objective: To study the relationship between regional cerebral blood flow and the presence and severity of the personality disturbance, apathy, in individuals with Alzheimer disease. Design: Analysis of the relationship between regional cerebral blood flow as measured by single photon emission computed tomography and severity of apathy as measured by the Neuropsychiatric Inventory using an analysis of variance design. We examined regional cerebral perfusion alterations as measured by xenon Xe-133-calibrated technetium Tc 99m hexamethyl-propyleneamine-oxime single photon emission computed tomography in relation to the presence and severity of apathy. Setting: The neurology clinics of the University of California, Los Angeles, UCLA School of Medicine, and Harbor-UCLA Medical Center. Participants: Thirty-one community-dwelling patients fulfilling National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association diagnostic criteria for probable Alzheimer disease who had a single photon computed tomographic scan performed within 3 months of administration of the Neuropsychiatric Inventory. Results: The presence of apathy was associated with more severe prefrontal and anterior temporal dysfunction. These regional cerebral perfusion relationships with apathy were independent of cognitive decline except in the dorsolateral prefrontal cortex. Conclusions: These results demonstrate the association of apathetic syndromes with prefrontal and anterior temporal regional brain dysfunction and are consistent with similar findings preciously reported in other disorders. C1 UNIV CALIF LOS ANGELES,SCH MED,REED NEUROL RES CTR,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,REED NEUROL RES CTR,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,BEHAV NEUROSCI SECT,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,HARBOR MED CTR,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,HARBOR MED CTR,DEPT RADIOL,LOS ANGELES,CA 90024. FU NIA NIH HHS [AG10123, AG00172] NR 36 TC 152 Z9 153 U1 3 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 1996 VL 53 IS 11 BP 1116 EP 1120 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA VR053 UT WOS:A1996VR05300006 PM 8912484 ER PT J AU Stern, Y Liu, XH Albert, M Brandt, J Jacobs, DM DelCastilloCastaneda, C Marder, K Bell, K Sano, M Bylsma, F AF Stern, Y Liu, XH Albert, M Brandt, J Jacobs, DM DelCastilloCastaneda, C Marder, K Bell, K Sano, M Bylsma, F TI Modeling the influence of extrapyramidal signs on the progression of Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID LEWY BODY DISEASE; DEMENTIA; PREDICTORS; DECLINE AB Objective: To determine how the advent of extrapyramidal signs influences the progression of Alzheimer disease as measured by standard clinical measures. Design: We applied growth curve models to prospective data to characterize patients' cognitive and functional changes over time. To detect changes in disease course related to extrapyramidal signs, their onset was treated as a time-dependent covariate. Setting: Three research medical centers. Participants: Patients (n=217) with probable Alzheimer disease. Intervention: Patients were followed up semiannually for 5 years. Main Outcome Measures: Scores on the modified Mini-Mental State Examination and measures of basic and instrumental activities of daily living from the Blessed Dementia Rating Scale. Results: For basic and instrumental activities of daily living, disease course was more rapid once extrapyramidal signs developed. Decline in the modified Mini-Mental State Examination score was greater at the time the signs developed, but not at subsequent visits. Conclusions: The point at which extrapyramidal signs emerge is associated with measurable acceleration in the progression of Alzheimer disease. This may in part explain why extrapyramidal signs are associated with a poorer prognosis. The differential influence of extrapyramidal signs on cognitive and functional measures suggests that the pathological changes underlying these disease features may vary. C1 COLUMBIA UNIV COLL PHYS & SURG, DEPT NEUROL, NEW YORK, NY 10032 USA. COLUMBIA UNIV COLL PHYS & SURG, DEPT PSYCHIAT, NEW YORK, NY 10032 USA. JOHNS HOPKINS UNIV, DEPT PSYCHIAT & BEHAV SCI, BALTIMORE, MD USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PSYCHIAT, BOSTON, MA USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT NEUROL, BOSTON, MA USA. RP Stern, Y (reprint author), COLUMBIA UNIV COLL PHYS & SURG, GERTRUDE H SERGIEVSKY CTR, 630 W 168TH ST, NEW YORK, NY 10032 USA. OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [RR00645]; NIA NIH HHS [AG07370] NR 30 TC 35 Z9 35 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 1996 VL 53 IS 11 BP 1121 EP 1126 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA VR053 UT WOS:A1996VR05300007 PM 8912485 ER PT J AU Zurier, RB Rossetti, RG Jacobson, EW DeMarco, DM Liu, NY Temming, JE White, BM Laposata, M AF Zurier, RB Rossetti, RG Jacobson, EW DeMarco, DM Liu, NY Temming, JE White, BM Laposata, M TI Gamma-linolenic acid treatment of rheumatoid arthritis - A randomized, placebo-controlled trial SO ARTHRITIS AND RHEUMATISM LA English DT Article ID UNSATURATED FATTY-ACIDS; EVENING PRIMROSE OIL; SMOOTH-MUSCLE CELLS; DIETARY FISH OIL; INDEPENDENT MECHANISM; BOTANICAL LIPIDS; CLINICAL-TRIALS; ATOPIC ECZEMA; VITAMIN-E; SUPPLEMENTATION AB Objective. To assess the clinical efficacy and adverse effects of gamma-linolenic acid (GLA), a plant seed oil-derived unsaturated fatty acid that suppresses inflammation and joint tissue injury in animal models, in the treatment of active rheumatoid arthritis (RA). Methods. Fifty-six patients with active RA were randomized to treatment groups in a 6-month, double-blind trial of GLA versus placebo. This was followed by a 6-month, single-blind trial during which all patients received GLA. Patients were treated with 2.8 gm/day of GLA as the free fatty acid or with sunflower seed oil (placebo) administered in identical capsules. Results. Treatment with GLA for 6 months resulted in statistically significant and clinically relevant reductions in the signs and symptoms of disease activity in patients with RA, Overall meaningful responses (at least 25% improvement in 4 measures) were also better in the GLA treatment group (14 of 22 patients versus 4 of 19 in the placebo group; P = 0.015). During the second 6 months, both groups exhibited improvement in disease activity. Thus, patients taking GLA during the entire study showed progressive improvement during the second 6 months, In this group, 16 of 21 patients showed meaningful improvement at 12 months compared with study entry. Conclusion. GLA at doses used in this study is a well-tolerated and effective treatment for active RA. GLA is available as a component of several plant seed oils and is usually taken in far lower doses than were used in this trial, It is not approved in the United States for the treatment of any condition, and should not be viewed as therapy for any disease. Further controlled studies of its use in RA are warranted. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Zurier, RB (reprint author), UNIV MASSACHUSETTS,MED CTR,55 LAKE AVE N,WORCESTER,MA 01655, USA. FU NIAMS NIH HHS [R0-1-AR-38501] NR 37 TC 105 Z9 107 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 1996 VL 39 IS 11 BP 1808 EP 1817 DI 10.1002/art.1780391106 PG 10 WC Rheumatology SC Rheumatology GA VR600 UT WOS:A1996VR60000005 PM 8912502 ER PT J AU Ogawa, N Dang, H Kong, LP Anaya, JM Liu, GT Talal, N AF Ogawa, N Dang, H Kong, LP Anaya, JM Liu, GT Talal, N TI Lymphocyte apoptosis and apoptosis-associated gene expression in Sjogren's syndrome SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; PROTO-ONCOGENE EXPRESSION; PERIPHERAL-BLOOD LYMPHOCYTES; PROGRAMMED CELL-DEATH; LYMPHOPROLIFERATIVE SYNDROME; MONONUCLEAR-CELLS; VIRAL-INFECTIONS; FAS ANTIGEN; T-CELLS; C-MYC AB Objective. To study the mechanism and regulation of apoptosis in peripheral blood T and B lymphocytes from patients with Sjogren's syndrome (SS). Methods. The mode of in vitro lymphocyte death in the peripheral blood of patients with SS was determined by fluorescence microscopic analysis, terminal deoxynucleotidyl transferase assay, and DNA fragmentation analysis. Apoptotic cell death of T add B cells was determined at 48 hours of culture by fluorescence-activated cell sorter analysis of propidium iodide-stained cells, Messenger RNA (mRNA) expression of bcl-2, bcl-x, bax, and c-myc in T and B cells was determined by enzyme-linked immunosorbent assay-polymerase chain reaction (ELISA-PCR). Expression of bcl-xL and bcl-xS was determined by Southern blot analysis of PCR products. Gene expression was calculated as the ratio of each gene message to the message of the GAPDH gene. Bcl-2 protein levels in SS T cells were determined by ELISA. Results. SS T cells showed increased in vitro apoptosis compared with normal T cells (mean +/- SD 12.3 +/- 4.5% versus 7.3 +/- 2.0%; P < 0.01). Freshly isolated SS T cells showed increased expression of bcl-2 mRNA compared with normal controls (mean +/- SD 1.50 +/- 0.65 versus 0.88 +/- 0.23; P < 0.05). There was no significant difference in levels of bax or c-myc mRNA in T cells and B cells between SS patients and normal controls, When SST lymphocytes were cultured in vitro for 72 hours, Bcl-2 protein levels decreased with time. Conclusion. SS T cells showed accelerated apoptosis in vitro. Freshly isolated SS T cells had increased expression of bcl-2. An increase in death-promoter signals and decrease in death suppressor signals in vitro may have been responsible, in part, for the apoptosis in SS T lymphocytes. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. OI Universidad del Rosario, Biblioteca/0000-0003-3491-9392; Anaya, Juan-Manuel/0000-0002-6444-1249 FU NIDCR NIH HHS [DE-10863, DE-09311] NR 42 TC 34 Z9 41 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 1996 VL 39 IS 11 BP 1875 EP 1885 DI 10.1002/art.1780391114 PG 11 WC Rheumatology SC Rheumatology GA VR600 UT WOS:A1996VR60000013 PM 8912510 ER PT J AU Johnson, ME Berk, DA Blankschtein, D Golan, DE Jain, RK Langer, RS AF Johnson, ME Berk, DA Blankschtein, D Golan, DE Jain, RK Langer, RS TI Lateral diffusion of small compounds in human stratum corneum and model lipid bilayer systems SO BIOPHYSICAL JOURNAL LA English DT Article ID SPATIAL FOURIER-ANALYSIS; X-RAY-DIFFRACTION; TRANSLATIONAL DIFFUSION; PHOSPHOLIPID MULTIBILAYERS; PHOTOBLEACHING RECOVERY; ERYTHROCYTE-MEMBRANE; ROTATIONAL DIFFUSION; NEUTRON-DIFFRACTION; FLUORESCENCE DECAY; MOLECULAR-MOTION AB An image-based technique of fluorescence recovery after photobleaching (video-FRAP) was used to measure the lateral diffusion coefficients of a series of nine fluorescent probes in two model lipid bilayer systems, dimyristoylphosphatidylcholine (DMPC) and DMPC/cholesterol (40 mol%), as well as in human stratum corneum-extracted lipids. The probes were all lipophilic, varied in molecular weight from 223 to 854 Da, and were chosen to characterize the lateral diffusion of small compounds in these bilayer systems. A clear molecular weight dependence of the lateral diffusion coefficients in DMPC bilayers was observed. Values ranged from 6.72 x 10(-8) to 16.2 x 10(-8) cm(2)/s, with the smaller probes diffusing faster than the larger ones. Measurements in DMPC/cholesterol bilayers, which represent the most thorough characterization of small-solute diffusion in this system, exhibited a similar molecular weight dependence, although the diffusion coefficients were lower, ranging from 1.62 x 10(-8) to 5.60 x 10(-8) cm(2)/s. Lateral diffusion measurements in stratum corneum-extracted lipids, which represent a novel examination of diffusion in this unique lipid system, also exhibited a molecular weight dependence, with values ranging from 0.306 x 10(-8) to 2.34 x 10(-8) cm(2)/s. Literature data showed that these strong molecular weight dependencies extend to even smaller compounds than those examined in this study. A two-parameter empirical expression is presented that describes the lateral diffusion coefficient in terms of the solute's molecular weight and captures the size dependence over the range examined. This study illustrates the degree to which small-molecule lateral diffusion in stratum corneum-extracted lipids can be represented by diffusion in DMPC and DMPC/cholesterol bilayer systems, and may lead to a better understanding of small-solute transport across human stratum corneum. C1 MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RI Johnson, Mark/B-6921-2009; Berk, David/A-4863-2012 OI Berk, David/0000-0002-3855-6886 FU NCI NIH HHS [R35 CA 56591]; NHLBI NIH HHS [HL-32854]; NIGMS NIH HHS [GM44884] NR 66 TC 90 Z9 91 U1 1 U2 13 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1996 VL 71 IS 5 BP 2656 EP 2668 PG 13 WC Biophysics SC Biophysics GA VQ520 UT WOS:A1996VQ52000037 PM 8913603 ER PT J AU Zwicky, CS Maddocks, AB Andersen, N Gribben, JG AF Zwicky, CS Maddocks, AB Andersen, N Gribben, JG TI Eradication of polymerase chain reaction detectable immunoglobulin gene rearrangement in non-Hodgkin's lymphoma is associated with decreased relapse after autologous bone marrow transplantation SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; B-CELL LYMPHOMA; HUMAN FOLLICULAR LYMPHOMAS; MINIMAL RESIDUAL DISEASE; HEAVY-CHAIN; PERIPHERAL-BLOOD; SOMATIC MUTATIONS; OLIGONUCLEOTIDE PROBES; CDR-III; BCL-2 AB In B-cell non-Hodgkin's lymphoma (NHL), as in other B-cell malignancies, clonal rearrangement of the third complementarity determining region (CDR III) of the immunoglobulin heavy chain gene (IgH) provides a useful marker for the detection of minimal residual disease (MRD) after treatment. To determine the clinical utility of IgH polymerase chain reaction (PCR). we analyzed peripheral blood (PB) and bone marrow (BM) samples from 25 patients with NHL with no PCR detectable chromosomal rearrangement who have undergone autologous bone marrow transplantation (ABMT). Patients with histologic bone marrow infiltration at the time of bone marrow harvest were selected for study since this provided us with diagnostic tissue samples. As an initial strategy DNA was amplified using consensus variable (VH) and joining (JH) region primers. In those cases failing to amplify using consensus region primers, PCR was performed using a panel of VH family-specific framework region 1 (FR1) primers. The clonal products were directly sequenced. From the V-N-D region nucleotide sequences, clone specific probes were constructed and used for subsequent detection of MRD. A clonal PCR product could be PCR amplified and directly sequenced in 18 (72%, 90% confidence intervals 54%-86%) of these 25 patients, 8 with diffuse and 10 with follicular NHL. Eight of these 18 patients have relapsed after ABMT. All had detectable lymphoma cells before relapse and the sequence of the CDR III region at the time of relapse was identical to that obtained at the time of ABMT, All 10 patients who remain in complete remission from 18 to 36 months after ABMT had eradication of PCR detectable lymphoma cells after ABMT, although in three patients PCR detectable MRD was detected early after ABMT. We conclude that sequencing and the use of patient specific IgH CDR III oligonucleotides probes provides a simple and highly reliable method to determine the specificity of the IgH PCR technique. The clinical utility of this technique is demonstrated by the finding that eradication of PCR detectable lymphoma cells in these patients is associated with decreased relapse after ABMT (P=.0002). (C) 1996 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA66996] NR 48 TC 67 Z9 70 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1996 VL 88 IS 9 BP 3314 EP 3322 PG 9 WC Hematology SC Hematology GA VP736 UT WOS:A1996VP73600005 PM 8896395 ER PT J AU Champ, JE Binkley, N Havighurst, T Colman, RJ Kemnitz, JW Roecker, EB AF Champ, JE Binkley, N Havighurst, T Colman, RJ Kemnitz, JW Roecker, EB TI The effect of advancing age on bone mineral content of female rhesus monkeys SO BONE LA English DT Article DE osteoporosis; rhesus monkey; bone mineral content; bone mineral density; aging; bone mass ID TRABECULAR BONE; DENSITY; ABSORPTIOMETRY; BABOONS; WOMEN; HISTOMORPHOMETRY; OVARIECTOMY; RATIOS; SPINE; MASS AB Dual-energy X-ray absorptiometry (DXA) can be used to assess bone mass in nonhuman primates; however, the changes in bone mineral across the lifespan have not been well described, The purpose of this cross-sectional study was to evaluate the effect of maturation and subsequent aging on bone mineral content (BMC) and bone size (two dimensional bone area) in female rhesus monkeys at sites analogous to those commonly evaluated in humans, Total body (n = 178) and lumbar spine (n = 167) DXA scans were performed on female rhesus monkeys aged 2.8 to 34.6 years, Radius scans (n = 86) were performed on monkeys aged 9.7 to 34.6 years, Measurement precision was comparable to that reported for humans, At all sites, BMC was highly correlated with bone area (p = 0.0001), which was positively correlated with both body weight (p less than or equal to 0.002) and age (p less than or equal to 0.08), Total body and lumbar spine BMC and bone area increased with maturation (p < 0.0001) until age 11 and then remained stable with further advancing age, There was little change in total body and lumbar spine area-adjusted BMC across the lifespan, At the radial sites, there were no significant changes in BMC or bone area with age, but the area-adjusted BMC and the weight- and area-adjusted BMC declined in older animals (p < 0.05), In conclusion, the female rhesus monkey does not attain peak bone mass until age 11, Significant bone loss at later ages was observed only at radial sites. (C) 1996 by Elsevier Science Inc. C1 UNIV WISCONSIN,WISCONSIN REG PRIMATE RES CTR,MADISON,WI. UNIV WISCONSIN,DEPT MED,INST AGING,MADISON,WI. UNIV WISCONSIN,DEPT BIOSTAT,INST AGING,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,GRECC,MADISON,WI 53705. FU NCRR NIH HHS [P51 RR00167]; NIA NIH HHS [P01 AG11915] NR 29 TC 44 Z9 44 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 8756-3282 J9 BONE JI Bone PD NOV PY 1996 VL 19 IS 5 BP 485 EP 492 DI 10.1016/S8756-3282(96)00243-8 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VR347 UT WOS:A1996VR34700009 PM 8922647 ER PT J AU Gage, I Schnitt, SJ Nixon, AJ Silver, B Recht, A Troyan, SL Eberlein, T Love, SM Gelman, R Harris, JR Connolly, JL AF Gage, I Schnitt, SJ Nixon, AJ Silver, B Recht, A Troyan, SL Eberlein, T Love, SM Gelman, R Harris, JR Connolly, JL TI Pathologic margin involvement and the risk of recurrence in patients treated with breast-conserving therapy SO CANCER LA English DT Article DE breast carcinoma; breast-conserving therapy; local recurrence; margins; extensive intraductal component ID EXTENSIVE INTRADUCTAL COMPONENT; RADIATION-THERAPY; CONSERVATIVE SURGERY; STAGE-I; LOCAL RECURRENCE; CANCER; CARCINOMA; EXCISION; RADIOTHERAPY; IRRADIATION AB BACKGROUND. The relationship between the microscopic margins of resection and ipsilateral breast recurrence (IBR) after breast-conserving therapy for carcinomas with or without an extensive intraductal component (EIC) has not been adequately defined. METHODS. Of 1,790 women with unilateral clinical Stage I or II breast carcinoma treated with radiation therapy as part of breast-conserving therapy, 343 had invasive ductal histology evaluable for an extensive intraductal component (EIC), had inked margins that were evaluable on review of their pathology slides, and received greater than or equal to 60 Gray to the tumor bed; these 343 women constitute the study population. The median follow-up was 109 months. All available slides were reviewed by one of the study pathologists. Final inked margins of excision were classified as negative > 1 mm (no invasive or in situ ductal carcinoma within 1 mm of the inked margin); negative less than or equal to 1 mm, or close (carcinoma less than or equal to 1 mm from the inked margin but not at the margin); or positive (carcinoma at the inked margin). A focally positive margin was defined as invasive or in situ ductal carcinoma at the margin in three or fewer low-power fields. The first site of recurrent disease was classified as either ipsilateral breast recurrence (IBR) or distant metastasis/regional lymph node failure. RESULTS. Crude rates for the first site of recurrence were calculated first for all 340 patients evaluable at 5 years, then separately for the 272 patients with EIC-negative cancers and the 68 patients with EIC-positive cancers. The 5-year rate of IBR for all patients with negative margins was 2%; and for all patients with positive margins, the rate was 16%. Among patients with negative margins, the 5-year rate of IBR was 2% for all patients with close margins (negative less than or equal to 1 mm) and 3% for those with negative > 1 mm margins. For patients with dose margins, the rates were 2% and 0% for EIC-negative and EIC-positive tumors, respectively; the corresponding rates for patients with negative margins > 1 mm were 1% and 14%. The 5-year rate of IBR for patients with focally positive margins was 9% (9% for EIC-negative and 7% for EIC-positive patients). The 5-year crude rate of IBR for patients with greater than focally positive margins was 28% (19% for EIC-negative and 42% for EIC-positive patients). CONCLUSIONS. Patients with negative margins of excision have a low rate of recurrence in the treated breast, whether the margin is > 1 mm or less than or equal to 1 mm and whether the carcinoma is EIC-negative or EIC-positive. Among patients with positive margins, those with focally positive margins have a considerably lower risk of local recurrence than those with more than focally positive margins, and could be considered for breast-conserving therapy. (C) 1996 American Cancer Society. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02215. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT SURG,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT SURG,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. UNIV CALIF LOS ANGELES,SCH MED,DEPT SURG,REVLON BREAST CTR,LOS ANGELES,CA 90024. JOHNS HOPKINS UNIV,JOHNS HOPKINS ONCOL CTR,DIV RADIAT ONCOL,BALTIMORE,MD 21205. NR 26 TC 225 Z9 229 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 1996 VL 78 IS 9 BP 1921 EP 1928 DI 10.1002/(SICI)1097-0142(19961101)78:9<1921::AID-CNCR12>3.0.CO;2-# PG 8 WC Oncology SC Oncology GA VN852 UT WOS:A1996VN85200012 PM 8909312 ER PT J AU Huang, M Sharma, S Mao, JT Zhu, L Miller, P Stolina, M Dubinett, SM AF Huang, M Sharma, S Mao, JT Zhu, L Miller, P Stolina, M Dubinett, SM TI Specific abrogation of tumor cyclooxygenase 2 (COX-2) expression restores Th1/TH2 cytokine balance in non small cell lung cancer (NSCLC) SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,IMMUNOL PULM LAB,DIV PULM & CRIT CARE MED,DEPT MED,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1996 VL 3 IS 6 SU S BP O9 EP O9 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA WC571 UT WOS:A1996WC57100009 ER PT J AU Flores, JF Walker, GJ Glendening, JM Haluska, FG Castresana, JS Rubio, MP Pastorfide, GC Boyer, LA Kao, WH Bulyk, ML Barnhill, RL Hayward, NK Housman, DE Fountain, JW AF Flores, JF Walker, GJ Glendening, JM Haluska, FG Castresana, JS Rubio, MP Pastorfide, GC Boyer, LA Kao, WH Bulyk, ML Barnhill, RL Hayward, NK Housman, DE Fountain, JW TI Loss of the p16(INK4a) and p15(INK4b) genes, as well as neighboring 9p21 markers, in sporadic melanoma SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; KINASE-4 INHIBITOR GENE; SQUAMOUS-CELL CARCINOMA; HOMOZYGOUS DELETIONS; FAMILIAL MELANOMA; CHROMOSOME 9P; MUTATIONAL ANALYSIS; MALIGNANT-MELANOMA; CYCLE INHIBITION; P16 AB Although homozygous deletions of the cyclin-dependent kinase inhibitor 2 gene p16(INK4a) on 9p21 have been reported frequently in metastatic melanoma cell lines, and intragenic mutations within the p16(INK4a) gene have been detected in familial melanoma kindreds, specific targeting of this gene in the development of sporadic melanoma in vivo remains controversial. Southern analyses were performed in this study to initially assess the frequency of hemi- or homozygous losses of p16(INK4a), as well as its neighboring family member, p15(INK4b) and other candidate regions within 9p21, in sporadic melanoma. Overall, 22 of 40 (55%) uncultured sporadic melanoma DNAs were determined to harbor deletions of 1-11 markers/genes located on 9p21. This included 10 tumors (25%; 10 of 40) with homozygous deletions limited to either the p16(INK4a) gene only (20%; 2 of 10), both the p16(INK4a) and p15(INK4b) genes (10%; 1 of 10), another novel 9p21 gene, FB19 (10%; 1 of 10), or all three of these genes plus surrounding markers (60%; 6 of 10). In subsequent single-strand conformation polymorphism and sequencing analyses, intragenic mutations in the p16(INK4a) gene were also revealed in two (10%; 2 of 21) melanoma DNAs that retained one copy of this locus. By comparison, the frequency of p16(INK4a) and p15(INK4b) homozygous deletions, as well as p16(INK4a) mutations, in melanoma cell lines (analyzed in parallel) was 2-3-fold higher at 61 (23 of 38) and 24% (9 of 38), respectively. These findings indicate that (a) p16(INK4a) is inactivated in vivo in over one-fourth (27.5%; 11 of 40) of sporadic melanomas; (b) mutation/deletion of p16(INK4a) may confer a selective growth advantage in vitro; and (c) other 9p21 tumor suppressor genes could be targeted during the development of melanoma. C1 UNIV SO CALIF,DEPT BIOCHEM & MOL BIOL,INST MED GENET,LOS ANGELES,CA 90033. QUEENSLAND INST MED RES,BRISBANE,QLD 4029,AUSTRALIA. MASSACHUSETTS GEN HOSP,DEPT ONCOL,BOSTON,MA 02114. CSIC,INST INVEST BIOMED,E-28029 MADRID,SPAIN. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. MIT,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA 02139. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RI Rubio, Mari-Paz/K-4364-2014; hayward, nicholas/C-1367-2015; OI Rubio, Mari-Paz/0000-0003-3963-5903; hayward, nicholas/0000-0003-4760-1033; Castresana, Javier S./0000-0002-2373-482X FU NCI NIH HHS [1-F32-CA08985, CA 17575]; NHGRI NIH HHS [HG00297] NR 58 TC 136 Z9 138 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1996 VL 56 IS 21 BP 5023 EP 5032 PG 10 WC Oncology SC Oncology GA VP486 UT WOS:A1996VP48600033 PM 8895759 ER PT J AU Spiegelman, BM Flier, JS AF Spiegelman, BM Flier, JS TI Adipogenesis and obesity: Rounding out the big picture SO CELL LA English DT Review ID PROLIFERATOR-ACTIVATED RECEPTORS; BINDING PROTEIN-ALPHA; NECROSIS-FACTOR-ALPHA; BROWN ADIPOSE-TISSUE; NEUROPEPTIDE-Y; FATTY-ACIDS; ADIPOCYTE DIFFERENTIATION; TRANSCRIPTION FACTOR; INSULIN-RESISTANCE; GENE-EXPRESSION C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV ENDOCRINOL,BETH ISRAEL DEACONESS MED CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RP Spiegelman, BM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [R37DK28082, R37DK315405] NR 112 TC 975 Z9 999 U1 15 U2 80 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 1 PY 1996 VL 87 IS 3 BP 377 EP 389 DI 10.1016/S0092-8674(00)81359-8 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VQ466 UT WOS:A1996VQ46600005 PM 8898192 ER PT J AU Suzuki, K BonnerWeir, S Hollister, J Weir, GC AF Suzuki, K BonnerWeir, S Hollister, J Weir, GC TI A method for estimating number and mass of islets transplanted within a membrane device SO CELL TRANSPLANTATION LA English DT Article DE planimetry; quantitative analysis; islet transplantation; membrane device ID IMMUNOSUPPRESSION; XENOGRAFTS; PANCREAS; RATS AB Immunobarrier devices may prevent the immune destruction of pancreatic islets transplanted into diabetic recipients, but there are concerns about the survival of islets within such devices. In this manuscript we described a method for estimating islet mass and number within a membrane device. Five hundred syngeneic mouse islets were placed in a membrane device, which was then transplanted into the epididymal space of streptozotocin diabetic mouse. After 14 days the device was removed from the recipient, fixed, and embedded in paraffin. Sections were made and then stained with hematoxylin. From a total of 58 sections, 12 sample sections were selected for analysis by computerized planimetry to determine area of the device chamber and the islet area for each of these sections. By making certain assumptions, it was possible to estimate the total volume of the device chamber, the number of islets contained within the chamber, and the mass of islet tissue. Two weeks after implantation of the chamber, into which approximately 500 microencapsulated islets were loaded, the blood glucose level of the recipient fell to 73 mg/dL. The volume of the device chamber, the total volume of islets in the device, and the total islet number within the device were 1.78 mu L, 0.57 mu L, and 277 islets, respectively. The detailed methodology, assumptions, and calculations for this approach are described in this manuscript. This new method makes it possible to determine islet mass within a membrane device by analyzing a relatively small number of selected sections. This approach should make it possible to carry out comprehensive studies on the fate of transplanted islets contained in such immunobarrier membrane devices. Copyright (C) 1996 Elsevier Science Inc. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. FU NIDDK NIH HHS [DK-35449, DK-36836] NR 13 TC 12 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD NOV-DEC PY 1996 VL 5 IS 6 BP 613 EP 625 DI 10.1016/S0963-6897(96)00083-8 PG 13 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA VV308 UT WOS:A1996VV30800002 PM 8951219 ER PT J AU PohlmannEden, B Hoch, DB Cochius, JI Hennerici, MG AF PohlmannEden, B Hoch, DB Cochius, JI Hennerici, MG TI Stroke and epilepsy: Critical review of the literature .1. Epidemiology and risk factors SO CEREBROVASCULAR DISEASES LA English DT Review DE stroke; seizures; epilepsy; seizure phenomenology; hemorrhagic conditions ID LATE-ONSET EPILEPSY; INTRACEREBRAL HEMORRHAGE; SUBARACHNOID HEMORRHAGE; CEREBRAL INFARCTION; EARLY SEIZURES; FREQUENCY; DISORDERS; ROCHESTER; MINNESOTA; ETIOLOGY AB Stroke-associated seizures and epilepsy provide an excellent clinical model to study both acute hyperexcitability after stroke and long-term tissue changes responsible for epileptogenic scar formation. The authors critically review the literature regarding stroke and seizures, to define the clinical spectrum of the association between stroke and seizures. Unfortunately, most of the studies performed in the past were either retrospective and heterogeneous or not designed to address this important issue. Constant improvements and advances in technology, including computerized tomography, magnetic resonance imaging, cerebral angiography and ultrasound, have made possible increasing sophistication in our investigation of patients with stroke and stroke-related seizures and emphasize the need for reassessment of this relationship, Part I gives an overview of the incidence of stroke-associated seizures, their phenomenology and dynamics, and attempts to identify specific risk factors for this association such as stroke subtypes starting with hemorrhagic conditions. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,EPILEPSY SERV4,BOSTON,MA 02114. RP PohlmannEden, B (reprint author), UNIV HEIDELBERG,MANNHEIM HOSP,DEPT NEUROL,D-68135 MANNHEIM,GERMANY. NR 61 TC 32 Z9 32 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PD NOV-DEC PY 1996 VL 6 IS 6 BP 332 EP 338 DI 10.1159/000108048 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VQ652 UT WOS:A1996VQ65200003 ER PT J AU Ray, CE Kaufman, JA Geller, SC Rivitz, SM Kanarek, DJ Waltman, AC AF Ray, CE Kaufman, JA Geller, SC Rivitz, SM Kanarek, DJ Waltman, AC TI Embolization of pulmonary catheter-induced pulmonary artery pseudoaneurysms SO CHEST LA English DT Article DE arteries; catheterization; Swan-Ganz; pulmonary artery; therapeutic blockade ID SWAN-GANZ CATHETER; DETACHABLE BALLOON; FALSE ANEURYSM; HEMORRHAGE; HEMOPTYSIS; DIAGNOSIS; RUPTURE AB Study objectives: To determine the outcome of patients with pulmonary catheter-induced pulmonary artery pseudoansurysms (PSAs) treated with embolization. Design: Retrospective outcomes review. Setting: Large urban tertiary-care hospital. Patients: All patients who presented to diagnostic angiography for ruptured pulmonary artery PSA caused by pulmonary artery catheters (PACs) from November 1990 to September 1995, A total of sis patients were examined. Interventions: Transcatheter embolotherapy with coils, absorbable gelatin sponges (Gelfoam), and suture material, Results: These procedures were technically successful in all patients, and none had recurrent hemoptysis, Four of the sis patients were discharged from the hospital. Conclusion: Embolotherapy is a useful alternative to surgery for some patients with PAC-induced pulmonary PSA. C1 MASSACHUSETTS GEN HOSP,DIV VASC RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV PULM MED,BOSTON,MA 02114. RP Ray, CE (reprint author), ROSWELL PK CANC INST,DIV ANGIOG & INTERVENT RADIOL,ELM & CARLETON ST,BUFFALO,NY 14263, USA. NR 20 TC 6 Z9 6 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD NOV PY 1996 VL 110 IS 5 BP 1370 EP 1373 DI 10.1378/chest.110.5.1370 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA VR835 UT WOS:A1996VR83500051 PM 8915253 ER PT J AU Newman, MF Wolman, R Kanchuger, M Marschall, K MoraMangano, C Roach, G Smith, LR Aggarwal, A Nussmeier, N Herskowitz, A Mangano, DT Clark, R Curling, PE Shenaq, S Communale, M Body, S Maddi, R Friedman, AS Fine, R Patafio, O Stanley, TE Ramsay, JG Bellows, WH DAmbra, MN Fabian, J Marschall, KE Tuman, KJ Stover, EP Siegel, LC Goldstein, M Slogoff, S Koch, C Starr, NJ Lell, W Ruo, W Trankina, M Ross, AF Wahr, J Savino, JS Spiess, B Ozanne, GM Matthew, JP AF Newman, MF Wolman, R Kanchuger, M Marschall, K MoraMangano, C Roach, G Smith, LR Aggarwal, A Nussmeier, N Herskowitz, A Mangano, DT Clark, R Curling, PE Shenaq, S Communale, M Body, S Maddi, R Friedman, AS Fine, R Patafio, O Stanley, TE Ramsay, JG Bellows, WH DAmbra, MN Fabian, J Marschall, KE Tuman, KJ Stover, EP Siegel, LC Goldstein, M Slogoff, S Koch, C Starr, NJ Lell, W Ruo, W Trankina, M Ross, AF Wahr, J Savino, JS Spiess, B Ozanne, GM Matthew, JP TI Multicenter preoperative stroke risk index for patients undergoing coronary artery bypass graft surgery SO CIRCULATION LA English DT Article DE atherosclerosis; cardiopulmonary bypass; cerebral infarction; stroke; surgery ID CROSS-VALIDATION; CARDIAC-SURGERY; PATIENTS OLDER; REGRESSION; PREDICTION; BOOTSTRAP; AGE AB Background The paradox of present cardiac surgery is that the more elderly and debilitated patients benefit most from cardiac surgery compared with medical therapy, yet they sustain greater overall risk for morbidity and mortality after cardiac surgery. The goal of the present study was to develop a preoperative index predicting major perioperative neurological events in patients undergoing coronary artery bypass graft surgery. Methods and Results As part of a prospective, multicenter, observational study (McSPI Research Group), we enrolled 2417 patients at 24 academic medical centers in the United States. Patients who died intraoperatively or had concomitant open-heart procedures were excluded from analysis, resulting in a total of 2107 for analysis. Sixty-eight patients (3.2%) developed adverse neurological events, defined as cerebrovascular accident, transient ischemic attack (TIA), or persistent coma. Bivariate analysis was applied to determine associations between preoperative variables and neurological events. Significant bivariate predictors were identified then logically grouped, and for each cluster, a score was calculated based on principal components. Key predictor variables were age, history of previous neurological disease, diabetes, history of vascular disease, previous coronary artery surgery, unstable angina, and history of pulmonary disease, the coefficients for which were used to develop a preoperative stroke risk index that was validated by bootstrap (c-index=0.778). Stroke risk could then be determined for each patient, calculating a patient's risk for stroke within 95% confidence intervals. Conclusions With the McSPI stroke risk index developed in this study, neurological risk can be estimated, and the most appropriate group for perioperative therapy can be identified. Further refinement and validation of this index, however, are necessary and are under way in current studies. C1 VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,DEPT ANESTHESIOL,RICHMOND,VA. NYU,MED CTR,DEPT ANESTHESIOL,NEW YORK,NY 10016. STANFORD UNIV,SCH MED,DEPT ANESTHESIOL,STANFORD,CA 94305. KAISER PERMANENTE MED CTR,DEPT ANESTHESIOL,SAN FRANCISCO,CA. MED COLL WISCONSIN,DEPT ANESTHESIOL,MILWAUKEE,WI 53226. MERCY MED CTR,DEPT ANESTHESIOL,REDDING,CA. ISCHEMIA RES EDUC FDN,DEPT ANESTHESIOL,SAN FRANCISCO,CA. DUKE HEART CTR,DEPT COMMUNITY & FAMILY MED,DURHAM,NC. BAYLOR COLL MED,HOUSTON,TX 77030. BETH ISRAEL HOSP,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. EMORY UNIV,SCH MED,ATLANTA,GA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. STANFORD UNIV,MED CTR,STANFORD,CA 94305. TEXAS HEART INST,HOUSTON,TX 77025. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. UNIV ALABAMA,BIRMINGHAM,AL. UNIV CHICAGO,CHICAGO,IL 60637. UNIV FLORIDA,GAINESVILLE,FL. UNIV IOWA,IOWA CITY,IA. UNIV MICHIGAN,ANN ARBOR,MI 48109. UNIV PENN,PHILADELPHIA,PA 19104. UNIV WASHINGTON,SEATTLE,WA 98195. VET ADM MED CTR,MILWAUKEE,WI 53295. VET ADM MED CTR,SAN FRANCISCO,CA 94121. YALE UNIV,SCH MED,NEW HAVEN,CT. RP Newman, MF (reprint author), DUKE UNIV,MED CTR,DUKE HEART CTR,DEPT ANESTHESIOL,BOX 3094,DURHAM,NC 27710, USA. NR 25 TC 117 Z9 118 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 1 PY 1996 VL 94 IS 9 SU S BP 74 EP 80 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VP690 UT WOS:A1996VP69000014 ER PT J AU Gerwin, N Friedrich, C PerezAtayde, A Rosen, FS GutierrezRamos, JC AF Gerwin, N Friedrich, C PerezAtayde, A Rosen, FS GutierrezRamos, JC TI Multiple antigens are altered on T and B lymphocytes from peripheral blood and spleen of patients with Wiskott-Aldrich syndrome SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE immunodeficiency; cell surface molecules; activation antigens; naive phenotype; sialyated proteins ID CELL-SURFACE; EXPRESSION; ACTIVATION; ADHESION; GLYCOSYLATION; FAMILY; SUBPOPULATIONS; GLYCOPROTEIN; BIOSYNTHESIS; PLATELETS AB The gene for Wiskott-Aldrich syndrome (CAS) has been recently identified and cloned, but our knowledge of downstream events affected in WAS is limited to a few leucocyte cell surface molecules. To identify cell surface molecules whose abnormal expression could contribute to the functional impairment observed in WAS B and T lymphocytes, we studied the expression of a large panel of antigens on peripheral blood lymphoid cells (PBLC) and on isolated lymphocyte subpopulations from the spleen of WAS patients. WAS T lymphocytes from peripheral blood express increased levels of the activation antigens 4F2, CD49d, CD49e, CD53 and the activation/memory marker CD45RO. In the spleen, however, WAS patients have more CD45RA CD4(+) and CD8(+) T lymphocytes than normal individuals, suggesting the selective accumulation of presumably naive cells in the WAS spleen. Interestingly, the naive phenotype of the lymphocytes that seem to accumulate in the WAS spleen is confirmed by the absence of increased expression of several activation antigens on their surface, and this correlated with their increased expression of CD43. These lymphocyte abnormalities were accompanied by an abnormal distribution of lymphocyte subsets within the spleen architecture, in particular by the lack of well developed germianl centres and T cell areas. We also found abnormal expression of CD43 and other sialyated proteins such as CDw75 and CD76, whose expression requires the action of specific sialyltransferases. This study shows that the combined impairment in cellular and humoral immunity observed in WAS is the result of multiple molecular abnormalities on the surface of WAS lymphocytes, that in turn might result in recirculation/migration anomalies. C1 CTR BLOOD RES INC,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. CHILDRENS HOSP,DIV IMMUNOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT PATHOL,BOSTON,MA 02115. FU NCRR NIH HHS [2 MO1 RR 02172]; NIAID NIH HHS [1 UO 1AI 31541]; PHS HHS [1 PO1 48675-02] NR 33 TC 11 Z9 12 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD NOV PY 1996 VL 106 IS 2 BP 208 EP 217 DI 10.1046/j.1365-2249.1996.d01-853.x PG 10 WC Immunology SC Immunology GA VQ338 UT WOS:A1996VQ33800005 PM 8918565 ER PT J AU Roth, CM Rajur, SB Reiken, SR Morgan, JR Yarmush, ML AF Roth, CM Rajur, SB Reiken, SR Morgan, JR Yarmush, ML TI Receptor targeted antisense for modulation of inflammatory responses. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR ENGN MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 1996 VL 42 IS 11 BP 23 EP 23 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA VQ332 UT WOS:A1996VQ33200059 ER PT J AU Carpenter, CA Jupiter, JB AF Carpenter, CA Jupiter, JB TI Blade plate reconstruction of metaphyseal nonunion of the tibia SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ILIZAROV AB Sixteen patients with nonunion of the metaphyseal region of the proximal or distal tibia after fracture or reconstructive procedures were surgically treated using a fixed angle blade plate and autogenous bone grafting, Eight of these nonunions were complicated by prior sepsis. The average time of followup assessment was 23 months. Fourteen of these 16 nonunions went on to uncomplicated union after the index procedure. Failure of the tibial fracture to unite in 2 patients required further surgical intervention with a ring external fixator. The authors recommend blade plate reconstruction for metaphyseal nonunion of the proximal and distal tibia, especially when complicated by angular deformity, small osteopenic metaphyseal fragments, and stiff adjacent joints. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ORTHOPAED HAND SERV,BOSTON,MA 02114. HARVARD UNIV,COMBINED RESIDENCY PROGRAM,BOSTON,MA 02115. NR 21 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 1996 IS 332 BP 23 EP 28 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA VR304 UT WOS:A1996VR30400005 PM 8913142 ER PT J AU Schneider, NG Olmstead, RE Steinberg, C Sloan, K Daims, RM Brown, HV AF Schneider, NG Olmstead, RE Steinberg, C Sloan, K Daims, RM Brown, HV TI Efficacy of buspirone in smoking cessation: A placebo-controlled trial SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID TOBACCO WITHDRAWAL SYMPTOMS; NICOTINE PATCH; REPLACEMENT; SMOKERS; GUM AB Buspirone, a non-sedating anxiolytic, has yielded contradictory results in smoking cessation pilot studies and trials. We tested buspirone (n = 51) versus placebo (n = 49) in a placebo-controlled, double-blind trial of smoking cessation. Survival analyses were performed with use of strict abstinence criteria for efficacy (carbon monoxide levels less than or equal to 8 ppm; no self-reported slips to smoking). No treatment differences mere observed between active and placebo groups. There were also no differences among ''anxiety'' level groups formed post hoc from high versus low, pre-quit anxiety test scores. A number of withdrawal symptoms increased significantly after subjects quit smoking for both the active drug and placebo groups, but these symptoms were not relieved by treatment. There appears to be little evidence that buspirone is effective in smoking cessation or in the relief of withdrawal associated with cessation in a general sample. Selecting for generalized anxiety or anxiety related to cessation is suggested for future testing. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. VANDERBILT UNIV,NASHVILLE,TN. RP Schneider, NG (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,T350,691-B151D NIMITZ,LOS ANGELES,CA 90073, USA. NR 26 TC 32 Z9 32 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 1996 VL 60 IS 5 BP 568 EP 575 DI 10.1016/S0009-9236(96)90153-8 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VV597 UT WOS:A1996VV59700010 PM 8941030 ER PT J AU Murphy, BL Gaa, J Papanicolaou, N Lee, MJ AF Murphy, BL Gaa, J Papanicolaou, N Lee, MJ TI Gonadal vein recruitment in renal cell carcinoma: Incidence, pathogenesis and clinical significance SO CLINICAL RADIOLOGY LA English DT Article AB Objective: Gonadal vein recruitment by collateral veins in patients with renal cell carcinoma is not routinely searched for during abdominal computed tomography, We performed a retrospective view to determine the incidence of gonadal vein recruitment for collateral venous drainage in patients with renal cell carcinoma and we discuss its potential importance, Patients and methods: Abdominal CT examinations were available for 58 of 95 patients with renal cell carcinoma identified during a 3-year-period, The presence of collateral veins and recruitment of the ipsilateral gonadal vein was recorded and correlated with the estimated blood loss at surgery, Results: Eighteen of 58 tumours were small (less than 5 cm). Multiple (greater than three) collateral renal capsular veins were noted in 26 of 58 patients and few (less than three) were noted in 11, Recruitment of the gonadal vein (range 4-18 mm, mean 8 mm) was seen in 18 of 58 patients (31%) who all had multiple collaterals, Gonadal vein recruitment was only seen in patients with tumours greater than 5 cm, Mean estimated blood loss at surgery was significantly different (P < 0.001) in 18 of 58 patients (mean, 1078 ml) with gonadal vein recruitment compared to 40 of 58 patients (mean 304 ml) without distinct visualization of the gonadal vein and compared to 22 of 40 patients with large tumours (mean 368 ml), Conclusion: Gonadal vein recruitment signifies well-developed arteriovenous shunting and high flow collateral venous drainage pathways and may be used as an index of tumour vascularity, This finding may have clinical potential in triaging patients toward pre-operative renal embolization. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 5 TC 0 Z9 1 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 NOV PY 1996 VL 51 IS 11 BP 797 EP 800 DI 10.1016/S0009-9260(96)80008-0 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VT791 UT WOS:A1996VT79100008 PM 8937323 ER PT J AU Krosnick, A AF Krosnick, A TI Editorial comment SO CLINICAL THERAPEUTICS LA English DT Editorial Material RP Krosnick, A (reprint author), JOSLIN DIABET CTR,BOSTON,MA, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD NOV-DEC PY 1996 VL 18 IS 6 BP 1005 EP 1005 DI 10.1016/S0149-2918(96)80056-7 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WC983 UT WOS:A1996WC98300001 ER PT J AU Krosnick, A AF Krosnick, A TI A review of long-term studies evaluating the efficacy of weight loss in ameliorating disorders associated with obesity - Editorial comment SO CLINICAL THERAPEUTICS LA English DT Editorial Material RP Krosnick, A (reprint author), JOSLIN DIABET CTR,BOSTON,MA 02215, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD NOV-DEC PY 1996 VL 18 IS 6 BP 1036 EP 1036 DI 10.1016/S0149-2918(96)80058-0 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WC983 UT WOS:A1996WC98300003 ER PT J AU Krosnick, A AF Krosnick, A TI Treatment regimens for patients with toxoplasmic encephalitis - Editorial comment SO CLINICAL THERAPEUTICS LA English DT Editorial Material RP Krosnick, A (reprint author), JOSLIN DIABET CTR,BOSTON,MA 02215, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD NOV-DEC PY 1996 VL 18 IS 6 BP 1057 EP 1057 DI 10.1016/S0149-2918(96)80060-9 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WC983 UT WOS:A1996WC98300005 ER PT J AU Blais, MA Conboy, CA Wilcox, N Norman, DK AF Blais, MA Conboy, CA Wilcox, N Norman, DK TI An empirical study of the DSM-IV defensive functioning scale in personality disordered patients SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID III-R; MECHANISMS; PREDICTORS; STYLES; AXIS AB The inclusion of the Defensive Functioning Scale (DFS) in the DSM-IV provides clinicians with the opportunity to incorporate psychodynamic information into their descriptive diagnoses. The DFS contains 27 specific defenses covering six levels of defensive functioning ranging from psychotic to normal. This study undertook an initial empirical evaluation of the DFS. A sample of 100 clinicians completed a questionnaire containing both the personality disorder (PD) symptoms and the DFS defenses of PD patients known to them. DFS ratings were not related to clinician orientation. Patient gender was related to only one defense level, with women being assigned significantly more action level defenses than men. Multiple regression analyses revealed unique and meaningful patterns of association between the defense levels and PD symptoms. Additionally, the DFS ratings provided unique information regarding level of impairment and treatment success. These results provide initial empirical support for the clinical application and relevance of the proposed DFS system. Copyright (C) 1996 by W.B. Saunders Company C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Blais, MA (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,INPATIENT PSYCHIAT SERV,FRUIT ST,BOSTON,MA 02114, USA. NR 18 TC 17 Z9 17 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD NOV-DEC PY 1996 VL 37 IS 6 BP 435 EP 440 DI 10.1016/S0010-440X(96)90027-9 PG 6 WC Psychiatry SC Psychiatry GA VT120 UT WOS:A1996VT12000008 PM 8932968 ER PT J AU Dutt, JE Ledoux, D Baer, H Foster, CS AF Dutt, JE Ledoux, D Baer, H Foster, CS TI Collagen abnormalities in conjunctiva of patients with cicatricial pemphigoid SO CORNEA LA English DT Article DE collagen; ocular cicatricial pemphigoid; immunohistochemistry; basement membrane zone AB The purpose of this study was to analyze the distribution and types of collagen in the substantia propria of the conjunctiva of patients with ocular cicatricial pemphigoid (OCP). Biopsy specimens were collected from 10 patients with active OCP, five patients with active Behcet's disease, nine patients with atopic keratoconjunctivitis, five patients with chronic rosacea blepharoconjunctivitis, and six normal patients undergoing cataract surgery. Cryostat tissue sections were cut and stained using an indirect immunofluorescence technique, employing a panel of primary antibodies directed against seven collagen types. Differences between OCP, Behcet's, and normal conjunctiva were seen in the staining for collagen types III, IV, and VII. The intensity of staining for type III collagen was increased in the substantia propria of OCP conjunctiva as compared to the other groups. The basement membrane zone (BMZ) of OCP patients was typically disrupted and fragmented in appearance when stained for type IV collagen, a finding not seen in the non-OCP specimens. The BMZ staining pattern for type VII collagen in OCP conjunctiva was even more disrupted than that seen for type IV collagen, particularly on the posterior side, which was thickened and reduplicated with short fibers extending into the superficial stroma. The production of type III collagen by fibroblasts of the substantia propria is a common feature of diseases associated with subepithelial fibrosis. The damage to the epithelial BMZ and the subsequent attempt at repair with aberrant type IV and VII collagen production are unique to conjunctiva affected by OCP. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,HILLES IMMUNOL LAB,BOSTON,MA 02114. NR 4 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD NOV PY 1996 VL 15 IS 6 BP 606 EP 611 PG 6 WC Ophthalmology SC Ophthalmology GA VM729 UT WOS:A1996VM72900011 PM 8899273 ER PT J AU Fuchs, CS AF Fuchs, CS TI Gastric malignancy SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article ID HELICOBACTER-PYLORI INFECTION; NON-HODGKINS-LYMPHOMA; 5-YEAR FOLLOW-UP; ONCOLOGY-GROUP; GASTROINTESTINAL-TRACT; INCREASING INCIDENCE; STOMACH-CANCER; PEPTIC-ULCER; TISSUE TYPE; PHASE-II AB Despite the marked decline in the incidence of distal gastric carcinoma in Western countries, the incidence of adenocarcinoma of the proximal stomach and gastroesophageal junction is steadily increasing, Although little is known about the etiologic factors responsible for proximal tumors, recent studies have better characterized the relationship between Helicobacter pylori infection, atrophic gastritis, and distal gastric carcinoma, Abnormalities of several growth factors and receptor systems have been identified in gastric carcinoma, and these mutations underscore the differences between proximal and distal gastric carcinomas. The treatment of gastric carcinoma remains limited because the majority of patients in Western countries present with stage III or IV disease. Furthermore, available data do not support the routine use of chemotherapy following a curative resection of gastric carcinoma. The relationship between H. pylori infection and primary In gastric lymphoma appears well established, especially for mucosal-associated lymphoid tissue lymphomas. Treatment of low-grade mucosal-associated lymphoid tissue lymphomas of the stomach by eradication of H. pylori appears promising, The optimal therapy for high-grade primary gastric lymphomas remains controversial. RP Fuchs, CS (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 83 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 1996 VL 12 IS 6 BP 530 EP 536 DI 10.1097/00001574-199611000-00007 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VX237 UT WOS:A1996VX23700007 ER PT J AU Walker, WA AF Walker, WA TI Immunology - Editorial overview SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material RP Walker, WA (reprint author), MASSACHUSETTS GEN HOSP,MUCOSAL IMMUNOL LAB,149 13TH ST,ROOM 3401,CHARLESTOWN,MA 02129, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 1996 VL 12 IS 6 BP 551 EP 553 DI 10.1097/00001574-199611000-00010 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VX237 UT WOS:A1996VX23700010 ER PT J AU Weinstock, R Leong, GB AF Weinstock, R Leong, GB TI Ethical issues in psychiatry SO CURRENT OPINION IN PSYCHIATRY LA English DT Article ID MANAGED CARE AB Psychiatrists continue to confront ethical dilemmas in both clinical and forensic contexts, as exemplified by issues such as dangerousness, informed consent, confidentiality, and civil litigation. The ascent in the USA of managed healthcare with its profit motive and business interests, with little regard for medical ethics, is rapidly changing the healthcare delivery system as well as the salient ethical concerns. Additionally, US court decisions by the Federal Court of Appeals in two circuits concerning end-of-life decisions have also propelled this issue into the forensic and ethical forefront of psychiatric practice. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. VET AFFAIRS OUTPATIENT CLIN,PSYCHIAT SERV,COLUMBUS,OH. RP Weinstock, R (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV W116AC,WILSHIRE & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. NR 26 TC 0 Z9 1 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD NOV PY 1996 VL 9 IS 6 BP 407 EP 411 DI 10.1097/00001504-199611000-00008 PG 5 WC Psychiatry SC Psychiatry GA VU538 UT WOS:A1996VU53800008 ER PT J AU Grubbe, R Adelglass, JM Casale, TB Cohen, R Jacobson, KW Klaustermeyer, WB Pleskow, W Southern, DL Webb, DR AF Grubbe, R Adelglass, JM Casale, TB Cohen, R Jacobson, KW Klaustermeyer, WB Pleskow, W Southern, DL Webb, DR TI Intranasal therapy with once-daily triamcinolone acetonide aerosol versus twice-daily beclomethasone dipropionate aqueous spray in patients with perennial allergic rhinitis SO CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL LA English DT Article ID NASAL SPRAY AB A single-masked, randomized, controlled, multicenter, parallel-group study compared the efficacy, tolerability, and specific treatment-related side effects of 4 weeks of intranasal therapy with 220-mu g once-daily triamcinolone acetonide aerosol versus 168-mu g twice-daily beclomethasone dipropionate aqueous spray in 313 patients with perennial allergic rhinitis. Both treatments produced similar improvement in rhinitis symptoms (nasal congestion, rhinorrhea, postnasal drip, sneezing, and nasal itching) and in mean total nasal symptom scores. There were no clinically or statistically significant between-group differences in physician global evaluation of symptom relief or in the number of patients who withdrew prematurely from the study because of insufficient therapeutic effect. The onset of action during the first week of therapy was comparable for the two treatments. The frequency of two specific treatment-related complaints-medication running down the throat and medication running out of the nose-was statistically significantly less with triamcinolone acetonide than with beclomethasone dipropionate. The severity of these two complaints, plus one other-bad medication taste-was statistically significantly greater with beclomethasone dipropionate. The frequency of drug-related adverse events was similar in the two treatment groups. The results of this trial indicate that triamcinolone acetonide, 220 mu g once daily, is comparable to beclomethasone dipropionate, 168 mu g twice daily, in relieving the nasal symptoms of perennial allergic rhinitis. Both treatments were well tolerated, although some specific treatment-related events were significantly more frequent and severe in the beclomethasone dipropionate aqueous spray group than In the triamcinolone acetonide aerosol group. C1 UNIV IOWA HOSP & CLIN,DEPT INTERNAL MED,IOWA CITY,IA 52242. ALLERGY & ASTHMA ASSOCIATES,EUGENE,OR. W LOS ANGELES VET AFFAIRS MED CTR,ALLERGY & IMMUNOL SECT,LOS ANGELES,CA 90073. PRINCETON ALLERGY & ASTHMA ASSOCIATES,PRINCETON,NJ. ALLERGY & ASTHMA ASSOCIATES,KIRKLAND,WA. RP Grubbe, R (reprint author), ANNISTON MED CLIN,1010 CHRISTINE AVE,ANNISTON,AL 36207, USA. RI Casale, Thomas/K-4334-2013 OI Casale, Thomas/0000-0002-3149-7377 NR 17 TC 4 Z9 4 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0011-393X J9 CURR THER RES CLIN E JI Curr. Ther. Res.-Clin. Exp. PD NOV PY 1996 VL 57 IS 11 BP 825 EP 838 DI 10.1016/S0011-393X(96)80016-6 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VV078 UT WOS:A1996VV07800001 ER PT J AU Kreidberg, JA Donovan, MJ Goldstein, SL Rennke, H Shepherd, K Jones, RC Jaenisch, R AF Kreidberg, JA Donovan, MJ Goldstein, SL Rennke, H Shepherd, K Jones, RC Jaenisch, R TI Alpha 3 beta 1 integrin has a crucial role in kidney and lung organogenesis SO DEVELOPMENT LA English DT Article DE alpha 3 beta 1 integrin; kidney; lung; basement membrane; branching morphogenesis; mouse ID FOCAL ADHESION KINASE; CHAIN CYTOPLASMIC DOMAINS; CELL-ADHESION; EPITHELIAL-CELLS; BRANCHING MORPHOGENESIS; ALPHA-3-BETA-1 INTEGRIN; MATRIX RECEPTORS; LAMININ ISOFORMS; EXPRESSION; VLA-3 AB A mutation was targeted to the murine alpha 3 integrin gene, Homozygous mutant mice survived to birth, but died during the neonatal period, The mutation caused abnormal kidney and lung development. Mutant kidneys displayed decreased branching of the medullary collecting ducts, although the number of nephrons was not altered. Proximal tubules exhibited two distinct subsets of abnormalities, with the epithelial cells either containing excess lysosomes or becoming microcystic. In addition, glomerular development was markedly affected, In mutant kidneys, the extent of branching of glomerular capillary loops was decreased, with capillary lumina being wider than normal. The glomerular basement membrane was disorganized and glomerular podocytes were unable to form mature foot processes. Branching of the bronchi in lungs of mutant mice was also decreased and the large bronchi extended to the periphery. These results indicate a role for integrin receptors in basement membrane organization and branching morphogenesis. C1 CHILDRENS HOSP,DIV NEWBORN MED,BOSTON,MA 02115. CHILDRENS HOSP,DEPT PATHOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115. WHITEHEAD INST,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA 02142. RP Kreidberg, JA (reprint author), CHILDRENS HOSP,DIV NEPHROL,300 LONGWOOD AVE,ENDERS 1262,BOSTON,MA 02115, USA. FU NCI NIH HHS [R5 CA44339]; NIDDK NIH HHS [T32DK07726] NR 58 TC 483 Z9 492 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 1996 VL 122 IS 11 BP 3537 EP 3547 PG 11 WC Developmental Biology SC Developmental Biology GA VV373 UT WOS:A1996VV37300019 PM 8951069 ER PT J AU Noramly, S Pisenti, J Abbott, U Morgan, B AF Noramly, S Pisenti, J Abbott, U Morgan, B TI Gene expression in the limbless mutant: Polarized gene expression in the absence of Shh and an AER SO DEVELOPMENTAL BIOLOGY LA English DT Article ID APICAL ECTODERMAL RIDGE; BONE MORPHOGENETIC PROTEINS; DEVELOPING CHICK LIMB; VERTEBRATE LIMB; SONIC-HEDGEHOG; SIGNALING CASCADE; FEEDBACK LOOP; GROWTH; MOUSE; BUDS AB Limb buds in the limbless chick begin to form normally but fail to form an AER and ultimately degenerate. Wnt7a and LMX-1, which are restricted to the dorsal half of a normal limb bud, are expressed throughout the ectoderm and mesenchyme of the mutant buds, respectively. Engrailed-1, normally expressed in ventral limb ectoderm, is not expressed in the limbless bud. This defect precedes the normal period of AER formation and no localized expression of genes normally found in the AER is observed in limbless buds. Consistent with the lack of molecular specialization of an AER, Shh and BMP-2 are not expressed in the ZPA of the mutant bud. Despite the lack of Shh, FGF-4, or BMP-2 expression, the herd genes are expressed at low levels in the posterior mesenchyme of the bud. Forced expression of Shh fails to rescue the positive feedback loop between the AER and the ZPA and does not lead to distal outgrowth. However, Shh does maintain the part of the bud formed during pre-AER stages. These results support the importance of the dorsal/ventral boundary in the initiation of AER formation and imply that Shh is not required for the initial activation of polarized herd gene expression during limb development. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. UNIV CALIF DAVIS,DEPT AVIAN SCI,DAVIS,CA 95616. CORNELL UNIV,GRAD SCH MED SCI,NEW YORK,NY 10021. NR 36 TC 59 Z9 59 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 1 PY 1996 VL 179 IS 2 BP 339 EP 346 DI 10.1006/dbio.1996.0265 PG 8 WC Developmental Biology SC Developmental Biology GA VT146 UT WOS:A1996VT14600004 PM 8903350 ER PT J AU Chiasson, JL Josse, RG Leiter, LA Mihic, M Nathan, DM Palmason, C Cohen, RM Wolever, TMS AF Chiasson, JL Josse, RG Leiter, LA Mihic, M Nathan, DM Palmason, C Cohen, RM Wolever, TMS TI The effect of acarbose on insulin sensitivity in subjects with impaired glucose tolerance SO DIABETES CARE LA English DT Article ID NIDDM; CARBOHYDRATE; RESISTANCE; OBESITY AB OBJECTIVE - To study the effect of acarbose, an alpha-glucosidase inhibitor, on postprandial plasma glucose and insulin and insulin sensitivity in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS - Subjects with IGT were randomly treated in a double-blind fashion with placebo (n = 10) or acarbose (n = 8) at 100 mg t.i.d. for 4 months. All subjects were submitted before randomization and at the end of the study to a standardized breakfast and a 12-h daytime plasma glucose and plasma insulin profile, and insulin sensitivity was measured as steady-state plasma glucose (SSPG) using the insulin suppression test. RESULTS-While placebo had no effect on postprandial plasma glucose and plasma insulin incremental area under the curve (AUG) (3.03 +/- 0.5 vs. 3.76 +/- 0.6 mmol . h(-1) . l(-1), P = NS; 1,488 +/- 229 vs. 1,609 +/- 253 pmol . h(-1) . l(-1), P = NS), acarbose resulted in a significant reduction for both glucose (1.44 +/- 0.3 vs. 4.45 +/- 0.9 mmol . h(-1) . l(-1), P = 0.002) and insulin (626.7 +/- 104.3 vs. 1,338.3 +/- 220.5 pmol . h(-1) . l(-1), P = 0.003). The reduction in 12-h plasma glucose and insulin AUC on acarbose (11.2 +/- 2.1 mmol . h(-1) . l(-1) and 7.5 +/- 0.7 nmol . h(-1) . l(-1)) was significantly greater than that on placebo (4.0 +/- 1.6 mmol . h(-1) . l(-1) and 0.8 +/- 0.4 nmol . h(-1) . l(-1)) (P = 0.014 and 0.041). While SSPG was not affected by placebo (13.9 +/- 0.4 vs. 13.8 +/- 0.3 mmol/l; P = NS), it was significantly improved by acarbose (10.9 +/- 1.4 vs. 13.1 +/- 1.5 mmol/l, P < 0.004) and was also significantly different from placebo at 4 months (P < 0.02). CONCLUSIONS - It is concluded that in subjects with IGT, acarbose treatment decreases postprandial plasma glucose and insulin and improves insulin sensitivity. Acarbose may therefore be potentially useful to prevent the progression of IGT to NIDDM. C1 UNIV MONTREAL,DEPT MED,MONTREAL,PQ H3C 3J7,CANADA. UNIV TORONTO,DEPT NUTR SCI,TORONTO,ON M5S 1A1,CANADA. UNIV TORONTO,ST MICHAELS HOSP,TORONTO,ON M5B 1W8,CANADA. ST JOSEPHS HLTH CTR,TORONTO,ON,CANADA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,BOSTON,MA 02115. BAYER INC,TORONTO,ON,CANADA. UNIV CINCINNATI,MED CTR,CINCINNATI,OH 45267. RP Chiasson, JL (reprint author), HOP HOTEL DIEU,RES CTR,3850 ST URBAIN ST,MONTREAL,PQ H2W 1T8,CANADA. NR 15 TC 114 Z9 116 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 1996 VL 19 IS 11 BP 1190 EP 1193 DI 10.2337/diacare.19.11.1190 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VN631 UT WOS:A1996VN63100003 PM 8908378 ER PT J AU Wood, CA Abrutyn, E AF Wood, CA Abrutyn, E TI Optimal treatment of urinary tract infections in elderly patients SO DRUGS & AGING LA English DT Review ID INDWELLING URETHRAL CATHETERS; ASYMPTOMATIC BACTERIURIA; TRIMETHOPRIM-SULFAMETHOXAZOLE; AMBULATORY WOMEN; RANDOMIZED TRIAL; SERUM CREATININE; ACUTE CYSTITIS; MORTALITY; DIAGNOSIS; PYURIA AB Elderly patients are at high risk for urinary tract infection (UTI). Infections of the urinary tract may he classified as asymptomatic bacteriuria, uncomplicated cystitis, uncomplicated pyelonephritis or complicated UTI. The micro-organisms responsible for causing UTI are largely predictable and dictate therapy when indicated, UTIs may he diagnosed by both nonculture and culture techniques. Asymptomatic bacteriuria, though quite common in the elderly, should rarely be treated. Treatment of symptomatic uncomplicated and complicated UTIs is largely dictated by the known or expected pathogen(s) and classification of the infection. Additional features affecting the treatment of UTI in the elderly include allergies, adverse reactions to therapy, drug interactions and modification for renal insufficiency. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. RP Wood, CA (reprint author), ALLEGHENY UNIV HLTH SCI,DIV INFECT DIS,CTR CITY,MAIL STOP 461,BROAD & VINE ST,PHILADELPHIA,PA 19102, USA. NR 64 TC 12 Z9 12 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PD NOV PY 1996 VL 9 IS 5 BP 352 EP 362 PG 11 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA VR374 UT WOS:A1996VR37400007 PM 8922562 ER PT J AU Huber, LA Pasquali, C Gagescu, R Zuk, A Gruenberg, J Matlin, KS AF Huber, LA Pasquali, C Gagescu, R Zuk, A Gruenberg, J Matlin, KS TI Endosomal fractions from viral K-ras-transformed MDCK cells reveal transformation specific changes on two-dimensional gel maps SO ELECTROPHORESIS LA English DT Article DE endosomes; two-dimensional polyacrylamide gel electrophoresis; K-ras; transformation; epithelium ID TRANS-GOLGI-NETWORK; EPITHELIAL-CELLS; FUSION INVITRO; ANNEXIN-II; PROTEIN; VESICLES; COMPONENT; MEMBRANE; PHENOTYPE; POLARITY AB We have investigated the effects of viral Kirsten ras oncogene expression in Madin-Darby canine kidney (MDCK) II epithelial cell on the differential protein expression of organelle proteins. MDCK cells, stably transformed via infection with a helper-independent retroviral vector construct, were grown on permeable filter supports. Whereas normal cells form highly polarized monolayers, ras-transformed cells display an unpolarized phenotype, detaching from the substratum and developing multilayers (Schoenenberger, C.-A. et al., J. Cell Biol. 1991, 112, 873-889). We postulate that this breakdown of epithelial polarity reflects disturbed intracellular protein transport and sorting, namely, proteins will no longer be sorted correctly in intracellular organelles and will therefore not reach their appropriate target membrane. Here we emphasize the role of endosomes as sorting platform in epithelial cells. We found significant differences in the molecular composition of endosomes from normal vs. oncogenic transformed epithelial cells, strengthening previous evidence indicating that oncogenic transformation results in abnormal expression of normal genes (Cells, J. E., Olsen, E., Electrophoresis 1994, Ii, 309-344) as well as the expression of new ones (Huber, L. A. et al., Electrophoresis 1994, IS, 468-473). C1 UNIV GENEVA,DEPT BIOCHEM,CH-1211 GENEVA,SWITZERLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. RP Huber, LA (reprint author), INST MOL PATHOL,RES INST MOL PATHOL,DR BOHRGASSE 7,A-1030 VIENNA,AUSTRIA. NR 34 TC 16 Z9 16 U1 1 U2 2 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD NOV PY 1996 VL 17 IS 11 BP 1734 EP 1740 DI 10.1002/elps.1150171111 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VY258 UT WOS:A1996VY25800010 PM 8982606 ER PT J AU Boll, W Ohno, H Zhou, SY Rapoport, I Cantley, LC Bonifacino, JS Kirchhausen, T AF Boll, W Ohno, H Zhou, SY Rapoport, I Cantley, LC Bonifacino, JS Kirchhausen, T TI Sequence requirements for the recognition of tyrosine-based endocytic signals by clathrin AP-2 complexes SO EMBO JOURNAL LA English DT Article DE adaptors; clathrin-associated proteins; coated vesicles; endocytosis; protein sorting ID TRANS-GOLGI NETWORK; TRANSFERRIN RECEPTOR INTERNALIZATION; FACTOR-II RECEPTOR; CYTOPLASMIC DOMAIN; COATED PITS; PROTEIN; LOCALIZATION; BINDING; TRAFFICKING; ADAPTORS AB We recently determined that fusion proteins containing tyrosine-based endocytic signals bind to the mu 2 subunit of AP-2, the complex that drives clathrin coat formation and mediates endocytosis from the plasma membrane, Here we analyze the selectivity of peptide recognition by mu 2 and by AP-2 using combinatorial selection methods and surface plasmon resonance, Both mu 2 and AP-2 are shown to interact with various sequences of the form tyrosine-polar-polar-hydrophobic (YppO) found on receptors that follow the clathrin pathway. The optimal sequence for interaction with mu 2 and with AP-2 has tyrosine as an anchor and prefers arginine at position Y+2 and leucine at position Y+3. In contrast, no preferred sequence is detected surrounding the YppO signal, indicating that recognition of the YppO endocytic signal does not require a prefolded structure. We conclude that sorting into the endocytic pathway is governed by a surprisingly simple interaction between the mu 2 chain and a tyrosine-containing tetrapeptide sequence. C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. BETH ISRAEL HOSP,DIV SIGNAL TRANSDUCT,BOSTON,MA 02115. RI Cantley, Lewis/D-1800-2014; Ohno, Hiroshi/L-7899-2014; OI Cantley, Lewis/0000-0002-1298-7653; Ohno, Hiroshi/0000-0001-8776-9661; Bonifacino, Juan S./0000-0002-5673-6370 FU NIGMS NIH HHS [R01 GM056203] NR 29 TC 226 Z9 227 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 1 PY 1996 VL 15 IS 21 BP 5789 EP 5795 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VR218 UT WOS:A1996VR21800006 PM 8918456 ER PT J AU Lerner, A Clayton, LK Mizoguchi, E Ghendler, Y vanEwijk, W Koyasu, S Bhan, AK Reinherz, EL AF Lerner, A Clayton, LK Mizoguchi, E Ghendler, Y vanEwijk, W Koyasu, S Bhan, AK Reinherz, EL TI Cross-linking of T-cell receptors on double-positive thymocytes induces a cytokine-mediated stromal activation process linked to cell death SO EMBO JOURNAL LA English DT Article DE apoptosis; cytokine; stroma; TCR; thymus ID THYMIC EPITHELIAL-CELLS; NEGATIVE SELECTION; MOLECULAR-CLONING; MONOCLONAL-ANTIBODIES; NUCLEOTIDE-SEQUENCE; ANTIGEN RECEPTOR; TRANSGENIC MICE; MOUSE THYMUS; GENE; CDNA AB To investigate molecular events associated with the intrathymic process of negative selection, we established an in vivo system using an anti-CD3 epsilon monoclonal antibody to induce synchronous apoptosis in the thymus of AND T-cell receptor (TCR) transgenic RAG-2(-/-) mice in a non-selecting haplotype, This model eliminates endogenous negative selection as well as gene activation in the mature thymocyte compartment, offering an ideal source of tester (anti-CD3 epsilon-treated) and driver (untreated) thymus RNA for representational difference analysis (RDA), Fourteen mRNA sequences that are up-regulated in the thymuses of such mice 2-6 h after anti-CD3 epsilon treatment were identified, Surprisingly, the majority of these transcripts were derived from stromal cells rather than the TCR-crosslinked CD4(+)CD8(+)TCR(low) thymocytes including the macrophage products IL-1, the chemokine Mig and the transcription factor LRG-21. IFN-gamma secretion from the CD4(+)CD8(+)TCR(low) thymocytes regulates macrophage Mig production, Three other cytokines (IL-4, GM-CSF and TNF-alpha), known to activate a variety of stromal cells, are also induced in the same thymocyte population undergoing apoptosis, Expression of a TNF-alpha-inducible gene, B94, in stromal cells after TCR ligation further supports the notion of cross-talk between thymocytes and stroma, Thus, TCR-triggered immature thymocytes elaborate cytokines which may regulate the delivery of further signals from stromal cells required for apoptosis. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. ERASMUS UNIV ROTTERDAM,DEPT PATHOL,NL-3000 DR ROTTERDAM,NETHERLANDS. RP Lerner, A (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. RI Koyasu, Shigeo/J-5583-2015 OI Koyasu, Shigeo/0000-0001-9585-3038 FU NIAID NIH HHS [AI19807]; NIDDK NIH HHS [DK43551, DK47677] NR 63 TC 50 Z9 50 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 1 PY 1996 VL 15 IS 21 BP 5876 EP 5887 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VR218 UT WOS:A1996VR21800015 PM 8918465 ER PT J AU Lee, K Lanske, B Karaplis, AC Deeds, JD Kohno, H Nissenson, RA Kronenberg, HM Segre, GV AF Lee, K Lanske, B Karaplis, AC Deeds, JD Kohno, H Nissenson, RA Kronenberg, HM Segre, GV TI Parathyroid hormone-related peptide delays terminal differentiation of chondrocytes during endochondral bone development SO ENDOCRINOLOGY LA English DT Article ID GENE-EXPRESSION; MESSENGER-RNA; CELL-DEATH; RECEPTOR; PROTEIN; RAT; CLONING; HYPERCALCEMIA; HYBRIDIZATION; LOCALIZATION AB To test the hypothesis that PTH-related peptide (PTHrP) is a paracrine regulator of endochondral bone development, we localized PTHrP and its cognate receptor during normal skeletal development at both messenger RNA (mRNA) and protein levels and compared the growth plate phenotypes of PTHrP-deficient [(PTHrP(-/-)] mice to those of normal littermates [PTHrP(+/+)]. PTHrP mRNA was expressed adjacent to uncavitated joints, in the perichondrium of long bones and to a lower level in proliferating chondrocytes. In contrast, PTHrP protein was most evident at the interface of proliferating and hypertrophic zones, where it colocalized with PTH/PTHrP receptor mRNA and protein. Most strikingly, the proliferating zone was dramatically shorter in PTHrP(-/-) cartilage, although the percentage of cells in S-phase of the cell cycle in the proliferating zone was indistinguishable between PTHrP(+/+) and PTHrP(-/-) mice. Terminal differentiation of chondrocytes, which was characterized by cell hypertrophy, apoptosis (DNA fragmentation and decreased bcl-2 mRNA expression), and matrix mineralization, was more advanced in growth cartilage of PTHrP(-/-), compared with PTHrP(+/+) animals. These data demonstrate that PTHrP acts principally as a paracrine factor, which promotes elongation of endochondral bone by restraining or delaying the pace of chondrocytic development and terminal differentiation of growth-plate chondrocytes. C1 MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02114 USA. MCGILL UNIV, SIR MORTIMER B DAVIS JEWISH HOSP, DIV ENDOCRINOL, DEPT MED, MONTREAL, PQ H3T 1E2, CANADA. VET AFFAIRS MED CTR, ENDOCRINE UNIT, SAN FRANCISCO, CA 94121 USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94121 USA. FU NIDDK NIH HHS [DK-47038, DK-47237] NR 25 TC 228 Z9 232 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1996 VL 137 IS 11 BP 5109 EP 5118 DI 10.1210/en.137.11.5109 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VN809 UT WOS:A1996VN80900073 PM 8895385 ER PT J AU Kieffer, TJ Heller, RS Unson, CG Weir, GC Habener, JF AF Kieffer, TJ Heller, RS Unson, CG Weir, GC Habener, JF TI Distribution of glucagon receptors on hormone-specific endocrine cells of rat pancreatic islets SO ENDOCRINOLOGY LA English DT Article ID GASTRIC-INHIBITORY POLYPEPTIDE; INSULIN RELEASE; SOMATOSTATIN RELEASE; GIP RECEPTORS; BETA-CELLS; B-CELL; GLUCOSE; EXPRESSION; PEPTIDE-1; BINDING AB Glucagon is insulinotropic, but it remains uncertain whether the insulinotropic action is mediated directly by glucagon receptors expressed on beta-cells or by cross-binding to the insulinotropic glucagonlike peptide-1 (GLP-1) receptor known to be expressed on beta-cells. Binding of [I-125]glucagon to GLP-1 receptors and not to glucagon receptors has been reported in tumor-derived beta-cells (15). The objectives of the current study were to use receptor-binding techniques and a glucagon receptor-specific antiserum to determine whether glucagon receptors are present on beta-cells. Specific binding (7.2 +/- 0.8%) of [I-125]GLP-1 to beta TC-3 cells was displaced equivalently with GLP-1 and exendin-(9-39) (K-d = 0.9 and 0.4 nM, respectively), whereas approximately 700-fold higher concentrations of glucagon were required for equal displacement (K-d = 400 nM). Binding of[I-125]glucagon to beta TC-3 cells (similar to 1%) was displaced equivalently with 1 mu M glucagon, GLP-1, or exendin-(9-39). These observations support earlier findings that beta TC-3 cells do not express functional glucagon receptors. However, specific binding of [I-125]glucagon was observed on INS-1 cells (2.3 +/- 0.2%); this was displaced with glucagon (K-d = 1 nM), but not 1 mu M GLP-1 or exendin-(9-39). To examine the distribution of glucagon receptors on native beta-cells, dispersed cultured rat islets were immunostained for glucagon, somatostatin, or insulin in combination with a polyclonal rabbit antiserum raised to an extracellular portion of the glucagon receptor (KD-14). The glucagon receptor antiserum colocalized staining with approximately 97% of immunoreactive insulin cells, 9% of immuoreactive glucagon cells, and 11% of immunoreactive somatostatin cells. Perfusion of the rat pancreas with concentrations of glucagon as low as 10(-12) M resulted in significant insulin release. These results suggest that whereas the tumor-derived beta-cell line beta TC-3 does not express functional glucagon receptors, INS-1 cells and isolated rat pancreatic beta-cells have specific glucagon receptors, as do a subpopulation of alpha- and delta-cells. A model is proposed for the role of glucagon in islet hormone secretion during feeding and fasting. C1 MASSACHUSETTS GEN HOSP, MOL ENDOCRINOL LAB, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, HOWARD HUGHES MED INST, BOSTON, MA 02114 USA. JOSLIN DIABET CTR, BOSTON, MA 02215 USA. ROCKEFELLER UNIV, NEW YORK, NY 10021 USA. RI Heller, R.Scott/A-7279-2008 FU NIDDK NIH HHS [DK-30834, DK-35449] NR 37 TC 54 Z9 54 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1996 VL 137 IS 11 BP 5119 EP 5125 DI 10.1210/en.137.11.5119 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VN809 UT WOS:A1996VN80900074 PM 8895386 ER PT J AU Rasmussen, PA Yang, YL Rutecki, PA AF Rasmussen, PA Yang, YL Rutecki, PA TI Propofol inhibits epileptiform activity in rat hippocampal slices SO EPILEPSY RESEARCH LA English DT Article DE GABA; propofol; epilepsy; chemoconvulsant; hippocampus; CA3 ID GENERAL ANESTHETIC PROPOFOL; GABA(A) RECEPTORS; A RECEPTORS; NEURONS; INFUSION; SEDATION; SEIZURES; BRAIN; CONVULSIONS; MANAGEMENT AB Propofol (2,6 di-isopropylphenol) is an intravenous general anesthetic used widely in neuroanesthesia, as a sedative in intensive care units, and has successfully aborted refractory status epilepticus. We investigated the effects of propofol on epileptiform activity in rat hippocampal slices. Interictal epileptiform activity was produced by bath applying one of the following: picrotoxin (PTX; 10 and 50 mu M), bicucculine methiodide (BMI; 10 and 50 mu M), 4-aminopyridine (4-AP; 50 ELM), 8.5 mM [K+](o) or 0 [Mg2+](o) artificial cerebrospinal fluid. Propofol was then added in increasing concentrations and the effect on the rate of extracellular field epileptiform discharges was measured. Ictal-like discharges > 2 Hz for > 2 s) were produced by 7.5 mM [K+](o) and pilocarpine(10 mu M) Propofol(30 mu g/ml, 168 mu M) completely abolished discharges induced by 8.5 mM [K+](o) and at 60 mu g/ml (337 mM) completely suppressed discharges induced by 4-AP and 0 [Mg2+](o). Propofol was less effective in reducing discharges produced by GABA(A)/Cl- receptor complex antagonists. Propofol at a concentration of 300 mu g/ml(1.7 mM) was needed to reduce BMI-induced (50 mu M) discharges by 77% and only reduced PTX-induced (50 mu M) discharges by 20%. Ictal-like discharges produced by pilocarpine were disrupted by low concentrations of propofol (3-10 mu g/ml, 16.9-56.2 mu M) and the duration of the ictal-like discharge period was significantly reduced. We found that propofol has significant in vitro antiepileptic effects. Additionally, propofol was less effective against GABA(A) antagonists suggesting that the GABA(A) receptor complex is the site of its action. C1 UNIV WISCONSIN, HOSP & CLIN, DEPT NEUROL, MADISON, WI 53705 USA. UNIV WISCONSIN, HOSP & CLIN, DEPT NEUROSURG, MADISON, WI 53705 USA. UNIV WISCONSIN, HOSP & CLIN, NEUROSCI TRAINING PROGRAM, MADISON, WI 53705 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, MADISON, WI 53705 USA. UNIV WISCONSIN HOSP & CLIN, DEPT NEUROSURG, MADISON, WI 53792 USA. UNIV WISCONSIN HOSP & CLIN, DEPT NEUROSURG, CLIN SCI CTR H4326, MADISON, WI 53792 USA. FU NINDS NIH HHS [NS28580] NR 37 TC 17 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD NOV PY 1996 VL 25 IS 3 BP 169 EP 175 DI 10.1016/S0920-1211(96)00075-7 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA VV202 UT WOS:A1996VV20200003 PM 8956913 ER PT J AU Lamartine, J Nichols, KE Yin, L Krainer, M Heitzmann, F Bernard, A Gaudi, S Lenoir, GM Sullivan, JL Ikeda, JE Porta, G Schlessinger, D Romeo, G Haber, DA Sylla, BS Harkin, DP AF Lamartine, J Nichols, KE Yin, L Krainer, M Heitzmann, F Bernard, A Gaudi, S Lenoir, GM Sullivan, JL Ikeda, JE Porta, G Schlessinger, D Romeo, G Haber, DA Sylla, BS Harkin, DP TI Physical map and cosmid contig encompassing a new interstitial deletion of the X-linked lymphoproliferative syndrome region SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE cosmid contig; interstitial deletions; X-linked lymphoproliferative syndrome ID SYNDROME XLP; CHROMOSOME; DISEASE; LOCUS; LINKAGE; LIBRARIES; STRATEGY; PROBES; DXS42; DXS37 AB The X-linked lymphoproliferative syndrome (XLP) is an inherited immunodeficiency to Epstein-Barr virus infection that has been mapped to chromosome Xq25. Molecular analysis of XLP patients from ten different families identified a small interstitial constitutional deletion in 1 patient (XLP-D), This deletion, initially defined by a single marker, DF83, known to map to interval Xq24-q26.1, is nested within a previously reported and much larger deletion in another XLP patient (XLP-739), A cosmid minilibrary was constructed from a single mega-YAC and used to establish a contig encompassing the whole XLP-D deletion and a portion of the XLP-739 deletion. Based on this contig, the size of the XLP-D deletion can be estimated at 130 kb. The identification of this minimal deletion, within which at least a portion of the XLP gene is likely to reside, should greatly facilitate efforts in isolating the gene. C1 INT AGCY RES CANC,F-69372 LYON 08,FRANCE. MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. UNIV MASSACHUSETTS,MED CTR,DEPT PEDIAT,WORCESTER,MA. TOKAY UNIV,SCH MED,INST MED SCI,KANAGAWA,JAPAN. OSPED SAN PAOLO,MED GENET LAB,MILAN,ITALY. WASHINGTON UNIV,SCH MED,CTR GENET MED,DEPT GENET,ST LOUIS,MO 63110. OI Gaudi, Simona/0000-0001-6079-6942 FU NCI NIH HHS [CA4509, CA4498]; Telethon [E.0294] NR 25 TC 16 Z9 16 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD NOV-DEC PY 1996 VL 4 IS 6 BP 342 EP 351 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA WG972 UT WOS:A1996WG97200009 PM 9043868 ER PT J AU Friedrich, C Cybulsky, MI GutierrezRamos, JC AF Friedrich, C Cybulsky, MI GutierrezRamos, JC TI Vascular cell adhesion molecule-1 expression by hematopoiesis-supporting stromal cells is not essential for lymphoid or myeloid differentiation in vivo or in vitro SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE vascular cell adhesion molecule-1; stromal cell clones; hematopoiesis ID MURINE BONE-MARROW; STEM-CELLS; B-CELL; FETAL LIVER; PRECURSORS; CULTURE; LYMPHOPOIESIS; PROLIFERATION; INTERLEUKIN-7; MIGRATION AB Binding of myeloid and lymphoid precursors to stromal cells in bone marrow has been suggested to be mediated through alpha 4 integrins (alpha 4) and vascular cell adhesion molecule-1 (VCAM-1) expressed on hematopoietic progenitors and stromal cells, respectively. It has not been shown, however, how essential the VCAM-1/alpha 4 interaction is for hematopoiesis in vivo and whether or not other adhesion pathways can provide similar functional binding between stromal cells and hematopoietic progenitors. We addressed this issue by analyzing myeloid and lymphoid differentiation in vivo in mice with VCAM-1-null or -hypomorphic mutations and in vitro in long-term hematopoietic cultures with stromal cell clones from wild-type mice, which express or do not express VCAM-1. Mice bearing VCAM-1 mutations had no gross hematopoietic insufficiencies in the myeloid or lymphoid compartments and the distribution of myeloid progenitors between bone marrow and periphery was normal. In Dexter type long-term bone marrow cultures from mutant mice, the formation of supportive stromal cell layers and myeloid proliferation and differentiation were not affected by the absence of VCAM-1. Long-term maintenance and proliferation of clonable pre-B cells, cobblestone formation and differentiation to IgM-secreting, mature B cells was equally possible on VCAM-1(+) and VCAM-1(-) stromal cell clones. We conclude from our data that VCAM-1 is not essential for the functional interaction between hematopoietic progenitors and stromal cells required for myeloid and B-lymphoid development in vivo or in vitro. C1 CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV VASC RES,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV FREIBURG,DEPT BIOL,FREIBURG,GERMANY. FU NHLBI NIH HHS [HL148675-02, HL36028] NR 25 TC 31 Z9 32 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 NOV PY 1996 VL 26 IS 11 BP 2773 EP 2780 DI 10.1002/eji.1830261133 PG 8 WC Immunology SC Immunology GA VT775 UT WOS:A1996VT77500032 PM 8921968 ER PT J AU Foitzik, T Hotz, HG Kinzig, M Sorgel, F Klar, E Warshaw, AL Buhr, HJ AF Foitzik, T Hotz, HG Kinzig, M Sorgel, F Klar, E Warshaw, AL Buhr, HJ TI Improvement of pancreatic capillary blood flow does not augment the pancreatic tissue concentration of imipenem in acute experimental pancreatitis SO EUROPEAN SURGICAL RESEARCH LA English DT Article DE pancreatitis, acute; capillary blood flow, experimental; necrosis; infection; isovolemic hemodilution; dextran; antibiotic therapy; imipenem ID ACUTE NECROTIZING PANCREATITIS; ISOVOLEMIC HEMODILUTION; MICROCIRCULATION; ANTIBIOTICS; INFECTION; PATHOGENESIS; PENETRATION; IMPAIRMENT; NECROSIS AB Background: Acute necrotizing pancreatitis (ANP) is characterized by decreased capillary pancreatic blood flow. Thus, antibiotics may not reach pancreatic necrosis in therapeutic concentrations and consequently fail to prevent bacterial infection of the pancreas which today is the major cause of morbidity and mortality in ANP. Objective: To evaluate whether improvement of impaired pancreatic microcirculation by isovolemic hemodilution with dextran leads to an increase in the pancreatic tissue concentration of imipenem (IMI), an antibiotic widely used in clinical ANP. Method: After induction of ANP rats were randomized for either standard fluid therapy with Ringer's lactate (RL) or isovolemic hemodilution with dextran 70,000 (IHD/DEX). Thereafter the animals received an intravenous injection of IMI, and 15 min later they were sacrificed for determination of IMI in serum and tissue. Capillary pancreatic blood flow (CPBF) at the time of antibiotic therapy was assessed by intravital microscopy in an additional set of animals. Results: There was no significant difference in the pancreatic tissue concentration of IMI in animals pretreated with either RL (11.7 +/- 0.6 mu g/g) or IHD/DEX (11.4 +/- 1.4 mu g/g), although CPBF was significantly increased in the latter group (1.3 +/- 0.05 vs. 0.8 +/- 0.04 nl/min/capillary). Conclusion: (1) IMI is concentrated by the pancreas in experimental ANP despite impaired CPBF. (2) Enhancement of pancreatic capillary blood flow by IHD/DEX does not increase the pancreatic tissue concentration of IMI. This suggests that CPBF is not a decisive factor influencing the accumulation of this antibiotic in the pancreas, which may be one reason for the high efficacy of IMI in clinical ANP. C1 INST BIOMED & PHARMACEUT RES,NURNBERG,GERMANY. FREE UNIV BERLIN,DEPT SURG,D-1000 BERLIN,GERMANY. UNIV HEIDELBERG,DEPT SURG,D-6900 HEIDELBERG,GERMANY. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. NR 30 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0014-312X J9 EUR SURG RES JI Eur. Surg. Res. PD NOV-DEC PY 1996 VL 28 IS 6 BP 395 EP 401 DI 10.1159/000129483 PG 7 WC Surgery SC Surgery GA VW078 UT WOS:A1996VW07800001 PM 8954315 ER PT J AU Rosenblatt, MR Jarvik, ME Olmstead, RE IwamotoSchaap, PN AF Rosenblatt, MR Jarvik, ME Olmstead, RE IwamotoSchaap, PN TI Memory for cigarette advertisements enhanced by smoking abstinence SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID NICOTINE AB Abstinent and nonabstinent smokers were exposed to a series of cigarette and automobile advertisements. After a distracter event, a subsequent task tested recognition. Nonabstinent smokers showed no differences in recognition for the 2 types of stimuli. Abstinent smokers, on the other hand, recognized more cigarette advertisements than automobile advertisements (p < .001). These results, coupled with previous research, indicate that although withdrawal induces general cognitive deficits, abstinent smokers selectively attend to, and remember, smoking stimuli. Such a bias may have ramifications for cessation efforts. C1 VET AFFAIRS MED CTR,PSYCHIAT SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. NR 13 TC 3 Z9 3 U1 1 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD NOV PY 1996 VL 4 IS 4 BP 447 EP 450 PG 4 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA WN347 UT WOS:A1996WN34700014 ER PT J AU Goldfeld, AE Tsai, EY AF Goldfeld, AE Tsai, EY TI TNF-alpha and genetic susceptibility to parasitic disease SO EXPERIMENTAL PARASITOLOGY LA English DT Review ID TUMOR-NECROSIS-FACTOR; CEREBRAL MALARIA; PROMOTER; POLYMORPHISM RP Goldfeld, AE (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,44 BINNEY RD,BOSTON,MA 02115, USA. NR 17 TC 16 Z9 19 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD NOV PY 1996 VL 84 IS 2 BP 300 EP 303 DI 10.1006/expr.1996.0117 PG 4 WC Parasitology SC Parasitology GA VV584 UT WOS:A1996VV58400022 PM 8932781 ER PT J AU Berthiaume, F Moghe, PV Toner, M Yarmush, ML AF Berthiaume, F Moghe, PV Toner, M Yarmush, ML TI Effect of extracellular matrix topology on cell structure, function, and physiological responsiveness: Hepatocytes cultured in a sandwich configuration SO FASEB JOURNAL LA English DT Article DE collagen; cell polarity; liver; 3-dimensional matrix; sandwich culture ID ADULT-RAT HEPATOCYTES; POTENTIAL BIOARTIFICIAL LIVER; PRIMARY MONOLAYER-CULTURES; HOLLOW FIBER BIOREACTOR; ACUTE-PHASE-RESPONSE; LONG-TERM CULTURE; COLLAGEN GEL; DIFFERENTIATED FUNCTIONS; 3-DIMENSIONAL MATRIX; DIMETHYL-SULFOXIDE AB Extracellular matrix (ECM) geometry is an important modulator of cell polarity and function, For example, 3-dimensional matrices often more effectively induce differentiated cell function than traditional 2-dimensional substrates, The effect of ECM topology can be investigated in a controlled fashion using a technique whereby cells cultured on a single surface are overlaid with a second layer of ECM, thereby creating a ''sandwich'' configuration, Confluent monolayers of epithelial or endothelial cells overlaid in this fashion often reorganize into structures that are reminiscent of their native tissue, In the case of hepatocytes, the overlay causes a dramatic reorganization of the cytoskeleton, adoption of in vivo-like morphology and polarity, and expression of a wide array of liver-specific functions. In this short review, we use the sandwiched hepatocyte culture system to illustrate the effect of ECM geometry on cellular function, Pertinent studies are summarized in the context of defining the parallels, strengths, and Limitations of this culture system as an in vitro model to study the physiology and morphogenesis of liver tissue, We also explore some of its a potential uses as a model to study liver pharmacology and toxicology, and for the development of Liver preservation techniques and liver-assist devices. C1 HARVARD UNIV,SCH MED,SHRINERS BURNS INST,DEPT SURG,BOSTON,MA 02114. RP Berthiaume, F (reprint author), MASSACHUSETTS GEN HOSP,CTR ENGN MED,SURG SERV,BIGALOW 1401,55 FRUIT ST,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK-43371] NR 62 TC 260 Z9 264 U1 2 U2 33 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 NOV PY 1996 VL 10 IS 13 BP 1471 EP 1484 PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA VU982 UT WOS:A1996VU98200004 PM 8940293 ER PT J AU Lieberman, D AF Lieberman, D TI Endoscopic colon screening: Is less more? SO GASTROENTEROLOGY LA English DT Editorial Material ID FECAL OCCULT BLOOD; COLONOSCOPIC MISS-RATE; COLORECTAL-CANCER; SIGMOIDOSCOPY; MORTALITY; POLYPS; HEMOCCULT; YIELD RP Lieberman, D (reprint author), OREGON HLTH SCI UNIV,PORTLAND VA MED CTR,PORTLAND,OR 97201, USA. NR 21 TC 14 Z9 14 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 NOV PY 1996 VL 111 IS 5 BP 1385 EP 1387 DI 10.1053/gast.1996.v111.agast961111385 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VQ005 UT WOS:A1996VQ00500028 PM 8898655 ER PT J AU Rustgi, AK AF Rustgi, AK TI MAD about colorectal cancer SO GASTROENTEROLOGY LA English DT Editorial Material ID GROWTH-FACTOR-BETA; MICROSATELLITE INSTABILITY; RECEPTOR; GENE; DROSOPHILA; INHIBITOR; CLONING RP Rustgi, AK (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,SCH MED,BOSTON,MA 02114, USA. NR 21 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 1996 VL 111 IS 5 BP 1387 EP 1389 DI 10.1053/gast.1996.v111.agast961111387 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VQ005 UT WOS:A1996VQ00500029 PM 8898656 ER PT J AU Kozarek, RA Raltz, S Brugge, WR Schapiro, RH Waxman, I Boyce, HW Baillie, J Branch, S Stevens, P Lightdale, CJ Lehman, GA Benjamin, S Fleischer, DE Axelrad, A Kortan, P Marcon, N AF Kozarek, RA Raltz, S Brugge, WR Schapiro, RH Waxman, I Boyce, HW Baillie, J Branch, S Stevens, P Lightdale, CJ Lehman, GA Benjamin, S Fleischer, DE Axelrad, A Kortan, P Marcon, N TI Prospective multicenter trial of esophageal Z-stent placement for malignant dysphagia and tracheoesophageal fistula SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID EXPANDING METAL STENTS; ESOPHAGORESPIRATORY FISTULAS; NITINOL STENT; PALLIATION; CANCER; OBSTRUCTION; EXPERIENCE; STENOSIS; CARDIA; TRACT AB Background: Conventional esophageal prosthesis placement has been associated with a 6% to 8% perforation rate and numerous postplacement complications. Expandable esophageal stents have been developed to preclude the above but there are few studies that have prospectively defined clinical results and subsequent stent-related complications. Methods: All patients who underwent esophageal Z-stent placement at nine university or referral hospitals were prospectively assessed. Data collected included patient demographics, acute and subacute placement problems, the ability to occlude airway fistulas, prestent and poststent dysphagia scores, and patient survival. Results: Fifty-four of 56 patients (96%) with refractory dysphagia or malignant esophagoairway fistulae had 73 Z-stents successfully inserted. Initial distal deployment occurred in 13% of the patients and an additional 17% required balloon dilation to achieve maximal diameter. Acute placement complications occurred in 11% of patients and included severe pain (3), bleeding from necrotic tumor (2), and hiatal hernia intussusception (1). No perforations occurred. Eight of 11 patients (73%) had complete tracheoesophageal fistula occlusion and mean dysphagia score (+/-SD) improved from 2.6 (0.7) to 1.1 (1.2) (p < 0.01). Fifteen stents (27%) had delayed migration at a mean of 1 month and 3 required surgery for retrieval. Three patients had ultimate stent erosion resulting in bleeding in 2 (exsanguination 1) or fistula (treated with a conventional stent). Conclusions: The authors conclude that esophageal Z-stents can be placed safely and successfully in the majority of patients. The tendency of distal deployment during placement and subsequent migration problems at a time distant from placement in a patient subset deserve attention and are currently being addressed. C1 HARVARD UNIV,BETH ISRAEL HOSP,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV S FLORIDA,TAMPA,FL 33620. DUKE UNIV,DURHAM,NC 27706. COLUMBIA UNIV,NEW YORK,NY 10027. INDIANA UNIV,INDIANAPOLIS,IN 46204. GEORGETOWN UNIV,WASHINGTON,DC 20057. UNIV TORONTO,WELLESLEY HOSP,TORONTO,ON M4Y 1J3,CANADA. RP Kozarek, RA (reprint author), VIRGINIA MASON MED CTR,1100 9TH AVE,POB 900 C3-GAS,SEATTLE,WA 98101, USA. NR 23 TC 108 Z9 113 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV PY 1996 VL 44 IS 5 BP 562 EP 567 DI 10.1016/S0016-5107(96)70009-3 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VT207 UT WOS:A1996VT20700009 PM 8934162 ER PT J AU Surman, OS Cosimi, AB AF Surman, OS Cosimi, AB TI Ethical dichotomies in organ transplantation - A time for bridge building SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 3rd Biennial Conference on Psychiatric, Psychosocial and Ethical Issues in Organ Transplantation CY OCT 04-06, 1994 CL RICHMOND, VA ID LIVER-TRANSPLANTATION; CANDIDATES; PATIENT AB Rapid advances of the past 15 years have resolved many of the technical and immunologic limitations to organ transplantation. With the success rates that can now be achieved, there is increased attention to the limited supply of donor organs and to cost considerations, the remaining obstacles to wide application of organ transplantation. Competition for organs and for funding demands greater focus on patient selection and resource allocation. As Charles Taylor, philosopher and political scientist, has written, ethical formulations inevitably conflict when each is taken to its logical end point. In the 1960s, a life boat ethics framework predominated for selection of transplant recipients. The opposing egalitarian framework of recent decades has allowed for enrollment of older transplant recipients and those with histories of substance abuse. In the United States, alcoholic liver disease has been the most common indication for orthotopic liver transplantation since 1987. Among those awaiting transplantation, urgency has been a priority over time waiting. But many potential transplant candidates who are young and who appear relatively stable die while waiting. Despite the shortage of cadaveric organs, physicians and ethicists have for the most part eschewed rewards or reimbursement for living related organ donation. Stich conventions are a function of the prevailing zeitgeist and are susceptible to a paradigm shift in parallel with overall changes in societal regulation of medical practice. Theorists and practitioners are immersed in the trends of the day and the approach at each moment seems preferable to that of the moment preceding. From a practical standpoint it may be possible to bridge disparate ethical constructs. For example, in the wait for solid organ transplantation, a bicameral approach could alternatively accommodate time waiting and urgency. Selection of older patients and those with a past substance abuse history could be limited to those with the best prognosis for compliance and posttransplantation quality of life. Living organ donors and families of nonliving donors could receive incentives of a noncoercive nature that would stimulate participation without sacrificing altruism. Creative approaches are needed to improve fairness and efficacy in solid organ transplantation. (C) 1996 Elsevier Science Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT SERV,BOSTON,MA 02114. RP Surman, OS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02114, USA. NR 29 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV PY 1996 VL 18 IS 6 SU S BP S13 EP S19 PG 7 WC Psychiatry SC Psychiatry GA VU378 UT WOS:A1996VU37800003 PM 8937918 ER PT J AU Knauf, U Newton, EM Kyriakis, J Kingston, RE AF Knauf, U Newton, EM Kyriakis, J Kingston, RE TI Repression of human heat shock factor 1 activity at control temperature by phosphorylation SO GENES & DEVELOPMENT LA English DT Article DE heat shock factor; transcription factor; HSF1; Raf/ERK; phosphorylation ID ACTIVATED PROTEIN-KINASE; HUMAN HSP70 PROMOTER; TRANSCRIPTION FACTOR; C-JUN; MAMMALIAN-CELLS; DROSOPHILA; STRESS; DOMAIN; YEAST; EXPRESSION AB Human heat shock transcription factor 1 (HSF1) is responsible for stress-induced transcription of heat shock protein genes. The activity of the HSF1 transcriptional activation domains is modulated by a separate regulatory domain, which confers repression at control temperature and heat inducibility. We show here that two specific proline-directed serine motifs are important for function of the regulatory domain: Mutation of these serines to alanine derepresses HSF1 activity at control temperature, and mutation to glutamic acid, mimicking a phosphorylated serine, results in normal repression at control temperature and normal heat shock inducibility. Tryptic mapping shows that these serines are the major phosphorylation sites of HSF1 at control temperature in vivo. Stimulation of the Raf/ERK pathway in vivo results in an increased level of phosphorylation of these major sites and the regulatory domain is an excellent substrate in vitro for the mitogen-activated MAPK/ERK. We conclude that phosphorylation of the regulatory domain of HSF1 decreases the activity of HSF1 at control temperature, and propose a mechanism for modification of HSF1 activity by growth control signals. C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIABET UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,CAMBRIDGE,MA 02138. FU NIGMS NIH HHS [GM43901] NR 56 TC 160 Z9 167 U1 2 U2 4 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 1 PY 1996 VL 10 IS 21 BP 2782 EP 2793 DI 10.1101/gad.10.21.2782 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA VT693 UT WOS:A1996VT69300010 PM 8946918 ER PT J AU Otsen, M denBieman, M Kuiper, MTR Pravenec, M Kren, V Kurtz, TW Jacob, HJ Lankhorst, AE vanZutphen, BFM AF Otsen, M denBieman, M Kuiper, MTR Pravenec, M Kren, V Kurtz, TW Jacob, HJ Lankhorst, AE vanZutphen, BFM TI Use of AFLP markers for gene mapping and QTL detection in the rat SO GENOMICS LA English DT Article ID RECOMBINANT INBRED STRAINS; SPONTANEOUSLY HYPERTENSIVE RATS; QUANTITATIVE TRAIT LOCI; LINKAGE ANALYSIS; MAPS AB The AFLP technique is a new DNA marker technology based on the selective amplification of restriction fragments. Multiple polymorphic markers are simultaneously produced and can be tested in one PCR No prior information on genomic DNA sequences is needed In the current study, we contribute 18 AFLP markers to the linkage map of the rat. Seven AFLP markers were assigned to specific chromosomes by analysis of a (BN x ACI)F1 x ACI backcross progeny. Another 11 AFLP markers were mapped by using a panel of the H x B/B x H recombinant inbred (RI) strains. Genotypes of these AFLP markers were also tested for correlations with some blood pressure phenotypes in the RI strains. Suggestive correlation was found between the mean arterial pressure and two closely linked AFLP markers located on chromosome 20. The current study illustrates the value of AFLP markers for the construction of linkage maps and the detection of quantitative trait loci. (C) 1996 Academic Press, Inc. C1 UNIV UTRECHT,DEPT LAB ANIM SCI,NL-3508 TD UTRECHT,NETHERLANDS. KEYGENE NV,NL-6700 AE WAGENINGEN,NETHERLANDS. ACAD SCI CZECH REPUBL,INST PHYSIOL,PRAGUE,CZECH REPUBLIC. CHARLES UNIV,FAC MED 1,DEPT BIOL,PRAGUE,CZECH REPUBLIC. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA. RI Pravenec, Michal/B-1666-2012; Kren, Vladimir/H-8461-2014; OI Kuiper, Martin/0000-0002-1171-9876 NR 23 TC 49 Z9 63 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 1 PY 1996 VL 37 IS 3 BP 289 EP 294 DI 10.1006/geno.1996.0562 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VU075 UT WOS:A1996VU07500003 PM 8938440 ER PT J AU Kim, YI Salomon, RN GraemeCook, F Choi, SW Smith, DE Dallal, GE Mason, JB AF Kim, YI Salomon, RN GraemeCook, F Choi, SW Smith, DE Dallal, GE Mason, JB TI Dietary folate protects against the development of macroscopic colonic neoplasia in a dose responsive manner in rats SO GUT LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the American-Gastroenterological-Association CY MAY 14-17, 1995 CL SAN DIEGO, CA SP Amer Gastroenterol Assoc, Astra AB, Goteborg DE colorectal cancer; chemoprevention; folate; dimethylhydrazine; DNA methylation ID COLORECTAL-CANCER; DNA METHYLATION; FOLIC-ACID; 1,2-DIMETHYLHYDRAZINE DIHYDROCHLORIDE; COORDINATE REGULATION; S-ADENOSYLMETHIONINE; ULCERATIVE-COLITIS; DEFICIENCY; CARCINOGENESIS; HOMOCYSTEINE AB Background and Aims-Diminished folate status is associated with enhanced colorectal carcinogenesis. This study investigated the potential chemopreventive role of dietary folate in the dimethylhydrazine colorectal cancer model. Subjects and Methods-Sprague-Dawley rats were fed diets containing either 0, 2 (daily dietary requirement), 8 or 40 mg folate/kg diet for 20 weeks. After five weeks of diet, rats were injected with dimethylhydrazine (44 mg/kg) weekly for 15 weeks. Fifteen weeks after the first injection of dimethylhydrazine, all rats were killed. Folate status was determined, and the entire colorectum from each rat was analysed for macroscopic and microscopic neoplasms. Results-Plasma and colonic folate concentrations correlated directly with dietary folate levels (p<0 . 005). The incidence of microscopic neoplasms was similar among the four groups. However, the incidence and the average number of macroscopic tumours per rat decreased progressively with increasing dietary folate levels up to 8 mg/kg diet (p<0 . 05). In the strongly procarcinogenic milieu used in this study, folate supplementation at 20 times the basal requirement was associated with rates of macroscopic tumour development that were intermediate, and not statistically distinct, from rates observed at either 0 or 8 mg/kg diet. Conclusions-These data indicate that in this rat model, (a) increasing dietary folate up to four times the basal requirement leads to a progressive reduction in the evolution of macroscopic neoplasms from microscopic foci; and (b) folate supplementation beyond four times the requirement does not convey further benefit. C1 TUFTS UNIV,USDA,HUMAN NUTR RES CTR AGING,DIV BIOSTAT,VITAMIN BIOAVAILABIL LAB,BOSTON,MA 02111. TUFTS UNIV,SCH MED,NEW ENGLAND MED CTR,DEPT MED,DIV GASTROENTEROL,BOSTON,MA 02111. TUFTS UNIV,SCH MED,NEW ENGLAND MED CTR,DEPT MED,DIV CLIN NUTR,BOSTON,MA 02111. TUFTS UNIV,NEW ENGLAND MED CTR,DEPT PATHOL,BOSTON,MA 02111. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. FU NCI NIH HHS [1UO1 CA63812-01] NR 70 TC 136 Z9 137 U1 0 U2 9 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD NOV PY 1996 VL 39 IS 5 BP 732 EP 740 DI 10.1136/gut.39.5.732 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WA445 UT WOS:A1996WA44500020 PM 9014775 ER PT J AU Naliboff, B Mayer, EA AF Naliboff, B Mayer, EA TI Sensational developments in the irritable bowel SO GUT LA English DT Editorial Material ID IBS PATIENTS; PERCEPTION; PAIN; OCTREOTIDE; DISTENSION; RESPONSES; HUMANS C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Naliboff, B (reprint author), UNIV CALIF LOS ANGELES,CURE DIGEST DIS RES CTR,NEUROENTER BIOL GRP,LOS ANGELES,CA 90073, USA. NR 17 TC 16 Z9 16 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD NOV PY 1996 VL 39 IS 5 BP 770 EP 771 DI 10.1136/gut.39.5.770 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WA445 UT WOS:A1996WA44500028 PM 9014782 ER PT J AU Hendrick, V Altshuler, LL Burt, VK AF Hendrick, V Altshuler, LL Burt, VK TI Course of psychiatric disorders across the menstrual cycle SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID PREMENSTRUAL TENSION SYNDROME; GENDER-RELATED DIFFERENCES; PANIC DISORDER; PSYCHOTIC SYMPTOMS; IMIPRAMINE BINDING; MONOAMINE-OXIDASE; ANXIETY DISORDER; ESTROGEN THERAPY; ALCOHOL-USE; RAT-BRAIN AB Women of reproductive age with psychiatric disorders may experience a fluctuating course of illness over the menstrual cycle. Some data suggest an exacerbation of symptoms during the premenstrual and menstrual phases. She usefulness of such reports is limited, however, by the lack of prospective assessments and the small. number of patients involved. Additionally, many reports do not specify whether the exacerbations reflect an intensification of the underlying psychiatric disorder or a new onset of symptoms that occur only during certain phases of the menstrual cycle. Because symptomatic intensification has been repented for illnesses including schizophrenia, bipolar disorder, depression, anxiety disorders, bulimia nervosa, and substance abuse, the data bring attention to the importance of assessing the relationship between a female patient's symptomatic exacerbation and the menstrual-cycle phase in which it occurs. We present a review of the literature on the course of psychiatric symptoms across the menstrual cycle and discuss the potential effects of estrogen and progesterone on these symptoms. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Hendrick, V (reprint author), UNIV CALIF LOS ANGELES,NEUROPSYCHIAT INST & HOSP,DEPT PSYCHIAT,300 MED PLAZA,ROOM 2200,LOS ANGELES,CA 90024, USA. NR 85 TC 51 Z9 52 U1 1 U2 12 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 NOV-DEC PY 1996 VL 4 IS 4 BP 200 EP 207 DI 10.3109/10673229609030544 PG 8 WC Psychiatry SC Psychiatry GA VV182 UT WOS:A1996VV18200003 PM 9384994 ER PT J AU Beresin, EV AF Beresin, EV TI The changing economics of child and adolescent psychiatry training SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID RESIDENCY RP Beresin, EV (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BULFINCH 449,BOSTON,MA 02114, USA. NR 7 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 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD NOV-DEC PY 1996 VL 4 IS 4 BP 218 EP 220 DI 10.3109/10673229609030547 PG 3 WC Psychiatry SC Psychiatry GA VV182 UT WOS:A1996VV18200006 PM 9384997 ER PT J AU Cutrer, FM Moskowitz, MA AF Cutrer, FM Moskowitz, MA TI The actions of valproate and neurosteroids in a model of trigeminal pain SO HEADACHE LA English DT Article DE valproate; allopregnanolone; migraine; c-fos; capsaicin; GABA ID RAT SPINAL-CORD; C-FOS EXPRESSION; GLUTAMIC-ACID DECARBOXYLASE; SODIUM VALPROATE; NUCLEUS CAUDALIS; CHEMICAL-STIMULATION; NEURONAL-ACTIVITY; GABA RECEPTORS; BRAIN-STEM; PROTEIN AB Gamma-aminobutyric acid (GABA) receptors are ubiquitous inhibitory receptors in the central and peripheral nervous systems. Valproic acid (2-propylpentanoic acid), which enhances GABA synthesis and blocks degradation, is useful in migraine treatment and may act through activation of GABA receptors to modulate trigeminal nociceptive neurons innervating the meninges. To investigate this possibility, we tested the effect of valproate and allopregnanolone, a metabolite of progesterone, which binds and modulates the GABA receptor in an animal model of cephalic pain. One hundred ten Hartley guinea pigs were pretreated with either valproate or allopregnanolone 30 minutes prior to activation of trigeminal afferent fibers via intracisternal injection of the irritant, capsaicin. The effects of valproic acid and allopregnanolone were examined on c-fos expression within the trigeminal nucleus caudalis (lamina I, IIo), the termination site for small unmyelinated C fibers projecting from the meninges. C-fos positive cells were counted at three representative levels (rostral, middle, and caudal) by an observer naive to the treatment group. We found that valproate (greater than or equal to 10 mg/kg, IP) reduced labeled cells by 52% (P<0.05) and allopregnanolone (greater than or equal to 100 mg/kg, IP) reduced labeled cells by 42% (P<0.01). Bicuculline (GABA(A) antagonist), but not phaclofen (GABA(B) antagonist), blocked the valproate effect, thereby documenting the importance of GABA(A) receptors. We conclude that the attenuation of c-fos-LI by valproate and allopregnanolone is mediated via GABA(A) receptors. These studies complement prior experiments showing that valproic acid and allopregnanolone block neurogenic inflammation within the meninges via GABA(A) receptor-mediated mechanisms. The findings suggest a potential strategy for discovering new antimigraine drugs with high affinity for the GABA(A) receptor and its modulatory sites. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,CHARLESTOWN,MA 02129. RP Cutrer, FM (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,149 13TH ST,CNY 6403,CHARLESTOWN,MA 02129, USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [K08 NS 01803, NS 21558] NR 39 TC 70 Z9 71 U1 1 U2 1 PU AMER ASSOC STUDY HEADACHE PI WOODBURY PA 875 KINGS HIGHWAY, STE 200, WOODBURY, NJ 08096 SN 0017-8748 J9 HEADACHE JI Headache PD NOV-DEC PY 1996 VL 36 IS 10 BP 579 EP 585 DI 10.1046/j.1526-4610.1996.3610579.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA VY757 UT WOS:A1996VY75700001 PM 8990596 ER PT J AU Jiang, L Weissman, NJ Guerrero, JL He, J Weyman, AE Levine, RA Picard, MH AF Jiang, L Weissman, NJ Guerrero, JL He, J Weyman, AE Levine, RA Picard, MH TI Percutaneous transvenous intracardiac ultrasound imaging in dogs: A new approach to monitor left ventricular function SO HEART LA English DT Article DE intracardiac echocardiography; left ventricular function; monitoring; systolic function ID AUTOMATED BORDER DETECTION; PRESSURE-AREA RELATIONS; IN-VITRO VALIDATION; INTRAVASCULAR ULTRASOUND; EJECTION FRACTION; DYNAMIC GEOMETRY; CATHETER; VOLUME; ECHOCARDIOGRAPHY; DIMENSIONS AB Objective-To evaluate the feasibility and ability of percutaneous transvenous intracardiac echocardiography (ICE) to image the left ventricle (LV) and monitor its function from the right ventricular (RV) cavity. Methods-A 10 MHz catheter was advanced into the RV from the jugular vein and positioned along the septum at the LV papillary muscle level in five dogs. The catheter was manipulated until a stable catheter position along the septum, which provided on-axis images of the LV, was obtained. Different states of LV size and systolic function (n = 80) were created with dobutamine or esmolol, both in the presence and absence of coronary stenoses. LV stroke area (cm(2)) obtained by ICE was measured at the mid-ventricular level and compared with stroke volume (cm(3)) obtained simultaneously with a transaortic flow probe. LV end diastolic, end systolic, and stroke areas obtained by ICE were also compared with those obtained by short-axis epicardial echocardiography. Results-In 96% of the stages, short axis images of the LV could be obtained and measured by ICE. LV end diastolic, end systolic, and stroke areas measured by ICE were not significantly different from epicardial echocardiographic values. Stroke area correlated with stroke volume in each dog (mean correlation coefficient 0.79 (SEE 0.19) cm(3)) (P < 0.001). Conclusions-Percutaneous intracardiac ultrasound imaging allows monitoring of LV function from the RV with an accuracy comparable to a short-suds epicardial echocardiogram. The present device can be used in closed chest experimental studies. With the development of lower frequency devices, this technique may be valuable for continuous monitoring of LV function in patients in the intensive care unit or operating room. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC ULTRASOUND LAB,BOSTON,MA 02114. OI Picard, Michael/0000-0002-9264-3243 NR 24 TC 15 Z9 15 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 1355-6037 J9 HEART JI Heart PD NOV PY 1996 VL 76 IS 5 BP 442 EP 448 DI 10.1136/hrt.76.5.442 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VT246 UT WOS:A1996VT24600017 PM 8944593 ER PT J AU Scaglioni, P Melegari, M Takahashi, M Chowdhury, JR Wands, J AF Scaglioni, P Melegari, M Takahashi, M Chowdhury, JR Wands, J TI Use of dominant negative mutants of the hepadnaviral core protein as antiviral agents SO HEPATOLOGY LA English DT Article ID HEPATITIS-B VIRUS; HUMAN ADENOVIRUS TYPE-5; GENE-TRANSFER; CELL-LINE; RETROVIRAL VECTORS; ANTISENSE OLIGODEOXYNUCLEOTIDES; E1-DELETED ADENOVIRUSES; EXPRESSION; REPLICATION; THERAPY AB Chronic hepatitis B virus (HBV) infection is a major cause of acute and chronic liver diseases. We have recently described HBV and woodchuck hepatitis virus (WHV) dominant negative (DN) core mutants that were capable of inhibiting wild-type viral replication by 95%. These mutants may represent a potent class of antiviral agents that act as ''intracellular immunogens.'' To facilitate their potential use in animal model systems, we now have studied the duck HBV (DHBV) and placed the DN mutant constructs in recombinant retroviral and adenoviral expression vectors. Transient expression of the DHBV molecular equivalent of the WHV and HBV DN constructs inhibited wild-type DHBV replication by 98%. Recombinant retroviral and adenoviral vectors containing the HBV and DHBV DN complementary DNAs (cDNAs) were used to transiently and stably transduce hepatoma derived cell Lines constitutively expressing replicating wild-type virus. These investigations show that the DN core mutants were powerful inhibitors of HBV and DHBV replication when delivered intracellularly and appear as promising antiviral agents for gene therapy of persistent viral infection of the liver. C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOL HEPATOL LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. ALBERT EINSTEIN COLL MED,CTR LIVER,BRONX,NY 10467. OI Scaglioni, Pier Paolo/0000-0002-6036-5138 FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169] NR 35 TC 57 Z9 64 U1 1 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 NOV PY 1996 VL 24 IS 5 BP 1010 EP 1017 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VQ934 UT WOS:A1996VQ93400006 PM 8903368 ER PT J AU Lindsay, KL Davis, GL Schiff, ER Bodenheimer, HC Balart, LA Dienstag, JL Perrillo, RP Tamburro, CH Goff, JS Everson, GT Silva, M Katkov, WN Goodman, Z Lau, JYN Maertens, G Gogate, J Sanghvi, B Albrecht, J Milstein, S Kniffen, J Roach, K Brodeur, C Regenstein, F Taylor, B DeMelia, HC Bodicky, C Miller, BL Danhour, G Bariletto, S AF Lindsay, KL Davis, GL Schiff, ER Bodenheimer, HC Balart, LA Dienstag, JL Perrillo, RP Tamburro, CH Goff, JS Everson, GT Silva, M Katkov, WN Goodman, Z Lau, JYN Maertens, G Gogate, J Sanghvi, B Albrecht, J Milstein, S Kniffen, J Roach, K Brodeur, C Regenstein, F Taylor, B DeMelia, HC Bodicky, C Miller, BL Danhour, G Bariletto, S TI Response to higher doses of interferon alfa-2b in patients with chronic hepatitis C: A randomized multicenter trial SO HEPATOLOGY LA English DT Article ID NON-B-HEPATITIS; CHRONIC NON-A; ALPHA-INTERFERON; VIRUS-RNA; THERAPY; PLACEBO; ASSAY AB To evaluate response rates to 3, 5, or 10 million units (MU) of interferon alfa-ab, given thrice weekly, and to determine whether higher doses of interferon increase the likelihood or durability of the response, a multicenter, randomized trial was performed at nine academic medical centers in the United States, Two hundred forty eight patients with chronic hepatitis C were randomized to receive 3, 5, or 10 MU of interferon alfa-ab thrice weekly for 12 weeks. Based on the alanine aminotransferase (ALT) response at treatment-week 12, the patients were rerandomized to additional therapy at the same or at increased doses for an additional 12 to 36 weeks; in the case of no response to the highest dose, the patients were discontinued from the study, Serum ALT concentrations and liver histology were measured. The overall complete response rates to 3, 5, or 10 MU were not different at treatment-week 12 (31% vs, 42% vs, 40%, not significant), The majority of week-12 responders continued to respond during additional treatment. When the treatment was discontinued, 15.4% to 19.0% of patients maintained their response, Of the nonresponders to 3 MU at week 12, who were continued on 3 MU for an additional 12 weeks, none responded, However, response to additional therapy occurred in 12% of week-12 nonresponders, whose dose was escalated from 3 or 5 MU to 10 MU. The only baseline features associated with the treatment response were the absence of fibrosis or cirrhosis on the pretreatment Liver biopsy and viral genotype, We conclude that the initial response to interferon in patients with chronic hepatitis C is not increased by treatment with higher doses of the drug, Patients who do not respond to 3 MU by treatment-week 12 will not respond with continued therapy at that dose; however, a proportion of patients who do not respond to 12 weeks of treatment with 3 or 5 MU may respond to higher doses, Although the long-term sustained response rates are marginally increased with interferon doses above 3 MU three times per week, the side effects are difficult to tolerate. The analysis of baseline factors in relation to response identified no single baseline factor associated with a low-enough response rate to warrant withholding interferon therapy from patients with chronic hepatitis C. C1 UNIV FLORIDA,SECT HEPATOBILIARY DIS,GAINESVILLE,FL. UNIV MIAMI,DIV HEPATOL,MIAMI,FL 33152. RHODE ISL HOSP,DEPT MED,PROVIDENCE,RI 02903. BROWN UNIV,PROVIDENCE,RI 02903. OCHSNER MED INST,NEW ORLEANS,LA. MASSACHUSETTS GEN HOSP,MED SERV,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. WASHINGTON UNIV,VET ADM MED CTR,ST LOUIS,MO. UNIV LOUISVILLE,DEPT MED,LOUISVILLE,KY 40292. UNIV COLORADO,HLTH SCI CTR,DENVER,CO 80202. ARMED FORCES INST PATHOL,BETHESDA,MD. INNOGENETICS,GHENT,BELGIUM. SCHERING PLOUGH RES INST,KENILWORTH,NJ. RP Lindsay, KL (reprint author), UNIV SO CALIF,DEPT MED,1355 SAN PABLO ST,SUITE 128,LOS ANGELES,CA 90033, USA. FU NCRR NIH HHS [5M01RR00082, M01RR01066, RR-00865] NR 28 TC 115 Z9 115 U1 0 U2 0 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 NOV PY 1996 VL 24 IS 5 BP 1034 EP 1040 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VQ934 UT WOS:A1996VQ93400009 PM 8903371 ER PT J AU Trigoso, WF Wesly, JM Meranda, DL Shenker, Y AF Trigoso, WF Wesly, JM Meranda, DL Shenker, Y TI Vasopressin and atrial natriuretic hormone response to hypertonic saline during the follicular and luteal phases of the menstrual cycle SO HUMAN REPRODUCTION LA English DT Article DE atrial natriuretic hormone; menstrual cycle; vasopressin ID ARGININE VASOPRESSIN; POSTERIOR PITUITARY; PEPTIDE; PLASMA; RELEASE; SECRETION; WOMEN; RAT; OSMOREGULATION; STIMULATION AB We studied the hormonal responses to hypertonic saline during the follicular (days 2-9) and luteal (days 21-28) phases of the menstrual cycle in nine healthy young women, aged 19-25 years, On both study days, each woman was infused with 5% hypertonic saline for 1 h at the rate of 0.1 ml/kg/min. Serum progesterone and oestradiol concentrations confirmed the reported stage of the menstrual cycle, No difference in weight or haematocrit was observed between the two stages of the study for each woman, Baseline blood pressure, serum sodium, plasma osmolality, plasma vasopressin and thirst levels were almost identical for both stages, and changed to the same degree during infusion of hypertonic saline, Baseline atrial natriuretic hormone concentrations were higher during the follicular phase and became significantly higher than during the luteal phase following infusion of hypertonic saline. We concluded that the intravascular volume during the luteal phase may be effectively decreased in comparison to the follicular phase. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MED SERV,ENDOCRINOL RES LAB,MADISON,WI 53705. SPRINGFIELD CLIN,SPRINGFIELD,IL 62704. UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. FU NCRR NIH HHS [RR-03186] NR 32 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD NOV PY 1996 VL 11 IS 11 BP 2392 EP 2395 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA WA428 UT WOS:A1996WA42800013 PM 8981117 ER PT J AU Rudd, CF AF Rudd, CF TI TCR zeta/CD3, CD28 and CTLA-4 receptor signalling in T-cells SO IMMUNOLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 1996 VL 89 SU 1 BP SN43 EP SN43 PG 1 WC Immunology SC Immunology GA VT999 UT WOS:A1996VT99900043 ER PT J AU Schmidt, J Huch, K Mithofer, K Hotz, HG Sinn, HP Buhr, HJ Warshaw, AL Herfarth, C Klar, E AF Schmidt, J Huch, K Mithofer, K Hotz, HG Sinn, HP Buhr, HJ Warshaw, AL Herfarth, C Klar, E TI Benefits of various dextrans after delayed therapy in necrotizing pancreatitis of the rat SO INTENSIVE CARE MEDICINE LA English DT Article DE acute pancreatitis; therapy; dextran; hypertonic; colloid; rat ID TRYPSINOGEN-ACTIVATION PEPTIDES; ACUTE BILIARY PANCREATITIS; HEMORRHAGIC-PANCREATITIS; ISOVOLEMIC HEMODILUTION; TRASYLOL THERAPY; MICROCIRCULATION; ISCHEMIA; RESUSCITATION; NECROSIS AB Objective: Ultrahigh-molecular dextran (500 000 Da) has been shown to prevent pancreatic necrosis when given 30 min after induction of pancreatitis. This study should clarify the following: (a) are dextrans still effective after prolongation of the therapy-free interval? (b) what is the impact of the molecular weight of the dextrans? and (c) is their effect influenced by the dextran concentration or by the addition of hypertonic saline? Animals and interventions: Acute pancreatitis was induced in 70 male dextran-tolerant Wistar rats using intraductal bile-salt infusion and intravenous hyperstimulation. After 3 h, animals were assigned to one of seven groups (n = 10 per group) receiving either Ringer solution or different dextrans (10%) including 70 000 Da (DEX-70), 160 000 Da (DEX-160), 300 000 Da (DEX-300) or 500 000 Da (DEX-500). Additional groups included DEX-70 (6%) and DEX-70 (10%) in combination with hypertonic NaCl (7.5%) (HHS-70). Ringer solution was given at 24 ml/kg and all dextrans at 8 ml/kg. Measurements and results: Trypsinogen activation peptides (TAP) were quantified in ascites and acinar necrosis after death or sacrifice at 9 h. As an index of less pathological trypsinogen activation, the mean TAP levels in ascites were significantly lower in DEX-70 and DEX-160 compared to Ringer controls (p < 0.05, t-test). Furthermore, the amount of acinar necrosis was significantly lower in all dextran groups except the HHS-70 in comparison with Ringer controls (p < 0.01, t-test). Finally, mortality was significantly reduced from 60% in Ringer controls to 10 and 0%, respectively, in the groups treated with DEX-70 and DEX-160 (p<0.03, Fisher's Exact test). There was a similar trend in all other groups except the HHS-70. Conclusions: Despite a therapy-free interval of 3 h, dextrans reduce trypsinogen activation, prevent acinar necrosis, and improve survival in necrotizing rodent pancreatitis. The molecular weight and concentration of dextran are of secondary importance for these beneficial effects. C1 UNIV HEIDELBERG,DEPT PATHOL,D-6900 HEIDELBERG,GERMANY. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. RP Schmidt, J (reprint author), UNIV HEIDELBERG,DEPT SURG,NEUENHEIMER FELD 110,D-69120 HEIDELBERG,GERMANY. RI Sinn, Hans-Peter/C-5661-2008 NR 40 TC 17 Z9 17 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD NOV PY 1996 VL 22 IS 11 BP 1207 EP 1213 DI 10.1007/s001340050240 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA VW501 UT WOS:A1996VW50100015 PM 9120115 ER PT J AU King, PD Sadra, A Han, A Liu, JR SunderPlassmann, R Reinherz, EL Dupont, B AF King, PD Sadra, A Han, A Liu, JR SunderPlassmann, R Reinherz, EL Dupont, B TI CD2 signaling in T cells involves tyrosine phosphorylation and activation of the Tec family kinase, EMT/ITK/TSK SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE co-stimulatory molecules; protein kinases; signal transduction; T lymphocytes ID X-LINKED AGAMMAGLOBULINEMIA; FUNCTION-ASSOCIATED ANTIGEN-3; NATURAL-KILLER-CELLS; LYMPHOCYTE-T; ERYTHROCYTE RECEPTOR; CYTOPLASMIC DOMAIN; BRUTON TYROSINE; SURFACE LIGAND; BINDING-SITE; SRC FAMILY AB Ligation of the CD2 cell surface glycoprotein expressed on T lymphocytes and NK cells induces protein tyrosine phosphorylation and activation of the Src kinases, LCK and FYN. We show here that in Jurkat T leukemia cells and in peripheral blood T cells, CD2 stimulation also leads to tyrosine phosphorylation and activation of the Tec family kinase, EMT/ITK/TSK. Activation of EMT by CD2 was induced by mitogenic pairs of CD2 mAb, certain single CD2 mAb followed by secondary antibody cross-linking, and CD58-bearing sheep red blood cells. With the use of different Jurkat cell mutants it was demonstrated that CD2-mediated activation of EMT required expression of LCK, but did not require surface expression of the CD3 zeta chain. Receptor-mediated activation of LCK does not in itself lead to activation of this Tec kinase since induction of LCK by ligation of CD4 or CD5 did not result in activation of EMT. The activation of EMT during CD2 signaling suggests an important role for this kinase in CD2 co-stimulation of T cell responses. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. RP King, PD (reprint author), MEM SLOAN KETTERING CANC CTR,PROGRAM IMMUNOL,1275 YORK AVE,NEW YORK,NY 10021, USA. RI King, Phil/C-7104-2013 FU NCI NIH HHS [CA08748, CA22507]; NIAID NIH HHS [AI37294] NR 61 TC 33 Z9 36 U1 0 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 NOV PY 1996 VL 8 IS 11 BP 1707 EP 1714 DI 10.1093/intimm/8.11.1707 PG 8 WC Immunology SC Immunology GA VT921 UT WOS:A1996VT92100008 PM 8943565 ER PT J AU Kozin, SV Hasegawa, T Kozina, LV Imamura, M Akagi, K Tanaka, Y Kagiya, VT AF Kozin, SV Hasegawa, T Kozina, LV Imamura, M Akagi, K Tanaka, Y Kagiya, VT TI The use of a hypoxic cell radiosensitizer AK-2123 gave no improvement in thermoradiotherapy combined with hydralazine SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE thermoradiotherapy; hydralazine; AK-2123; tumour growth delay; blood flow ID BLOOD-FLOW; HYPERTHERMIA; TUMOR AB An electron-affinic compound, AK-2123, and the anti-hypertensive agent, hydralazine, were combined with radiation and hyperthermia for treatment of murine SCC-VII tumours. Hydralazine markedly decreased tumour perfusion while AK-2123 had no influence on it. Hydralazine enhanced the tumouricidal effects of hyperthermia alone and in combination with radiation. AK-2123 provided a radiosensitization which was significant only in tumours irradiated without supplementary hyperthermia. The greatest tumour response was achieved when thermoradiotherapy was combined with hydralazine alone; the additional use of AK-2123 with this treatment combination did not further increase the effect. II is concluded that hydralazine plus heat virtually eliminated a hypoxia-related radioresistance in tumours, thus removing the requirement for AK-2123 administration. C1 KANSAI MED UNIV,OSAKA 570,JAPAN. HLTH RES FDN,KYOTO 606,JAPAN. RUSSIAN ACAD MED SCI,CANC RES CTR,MOSCOW 115478,RUSSIA. RP Kozin, SV (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114, USA. NR 20 TC 7 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD NOV-DEC PY 1996 VL 12 IS 6 BP 771 EP 777 DI 10.3109/02656739609027683 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA VW561 UT WOS:A1996VW56100006 PM 8950157 ER PT J AU Maxwell, M Galanopoulos, T Antoniades, HN AF Maxwell, M Galanopoulos, T Antoniades, HN TI Coexpression of EGF receptor and TGF alpha mRNA and protein occurs in primary meningiomas SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE meningioma; EGFR; TGF alpha; tumorigenesis ID EPIDERMAL GROWTH-FACTOR; PRIMARY HUMAN ASTROCYTOMAS; MESSENGER-RNAS; BRAIN-TUMORS; NEUROFIBROMATOSIS TYPE-2; TRANSGENIC MICE; PDGF-RECEPTOR; EXPRESSION; CELLS; GENE AB Meningiomas are benign brain tumors thought to arise by multi-step tumorigenesis, involving both the activation of proto-oncogenes and the loss of tumor suppressor genes. The EGFR gene encodes a protooncogenic tyrosine kinase growth factor receptor implicated in the pathogenesis of several types of cancer, including gliomas. TGF alpha, the ligand for EGFR, is thought to act through autocrine stimulation of EGFR present on the same and adjacent cells. Northern blot analysis revealed expression of EGFR mRNA in 9 of 11 (82%), and TGF alpha mRNA in 2 of 11 (18%), primary meningioma specimens. III situ hybridization verified EGFR and TGF alpha gene expression by meningioma cells. Immunocytochemistry using specific antibodies for EGFR and TGF alpha showed strong positivity amongst meningeal cells in the same meningioma samples. No EGFR or TGF alpha protein was detected in a sample of normal meninges. These data indicate that the autocrine coexpression of EGFR and TGF alpha mRNA and protein may occur in only a small proportion of primary meningiomas. C1 HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,CTR BLOOD RES,BOSTON,MA 02115. RP Maxwell, M (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,HOUSE MALL,BOSTON,MA 02114, USA. NR 48 TC 2 Z9 2 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD NOV PY 1996 VL 9 IS 5 BP 917 EP 922 PG 6 WC Oncology SC Oncology GA VP104 UT WOS:A1996VP10400008 PM 21541596 ER PT J AU Nozue, M Lee, IT Hartford, A Tanda, S Suit, HD Jain, RK AF Nozue, M Lee, IT Hartford, A Tanda, S Suit, HD Jain, RK TI pO(2) measurement in murine tumors by Eppendorf 'Histograph': Calibration, reproducibility and comparison with Diamond-General device SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE pO(2) measurement; Eppendorf 'Histograph'; mouse tumor; Diamond-General set-up; reproducibility ID O2 TENSION MEASUREMENTS; OXYGEN DISTRIBUTION; UTERINE CERVIX; BLOOD-FLOW; CARBOGEN; PO2; PENTOXIFYLLINE; THERAPY; CANCER AB The purpose of this study was to assess the usefulness of the Eppendorf 'Kistograph' as a device for measuring pO(2) in tumor and normal tissues of the laboratory mouse. To determine the appropriate calibration and electrode condition, nitrogen bubbling time was changed, and the current during calibration was recorded. Reproducibility of pO(2) measurements was tested in the series of human xenografts and murine isoplants at different time points or in the same tumor in successive determinations. pO(2) values obtained with the Eppendorf 'Histograph' were compared to those obtained with a manually controlled needle-type electrode manufactured by the Diamond-General Company. The pO(2) values after 9 min of nitrogen bubbling were closer to the expected values than those after 3 min bubbling. The current during nitrogen bubbling in calibration declined following the pO(2) measurement by an amount corresponding to 0.8 mm Hg. Good reproducibility of pO(2) measurement was shown in i) pO(2) values in the same cell line at different time points and ii) pO(2) values in two or three consecutive measurements in related regions within the same tumor. The Eppendorf 'Histograph' and the Diamond-General device showed no significant differences in pO(2) distribution in either subcutaneous tissue or MCaIV tumors. In conclusion, results of the Eppendorf 'Histograph' were consistent and reproducible and were similar to those obtained by the Diamond-General set-up. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. NR 32 TC 1 Z9 1 U1 0 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD NOV PY 1996 VL 9 IS 5 BP 955 EP 962 PG 8 WC Oncology SC Oncology GA VP104 UT WOS:A1996VP10400013 PM 21541601 ER PT J AU Vorwerk, CK Kreutz, MR Dreyer, EB Sabel, BA AF Vorwerk, CK Kreutz, MR Dreyer, EB Sabel, BA TI Systemic L-kynurenine administration partially protects against NMDA, but not kainate-induced degeneration of retinal ganglion cells, and reduces visual discrimination deficits in adult rats SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE brightness discrimination; excitotoxicity; glutamate; kainic acid; L-kynurenine; N-methyl-D-aspartate; retina; retinal ganglion cells ID AMINO-ACID RECEPTORS; KAINIC ACID; GLUTAMATE NEUROTOXICITY; INTRAOCULAR INJECTION; MAMMALIAN RETINA; QUINOLINIC ACID; NERVOUS-SYSTEM; BRAIN INJURY; OPTIC-NERVE; ANTAGONISTS AB Purpose. Kynurenic acid (KYNA), an endogenous tryptophan metabolite, is an N-methyl-D-aspartate (NMDA) antagonist active at the glycine-binding site of the NMDA-receptor complex. The authors investigated whether svstemic administration of a biochemical precursor of KYNA, L-kynurenine (L-Kyn), could block NMDA- or kainic acid (KA)-induced cell death in adult rat retinal ganglion cells (RGCs) and protect NMDA-treated animals from lesion-induced visual deficits. Methods. Rats were injected with 20-nmol NMDA or 5-nmol KA intraocularly. To quantify the number of surviving RGCs, the retrograde tracer horseradish-peroxidase was injected into the superior colliculus contralateral to the lesioned eye. Surviving RGCs were counted on wholemounted retinae in a centroperipheral gradient, as well as in the four quadrants, using a computer-assisted image analysis system. Results. The NMDA-injections resulted in an approximately 82% RGC loss in the adult rat retina compared,vith control retinae and a cell loss of approximately 50% in KA-treated retinae. Pretreatment with L-Kyn significantly reduced NMDA-induced RGC degeneration to values of approximately 60%, but KA toxicity was not significantly affected by L-Kyn pretreatment. Intraocular injections of NMDA resulted in an impairment of visual discrimination behavior, which partially recovered within a period of approximately 3 weeks. However, when treated systemically with L-Kyn, brightness discrimination was significantly improved as compared with NMDA-treated rats. Conclusions. These findings show that systemic administration of L-Kyn in adult rats can block NMDA-induced retinal ganglion cell death in vivo and preserves brightness discrimination performance. C1 OTTO VON GUERICKE UNIV,INST MED PSYCHOL,FAC MED,D-39120 MAGDEBURG,GERMANY. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI Sabel, Bernhard/E-6579-2013; OI Sabel, Bernhard/0000-0002-4472-5543 NR 57 TC 35 Z9 36 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 NOV PY 1996 VL 37 IS 12 BP 2382 EP 2392 PG 11 WC Ophthalmology SC Ophthalmology GA VT378 UT WOS:A1996VT37800007 PM 8933755 ER PT J AU Joseph, RM Li, TS AF Joseph, RM Li, TS TI Overexpression of Bcl-2 or Bcl-X(L) transgenes and photoreceptor degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE apoptosis; bcl-2; bcl-X; light damage; retinal degeneration ID PROGRAMMED CELL-DEATH; RETINAL LIGHT-DAMAGE; RD MOUSE; CGMP-PHOSPHODIESTERASE; RETINITIS-PIGMENTOSA; CLUSTERIN EXPRESSION; PREVENT APOPTOSIS; BETA-SUBUNIT; GENE; PROTEIN AB Purpose. To test the hypothesis that overexpression of genes coding for the anti-apoptotic proteins Bcl-2 or Bcl-X(L) in photoreceptor cells may prevent or delay photoreceptor degenerations. Methods. Transgenic mice were generated in which the bcl-2 or bcl-X(L) transgenes were expressed in photoreceptor cells under the transcriptional control of a rhodopsin gene promoter. Bcl-2 or bcl-X(L) transgenic mice were crossed separately to a mouse strain carrying the rd/rd mutation and to another mouse line carrying a dominant rhodopsin gene mutation; both genetic defects result in photoreceptor degeneration. Photoreceptor cell death in mice expressing one of the bcl transgenes and carrying either the rd mutation homozygously or the rhodopsin mutation heterozygously was examined by histologic and electroretinographic measurements. Bcl-2 and bcl-X(L) transgenic mice also were tested for possible resistance to light-induced photoreceptor damage under two different experimental conditions. Results. Bcl-2 or bcl-X(L) transgenes were expressed in photoreceptor cells of all lines of transgenic mice. In both the rd and the rhodopsin mutant mice, expression of either bcl-2 or bcl-X(L) transgenes did not prevent or measurably delay photoreceptor degeneration. Apoptosis-related nuclear DNA fragmentation, as assessed by in situ labeling with terminal deoxynucleotidyl transferase, was present in 13-day-old rd/rd mouse retinas with or without transgene expression. Twelve days after exposure to 2 hours of high-intensity light, bcl-2 transgenic mice retained approximately four rows of photoreceptor cells in the central retina as compared to none in littermate controls, whereas bcl-X(L) transgenic mice showed no increased resistance to light damage. Expression of the bcl-2 but not the bcl-X(L) transgene also was associated with a reduction in rhodopsin content. Conclusions. Overexpression of bcl-2 or bcl-X(L) transgenes does not rescue photoreceptor cells from apoptosis caused by the two genetic mutations tested. Resistance to light damage seen in the bcl-2 transgenic mice is likely from a reduction in rhodopsin content rather than an anti-cell death activity of Bcl-2. Cell death pathways not regulated by Bcl-2 may be operative in photoreceptor degeneration. C1 HARVARD UNIV,MED SCH,MASSACHUSETTS EYE & EAR INFIRM,BERMAN GUND LAB,STUDY RETINAL DEGENERAT,BOSTON,MA 02114. FU NEI NIH HHS [EY10309, EY10581]; NICHD NIH HHS [N01-HD-0-2911] NR 52 TC 80 Z9 82 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 NOV PY 1996 VL 37 IS 12 BP 2434 EP 2446 PG 13 WC Ophthalmology SC Ophthalmology GA VT378 UT WOS:A1996VT37800012 PM 8933760 ER PT J AU Takagi, C Bursell, SE Lin, YW Takagi, H Duh, E Jiang, Z Clermont, AC King, GL AF Takagi, C Bursell, SE Lin, YW Takagi, H Duh, E Jiang, Z Clermont, AC King, GL TI Regulation of retinal hemodynamics in diabetic rats by increased expression and action of endothelin-1 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE diabetes; endothelin; endothelin-converting enzyme; endothelin receptor; retinal hemodynamics ID MEDULLARY COLLECTING DUCT; ELEVATED GLUCOSE-LEVELS; MEAN CIRCULATION TIME; SMOOTH-MUSCLE CELLS; BLOOD-FLOW; DEPENDENT REGULATION; PROVIDES EVIDENCE; MESSENGER-RNA; MELLITUS; RECEPTOR AB Purpose. To investigate the role of endogenous endothelin-1 (ET-1) expression and its interaction with the ET(A) receptor in the physiologic regulation of vascular tone as well as in the development of abnormal retinal hemodynamics in diabetes. Methods. Retinal blood flow, using digitized video fluorescein angiography recordings, was quantitated after intravitreous injections of ET-1; BQ-123, an ET(A) receptor antagonist; and phosphoramindon, an endothelin converting enzyme inhibitor in the eyes of diabetic and nondiabetic rats. A total of 154 rats were used for these experiments. Message levels of preproendothelin-1 (preproET-1) were measured from the retina of diabetic and nondiabetic rats using competitive polymerase chain reaction (PCR) techniques. Results. Retinal blood flow was reduced (33%, P <0.001) in diabetic rats compared to nondiabetic rats. BQ-123, an ET(A) receptor antagonist, but not saralasin, an angiotensin receptor antagonist, increased retinal blood flow in a dose-dependent manner in diabetic (EC(50) of 8x10(-7) M) and in nondiabetic rats (EC(50) of 8x10(-8) M). Besides being resistant to BQ-123, the maximal response in diabetic animals occurred 20 minutes later than in nondiabetic animals. Decreasing ET-1 levels by inhibiting endothelin-converting enzyme with phosphoramidon normalized retinal blood flow in diabetic rats, In nondiabetic rats, the intravitreous injection of exogenous ET-1 (10(-8) M) resulted in retinal blood flow decreases comparable to those measured in diabetic animals, and the subsequent injection of 10(-4) M BQ-123 produced retinal blood flow changes comparable to those measured in BQ-123 injected diabetic rats, Comparison of preproET-1 messenger RNA expression in the retina, brain, and lung of control and diabetic rats using quantitative PCR and Northern blot analysis showed 2.0- and 1.7-fold increases in the retina and the brain, respectively, without changes in the lung. Conclusions. These data suggest that ET-1 is involved in the regulation of retinal blood flow in normal physiologic outcome, and an increase in the endogenous expression of ET-1 contributes to the reduction of retinal blood flow reported in the early stages of diabetes mellitus. C1 HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,DEPT MED,JOSLIN DIABET CTR,RES DIV,BOSTON,MA. FU NEI NIH HHS [EY09178]; PHS HHS [36836] NR 63 TC 103 Z9 110 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 NOV PY 1996 VL 37 IS 12 BP 2504 EP 2518 PG 15 WC Ophthalmology SC Ophthalmology GA VT378 UT WOS:A1996VT37800019 PM 8933767 ER PT J AU Philbin, EF Lynch, LJ Rocco, TA Lindenmuth, NW Ulrich, K McCall, M Jenkins, P Roerden, JB AF Philbin, EF Lynch, LJ Rocco, TA Lindenmuth, NW Ulrich, K McCall, M Jenkins, P Roerden, JB TI Does QI work? The management to improve survival in congestive heart failure (MISCHF) study SO JOINT COMMISSION JOURNAL ON QUALITY IMPROVEMENT LA English DT Article ID HOSPITAL MORTALITY-RATES; ELDERLY PATIENTS; STAY; SEVERITY; LENGTH; CARE; DETERMINANTS; READMISSION; CALIFORNIA; OUTCOMES AB Background: In an ongoing study, a randomized, controlled trial is being conducted on the effects of a collaborative quality improvement program on practice patterns and patient outcomes regarding congestive heart failure (CHF) in community hospitals in upstate New York, CHF is associated with severe morbidity and mortality, with annual rates of death exceeding 50% among patients with the most severe disease. Phase I: Phase I of the study was designed to model the processes of care and outcomes, develop valid disease-specific risk adjustment techniques, and target areas for quality improvement (QI) intervention. Beginning April 1, 1995, and ending December 31, 1995, baseline data were collected during hospitalization and for six months postdischarge for all 1,402 consecutive patients assigned diagnosis-related groups (DRGs) 127 and 124. Preliminary analyses revealed high rates of hospital readmission (46%) and postdischarge death (18%), with significant interhospital variation. QI initiatives: Initiatives include educational programs on CHF, feedback of Phase I data to clinicians and administrators, design and implementation of a clinical care pathway, improvement of the emergency department (prehospital) phase of CHF management, and improvement in patient education and discharge planning. Summary and conclusions: The study suggests that community hospitals, many without extensive experience in clinical investigation, can voluntarily collaborate to design and implement a timely QI initiative that is evidence based, clinically relevant, and scientifically sound. Preliminary results have led to better understanding of the processes of care and determinants of outcome for patients with heart failure. Phase II of the study should yield insights into the providers' response to a locally derived intervention and the effects of such a program on patient outcomes. C1 BASSET HEALTHCARE,DIV CARDIOL,COOPERSTOWN,NY. VHA UPSTATE NEW YORK INC,QUAL RESOURCE CTR,E SYRACRUSE,NY. PK RIDGE HLTH SYST,ROCHESTER,NY. GENEVA GEN HOSP,GENEVA,SWITZERLAND. FAXTON HOSP,UTICA,NY. ST LUKES MEM HOSP,UTICA,NY. RP Philbin, EF (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,HEART FAILURE & TRANSPLANTAT SERV,BIGELOW 645,55 FRUIT ST,BOSTON,MA 02114, USA. NR 37 TC 18 Z9 18 U1 1 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1070-3241 J9 JOINT COMM J QUAL IM JI Jt. Comm. J. Qual. Improv. PD NOV PY 1996 VL 22 IS 11 BP 721 EP 733 PG 13 WC Health Policy & Services SC Health Care Sciences & Services GA XT181 UT WOS:A1996XT18100002 PM 8937947 ER PT J AU Toussaint, JF Kwong, KK MKparu, F Weisskoff, RM LaRaia, PJ Kantor, HL AF Toussaint, JF Kwong, KK MKparu, F Weisskoff, RM LaRaia, PJ Kantor, HL TI Interrelationship of oxidative metabolism and local perfusion demonstrated by NMR in human skeletal muscle SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE nuclear magnetic resonance; magnetic resonance imaging; magnetic resonance spectroscopy ID CONGESTIVE-HEART-FAILURE; MAGNETIC-RESONANCE; BLOOD-FLOW; GASTROCNEMIUS-MUSCLE; IN-VIVO; EXERCISE; SPECTROSCOPY; RESPIRATION; PHOSPHOCREATINE; ABNORMALITIES AB Using nuclear magnetic resonance (NMR), we have examined the relationship of high-energy phosphate metabolism and perfusion in human soleus and gastrocnemius muscles. With P-31-NMR spectroscopy, we monitored phosphocreatine (PCr) decay and recovery in eight normal volunteers and four heart failure patients performing ischemic plantar flexion. By using echo-planar imaging, perfusion was independently measured by a local [inversion-recovery (T1-flow)] and a regional technique (NMR-plethysmography). After correction for its pH dependence, PCr recovery time constant is 27.5 +/- 8.0 s in normal volunteers, with mean flow 118 +/- 75 (soleus and gastrocnemius T1-flow) and 30.2 +/- 9.7 ml . 100 ml(-1). min(-1) (NMR-plethysmography-flow). We demonstrate a positive correlation between PCr time constant and local perfusion given by gamma = 50 - 0.15x (r(2) = 0.68, P = 0.01) for the 8 normal subjects, and y = 64 - 0.24x (r(2) = 0.83, P = 0.0001) for the 12 subjects recruited in the study. Regional perfusion techniques also show a significant but weaker correlation. Using this totally noninvasive method, we conclude that aerobic ATP resynthesis is related to the magnitude of perfusion, i.e., Oa availability, and demonstrate that magnetic resonance imaging and magnetic resonance spectroscopy together can accurately assess muscle functional status. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NUCL MAGNET RESONANCE CTR,BOSTON,MA 02114. RP Toussaint, JF (reprint author), CEA,SERV HOSP FREDERIC JOLIOT,GRP RESONANCE MAGNET NUCL,4 PL GEN LECLERC,F-91401 ORSAY,FRANCE. FU NHLBI NIH HHS [R01-HL-39371] NR 43 TC 27 Z9 28 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 NOV PY 1996 VL 81 IS 5 BP 2221 EP 2228 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA VT205 UT WOS:A1996VT20500049 PM 8941548 ER PT J AU Gunn, JS Hohmann, EL Miller, SI AF Gunn, JS Hohmann, EL Miller, SI TI Transcriptional regulation of Salmonella virulence: A phoQ periplasmic domain mutation results in increased net phosphotransfer to phoP SO JOURNAL OF BACTERIOLOGY LA English DT Article ID TYPHIMURIUM VIRULENCE; INVASION; MACROPHAGES; PROTEINS; REGULON; GENE; PHOSPHORYLATION; DETERMINANTS; RESISTANCE; CELLS AB A mutation in the phoP/phoQ locus (pho-24) that results in unregulated expression of PhoP-activated genes (phenotype PhoP constitutive [PhoP(c)]) was mapped to phoQ. Change of a Thr to Ile at position 48 of PhoQ was responsible for the PhoP(c) phenotype (attenuation of mouse virulence, defects in epithelial cell invasion, and macrophage spacious phagosome formation). PhoP phosphorylation by membrane extracts required PhoQ, and PhoQ Ile-48-containing membranes demonstrated increased net phosphorylation of PhoP. C1 UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MICROBIOL,SEATTLE,WA 98195. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Gunn, John/E-3167-2011 FU NIAID NIH HHS [AI30479] NR 31 TC 67 Z9 69 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 NOV PY 1996 VL 178 IS 21 BP 6369 EP 6373 PG 5 WC Microbiology SC Microbiology GA VP984 UT WOS:A1996VP98400041 PM 8892844 ER PT J AU PedrazaAlva, G Merida, LB Burakoff, SJ Rosenstein, Y AF PedrazaAlva, G Merida, LB Burakoff, SJ Rosenstein, Y TI CD43-specific activation of T cells induces association of CD43 to Fyn kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WISKOTT-ALDRICH SYNDROME; PHOSPHATIDYLINOSITOL 3-KINASE; SURFACE SIALOGLYCOPROTEIN; SIALOPHORIN; ANTIGEN; RECEPTOR; BINDING; DOMAIN; PHOSPHORYLATION; PROLIFERATION AB CD43, the most abundant membrane protein of T lymphocytes, is able to initiate signal transduction pathways that lead to Ca2+ mobilization and interleukin-2 production, yet the molecular events involved in CD43's signal transduction pathway are poorly understood. In the present report we show that: activation of both purified T lymphocytes and Jurkat cells, through CD43 cross-linking with the anti-CD43 L10 monclonal antibody, induced CD43 association to Fyn kinase, This association is mediated by the Sre Homology 3 (SH3) domain of Fyn, since a glutathione S-transferase-Fyn SH3 fusion protein was able to precipitate CD43 from lysates of CD43-activated T cells. A synthetic peptide containing the SH3 binding sites of p85, located within the amino acid sequence (300)ERQPAPALPPKPPKP(314) was able to inhibit binding of CD43 to Fyn as well as to the glutathione S-transferase-Fyn SH3 fusion protein. We also provide evidence that upon CD48 cross-linking Fyn is tyrosine-phosphorylated in a time-dependent manner. Our results suggest that CD43 cross-linking on the T cell surface induces the interaction between CD43 and Fyn, presumably through the Fyn SH3 domain and a putative SH3 binding site in CD43, leading to Fyn tyrosine phosphorylation and signal propagation. C1 UNIV NACL AUTONOMA MEXICO,INST BIOTECHNOL,CUERNAVACA 62250,MORELOS,MEXICO. DANA FARBER CANC INST,BOSTON,MA 02115. NR 30 TC 59 Z9 59 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 1 PY 1996 VL 271 IS 44 BP 27564 EP 27568 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VQ679 UT WOS:A1996VQ67900060 PM 8910342 ER PT J AU Grimes, RY Pulido, GA Levine, RA Yoganathan, AP AF Grimes, RY Pulido, GA Levine, RA Yoganathan, AP TI Quasisteady behavior of pulsatile, confined, counterflowing jets: Implications for the assessment of mitral and tricuspid regurgitation SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID COLOR DOPPLER FLOW; ORIFICE AREA; IN-VITRO; ECHOCARDIOGRAPHY; SIZE; DIRECTION; PRESSURE; SEVERITY; ALTER AB Mitral and tricuspid regurgitation create turbulent jets within the atria. Clinically, for the purpose of estimating regurgitant severity, jet size is assumed to be proportional to peak jet flow rate and regurgitant volume. Unfortunately, the relationship is more complex because the determinants of jet size include interactions between jet pulsatility, jet momentum, atrial width, adn the velocity of ambient atrial counterflows. These effects on fluorescent jet penetration were measured using an in vitro simulation. Both steady and pulsatile jets were driven into an opposing counterflow velocity field peak jet length (L(jp)) measurements made as a function of (1) peak orifice velocity (U-jp), (2) the time required for the jet to accelerate from zero to peak velocity and begin to decelerate (T-jp), (3) jet orifice diameter (D-j), (4) counterflow velocity (U-c), and (5) counterflow tube diameter (D-c). A compact mathematical description was developed using dimensional analysis. Results showed that peak jet length was a function of the counterflow tube diameter, the ratio of peak jet to counterflow momentum, (M(jp)/M(c)) = ((UJPDj2)-D-2)/((UcDc2)-D-2), and a previously undescribed jet pulsatility parameter, the pulsatility index (PI), PI = D-c(2)/(TjpUjpDj). For the same jet orifice flow conditions, jet penetration decreased as chamber diameter decreased, as the jet PI increased, and as the momentum ratio decreased. These interactions provide insight into why regurgitant jet size is not always a good estimate of regurgitant severity. C1 GEORGIA INST TECHNOL,SCH CHEM ENGN,ATLANTA,GA 30332. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIAC ULTRASOUND LAB,BOSTON,MA. RP Grimes, RY (reprint author), GEORGIA INST TECHNOL,SCH MECH ENGN,CARDIOVASC FLUID MECH LAB,ATLANTA,GA 30332, USA. FU NHLBI NIH HHS [HL 45485] NR 31 TC 2 Z9 2 U1 0 U2 1 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD NOV PY 1996 VL 118 IS 4 BP 498 EP 505 DI 10.1115/1.2796036 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA VX043 UT WOS:A1996VX04300009 PM 8950653 ER PT J AU Reddy, SV Singer, FR Mallette, L Roodman, GD AF Reddy, SV Singer, FR Mallette, L Roodman, GD TI Detection of measles virus nucleocapsid transcripts in circulating blood cells from patients with Paget disease SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID HUMAN MARROW CULTURES; BONE-MARROW; PRECURSORS; ANTIGENS; SEQUENCE; ACID; DNA AB Paget disease of bone is characterized by abnormalities in all phases of bone remodeling but the fundamental cellular abnormality resides in the osteoclast (OCL). Osteoclasts in bone involved by Paget disease contain viral-like nuclear and cytoplasmic inclusions that react with antibodies directed against paramyxovirus nucleocapsid proteins, such as measles virus, respiratory syncytial virus, or canine distemper virus, However, the identity of the virus or the mechanisms responsible for its persistence or pathologic role in Paget disease is unclear, Furthermore, although Paget disease persists for many years, it remains a highly localized process with new lesions rarely if ever developing in previously unaffected bones, Since osteoclasts are formed by fusion of mononuclear precursors derived from colony forming unit-granulocyte macrophage (CFU-GM), the granulocyte-macrophage progenitor we used reverse transcriptase polymerase chain reaction (RT-PCR) analysis to determine if CFU-GM, more differentiated osteoclast precursors, and peripheral blood cells derived from CFU-GM express measles virus nucleocapsid (MV-N) transcripts, We found that osteoclast precursors, as well as peripheral blood mononuclear cells, express MV transcripts in 9 of 13 patients, Sequence analysis of the PCR amplified products confirmed nucleotide identity of M V-N transcripts expressed in peripheral blood and bone marrow-derived cells from the same patient, In contrast, MV-N transcripts were not detected in OCL precursors or the peripheral blood from 10 normal subjects, In situ hybridization studies using S-35-labeled antisense riboprobes to MV-N transcripts further confirmed the expression of MV transcripts in these cells, Sequence analysis of the PCR amplified product from one of these patients also identified a novel mutation that converted lysine(441) to glutamic acid(441) in the MV-N transcript, These data demonstrate that OCL precursors and circulating peripheral blood cells also expressing transcripts in patients with Paget disease and suggest that the pagetic marrow microenvironment plays a critical role in maintaining the highly localized nature of the lesions in Paget disease. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED HEMATOL,SAN ANTONIO,TX. JOHN WAYNE CANC INST,SANTA MONICA,CA. VET ADM MED CTR,HOUSTON,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. FU NIADDK NIH HHS [AM35188]; NIAMS NIH HHS [AR41336, AR39529] NR 20 TC 62 Z9 65 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 NOV PY 1996 VL 11 IS 11 BP 1602 EP 1607 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VQ705 UT WOS:A1996VQ70500002 PM 8915767 ER PT J AU Marfatia, SM Cabral, JHM Lin, LH Hough, C Bryant, PJ Stolz, L Chishti, AH AF Marfatia, SM Cabral, JHM Lin, LH Hough, C Bryant, PJ Stolz, L Chishti, AH TI Modular organization of the PDZ domains in the human discs-large protein suggests a mechanism for coupling PDZ domain-binding proteins to ATP and the membrane cytoskeleton SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; GATED POTASSIUM CHANNELS; GLYCOPHORIN-C; MOLECULAR CHARACTERIZATION; SEPTATE JUNCTIONS; K+ CHANNELS; DLG-A; DROSOPHILA; HOMOLOG; TIGHT AB The human homologue (hDlg) of the Drosophila discs-large tumor suppressor (Dlg) is a multidomain protein consisting of a carboxyl-terminal guanylate kinase-like domain, an SH3 domain, and three slightly divergent copies of the PDZ (DHR/GLGF) domain. Here we have examined the structural organization of the three PDZ domains of hDlg using a combination of protease digestion and in vitro binding measurements. Our results show that the PDZ domains are organized into two conformationally stable modules, one (PDZ(1+2)) consisting of PDZ domains 1 and 2, and the other (PDZ(3)) corresponding to the third PDZ domain. Using amino acid sequencing and mass spectrometry, we determined the boundaries of the PDZ domains after digestion with endoproteinase Asp-N, trypsin, and alpha-chymotrypsin. The purified PDZ(1+2), but not the PDZ(3) domain, contains a high affinity binding site for the cytoplasmic domain of Shaker-type K+ channels. Similarly, we demonstrate that the PDZ(1+2) domain can also specifically bind to ATP. Furthermore, we provide evidence for an in vivo interaction between hDlg and protein 4.1 and show that the hDlg protein contains a single high affinity protein 4.1-binding site that is not located within the PDZ domains. The results suggest a mechanism by which PDZ domain-binding proteins may be coupled to ATP and the membrane cytoskeleton via hDlg. C1 TUFTS UNIV,SCH MED,ST ELIZABETHS MED CTR,DEPT BIOMED RES,LAB TUMOR CELL BIOL,BOSTON,MA 02135. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,LAB XRAY CRYSTALLOG,BOSTON,MA 02115. UNIV CALIF IRVINE,CTR DEV BIOL,IRVINE,CA 92717. PHARM BIOSENSOR,CAMBRIDGE,MA 02139. RI Morais-Cabral, Joao/J-4914-2013 OI Morais-Cabral, Joao/0000-0002-4461-9716 FU NCI NIH HHS [CA66263]; NHLBI NIH HHS [HL 51445] NR 50 TC 82 Z9 83 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV PY 1996 VL 135 IS 3 BP 753 EP 766 DI 10.1083/jcb.135.3.753 PG 14 WC Cell Biology SC Cell Biology GA VR268 UT WOS:A1996VR26800017 PM 8909548 ER PT J AU Fuhlbrigge, RC Alon, R Puri, KD Lowe, JB Springer, TA AF Fuhlbrigge, RC Alon, R Puri, KD Lowe, JB Springer, TA TI Sialylated, fucosylated ligands for L-selectin expressed on leukocytes mediate tethering and rolling adhesions in physiologic flow conditions SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HIGH ENDOTHELIAL VENULES; HUMAN ALPHA(1,3)FUCOSYLTRANSFERASE GENE; P-SELECTIN; MOLECULAR-CLONING; CELL-ADHESION; LEWIS-X; NEUTROPHIL AGGREGATION; DETERMINES EXPRESSION; SIALOMUCIN CD34; HOMING RECEPTOR AB Interaction of leukocytes in flow with adherent Ieukocytes may contribute to their accumulation at sites of inflammation. Using L-selectin immobilized in a flow chamber, a model system that mimics presentation of L-selectin by adherent leukocytes, we characterize ligands for L-selectin on leukocytes and show that they mediate tethering and rolling in shear now. We demonstrate the presence of L-selectin ligands on granulocytes, monocytes, and myeloid and lymphoid cell lines, and not on peripheral blood T lymphocytes. These ligands are calcium dependent, sensitive to protease and neuraminidase, and structurally distinct from previously described ligands for L-selectin on high endothelial venules (HEV). Differential sensitivity to O-sialoglycoprotease provides evidence for ligand activity on both mucin-like and nonmucin-like structures. Transfection with fucosyltransferase induces expression of functional L-selectin ligands on both a lymphoid cell line and a nonhematopoietic cell line. L-selectin presented on adherent cells is also capable of supporting tethering and rolling interactions in physiologic shear flow. L-selectin ligands on leukocytes may be important in promoting leukocyte-leukocyte and subsequent leukocyte-endothelial interactions in vivo, thereby enhancing leukocyte localization at sites of inflammation. C1 CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT MED,DIV ALLERGY & IMMUNOL,BOSTON,MA 02115. UNIV MICHIGAN,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109. FU NHLBI NIH HHS [HL 48675] NR 64 TC 86 Z9 86 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV PY 1996 VL 135 IS 3 BP 837 EP 848 DI 10.1083/jcb.135.3.837 PG 12 WC Cell Biology SC Cell Biology GA VR268 UT WOS:A1996VR26800024 PM 8909555 ER PT J AU Alon, R Fuhlbrigge, RC Finger, EB Springer, TA AF Alon, R Fuhlbrigge, RC Finger, EB Springer, TA TI Interactions through L-selectin between leukocytes and adherent leukocytes nucleate rolling adhesions on selectins and VCAM-1 in shear flow SO JOURNAL OF CELL BIOLOGY LA English DT Article ID BLOCKING MONOCLONAL-ANTIBODY; HIGH ENDOTHELIAL VENULES; NODE HOMING RECEPTOR; P-SELECTIN; VASCULAR ENDOTHELIUM; CELL-ADHESION; NEUTROPHIL AGGREGATION; GLYCOPROTEIN LIGAND; DEFICIENT MICE; IN-VIVO AB We demonstrate an additional step and a positive feedback loop in leukocyte accumulation on inflamed endothelium. Leukocytes in shear flow bind to adherent leukocytes through L-selectin/ligand interactions and subsequently bind downstream and roll on inflamed endothelium, purified E-selectin, P-selectin, L-selectin, VCAM-1, or peripheral node addressin. Thus, adherent leukocytes nucleate formation of strings of rolling cells and synergistically enhance leukocyte accumulation. Neutrophils, monocytes, and activated T cell lines, but not peripheral blood T lymphocytes, tether to each other through L-selectin. L-selectin is not involved in direct binding to either E- or P-selectin and is not a major counterreceptor of endothelial selectins. Leukocyte-leukocyte tethers are more tolerant to high shear than direct tethers to endothelial selectins and, like other L-selectin-mediated interactions, require a shear threshold. Synergism between leukocyte-leukocyte and leukocyte-endothelial interactions introduces novel regulatory mechanisms in recruitment of leukocytes in inflammation. C1 CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL 48675] NR 63 TC 161 Z9 164 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV PY 1996 VL 135 IS 3 BP 849 EP 865 DI 10.1083/jcb.135.3.849 PG 17 WC Cell Biology SC Cell Biology GA VR268 UT WOS:A1996VR26800025 PM 8909556 ER PT J AU Rao, SM Bandettini, PA Binder, JR Bobholz, JA Hammeke, TA Stein, EA Hyde, JS AF Rao, SM Bandettini, PA Binder, JR Bobholz, JA Hammeke, TA Stein, EA Hyde, JS TI Relationship between finger movement rate and functional magnetic resonance signal change in human primary motor cortex SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE functional magnetic resonance imaging; brain activation; primary motor cortex; movement rate; cerebral blood flow ID HUMAN BRAIN; STIMULUS RATE; ACTIVATION; CONTRAST; EPI AB Functional magnetic resonance imaging (FMRI) is a noninvasive technique for mapping regional brain changes in response to sensory, motor, or cognitive activation tasks. Interpretation of these activation experiments may be confounded by more elementary task parameters, such as stimulus presentation ration or movement rates. We examined the effect of movement rate on the FMRI response recorded from the contralateral primary motor cortex. Four right-handed healthy subjects performed flexion-extension movements of digits 2-5 of the right hand at rates of 1, 2, 3, 4, or 5 Hz. Results of this study indicated a positive linear relationship between movement rate and FMRI signal change. Additionally, the number of voxels demonstrating functional activity increased significantly with faster movement rates. The magnitude of the signal change at each movement rate remained constant over the course of three 8-min scanning series. These findings are similar to those of previous rate studies of the visual and auditory system performed with positron emission tomography (PET) and FMRI. C1 MED COLL WISCONSIN,DEPT PSYCHIAT & BEHAV MED,MILWAUKEE,WI 53226. MED COLL WISCONSIN,BIOPHYS RES INST,MILWAUKEE,WI 53226. MASSACHUSETTS GEN HOSP,NMR CTR,DEPT RADIOL,CHARLESTOWN,MA. RP Rao, SM (reprint author), MED COLL WISCONSIN,DEPT NEUROL,SECT NEUROPSYCHOL,9200 W WISCONSIN AVE,MILWAUKEE,WI 53226, USA. RI Stein, Elliot/C-7349-2008; Rao, Stephen/A-2460-2010; Bandettini, Peter/F-5871-2012; OI Rao, Stephen/0000-0002-6463-7460; Binder, Jeffrey/0000-0002-2233-5640 FU NIDA NIH HHS [R01DA09465]; NIMH NIH HHS [P01MH51358]; NINDS NIH HHS [R01NS33576] NR 14 TC 218 Z9 222 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 1996 VL 16 IS 6 BP 1250 EP 1254 PG 5 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA VP540 UT WOS:A1996VP54000020 PM 8898698 ER PT J AU Weber, JR Angstwurm, K Bove, GM Burger, W Einhaupl, KM Dirnagl, U Moskowitz, MA AF Weber, JR Angstwurm, K Bove, GM Burger, W Einhaupl, KM Dirnagl, U Moskowitz, MA TI The trigeminal nerve and augmentation of regional cerebral blood flow during experimental bacterial meningitis SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE bacterial meningitis; trigeminal nerve ID EXPERIMENTAL PNEUMOCOCCAL MENINGITIS; GENE-RELATED PEPTIDE; VASOACTIVE INTESTINAL POLYPEPTIDE; NECROSIS-FACTOR-ALPHA; STORING SUBSTANCE-P; NITRIC-OXIDE; EARLY PHASE; MICROVASCULAR CHANGES; ICAM-1 EXPRESSION; ENDOTHELIAL-CELLS AB We investigated whether trigeminal nerve fibers contribute to enhanced regional cerebral blood flow (rCBF) in a rat model of experimental bacterial meningitis. rCBF was measured continuously for 6 h by laser Doppler flowmetry through thinned bone over the frontal cortex. Meningitis was induced with pneumococcal cell wall components and confirmed by a significant increase of (a) leukocytes within the cerebrospinal fluid, (b) brain water content, (c) intracranial pressure and (d) rCBF. The increase of rCBF was significantly attenuated (p < 0.05) at 3, 4, 5, and 6 h in animals after a chronic (200 +/- 21% versus 138 +/- 13% at 6 h on the intact and denervated sides, respectively) but not after an acute section of the nasociliary branch of the trigeminal nerve. We conclude that elevations in blood flow during the early phase of bacterial meningitis are mediated in part by the trigeminal nerve, probably by local perivascular release of neuropeptides from afferent axons innervating the meninges. C1 HUMBOLDT UNIV BERLIN,KLINIKUM CHARITE,INST MICROBIOL & HYG,D-10098 BERLIN,GERMANY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. RP Weber, JR (reprint author), HUMBOLDT UNIV BERLIN,KLINIKUM CHARITE,DEPT NEUROL,SCHUMANNSTR 20-21,D-10098 BERLIN,GERMANY. RI Moskowitz, Michael/D-9916-2011; OI Dirnagl, Ulrich/0000-0003-0755-6119 FU NINDS NIH HHS [NS 21558] NR 50 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 1996 VL 16 IS 6 BP 1319 EP 1324 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA VP540 UT WOS:A1996VP54000029 PM 8898707 ER PT J AU Cramer, SC Schaefer, PW Krishnamoorthy, KS AF Cramer, SC Schaefer, PW Krishnamoorthy, KS TI Microgyria in the distribution of the middle cerebral artery in a patient with DiGeorge syndrome SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID CARDIO-FACIAL SYNDROME; ANOMALIES; SEQUENCE C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. RP Cramer, SC (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114, USA. NR 22 TC 19 Z9 19 U1 0 U2 0 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 NOV PY 1996 VL 11 IS 6 BP 494 EP 497 PG 4 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA VW886 UT WOS:A1996VW88600017 PM 9120232 ER PT J AU Grinspoon, S Gulick, T Askari, H Landt, M Lee, K Anderson, E Ma, ZM Vignati, L Bowsher, R Herzog, D Klibanski, A AF Grinspoon, S Gulick, T Askari, H Landt, M Lee, K Anderson, E Ma, ZM Vignati, L Bowsher, R Herzog, D Klibanski, A TI Serum leptin levels in women with anorexia nervosa SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IGF-BINDING PROTEINS; OBESE GENE-PRODUCT; BODY-WEIGHT; MOUSE AB Leptin is a protein encoded by the ob gene that is expressed in adipocytes and regulates eating behavior via central neuroendocrine mechanisms. Serum leptin levels have been shown to correlate with weight and percent body fat in normal and obese individuals; however, it is not known whether the regulation of leptin is normal below a critical threshold of body fat in chronic undernutrition. We investigated serum leptin levels in 22 women, aged 23 +/- 4 yr, with anorexia nervosa. Duration of disease, weight, BMI, percent body fat, and serum leptin levels were determined for each patient. Nutritional status was assessed further by caloric intake and measurement of insulin and insulin-like growth factor I (IGF-I) levels. Twenty-three healthy women, aged 23 +/- 4 yr, taking no medications, with normal menstrual function and body mass index (BMI) between 20-26 kg/m(2) (mean, 23.7 +/- 1.7 kg/m(2)), served as a control population for compar ison of leptin levels. Subjects with anorexia nervosa were low weight (BMI, 16.3 +/- 1.6 kg/m(2); normal, 20-26 kg/m(2)) and exhibited a striking reduction in percent body fat (7 +/- 2%; normal, 20-30%). The mean serum leptin level was significantly decreased in subjects with anorexia nervosa compared with that in age- and sex-matched controls of normal body weight (5.6 +/- 3.7 vs. 19.1 +/- 8.1 ng/mL; P < 0.0001). Serum leptin levels were correlated highly with weight, as expressed either BMI (r = 0.66; P = 0.002) or percent ideal body weight (r = 0.68; P = 0.0005), body fat (r = 0.70; P = 0.0003), and IGF-I (r = 0.64; P = 0.001), but not with caloric intake or serum levels of estradiol or insulin in subjects with anorexia nervosa. The correlation between leptin and body fat was linear, with progressively lower, but detectable, leptin levels measured even in patients with less than 5% body fat, but was not significant when the effects of weight were taken into account. In contrast, the correlation between leptin and IGF-I remained significant when the effects of weight, body fat, and caloric intake were taken into account. In normal controls, leptin correlated with BMI (r = 0.55; P = 0.007) and IGF-I (r = 0.44; P < 0.05), but not with fat mass. These data demonstrate that serum leptin levels are reduced in association with low weight and percent body fat in subjects with anorexia nervosa compared to normal controls. Leptin levels correlate highly with weight, percent body fat, and IGF-I in subjects with anorexia nervosa, suggesting that the physiological regulation of leptin is maintained in relation to nutritional status even at an extreme of low weight and body fat. C1 MASSACHUSETTS GEN HOSP, DIABET RES LABS, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, PSYCHIAT UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CLIN RES CTR, BOSTON, MA 02114 USA. WASHINGTON UNIV, SCH MED, DEPT PEDIAT, ST LOUIS, MO 63021 USA. ELI LILLY & CO, INDIANAPOLIS, IN USA. FU NCRR NIH HHS [MO1-RR-01066]; NIDDK NIH HHS [F32-DK-08783, P32-DK-07028] NR 17 TC 312 Z9 316 U1 0 U2 10 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1996 VL 81 IS 11 BP 3861 EP 3863 DI 10.1210/jc.81.11.3861 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VT446 UT WOS:A1996VT44600013 PM 8923829 ER PT J AU Grinspoon, S Baum, H Lee, K Anderson, E Herzog, D Klibanski, A AF Grinspoon, S Baum, H Lee, K Anderson, E Herzog, D Klibanski, A TI Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BIOCHEMICAL MARKERS; SOMATOMEDIN-C; OSTEOCLAST FORMATION; OSTEOBLASTIC CELLS; URINARY-EXCRETION; ADOLESCENT GIRLS; BINDING PROTEIN; YOUNG-WOMEN; HORMONE; ESTROGEN AB Significant osteoporosis affects over half of all women with anorexia nervosa (AN). The mechanisms of bone loss in this condition are not known, and estrogen administration alone has not been shown to prevent bone loss. Insulin-like growth factor I (IGF-I), a nutritionally dependent bone trophic hormone, is known to stimulate osteoblast function and collagen synthesis in vivo and in vitro. We hypothesized that short term administration of recombinant human IGF-I (rhIGF-I) would increase bone turnover in young women with AN. We studied 23 women, aged 18-29 yr (mean +/- SD, 23 +/- 4 yr) with AN. Spinal bone density was significantly reduced compared to that in age-matched controls (0.85 +/- 0.11 vs. 1.19 +/- 0.12 g/cm(2) by dual energy x-ray absorptiometry; P < 0.001) and was below the normal mean in 54% of the women. Patients were randomized to receive rhIGF-I (100 or 30 mu g/kg) or placebo sc twice a day for 6 days. Bone turnover was assessed at baseline and after 3 and 6 days of treatment using two markers of bone formation [osteocalcin (OC) and type I procollagen carboxyl-terminal propeptide (PICP)] and three specific markers of bone resorption [pyridinoline (PYRX), deoxypyridinoline (DPYRX), and N-telopeptide (NTX)]. Serum OC was reduced significantly (P < 0.001) in women with AN compared to normal premenopausal women (5.4 +/- 3.8 vs. 8.6 +/- 4.5 ng/mL) and correlated with percent fat mass (r = 0.60; P < 0.01) and body mass index (r = 0.50; P < 0.05). Markers of bone resorption were elevated significantly compared to normal levels [DPYRX, 18.2 +/- 7.0 vs. 11.4 +/- 5.2 nmol/mmol creatinine, (P < 0.001); NTX, 53.5 +/- 22.5 vs. 36.5 +/- 14.6 nmol BCE/mmol creatinine (P < 0.01)]. IGF-I levels were relatively low at baseline compared to those in age-matched controls (203 +/- 93 vs. 262 +/- 84 ng/mL; P < 0.01) and increased to 673 +/- 268 ng/mL [P < 0.05; 100 mu g/kg twice daily (BID)] and 545 +/- 255 ng/mL (P < 0.05; 30 mu g/kg BID). During short term administration of rhIGF-I at a dose of 100 mu g/kg BID, there was a significant (P < 0.05) increase in markers of bone formation, as assessed by both PICP (147 +/- 33 to 303 +/- 187 ng/mL) and OC (5.3 +/- 3.8 to 10.9 +/- 7.4 ng/mL). There was also a significant (P < 0.05) increase in markers of bone resorption as assessed by PYRX (51.0 +/- 16.6 to 87.1 +/- 8.2 nmol/mmol creatinine) and DPYRX (17.3 +/- 4.5 to 26.3 +/- 3.7 nmol/mmol creatinine). The group randomized to receive short term administration of rhIGF-I at a dose of 30 mu g/kg BID demonstrated a significant (P < 0.05) increase in PICP (110.9 +/- 47.0 to 134.8 +/- 43.2 ng/mL) and an insignificant increase in OC levels (4.5 +/- 3.2 to 6.8 +/- 5.9 ng/mL). However, markers of bone resorption were unchanged during rhIGF-I administration at this dose. Serum PTH and serum and urinary calcium were unchanged in both treatment groups compared to placebo levels. These data demonstrate that young women with anorexia nervosa have decreased markers of bone formation and increased bone resorption. This is the first demonstration that short term rhIGF-I administration increases markers of bone turnover in severely osteopenic women with AN. The effects of short term rhIGF-I on bone turnover are dose dependent. At a dose of 100 mu g BID, rhIGF-I administration significantly stimulated both markers of bone formation and bone resorption. At a dose of rhIGF-I of 30 mu g BID, there was an increase in one marker of bone formation, PICP, without a change in markers of bone resorption. Further studies are required to determine whether chronic administration of rhIGF-I can affect bone mass in young women with profound osteopenia due to anorexia nervosa. C1 MASSACHUSETTS GEN HOSP, NEUROENDOCRINE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, PSYCHIAT UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, GEN CLIN RES CTR, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [P32-DK-07028, F32-DK-08783] NR 48 TC 161 Z9 164 U1 0 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 NOV PY 1996 VL 81 IS 11 BP 3864 EP 3870 DI 10.1210/jc.81.11.3864 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VT446 UT WOS:A1996VT44600014 PM 8923830 ER PT J AU Grinspoon, S Corcoran, C Lee, K Burrows, B Hubbard, J Katznelson, L Walsh, M Guccione, A Cannan, J Heller, H Basgoz, N Klibanski, A AF Grinspoon, S Corcoran, C Lee, K Burrows, B Hubbard, J Katznelson, L Walsh, M Guccione, A Cannan, J Heller, H Basgoz, N Klibanski, A TI Loss of lean body and muscle mass correlates with androgen levels hypogonadal men with acquired immunodeficiency syndrome and wasting SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-FACTOR-I; CORTICOSTEROID-BINDING GLOBULIN; IMMUNE-DEFICIENCY SYNDROME; X-RAY ABSORPTIOMETRY; VIRUS INFECTION; LUNG-DISEASE; HORMONE; PROTEIN; TESTOSTERONE; AMPLITUDE AB The acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS) is a devastating complication of human immunodeficiency virus infection characterized by a disproportionate decrease in lean body mass. The pathogenesis of the AWS is unknown, but recent data suggest that endogenous secretion of the potent anabolic hormone, testosterone, is decreased in 30-50% of men with AIDS. However, it is unknown whether decreased androgen levels are associated with decreased lean body mass and/or functional decreases in muscle strength and aerobic capacity in hypogonadal men with the AWS. In addition, testosterone is known to have stimulatory effects on GH secretion, and the loss of these effects on the GH-insulin-like growth factor I (IGF-I) axis may be an additional mechanism of decreased lean body mass in this population. Twenty hypogonadal subjects (free-testosterone <12 pg/mL) with weight loss >10% of preillness weight or absolute weight <90% ideal body weight (IBW) were enrolled in the study. None of the subjects were receiving Megace. Lean body mass and fat-free mass were determined by potassium-40 isotope analysis (K-40) and dual-energy x-ray absorptiometry, respectively, and analyzed with respect to gonadal function by linear regression analysis. Muscle mass was determined by urinary creatinine excretion, and exercise functional capacity was assessed by a 6-min walk test, a sit-to-stand test, and a timed get-up-and-go test. Results also were compared with gonadal function by regression analysis. IGF-I and mean overnight GH levels, determined from frequent sampling (q20 min from 2000-0800 h), were compared with results obtained from age- and sex-matched normal controls. Subjects were 26-58 yr of age (39 +/- 7 yr, mean +/- SD) with a CD4 cell count of 150 +/- 186 cells/mm(3). Serum levels of FSH were elevated in 30% of the subjects. Muscle mass was significantly reduced, compared with expected mass for height (23.3 +/- 5.5 vs. 29.3 +/- 1.7 kg, P = 0.0001) and was decreased disproportionately to weight (77% of expected value for muscle mass vs. 93% of expected value for weight). Free-testosterone levels were correlated with total body potassium (R = 0.45, P < 0.05) and muscle mass (R = 0.45, P < 0.05). Total-testosterone levels were correlated with exercise functional capacity (R = 0.64, P = 0.01 for the sit-to-stand test and R = 0.53, P < 0.05 for the B-min walk test). Mean GH levels were significantly increased (3.03 +/- 1.76 vs. 0.90 +/- 0.37 ng/mL, P < 0.001) and IGF-I levels decreased (167 +/- 66 vs. 225 +/- 69 ng/mL, P < 0.01), compared with age- and sex-matched eugonadal controls. GH levels were inversely correlated with caloric intake (R = -0.60, P = 0.02) and percent fat mass by dual-energy x-ray absorptiometry (R = 0.58, P = 0.02). Six additional hypogonadal subjects receiving Megace for AIDS wasting were analyzed separately. Nutritional status and parameters of body composition were compared in the Megace and non-Megace-treated subjects. No significant differences in caloric intake, lean body mass, fat mass, or muscle mass were demonstrated. These data demonstrate that changes in body composition, including loss of lean body and muscle mass, and deterioration in exercise functional capacity are highly correlated with androgen levels in hypogonadal men with the AWS. Furthermore, our data demonstrate significantly increased GH levels and decreased IGF-I in association with low weight in this population. These data suggest that androgen deficiency combined with classical GH resistance may contribute to the critical loss of lean body and muscle mass in hypogonadal men with the AWS. These data are the first to link muscle and lean body wasting with progressive gonadal dysfunction among the large percentage of men with AIDS wasting who are hypogonadal. This demonstrates the need for additional studies to determine the efficacy of gonadal steroid replacement to increase lean body mass in this population. C1 MASSACHUSETTS GEN HOSP, INFECT DIS UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, PHYS THERAPY UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, GEN CLIN RES CTR, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. VET ADM MED CTR JAMAICA PLAIN, BOSTON, MA 02130 USA. BOSTON UNIV, MED CTR, BOSTON, MA 02130 USA. RP Grinspoon, S (reprint author), MASSACHUSETTS GEN HOSP, NEUROENDOCRINE UNIT, BOSTON, MA 02114 USA. FU NCRR NIH HHS [MO1-RR-01066]; NIDDK NIH HHS [R01-DK-49302, P32-DK-07028] NR 54 TC 149 Z9 151 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1996 VL 81 IS 11 BP 4051 EP 4058 DI 10.1210/jc.81.11.4051 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VT446 UT WOS:A1996VT44600044 PM 8923860 ER PT J AU Ibanez, L Hall, JE Potau, N Carrascosa, A Prat, N Taylor, AE AF Ibanez, L Hall, JE Potau, N Carrascosa, A Prat, N Taylor, AE TI Ovarian 17-hydroxyprogesterone hyperresponsiveness to gonadotropin-releasing hormone (GnRH) agonist challenge in women with polycystic ovary syndrome is not mediated by luteinizing hormone hypersecretion: Evidence from GnRH agonist and human chorionic gonadotropin stimulation testing SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LEYDIG-CELLS; INDUCED DESENSITIZATION; ANDROGEN BIOSYNTHESIS; HYPERANDROGENISM; SECRETION; STEROIDOGENESIS; DYSREGULATION; NAFARELIN; EXCESS; SINGLE AB Women with polycystic ovary syndrome (PCOS: hyperandrogenism and oligomenorrhea) have been shown to have exaggerated ovarian 17-hydroxyprogesterone (17-OHP) responses after GnRH agonist stimulation, suggestive of disordered ovarian cytochrome P450c17 alpha activity. However, most hyperandrogenic women also have an exaggerated LH response to both native GnRH and GnRH agonists. To assess whether the known LH hyperresponsiveness in PCOS patients mediates their exaggerated 17-OHP response to GnRH agonist challenge or whether the 17-OHP response can be duplicated by direct stimulation of the ovary with a fixed amount of hCG, 25 PCOS women [age, 20.6 +/- 1.1 yr; body mass index (BMI), 24.9 +/- 1.3 kg/m(2)] and 5 controls (age, 29.4 +/- 2.3 yr; BMI, 29.2 +/- 3.0) underwent both GnRH agonist (leuprolide acetate) and hCG testing. In addition, 23 normal women (age, 26.5 +/- 1.5 yr; BMI, 27.2 +/- 1.7 kg/m(2)) underwent hCG testing, and 21 other normal women (age, 19.3 +/- 0.5 yr; BMI, 23.0 +/- 0.8 kg/m(2)) underwent leuprolide acetate challenge. Blood was sampled before and 24 h after (the previously determined time of the peak response) leuprolide acetate (500 mu g, sc) and hCG (5000 IU, im) stimulation tests. The tests were administered during the early follicular phase in women who were ovulatory and in randomized order in the subjects receiving both stimuli. Peak serum 17-OHP levels did not differ between leuprolide acetate or hCG stimulation in PCOS patients or controls when measured at 24 h (324.9 +/- 41.9 vs. 360.4 +/- 54.0 in PCOS; 183.2 +/- 19.6 us. 141.2 +/- 11 ng/dL in controls). Peak 17-OHP levels after hCG challenge and GnRH agonist stimulation were highly correlated (r = 0.82; P < 0.001) in the subjects receiving both stimuli. Although leuprolide acetate elicited a higher estradiol (E(2)) response than hCG in all subjects, serum E(2) levels increased significantly after hCG treatment in both patients and controls (P < 0.001 and P < 0.0001). The small, but significant, increase in serum E(2) after hCG stimulation suggests that a rigid two-cell model of ovarian steroidogenesis may be an oversimplification of in vivo physiology. Our results suggest that exaggerated 17-OHP responses to GnRH agonist stimulation in hyperandrogenic women are not mediated by the known hyperresponsiveness of LH in these patients, but are due to increased ovarian androgen sensitivity to LR stimulation. C1 AUTONOMOUS UNIV BARCELONA, HOSP MATERNOINFANTIL VALL HEBRON, ADOLESCENT & ENDOCRINOL UNIT, BARCELONA, SPAIN. HOSP VILADECANS, DEPT GYNECOL, BARCELONA, SPAIN. MASSACHUSETTS GEN HOSP, DEPT MED, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT MED, REPROD ENDOCRINE SCI CTR, BOSTON, MA 02114 USA. RI Audi, Laura/H-7134-2012; Ibanez, Lourdes/F-8316-2014 OI Audi, Laura/0000-0002-5031-4097; Ibanez, Lourdes/0000-0002-5058-1603 FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [P30-HD-28138, U54-HD-29164] NR 31 TC 61 Z9 63 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1996 VL 81 IS 11 BP 4103 EP 4107 DI 10.1210/jc.81.11.4103 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VT446 UT WOS:A1996VT44600051 PM 8923867 ER PT J AU Lei, HQ Furth, EE Kalluri, R Chiou, T Tilly, KI Tilly, JL Elkon, KB Jeffrey, JJ Strauss, JF AF Lei, HQ Furth, EE Kalluri, R Chiou, T Tilly, KI Tilly, JL Elkon, KB Jeffrey, JJ Strauss, JF TI A program of cell death and extracellular matrix degradation is activated in the amnion before the onset of labor SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE amnion; apoptosis; collagen; interstitial collagenase; ribosomes ID HUMAN FETAL MEMBRANES; APOPTOSIS; METALLOPROTEINASES; COLLAGENASE; CLEAVAGE; ORGANIZATION; PARTURITION; PROTEINS; SITE; DNA AB Fetal membranes usually rupture during the process of labor. Premature fetal membrane rupture occurs not infrequently and is associated with significant fetal and maternal morbidity, The mechanisms of normal and pathologic fetal membrane rupture are not well understood, We have examined structural and biochemical changes in the rat amnion as labor approaches in order to characterize this process in normal pregnancy, Here we report that before the onset of active labor the amnion epithelial cells undergo apoptotic cell death which encompasses degradation of 28S ribosomal subunit RNA and associated P proteins and fragmentation of nuclear DNA. Concurrent with these cellular changes, the amnion type I collagen matrix is degraded with the accumulation of three-quarter length type I collagen fragments in extraembryonic fluid, characteristic of the cleavage of fibrillar collagen by interstitial collagenase. Western blot and immunohistochemical analyses confirmed that interstitial collagenase protein appears in association with the loss of amnion type I collagen. We conclude that amnion epithelial cells undergo a process of programmed cell death associated with orchestrated extracellular matrix degradation which begins before the onset of active labor. Thus, fetal membrane rupture is likely to be the result of biochemical changes as well as physical forces. C1 UNIV PENN,DEPT OBSTET & GYNAECOL,PHILADELPHIA,PA 19104. UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. UNIV PENN,DEPT MED,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,VINCENT CTR REPROD BIOL,BOSTON,MA 02114. CORNELL UNIV,HOSP SPECIAL SURG,COLL MED,NEW YORK,NY 10021. ALBANY MED COLL,DEPT PHARMACOL & TOXICOL,ALBANY,NY 12208. RI Kalluri, Raghu/E-2677-2015 OI Kalluri, Raghu/0000-0002-2190-547X FU NIA NIH HHS [AG-12279]; NICHD NIH HHS [HD-34226, HD-34612] NR 31 TC 92 Z9 97 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV 1 PY 1996 VL 98 IS 9 BP 1971 EP 1978 DI 10.1172/JCI119001 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VR563 UT WOS:A1996VR56300007 PM 8903315 ER PT J AU Shi, B DeGirolami, U He, JL Wang, S Lorenzo, A Busciglio, J Gabuzda, D AF Shi, B DeGirolami, U He, JL Wang, S Lorenzo, A Busciglio, J Gabuzda, D TI Apoptosis induced by HIV-1 infection of the central nervous system SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE AIDS; HIV; encephalitis; apoptosis; dementia ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS DEMENTIA COMPLEX; PROGRAMMED CELL-DEATH; BLOOD-BRAIN-BARRIER; IMMUNOHISTOCHEMICAL LOCALIZATION; NEOCORTICAL DAMAGE; ENDOTHELIAL-CELLS; IN-VIVO; TYPE-1; NEUROTOXICITY AB Apoptosis plays a role in AIDS pathogenesis in the immune system, but its role in HIV-l-induced neurological disease is unknown. In this study, we examine apoptosis induced by HIV-1 infection of the central nervous system (CNS) in an in vitro model and in brain tissue from AIDS patients. HIV-I infection of primary brain cultures induced apoptosis in neurons and astrocytes in vitro as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and propidium iodide staining and by electron microscopy. Apoptosis was not significantly induced until 1-2 wk after the time of peak virus production, suggesting induction by soluble factors rather than by direct viral infection, Apoptosis of neurons and astrocytes was also detected in brain tissue from 10/11 AIDS patients, including 5/5 patients with HIV-1 dementia and 4/5 nondemented patients. In addition, endothelial cell apoptosis was frequently detected in the brain of AIDS patients and was confirmed by electron microscopy, Most of the apoptotic cells were not localized adjacent to HIV-l-infected cells, providing further evidence for induction by soluble factors, In six non-AIDS control patients with normal brain, apoptotic cells were absent or limited to rare astrocytes. However, TUNEL-positive neurons and astrocytes were frequently detected in seven patients with Alzheimer's disease or abundant senile plaques. These studies suggest that apoptosis is a mechanism of CNS injury in AIDS which is likely to be induced by soluble factors. The apoptosis of endothelial cells in the CNS raises the possibility that some of these factors may be blood-derived. C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. CHILDRENS HOSP,MED CTR,DEPT NEUROL,BOSTON,MA 02115. RI wang, shu /H-6744-2012 FU NINDS NIH HHS [NS35734] NR 50 TC 192 Z9 197 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV 1 PY 1996 VL 98 IS 9 BP 1979 EP 1990 DI 10.1172/JCI119002 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VR563 UT WOS:A1996VR56300008 PM 8903316 ER PT J AU Xia, P Aiello, LP Ishii, H Jiang, ZY Park, DJ Robinson, GS Takagi, H Newsome, WP Jirousek, MR King, GL AF Xia, P Aiello, LP Ishii, H Jiang, ZY Park, DJ Robinson, GS Takagi, H Newsome, WP Jirousek, MR King, GL TI Characterization of vascular endothelial growth factor's effect on the activation of protein kinase C, its isoforms, and endothelial cell growth SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE vascular endothelial growth factor; signal transduction; phospholipase C gamma; protein kinase C; proliferation ID PHOSPHATIDYLINOSITOL 3-KINASE; PERMEABILITY FACTOR; SIGNAL-TRANSDUCTION; INSULIN STIMULATION; ANGIOGENESIS; RECEPTORS; FAMILY; INHIBITION; MECHANISM; TISSUES AB Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen which mediates its effects by binding to tyrosine kinase receptors, We have characterized the VEGF-activated intracellular signal transduction pathway in bovine aortic endothelial cells and correlated this to its mitogenic effects, VEGF induced concentration- and time-dependent increases in protein kinase C (PKC) activation with a maximum of 2.2-fold above the basal level at 5 x 10(-10) M within 10 min as measured both by in situ and translocation assays, Immunoblotting analysis of PKC isoforms in cytosolic and membrane fractions indicated that after VEGF stimulation the content of Ca2+-sensitive PKC isoforms (alpha and beta II) was increased in the membrane fractions, whereas no changes were observed for PKC isoforms delta and epsilon. The stimulation of PKC activity by VEGF was preceded by the activation of phospholipase C gamma (PLC gamma), This was demonstrated by parallel increases in PLC gamma tyrosine phosphorylation, [H-3]inositol phosphate production, and [H-3]arachidonic acid-labeled diacylglycerol formation in bovine aortic endothelial cells, In addition, VEGF increased phosphatidylinositol 3-kinase activity 2.1-fold which was inhibited by wortmannin, a phosphatidylinositol 3-kinase inhibitor, without decreasing the VEGF-induced increase in PKC activity or endothelial cell growth, Interestingly, genistein, a tyrosine kinase inhibitor, and GFX or H-7, PKC inhibitors, abolished both VEGF-induced PKC activation and endothelial cell proliferation, VEGF's mitogenic effect was inhibited by a PKC isoform beta-selective inhibitor, LY33-3531, in a concentration-dependent manner. In contrast, antisense PKC-alpha oligonucleotides enhanced VEGF-stimulated cell growth with a simultaneous decrease of 70% in PKC-alpha protein content, Thus, VEGF appears to mediate its mitogenic effects partly through the activation of the PLC gamma and PKC pathway, involving predominately PKC-beta isoform activation in endothelial cells. C1 BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DEPT MED,DIV RES,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DEPT MED,BEETHAM EYE INST,BOSTON,MA 02215. HYBRIDON INC,WORCESTER,MA. LILLY RES LABS,INDIANAPOLIS,IN 46285. RI Xia, Pu/G-3090-2010; Park, Do-Joon/J-2736-2012 OI Xia, Pu/0000-0003-4705-8878; FU NEI NIH HHS [EY05110, EY10827]; NIDDK NIH HHS [DK36433] NR 35 TC 428 Z9 443 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV 1 PY 1996 VL 98 IS 9 BP 2018 EP 2026 DI 10.1172/JCI119006 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VR563 UT WOS:A1996VR56300012 PM 8903320 ER PT J AU Broaddus, VC Yang, L Scavo, LM Ernst, JD Boylan, AM AF Broaddus, VC Yang, L Scavo, LM Ernst, JD Boylan, AM TI Asbestos induces apoptosis of human and rabbit pleural mesothelial cells via reactive oxygen species SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE oxygen radicals; annexin V; flow cytometry; deferoxamine; internalization ID DNA STRAND-BREAKS; CROCIDOLITE ASBESTOS; EPITHELIAL-CELLS; DEATH; INDUCTION; FIBERS; POLYMERASE; CYTOTOXICITY; MACROPHAGES; INHIBITION AB Mesothelial cells, the progenitor cell of the asbestos-induced tumor mesothelioma, are particularly sensitive to the toxic effects of asbestos, although the molecular mechanisms by which asbestos induces injury in mesothelial cells are not known, We asked whether asbestos induced apoptosis in mesothelial cells and whether reactive oxygen species were important. Pleural mesothelial cells (rabbit or human) were exposed to asbestos (crocidolite, amosite, or chrysotile) or control particles at moderate doses (1-10 mu g/cm(2)) over 24 h and evaluated for oligonucleosomal DNA fragmentation, loss of membrane phospholipid asymmetry, and nuclear condensation, Asbestos fibers, not control particles, induced apoptosis in mesothelial cells by all assays and induction of apoptosis was dose dependent for all types of asbestos, with crocidolite (5 mu g/cm(2)) inducing 15.0+/-1.1% (mean+/-SE; n = 12) apoptosis versus control particles < 4%. Apoptosis induced by asbestos, but not by actinomycin D, was inhibited by extracellular catalase, superoxide dismutase in the presence of catalase, hypoxia (8% oxygen.), deferoxamine, 3-aminobenzamide [an inhibitor of poly(ADP-ribosyl) polymerase], and cytochalasin B. Only catalase and cytochalasin B decreased fiber uptake, We conclude that asbestos induces apoptosis in mesothelial cells via reactive oxygen species, Escape from this pathway could allow the abnormal survival of mesothelial cells with asbestos-induced mutations. C1 SAN FRANCISCO GEN HOSP,DEPT MED,SAN FRANCISCO,CA 94143. SAN FRANCISCO GEN HOSP,LUNG BIOL CTR,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,CARDIOVASC RES INST,SAN FRANCISCO,CA 94143. SAN FRANCISCO GEN HOSP,DEPT MED,SAN FRANCISCO,CA 94143. SAN FRANCISCO GEN HOSP,ROSALIND RUSSELL ARTHRIT LAB,SAN FRANCISCO,CA 94143. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. MED UNIV S CAROLINA,RALPH H JOHNSON VET ADM MED CTR,CTR MOL & STRUCT BIOL,CHARLESTON,SC 29425. FU NHLBI NIH HHS [PPG HL24075]; NIEHS NIH HHS [KO8 ES00253, R01 ESO6331] NR 54 TC 106 Z9 107 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV 1 PY 1996 VL 98 IS 9 BP 2050 EP 2059 DI 10.1172/JCI119010 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VR563 UT WOS:A1996VR56300016 PM 8903324 ER PT J AU Tanaka, S Wands, JR AF Tanaka, S Wands, JR TI Carboxy-terminal truncated insulin receptor substrate-1 dominant negative protein reverses the human hepatocellular carcinoma malignant phenotype SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE human hepatoma; signal transduction; carcinogenesis ID TYROSINE-PHOSPHORYLATED PROTEINS; RAT HEPATOCYTE PROLIFERATION; PLECKSTRIN HOMOLOGY DOMAINS; EPIDERMAL GROWTH-FACTOR; MAP KINASE KINASE; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3'-KINASE; NEOPLASTIC TRANSFORMATION; LIVER REGENERATION; DEFINED MEDIUM AB Insulin receptor substrate-1 (IRS-1), a substrate of various receptor tyrosine kinases transmits mitogenic signals initiated by extracellular ligands. This protein is involved in normal hepatocyte growth and has been found to be overexpressed in human hepatocellular carcinoma. Expression of a carboxy-terminal truncated IRS-1 molecule containing the pleckstrin homology and phosphotyrosine-binding domains associates with the insulin receptor and prevents tyrosyl phosphorylation of endogenous IRS-1 and She proteins. Thus, subsequent activation of downstream signaling molecules induced by insulin and IGF-1 such as phosphatidylinositol-3 kinase and mitogen activated protein kinase is inhibited. The morphologic features of transformed human hepatocellular carcinoma cells change to a differentiated hepatocyte appearance and characteristics of the malignant phenotype as manifested by anchorage independent cell growth and tumor formation in nude mice are lost. These studies demonstrate that signal transduction pathways mediated through or by IRS-1 are important in hepatocyte and human hepatocellular carcinoma cell growth. C1 MASSACHUSETTS GEN HOSP,MOL HEPATOL LAB,CTR CANC,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666] NR 49 TC 68 Z9 68 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV 1 PY 1996 VL 98 IS 9 BP 2100 EP 2108 DI 10.1172/JCI119016 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VR563 UT WOS:A1996VR56300022 PM 8903330 ER PT J AU Jorgensen, JH Swenson, JM Tenover, FC Barry, A Ferraro, MJ Murray, PR Reller, LB AF Jorgensen, JH Swenson, JM Tenover, FC Barry, A Ferraro, MJ Murray, PR Reller, LB TI Development of interpretive criteria and quality control limits for macrolide and clindamycin susceptibility testing of Streptococcus pneumoniae SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ANTIBIOTICS; INFECTIONS; RESISTANCE AB A six-laboratory collaborative study was conducted to develop MIC and zone diameter quality control limits and interpretive criteria for antimicrobial susceptibility testing of Streptococcus pneumoniae with azithromycin, clarithromycin, dirithromycin, and clindamycin. The MICs of all of the agents plus erythromycin for 302 clinical isolates of pneumococci that had been selected with an emphasis on resistant strains were determined by use of the National Committee for Clinical Laboratory Standards (NCCLS)-recommended broth microdilution procedure, The zone diameters of the isolates were also determined for the same agents except erythromycin by the NCCLS disk diffusion test procedure, Repeated testing of S. pneumoniae ATCC 49619 with different sources and lots of media and disks allowed development of MIC and zone diameter quality control ranges for these agents, Interpretive criteria for the MIC of azithromycin were established and were as follows: susceptible, less than or equal to 0.5 mu g/ml; intermediate, 1 mu g/ml; and resistant, greater than or equal to 2 mu g/ml. The interpretive criteria advocated for the MICs of clarithromycin and clindamycin were as follows: susceptible, less than or equal to 0.25 mu g/ml; intermediate, 0.5 mu g/ml; and resistant, greater than or equal to 1 mu g/ml. Comparison of MICs and disk diffusion zone diameters led to the development of interpretive criteria for the zone diameters for azithromycin, clarithromycin, and clindamycin that correlated well with these MIC breakpoints. Testing of this organism collection also led to the reestablishment of the erythromycin MIC breakpoints as being identical to those of clarithromycin, which resulted in equivalent cross-susceptibility and cross-resistance for the three macrolides that are currently marketed in the United States, Thus, the susceptibility of pneumococci to azithromycin and clarithromycin can be predicted accurately by testing only erythromycin in clinical laboratories, This recommendation, as well as the interpretive and quality control criteria that are described, have been accepted by NCCLS and are included in the latest NCCLS susceptibility testing guidelines. C1 CTR DIS CONTROL & PREVENT,NOSOCOMIAL PATHOGENS LAB BRANCH,ATLANTA,GA 30333. CLIN MICROBIOL INST INC,TUALATIN,OR 97062. MASSACHUSETTS GEN HOSP,MICROBIOL LAB,BOSTON,MA 02114. WASHINGTON UNIV,MED CTR,DEPT LAB MED,ST LOUIS,MO. DUKE UNIV,MED CTR,CLIN MICROBIAL LAB,DURHAM,NC 27710. RP Jorgensen, JH (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284, USA. NR 18 TC 19 Z9 20 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 1996 VL 34 IS 11 BP 2679 EP 2684 PG 6 WC Microbiology SC Microbiology GA VM556 UT WOS:A1996VM55600009 PM 8897164 ER PT J AU Calderwood, SB Baker, MA Carroll, PA Michel, JL Arbeit, RD Ausubel, FM AF Calderwood, SB Baker, MA Carroll, PA Michel, JL Arbeit, RD Ausubel, FM TI Use of cleaved amplified polymorphic sequences to distinguish strains of Staphylococcus epidermidis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PROSTHETIC VALVE ENDOCARDITIS; POLYMERASE CHAIN-REACTION; PCR; IDENTIFICATION; OUTBREAK; AUREUS; DNA AB We examined the utility of a PCR-based termed cleaved amplified polymorphic sequences (CAPS) to type 35 well-characterized isolates of Staphylococcus epidermidis. The results were compared with detailed epidemiologic information and typing obtained by using pulsed-field gel electrophoresis (PFGE). To identify CAPS markers for this study, eight pairs of oligonucleotide primers corresponding to five previously sequenced S. epidermidis genes were synthesized and then used to amplify DNA sequences from the S. epidermidis strains by using PCR. Amplified products were reproducibly obtained for seven of eight primer pairs from chromosomal DNA of 33 of the 35 isolates. Seven restriction site polymorphisms were found in five of the amplified products when they were subjected to digestion with a panel of restriction endonucleases. Each fragment-enzyme combination that was polymorphic demonstrated only two alleles in the 33 S. epidermidis isolates analyzed, corresponding to the presence or absence of a single restriction site. Overall, five distinct combinations of alleles were detected and were designated CAPS types A through E. There was a close correlation between the CAPS grouping, the epidemiologic information for the strains, and grouping by PFGE following SmaI digestion of chromosomal DNA. Although PFGE analysis was more discriminatory than typing based on the limited number of CAPS markers used in this study (isolates from the same CAPS group were sometimes distributed into more than one PFGE group), no isolates from the same PFGE group were found in more than one CAPS group. The CAPS procedure was highly reproducible, in contrast to published experience with arbitrarily primed PCR. These preliminary data suggest that CAPS represents a PCR-based technique for strain typing that is highly reproducible, rapid, utilizes widely available technologies, and provides results that are relatively easy to interpret and express. C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,CHANNING LABS,BOSTON,MA 02115. VET AFFAIRS MED CTR,RES SERV,BOSTON,MA 02130. RP Calderwood, SB (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114, USA. NR 15 TC 5 Z9 6 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 1996 VL 34 IS 11 BP 2860 EP 2865 PG 6 WC Microbiology SC Microbiology GA VM556 UT WOS:A1996VM55600047 PM 8897202 ER PT J AU PohlmannEden, B Hoch, DB Cochius, JI Chiappa, KH AF PohlmannEden, B Hoch, DB Cochius, JI Chiappa, KH TI Periodic lateralized epileptiform discharges - A critical review SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Review DE periodic lateralized epileptiform discharge; stroke; focal hyperexcitability; seizures ID POSITRON EMISSION TOMOGRAPHY; CREUTZFELDT-JAKOB DISEASE; CLINICAL-SIGNIFICANCE; CAROTID ENDARTERECTOMY; CEREBRAL INFARCTION; EEG PATTERNS; SEIZURES; PLEDS; ELECTROENCEPHALOGRAM; ABNORMALITIES AB It is the purpose of this review to critically consider and organize the literature dealing with the ephemeral electroencephalographic (EEG) pattern periodic lateralized epileptiform discharges (PLEDs). Although the retrospective nature of these studies limits their ability to discuss accurately the clinical and pathophysiological aspects of this EEG entity, the available data strongly emphasize stroke as the dominant etiology and its high association with seizures. Recent evidence, particularly from functional neuroimaging studies, strongly suggests that PLEDs might reflect a key pattern for focal hyperexcitability in the penumbra zone of ischemic stroke. The authors prefer to consider PLEDs as an EEG signature of a dynamic pathophysiological state in which unstable neurobiological processes create an ictal-interictal continuum, with the nature of the underlying neuronal injury, the patient's preexisting propensity to have seizures, and the co-existence of any acute metabolic derangements all contributing to whether seizures occur or not. This review underlines the need for further sophisticated prospective controlled studies implementing early continuous EEG monitoring in order to contribute to an understanding of the incidence, dynamics, and relevance of this pattern. C1 MASSACHUSETTS GEN HOSP, DEPT NEUROL, EPILEPSY SERV, BOSTON, MA 02114 USA. RP PohlmannEden, B (reprint author), UNIV HEIDELBERG, MANNHEIM HOSP, DEPT NEUROL, D-68135 MANNHEIM, GERMANY. OI Hoch, Daniel/0000-0002-4294-024X NR 55 TC 131 Z9 131 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD NOV PY 1996 VL 13 IS 6 BP 519 EP 530 DI 10.1097/00004691-199611000-00007 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VZ924 UT WOS:A1996VZ92400007 PM 8978624 ER PT J AU McLaughlin, PW Sandler, HM Jiroutek, MR AF McLaughlin, PW Sandler, HM Jiroutek, MR TI Prostate-specific antigen following prostate radiotherapy: How low can you go? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID RANDOMIZED COMPARATIVE TRIAL; EXTERNAL-BEAM RADIOTHERAPY; RADIATION-THERAPY; CANCER; CARCINOMA; IRRADIATION C1 PROVIDENCE HOSP,ANN ARBOR,MI 48109. DANA FARBER CANC INST,BOSTON,MA 02115. RP McLaughlin, PW (reprint author), UNIV MICHIGAN,ANN ARBOR,MI 48109, USA. NR 17 TC 20 Z9 20 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 NOV PY 1996 VL 14 IS 11 BP 2889 EP 2892 PG 4 WC Oncology SC Oncology GA VU591 UT WOS:A1996VU59100001 PM 8918484 ER PT J AU Ayash, LJ Elias, A Schwartz, G Wheeler, C Ibrahim, J Teicher, BA Reich, E Warren, D Lynch, C Richardson, P Schnipper, L Frei, E Antman, K AF Ayash, LJ Elias, A Schwartz, G Wheeler, C Ibrahim, J Teicher, BA Reich, E Warren, D Lynch, C Richardson, P Schnipper, L Frei, E Antman, K TI Double dose-intensive chemotherapy with autologous stem-cell support for metastatic breast cancer: No improvement in progression-free survival by the sequence of high-dose melphalan followed by cyclophosphamide, thiotepa, and carboplatin SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ANTITUMOR ALKYLATING-AGENTS; MARROW SUPPORT; CROSS-RESISTANCE; PHASE-II; INVITRO; TRANSPORT; INTENSIFICATION; MITOXANTRONE; COMBINATION; CARRIER AB Purpose: Twenty-one percent of responding metastatic breast cancer patients remain progression-free a median 50 months following one intensification cycle of cyclophosphamide (6,000 mg/m(2)), thiotepa (500 mg/m(2)), and carboplatin (800 mg/m(2)) (CTCb) with autologous bone marrow transplantation (ABMT). This trial studied whether the sequence of high-dose melphalan followed by CTCb resulted in improved disease response and duration. Methods: Women with at least partial responses (PRs) to induction received melphalan (140 or 180 mg/m(2)) with peripheral-blood progenitor cell (PBPC) and granulocyte colony-stimulating factor (G-CSF) support. They were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support. Results: Data on 67 women, at a median of 25 months from CTCb, were examined. After melphalan, 49 (73%) required admission for fever (89%), mucositis (35%), or infection (15%) (median stay, 8 days). All received CTCb. For the first 33 patients, the median days from start of melphalan to CTCb was 24. After liver toxicity (one death from venoocclusive disease [VOD]) developed in 11 patients during CTCb, the interval between intensifications was increased to 35 days without incident. Twenty-three patients (34%) are progression-free a median of 16 months post-CTCb. The median progression-free survival (PFS) and survival rimes for the whole group are estimated at 11 and 20 months, respectively. Conclusion: Treatment with this sequence of high-dose melphalan followed by CTCb has not resulted in superior PFS to date, when compared with single-intensification CTCb. This report discusses factors related to patient selection, the role of induced drug resistance, and the schedule of administration of alkylating agents that may adversely influence outcome. (C) 1996 by American Society of Clinical Oncology. C1 DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,BOSTON,MA. RP Ayash, LJ (reprint author), DANA FARBER CANC INST,DEPT CANC PHARMACOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [P01-CA-38493] NR 27 TC 53 Z9 53 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 NOV PY 1996 VL 14 IS 11 BP 2984 EP 2992 PG 9 WC Oncology SC Oncology GA VU591 UT WOS:A1996VU59100013 PM 8918496 ER PT J AU Borrelli, B Niaura, R Keuthen, NJ Goldstein, MG DePue, JD Murphy, C Abrams, DB AF Borrelli, B Niaura, R Keuthen, NJ Goldstein, MG DePue, JD Murphy, C Abrams, DB TI Development of major depressive disorder during smoking-cessation treatment SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID CLONIDINE; SMOKERS; WITHDRAWAL; NICOTINE; SYMPTOMS AB Background: Several studies have shown an association between smoking and major depressive disorder (MDD), but few have prospectively examined subjects who develop MDD after quitting smoking. This descriptive study evaluated the development of MDD after smoking cessation, as assessed by a structured clinical interview at both baseline and the end of treatment. Method: Nondepressed participants (N = 114) in a trial investigating the effect of fluoxetine on smoking cessation were administered the Structured Clinical Interview for DSM-III-R at baseline and posttreatment to evaluate the impact of quitting smoking on the development of MDD. Depressive symptoms were additionally assessed with the Beck Depression Inventory and the Hamilton Rating Scale for Depression. Results: At baseline, 32% of the subjects reported a history of MDD. Sixty-nine subjects completed the SCID at baseline and posttreatment. At posttreatment, 5 subjects (7%) met threshold criteria for MDD; none were taking the highest dose of fluoxetine (60 mg), 4 were taking 30 mg, and 1 was taking placebo. All 5 had a history of MDD; 3 were women. Four had a history of substance abuse and attained at least 3 consecutive biochemically verified weeks of smoking abstinence. Those who developed MDD after treatment scored significantly higher on measures of depressed mood at baseline than those who did not develop MDD after smoking-cessation treatment. Conclusion: The results from this descriptive study suggest that a subset of smokers may be at risk for developing MDD after smoking cessation. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Borrelli, B (reprint author), BROWN UNIV,MIRIAM HOSP,SCH MED,DIV BEHAV & PREVENT MED,164 SUMMIT AVE RISE,PROVIDENCE,RI 02906, USA. NR 27 TC 86 Z9 86 U1 0 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 1996 VL 57 IS 11 BP 534 EP 538 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA VX059 UT WOS:A1996VX05900006 PM 8968303 ER PT J AU Sims, CD Butler, PEM Casanova, R Randolph, MA Ahn, DK Yaremchuk, MJ AF Sims, CD Butler, PEM Casanova, R Randolph, MA Ahn, DK Yaremchuk, MJ TI Surgical model to assess the effects and optimal timing of craniofacial fixation SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE in utero craniofacial fetal fixation ID GROWTH; RABBITS AB An in utero swine model of craniofacial deformity was developed as a potential alternative to neonatal models currently used For evaluating the optimal timing and long-term effects of rigid fixation techniques on a growing cranium. At 75% gestation, seven fetal piglets were randomly selected to undergo periosteal stripping of frontal and parietal bone segments with and without extensive coronal suture fusion procedures with cyanoacrylate adhesive. Fetal. swine were killed postpartum at 4 and 11 weeks after fusion to assess craniofacial deformity. Piglets undergoing coronal fusion had slight deviation of the nose-snout toward the side of fusion and taller cranial vaults. The vertical cranial index of the experimental fusion group was 0.34 in comparison to a vertical index of 0.27 for the controls, suggesting abnormal vertical height expansion. There was no difference in the horizontal cranial index of either control or experimental fusion groups. Neither sows nor piglets were lost to anesthetic complications, uterine sepsis, or preterm labor during the initial laparotomy or subsequent cesarean delivery. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV PLAST SURG,BOSTON,MA 02114. NR 10 TC 4 Z9 4 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD NOV PY 1996 VL 7 IS 6 BP 412 EP 416 DI 10.1097/00001665-199611000-00004 PG 5 WC Surgery SC Surgery GA VU661 UT WOS:A1996VU66100004 PM 10332259 ER PT J AU Yaremchuk, MJ Rubin, JP Posnick, JC AF Yaremchuk, MJ Rubin, JP Posnick, JC TI Implantable materials in facial aesthetic and reconstructive surgery: Biocompatibility and clinical applications SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Editorial Material DE implantable materials; alloplast; biocompatibility; liability AB On October 6, 1995, the American Society of Maxillofacial Surgeons sponsored a 1-day symposium entitled ''Implantable Materials in Facial Aesthetic and Reconstructive Surgery: Biocompatibility and Clinical Applications.'' The symposium examined issues relating to the biocompatibility and clinical role of alloplastic materials commonly used for facial bone and soft-tissue replacement and augmentation, It provided a forum for the interaction of basic scientists, clinicians, and manufacturers. Clinical and laboratory data concerning a variety of implantable materials were presented and discussed. The program consisted of three parts. The first session was designed to provide historical and scientific background as well as perspective on legal issues surrounding the use of implantable biomaterials. The second session involved the presentation of clinical data on bone and bone substitutes for augmentation of the facial skeleton. The third session was devoted to clinical reports of bone and bone substitutes used for the reconstruction of cranial vault and cranial base skull defects. C1 MASSACHUSETTS GEN HOSP,DIV PLAST & RECONSTRUCT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. GEORGETOWN UNIV,MED CTR,DIV PLAST SURG,WASHINGTON,DC 20057. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD NOV PY 1996 VL 7 IS 6 BP 473 EP 484 DI 10.1097/00001665-199611000-00015 PG 12 WC Surgery SC Surgery GA VU661 UT WOS:A1996VU66100015 PM 10332269 ER PT J AU Kashket, S Zhang, J VanHoute, J AF Kashket, S Zhang, J VanHoute, J TI Accumulation of fermentable sugars and metabolic acids in food particles that become entrapped on the dentition SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE acids; cariogenicity; dentition; foods; human; retention; starch ID DENTAL-CARIES; WHEAT-STARCH; SNACK FOODS; PLAQUE PH; CARIOGENICITY; DEMINERALIZATION; AVAILABILITY; RETENTION; SUCROSE; RATS AB Earlier studies (Kashket et al., 1991) showed that particles of high-starch snack foods remained longer on the teeth than those of high-sucrose, low-starch foods. The question arose whether the prolonged presence of food particles enhances cariogenicity. A study was undertaken to measure sugars, starches, and metabolic acids in retained food particles. Subjects consumed portions of different foods, and particles were removed from all bicuspids and first molars at defined times after swallowing. Dry weights, sugars, and short-chain carboxylic acids were determined. High-sucrose foods were cleared rapidly from the teeth, while high-starch foods were retained for up to 20 min. Sucrose, glucose, and fructose persisted in the retained particles. Particles of high-starch foods accumulated maltose and maltotriose, presumably from the breakdown of starch by salivary amylase. At maximum, maltose plus maltotriose constituted 94% of total sugars in particles of potato chips; corresponding values in doughnuts, peanut butter cookies, and salted crackers were 43, 51, and 61%, respectively. Total fermentable sugars in the particles of high-starch foods were similar to those for the high-sucrose confectionery products. Carboxylic acids accumulated within the particles, presumably due to the fermentation of the sugars by entrapped salivary micro-organisms. At maximum (5 to 7 min), acetic, formic, lactic, and propionic acids rose 17-, 30-, 15-, and 1.3-fold, respectively, in dough-nuts, and to smaller degrees in potato chips, salted crackers, and chocolate-caramel-peanut bars. In summary, the study demonstrated the persistence of sugars, the progressive accumulation of starch breakdown products, and the fermentation of the accumulated sugars in retained food particles. The findings support the view that high-starch foods contribute to the development of caries lesions. C1 FORSYTH DENT CTR,DEPT MICROBIOL,BOSTON,MA 02115. FORSYTH DENT CTR,CTR RES ORAL & BIOL EFFECTS FOODS,BOSTON,MA 02115. RP Kashket, S (reprint author), FORSYTH DENT CTR,DEPT NUTR,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-05253, DE-08415] NR 29 TC 31 Z9 31 U1 1 U2 4 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 1996 VL 75 IS 11 BP 1885 EP 1891 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WA880 UT WOS:A1996WA88000011 PM 9003236 ER PT J AU Bauman, RA Gell, G Dwyer, SJ AF Bauman, RA Gell, G Dwyer, SJ TI Large picture archiving and communication systems of the world .2. SO JOURNAL OF DIGITAL IMAGING LA English DT Article DE computers; radiology; picture archiving and communication systems (PACS); survey AB A survey of 82 institutions worldwide was done in 1995 to identify large picture archiving and communication systems (PACS) in clinical operation. A continuing strong trend toward the creation and operation of large PACS was identified. In the 15 months since the first such survey the number of clinical large PACS went from 13 to 23, almost a doubling in that short interval. New systems were added in Asia, Europe, and North America. A strong move to primary interpretation from soft copy was identified, and filmless radiology has become a reality. Workstations for interpretation reside mainly within radiology, but one-third of reporting PACS have more than 20 workstations outside of radiology. Fiber distributed data interface networks were the most numerous. but a variety of networks was reported to he in use. Replies on various display times showed surprisingly good, albeit diverse, speeds. The planned archive length of many systems was 60 months, with usually more than 1 year of data on-line. The main large archive and oft-line storage media for these systems were optical disks and magneto-optical disks. Compression was not used before interpretation in most cases. but many systems used 2.5:1 compression for on-line, interpreted cases and 10:1 compression for longer-term archiving. A move to digital imaging and communication in medicine interface usage was identified. Copyright (C) 1996 by W.B. Saunders Company C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. GRAZ UNIV,INST MED INFORMAT,GRAZ,AUSTRIA. UNIV VIRGINIA,DEPT RADIOL,CHARLOTTESVILLE,VA. NR 2 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 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD NOV PY 1996 VL 9 IS 4 BP 172 EP 177 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VU807 UT WOS:A1996VU80700003 PM 8951096 ER PT J AU Brown, D Breton, S AF Brown, D Breton, S TI Mitochondria-rich, proton-secreting epithelial cells SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Review DE intercalated cell; H+V-ATPase; anion exchanger; carbonic anhydrase; kidney; epididymis; amphibian bladder; amphibian epidermis; turtle bladder ID VACUOLAR H+-ATPASE; MEDULLARY COLLECTING DUCT; TOAD URINARY-BLADDER; CARBONIC-ANHYDRASE ACTIVITY; BETA-INTERCALATED CELLS; TOBACCO HORNWORM MIDGUT; TRANSPORTING PLASMA-MEMBRANES; ROD-SHAPED PARTICLES; TURTLE-BLADDER; RAT-KIDNEY AB Several transporting epithelia in vertebrates and invertebrates contain cells that are specialized for proton or bicarbonate secretion. These characteristic 'mitochondria-rich' (MR) cells have several typical features, the most important of which is an extremely high expression of a vacuolar-type proton-pumping ATPase (H+V-ATPase) both on intracellular vesicles and on specific domains of their plasma membrane. Physiological modulation of proton secretion is achieved by recycling the H+V-ATPase between the plasma membrane and the cytoplasm in a novel type of nonclathrin-coated vesicle. In the kidney, these cells are involved in urinary acidification, while in the epididymis and vas deferens they acidify the luminal environment to allow normal sperm development. Osteoclasts are non-epithelial MR cells that use H+V-ATPase activity for bone remodeling, In some insects, similar cells in the midgut energize K+ secretion by means of a plasma membrane H+V-ATPase. This review emphasizes important structural and functional features of proton-secreting cells, describes the tissue distribution of these cells and discusses the known functions of these cells in their respective epithelia. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NIDDK NIH HHS [DK42596] NR 156 TC 164 Z9 166 U1 0 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD NOV PY 1996 VL 199 IS 11 BP 2345 EP 2358 PG 14 WC Biology SC Life Sciences & Biomedicine - Other Topics GA VR637 UT WOS:A1996VR63700001 PM 9114500 ER PT J AU Jia, GQ Gonzalo, JA Lloyd, C Kremer, L Lu, L Martinez, C Wershil, BK GutierrezRamos, JC AF Jia, GQ Gonzalo, JA Lloyd, C Kremer, L Lu, L Martinez, C Wershil, BK GutierrezRamos, JC TI Distinct expression and function of the novel mouse chemokine monocyte chemotactic protein-5 in lung allergic inflammation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TRANSGENIC MICE; LYMPHOCYTE; CELLS; GENE; IDENTIFICATION; INTERLEUKIN-5; ENDOTHELIUM; EOSINOPHIL; DISEASE; CLONING AB We have cloned a novel mouse CC chemokine cDNA from the lung during an allergic inflammatory reaction. The protein encoded by this cDNA is chemotactic for eosinophils, monocytes, and lymphocytes in vitro and in vivo. Based on its similarities in sequence and function with other CC chemokines, we have named it mouse monocyte chemotactic protein-5 (mMCP-5). Under noninflammatory conditions, expression of mMCP-5 in the lymph nodes and thymus is constitutive and is generally restricted to stromal cells. Neutralization of mMCP-5 protein with specific antibodies during an allergic inflammatory reaction in vivo resulted in a reduction in the number of eosinophils that accumulated in the lung. Moreover, mMCP-5 mRNA expression in vivo is regulated differently from that of other major CC chemokines in the lung during the allergic reaction, including Eotaxin. The presence of lymphocytes is essential for expression of mMCP-5 by alveolar macrophages and smooth muscle cells in the lung, and the induction of mMCP-5 RNA occurs earlier than that of the eosinophil chemokine Eotaxin during allergic inflammation. In contrast to Eotaxin, mRNA for mMCP-5 can be produced by mast cells. From these results, we postulate that mMCP-5 plays a pivotal role during the early stages of allergic lung inflammation. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES INC,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. UNIV AUTONOMA MADRID,CSIC,CTR NACL BIOTECNOL,DEPT IMMUNOL,E-28049 MADRID,SPAIN. CHILDRENS HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02115. RI Kremer, Leonor/L-5445-2015 OI Kremer, Leonor/0000-0002-2235-2010 FU NHLBI NIH HHS [HL-148675-02]; NIDDK NIH HHS [DK1543, DK33506]; Wellcome Trust [087618] NR 39 TC 66 Z9 68 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1996 VL 184 IS 5 BP 1939 EP 1951 DI 10.1084/jem.184.5.1939 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VT694 UT WOS:A1996VT69400033 PM 8920881 ER PT J AU Rosowsky, A Mota, CE Queener, SF AF Rosowsky, A Mota, CE Queener, SF TI Brominated trimetrexate analogues as inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase SO JOURNAL OF HETEROCYCLIC CHEMISTRY LA English DT Article ID LIPID-SOLUBLE ANTIFOLATE; TRIMETHOPRIM-SULFAMETHOXAZOLE; POTENTIAL ANTIPNEUMOCYSTIS; PIRITREXIM; PNEUMONIA; AIDS; ANTITOXOPLASMA; LEUCOVORIN; TRIAL AB Five previously undescribed trimetrexate analogues with bulky 2'-bromo substitution on the phenyl ring were synthesized in order to assess the effect of this structure modification on dihydrofolate reductase inhibition. Condensation of 2-[2-(2-bromo-3,4,5-trimethoxyphenyl)ethyl]-1,1-dicyanopropene with sulfur in the presence of N,N-diethylamine afforded 2-amino-5-(2'-bromo-3',4',5'-trimethoxybenzyl)-4-methylthiophene-3-carbonitrile (15) and 2-amino-4-[2-(2'-bromo-3',4',5'-trimethoxyphenyl)ethyl]thiophene-3-carbonitrile(16). Further reaction with chloroformamidine hydrochloride converted 15 and 16 into 2,4-diamino-5-(2'-bromo-3',4',5'-trimethoxybenzyl)-4- methylthieno[2,3-d]pyrimidine (8a) and 2,4-diamino-4-[2-(2'-bromo-3',4',5'-trimethoxyphenyl)ethylthieno [2,3-d]pyrimidine (12) respectively. Other analogues, obtained by reductive coupling of the appropriate 2,4-diaminoquinazoline-6 (or 5)-carbonitriles with 2-bromo-3,4,5-trimethoxyaniline, were 2,4-diamino-6-(2'-bromo-3',4',5'-trimethoxyanilinomethyl)-5- chloroquinazoline (9a), 2,4-diamino-5-(2'-bromo-3',4',5'-trimethoxyanilinomethyl) quinazoline (10), and 2,4-diamino-6-(2'-bromo-3',4',5'-trimethoxyanilinomethyl) quinazoline (11). Enzyme inhibition assays revealed that space-filling 2'-bromo substitution in this limited series of dicyclic 2,4-diaminopyrimidines with a 3',4',5'-trimethoxyphenyl side chain and a CH2, CH2CH2, or CH2NH bridge failed to improve species selectivity against either P. carinii or T. gondii dihydrofolate reductase relative to rat liver dihydrofolate reductase. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. INDIANA UNIV,SCH MED,DEPT PHARMACOL & TOXICOL,INDIANAPOLIS,IN 46202. RP Rosowsky, A (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 36 TC 18 Z9 18 U1 0 U2 1 PU HETERO CORPORATION PI ODESSA PA PO BOX 993, ODESSA, FL 33556-0993 SN 0022-152X J9 J HETEROCYCLIC CHEM JI J. Heterocycl. Chem. PD NOV-DEC PY 1996 VL 33 IS 6 BP 1959 EP 1966 PG 8 WC Chemistry, Organic SC Chemistry GA WE320 UT WOS:A1996WE32000065 ER PT J AU Leivo, I Tani, T Laitinen, L Bruns, R Kivilaakso, E Lehto, VP Burgeson, RE Virtanen, I AF Leivo, I Tani, T Laitinen, L Bruns, R Kivilaakso, E Lehto, VP Burgeson, RE Virtanen, I TI Anchoring complex components laminin-5 and type VII collagen in intestine: Association with migrating and differentiating enterocytes SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE anchoring complex; basement membrane; cell adhesion; collagen; enterocyte differentiation; hemidesmosome; immunohistochemistry; integrin; intestine; laminin ID CRYPT-VILLUS AXIS; BASEMENT-MEMBRANE ADHESION; A-CHAIN ISOFORMS; EPITHELIAL-CELLS; ALPHA-6-BETA-4 INTEGRIN; EPIDERMOLYSIS-BULLOSA; MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; SCATTER FACTOR; MOUSE STOMACH AB Anchoring complex component laminin-5 and its subunits laminin (Ln)-alpha 3 and Ln-beta 3 chains, Type VII collagen, and integrin chains alpha 3, alpha 6, and beta 4 were studied in developing and adult human intestine and compared with findings on Ln-alpha 1 and Ln-alpha 2 chains. In adult human duodenum, jejunum, and ileum, Ln-5 detected with a polyclonal antiserum and Ln-alpha 3 and Ln-beta 3 chains, detected with monoclonal antibodies (MAbs), were restricted to the epithelial basement membranes (BMs) of villi, whereas Ln-alpha 2 chain was seen only focally in crypt bottoms. In double labeling experiments, the stretch of crypt BM corresponding to the proliferative cell compartment was found to be devoid of both Ln-alpha 3 and Ln-alpha 2 chains. Double labeling for Ln-5 and proliferating cell nuclear antigen also showed an abrupt onset of Ln-5 expression exactly at the upper edge of the proliferative cell compartment, Type VII collagen was negligible in duodenum and showed a rising duodenal-ileal gradient localizing to villar BMs, Double labeling for Ln-5 and Type VII collagen, however, indicated only partial co-distribution in the intestine. Electron microscopy of ileum revealed both anchoring filaments and anchoring fibrils but no hemidesmosomal plaques. Our results demonstrate the expression of Ln-5 in BMs outside of stratified epithelia and indicate that Ln-5 in the intestine is associated with the compartment of migrating and differentiating enterocytes. Absence of hemidesmosomes and the presence of other anchoring complex components, such as Ln-5, Type VII collagen, and integrin chains alpha 3, alpha 6, and beta 4, suggests unique properties for epithelial cell attachment in the intestine. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. UNIV HELSINKI,DEPT ANAT,INST BIOMED,FIN-00014 HELSINKI,FINLAND. UNIV HELSINKI,CENT HOSP,DEPT SURG 2,HELSINKI,FINLAND. UNIV OULU,BIOCTR,OULU,FINLAND. UNIV OULU,DEPT PATHOL,OULU,FINLAND. NR 63 TC 51 Z9 51 U1 0 U2 1 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD NOV PY 1996 VL 44 IS 11 BP 1267 EP 1277 PG 11 WC Cell Biology SC Cell Biology GA VR657 UT WOS:A1996VR65700008 PM 8918902 ER PT J AU Carrera, AC Calvo, V Borlado, LR Paradis, H Alemany, S Roberts, TM Martinet, C AF Carrera, AC Calvo, V Borlado, LR Paradis, H Alemany, S Roberts, TM Martinet, C TI The catalytic domain of pp56(lck) but not its regulatory domain, is sufficient for inducing IL-2 production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TYROSINE-PROTEIN-KINASE; T-CELL ACTIVATION; ANTIGEN RECEPTOR; SIGNAL TRANSDUCTION; SH3 DOMAINS; THYMOCYTE DEVELOPMENT; BIOLOGICAL FUNCTION; NUCLEAR FACTOR; MUTANT MICE; P56LCK AB The lymphoid src kinase pp56(lck) has been shown to be essential for the induction of different T lymphocyte responses, including CD4-mediated enhancement of Ag-induced T cell activation, early T cell differentiation, induction of IL-2 production, and cytotoxicity, It is assumed that pp56(lck) acts on these processes by phosphorylating substrates. However, it has been recently reported that the NH2 regulatory domain is sufficient to mediate CD4 accessory function. In this report we address the contribution of the regulatory and catalytic domains of pp56(lck) to another function of this enzyme independent of CD4: TCR-induced IL-2 production. Two pp56(lck) mutants lacking either the entire catalytic domain or the entire NH2 regulatory domain were generated, and their abilities to trigger transactivation of the TCR-regulated nuclear factor of activated T cells (NF-AT) region of the IL-2 promoter were compared, Only the catalytic, but not the NH2 regulatory, domain of pp56(lck) was able to induce NF-AT region transactivation on its own and to cooperate with other intracellular signals to trigger this response, Moreover, the catalytic domain of pp56(lck) was able to induce IL-2 cytokine production to an extent similar to that of wild-type pp56(lck). We conclude that different domains of the pp56(lck) molecule contribute to regulate distinct biologic functions. In fact, while the NH2 regulatory domain is sufficient to mediate CD4 accessory function, we show here that the catalytic domain of pp56(lck) is sufficient for induction of IL-2 production, mimicking TCR ligation. C1 UNIV AUTONOMA MADRID,CSIC,INST INVEST BIOMED,MADRID 28049,SPAIN. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT CELLULAR & MOL BIOL,BOSTON,MA 02115. RP Carrera, AC (reprint author), UNIV AUTONOMA MADRID,CTR NACL BIOTECNOL,DEPT IMMUNOL & ONCOL,CAMPUS CANTOBLANCO,MADRID 28049,SPAIN. RI Alemany, Susana/J-6307-2014; Calvo, Victor/L-5024-2014; OI Calvo, Victor/0000-0002-5913-7058; Carrera, Ana/0000-0002-3999-5434; alemany, susana/0000-0002-4089-7620 NR 45 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1996 VL 157 IS 9 BP 3775 EP 3782 PG 8 WC Immunology SC Immunology GA VP227 UT WOS:A1996VP22700002 PM 8892605 ER PT J AU Zhang, CH Ao, ZH Seth, A Schlossman, SF AF Zhang, CH Ao, ZH Seth, A Schlossman, SF TI Mitochondrial membrane protein defined by a novel monoclonal antibody is preferentially detected in apoptotic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; DNA FRAGMENTATION; DEATH; EXPRESSION; BCL-2; IDENTIFICATION; ANTIGENS; NUCLEAR; DEGRADATION; THYMOCYTES AB Studies toward the biologic and molecular understanding of programmed cell death have been stimulated by the recent identification of genes and their products that regulate apoptosis. A panel of mAbs has been raised against dying cells in the present study by immunizing mice with apoptotic Jurkat cells. One of these Abs, anti-7A6, was found to react with apoptotic cells. Using ELISA or flow cytometry, little reactivity of anti-7A6 was observed in normal or desitonin-permeabilized human peripheral blood lymphocytes and a number of hemopoietic cell lines tested. The Ab, however, strongly reacted with these cells when they were induced to undergo apoptosis by irradiation or treatment with apoptosis-inducing agents, Cell sorting and DNA fragmentation experiments revealed that 7A6-positive cells, but neat 7A6-negative cells, had apparent DNA fragments characteristic of cells undergoing apoptosis. By immunoblot, under reducing conditions, anti-7A6 detected a 38-KDa protein band in the cell lysates prepared from apoptotic cells; Immunoelectron microscopy showed the 7A6 Ag to be localized to the membrane of mitochondria in apoptotic jurkat cells. These results indicate that anti-7A6 defines a novel epitope on the mitochondrial membrane protein that appears to he exposed on cells undergoing apoptosis, suggesting that the 7A6 molecule may be involved in the molecular cascade of apoptotic cell death. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. RP HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV TUMOR IMMUNOL, 44 BINNEY ST, BOSTON, MA 02115 USA. FU NIAID NIH HHS [AI 12069] NR 42 TC 224 Z9 241 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1996 VL 157 IS 9 BP 3980 EP 3987 PG 8 WC Immunology SC Immunology GA VP227 UT WOS:A1996VP22700028 PM 8892631 ER PT J AU Vlock, DR Andersen, J Kalish, LA Johnson, JT Kirkwood, JM Whiteside, T Herberman, RB Adams, GS Oken, MM Haselow, RE AF Vlock, DR Andersen, J Kalish, LA Johnson, JT Kirkwood, JM Whiteside, T Herberman, RB Adams, GS Oken, MM Haselow, RE TI Phase II trial of interferon-alpha in locally recurrent or metastatic squamous cell carcinoma of the head and neck: Immunological and clinical correlates SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE interferon-alpha; head and neck cancer ID HUMAN-LEUKOCYTE INTERFERON; COOPERATIVE-ONCOLOGY-GROUP; PULSE THERAPY SCHEDULE; RANDOMIZED TRIAL; CANCER; CHEMOTHERAPY; RADIOTHERAPY; CISPLATIN; METHOTREXATE; COMBINATION AB The objective of this study was to study the antitumor, host toxicity, and immunomodulatory effects of recombinant interferon-alpha 2b (IFN) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Seventy-one patients with recurrent or metastatic SCCHN were entered into a phase II noncomparative randomized trial of IFN at two dosage schedules. Eligible patients with histologically proven SCCHN were randomized to receive low-dose IFN, 6 x 10(6) U/m(2) daily x 3 every 4 weeks or high-dose IFN, 12 x 10(6) U/m(2), 3 x/week. Pretreatment levels of natural killer (NK) activity, CD3, CD4, CD5, CD8, CD16, CD19, CD56, DR, and the CD4/CD8 ratio were evaluated for any relationship with survival. The toxicity encountered in patients receiving low-dose IFN was for the most part mild to moderate. With high-dose IFN, toxicity was greater with significantly more episodes of grade 3 and 4 toxicity encountered. Dosage reduction was required in the majority of patients receiving high-dose IFN. Of the four lethal complications, only one was thought to be possibly associated with therapy. Of the 32 evaluable patients receiving low-dose IFN, there were 1 complete response, 1 stable disease, 24 patients with progressive disease, and 6 unevaluable. Of the 29 evaluable patients taking high-dose IFN, there were 2 complete responses, 7 with stable disease, 16 with progressive disease, and 4 patients were unevaluable. Median survival in the two arms was similar (6.2 months). Because it was postulated that a more prolonged exposure to IFN might be needed for it to be effective, patients receiving greater than or equal to 6 weeks of therapy were evaluated. Median survival in that subset was 10 and 12 months for patients receiving low- and high-dose IFN, respectively. None of the immune parameters tested was a significant predictor of survival when evaluated in all cases entered into study regardless of therapy duration. No difference in baseline NK activity was noted between patients who received < 6 or greater than or equal to 6 weeks of IFN (p = 0.90). However, among the 35 patients who received greater than or equal to 6 weeks of therapy, a high baseline NK activity was a significant predictor of the duration of survival (p = 0.04). IFN was well tolerated in patients with recurrent or metastatic SCCHN. The higher incidence of toxicity encountered in the high-dose arm could be ameliorated by reducing the dose 50%. In patients receiving 6 or more weeks of therapy, elevated baseline NK activity was associated with increases in survival, suggesting that IFN may play an immunomodulatory role. Although the overall response rates were low, disease stabilization was noted, suggesting an antiproliferative, noncytotoxic role of IFN in this group of heavily pretreated patients. C1 UNIV PITTSBURGH,PITTSBURGH CANC INST,DEPT MED,PITTSBURGH,PA. UNIV PITTSBURGH,PITTSBURGH CANC INST,DEPT PATHOL,PITTSBURGH,PA. UNIV PITTSBURGH,PITTSBURGH CANC INST,DEPT OTOLARYNGOL,PITTSBURGH,PA. UNIV MINNESOTA,DEPT OTOLARYNGOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT MED,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT RADIAT THERAPY,MINNEAPOLIS,MN 55455. DANA FARBER CANC INST,BOSTON,MA 02115. EASTERN COOPERAT ONCOL GRP,BOSTON,MA. FU NCI NIH HHS [5U10CA39229, 5U10CA24598] NR 32 TC 23 Z9 23 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV PY 1996 VL 19 IS 6 BP 433 EP 442 DI 10.1097/00002371-199611000-00008 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA WH308 UT WOS:A1996WH30800008 PM 9041463 ER PT J AU Burgeson, RE Champliaud, MF Amano, S Gerecke, DR Rousselle, P Keene, DR Leivo, I Hudson, D Milbury, C AF Burgeson, RE Champliaud, MF Amano, S Gerecke, DR Rousselle, P Keene, DR Leivo, I Hudson, D Milbury, C TI Structural macromolecules of the basement membrane zone. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 1996 VL 107 IS 5 BP 4 EP 4 PG 1 WC Dermatology SC Dermatology GA VN440 UT WOS:A1996VN44000030 ER PT J AU Uitto, J Burgeson, RE Christiano, AM Moshell, AN AF Uitto, J Burgeson, RE Christiano, AM Moshell, AN TI Symposium on epidermolysis bullosa: Molecular genetics of the cutaneous basement membrane zone, Jefferson Medical College, Philadelphia, Pennsylvania, April 29 and 30, 1996 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT CUTANEOUS BIOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT BIOCHEM,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT MOL PHARMACOL,PHILADELPHIA,PA 19107. MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. HARVARD UNIV,COLL MED,DEPT DERMATOL,BOSTON,MA. COLUMBIA UNIV,DEPT DERMATOL,NEW YORK,NY 10027. NIAMSD,BETHESDA,MD 20892. RP Uitto, J (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT DERMATOL,PHILADELPHIA,PA 19107, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 1996 VL 107 IS 5 BP 787 EP 788 DI 10.1111/1523-1747.ep12371847 PG 2 WC Dermatology SC Dermatology GA VN440 UT WOS:A1996VN44000025 PM 8875967 ER PT J AU Goldfinger, SM Schutt, RK Seidman, LJ Turner, WM Penk, WE Tolomiczenko, GS AF Goldfinger, SM Schutt, RK Seidman, LJ Turner, WM Penk, WE Tolomiczenko, GS TI Self-report and observer measures of substance abuse among homeless mentally ill persons in the cross-section and over time SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article; Proceedings Paper CT Eastern-Sociological-Society Annual Meeting CY MAR 17-20, 1994 CL BALTIMORE, MD SP E Sociol Soc ID ADDICTION SEVERITY INDEX; USE DISORDERS; PSYCHIATRIC-INPATIENTS; RELIABILITY; ALCOHOL; VALIDITY; SCHIZOPHRENIA; DIAGNOSIS; INTERVIEW; HISTORY AB The comparability of self-report and observer measures of substance abuse among 118 homeless mentally ill persons was assessed using cross-sectional and longitudinal measures. Possible correlates of nondisclosure were identified from demographic variables and clinical indicators. Lifetime abuse reported at baseline was a sensitive predictor of subsequent abuse. behavior in the project, but cross-sectional measures based only on self-report or observer ratings failed to identify many abusers. A total of 17% of the subjects never disclosed abuse that was observed during the project. The level of substance abuse is likely to be severely underestimated among homeless mentally ill persons when only one self-report measure is used at just one point in time. This problem can, however, largely be overcome by incorporating information from observers and from multiple follow-ups or by focusing on Lifetime rather than current abuse. We also conclude that underreporting may bias estimates of some correlates of substance abuse. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. UNIV MASSACHUSETTS,DEPT SOCIOL,BOSTON,MA 02125. EDITH NOURSE ROGERS MEM VET HOSP,BEDFORD,MA. UNIV TORONTO,CLARKE INST PSYCHIAT,TORONTO,ON,CANADA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. RP Goldfinger, SM (reprint author), MASSACHUSETTS MENTAL HLTH CTR,74 FENWOOD RD,BOSTON,MA 02116, USA. FU NIMH NIH HHS [1R18-MH4808001] NR 37 TC 47 Z9 47 U1 2 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 1996 VL 184 IS 11 BP 667 EP 672 DI 10.1097/00005053-199611000-00003 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VW027 UT WOS:A1996VW02700003 PM 8955679 ER PT J AU Alterman, AI Rutherford, MJ Cacciola, JS McKay, JR Woody, GE AF Alterman, AI Rutherford, MJ Cacciola, JS McKay, JR Woody, GE TI Response to methadone maintenance and counseling in antisocial patients with and without major depression SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID ADDICTION SEVERITY INDEX; PERSONALITY-DISORDER; SUBSTANCE-ABUSERS; RELIABILITY; ALCOHOLICS; VALIDITY AB This study compared the treatment response of four groups of psychiatrically diverse opiate-dependent, methadone maintenance patients receiving drug counseling. The four groups were patients with no other nonsubstance abuse axis I psychiatric diagnoses (OF only; N = 65), patients with lifetime major depression (DEP; N = 60), patients with both antisocial personality disorder and Lifetime major depression (APD+DEP; N = 35), and patients with only APD (APD only; N = 24). Patients were assessed at intake, during treatment, and 7 months after treatment admission. No statistically significant differences were found among the groups in treatment retention/attendance. Few significant group differences were revealed during-treatment urine screens, except that barbiturate use was more common for the APD only group. The APD only group also had significantly more positive urine screens for benzodiazepines than the other three groups at 7-month follow-up. All groups reported considerable improvement in problem level at 7 months compared with admission status. The APD only group reported fewer gains in legal and employment problems than the other groups but reported greater improvement in the drug area. Thus, there was some limited support for a prior finding, based on individual psychotherapy, that the treatment response of APD only patients was inferior to that of APD+DEP patients or non-APD patients. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. FU NIDA NIH HHS [DA05858, DA05186] NR 18 TC 38 Z9 38 U1 2 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 1996 VL 184 IS 11 BP 695 EP 702 DI 10.1097/00005053-199611000-00007 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VW027 UT WOS:A1996VW02700007 PM 8955683 ER PT J AU Frim, DM Wollman, L Evans, AB Ojemann, RG AF Frim, DM Wollman, L Evans, AB Ojemann, RG TI Acute pulmonary edema after low-level air embolism during craniotomy - Case report SO JOURNAL OF NEUROSURGERY LA English DT Article DE craniotomy; pulmonary edema; venous air embolism ID VASCULAR-PERMEABILITY; SHEEP; INJURY AB Acute pulmonary edema after a large air embolus occurring during neurosurgery is a recognized phenomenon. The authors describe the course of a 76-year-old man who presented with noncardiogenic pulmonary edema shortly after undergoing resection of a high convexity meningioma. Transthoracic Doppler sonography, however, showed no evidence of a large intraoperative emboli; the evidence for ongoing but low-magnitude air embolus included visualization of bone aspiration of irrigant before bone-edge waxing, transient intraoperative declines in end-tidal CO2 tension, and an increase of the fraction of inspired oxygen to maintain adequate saturation after removal of the craniotomy flap. There was no hemodynamic instability noted. The airspace disease was self-limited and resolved on supportive treatment after approximately 1 week, as would be expected for pulmonary edema caused by a single large intravenous air embolus. The authors present this case as the first report of pulmonary edema resulting from low-level air embolus occurring during craniotomy. This situation may go unrecognized intraoperatively but can cause the same significant postoperative morbidity as larger, more easily identified air emboli. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ANESTHESIA SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PULM CRIT CARE SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 20 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 1996 VL 85 IS 5 BP 937 EP 940 DI 10.3171/jns.1996.85.5.0937 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA VP489 UT WOS:A1996VP48900027 PM 8893735 ER PT J AU Parker, JA Coleman, RE Siegel, BA Sostman, HD McKusick, KA Royal, HD AF Parker, JA Coleman, RE Siegel, BA Sostman, HD McKusick, KA Royal, HD TI Procedure guideline for lung scintigraphy: 1.0 SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE lung scintigraphy; pulmonary embolism; practice guidelines C1 BETH ISRAEL HOSP,BOSTON,MA 02215. DUKE UNIV,MED CTR,DURHAM,NC. WASHINGTON UNIV,MED CTR,MALLINCKRODT INST RADIOL,ST LOUIS,MO 63110. NEW YORK HOSP,CORNELL MED CTR,NEW YORK,NY 10021. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 29 Z9 30 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 1996 VL 37 IS 11 BP 1906 EP 1910 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VR846 UT WOS:A1996VR84600045 PM 8917201 ER PT J AU Groer, MW OConnor, B Droppleman, PG AF Groer, MW OConnor, B Droppleman, PG TI A course in health care spirituality SO JOURNAL OF NURSING EDUCATION LA English DT Article C1 EASTERN MICHIGAN UNIV,YPSILANTI,MI 48197. UNIV TENNESSEE,KNOXVILLE,TN. COLL NURSING,KNOXVILLE,TN. RP Groer, MW (reprint author), MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114, USA. NR 0 TC 4 Z9 4 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0148-4834 J9 J NURS EDUC JI J. Nurs. Educ. PD NOV PY 1996 VL 35 IS 8 BP 375 EP 377 PG 3 WC Nursing SC Nursing GA WQ918 UT WOS:A1996WQ91800007 PM 8923314 ER PT J AU Urban, SD Keith, DA Goodman, M AF Urban, SD Keith, DA Goodman, M TI Hyalinizing clear cell carcinoma: Report of a case SO JOURNAL OF ORAL PATHOLOGY & MEDICINE LA English DT Article DE clear cell; hyalinizing clear cell carcinoma; minor salivary gland ID MINOR SALIVARY-GLANDS; TUMORS AB Hyalinizing clear cell carcinoma (HCCC) is a recently described low-grade malignant neoplasm of minor salivary glands. Of the thirteen reported patients with this neoplasm. the majority have occurred in the oral cavity of elderly women. We report another case and add further supporting evidence that hyalinizing clear cell carcinoma is a distinct pathological entity. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH DENT MED,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. NR 10 TC 16 Z9 17 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0904-2512 J9 J ORAL PATHOL MED JI J. Oral Pathol. Med. PD NOV PY 1996 VL 25 IS 10 BP 562 EP 564 DI 10.1111/j.1600-0714.1996.tb01732.x PG 3 WC Dentistry, Oral Surgery & Medicine; Pathology SC Dentistry, Oral Surgery & Medicine; Pathology GA VY572 UT WOS:A1996VY57200008 PM 8986969 ER PT J AU Miller, TL Lang, P Liberthson, R Grillo, HC Israel, EJ AF Miller, TL Lang, P Liberthson, R Grillo, HC Israel, EJ TI Upper gastrointestinal hemorrhage as a late complication of congenital heart disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PEDIAT CARDIOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,GEN THORAC SURG UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SERV PEDIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIDDK NIH HHS [T32-DK 07477, F32 DK 08518] NR 8 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD NOV PY 1996 VL 23 IS 4 BP 452 EP 456 DI 10.1097/00005176-199611000-00017 PG 5 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA VV652 UT WOS:A1996VV65200017 PM 8956186 ER PT J AU Tubergen, DG Stewart, CF Pratt, CB Zamboni, WC Winick, N Santana, VM Dryer, ZA Kurtzberg, J Bell, B Grier, H Vietti, TJ AF Tubergen, DG Stewart, CF Pratt, CB Zamboni, WC Winick, N Santana, VM Dryer, ZA Kurtzberg, J Bell, B Grier, H Vietti, TJ TI Phase I trial and pharmacokinetic (PK) and pharmacodynamics (PD) study of topotecan using a five-day course in children with refractory solid tumors: A pediatric oncology group study SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE phase I; topotecan; children; solid tumors; pharmacokinetics; pharmacodynamics ID 24-HOUR CONTINUOUS-INFUSION; INHIBITOR TOPOTECAN; ACUTE-LEUKEMIA AB Purpose: A phase I trial was conducted in children with refractory solid tumors to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics, and pharmacodynamics for topotecan administered by a 30-min infusion for 5 consecutive days. Patients and Methods: Forty children with a variety of recurrent solid tumors, including nine patients with neuroblastoma and 10 with brain tumors, were given topotecan as a 30-min infusion for 5 consecutive days, beginning with a dose of 1.4 mg/m(2)/day. The dose was escalated in 20% increments after establishing that DLT was not present at the prior dose. Drug toxicity was graded using standard criteria. Dose-limiting toxicity was defined as grade 3 or 4 nonhematopoietic toxicity or grade 4 hematopoietic toxicity lasting >7 days. Pharmacokinetic studies were performed during the first infusion course. Results: The DLT was hematopoietic and involved both platelets and neutrophils. Grade 4 hematopoietic toxicity of brief duration was seen at all dose levels. Over half of the patients received red blood cell transfusion support, and 19/40 received platelet transfusions. Hospital admissions for fever and neutropenia or for documented infections occurred in 32 of 169 courses of therapy. Gastrointestinal symptoms with nausea and vomiting or diarrhea were mild to moderate in 12 of the 40 patients. Antitumor responses were seen in three patients with neuroblastoma. An additional four patients (one with neuroblastoma, two with anaplastic astrocytomas, one with Ewing) had stable disease with continued therapy for >6 months. Using a limited sampling model, pharmacokinetic studies were performed in 36 of the 40 patients. Topotecan lactone and total clearance were similar to those reported in other pediatric populations receiving topotecan by continuous infusion. A pharmacodynamic relation between systemic exposure to topotecan lactone and myelosuppression was observed. Conclusions: In heavily pretreated children, the MTD for topotecan given by intermittent 30-min infusion for 5 days is 1.4 mg/m(2) without GCSF and 2.0 mg/m(2)/day with GCSF. The dose-limiting toxicity is hematopoietic. Data from this study provide the basis for further studies of topotecan in children with cancer. C1 UNIV TEXAS, MD ANDERSON CANC CTR, HOUSTON, TX USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. UNIV TEXAS, SW MED CTR, DALLAS, TX USA. BAYLOR COLL MED, HOUSTON, TX 77030 USA. DUKE UNIV, MED CTR, DURHAM, NC USA. EMORY UNIV, SCH MED, ATLANTA, GA USA. HARVARD UNIV, CHILDRENS HOSP, DANA FARBER CANC INST, BOSTON, MA 02115 USA. WASHINGTON UNIV, SCH MED, ST LOUIS, MO USA. FU NCI NIH HHS [CA-29691, CA-57745, CA-03161] NR 20 TC 109 Z9 109 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD NOV PY 1996 VL 18 IS 4 BP 352 EP 361 DI 10.1097/00043426-199611000-00004 PG 10 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA VN840 UT WOS:A1996VN84000004 PM 8888741 ER PT J AU Simpson, BB Reynolds, EM Kim, SH Ferguson, WS GraemeCook, F Doody, DP AF Simpson, BB Reynolds, EM Kim, SH Ferguson, WS GraemeCook, F Doody, DP TI Infantile intestinal leiomyosarcoma: Surgical resection (without adjuvant therapy) for cure SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE leiomyosarcoma; intestinal ID PROGNOSTIC FACTORS; SMALL BOWEL; CHILDHOOD; COLON AB A 7-week-old boy presented with a 6-week history of failure to thrive, acute intestinal obstruction, and an apparently irreducible intussusception (noted on contrast enema). He underwent abdominal exploration, during which a cecal mass was identified and resected. The mass proved to be a leiomyosarcoma. Histologically, it was an intermediate-grade malignancy with a predicted 5-year survival rate of 16% to 23% based on data from the adult experience. Three years after resection and without having received adjuvant therapy, he is healthy and free of disease. A review of the literature showed that in infants these tumors are predominantly colonic, compared with the predilection for small intestinal lesions found in the older pediatric and adult populations. Infantile intestinal leiomyosarcomata are rare malignancies that do well if complete surgical excision of the disease can be accomplished. The histological prognostic indicators proposed for intestinal leiomyosarcomas in the adult population cannot be extrapolated to infants because when they occur in infants, they appear to be less aggressive, and these patients do well without adjuvant therapy. Copyright (C) 1996 by W.B. Saunders Company C1 MASSACHUSETTS GEN HOSP,DEPT PEDIAT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT HEMATOL ONCOL,BOSTON,MA 02114. NR 22 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD NOV PY 1996 VL 31 IS 11 BP 1577 EP 1580 DI 10.1016/S0022-3468(96)90184-0 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA VT142 UT WOS:A1996VT14200027 PM 8943129 ER PT J AU Petit, MDA Stashenko, P AF Petit, MDA Stashenko, P TI Extracts of periodontopathic microorganisms lack functional superantigenic activity for murine T cells SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE periodontopathic microorganisms; superantigens; T cells ID STAPHYLOCOCCAL-ENTEROTOXIN-B; CHRONIC ADULT PERIODONTITIS; BLOOD MONONUCLEAR-CELLS; HEAT-SHOCK PROTEIN; PORPHYROMONAS-GINGIVALIS; BASIC-PROTEIN; DISEASE; ANTIGEN; CLONES; LYMPHOCYTES AB Products of periodontopathic bacteria exert immunomodulatory effects on various lymphoid cell populations, some of which have been implicated in the pathogenesis of periodontitis. It has recently been suggested that some of these bacterial products may possess superantigenic (SAg) activity. SAg bind simultaneously to the V-beta chain of T cell receptors and to class II major histocompatibility complex molecules, thereby activating as many as 35% of T cells to proliferate and produce cytokines. In order to examine this question, the proliferation of splenic and thymic T cells from immunologically naive, 3-6-wk-old Balb/c (H-2(d)), C57BL/6 (H-2(b)) and C3H/HeJ (H-2(k)) mice was assessed in response to sonic extracts of periodontopathogens. Laboratory and/or reference strains of a.o. Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and Prevotella nigrescens were used as stimulants. Staphylococcal enterotoxin B (SEE), a known superantigen, was utilized as a positive control. Unfractionated spleen cells responded to several of the tested preparations of the different bacteria, as well as to SEE, Con A and Escherichia coli LPS. Thymocytes responded to Con A and SEE, but not to LPS or to any sonic extract. Spleen cells depleted of B cells by panning responded to SEE and Con A, but not to LPS and showed a reduced response to sonicates. The residual response of B cell-depleted spleen cells was reduced essentially to background by treatment with anti-Thy 1.2 + C'. Similar results were obtained in the presence of 5% added mitomycin-treated antigen presenting cells, indicating that these cells were not limiting. These results demonstrate that extracts of periodontopathic bacteria do not stimulate murine T cells in a manner consistent with superantigenic activation. C1 FORSYTH DENT CTR,DEPT CYTOKINE BIOL,BOSTON,MA 02115. RP Petit, MDA (reprint author), ACAD CTR DENT AMSTERDAM,DEPT PERIODONTOL,LOUWESWEG 1,NL-1066 EA AMSTERDAM,NETHERLANDS. NR 52 TC 11 Z9 11 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD NOV PY 1996 VL 31 IS 8 BP 517 EP 524 DI 10.1111/j.1600-0765.1996.tb00515.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VX275 UT WOS:A1996VX27500001 PM 8971649 ER PT J AU Fischman, AJ Bonab, AA Babich, JW Alpert, NM Rauch, SL Elmaleh, DR Shoup, TM Williams, SA Rubin, RH AF Fischman, AJ Bonab, AA Babich, JW Alpert, NM Rauch, SL Elmaleh, DR Shoup, TM Williams, SA Rubin, RH TI Positron emission tomographic analysis of central 5-hydroxytryptamine(2) receptor occupancy in healthy volunteers treated with the novel antipsychotic agent, ziprasidone SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID D2 DOPAMINE-RECEPTORS; SCHIZOPHRENIC-PATIENTS; PROLACTIN LEVELS; C-11 RACLOPRIDE; SERUM PROLACTIN; BRAIN DOPAMINE; DRUGS; CLOZAPINE; INVIVO; BINDING AB Ziprasidone is a novel antipsychotic agent, with high affinity for dopamine D-2 and serotonin (5-HT2) receptors in vitro and in animal models. The goal of this study was to determine the time course of 5-HT2 receptor occupancy (%RO) in healthy humans after a single p.o. dose. Positron emission tomography with the 5-HT2 ligand, [F-18]setoperone, was performed in eight male volunteers, in the drug-naive, base-line (BL) state and 4 to 18 hr after ziprasidone (40 mg). Cerebral cortical binding potential [BP, maximum number of available receptors/K-D or association rate for specific binding (k(3))/dissociation rate for specific binding (k(4))] was estimated using the cerebellum as reference. Transport rate from plasma to brain (K-1), transport rate from brain to plasma (k(2)), association rate of nonspecific binding (k(5)) and dissociation rate of nonspecific binding (k(6)) were derived by fitting cerebellar time-activity curves to a three-compartment model. Fitting of cortical data to a 4-compartment model with K-1/k(2), k(5) and k(6), fixed at cerebellar values, was used to determine k(3) and k(4). %RO was calculated using the relation: %RO = [(BPBL - BPDRUG/BPBL] x 100%. At BL, cortical parameter (mean +/- S.E.M) were: K-1 = 0.121 +/- 0.0072 ml . min(-1) . g(-1); k(2) = 0.0581 +/- 0.004 min(-1); k(3) = 0.321 +/- 0.0026 min(-1); k(4) = 0.0957 +/- 0.0059 min(-1); k(5) = 0.0147 +/- 0.00066 min(-1) and k(6) = 0.0059 +/- 0.00042 min(-1). Ziprasidone did not effect K-1, k(2), k(5) or k(6); however, k(3) was reduced and k(4) was elevated (P < .01). RO was nearly complete at 4 hr after dosing (98%) and remained elevated at 18 hr (46%). Plasma concentrations were well described by a biexponential function and decreased much more rapidly than RO. These results establish that ziprasidone has high potency for blocking 5-HT2 receptors in healthy humans; a potentially important characteristic of atypical antipsychotic agents. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD MIT,CTR EXPT PHARMACOL & THERAPEUT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA. EMORY UNIV,DEPT RADIOL,ATLANTA,GA 30322. PFIZER INC,DIV CENT RES,GROTON,CT 06340. RP Fischman, AJ (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,32 FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [T32-CA09362]; NCRR NIH HHS [RR-00088]; NIMH NIH HHS [MH 01215] NR 64 TC 59 Z9 59 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 1996 VL 279 IS 2 BP 939 EP 947 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VT122 UT WOS:A1996VT12200060 PM 8930203 ER PT J AU Szeimies, RM CalzavaraPinton, P Karrer, S Ortel, B Landthaler, M AF Szeimies, RM CalzavaraPinton, P Karrer, S Ortel, B Landthaler, M TI Topical photodynamic therapy in dermatology SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article; Proceedings Paper CT Meeting on Perspectives in Photodynamic Therapy CY FEB, 1995 CL INNSBRUCK, AUSTRIA DE aminolevulinic acid; hematoporphyrin derivative; tetrasodium-mesotetraphenyl-porphinesulfonate; photodynamic therapy; skin cancer; inflammatory skin diseases ID DELTA-AMINOLEVULINIC-ACID; 5-AMINOLEVULINIC ACID; ENDOGENOUS PORPHYRINS; PROTOPORPHYRIN-IX; SKIN TUMORS; FLUORESCENCE; CELLS; ALA; PHOTOSENSITIZATION; SENSITIZATION AB Although photodynamic therapy (PDT) was first used in the treatment of skin diseases, phase-III-clinical trials were primarily conducted for the treatment of bladder cancer, endobronchial and oesophageal carcinoma. In dermatology PDT has most extensively been used for the treatment of malignant cutaneous lesions. Up to now those patients have been treated systemically with first-generation photosensitizers. However, prolonged skin photosensitivity is a major disadvantage of this form of therapy. Topical PDT utilizing a variety of sensitizers bypass this unwanted effect. Of strong interest is 5-aminolevulinic acid (ALA), first introduced in the topical PDT of skin disorders in 1990 by Kennedy and co-workers. ALA serves as a pro-drug, i.e. the active photosensitizing compound is protoporphyrin IX which is synthesized in vivo after exogenous application of ALA. In several oncologic and non-oncologic skin conditions including non-melanoma skin cancer, premalignant conditions like actinic keratoses and in psoriasis, topical ALA-PDT showed it's effectiveness. Besides ALA, new sensitizers like benzoporphyrines and porphycenes may play a role in topical PDT. However, at the moment, there is still a need for comparative studies and standardized therapeutic protocols to define the place of topical PDT in Dermatology. C1 UNIV BRESCIA, DEPT DERMATOL, I-25125 BRESCIA, ITALY. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, WELLMAN LABS PHOTOMED, BOSTON, MA 02114 USA. RP Szeimies, RM (reprint author), UNIV REGENSBURG, DEPT DERMATOL, D-93402 REGENSBURG, GERMANY. OI calzavara-pinton, piergiacomo/0000-0002-0935-7204 NR 43 TC 66 Z9 67 U1 0 U2 5 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD NOV PY 1996 VL 36 IS 2 BP 213 EP 219 DI 10.1016/S1011-1344(96)07375-7 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WA351 UT WOS:A1996WA35100025 PM 9002264 ER PT J AU CalzavaraPinton, PG Szeimies, RM Ortel, B Zane, C AF CalzavaraPinton, PG Szeimies, RM Ortel, B Zane, C TI Photodynamic therapy with systemic administration of photosensitizers in dermatology SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article; Proceedings Paper CT Meeting on Perspectives in Photodynamic Therapy CY FEB, 1995 CL INNSBRUCK, AUSTRIA DE breast carcinoma; hematoporphyrin derivative; Kaposi's sarcoma; photodynamic therapy; photofrin; psoriasis; skin cancer ID BASAL-CELL CARCINOMA; PHOTORADIATION THERAPY; BOWENS DISEASE; SKIN; PSORIASIS; LESIONS; CANCER; LIGHT; RECURRENCE AB We have reviewed the results of clinical investigations into the use of photodynamic therapy (PDT) with intravenous injection of hematoporphyrin derivative (HpD), Photofrin (PF) and Sn-protoporphyrin (Sn-Pp) or oral administration of delta-aminolevulinic acid in the treatment of skin cancers and/or psoriasis. Bowen's disease was highly responsive, provided that adequate light and HpD or PF doses were delivered. In contrast, poor results were shown for squamous cell carcinoma, and the rates of complete response of basal cell carcinoma ranged between 0% and 100%. Treatment failures could be related to the delivery of low drug and/or light doses, but differences in the thickness and pigmentation of the treated lesions may play a relevant role. Good palliation was almost always achieved in patients affected by primary and secondary breast carcinomas, although complete eradication of tumors was very rare. PDT is a very promising treatment modality for both Mediterranean and HIV-related Kaposi's sarcoma, because it appears to be effective, can be repeated and is not associated with immunosuppressive activity or significant systemic toxicity. PDT of psoriasis with low doses of Sn-Pp, HpD or PF plus UVA light and PF plus 630 nm light proved to be effective and was associated with mild, dose-related and reversible photosensitivity. C1 UNIV REGENSBURG,DEPT DERMATOL,D-8400 REGENSBURG,GERMANY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA. RP CalzavaraPinton, PG (reprint author), BRESCIA UNIV HOSP,DEPT DERMATOL,P SPEDALI CIVILI 1,I-25125 BRESCIA,ITALY. OI calzavara-pinton, piergiacomo/0000-0002-0935-7204 NR 35 TC 38 Z9 38 U1 0 U2 2 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD NOV PY 1996 VL 36 IS 2 BP 225 EP 231 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WA351 UT WOS:A1996WA35100027 PM 9002266 ER PT J AU Fava, M Davidson, K Alpert, JE Nierenberg, AA Worthington, J OSullivan, R Rosenbaum, JF AF Fava, M Davidson, K Alpert, JE Nierenberg, AA Worthington, J OSullivan, R Rosenbaum, JF TI Hostility changes following antidepressant treatment: Relationship to stress and negative thinking SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article ID DEPRESSION RATING-SCALE; FLUOXETINE TREATMENT; PERCEIVED STRESS; ANGER ATTACKS; QUESTIONNAIRE; OUTPATIENTS AB It is unclear whether changes in hostility following treatment are primarily related to improvement in depressive symptoms or are also closely associated with reductions in negative thinking or perceived stress. We evaluated 94 outpatients with major depression before and after eight weeks of fluoxetine treatment by administering the Symptom Questionnaire (SQ) Hostility Scale, the Hamilton Rating Scale for Depression (HAM-D), the Cognitions Questionnaire (CQ) and the Perceived Stress Scale (PSS). We observed significant elevations in scores on these questionnaires in depressed patients as compared to normal controls. Following treatment with fluoxetine, there was a statistically significant reduction in scores on all four questionnaires. We observed that changes in SQ Hostility were significantly positively related to changes in both depression severity and perceived stress, with these relationships remaining significant after adjusting for gender and baseline SQ Hostility. The relationship between SQ Hostility changes and reductions in negative thinking became significant only after adjusting for gender and baseline SQ hostility. Our results suggest that the marked decrease in hostility following antidepressant treatment is related to a reduction in depressive symptoms, stress levels and negative thinking. Copyright (C) 1996 Elsevier Science Ltd. RP Fava, M (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS RES PROGRAM,BOSTON,MA 02114, USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R0IMH48483-01] NR 22 TC 25 Z9 25 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD NOV-DEC PY 1996 VL 30 IS 6 BP 459 EP 467 DI 10.1016/S0022-3956(96)00034-9 PG 9 WC Psychiatry SC Psychiatry GA WE495 UT WOS:A1996WE49500005 PM 9023789 ER PT J AU Merkel, PA Dooley, MA Dawson, DV Pisetsky, DS Polisson, RP AF Merkel, PA Dooley, MA Dawson, DV Pisetsky, DS Polisson, RP TI Interleukin-2 receptor levels in sera of patients with rheumatoid arthritis treated with sulfasalazine, parenteral gold, or placebo SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; interleukin-2; sulfasalazine; gold ID NECROSIS-FACTOR-ALPHA; DISEASE-ACTIVITY; SYNOVIAL-FLUIDS; ACTIVATION; THERAPY; CELLS; METHOTREXATE; AZATHIOPRINE; ASSOCIATION; EXPRESSION AB Objective. To evaluate the associations of soluble serum interleukin-2 receptor (sIL-2R) levels in patients with rheumatoid arthritis (RA) with clinical and laboratory measures of disease activity and the predicted response to therapy. Methods. sIL-2R levels were determined by ELISA in 137 patients with RA, not previously treated with 2nd line therapy. Patients were enrolled in a prospective, randomized, placebo controlled trial of sulfasalazine (SSZ) versus gold sodium thiomalate (GSTM), sponsored by the Cooperative Systematic Studies of Rheumatic Diseases. Using correlation analysis and regression modeling, the clinical utility of sIL-2R as a measure of disease activity and predictor of outcome was assessed. Results. 91 women and 46 men with a mean age of 51 +/- 13 years and mean duration of disease of 64 +/- 78 months participated in this study, The mean sIL-2R level in all patients with RA was markedly elevated (980 +/- 589 U/ml) compared with that in healthy control subjects (446 +/- 196 U/ml; p = < 0.0001). There was no correlation between the sIL-2R levels and the joint pain/tenderness count, either at study entry or completion. There were significant positive correlations between the baseline sIL-2R and baseline erythrocyte sedimentation rate (ESR) and between the change in sIL-2R and the change in ESR. Both a multiple linear regression model and a multiple logistic regression model showed that baseline sIL-2R levels were not predictive of clinical outcome, Conclusion, sIL-2R levels are significantly elevated in patients with active RA and correlate positively with ESR. However, these results indicate that in patients with early RA, sIL-2R levels are neither associated with standard disease activity criteria nor predictive of the response to therapy with SSZ or GSTM, even after controlling for the simultaneous effects of other important clinical variables. C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM VA HOSP,DIV RHEUMATOL & IMMUNOL,DURHAM,NC 27710. CASE WESTERN RESERVE UNIV,DEPT EPIDEMIOL & BIOSTAT,CLEVELAND,OH 44106. RP Merkel, PA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,ARTHRIT UNIT,BULFINCH 165,BOSTON,MA 02114, USA. FU NCRR NIH HHS [M01 RR01066]; NIAMS NIH HHS [AR 39162] NR 38 TC 7 Z9 7 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 1996 VL 23 IS 11 BP 1856 EP 1861 PG 6 WC Rheumatology SC Rheumatology GA VR075 UT WOS:A1996VR07500007 PM 8923356 ER PT J AU Colvett, KT Althausen, AF Bassil, B Heney, NM McGovern, FV Young, HH Kaufman, DS Zietman, AL Shipley, WU AF Colvett, KT Althausen, AF Bassil, B Heney, NM McGovern, FV Young, HH Kaufman, DS Zietman, AL Shipley, WU TI Opportunities with combined modality therapy for selective organ preservation in muscle-invasive bladder cancer SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE organ preservation; transurethral surgery; combined-modality therapy ID TRANSITIONAL-CELL-CARCINOMA; 5-YEAR FOLLOW-UP; RADICAL RADIOTHERAPY; PARTIAL CYSTECTOMY; TRANSURETHRAL RESECTION; CISPLATIN CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; SEGMENTAL RESECTION; SALVAGE CYSTECTOMY; CLINICAL-TRIAL AB Combined-modality therapy for organ preservation represents an appropriate alternative to radical surgery in the management of several malignant diseases. The standard therapy for muscle-invasive bladder cancer in the United States has been radical cystectomy. Although the sequelae of radical surgery have been ameliorated somewhat by techniques for the construction of orthotopic bladders, the ideal therapy should both cure the patient of cancer and maintain a functioning natural bladder. Years of experience in Europe and Canada with bladder preservation using radiation therapy are documented. Advances in transurethral surgery technique and in the combination of radiation and chemotherapy have led to safe and effective regimens for patients with bladder cancer. Several recent trials with combined-modality therapy have established this treatment as a viable alternative to radical cystectomy in selected patients. (C) 1996 Wiley-Liss, Inc. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL, GENITOURINARY ONCOL UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT UROL, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT MED ONCOL, BOSTON, MA 02114 USA. NR 66 TC 4 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD NOV PY 1996 VL 63 IS 3 BP 201 EP 208 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA VW032 UT WOS:A1996VW03200013 PM 8944067 ER PT J AU Stefanovich, P Matthew, HWT Toner, M Tompkins, RG Yarmush, ML AF Stefanovich, P Matthew, HWT Toner, M Tompkins, RG Yarmush, ML TI Extracorporeal plasma perfusion of cultured hepatocytes: Effect of intermittent perfusion on hepatocyte function and morphology SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID BIOARTIFICIAL LIVER; BILIRUBIN CONJUGATION; HEPATIC-FAILURE; RATS AB The most promising approaches to developing a temporary bioartificial liver support system involve incorporating cultured primary hepatocytes into an extracorporeal perfusion device. As a result, it is important to characterize both the phenotypic response of these cells during extracorporeal perfusion and the critical factors involved in maintaining differentiated cell function over extended periods of perfusion. In this study, hepatocytes cultured in a collagen sandwich configuration were connected to a rat via a hollow fiber plasma separator and perfused with plasma on line. Perfusions were either continuous for 48 hr or intermittent for up to 174 hr with 6 hr per day of extracorporeal plasma perfusion alternating with 18 hr of culture medium perfusion. During perfusion cell morphology was continuously monitored by time-lapse video microscopy. After the procedure, hepatocytes were returned to static culture and function was evaluated by measuring the rates of urea synthesis daily for 7 days. During plasma perfusion all hepatocytes accumulated cytoplasmic lipid droplets in a time dependent manner. Urea synthesis was maintained at initial levels for up to 20 hr of continuous plasma perfusion. However, urea synthesis rates were reduced by 31 and 52% after 30 and 48 hr of continuous plasma exposure, respectively. With intermittent perfusions, as well as with control cells perfused with culture medium only, urea synthesis rates did not decrease for at least 78 hr of total perfusion. There was no difference between the urea synthesis rates after 48 hr of cumulative plasma exposure time between cells subjected to continuous and intermittent plasma perfusion. These results suggest that cultured hepatocytes may be exposed to plasma for at least 20 hr with no significant reduction in liver-specific function. Furthermore, an intermittent plasma perfusion schedule can be used to divide the useful plasma perfusion time over several days with no adverse effects on cell function. (C) 1996 Academic Press, Inc. C1 SHRINERS BURNS INST, BOSTON, MA 02114 USA. RP Stefanovich, P (reprint author), MASSACHUSETTS GEN HOSP, CTR ENGN MED & SURG SERV, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK 41709]; NIGMS NIH HHS [GM 07035] NR 30 TC 26 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD NOV PY 1996 VL 66 IS 1 BP 57 EP 63 DI 10.1006/jsre.1996.0372 PG 7 WC Surgery SC Surgery GA VZ434 UT WOS:A1996VZ43400010 PM 8954832 ER PT J AU Faraone, SV Biederman, J Mennin, D Gershon, J Tsuang, MT AF Faraone, SV Biederman, J Mennin, D Gershon, J Tsuang, MT TI A prospective four-year follow-up study of children at risk for ADHD: Psychiatric, neuropsychological, and psychosocial outcome SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit hyperactivity disorder; genetics; comorbidity; follow-up ID DEFICIT HYPERACTIVITY DISORDER; SOCIAL-ADJUSTMENT INVENTORY; ATTENTION-DEFICIT; BEHAVIORAL-INHIBITION; LEARNING-DISABILITIES; FAMILIAL ASSOCIATION; ANXIETY DISORDERS; ADOLESCENTS; COMORBIDITY; PROBANDS AB Background: Attention-deficit hyperactivity disorder (ADHD) is a familial disorder that places the siblings of ADHD children at high risk for ADHD, conduct, mood, and anxiety disorders. Although the pattern of psychiatric risk has been well documented by prior family studies, neither the short- nor long-term outcome of these high-risk siblings has been prospectively examined. Objective: To document the 4-year psychiatric, psychosocial, and neuropsychological outcome of the siblings of children with ADHD. Method: DSM-III-R structured diagnostic interviews and blind raters were used to conduct a 4-year follow-up of siblings from ADHD and control families. The siblings were also evaluated for cognitive, achievement, social, school, and family functioning. Results: At follow-up, significant elevations of behavioral, mood, and anxiety disorders were found among the siblings of ADHD children. The high-risk siblings had high rates of school failure and showed evidence of neuropsychological and psychosocial dysfunction. These impairments aggregated among the siblings who had ADHD. Conclusions: The siblings of ADHD children are at high risk for clinically meaningful levels of psychopathology and functional impairment. In addition to supporting hypotheses about the familial transmission of ADHD, the results suggest that the high-risk siblings might be appropriate targets for primary preventive interventions. C1 MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. VET AFFAIRS MED CTR,BROCKTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,CAMBRIDGE,MA 02138. OI Faraone, Stephen/0000-0002-9217-3982 NR 48 TC 54 Z9 55 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 NOV PY 1996 VL 35 IS 11 BP 1449 EP 1459 DI 10.1097/00004583-199611000-00013 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA VN954 UT WOS:A1996VN95400013 PM 8936911 ER PT J AU Spencer, TJ Biederman, J Harding, M ODonnell, D Faraone, SV Wilens, TE AF Spencer, TJ Biederman, J Harding, M ODonnell, D Faraone, SV Wilens, TE TI Growth deficits in ADHD children revisited: Evidence for disorder-associated growth delays? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit hyperactivity disorder; growth; stimulants ID HYPERACTIVE-CHILDREN; PSYCHIATRIC-DISORDERS; NUTRITIONAL-STATUS; STIMULANT-DRUGS; RENAL DISEASES; METHYLPHENIDATE; CLASSIFICATION; MALNUTRITION; ADOLESCENTS; PROBANDS AB Objective: To reevaluate the hypothesis that stimulants cause growth deficits in children with attention-deficit hyperactivity disorder (ADHD). Method: Growth deficits in height and weight were examined in 124 children and adolescents with ADHD and 109 controls, using appropriate correction by age and parental height measures and attending to issues of pubertal stage, treatment, and psychiatric comorbidity. Results: Small but significant differences in height were identified between ADHD children and controls. However, height deficits were evident in early but not late adolescent ADHD children and were unrelated to use of psychotropic medications. There was no evidence of weight deficits in ADHD children relative to controls, and no relationship between measures of malnutrition and short stature was identified. Conclusions: ADHD may be associated with temporary deficits in growth in height through mid-adolescence that may normalize by late adolescence. This effect appears to be mediated by ADHD and not its treatment. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Spencer, TJ (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT ACC 725,FRUIT ST,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K20 MH01169-01] NR 47 TC 132 Z9 136 U1 0 U2 8 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 1996 VL 35 IS 11 BP 1460 EP 1469 DI 10.1097/00004583-199611000-00014 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA VN954 UT WOS:A1996VN95400014 PM 8936912 ER PT J AU Mick, E Biederman, J Faraone, SV AF Mick, E Biederman, J Faraone, SV TI Is season of birth a risk factor for attention-deficit hyperactivity disorder? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit hyperactivity disorder; seasonality; learning disability; comorbidity ID PSYCHIATRIC COMORBIDITY; LEARNING-DISABILITIES; CHILDREN; ADHD; SCHIZOPHRENIA; PERFORMANCE; PREVALENCE; RELATIVES; PATTERNS; ISSUES AB Objective: To investigate seasonal variations in the birth patterns of children with attention-deficit hyperactivity disorder (ADHD) in reference to a group of normal control children, attending to issues of comorbidity, familiality, and learning disability. Method: Subjects were boys with DSM-III-R ADHD (n = 140) and normal controls (n = 120). The ADHD children were stratified by the presence of comorbid psychiatric disorders, learning disability, and family history of ADHD, and logistic regression was used to estimate relative risks. Results: No statistically major effect for season of birth was observed in the comparison of ADHD and control children. However, significant effects were found for September births for ADHD children with learning disability (odds ratio = 5.4) and for ADHD children without psychiatric comorbidity (odds ratio = 4.5). A trend was also noted for winter births in ADHD children with learning disabilities, no psychiatric comorbidity, and positive family history for ADHD. Conclusions: These preliminary results suggest that there may be a seasonal pattern of birth for subtypes of ADHD. If season of birth serves as a proxy for the timing of seasonally mediated viral infections, it may lead to a greater understanding of the etiology and pathophysiology of ADHD. C1 MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT ACC 725,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-41314-01A2] NR 34 TC 30 Z9 30 U1 1 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 NOV PY 1996 VL 35 IS 11 BP 1470 EP 1476 DI 10.1097/00004583-199611000-00015 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA VN954 UT WOS:A1996VN95400015 PM 8936913 ER PT J AU Wilens, TE Biederman, J Abrantes, AM Spencer, TJ AF Wilens, TE Biederman, J Abrantes, AM Spencer, TJ TI A naturalistic assessment of protriptyline for attention-deficit hyperactivity disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE protriptyline; tricyclic antidepressant; attention-deficit hyperactivity disorder; comorbidity ID DOUBLE-BLIND; STIMULANT MEDICATION; CONTROLLED TRIAL; DESIPRAMINE; CHILDREN; PLACEBO; METHYLPHENIDATE; NORTRIPTYLINE; IMIPRAMINE; PLASMA AB Objective: To evaluate the potential benefit of the tricyclic antidepressant, protriptyline, in the treatment of children and adolescents with attention-deficit hyperactivity disorder (ADHD). Method: All clinic patients in an outpatient pediatric psychopharmacology unit treated with protriptyline for ADHD were monitored for response to treatment. Thirteen subjects (11 male, 2 female) were treated naturalistically with protriptyline for ADHD and were administered the ADHD Symptom Rating Scale and Clinical Global Impression of Severity (CGI-S) and Improvement (CGI-I) at baseline and while taking medication. All patients had failed to respond to at least one previous medication trial, and 46% had psychiatric comorbidity. Results: Patients received an average protriptyline dose of 17 mg (range 5 to 30 mg) for 11.5 +/- 6.8 weeks. Of the 11 patients who continued to take protriptyline for at least 4 weeks, there was a modest reduction in the ADHD symptom checklist (p < .004) and the CGI-S (p = .032). However, using a predefined criteria of response, only 45% of patients were considered positive responders. Adverse effects were prominent, with 46% of patients reporting clinically significant problems and 38% of patients discontinuing treatment because of intolerable side effects. Conclusion: These findings do not support the clinical utility of protriptyline in the routine management of complex cases of ADHD in children and adolescents. However, the usefulness in noncomorbid, medication-naive ADHD individuals remains unclear. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Wilens, TE (reprint author), MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,ACC 725,BOSTON,MA 02114, USA. FU NIMH NIH HHS [MH-K2001175A02, MH41314] NR 45 TC 14 Z9 14 U1 2 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 NOV PY 1996 VL 35 IS 11 BP 1485 EP 1490 DI 10.1097/00004583-199611000-00017 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA VN954 UT WOS:A1996VN95400017 PM 8936915 ER PT J AU Wilens, TE Biederman, J Baldessarini, RJ Geller, B Schleifer, D Spencer, TJ Birmaher, B Goldblatt, A AF Wilens, TE Biederman, J Baldessarini, RJ Geller, B Schleifer, D Spencer, TJ Birmaher, B Goldblatt, A TI Cardiovascular effects of therapeutic doses of tricyclic antidepressants in children and adolescents SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE cardiovascular; electrocardiography; tricyclic antidepressants; children; adolescents ID OBSESSIVE-COMPULSIVE DISORDER; PLASMA-LEVELS; SUDDEN-DEATH; DEPRESSED CHILDREN; CLINICAL-RESPONSE; MAJOR DEPRESSION; HEART-RATE; DESIPRAMINE; IMIPRAMINE; NORTRIPTYLINE AB Objective: Tricyclic antidepressants (TCAs) play an important role in the treatment of pediatric psychiatric disorders. Despite widespread clinical use, concerns about their possible cardiovascular risk have arisen following several published reports of sudden death associated with their use in children. Accordingly, available evidence concerning TCA-associated cardiovascular effects in children and adolescents was surveyed. Method: A systematic literature search from 1967 to 1996 identified relevant pediatric studies that evaluated cardiovascular effects of TCAs. Results: Twenty-four studies involving 730 children and adolescents given imipramine, amitriptyline, desipramine, or nortriptyline were found. TCA treatment was associated with minor increases in systolic and diastolic blood pressure, in heart rate, and in the electrocardiographic (EGG) conduction parameters PR, QRS, and QT,. Holter ECG monitoring and exercise testing also revealed minor treatment effects. Some ECG changes related to specific TCAs emerged. Few age-related ECG differences in TCA-treated children, adolescents, or adults were detected. Associations of ECG abnormalities and relatively higher serum TCA levels were found. Conclusion: TCA treatment in children and adolescents, like that in adults, is associated with cardiovascular changes of uncertain, but probably minor, clinical significance. More information is needed on the contribution of other physiological conditions on the cardiovascular system during exposure to TCAs. Guidelines for using TCAs in children and adolescents are presented. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,ADULT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT & NEUROSCI,MCLEAN DIV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DIV PEDIAT CARDIOL,BOSTON,MA 02114. WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO 63110. UNIV PITTSBURGH,WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA 15213. RP Wilens, TE (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,ACC 725,BOSTON,MA 02114, USA. FU NIMH NIH HHS [MH-01175, MH-31154, MH-47370] NR 80 TC 85 Z9 87 U1 2 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 1996 VL 35 IS 11 BP 1491 EP 1501 DI 10.1097/00004583-199611000-00018 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA VN954 UT WOS:A1996VN95400018 PM 8936916 ER PT J AU Glass, M Glass, R AF Glass, M Glass, R TI From the patient's perspective SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material RP Glass, M (reprint author), FORSYTH RES INST,JAW JOINTS & ALLIED MUSCULOSKELETAL DISORDERS FDN,140 FENWAY,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 1996 VL 127 IS 11 BP 1600 EP 1600 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VR077 UT WOS:A1996VR07700016 ER PT J AU Hersh, EV Houpt, MI Cooper, SA Feldman, RS Wolff, MS Levin, LM AF Hersh, EV Houpt, MI Cooper, SA Feldman, RS Wolff, MS Levin, LM TI Analgesic efficacy and safety of an intraoral lidocaine patch SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID ANESTHESIA AB The effectiveness of intraoral lidocaine patches was tested by asking participants to rate the pain experienced after insertions of a 25-gauge needle. Needlesticks were performed at baseline and at various time points after patch placement. Each needlestick included contact with the periosteum. Lidocaine patches achieved significantly better analgesia than the placebo within 2.5 to five minutes after placement. Drug-related side effects were minimal and venous blood levels of lidocaine were low, averaging 10 to 14 times less than those achieved with a typical injection of lidocaine plus epinephrine. The authors conclude that the lidocaine patches used in this study are effective and safe in reducing needle insertion pain in adults. C1 UNIV PENN,SCH DENT MED,DIV PHARMACOL & THERAPEUT,PHILADELPHIA,PA 19104. UNIV MED & DENT NEW JERSEY,NEW JERSEY DENT SCH,DEPT PEDIAT DENT,NEWARK,DE. VET AFFAIRS MED CTR,DENT SERV,PHILADELPHIA,PA. SUNY STONY BROOK,SCH DENT MED,DEPT GEN DENT,STONY BROOK,NY 11794. TEMPLE UNIV,SCH DENT,DEPT ORAL SURG,PHILADELPHIA,PA. RP Hersh, EV (reprint author), UNIV PENN,SCH DENT MED,DEPT ORAL SURG & PHARMACOL,4001 SPRUCE ST,PHILADELPHIA,PA 19104, USA. NR 18 TC 29 Z9 30 U1 1 U2 1 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 1996 VL 127 IS 11 BP 1626 EP 1634 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VR077 UT WOS:A1996VR07700021 PM 8952239 ER PT J AU Wheeler, ML Franz, M Barrier, P Holler, H Cronmiller, N Delahanty, LM AF Wheeler, ML Franz, M Barrier, P Holler, H Cronmiller, N Delahanty, LM TI Macronutrient and energy database for the 1995 Exchange Lists for Meal Planning: A rationale for clinical practice decisions SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID INSTRUCTION; DIET AB For more than 50 years the exchange lists have been one method of meal planning for persons with diabetes as well as for those on weight-loss regimens. Little research has been conducted, however, concerning the methodologic basis of the system or its clinical effectiveness. Justification for specific food inclusions and general food groupings for the 1995 revision of the Exchange Lists for Meal Planning is provided by a database of foods and associated energy and macronutrient values. The mean energy and macronutrient values for each of the lists and sublists (starch, fruit, milk, and vegetables from the carbohydrate group. the meat and meat substitutes group, and the fat group) closely match the mean exchange values; however. the standard deviation and range are large. Interpretation of the database provides a rationale and guidance for decision making in clinical practice when using exchanges for meal planning, recipe, and food label calculations. C1 INT DIABET CTR,MINNEAPOLIS,MN. AMER DIABET ASSOC,ALEXANDRIA,VA. AMER DIETET ASSOC,GOVERNANCE TEAM,CHICAGO,IL. EMORY CLIN,NUTR SERV,ATLANTA,GA 30322. MASSACHUSETTS GEN HOSP,DEPT DIETET,BOSTON,MA 02114. RP Wheeler, ML (reprint author), INDIANA UNIV,MED CTR,CTR DIABET RES & TRAINING,IF ROOM 122,250 UNIV BLVD,INDIANAPOLIS,IN 46202, USA. FU NIDDK NIH HHS [P-60 DK 20542] NR 28 TC 24 Z9 24 U1 0 U2 2 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD NOV PY 1996 VL 96 IS 11 BP 1167 EP 1171 DI 10.1016/S0002-8223(96)00299-4 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WD526 UT WOS:A1996WD52600009 PM 8906142 ER PT J AU Buckley, MJ AF Buckley, MJ TI I would like to be a thoracic surgeon SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material RP Buckley, MJ (reprint author), MASSACHUSETTS GEN HOSP,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 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 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD NOV PY 1996 VL 112 IS 5 BP 1135 EP 1142 DI 10.1016/S0022-5223(96)70126-5 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA VV632 UT WOS:A1996VV63200001 PM 8911309 ER PT J AU Wright, CD Wain, JC Mathisen, DJ Grillo, HC AF Wright, CD Wain, JC Mathisen, DJ Grillo, HC TI Postpneumonectomy bronchopleural fistula after sutured bronchial closure: Incidence, risk factors, and management SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 76th Annual Meeting of the American-Association-for-Thoracic-Surgery CY APR 28-MAY 01, 1996 CL SAN DIEGO, CA SP Amer Assoc Thorac Surg ID LUNG-CANCER; PNEUMONECTOMY AB Objective: Postpneumonectomy bronchopleural fistula remains a morbid complication after pneumonectomy, The incidence, risk factors, and management of postpneumonectomy bronchopleural fistula were evaluated in 256 consecutive patients who underwent pneumonectomy with a standardized suture closure of the bronchus, Methods: Pneumonectomy was performed for lung cancer in 198 cases, for other malignancy in 20 cases, and for benign causes in 38 cases, The bronchial stump was closed with interrupted simple sutures to emphasize a long, membranous wall flap, All stumps were covered by autologous tissue, Results: The incidence of postpneumonectomy bronchopleural fistula was 3.1%, Risk factors for bronchopleural fistula were the need for postoperative ventilation (p = 0.0001) and right pneumonectomy (p = 0.04), Five patients had bronchopleural fistulas as a result of pulmonary complications necessitating ventilation; the cause in the remaining three cases appeared to be technical, Reclosure was successful in five cases (mean postoperative day 12); in one case a pinhole fistula was healed by drainage alone, Two (25%) of the eight patients, who had bronchopleural fistulas died, Conclusions: Careful, sutured closure of the main bronchus with a tissue buttress after pneumonectomy yields excellent results, The most significant risk factor for bronchopleural fistula is a pulmonary complication necessitating ventilation, Contrary to previous reports, reclosure is usually successful even if performed late. RP Wright, CD (reprint author), MASSACHUSETTS GEN HOSP,GEN THORAC SURG UNITY,WARREN 1212,BOSTON,MA 02114, USA. NR 16 TC 90 Z9 105 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD NOV PY 1996 VL 112 IS 5 BP 1367 EP 1371 DI 10.1016/S0022-5223(96)70153-8 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA VV632 UT WOS:A1996VV63200054 PM 8911336 ER PT J AU Levin, LA Joseph, MP AF Levin, LA Joseph, MP TI Penetrating trauma with a meat thermometer SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID NECK TRAUMA; SELECTIVE MANAGEMENT; PHYSICAL-EXAMINATION; INJURIES; ARTERIOGRAPHY; ANGIOGRAPHY C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. RP Levin, LA (reprint author), UNIV WISCONSIN,SCH MED,DEPT OPHTHALMOL & VISUAL SCI,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 20 TC 3 Z9 3 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 NOV PY 1996 VL 41 IS 5 BP 926 EP 929 DI 10.1097/00005373-199611000-00035 PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA VR635 UT WOS:A1996VR63500037 PM 8913234 ER PT J AU Koenig, F McGovern, FJ Althausen, AF Deutsch, TF Schomacker, KT AF Koenig, F McGovern, FJ Althausen, AF Deutsch, TF Schomacker, KT TI Laser induced autofluorescence diagnosis of bladder cancer SO JOURNAL OF UROLOGY LA English DT Article DE lasers, bladder neoplasms, diagnosis, fluorescence ID INDUCED FLUORESCENCE; PAPILLARY CARCINOMA; DYSPLASIA; INSITU AB Purpose: We assessed the ability of laser induced autofluorescence to differentiate malignant from nonmalignant bladder lesions. Materials and Methods: We studied 53 patients with bladder cancer undergoing mucosal biopsies or transurethral resection of a bladder tumor. A quartz optical fiber was advanced through the working channel of a cystoscope and placed in gentle contact with the bladder. Tissue fluorescence was excited by 337 nm. light pulses (nitrogen laser). One fiber was used for transmission of the excitation and emission (fluorescence) light. An optical multichannel analyzer system was used to record fluorescence spectra of the sites of interest. Results: We analyzed the fluorescence spectra of 114 bladder areas (1 carcinoma in situ as well as 28 malignant, 35 inflammatory, 7 dysplastic, 1 squamous metaplastic and 42 normal areas). These lesions included 44 difficult to diagnose suspicious tumors (11 malignant and 33 nonmalignant). We developed an algorithm that used the I385:I455 nm. fluorescence ratio to distinguish malignant from nonmalignant lesions, including inflammatory areas. By analyzing the data on all 114 lesions, we noted the sensitivity, specificity, and positive and negative predictive values of this method for differentiating malignant from nonmalignant bladder lesions to be 97, 98, 93 and 99%, respectively. Conclusions: Under excitation with 337 nm. light a clear differentiation between malignant and nonmalignant bladder tissues can be made using the I385:I455 nm. autofluorescence ratio. C1 MASSACHUSETTS GEN HOSP,DEPT UROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Koenig, F (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,WEL 224,50 BLOSSOM ST,BOSTON,MA 02114, USA. NR 23 TC 57 Z9 59 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1996 VL 156 IS 5 BP 1597 EP 1601 DI 10.1016/S0022-5347(01)65456-9 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA VM117 UT WOS:A1996VM11700012 PM 8863546 ER PT J AU Chang, TD Dretler, SP AF Chang, TD Dretler, SP TI Laparoscopic pyelolithotomy in an ectopic kidney SO JOURNAL OF UROLOGY LA English DT Article DE kidney; calculi; laparoscopy C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. RP Chang, TD (reprint author), NO CALIF HLTH SYST,DEPT UROL SURG,MARTINEZ,CA, USA. NR 4 TC 17 Z9 17 U1 1 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 NOV PY 1996 VL 156 IS 5 BP 1753 EP 1753 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VM117 UT WOS:A1996VM11700056 PM 8863588 ER PT J AU Salamipour, H Rivitz, SM Kaufman, JA AF Salamipour, H Rivitz, SM Kaufman, JA TI Percutaneous transfemoral retrieval of a partially deployed Simon-Nitinol filter misplaced into the ascending lumbar vein SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE foreign bodies; interventional procedures, complications; venae cavae, filters ID TITANIUM GREENFIELD FILTER; VENA-CAVAL FILTERS; FOLLOW-UP C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. DEPT RADIOL,BOSTON,MA. TUFTS UNIV,SCH MED,BOSTON,MA 02111. NR 10 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD NOV-DEC PY 1996 VL 7 IS 6 BP 917 EP 919 DI 10.1016/S1051-0443(96)70870-9 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA WJ727 UT WOS:A1996WJ72700019 PM 8951760 ER PT J AU Frazier, DP Cox, D Godshalk, EM Schaffer, PA AF Frazier, DP Cox, D Godshalk, EM Schaffer, PA TI The herpes simplex virus type 1 latency-associated transcript promoter is activated through Ras and Raf by nerve growth factor and sodium butyrate in PC12 cells SO JOURNAL OF VIROLOGY LA English DT Article ID CAMP-RESPONSE ELEMENT; LONG TERMINAL REPEAT; GENE-EXPRESSION; LAT PROMOTER; SYMPATHETIC NEURONS; TRIGEMINAL GANGLION; MESSENGER-RNA; INFECTED MICE; N-BUTYRATE; C-FOS AB Herpes simples virus establishes latent infections in the nuclei of sensory neurons, These infections are characterized by the abundant expression of a series of 5' coterminal transcripts termed the latency-associated transcripts (LATs). Available evidence indicates that LAT expression is specifically regulated in latently infected neurons, Although previous studies have examined the regulation of LAT expression in neuronal and nonneuronal cells, the mechanism of regulation of LAT expression in neuronal cells in response to external factors has not been investigated, To address this question. we characterized the activity of LAT promoter fusion constructs in PC12 cells following treatment with nerve growth factor (NGF) and/or sodium butyrate (NaB), agents that affect expression of cell cycle-associated genes, Expression from the LAT promoter was induced 8- to 12-fold by either NGF or NaB alone and 40- to 60-fold when the two agents were added simultaneously. Fibroblast growth factor also induced expression from the LAT promoter but to a lesser extent than NGF, Treatment with factors such as epidermal growth factor, phorbol myristate acetate, cyclic AMP, or KCl had no significant effect on LAT promoter activity. Notably, promoter-reporter constructs containing immediate-early (ICP0 and ICP4), early (ICP8 and UL9), and late (UL10 and UL30) viral promoters were induced only two to fourfold by NGF, suggesting that the LAT promoter may be unusual among herpes simplex virus genes in the magnitude of its response to this factor, To identify pathways leading to LAT activation in vitro, we characterized the response of the LAT promoter to NGF and/or NaB in PC12-derived cell lines containing mutations in specific signal transduction pathways, We found that activation of the LAT promoter requires Ras activation and that activation of the serine/threonine kinase, Raf, is sufficient to induce LAT expression, Together, these results indicate that the LAT promoter is regulated via the Ras/Raf signal transduction pathway in response to external factors such as NGF and NaB and that LAT expression may be regulated by NGF in latently infected neurons. C1 DANA FARBER CANC INST,DIV MOL GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. FU NCI NIH HHS [R37CA20260]; NIAID NIH HHS [P01AI24010]; NIGMS NIH HHS [T32GM07196] NR 66 TC 22 Z9 22 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1996 VL 70 IS 11 BP 7424 EP 7432 PG 9 WC Virology SC Virology GA VL792 UT WOS:A1996VL79200008 PM 8892860 ER PT J AU Frazier, DP Cox, D Godshalk, EM Schaffer, PA AF Frazier, DP Cox, D Godshalk, EM Schaffer, PA TI Identification of cis-acting sequences in the promoter of the herpes simplex virus type 1 latency-associated transcripts required for activation by nerve growth factor and sodium butyrate in PC12 cells SO JOURNAL OF VIROLOGY LA English DT Article ID SYNAPSIN-I GENE; NEURON-SPECIFIC EXPRESSION; UPSTREAM REGULATORY ELEMENTS; TRANSGENIC MICE; C-FOS; LAT PROMOTER; INDUCED REACTIVATION; INVIVO REACTIVATION; SILENCER ELEMENT; CHANNEL GENE AB In the absence of detectable viral proteins, expression of the latency-associated transcripts (LATs) is likely regulated by cellular factors during latent infection of neurons with herpes simplex virus type 1. The amounts and activation states of these factors may in turn be regulated by extracellular regulatory factors. Consistent with this hypothesis, we have recently demonstrated that LAT expression is significantly enhanced by nerve growth factor (NGF) and sodium butyrate (NaB) in neurally derived PC12 cells. With the ultimate goal of identifying trans-acting cellular factors involved in regulating LAT expression during latency, we have attempted to identify the cis-acting elements to which these putative cellular factors bind by characterizing the LAT promoter and a series of 5' promoter deletion mutants in PC12 cells following treatment with the LAT-enhancing agents NGF and NaB. Transient expression assays demonstrated that distinct cis-acting sequences mediate basal and induced LAT promoter expression. Basal activity in PC12 cells is mediated by two elements: a negative regulatory element between -435 and -270 and a positive element between -240 and -204. The positive element contains binding sites for the transactivator Sp-1, whereas the negative element bears some resemblance to known neuron-specific silencer elements. In contrast to basal expression, maximum induction of the LAT promoter by NGF and NaB requires sequences between -159 and -81. Using gel mobility shift assays, we have identified three sets of protein-DNA complexes that bind to this 78-bp region and shown by competition analysis that binding is specific. The abundance and mobility of these complexes were altered by treatment with NGF or NaB. The nucleotide sequences to which these complexes bind were fine mapped by competition analysis with oligonucleotide probes containing substitution mutations. The target sequences identified exhibit no homology to binding sites of known transcription factors. These regions were critical for complex formation in vitro and for maximum induction of the LAT promoter by NGF and NaB in transient expression assays. The protein complexes that form with target sequences likely participate in the regulation of LAT expression in response to physiological stimuli in neurons in vivo. C1 DANA FARBER CANC INST,DIV MOL GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. FU NCI NIH HHS [R37CA20260]; NIAID NIH HHS [P01AI24010]; NIGMS NIH HHS [T32GM07196] NR 59 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1996 VL 70 IS 11 BP 7433 EP 7444 PG 12 WC Virology SC Virology GA VL792 UT WOS:A1996VL79200009 PM 8892861 ER PT J AU Kaur, A Daniel, MD Hempel, D LeeParritz, D Hirsch, MS Johnson, RP AF Kaur, A Daniel, MD Hempel, D LeeParritz, D Hirsch, MS Johnson, RP TI Cytotoxic T-lymphocyte responses to cytomegalovirus in normal and simian immunodeficiency virus-infected rhesus macaques SO JOURNAL OF VIROLOGY LA English DT Article ID CYTO-TOXIC LYMPHOCYTES; ALLOGENEIC BONE-MARROW; MOLECULAR-INTERACTIONS; TRANSPLANT RECIPIENTS; GENE-EXPRESSION; CELL CLONES; ANTIGENS; DISEASE; TYPE-1; RECONSTITUTION AB Disseminated cytomegalovirus (CMV) infection is a frequent occurrence in human immunodeficiency virus-infected humans and in simian immunodeficiency virus (SIV)-infected rhesus macaques. Rhesus macaques are a suitable animal model with which to study in vivo interactions between CMV and AIDS-associated retroviruses. Since cytotoxic T lymphocytes (CTL) play a major role in control of viral infections, we have characterized CMV-specific CTL responses in SIV-infected and uninfected rhesus macaques. Autologous fibroblasts infected with rhesus CMV were used to stimulate freshly isolated peripheral blood mononuclear cells from CMV-seropositive animals. Following in vitro stimulation, specific CTL activity against CMV-infected autologous fibroblasts was detected in CMV-seropositive but not in CMV-seronegative normal macaques. CMV-specific CTL activity comparable to that in normal animals was also detected in two CMV-seropositive macaques infected with a live attenuated SIV strain (SIV Delta 3) and in two of three macaques infected with pathogenic SIV strains. The CMV-specific CTL response was class I major histocompatibility complex restricted and mediated by CD8(+) cells. An early CN protein(s) was the dominant target recognized by bulk CTL, although the pattern of CTL recognition of CMV proteins varied among animals. Analysis of CMV-specific CTL responses in macaques should serve as a valuable model for CMV immunopathogenesis and will facilitate prospective in vivo studies of immune interactions between CMV and SIV in AIDS. C1 HARVARD UNIV,SCH MED,NEW ENGLAND REG PRIMATE RES CTR,DIV IMMUNOL,SOUTHBOROUGH,MA 01722. HARVARD UNIV,SCH MED,NEW ENGLAND REG PRIMATE RES CTR,DIV MICROBIOL,SOUTHBOROUGH,MA 01722. HARVARD UNIV,SCH MED,NEW ENGLAND REG PRIMATE RES CTR,DIV PRIMATE MED,SOUTHBOROUGH,MA 01722. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,AIDS RES CTR,BOSTON,MA 02115. FU FIC NIH HHS [D43TW00004]; NCRR NIH HHS [RR 00055, RR 00168] NR 48 TC 40 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1996 VL 70 IS 11 BP 7725 EP 7733 PG 9 WC Virology SC Virology GA VL792 UT WOS:A1996VL79200041 PM 8892893 ER PT J AU Poma, EE Kowalik, TF Zhu, LA Sinclair, JH Huang, ES AF Poma, EE Kowalik, TF Zhu, LA Sinclair, JH Huang, ES TI The human cytomegalovirus IE1-72 protein interacts with the cellular p107 protein and relieves p107-mediated transcriptional repression of an E2F-responsive promoter SO JOURNAL OF VIROLOGY LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; IMMEDIATE-EARLY PROTEINS; LARGE-T-ANTIGEN; 2.7-KILOBASE RNA PROMOTER; IE2 86-KILODALTON PROTEIN; BOX-BINDING-PROTEIN; EARLY REGION-2 GENE; TATA-BOX; TRANS-ACTIVATION; SUSCEPTIBILITY GENE AB The Rb-related p107 protein has been implicated as an important control element in proper cell cycle progression. The p107 protein is thought to restrict cellular proliferation in part through its interaction with the E2F family of transcription factors and is, therefore, a specific target for regulation by several DNA viruses. Here, we demonstrate that p107 protein levels are induced in a biphasic manner in human fibroblasts during productive infection by the human cytomegalovirus (HCMV). Expression patterns of p107 protein levels during HCMV infection of human embryonic lung cells (HELs) demonstrate a sustained induction from early to late times of infection. We also demonstrate that the HCMV immediate-early protein IE1-72 complexes in vivo with the p107 protein and that this interaction can be reconstituted in an in vitro system by using reticulocyte-translated protein. Our data demonstrate that the interaction between p107 and the IE1-72 protein occurs at times of infection that temporally match the second tier of p107 protein induction and the phosphorylation pattern of the IE1-72 protein. Furthermore, we show here that the ability of p107 to transcriptionally repress E2F-responsive promoters can he overcome by expression of the IE1-72 protein. This effect appears to be specific, since the IE1-72 protein is not capable of relieving Rb-mediated repression of an E2F-responsive promoter. Finally, our data demonstrate that HCMV infection can induce cellular proliferation in quiescent cells and that IE1-72 expression alone can, to a degree, drive a similar progression through the cell cycle. These data suggest that IE1-72-mediated transactivation of E2F-responsive promoters through alleviation of p107 transcriptional repression may play a key role in the cell cycle progression stimulated by HCMV infection. C1 UNIV N CAROLINA,DEPT MICROBIOL & IMMUNOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27599. DUKE UNIV,MED CTR,HOWARD HUGHES MED INST,DEPT GENET,DURHAM,NC 27710. MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. UNIV CAMBRIDGE,DEPT MED,CAMBRIDGE CB2 2QQ,ENGLAND. RP Poma, EE (reprint author), UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599, USA. FU NCI NIH HHS [CA19014]; NIAID NIH HHS [AI12717] NR 97 TC 96 Z9 98 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1996 VL 70 IS 11 BP 7867 EP 7877 PG 11 WC Virology SC Virology GA VL792 UT WOS:A1996VL79200057 PM 8892909 ER PT J AU Schaefer, BC Strominger, JL Speck, SH AF Schaefer, BC Strominger, JL Speck, SH TI A simple reverse transcriptase PCR assay to distinguish EBNA1 gene transcripts associated with type I and II latency from those arising during induction of the viral lytic cycle SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; BURKITTS-LYMPHOMA CELLS; NASOPHARYNGEAL CARCINOMA; NUCLEAR ANTIGEN-1; INFECTED LYMPHOCYTES; HODGKINS-DISEASE; INITIATION SITE; F-PROMOTER; EXPRESSION; DISTINCT AB In Epstein-Barr virus (EBV)-associated tumors that arise in immunocompetent individuals, the pattern of viral gene expression is very restricted compared with that of latently infected B cells in tissue culture. A hallmark of viral gene expression in these tumors is the exclusive expression of only one EBV encoded nuclear antigen, EBNA1, which is driven from a promoter (Qp) that lies near the junction of the viral BamHI F and Q fragments. During induction of the lytic cycle, a viral promoter, Fp, which lies ca, 200 hp upstream of Qp, gives rise to transcripts which overlap with Qp-initiated EBNA1 gene transcripts. Distinguishing between latency associated EBNA1 gene transcripts and those associated with the early phase of the viral lytic cycle is critical for correct identification of restricted viral latency. Here we describe a reverse transcriptase PCR protocol which employs a nested set of upstream primers from the BamHI Q region of the viral genome and readily distinguishes Fp-initiated transcripts from Qp-initiated transcripts. A single set of amplification conditions was used for the various PCR primer combinations, which allowed all reactions to be run simultaneously. An in vitro-generated transcript, diluted in RNA from an EBV-negative cell line, was used to demonstrate that the efficiencies of amplification with the different primer combinations were very similar. This protocol was used to demonstrate that EBNA1 gene transcription in two previously uncharacterized EBV-positive epithelial cell lines initiates from Qp. In addition, we assessed the site(s) of initiation of EBNA1 gene transcripts in cell lines exhibiting restricted viral latency. Contrary to the results of Nonkwelo et al. (J. Virol. 70:623-627, 1996), which indicated that EBNA1 gene transcription during restricted viral latency initiates at multiple sites downstream of Fp, we show here that nearly all EBNA1 transcripts start at the previously identified Qp transcription initiation site. C1 WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MOL MICROBIOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DIV MOL ONCOL,ST LOUIS,MO 63110. DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02111. OI Schaefer, Brian C/0000-0001-8877-3507 FU NCI NIH HHS [CA47554, CA58524] NR 29 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1996 VL 70 IS 11 BP 8204 EP 8208 PG 5 WC Virology SC Virology GA VL792 UT WOS:A1996VL79200102 PM 8892954 ER PT J AU Buchner, DM Cress, ME Esselman, PC Margherita, AJ deLateur, BJ Campbell, AJ Wagner, EH AF Buchner, DM Cress, ME Esselman, PC Margherita, AJ deLateur, BJ Campbell, AJ Wagner, EH TI Factors associated with changes in gait speed in older adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID PHYSICAL PERFORMANCE; FICSIT TRIALS; EXERCISE; STRENGTH; FRAILTY; WOMEN; MEN AB Background. The study addressed whether changes in gait speed in community-dwelling older adults were associated with changes in fitness (strength and aerobic capacity), physical health status, and/or depressive symptoms. Methods. The study sample comprised 152 community-dwelling adults aged 68-85 who had participated in an exercise study. Study measures at baseline and 6-month follow-up included gait speed, a leg strength score, maximal aerobic capacity (VO(2)max), CES-Depression scale, and physical health status (SIP Physical Dimension). Results. In cross-sectional regression analyses, leg strength, VO(2)max, weight, and the strength by VO(2)max interaction term were significant independent predictors of gait speed (R(2) = 26%). Based upon the observed 7% increase in VO(2)max and 8% increase in strength in the exercise groups, the regression model predicted only a 2% (1.5 m/min) increase in gait speed, which did not differ significantly from the observed increase of 0% (.32 m/min). The strongest correlate of change in gait speed was change in CES-D scores (partial R = -.37). Change in physical health status also correlated with change in gait speed (partial R = -.28), while change in fitness did not. Conclusions. The results suggest, in the range of fitness of the study sample, that changes in gait speed are related to changes in depressive symptoms and physical health status, but not to modest changes in fitness. A model assuming nonlinear relationships may be appropriate for understanding how strength and aerobic capacity affect gait speed. C1 UNIV WASHINGTON,NW PREVENT EFFECT CTR,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT REHABIL MED,SEATTLE,WA 98195. VA PUGET SOUND HLTH CARE SYST,NW CTR OUTCOMES RES OLDER ADULTS,SEATTLE,WA. JOHNS HOPKINS UNIV,DEPT PHYS MED & REHABIL,BALTIMORE,MD 21218. UNIV OTAGO,DEPT MED,DUNEDIN,NEW ZEALAND. GRP HLTH COOPERAT PUGET SOUND,CTR HLTH STUDIES,SEATTLE,WA 98101. RP Buchner, DM (reprint author), UNIV WASHINGTON,DEPT HLTH SERV,BOX 358852,SEATTLE,WA 98195, USA. FU NIA NIH HHS [R01/AG10943, UO1/AG09095]; PHS HHS [R48/CCR002181] NR 18 TC 51 Z9 52 U1 3 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 1996 VL 51 IS 6 BP M297 EP M302 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA WD352 UT WOS:A1996WD35200018 PM 8914502 ER PT J AU Nadol, JB AF Nadol, JB TI Schuknecht: ''Presbycusis'' (Laryngoscope. 1955;65:402-419) SO LARYNGOSCOPE LA English DT Article RP Nadol, JB (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTORHINOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 10 TC 2 Z9 2 U1 1 U2 3 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD NOV PY 1996 VL 106 IS 11 BP 1327 EP 1329 DI 10.1097/00005537-199611000-00004 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA VT173 UT WOS:A1996VT17300003 PM 8914895 ER PT J AU Pradhan, PS Gliklich, RE Winkelman, J AF Pradhan, PS Gliklich, RE Winkelman, J TI Screening for obstructive sleep apnea in patients presenting for snoring surgery SO LARYNGOSCOPE LA English DT Article ID HEALTH SURVEY QUESTIONNAIRE; OUTCOME MEASURE; SF-36; MORTALITY; OXIMETRY; SNORERS; INDEX AB Excessive mortality is associated with obstructive sleep apnea (OSA). Therefore it is important to diagnose OSA in patients presenting for snoring surgery. A prospective study was performed to develop screening models to detect OSA compared with universal polysomnography for sensitivity and cost. Multivariate analysis of 150 consecutive patients was based on clinical data, questionnaire data, and polysomnography, Two screening models obtained 100% sensitivity and reduced the need for polysomnograms. Cost savings of screening based on clinical data was projected to be $35 to $80 per patient using reported prevalence rates of OSA among snorers. A screening model for OSA using clinical data alone is more cost-effective than one that combines these data with pulse oximetry data, but savings over universal polysomnography were modest. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,CLIN OUTCOMES RES UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MCLEAN HOSP,SLEEP DISORDERS CTR,BELMONT,MA 02178. NR 17 TC 21 Z9 21 U1 0 U2 0 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD NOV PY 1996 VL 106 IS 11 BP 1393 EP 1397 DI 10.1097/00005537-199611000-00016 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA VT173 UT WOS:A1996VT17300015 PM 8914907 ER PT J AU Postle, BR Corkin, S Growdon, JH AF Postle, BR Corkin, S Growdon, JH TI Intact implicit memory for novel patterns in Alzheimer's disease SO LEARNING & MEMORY LA English DT Article ID ADULT OWL MONKEYS; DISCRIMINATION TASK; DOUBLE DISSOCIATION; NORMAL HUMANS; TERM-MEMORY; AMNESIA; CORTEX; MECHANISMS; RETRIEVAL; EXPLICIT AB Repetition priming is a kind of implicit memory (learning without awareness) that does not depend on the medial temporal-lobe system. For example, the amnesic patient H.M., who underwent bilateral medial temporal-lobe resection, shows intact priming with novel patterns, suggesting that perceptual priming with nonverbal material does not depend on areas critical for explicit memory, A logical candidate for the neural substrate that supports this kind of priming is the peristriate cortex, an area that is relatively spared in Alzheimer's disease (AD). We therefore predicted that AD subjects would be unimpaired on pattern priming. Subjects copied each of six target figures onto dot patterns. After performing a S-min distracter task, they were given the same dot patterns (without lines) and asked to draw the first figure that came to mind by connecting the dots with straight lines. Subsequently, in a test of recognition (explicit) memory, subjects viewed each of the six patterns of dots that they had copied previously and were asked to indicate which of four possible completions corresponded to the figure that they had copied 3 min earlier. The AD and control groups achieved comparable priming scores, but AD subjects were significantly impaired in recognizing the patterns explicitly. Our finding of intact pattern priming in AD provides, for the first time, evidence that pattern printing depends on the peristriate cortex. C1 MIT,CLIN RES CTR,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP Postle, BR (reprint author), MIT,DEPT BRAIN & COGNIT SCI,E25-618,CAMBRIDGE,MA 02139, USA. FU NCRR NIH HHS [RR00088]; NIA NIH HHS [AG08812, AG 06605] NR 50 TC 21 Z9 21 U1 2 U2 5 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD NOV-DEC PY 1996 VL 3 IS 4 BP 305 EP 312 DI 10.1101/lm.3.4.305 PG 8 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA WB803 UT WOS:A1996WB80300003 PM 10456100 ER PT J AU Frank, DA Varticovski, L AF Frank, DA Varticovski, L TI BCR/abl leads to the constitutive activation of Stat proteins, and shares an epitope with tyrosine phosphorylated Stats SO LEUKEMIA LA English DT Article DE BCR/abl; Stats; transformation; IL-3; phosphorylation ID CHRONIC MYELOGENOUS LEUKEMIA; BCR-ABL ONCOGENE; COLONY-STIMULATING FACTOR; CHRONIC MYELOID-LEUKEMIA; PHILADELPHIA-CHROMOSOME; RAS; TRANSFORMATION; INTERLEUKIN-3; KINASE; MICE AB The mechanism by which BCR/abl leads to the transformation of hematopoietic cells is not understood. The introduction of BCR/abl into BaF3 cells, an IL-3-dependent pro-lymphocytic cell line, abrogates the requirement of IL-3 for growth, Given that IL-3 leads to the phosphorylation of Stat proteins, we tested the hypothesis that BCR/abl transformation of hematopoietic cells induces the phosphorylation of Stats. We found that BaF3 cells transformed by either the p190 or p210 forms of BCR/abl possess constitutively phosphorylated Stat1 and Stat5. Phosphorylation of Stat proteins was greater in cells transformed by p190 BCR/abl than in cells transformed by p210 BCR/abl, suggesting that the magnitude of phosphorylation of Stat, proteins may play a role in the, biological effects of BCR/abl. Expression of BCR/abl containing a mutation (Y177F) that prevents its interaction with GRB2 led to a decrease in the phosphorylation of Stat1 and Stat5. This suggested that GRB2, or its binding site on BCR/abl, may participate in the phosphorylation of Stat proteins. We also observed that the antiphospho-Stat antibody directly recognized both the p190 and p210 forms of BCR/abl. This indicated that a tyrosine residue that becomes phosphorylated in BCR/abl may share homology with the tyrosine phosphorylation site of Stat1 and Stat5. These findings may have implications for the mechanisms by which BCR/abl interacts with signaling pathways to confer growth factor independence and induce transformation of hematopoietic cells. C1 TUFTS UNIV,SCH MED,ST ELIZABETHS MED CTR,DEPT BIOMED RES,BOSTON,MA 02111. TUFTS UNIV,SCH MED,ST ELIZABETHS MED CTR,DIV HEMATOL & ONCOL,BOSTON,MA 02111. RP Frank, DA (reprint author), DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [R29CA53094] NR 36 TC 116 Z9 118 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 1996 VL 10 IS 11 BP 1724 EP 1730 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA VQ581 UT WOS:A1996VQ58100010 PM 8892675 ER PT J AU Cheng, LL Lean, CL Bogdanova, A Wright, SC Ackerman, JL Brady, TJ Garrido, L AF Cheng, LL Lean, CL Bogdanova, A Wright, SC Ackerman, JL Brady, TJ Garrido, L TI Enhanced resolution of proton NMR spectra of malignant lymph nodes using magic-angle spinning SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE proton NMR; magic-angle spinning; lymph nodes; metastases ID MAGNETIC-RESONANCE SPECTROSCOPY; CELL-LINES; EX-VIVO; CANCER; MEMBRANES; MAS; DIFFERENTIATION; METABOLITE; CARCINOMA; NEOPLASIA AB Proton NMR spectroscopy has proven useful in the detection of cancer in lymph node tissue, However, due to the high fat content of this type of tissue, 2D H-1 COSY measurements (requiring acquisition times of 4-5 h or longer) are necessary to obtain the spectral information necessary for diagnosis. T-2-filtered proton magic-angle spinning (MAS) NMR spectroscopy provides 1D spectra of lymph nodes in approximately 20 min with sufficient spectral resolution allowing for identification of changes in cellular chemistry due to the presence of malignant cells. MAS data from lymph nodes of five control and six rats with mammary adenocarcinoma (R13762) demonstrated increases in the signal intensity of resonances associated primarily with lactate (delta = 4.12 ppm) P < 0.0004, creatines/lysine (delta = 3.04 ppm) P < 0.0032, and glutamate/glutamine (delta = 2.36 ppm) P < 0.0002 in metastatic compared with normal lymph nodes. The infiltration of lymph nodes by malignant cells is an important prognostic factor for many cancers. The rapid assessment of node tissue without the introduction of sampling errors (inherent in currently employed histological procedures) would allow postoperative therapy decisions to be made more efficiently. C1 MASSACHUSETTS GEN HOSP,NMR CTR,DEPT RADIOL,BIOMAT LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. RI Garrido, Leoncio/K-3092-2014; Ackerman, Jerome/E-2646-2015 OI Garrido, Leoncio/0000-0002-7587-1260; Ackerman, Jerome/0000-0001-5176-7496 NR 25 TC 136 Z9 142 U1 0 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD NOV PY 1996 VL 36 IS 5 BP 653 EP 658 DI 10.1002/mrm.1910360502 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VQ363 UT WOS:A1996VQ36300001 PM 8916014 ER PT J AU Bashir, A Gray, ML Burstein, D AF Bashir, A Gray, ML Burstein, D TI Gd-DTPA(2-) as a measure of cartilage degradation SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cartilage; arthritis; Gd-DTPA(2-); MRI ID ARTHRITIS AB Glycosaminoglycans (GAGs) are the main source of tissue fixed charge density (FCD) in cartilage, and are lost early in arthritic diseases. We tested the hypothesis that, like Na+, the charged contrast agent Gd-DTPA(2-) (and hence proton T-1) could be used to measure tissue FCD and hence GAG concentration, NMR spectroscopy studies of cartilage explants demonstrated that there was a strong correlation (r > 0.96) between proton T-1 in the presence of Gd-DTPA(2-) and tissue sodium and GAG concentrations. An ideal one-compartment electrochemical (Donnan) equilibrium model was examined as a means of quantifying FCD from Gd-DTPA(2-) concentration, yielding a value 50% less but linearly correlated with the validated method of quantifying FCD from Na+. These data could be used as the basis of an empirical model with which to quantify FCD from Gd-DTPA(2-) concentration, or a more sophisticated physical model could be developed. Spatial distributions of FCD were easily observed in T-1-weighted MRI studies of trypsin and interleukin-1 induced cartilage degradation, with good histological correlation. Therefore, equilibration of the tissue in Gd-DTPA(2-) gives us the opportunity to directly image (through T-1 weighting) the concentration of GAG, a major and critically important macromolecule in cartilage. Pilot clinical studies demonstrated Gd-DTPA(2-) penetration into cartilage, suggesting that this technique is clinically feasible. C1 BETH ISRAEL HOSP,DEPT RADIOL,CHARLES A DANA RES INST,BOSTON,MA 02215. MIT,DEPT ELECT ENGN & COMP SCI,ELECTROMAGNET & ELECT SYST LAB,CONTINUUM ELECTROMECH GRP,CAMBRIDGE,MA 02139. HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,ARTHRITIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIAMS NIH HHS [AR41713, AR42773] NR 16 TC 361 Z9 370 U1 1 U2 15 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 NOV PY 1996 VL 36 IS 5 BP 665 EP 673 DI 10.1002/mrm.1910360504 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VQ363 UT WOS:A1996VQ36300003 PM 8916016 ER PT J AU Ostergaard, L Weisskoff, RM Chesler, DA Gyldensted, C Rosen, BR AF Ostergaard, L Weisskoff, RM Chesler, DA Gyldensted, C Rosen, BR TI High resolution measurement of cerebral blood flow using intravascular tracer bolus passages .1. Mathematical approach and statistical analysis SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cerebral blood flow (CBF); dynamic magnetic resonance imaging (MRI); nonparametric deconvolution; susceptibility contrast ID COMPUTED-TOMOGRAPHY; CONTRAST AGENTS; DECONVOLUTION; VOLUME; TRANSIT AB The authors review the theoretical basis of determination of cerebral blood flow (CBF) using dynamic measurements of nondiffusible contrast agents, and demonstrate how parametric and nonparametric deconvolution techniques can be modified for the special requirements of CBF determination using dynamic MRI. Using Monte Carlo modelling, the use of simple, analytical residue models is shown to introduce large errors in flow estimates when actual, underlying vascular characteristics are not sufficiently described by the chosen function. The determination of the shape of the residue function on a regional basis is shown to be possible only at high signal-to-noise ratio. Comparison of several nonparametric deconvolution techniques showed that a nonparametric deconvolution technique (singular value decomposition) allows estimation of flow relatively independent of underlying vascular structure and volume even at low signal-to-noise ratio associated with pixel-by-pixel deconvolution. C1 AARHUS UNIV HOSP, DEPT NEURORADIOL, AARHUS, DENMARK. AARHUS UNIV HOSP, PET CTR, AARHUS, DENMARK. HARVARD UNIV, SCH MED,MASSACHUSETTS GEN HOSP,DEPT RADIOL,NMR CTR, CHARLESTOWN, MA USA. RI Ostergaard, Leif/A-9281-2008 OI Ostergaard, Leif/0000-0003-2930-6997 FU NCI NIH HHS [R01-CA40303, R01-CA66072]; NHLBI NIH HHS [R01-HL39810] NR 33 TC 1007 Z9 1012 U1 5 U2 40 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 1996 VL 36 IS 5 BP 715 EP 725 DI 10.1002/mrm.1910360510 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VQ363 UT WOS:A1996VQ36300009 PM 8916022 ER PT J AU Ostergaard, L Sorensen, AG Kwong, KK Weisskoff, RM Gyldensted, C Rosen, BR AF Ostergaard, L Sorensen, AG Kwong, KK Weisskoff, RM Gyldensted, C Rosen, BR TI High resolution measurement of cerebral blood flow using intravascular tracer bolus passages .2. Experimental comparison and preliminary results. SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cerebral blood flow (CBF); dynamic magnetic resonance imaging (MRI); humans; susceptibility contrast ID CONTRAST AGENTS; PERFUSION; VOLUME AB This report evaluates several methods to map relative cerebral blood flow (rCBF) by applying both parametric and nonparametric techniques to deconvolve high resolution dynamic MRI measurements of paramagnetic bolus passages with noninvasively determined arterial inputs, We found a nonparametric (singular value decomposition (SVD)) deconvolution technique produced the most robust results, giving mean gray:white flow ratio of 2.7 +/- 0.5 (SEM) in six normal volunteers, in excellent agreement with recent PET literature values for age-matched subjects. Similar results were obtained by using a model-dependent approach that assumes an exponential residue function, but not for a Gaussian-shaped residue function or for either Fourier or regularization-based model-independent approaches, Pilot studies of our CBF mapping techniques in patients with tumor, stroke, and migraine aura demonstrated that these techniques can be readily used on data routinely acquired by using current echo planar imaging technology, By using these techniques, the authors visualized important regional hemodynamic changes not detectable with rCBV mapping algorithms. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT RADIOL,NMR CTR,CHARLESTOWN,MA. AARHUS UNIV HOSP,DEPT NEURORADIOL,DK-8000 AARHUS,DENMARK. AARHUS UNIV HOSP,PET CTR,DK-8000 AARHUS,DENMARK. RI Ostergaard, Leif/A-9281-2008 OI Ostergaard, Leif/0000-0003-2930-6997 FU NCI NIH HHS [R01-CA40303, R01-CA66072]; NHLBI NIH HHS [R01-HL39810] NR 20 TC 599 Z9 600 U1 3 U2 26 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 NOV PY 1996 VL 36 IS 5 BP 726 EP 736 DI 10.1002/mrm.1910360511 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VQ363 UT WOS:A1996VQ36300010 PM 8916023 ER PT J AU Li, FP Breslow, NE Morgan, JM Ghahremani, M Miller, GA Grundy, PE Green, DM Diller, LR Pelletier, J AF Li, FP Breslow, NE Morgan, JM Ghahremani, M Miller, GA Grundy, PE Green, DM Diller, LR Pelletier, J TI Germline WT1 mutations in Wilms' tumor patients: Preliminary results SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article; Proceedings Paper CT 2nd International Conference on Molecular and Clinical Genetics of Childhood Renal Tumors CY MAY, 1995 CL PHILADELPHIA, PA DE germline WT1 mutations; Denys-Drash syndrome; genetic predisposition ID LINE P53 MUTATIONS; CANCER-SUSCEPTIBILITY; BREAST-CANCER; GENE; MAP; CHROMOSOME-11; REGION; KIDNEY; LOCUS AB We conducted a comparative study of the prevalence of germline WT1 mutations in patients with Wilms' tumor. Patients in Group 1 have familiar Wilms' tumor, bilateral disease, associated urogenital anomalies, and/or second cancers. Those in Group 2 are unilateral, sporadic Wilms' patients without other associated conditions. Patients with aniridia or Denys-Drash syndrome are known to have WT1 alterations, and are excluded from this study. Preliminary results on 96 subjects show that the overall germline WT1 mutation frequency is low (<5%). The work to date establishes the feasibility of identifying patients with germline WT1 mutations and, in the future, offering genetic predisposition testing to at-risk relatives. However, genetic predisposition testing of children for WT1 mutations raises many ethical, legal, and psychosocial issues; research is needed to evaluate risks and benefits. (C) 1996 Wiley-Liss, Inc. C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. CROSS CANC INST,EDMONTON,AB T6G 1Z2,CANADA. INTEGRATED GENET INC,FRAMINGHAM,MA 01701. ROSWELL PK MEM INST,BUFFALO,NY. MCGILL CANC CTR,MONTREAL,PQ,CANADA. RP Li, FP (reprint author), DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 41 TC 11 Z9 11 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD NOV PY 1996 VL 27 IS 5 BP 404 EP 407 PG 4 WC Oncology; Pediatrics SC Oncology; Pediatrics GA VJ705 UT WOS:A1996VJ70500004 PM 8827066 ER PT J AU Haber, DA Englert, C Maheswaran, S AF Haber, DA Englert, C Maheswaran, S TI Functional properties of WT1 SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article; Proceedings Paper CT 2nd International Conference on Molecular and Clinical Genetics of Childhood Renal Tumors CY MAY, 1995 CL PHILADELPHIA, PA DE Wilms' tumor; WT1; apoptosis; alternative splicing ID WILMS-TUMOR; GROWTH AB WT1 encodes a zinc finger transcription factor that is inactivated in a subset of Wilms' tumors. We have recently shown that introduction of wild-type WT1 into a Wilms' tumor-derived cell line, RM1, results in growth suppression, consistent with its function as a tumor suppressor gene. WT1-mediated growth suppression was also observed in other cells derived from embryonal tumors, including two osteosarcoma cell lines, U2OS and Saos-2, notable for the respective presence or absence of wild-type p53. To further characterize the functional properties of WT1, multiple U2OS and Saos-2 cell lines were established, expressing either wild-type WT1 splicing variants or naturally occurring mutants under control of a tightly regulated tetracycline repressable promoter. Induction of WT1 in these cells resulted in programmed cell death. This effect was preferentially mediated by WT1 isoform B (encoding alternative splice 1, lacking alternative splice II ''KTS''), and it was independent of p53, occurring in both U2OS and Saos-2 cells. WT1-mediated apoptosis was associated with transcriptional repression of the epidermal growth factor receptor (EGFR) and reduced synthesis of endogenous EGFR protein synthesis. Constitutive expression of EGFR abrogated WT1-mediated cell death. We conclude that wild-type WT1 can induce apoptosis in embryonal cancer cells, presumably through the withdrawal of required growth factor survival signals, and that EGFR is a physiological target gene for WT1. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA. RP Haber, DA (reprint author), HARVARD UNIV,SCH MED,CNY 7,BLDG 149,13TH ST,CHARLESTOWN,MA 02129, USA. NR 4 TC 26 Z9 27 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD NOV PY 1996 VL 27 IS 5 BP 453 EP 455 PG 3 WC Oncology; Pediatrics SC Oncology; Pediatrics GA VJ705 UT WOS:A1996VJ70500012 PM 8827073 ER PT J AU Rochon, PA Katz, JN Morrow, LA McGlincheyBerroth, R Ahlquist, MM Sarkarati, M Minaker, KL AF Rochon, PA Katz, JN Morrow, LA McGlincheyBerroth, R Ahlquist, MM Sarkarati, M Minaker, KL TI Comorbid illness is associated with survival and length of hospital stay in patients with chronic disability - A prospective comparison of three comorbidity indices SO MEDICAL CARE LA English DT Article DE comorbidity; aged; aging; spinal cord injury ID MYOCARDIAL-INFARCTION; CLINICAL-TRIALS; CO-MORBIDITY; RATING-SCALE; LATE-LIFE; DEPRESSION; AGE; VALIDATION; PREDICTORS; OUTCOMES AB OBJECTIVES. This study was designed to determine if comorbidity added more information than knowing only the patient's age in predicting survival and length of hospital stay. METHODS. The authors compared the relative predictive validity of three comorbidity indices: the Cumulative Illness Rating Scale, the Charlson Index, and a count of International Classification of Diseases, 9th Revision, Clinical Modification medical diagnoses in relation to survival and length of hospital stays in patients with spinal cord injury. The sample consisted of 330 longitudinally followed spinal-cord injured patients admitted between January 1989 and December 1990 who were followed for an additional 18 months. RESULTS. During the follow-up, 25 (7.5%) patients died and 249 (75.5%) were readmitted to hospital with a median of one admission (range, 1-8). The corresponding lengths of hospital stay ranged from 0 to 548 days, with a median of 7 days. CONCLUSIONS. Patients who died were not significantly older but had higher comorbidity scores. Using patients alive at the end of the follow-up period, linear regression models were fit to the data to determine if comorbidity added more information regarding length of hospital stay than knowing only the patient's age. In the model that included only age as an independent variable, there was a significant relation between age and length of stay (F(1,303) = 5.2; P = 0.012). The R2 value for this model was 0.017. In further models that included age and each of the three comorbidity scores (separately) as the independent variables, the model that included age and the Cumulative Illness Rating Scale yielded the highest R2 value (R2 = 0.062). This study is among the first to compare three different measures of comorbidity and documents that comorbidity provides more information than knowing only the patient's age in relation to survival and length of hospital stay. C1 UNIV TORONTO,DEPT MED,TORONTO,ON M5S 1A1,CANADA. UNIV TORONTO,DEPT PREVENT MED & BIOSTAT,TORONTO,ON M5S 1A1,CANADA. HARVARD UNIV,SCH MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT RHEUMATOL & IMMUNOL,ROBERT B BRIGHAM MULTIPURPOSE ARTHRIT & MUSCULOSK,BOSTON,MA 02115. BROCKTON W ROXBURY VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,W ROXBURY,MA. BROCKTON W ROXBURY VET AFFAIRS MED CTR,SPINAL CORD INJURY SERV,W ROXBURY,MA. RP Rochon, PA (reprint author), BAYCREST CTR GERIATR CARE,DEPT MED,3560 BATHURST ST,N YORK,ON M6A 2E1,CANADA. RI Rochon, Paula/J-2918-2016; McGlinchey, Regina/R-1971-2016 FU NIA NIH HHS [AG 00599]; NIAMS NIH HHS [AR 36308, AR 3992] NR 37 TC 183 Z9 183 U1 3 U2 8 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 1996 VL 34 IS 11 BP 1093 EP 1101 DI 10.1097/00005650-199611000-00004 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA VQ875 UT WOS:A1996VQ87500004 PM 8911426 ER PT J AU Smith, MW Kreutzer, RA Goldman, L CaseyPaal, A Kizer, KW AF Smith, MW Kreutzer, RA Goldman, L CaseyPaal, A Kizer, KW TI How economic demand influences access to medical care for rural Hispanic children SO MEDICAL CARE LA English DT Article DE Hispanic children; demand; access to care; health services research; physician availability ID HEALTH-CARE; MEXICAN-AMERICANS; EMPIRICAL-EVIDENCE; HHANES 1982-84; SERVICES; BARRIERS AB OBJECTIVES. In a study of access to medical care, the authors analyzed the relationship between factors influencing demand, local unmet needs, and the availability of physicians in a rural California community. METHODS. The California Department of Health Services screened 1,697 (90%) of children aged 1 to 12 years in McFarland, CA. The relation of demand to unmet needs was examined using multiple logistic regression. Factors influencing demand for medical care were: ability to pay (income, health insurance) desire to purchase care (ethnicity, education, perceived need), and incidental costs (transportation, child care, etc). Questions from the Hispanic Health and Nutrition Survey were reconstrued to fit the demand model. Local need and demand for physicians was compared with state levels to assess whether sufficient physicians were available. RESULTS. Eighty-six percent of the children were of Mexican ancestry. Factors influencing demand were linked with specific unmet needs. Although unmet needs were high, demand was low; 46% of all families were below the poverty level. Although four primary care physicians were needed, only one could be supported in the private sector because of low demand. CONCLUSIONS. Advantages to the demand model are: (1) it shows why medical services are underused and lacking in low-income areas although need is high, (2) it permits an economic rationale for extra services for poor diverse populations, (3) it estimates the amount of resources lacking to assure adequate levels of care, (4) it shows why facilitated access is needed for certain groups. C1 CALIF DEPT HLTH SERV,ENVIRONM HLTH INVEST BRANCH,BERKELEY,CA 94704. US EPA,OFF PREVENT PESTICIDES & TOX SUBST,WASHINGTON,DC 20460. MINNESOTA DEPT HLTH,CANC CONTROL SECT,MINNEAPOLIS,MN 55414. US DEPT VET AFFAIRS,WASHINGTON,DC. RP Smith, MW (reprint author), CALIF DEPT HLTH SERV,HUMAN POPULAT LAB,2151 BERKELEY WAY,ANNEX 2,BERKELEY,CA 94704, USA. NR 39 TC 11 Z9 11 U1 2 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 1996 VL 34 IS 11 BP 1135 EP 1148 DI 10.1097/00005650-199611000-00007 PG 14 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA VQ875 UT WOS:A1996VQ87500007 PM 8911429 ER PT J AU Threlkeld, SC Hirsch, MS AF Threlkeld, SC Hirsch, MS TI Antiretroviral therapy SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; TYPE-1 REVERSE-TRANSCRIPTASE; HIGH-LEVEL RESISTANCE; PLACEBO-CONTROLLED TRIAL; COLONY-STIMULATING FACTOR; RECOMBINANT SOLUBLE CD4; PHASE-I TRIAL; HIV-INFECTION; DOUBLE-BLIND AB A number of drugs inhibit the HIV replication cycle, but currently available agents have shown only limited clinical effectiveness, and many important questions remain about optimal therapy for patients with HIV infection. The authors review the available antiretroviral drugs as well as promising agents under development. In addition, they discuss some of the common clinical issues in antiretroviral therapy based on current clinical trials' data. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Threlkeld, SC (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,GRAY 5,55 FRUIT ST,BOSTON,MA 02114, USA. NR 107 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD NOV PY 1996 VL 80 IS 6 BP 1263 EP & PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA VV067 UT WOS:A1996VV06700004 PM 8941223 ER PT J AU Kinsley, BT Levy, CJ Simonson, DC AF Kinsley, BT Levy, CJ Simonson, DC TI Prolactin and beta-endorphin responses to hypoglycemia are reduced in well-controlled insulin-dependent diabetes mellitus SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID DEFECTIVE GLUCOSE COUNTERREGULATION; PITUITARY HORMONAL RESPONSES; BLOOD-BRAIN-BARRIER; GLYCEMIC CONTROL; RECURRENT HYPOGLYCEMIA; SUBSEQUENT HYPOGLYCEMIA; INDUCED HYPERGLYCEMIA; CHOLINERGIC BLOCKADE; INTENSIVE THERAPY; AUTONOMIC FAILURE AB Several pituitary hormones, including corticotropin (ACTH), growth hormone (GH), prolactin, and B-endorphin (but not thyrotropin, follicle-stimulating hormone, dr luteinizing hormone), are released in response to hypoglycemia in normal subjects. In patients with insulin-dependent diabetes mellitus (IDDM), the degree of glycemic control is known to alter ACTH and GH responses to hypoglycemia. The current study was performed to examine the effect of glycemic control on prolactin and B-endorphin responses to hypoglycemia in subjects with IDDM. We performed 8-hour stepped hypoglycemic-hyperinsulinemic clamp studies (12 pmol/kg/min) during which plasma glucose was decreased from 5.0 mmol/L to 2.2 mmol/L in steps of 0.6 mmol/L every 30 minutes in 20 subjects with uncomplicated IDDM (12 males and eight females; age, 26 +/- 2 years; IDDM duration, 10 +/- 1 years; body mass index, 23.6 +/- 0.6 kg/m(2)) and 10 healthy subjects (five males and five females aged 30 +/- 1 years). The 10 diabetic subjects in good glycemic control (mean hemoglobin A(1) [HbA(1)], 7.5% +/- 0.3%; normal range, 5.4% to 7.4%) were compared with the 10 poorly controlled patients (mean HbA(1), 12.6% +/- 0.5%; P <.001 v well-controlled diabetic group). During hypoglycemia, prolactin levels in the well-controlled diabetic group did not change (7 +/- I mu g/L at plasma glucose 5.0 mmol/L to 9 +/- 2 mu g/L at plasma glucose 2.2 mmol/L), whereas prolactin levers increased markedly in the poorly controlled diabetic group (7 +/- 2 mu g/L to 44 +/- 17 mu g/L) and healthy volunteers (12 +/- 2 mu g/L to 60 +/- 19 mu g/L, P <.05 between IDDM groups). The plasma glucose threshold required for stimulation of prolactin secretion was 2.2 +/- 0.1 mmol/L in well-controlled IDDM, 3.0 +/- 0.4 mmol/L in poorly controlled IDDM, and 2.4 +/- 0.1 mmol/L in healthy subjects (P <.05 between IDDM groups). Responses in males and females were similar. The increase in beta-endorphin levels was also attenuated in well-controlled IDDM patients (4 +/- 1 mu mol/L at plasma glucose 5.0 mmol/L to 11 +/- 4 pmol/L at plasma glucose 2.2 mmol/L) versus poorly controlled IDDM patients (5 +/- 1 pmol/L to 26 +/- 7 pmol/L) and healthy subjects (8 +/- 1 pmol/L to 56 +/- 13 pmol/L). The plasma glucose threshold required for stimulation of beta-endorphin release was again lower in well-controlled IDDM versus poorly controlled IDDM patients (2.2 +/- 0.1 v 3.0 +/- 0.3 mmol/L) and healthy subjects (2.5 +/- 0.4 mmol/L,P <.05 between IDDM groups). In conclusion, prolactin and beta-endorphin responses to a standardized hypoglycemic stimulus (plasma glucose, 2.2 mmol/L) are reduced and plasma glucose levels required to stimulate release of prolactin and beta-endorphin are lower in well-controlled IDDM compared with poorly controlled IDDM and healthy subjects. Thus, stress hormones not previously considered to have a primary role in plasma glucose recovery from hypoglycemia are affected by glycemic control, suggesting a more generalized alteration of hypothalamic-pituitary responses to hypoglycemia in IDDM patients with strict glycemic control. Copyright (C) 1996 by W.B. Saunders Company C1 HARVARD UNIV, SCH MED, BOSTON, MA USA. RP Kinsley, BT (reprint author), BRIGHAM & WOMENS HOSP, JOSLIN DIABET CTR, DEPT MED, SECT DIABET & METAB, 221 LONGWOOD AVE, BOSTON, MA 02115 USA. FU NIDDK NIH HHS [DK-36836] NR 60 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 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 1996 VL 45 IS 11 BP 1434 EP 1440 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VT180 UT WOS:A1996VT18000020 PM 8931651 ER PT J AU Tanner, A Maiden, MFJ AF Tanner, A Maiden, MFJ TI Gingivitis and the initial periodontal lesion SO MICROBIAL ECOLOGY IN HEALTH AND DISEASE LA English DT Article; Proceedings Paper CT Colloquium on Oral Microbiology at the 7th International Congress of Bacteriology and Applied Microbiology Division of International-Union-of-Microbiological-Societies CY JUL 03-08, 1994 CL PRAGUE, CZECH REPUBLIC SP Int Union Microbiol Soc DE periodontitis; microbiology; bacteria ID ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; BACTEROIDES-INTERMEDIUS; ATTACHMENT LOSS; BACTERIOLOGY; MICROBIOTA; DISEASES; MICROFLORA; ANTIBODY; PLAQUE; SITES AB This project aimed to determine which subgingival microbial species characterised clinically healthy sites, gingivitis sites, and sites that showed increase in periodontal probing depth. Fifteen medically healthy adults with minimal periodontal attachment loss were monitored clinically for 8 to 12 mths, at 2 to 3 mth intervals. Microbial samples were taken from 20 sites using strict anaerobic methods, and the predominant cultivable microbiota determined. Six subjects showed increases in probing depth measurements, and were considered putative active subjects. Cluster analysis of species colonising sites separated sites into two major groups. Actinomyces naeslundii, and Campylobacter gracilis were in both cluster groups. Mean gingivitis levels were higher in cluster 1, which was characterised by Peptostreptococcus micros, eubacteria and Campylobacter rectus, whereas cluster 2 sites, were differentiated by Streptococcus oralis and higher levels of Actinomyces naeslundii. Healthy sites were characterised by S. oralis and S. gordonii, whereas gingivitis sites harbored higher proportions of Prevotella nigrescens, Actinomyces israelli, C. rectus, and Prevotella denticola. Subjects with suspected active sites harbored higher proportions of A. israelii, P. nigrescens, and Selenomonas noxia, compared with inactive subjects. These latter species are candidates for the initiation of periodontal loss. RP Tanner, A (reprint author), FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02115, USA. NR 35 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0891-060X J9 MICROB ECOL HEALTH D JI Microb. Ecol. Health Dis. PD NOV-DEC PY 1996 VL 9 IS 6 BP 359 EP 365 PG 7 WC Ecology; Immunology; Microbiology SC Environmental Sciences & Ecology; Immunology; Microbiology GA WX782 UT WOS:A1996WX78200016 ER PT J AU DeHoratius, C Silver, PA AF DeHoratius, C Silver, PA TI Nuclear transport defects and nuclear envelope alterations are associated with mutation of the Saccharomyces cerevisiae NPL4 gene SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID PORE COMPLEX PROTEINS; MESSENGER-RNA TRANSPORT; INTACT YEAST-CELLS; ENDOPLASMIC-RETICULUM; POLY(A)(+) RNA; MEMBRANE-PROTEIN; CHROMOSOME CONDENSATION; ACTIVATING PROTEIN; BINDING PROTEINS; IMPORT SUBSTRATE AB To identify components involved in nuclear protein import, we used a genetic selection to isolate mutants that mislocalized a nuclear-targeted protein. We identified temperature-sensitive mutants that accumulated several different nuclear proteins in the cytoplasm when shifted to the semipermissive temperature of 30 degrees C; these were termed npl (nuclear protein localization) mutants. We now present the properties of yeast strains bearing mutations in the NPL4 gene and report the cloning of the NPL4 gene and the characterization of the Npl4 protein. The npl4-1 mutant was isolated by the previously described selection scheme. The second allele, npl4-2, was identified from an independently derived collection of temperature-sensitive mutants. The npl4-1 and npl4-2 strains accumulate nuclear-targeted proteins in the cytoplasm at the nonpermissive temperature consistent with a defect in nuclear protein import. Using an in vitro nuclear import assay, we show that nuclei prepared from temperature-shifted npl4 mutant cells are unable to import nuclear-targeted proteins, even in the presence of cytosol prepared from wildtype cells. In addition, npl4-2 cells accumulate poly(A)(+) RNA in the nucleus at the nonpermissive temperature, consistent with a failure to export mRNA from the nucleus. The npl4-1 and npl4-2 cells also exhibit distinct, temperature-sensitive structural defects: npl4-1 cells project extra nuclear envelope into the cytoplasm, whereas npl4-2 cells form nuclear envelope herniations that appear to be filled with poly(A)(+) RNA. The NPL4 gene encodes an essential M(r) 64,000 protein that is located at the nuclear periphery and localizes in a pattern similar to nuclear pore complex proteins. Taken together, these results indicate that this gene encodes a novel nuclear pore complex or nuclear pore complex-associated component required for nuclear membrane integrity and nuclear transport. C1 DANA FARBER CANC INST, BOSTON, MA 02115 USA. PRINCETON UNIV, DEPT MOL BIOL, PRINCETON, NJ 08544 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOL PHARMACOL, BOSTON, MA 02115 USA. NR 100 TC 50 Z9 52 U1 1 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1996 VL 7 IS 11 BP 1835 EP 1855 PG 21 WC Cell Biology SC Cell Biology GA VT571 UT WOS:A1996VT57100015 PM 8930904 ER PT J AU Standaert, DG Landwehrmeyer, GB Kerner, JA Penney, JB Young, AB AF Standaert, DG Landwehrmeyer, GB Kerner, JA Penney, JB Young, AB TI Expression of NMDAR2D glutamate receptor subunit mRNA in neurochemically identified interneurons in the rat neostriatum, neocortex and hippocampus SO MOLECULAR BRAIN RESEARCH LA English DT Article DE NMDA receptor; neostriatum; interneuron; somatostatin; choline acetyltransferase; GABAergic ID INSITU HYBRIDIZATION HISTOCHEMISTRY; NITRIC-OXIDE SYNTHASE; DENTATE HILAR NEURONS; MESSENGER-RNAS; BASAL GANGLIA; EXCITOTOXIN LESIONS; PROJECTION NEURONS; NADPH-DIAPHORASE; GABA NEURONS; BRAIN AB NMDA receptors are composed of proteins from two families: NMDAR1, which are required for channel activity, and NMDAR2, which modulate properties of the channels. The mRNA encoding the NMDAR2D subunit has a highly restricted pattern of expression: in the forebrain, it is found in only a small subset of cortical, neostriatal and hippocampal neurons. We have used a quantitative double-label in situ hybridization method to examine the expression of NMDAR2D mRNA in neurochemically defined populations of neurons. In the neostriatum, NMDAR2D was expressed by the interneuron populations marked by preprosomatostatin (SOM), the 67-kDa form of glutamic acid decarboxylase (GAD(67)), parvalbumin (PARV), and choline acetyltransferase (ChAT) mRNAs but not by the projection neurons expressing beta-preprotachykinin (SP) or preproenkephalin (ENK) mRNAs. In the neocortex, NMDAR2D expression was observed in only a small number of neurons, but these included almost all of the SOM-, GAD(67)- and PARV-expressing interneurons. In the hippocampus, NMDAR2D was not present in pyramidal or granule cells, but was abundant in SOM-, GAD(67)-, and PARV-positive interneurons. NMDAR2D expression appears to be a property shared by interneurons in several regions of the brain. The unique electrophysiological characteristics conveyed by this subunit, which include resistance to blockade by magnesium ion and long channel offset latencies, may be important for the integrative functions of these neurons. NMDAR2D-containing receptor complexes may prove to be important therapeutic targets in human disorders of movement. In addition, the presence of NMDAR2D subunits may contribute to the differential vulnerability of interneurons to excitotoxic injury. RP Standaert, DG (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,FRUIT ST,BOSTON,MA 02114, USA. OI Standaert, David/0000-0003-2921-8348 NR 56 TC 120 Z9 122 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD NOV PY 1996 VL 42 IS 1 BP 89 EP 102 DI 10.1016/S0169-328X(96)00117-9 PG 14 WC Neurosciences SC Neurosciences & Neurology GA VP334 UT WOS:A1996VP33400011 ER PT J AU Zhang, B Berger, J Hu, EI Szalkowski, D WhiteCarrington, S Spiegelman, BM Moller, DE AF Zhang, B Berger, J Hu, EI Szalkowski, D WhiteCarrington, S Spiegelman, BM Moller, DE TI Negative regulation of peroxisome proliferator-activated receptor-gamma gene expression contributes to the antiadipogenic effects of tumor necrosis factor-alpha SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ENHANCER-BINDING-PROTEIN; LIPOPROTEIN-LIPASE ACTIVITY; MESSENGER-RNA CONTENT; ADIPOSE CELL LINE; 3T3-L1 CELLS; ADIPOCYTE DIFFERENTIATION; PREADIPOCYTE DIFFERENTIATION; TRANSCRIPTION FACTOR; GLUCOSE-TRANSPORT; LIPID-METABOLISM AB Recent studies indicate that a peroxisome proliferator-activated receptor, PPAR gamma, functions as an important adipocyte determination factor. In contrast, tumor necrosis factor-alpha (TNF alpha) inhibits adipogenesis, causes dedifferentiation of mature adipocytes, and reduces the expression of several adipocyte-specific genes. Here, we report that treatment of 3T3-L1 adipocytes with TNF alpha resulted in a time- and concentration-dependent decrease in PPAR gamma mRNA expression to the level detected in preadipocytes. PPAR gamma mRNA levels were reduced by 95% with 3 nM TNF alpha treatment for 24 h. Half-maximal effects were seen after 3 h treatment with 3 nM TNF alpha or with 50 pM TNF alpha (24-h exposure). Parallel reductions in PPAR gamma protein levels were also observed after treatment of 3T3-L1 adipocytes with TNF alpha. Using a ribonuclease protection assay, both alternatively spliced PPAR gamma isoforms (gamma 1 and gamma 2) were shown to be negatively regulated by TNF alpha. The down-regulation of PPAR gamma by TNF-alpha preceded the diminution in expression of other adipocyte-specific genes including CCAAT/enhancer binding protein and adipocyte fatty acid-binding protein (aP2). The effect of TNF alpha was specific for the gamma-isoform of PPARs, since the expression of PPAR delta mRNA was not affected by treatment with TNF alpha. Low revel constitutive expression of PPAR gamma in 3T3-L1 adipocytes (at levels approximate to 2- to 3-fold higher than in preadipocytes) partially blocked the inhibitory effect of TNF alpha on aP2 and adipsin expression. These findings support the following conclusions: 1) PPAR gamma expression is necessary for the maintenance of the adipocyte phenotype. 2) ppAR gamma, but not PPAR delta, expression is sufficient to attenuate TNF alpha-mediated effects on adipocyte phenotype. 3) Reduced PPAR gamma gene expression is likely to represent an important component of the mechanism by which TNF alpha exerts its antiadipogenic effects. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02215 USA. RP Zhang, B (reprint author), MERCK RES LABS, DEPT MOL ENDOCRINOL, R80W-250, POB 2000, RAHWAY, NJ 07065 USA. NR 60 TC 256 Z9 263 U1 0 U2 11 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 1996 VL 10 IS 11 BP 1457 EP 1466 DI 10.1210/me.10.11.1457 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VR430 UT WOS:A1996VR43000015 PM 8923470 ER PT J AU Weaver, DR Liu, C Reppert, SM AF Weaver, DR Liu, C Reppert, SM TI Nature's knockout: The Mel(1b) receptor is not necessary for reproductive and circadian responses to melatonin in Siberian hamsters SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID LUTEINIZING-HORMONE RECEPTOR; PHODOPUS-SUNGORUS-SUNGORUS; DJUNGARIAN HAMSTERS; RETINITIS-PIGMENTOSA; SYRIAN-HAMSTERS; RHODOPSIN GENE; MUTATION; LOCALIZATION; PSEUDOGENE; INFUSION AB The pineal hormone melatonin regulates seasonal reproduction and influences the timing of circadian rhythms. The Mel(1a) and Mel(1b) receptors are the high-affinity melatonin receptors present in mammals. Unexpectedly, the Mel(1b) receptor gene of the Siberian hamster, Phodopus sungorus, cannot encode a functional receptor; two nonsense mutations are present within the coding region. Southern blot analysis indicates that this is a single copy gene. The Mel(1b) receptor gene is nonfunctional in outbred populations of P. sungorus and Phodopus campbelli. Siberian hamsters lacking a functional Mel(1b) receptor nevertheless show seasonal reproductive and circadian responses to melatonin, indicating that the Mel(1b) receptor is not necessary for these responses. These data support the hypothesis that the Mel(1a) receptor, which does encode a functional receptor in this species, mediates reproductive and circadian responses to melatonin. C1 HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02114 USA. RP Weaver, DR (reprint author), MASSACHUSETTS GEN HOSP, LAB DEV CHRONOBIOL, SERV PEDIAT, GRJ 1226, BOSTON, MA 02114 USA. FU NICHD NIH HHS [R37 HD-14427] NR 45 TC 158 Z9 166 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 1996 VL 10 IS 11 BP 1478 EP 1487 DI 10.1210/me.10.11.1478 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VR430 UT WOS:A1996VR43000017 PM 8923472 ER PT J AU Palsson, R Sharma, CP Kim, K McLaughlin, M Brown, D Arnaout, MA AF Palsson, R Sharma, CP Kim, K McLaughlin, M Brown, D Arnaout, MA TI Characterization and cell distribution of polycystin, the product of autosomal dominant polycystic kidney disease gene 1 SO MOLECULAR MEDICINE LA English DT Article ID HUMAN ADULT; 2ND GENE; LOCALIZATION; BIOLOGY AB Background: In a majority of cases, autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations within a putative open reading frame of the PKD1 gene. The encoded protein, polycystin, is predicted to span the plasma membrane several times and contains extracellular domains, suggestive of a role in cell adhesion. The cellular distribution and function of polycystin is not known. Materials and Methods: We selected as immunogens two conserved 15 amino acid peptides: P1, located in a predicted extracellular region of polycystin, and P2, located in the C-terminal putative cytoplasmic tail. The anti-peptide antibodies from immunized rabbits were affinity purified on peptide-coupled resins and their specificity confirmed by their selective binding to recombinant polycystin fusion proteins. Western blotting and immunohistochemistry were used to characterize the size, tissue, and cell distribution of polycystin. Results: A high-molecular mass protein (about 642 kD) was detected by Western blotting in rat brain tissue. A few additional bands, in the 100- to 400-kD range, probably representing tissue-specific variants and/or proteolytic fragments, were recognized in human and rat tissues. Polycystin was abundantly expressed in fetal kidney epithelia, where it displayed basolateral and apical membrane distribution in epithelial cells of the ureteric buds, collecting ducts, and glomeruli. In normal human adult kidney, polycystin was detected at moderate levels and in a cell surface-associated distribution in cortical collecting ducts and glomerular visceral epithelium. Expression of polycystin was significantly increased in cyst-lining epithelium in ADPKD kidneys, but was primarily intracellular. Conclusions: Polycystin appears to be a developmentally regulated and membrane-associated glycoprotein. Its intracellular localization in the cyst-lining epithelium of ADPKD kidneys suggests an abnormality in protein sorting in this disease. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,DEPT MED,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PATHOL,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIDDK NIH HHS [DK51051] NR 28 TC 55 Z9 56 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1076-1551 J9 MOL MED JI Mol. Med. PD NOV PY 1996 VL 2 IS 6 BP 702 EP 711 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VX836 UT WOS:A1996VX83600007 PM 8972485 ER PT J AU Jubinsky, PT Shikama, Y Laurie, A Nathan, DG Carroll, M Sieff, CA AF Jubinsky, PT Shikama, Y Laurie, A Nathan, DG Carroll, M Sieff, CA TI The beta c component of the granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin 3 (IL-3)/IL-5 receptor interacts with a hybrid GM-CSF/erythropoietin receptor to influence proliferation and beta-globin mRNA expression SO MOLECULAR MEDICINE LA English DT Article ID ERYTHROPOIETIN RECEPTOR; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; CYTOPLASMIC DOMAINS; CSF RECEPTOR; SUBUNIT; GROWTH; DIFFERENTIATION; ACTIVATION; CLONING AB Background: The interaction of different members of the hematopoietic growth factor receptor family may be relevant to the increased proliferation and the failure of differentiation that characterizes the myeloid leukemias. We recently demonstrated that a chimeric receptor (GMER) that is composed of the extracellular and transmembrane domains of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha-chain (GMR alpha) and the cytoplasmic domain of the mu nine erythropoietin receptor mEpoR binds hGM-CSF with low affinity (3 nM) and confers both proliferative and differentiation signals to stably transfected murine Ba/F3 cells. Materials and Methods: To investigate whether the common beta-subunit of the GM-CSF receptor (beta c) can interact with GMER, either the entire beta-subunit or a mutant, truncated beta-subunit that completely lacks the cytoplasmic domain (beta tr) was introduced into Ba/F3 cells that express GMER, and the binding of GM-CSF as well as proliferation and differentiation responses were measured. Results: Scatchard analysis showed that both GMER + beta c and GMEP + beta tr bound hGM-CSF with high affinity (K-d 40 pM to 65 pM). Proliferation assays showed that the maximum growth of cells expressing GMER + beta c was identical to that of cells with GMER alone. However, proliferation of the cells that expressed GMER + beta tr was reduced by 80-95% of GMER. Dose-response curves showed that the concentration of GM-CSF required for half-maximal growth was 0.5-5.0 pM for GMER + beta c and 0.5-5 nM for GMER and GMER + beta tr. The EpoR cytoplasmic domain of GMER also undergoes ligand-inducible tyrosine phosphorylation. However, the tyrosine phosphorylation did not correlate with growth in cells expressing beta tr. coexpression of beta c with GMER in Ba/F3 cells grown in hGM-CSF markedly enhanced beta-globin mRNA expression. Conclusions: These results indicate that beta c can transduce a unique signal in association with GMER to influence both proliferative and differentiation signal pathways. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT HEMATOL & ONCOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP Jubinsky, PT (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [R01 CA45559]; NIGMS NIH HHS [GM 13452] NR 27 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1076-1551 J9 MOL MED JI Mol. Med. PD NOV PY 1996 VL 2 IS 6 BP 766 EP 773 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VX836 UT WOS:A1996VX83600013 PM 8972491 ER PT J AU Johnston, C Pegues, DA Hueck, CJ Lee, CA Miller, SI AF Johnston, C Pegues, DA Hueck, CJ Lee, CA Miller, SI TI Transcriptional activation of Salmonella typhimurium invasion genes by a member of the phosphorylated response-regulator superfamily SO MOLECULAR MICROBIOLOGY LA English DT Article ID EPITHELIAL-CELL MONOLAYER; ESCHERICHIA-COLI; PROTEIN SECRETION; IDENTIFICATION; VIRULENCE; ENTRY; MACROPINOCYTOSIS; NEUTROPHILS; MECHANISM; HOMOLOGY AB The Salmonella typhimurium PhoP-repressed locus prgHIJK encodes components of a sec-independent type III secretion apparatus. This apparatus is composed of at least 17 proteins encoded on a 40 kb pathogenicity island located at centisome 63 on the S. typhimurium chromosome. The secretion apparatus and some of its targets, SspB, SspC and SspD, are necessary for epithelial cell invasion. The transcription of many invasion genes, including prgHIJK, is coordinately activated by HilA, a transcription factor encoded within the pathogenicity island. In this report we identify sirA, a gene located outside the pathogenicity island that is essential for induction of prgHIJK and hilA transcription, sirA encodes a 234-amino-acid protein that is essential for S. typhimurium Ssp (Salmonella secreted protein) secretion and invasion and is similar to response regulators of two-component regulatory systems, sirA-mutant phenotypes could be suppressed by two DNA clones from unlinked loci, designated sirB and sirC, These data suggest that SirA may be phosphorylated in response to S. typhimurium sensing a mammalian microenvironment. Furthermore, SirA phosphorylation is predicted to initiate a cascade of transcription-factor synthesis which results in invasion-gene transcription, Ssp secretion, and bacterial invasion of epithelia. C1 UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MICROBIOL,SEATTLE,WA 98195. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. FU NIAID NIH HHS [AI30479, AI08873, AI33444, K23 AI079394] NR 65 TC 160 Z9 163 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 1996 VL 22 IS 4 BP 715 EP 727 DI 10.1046/j.1365-2958.1996.d01-1719.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA VU689 UT WOS:A1996VU68900011 PM 8951818 ER PT J AU Rogers, EE Glazebrook, J Ausubel, FN AF Rogers, EE Glazebrook, J Ausubel, FN TI Mode of action of the Arabidopsis thaliana phytoalexin camalexin and its role in Arabidopsis-pathogen interactions SO MOLECULAR PLANT-MICROBE INTERACTIONS LA English DT Article DE plant-pathogen interaction ID SYSTEMIC ACQUIRED-RESISTANCE; HAEMATOCOCCA MP-VI; ARTIFICIAL MEMBRANE-VESICLES; CAMPESTRIS PV CAMPESTRIS; NECTRIA-HAEMATOCOCCA; DISEASE RESISTANCE; ESCHERICHIA-COLI; NONDEGRADATIVE TOLERANCE; HYPERSENSITIVE REACTION; PSEUDOMONAS-AERUGINOSA AB The virulent Arabidopsis thaliana pathogen Pseudomonas syringae pv. maculicola strain E54326 (Psm E54326) and other gram-negative bacteria are sensitive to camalexin (3-thiazol-2'-yl-indole), the Arabidopsis phytoalexin, Furtfiermore, Psm E54326 is unable to degrade camalexin or to become tolerant to it. Apparently, Psm E54326 is a successful pathogen even though it elicits synthesis of a host phytoalexin to which it is sensitive. Assays of membrane integrity revealed that, like other phytoalexins, camalexin disrupts bacterial membranes, suggesting that camalexin toxicity is a consequence of membrane disruption. A screen for camalexin-resistant mutants of Psm ES4326 yielded only partially resistant mutants, which displayed partial resistance in both killing and membrane integrity assays, These mutants were also resistant to low concentrations of tetracycline and nalidixic acid, suggesting that they were affected in components of the outer membrane, The mutants were not distinguishable from Psm ES4326 in virulence assays, Camalexin was toxic to Arabidopsis cells growing in tissue culture, However, comparison of the extent of cell death associated with disease symptoms in infected leaves of wild-type Arabidopsis and a camalexin-deficient mutant suggested that camalexin does not contribute significantly to cell death in infected tissue. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. RI Rogers, Elizabeth/D-2087-2009; OI Rogers, Elizabeth/0000-0002-0545-4744; Glazebrook, Jane/0000-0001-5167-736X FU NIGMS NIH HHS [GM48707] NR 76 TC 80 Z9 81 U1 3 U2 17 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 NOV PY 1996 VL 9 IS 8 BP 748 EP 757 DI 10.1094/MPMI-9-0748 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Plant Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Plant Sciences GA VL892 UT WOS:A1996VL89200010 PM 8870273 ER PT J AU Sikorski, RS Peters, R AF Sikorski, RS Peters, R TI Apoptosis on the Web SO NATURE BIOTECHNOLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 1996 VL 14 IS 11 BP 1606 EP 1606 DI 10.1038/nbt1196-1606 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA VP833 UT WOS:A1996VP83300032 ER PT J AU DAndrea, AD AF DAndrea, AD TI Fanconi anaemia forges a novel pathway SO NATURE GENETICS LA English DT Editorial Material ID ANEMIA; GENE; FACC; COMPLEMENTATION; LOCALIZATION; CYTOPLASM; MUTATION C1 HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA 02115 USA. RP DAndrea, AD (reprint author), DANA FARBER CANC INST, 44 BINNEY ST, BOSTON, MA 02115 USA. NR 19 TC 16 Z9 16 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 1996 VL 14 IS 3 BP 240 EP 242 DI 10.1038/ng1196-240 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA VQ146 UT WOS:A1996VQ14600004 PM 8896546 ER PT J AU Salomon, R Attie, T Pelet, A Bidaud, C Eng, C Amiel, J Sarnacki, S Goulet, O Ricour, C NihoulFekete, C Munnich, A Lyonnet, S AF Salomon, R Attie, T Pelet, A Bidaud, C Eng, C Amiel, J Sarnacki, S Goulet, O Ricour, C NihoulFekete, C Munnich, A Lyonnet, S TI Germline mutations of the RET ligand GDNF are not sufficient to cause hirschsprung disease SO NATURE GENETICS LA English DT Article ID TYROSINE KINASE; NEUROTROPHIC FACTOR; GENE; CHROMOSOME-10; PROTOONCOGENE; NEURONS; MAPS C1 HOP ENFANTS MALAD,INST NECKER,FEDERAT GENET,CLIN CHIRURG INFANTILE,INSERM,U393,F-75743 PARIS 15,FRANCE. HOP ENFANTS MALAD,INST NECKER,SERV NUTR & GASTROENTEROL PEDIAT,F-75743 PARIS 15,FRANCE. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. OI Eng, Charis/0000-0002-3693-5145 NR 29 TC 143 Z9 144 U1 2 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 1996 VL 14 IS 3 BP 345 EP 347 DI 10.1038/ng1196-345 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA VQ146 UT WOS:A1996VQ14600034 PM 8896569 ER PT J AU Tonin, P Weber, B Offit, K Couch, F Rebbeck, TR Neuhausen, S Godwin, AK Daly, M WagnerCostalos, J Berman, D Grana, G Fox, E Kane, MF Kolodner, RD Krainer, M Haber, DA Struewing, JP Warner, E Rosen, B Lerman, C Peshkin, B Norton, L Serova, O Foulkes, WD Lynch, HT Lenoir, GM Narod, SA Garber, JE AF Tonin, P Weber, B Offit, K Couch, F Rebbeck, TR Neuhausen, S Godwin, AK Daly, M WagnerCostalos, J Berman, D Grana, G Fox, E Kane, MF Kolodner, RD Krainer, M Haber, DA Struewing, JP Warner, E Rosen, B Lerman, C Peshkin, B Norton, L Serova, O Foulkes, WD Lynch, HT Lenoir, GM Narod, SA Garber, JE TI Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families SO NATURE MEDICINE LA English DT Editorial Material ID GENE C1 MCGILL UNIV,DEPT HUMAN GENET,MONTREAL,PQ H3G 1A4,CANADA. MONTREAL GEN HOSP,RES INST,MONTREAL,PQ H3G 1A4,CANADA. UNIV PENN,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,DEPT GENET,PHILADELPHIA,PA 19104. MEM SLOAN KETTERING CANC CTR,DEPT HUMAN GENET,CLIN GENET SERV,NEW YORK,NY 10021. UNIV PENN,DEPT BIOSTAT & EPIDEMIOL,PHILADELPHIA,PA 19104. UNIV UTAH,DEPT MED INFORMAT,GENET EPIDEMIOL GRP,SALT LAKE CITY,UT 84108. FOX CHASE CANC CTR,DIV BASIC SCI,PHILADELPHIA,PA 19111. FOX CHASE CANC CTR,DIV POPULAT SCI,PHILADELPHIA,PA 19111. COOPER HOSP UNIV MED CTR,DEPT MED,DIV HEMATOL ONCOL,CAMDEN,NJ 08103. DANA FARBER CANC INST,DIV HUMAN CANC GENET,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CTR CANC,CTR CANC RISK ANAL,CHARLESTOWN,MA 02129. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. NIH,LAB GENE TRANSFER,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. TORONTO SUNNYBROOK REG CANC CTR,DIV MED ONCOL,TORONTO,ON M4N 3M5,CANADA. TORONTO GEN HOSP,DEPT OBSTET & GYNECOL,TORONTO,ON M5G 2C4,CANADA. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. MEM SLOAN KETTERING CANC CTR,DEPT MED,BREAST CANC MED SERV,NEW YORK,NY 10021. INT AGCY RES CANC,F-69372 LYON,FRANCE. SIR MORTIMER B DAVIS JEWISH HOSP,CANC PREVENT RES UNIT,MONTREAL,PQ H3T 1E2,CANADA. CREIGHTON UNIV,SCH MED,DEPT PREVENT MED & PUBL HLTH,OMAHA,NE 68178. UNIV TORONTO,WOMENS COLL HOSP,DEPT MED,TORONTO,ON M5G 1N8,CANADA. MCGILL UNIV,DEPT MED,DIV MED GENET,MONTREAL,PQ H3G 1A4,CANADA. RP Tonin, P (reprint author), UNIV TORONTO,WOMENS COLL HOSP,DEPT MED,790 BAY ST,ROOM 750,TORONTO,ON M5G 1N8,CANADA. RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 FU NCI NIH HHS [CA 55914, CA 06516]; NIAID NIH HHS [AI 28691] NR 25 TC 211 Z9 212 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 1996 VL 2 IS 11 BP 1179 EP 1183 DI 10.1038/nm1196-1179 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VQ101 UT WOS:A1996VQ10100023 PM 8898735 ER PT J AU Zhao, Y Swenson, K Sergio, JJ Arn, JS Sachs, DH Sykes, M AF Zhao, Y Swenson, K Sergio, JJ Arn, JS Sachs, DH Sykes, M TI Skin graft tolerance across a discordant xenogeneic barrier SO NATURE MEDICINE LA English DT Article ID T-CELL TOLERANCE; TRANSPLANTATION TOLERANCE; THYMIC EPITHELIUM; CLONAL DELETION; MONOCLONAL-ANTIBODIES; NEGATIVE SELECTION; CLASS-I; ANTIGENS; ANERGY; MICE AB Specific T-cell tolerance may be essential for successful xenotransplantation in humans. Grafting of thymectomized, T cell-depleted normal mice with xenogeneic fetal pig thymus and liver (FP THY/LIV) tissue results in the recovery of functional CD4 antigen-positive cells. We have tested T-cell tolerance by skin grafting. Donor-matched pig skin survived permanently (>200 days), whereas allogeneic mouse skin was rapidly rejected. Nontolerant control mice rejected pig skin within 26 days. Both porcine and murine histocompatibility class IIhigh cells were detected in long-term thymus grafts, and T-cell repertoire analyses suggested that tolerance to both donors and recipients developed, at least in part, by intragraft clonal deletion. This study demonstrates the principle that tolerance, measured by the stringent criterion of skin grafting, can be induced across a widely disparate species barrier. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG SERV,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. FU NIAID NIH HHS [P01 AI 39755] NR 46 TC 137 Z9 139 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 1996 VL 2 IS 11 BP 1211 EP 1216 DI 10.1038/nm1196-1211 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VQ101 UT WOS:A1996VQ10100035 PM 8898747 ER PT J AU Choate, KA Medalie, DA Morgan, JR Khavari, PA AF Choate, KA Medalie, DA Morgan, JR Khavari, PA TI Corrective gene transfer in the human skin disorder lamellar ichthyosis SO NATURE MEDICINE LA English DT Article ID KERATINOCYTE TRANSGLUTAMINASE; EPIDERMAL-KERATINOCYTES; BARRIER FUNCTION; DIFFERENTIATION; THERAPY; EXPRESSION; ANTIBODIES; TISSUE; CELLS; MICE AB Lamellar ichthyosis (LI) is a disfiguring skin disease characterized by abnormal epidermal differentiation and defective cutaneous barrier function(1,2). LI has been associated with loss of keratinocyte transglutaminase 1 (TGase1)(3,4) an enzyme believed necessary for normal formation of the cornified epidermal barrier. Using LI as a prototype for therapeutic cutaneous gene delivery, we have used the human skin/immunodeficient mouse xenograft model to correct the molecular, histologic and functional abnormalities of LI patient skin in vivo. We have used TGase1-deficient primary keratinocytes from LI patients combined with high-efficiency transfer of functional TGase1 to regenerate engineered human LI epidermis on immunodeficient mice. Engineered LI epidermis displayed normal TGase1 expression in vivo, unlike unengineered LI epidermis where TGase1 was absent. Epidermal architecture was also normalized by TGase1 restoration, as was expression of the epidermal differentiation marker filaggrin. Engineered LI skin demonstrated restoration of cutaneous barrier function measures to levels seen in epidermis regenerated by keratinocytes from patients with normal skin, indicating functional correction in vivo of the proposed primary pathophysiologic defect in LI. These results confirm a major role for TGase1 in epidermal differentiation and demonstrate a potential future approach to therapeutic gene delivery in human skin. C1 STANFORD UNIV,SCH MED,MSLS,DEPT DERMATOL,STANFORD,CA 94305. VET ADM MED CTR,VET AFFAIRS PALO ALTO HLTH CARE SYST,PALO ALTO,CA 94304. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,SURG SERV,CAMBRIDGE,MA 02139. SHRINERS BURN INST,RES CTR,CAMBRIDGE,MA 02139. OI Morgan, Jeffrey/0000-0002-7546-3443 NR 30 TC 119 Z9 122 U1 1 U2 4 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 1996 VL 2 IS 11 BP 1263 EP 1267 DI 10.1038/nm1196-1263 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VQ101 UT WOS:A1996VQ10100046 PM 8898758 ER PT J AU Hyman, BT GomezIsla, T AF Hyman, BT GomezIsla, T TI Neuropathological markers of impaired cognition in the entorhinal cortex SO NEUROBIOLOGY OF AGING LA English DT Editorial Material ID ALZHEIMERS-DISEASE; SENILE PLAQUES; TANGLES RP Hyman, BT (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,WARREN 408,BOSTON,MA 02114, USA. NR 8 TC 1 Z9 1 U1 0 U2 0 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 NOV-DEC PY 1996 VL 17 IS 6 BP 940 EP 941 DI 10.1016/S0197-4580(96)00174-1 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA VY127 UT WOS:A1996VY12700018 PM 9363808 ER PT J AU Litvan, I Mega, MS Cummings, JL Fairbanks, L AF Litvan, I Mega, MS Cummings, JL Fairbanks, L TI Neuropsychiatric aspects of progressive supranuclear palsy SO NEUROLOGY LA English DT Article ID RICHARDSON-OLSZEWSKI SYNDROME; ADVANCED PARKINSONS-DISEASE; NURSING-HOME PLACEMENT; ALZHEIMERS-DISEASE; PSYCHIATRIC-SYMPTOMS; BASAL GANGLIA; DEMENTIA; DEPRESSION; IMPAIRMENT; COGNITION AB Administering the Neuropsychiatric Inventory (NPI), we examined the behavioral symptoms of 22 patients with progressive supranuclear palsy (PSP), 50 patients with Alzheimer's disease, and 40 controls. PSP patients exhibited apathy (91%), disinhibition (36%), dysphoria (18%) and anxiety (18%), but rarely (<9%) irritability, abnormal motor behaviors, or agitation. Apathy in PSP was significantly associated with executive dysfunction. The presence of high apathy and low agitation and anxiety scale scores correctly identified the PSP patients 85% of the time. Evaluating the behavioral abnormalities of patients with neurodegenerative disorders will aid diagnosis and facilitate management. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,BEHAV NEUROSCI SECT,PSYCHIAT SERV,LOS ANGELES,CA 90073. RP Litvan, I (reprint author), NINCDS,NEUROEPIDEMIOL BRANCH,NIH,FED BLDG,ROOM 714,BETHESDA,MD 20892, USA. OI Litvan, Irene/0000-0002-3485-3445 FU NIA NIH HHS [AG10123] NR 60 TC 134 Z9 137 U1 0 U2 5 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1996 VL 47 IS 5 BP 1184 EP 1189 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA VR425 UT WOS:A1996VR42500012 PM 8909427 ER PT J AU Mendez, MF Cherrier, M Perryman, KM Pachana, N Miller, BL Cummings, JL AF Mendez, MF Cherrier, M Perryman, KM Pachana, N Miller, BL Cummings, JL TI Frontotemporal dementia versus Alzheimer's disease: Differential cognitive features SO NEUROLOGY LA English DT Article ID FRONTAL-LOBE DEGENERATION; KLUVER-BUCY SYNDROME; PICKS-DISEASE; NEUROPSYCHOLOGICAL FINDINGS; EMISSION TOMOGRAPHY; PRESENILE-DEMENTIA; ATROPHY; DIAGNOSIS; SCALE AB Frontotemporal dementia (FTD) is a common neurodegenerative dementia that can be difficult to distinguish clinically from Alzheimer's disease (AD). The differential distribution of pathology in FTD and AD predicts the presence of differential cognitive features on mental status examination. We compared 39 FTD patients with 101 AD patients on the Consortium to Establish a Registry in AD examination supplemented by cognitive areas from the Neurobehavioral Cognitive Status Examination. The FTD patients were diagnosed using noncognitive clinical and neuroimaging criteria and were comparable to the AD patients in terms of gender, educational level, and dementia severity ratings. The FTD patients performed significantly better than the AD patients on constructions and calculations. These findings were at the lower limits of normal for older normal controls and persisted after covarying for younger age and higher Mini-Mental Status Examination scores in the FTD group. In addition to personality and neuroimaging features, relatively preserved performance of elementary drawings and calculations in FTD suggests additional features for distinguishing FTD patients from comparably demented AD patients. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. RP Mendez, MF (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,NEUROBEHAV UNIT 691 1164F,PSYCHIAT SERV,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. RI Pachana, Nancy/C-6807-2016 OI Pachana, Nancy/0000-0002-8927-4205 NR 43 TC 76 Z9 76 U1 0 U2 6 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1996 VL 47 IS 5 BP 1189 EP 1194 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA VR425 UT WOS:A1996VR42500013 PM 8909428 ER PT J AU Breiter, HC Etcoff, NL Whalen, PJ Kennedy, WA Rauch, SL Buckner, RL Strauss, MM Hyman, SE Rosen, BR AF Breiter, HC Etcoff, NL Whalen, PJ Kennedy, WA Rauch, SL Buckner, RL Strauss, MM Hyman, SE Rosen, BR TI Response and habituation of the human amygdala during visual processing of facial expression SO NEURON LA English DT Article ID STIMULUS-REWARD ASSOCIATIONS; HUMAN BRAIN; IMPAIRED RECOGNITION; UNIPOLAR DEPRESSION; SENSORY STIMULATION; OVERLYING AREAS; TEMPORAL CORTEX; MONKEY; NEURONS; FACES AB We measured amygdala activity in human volunteers during rapid visual presentations of fearful, happy, and neutral faces using functional magnetic resonance imaging (fMRI). The first experiment involved a fixed order of conditions both within and across runs, while the second one used a fully counterbalanced order in addition to a low level baseline of simple visual stimuli. In both experiments, the amygdala was preferentially activated in response to fearful versus neutral faces. In the counterbalanced experiment, the amygdala also responded preferentially to happy versus neutral faces, suggesting a possible generalized response to emotionally valenced stimuli. Rapid habituation effects were prominent in both experiments. Thus, the human amygdala responds preferentially to emotionally valenced faces and rapidly habituates to them. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,NUCL MAGNET RESONANCE CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. RP Breiter, HC (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,CHARLESTOWN,MA 02129, USA. RI Frank, David/E-8213-2012 FU NHLBI NIH HHS [HL39810]; NIDA NIH HHS [DA00265, DA09467] NR 71 TC 1091 Z9 1105 U1 11 U2 80 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1996 VL 17 IS 5 BP 875 EP 887 DI 10.1016/S0896-6273(00)80219-6 PG 13 WC Neurosciences SC Neurosciences & Neurology GA VV151 UT WOS:A1996VV15100010 PM 8938120 ER PT J AU Sauman, I Reppert, SM AF Sauman, I Reppert, SM TI Circadian clock neurons in the silkmoth Antheraea pernyi: Novel mechanisms of period protein regulation SO NEURON LA English DT Article ID DROSOPHILA-MELANOGASTER; NERVOUS-SYSTEM; GENE-PRODUCT; TIMELESS; EXPRESSION; CLONING; AUTOREGULATION; FEEDBACK; SEQUENCE; REVEALS AB We examined Period (PER) protein regulation in the brain of the silkmoth Antheraea pernyi. PER expression is restricted to the cytoplasm and axons of eight neurons, with no evidence of temporal movement into the nucleus. These neurons appear to be circadian clock cells, because PER and per mRNA are colocalized and their levels oscillate in these cells, Timeless protein immunoreactivity is coexpressed in each PER-positive neuron, and clock protein and mRNA oscillations are all suppressed in these neurons by constant light. A per antisense RNA oscillation was detected that is spatially restricted to PER-expressing cells, suggesting a novel mechanism of PER regulation. PER-positive neurons and their projections are strategically positioned for regulating prothoracicotropic hormone and eclosion hormone, two neurohormones under circadian control. Differences in the molecular details of PER expression and regulation between the brains of silkmoths and fruitflies provide insights into the mechanisms of clock gene regulation. C1 MASSACHUSETTS GEN HOSP,SERV PEDIAT,LAB DEV CHRONOBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Sauman, Ivo/H-2071-2014 FU NICHD NIH HHS [R37 HD14427] NR 38 TC 170 Z9 172 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1996 VL 17 IS 5 BP 889 EP 900 DI 10.1016/S0896-6273(00)80220-2 PG 12 WC Neurosciences SC Neurosciences & Neurology GA VV151 UT WOS:A1996VV15100011 PM 8938121 ER PT J AU Sauman, I Tsai, T Roca, AL Reppert, SM AF Sauman, I Tsai, T Roca, AL Reppert, SM TI Period protein is necessary for circadian control of egg hatching behavior in the silkmoth Antheraea pernyi SO NEURON LA English DT Article ID CLOCKS AB We examined the molecular basis of the circadian control of egg hatching behavior in the silkmoth Antheraea pernyi. Egg hatching is rhythmically gated, persists under constant darkness, and can be entrained by light by midembryogenesis. The time of appearance of photic entrainment by the silkmoth embryo coincides with the appearance of Period (PER) and Timeless (TIM) proteins in eight cells in embryonic brain. Although daily rhythms in PER and/or TIM immunoreactivity in embryonic brain were not detected, a robust circadian oscillation of PER immunoreactivity is present in the nuclei of midgut epithelium. per antisense oligodeoxynucleotide treatment of pharate larvae on the day before hatching consistently abolishes the circadian gate of egg hatching behavior. per antisense treatment also causes a dramatic decrease in PER immunoreactivity in newly hatched larvae. The results provide direct evidence that PER is a necessary element of a circadian system in the silkmoth. C1 MASSACHUSETTS GEN HOSP,SERV PEDIAT,LAB DEV CHRONOBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Sauman, Ivo/H-2071-2014 FU NICHD NIH HHS [R37 HD14427] NR 15 TC 42 Z9 43 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1996 VL 17 IS 5 BP 901 EP 909 DI 10.1016/S0896-6273(00)80221-4 PG 9 WC Neurosciences SC Neurosciences & Neurology GA VV151 UT WOS:A1996VV15100012 PM 8938122 ER PT J AU Babich, JW Rubin, RH Graham, WA Wilkinson, RA Vincent, J Fischman, AJ AF Babich, JW Rubin, RH Graham, WA Wilkinson, RA Vincent, J Fischman, AJ TI F-18-labeling and biodistribution of the novel fluoro-quinolone antimicrobial agent, trovafloxacin (CP 99,219) SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE trovafloxacin; CP 99,219; pharmacokinetics; PET exchange ID POSITRON EMISSION TOMOGRAPHY; F-18 LABELED FLUCONAZOLE; HEALTHY-HUMAN SUBJECTS; PHARMACOKINETICS; FLEROXACIN; RABBITS; INFECTIONS; CP-99,219 AB [F-18]CP 99,219 [(1 alpha,5 alpha,6 alpha)-7-(6-amino-3-azabicyclo [3.1.0]hex-3-yl) 1-(2,4-difluorophenyl)-6-fluoro-1,4- dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid] was prepared by F-18 for F-19 exchange followed by reverse-phase HPLC purification. Studies of the effects of reaction time and temperature on F-18 incorporation demonstrated that heating 1.0 mg of CP 99,219 in 0.5 cc of DMSO with 4.5 mg of K2CO3 and 24 mg of Kryptofix for 15 min at 160 degrees C results in the optimal compromise between radiochemical yield and purity. This method routinely provides radiochemical yields of 15-30% [EOS] with radio chemical purities of >97%. Varying the concentration of CP 99,219 in the reaction mixture had no effect on yield. Biodistribution studies in rats demonstrated that significant concentrations of drug accumulate in most tissues. The tissues with the highest concentrations of drug were intestine, liver, kidney, and stomach. Copyright (C) 1996 Elsevier Science Inc. C1 MASSACHUSETTS GEN HOSP,DIV NUCL MED,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. MIT,HARVARD MIT DIV HLTH SCI & TECHNOL,CTR EXPT PHARMACOL & THERAPEUT,CAMBRIDGE,MA 02139. PFIZER INC,DIV CENT RES,GROTON,CT 06340. NR 16 TC 20 Z9 20 U1 0 U2 1 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 NOV PY 1996 VL 23 IS 8 BP 995 EP 998 DI 10.1016/S0969-8051(96)00153-9 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VZ520 UT WOS:A1996VZ52000008 PM 9004287 ER PT J AU Huang, Z Szostak, JW AF Huang, Z Szostak, JW TI A simple method for 3'-labeling of RNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESCHERICHIA-COLI; MESSENGER-RNA; POLYMERASE-I AB We describe a simple method for 3'-end labeling RNAs of known sequence. A short DNA template is designed to anneal to the 3'-end of the RNA, with a two nucleotide 5' overhang of 3'-TA-5', 3'-TG-5' or 3'-TC-5'. The Klenow fragment of DNA polymerase I can then cleanly and efficiently extend the 3'-end of the RNA by the incorporation of a single alpha-P-32-labeled dATP residue. This method can be used to label one RNA in a mixture of RNAs, or to label 5'-blocked RNAs such as mRNA. C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. NR 14 TC 70 Z9 70 U1 3 U2 7 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 1 PY 1996 VL 24 IS 21 BP 4360 EP 4361 DI 10.1093/nar/24.21.4360 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT249 UT WOS:A1996VT24900039 PM 8932396 ER PT J AU Choy, LN Spiegelman, BM AF Choy, LN Spiegelman, BM TI Regulation of alternative pathway activation and C3a production by adipose cells SO OBESITY RESEARCH LA English DT Article DE acylation stimulating protein; adipsin; Crry/p65; properdin; obesity ID ACYLATION STIMULATING PROTEIN; TUMOR-NECROSIS-FACTOR; COMPLEMENT FACTOR-H; MESSENGER-RNA; SERINE PROTEASE; FACTOR-ALPHA; OBESE GENE; IFN-GAMMA; ADIPSIN; EXPRESSION AB Adipose tissue is re major source of adpisin/factor D of the alternative pathway of complement. Adipose tissue also expresses the two other complement components which are involved in the first activation step of the alternative pathway, factor B and C3, and this step is activated in adipose tissue, producing C3a/Acylation Stimulating Protein (C3a/ASP), a stimulator of triglyceride synthesis, Complement activation is a highly regulated process, however, nothing is known about regulation of complement activation in adipose tissue, To gain insight into the nature of adipose complement activation and its regulation, we have now examined the expression of several complement activation regulatory genes, and analyzed the production of C3a/ASP in lean vs, obese, adipsin-deficient mice, We found that undifferentiated preadipocytes expressed the mRNAs encoding the negative regulatory proteins Crry and factor H, but expression of both genes was decreased upon differentiation, The positive regulator properdin, as well as Crry and factor ii, were found in adipose tissue, None of these genes was regulated in murine genetic obesity, To investigate the relative levels of complement activation in lean vs, adipsin-deficient obese mice, we developed a radioimmunoassay for measurement of murine C3a/ASP in plasma, We report that there was no significant difference in the level of C3a in lean vs, obese plasma; however, we found a positive correlation between C3a and plasma triglyceride levels in normal lean mice. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,DANA FARBER CANC INST,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 31405] NR 47 TC 31 Z9 33 U1 1 U2 1 PU NORTH AMER ASSOC STUDY OBESITY PI BATON ROUGE PA 6400 PERKINS RD, BATON ROUGE, LA 70808 SN 1071-7323 J9 OBES RES JI Obes. Res. PD NOV PY 1996 VL 4 IS 6 BP 521 EP 532 PG 12 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA VV235 UT WOS:A1996VV23500003 PM 8946437 ER PT J AU Steidl, SM Hirose, T Sang, D Hartnett, ME AF Steidl, SM Hirose, T Sang, D Hartnett, ME TI Difficulties in excluding the diagnosis of retinoblastoma in cases of advanced coats' disease: A clinicopathologic report SO OPHTHALMOLOGICA LA English DT Article DE Coats' disease; leukocoria; retinoblastoma AB We highlight the difficulty in differentiating Coats' disease from retinoblastoma, Two patients with bullous exudative retinal detachment and abnormal vessels are discussed. Histologic evaluation of the 5-year-old patient revealed retinoblastoma. The 1-year-old patient had Coats' disease by histologic identification. With this in mind, we suggest enucleation of such eyes if diagnostic uncertainty exists, since failure to treat retinoblastoma is a more serious error than enucleation of an eye with minimal function. C1 SCHEPENS RETINA ASSOCIATES,SCHEPENS EYE RES INST,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02114. NR 11 TC 11 Z9 12 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3755 J9 OPHTHALMOLOGICA JI Ophthalmologica PD NOV-DEC PY 1996 VL 210 IS 6 BP 336 EP 340 PG 5 WC Ophthalmology SC Ophthalmology GA VH982 UT WOS:A1996VH98200005 PM 8887390 ER PT J AU Tolentino, MJ Miller, JW Gragoudas, ES Jakobiec, FA Flynn, E Chatzistefanou, K Ferrara, N Adamis, AP AF Tolentino, MJ Miller, JW Gragoudas, ES Jakobiec, FA Flynn, E Chatzistefanou, K Ferrara, N Adamis, AP TI Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate SO OPHTHALMOLOGY LA English DT Article ID EXPERIMENTAL IRIS NEOVASCULARIZATION; PROLIFERATIVE DIABETIC-RETINOPATHY; PERMEABILITY FACTOR; FACTOR VEGF; TUMOR ANGIOGENESIS; CELLS; EXPRESSION; MITOGEN; HYPOXIA; IDENTIFICATION AB Purpose: The purpose of the study is to determine the effect of exogenous vascular endothelial growth factor (VEGF) on the primate retina and its vasculature. Methods: Ten eyes of five animals were studied. Physiologlcally relevant amounts of the 165 amino acid isoform of human recombinant VEGF were injected into the vitreous of six healthy cynomolgus monkey eyes. inactivated human recombinant VEGF or vehicle was injected into four contralateral control subject eyes. Eyes were assessed by slit-lamp biomicroscopy, tonometry, fundus color photography, fundus fluorescein angiography, light microscopy, and immunostaining with antibodies against proliferating cell nuclear antigen and factor VIII antigen, Results: Ail six bioactive VEGF-injected eyes developed dilated, tortuous retinal vessels that leaked fluorescein. Eyes receiving multiple injections of VEGF developed progressively dilated and tortuous vessels, Venous beading, edema, microaneurysms, intraretinal hemorrhages and capillary closure with ischemia. The severity of the retinopathy correlated with the number of VEGF injections. None of the four control eyes exhibited any abnormal retinal vascular changes. The endothelial cells of retinal blood vessels were proliferating cell nuclear antigen positive only in the bioactive VEGF-injected eyes. Conclusion: Vascular endothelial growth factor is sufficient to produce many of the vascular abnormalities common to diabetic retinopathy and other ischemic retinopathies, such as hemorrhage, edema, venous beading, capillary occlusion with ischemia, microaneurysm formation, and intraretinal vascular proliferation. C1 HARVARD UNIV, MASSACHUSETTS EYE & EAR INFIRM, DEPT OPHTHALMOL, BOSTON, MA 02114 USA. CHILDRENS HOSP, DEPT SURG, SURG RES LAB, BOSTON, MA USA. GENENTECH INC, S SAN FRANCISCO, CA 94080 USA. NR 46 TC 314 Z9 330 U1 1 U2 6 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 NOV PY 1996 VL 103 IS 11 BP 1820 EP 1828 PG 9 WC Ophthalmology SC Ophthalmology GA VU097 UT WOS:A1996VU09700029 PM 8942877 ER PT J AU Dana, MR MerayoLloves, J Schaumberg, DA Foster, CS AF Dana, MR MerayoLloves, J Schaumberg, DA Foster, CS TI Prognosticators for visual outcome in sarcoid uveitis SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT American-Academy-of-Ophthalmology Annual Meeting CY OCT-NOV -, 1995 CL ATLANTA, GA SP Amer Acad Ophthalmol ID OCULAR SARCOIDOSIS; DISEASE; INVOLVEMENT; DIAGNOSIS AB Purpose: The purpose of the study is to delineate the visual prognosticators in sarcoid-associated uveitis given the current standards of care. Methods: The records of 60 patients with sarcoid-associated uveitis who were observed for at least 6 months were studied retrospectively. Multivariate regression models using the generalized estimating equations approach to adjust for the correlation between fellow eyes were applied to determine disease, patient, and treatment characteristics that altered the odds of visual rehabilitation. Results: One hundred twelve eyes of 43 women and 17 men who met the inclusion criteria were identified. Seventy-seven percent of patients were white, 15% black, and 8% of Hispanic origin. Uveitis developed in the patients at a mean age of 42 (range, 4-82) years. Of the 112 affected eyes, 81% had granulomatous and 15% nongranulomatous uveitis. Most patients (66%) had anterior or intermediate uveitis alone. Ninety-one percent had chronically smoldering disease; another 7% had recurrent flares, and only 1 patient had a monophasic acute course to her uveitis. Vision-threatening complications developed in many patients, including 58% in whom cystoid macular edema developed and 25% in whom media opacities developed, requiring cataract surgery or vitrectomy or both. Overall, 34% of treated eyes and 51% of patients had final visual acuities that were superior to their acuities at presentation. The factors most significantly associated with a final visual acuity of worse than 20/40 after controlling for potential confounders were as follows: delay in presentation to a subspecialist (odds ratio [OR] = 2.94, P = 0.05), total duration of uveitis (OR = 1.04, P = 0.09), development of cystoid macular edema (OR = 0.37, P = 0.07) or glaucoma (OR = 4.54, P = 0.02), presence of intermediate (OR = 5.00, P = 0.01) or posterior uveitis (OR = 8.33, P = 0.04), and systemic steroid use (OR = 0.30, P = 0.03) were the parameters most strongly correlated with a lack of visual acuity improvement. Delay in presentation to a subspecialist (OR = 20.00, P = 0.01), development of glaucoma (OR = 50.00, P = 0.005), presence of intermediate (OR = 25.00, P = 0.02) or posterior uveitis (OR = 50.00, P = 0.02), black race (OR = 11.11, P = 0.02), (log) visual acuity at presentation (OR = 0.05, P = 0.0001), and use of systemic steroids (OR = 0.07, P = 0.02). Conclusion: Multivariate outcomes analysis, particularly after correcting for the correlation between fellow eyes, is a useful analytic tool for optimization of standards of care and for disease risk stratification to aid both physicians and patients. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV PREVENT MED,BOSTON,MA 02115. RP Dana, MR (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,IMMUNOL & UVEITIS SERV,BOSTON,MA 02114, USA. NR 31 TC 57 Z9 58 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 1996 VL 103 IS 11 BP 1846 EP 1853 PG 8 WC Ophthalmology SC Ophthalmology GA VU097 UT WOS:A1996VU09700032 PM 8942880 ER PT J AU Shy, C Anderson, H Ducatman, A Fleissner, ML Fox, M Jackson, R Kenneally, F Mather, S Mirza, N Ron, E Ross, D Royal, H Sandler, D Schneider, A Shore, R AF Shy, C Anderson, H Ducatman, A Fleissner, ML Fox, M Jackson, R Kenneally, F Mather, S Mirza, N Ron, E Ross, D Royal, H Sandler, D Schneider, A Shore, R TI Summary report of the panel SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Editorial Material C1 UNIV N CAROLINA,CHAPEL HILL,NC. WISCONSIN DEPT PUBL HLTH,MADISON,WI. W VIRGINIA UNIV,SCH MED,MORGANTOWN,WV 26506. CONNECTICUT DEPT PUBL HLTH & ADDICT SERV,HARTFORD,CT 06106. VET FOREIGN WARS,WASHINGTON,DC. SUBMARINE SURVIVORS HOTLINE,CIVILIAN DIV,WATERFORD,CT. DEPT VET AFFAIRS,WASHINGTON,DC. VET AFFAIRS MED CTR,PHILADELPHIA,PA. NCI,BETHESDA,MD 20892. W HAVEN VET AFFAIRS MED CTR,W HAVEN,CT. WASHINGTON UNIV,MED CTR,MALLINCKRODT INST RADIOL,ST LOUIS,MO 63110. NIEHS,RES TRIANGLE PK,NC 27709. UNIV ILLINOIS,CHICAGO,IL. NYU,NEW YORK,NY. NR 1 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 1996 VL 115 IS 5 BP 442 EP 446 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA VU694 UT WOS:A1996VU69400015 PM 8903445 ER PT J AU Avery, RK Eavey, RD Torre, TD Ramos, D Pasternack, MS AF Avery, RK Eavey, RD Torre, TD Ramos, D Pasternack, MS TI Bilateral otitis media and mastoiditis caused by a highly resistant strain of Mycobacterium chelonae SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE otitis media; mastoiditis; Mycobacterium chelonae; imipenem ID RAPIDLY GROWING MYCOBACTERIA; STERNAL WOUND INFECTIONS; FORTUITUM COMPLEX; AUGMENTATION MAMMAPLASTY; PATIENT; ORGANISMS; SURGERY; CLARITHROMYCIN; SUSCEPTIBILITY; DIALYSIS C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,CHARLESTOWN,MA 02129. CLEVELAND CLIN FDN,DEPT INFECT DIS,CLEVELAND,OH 44195. MASSACHUSETTS EYE & EAR INFIRM,DEPT PEDIAT OTOLARYNGOL,BOSTON,MA 02114. PAPAZIAN TARRO & DELLA TORRE INC,PAWTUCKET,RI. NR 46 TC 12 Z9 12 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 1996 VL 15 IS 11 BP 1037 EP 1040 DI 10.1097/00006454-199611000-00020 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA VT450 UT WOS:A1996VT45000011 PM 8933554 ER PT J AU Newacheck, PW Stein, REK Walker, DK Gortmaker, SL Kuhlthau, K Perrin, JM AF Newacheck, PW Stein, REK Walker, DK Gortmaker, SL Kuhlthau, K Perrin, JM TI Monitoring and evaluating managed care for children with chronic illnesses and disabilities SO PEDIATRICS LA English DT Article DE children; managed care; chronic illness; disability; HMO ID SEVERITY; ISSUES AB Objective. Children with chronic illnesses and disabilities are increasingly enrolling in managed care arrangements. Yet, the rapid expansion of managed care has unknown consequences for children with chronic conditions and disabilities. As managed care is likely to become the predominant mode of medical practice for children with chronic health problems, information gained from a thorough assessment of existing managed care models could be helpful in indicating adjustments and modifications that could result in improved outcomes for this population. The purpose of this article is to outline a new strategy for collecting needed information on the effects of managed care on children with chronic health problems. Methods. We reviewed the literature on the effects of managed care on children with chronic conditions and disabilities. We identified key domains relevant to monitoring and evaluating managed care for this population. Results. Two research approaches can provide helpful information for assessing the effects of managed care on children with chronic conditions. First, a monitoring strategy could be pursued in which enrollment trends in managed care, enrollee perceptions of access and satisfaction with care, and other general indicators of outcomes would be tracked over time using inexpensive and rapid turnaround data sources. Second, an evaluative strategy could be pursued using experimental or quasiexperimental designs, in which outcomes across a variety of domains for children with chronic conditions in managed care are compared with: (a) outcomes for the same children before enrollment in managed care; or (b) outcomes for similar children remaining in traditional fee-for-service settings. Evaluation and monitoring strategies should focus on outcomes in a number of domains including: (1) access to care; (2) utilization of services; (3) quality of care; (4) satisfaction with care; (5) expenditures for care; (6) health outcomes; and (7) family impact. Conclusion. Assessing outcomes that result from enrollment in managed care for children with chronic health problems presents a formidable challenge. The research strategy outlined in this article presents one approach to meeting that challenge. The monitoring and evaluation strategies described here would require commitment of additional resources on the part of government, private foundations, and/or health plans. Given the paucity of existing information and the stakes for children with chronic conditions and their families, investment of added resources in a comprehensive monitoring and evaluation strategy is essential. C1 UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94109. ALBERT EINSTEIN COLL MED,DEPT PEDIAT,BRONX,NY 10467. MASSACHUSETTS DEPT PUBL HLTH,BUR FAMILY & COMMUNITY HLTH,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH & SOCIAL BEHAV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,DIV GEN PEDIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Newacheck, PW (reprint author), UNIV CALIF SAN FRANCISCO,INST HLTH POLICY STUDIES,1388 SUTTER ST,11TH FLOOR,SAN FRANCISCO,CA 94109, USA. FU PHS HHS [MCJ-25R026] NR 18 TC 56 Z9 56 U1 1 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 1996 VL 98 IS 5 BP 952 EP 958 PG 7 WC Pediatrics SC Pediatrics GA VR466 UT WOS:A1996VR46600015 PM 8909492 ER PT J AU Trauner, KB Hasan, T AF Trauner, KB Hasan, T TI Photodynamic treatment of rheumatoid and inflammatory arthritis SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Review ID ANTI-CD4 MONOCLONAL-ANTIBODY; ADJUVANT-ENHANCED ARTHRITIS; SYNOVIAL-FLUID; ARTHROSCOPIC SYNOVECTOMY; KNEE-JOINT; T-CELL; EXTRACORPOREAL PHOTOCHEMOTHERAPY; DENDRITIC CELLS; FOLLOW-UP; THERAPY C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02114. RP Trauner, KB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ORTHOPAED SURG,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. NR 123 TC 44 Z9 45 U1 0 U2 1 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 NOV PY 1996 VL 64 IS 5 BP 740 EP 750 DI 10.1111/j.1751-1097.1996.tb01829.x PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VT662 UT WOS:A1996VT66200003 PM 8931370 ER PT J AU Gonschior, P Gerheuser, F Fleuchaus, M Huehns, TY Goetz, AE Welsch, U Sroka, R Dellian, M Lehr, HA Hofling, B AF Gonschior, P Gerheuser, F Fleuchaus, M Huehns, TY Goetz, AE Welsch, U Sroka, R Dellian, M Lehr, HA Hofling, B TI Local photodynamic therapy reduces tissue hyperplasia in an experimental restenosis model SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ARTERY; ANGIOPLASTY; DELIVERY; CATHETER; INJURY AB Local photodynamic therapy may have potential in preventing myointimal hyperplasia after angioplasty. In this study, the effect of photodynamic therapy was evaluated in an experimental model of restenosis. Standardized unidirectional arterial injury with a directional atherectomy catheter was performed in porcine arteries. Animals were randomly allocated to four groups: group 1, unidirectional injury only; group 2, injury followed by local delivery of photosensitizer; group 3, injury followed by local exposure to monochromatic light; and group 4, where injury was followed by local drug delivery of photosensitizer and subsequent exposure to light (photodynamic therapy). Seven, 14 or 21 days after treatment, all experimental vessel were excised, fixed and processed for histology. An inflammatory and myoproliferative response was observed after injury in vessels from groups 1, 2 and 3. In group 4, after injury followed by photodynamic therapy, the myoproliferative response was significantly reduced. Thus, in this study, tissue hyperplasia after unidirectional injury was effectively suppressed by photodynamic therapy. C1 UNIV MUNICH,KLINIKUM GROSSHADERN,INST ANESTHESIA,D-81377 MUNICH,GERMANY. UNIV MUNICH,INST ANAT,D-81377 MUNICH,GERMANY. GSF MUNICH,LASER RES DEPT,MUNICH,GERMANY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. RP Gonschior, P (reprint author), UNIV MUNICH,KLINIKUM GROSSHADERN,DEPT MED 1,MARCHIONINISTR 15,D-81377 MUNICH,GERMANY. RI Sroka, Ronald/I-2765-2013 NR 26 TC 24 Z9 27 U1 0 U2 0 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 NOV PY 1996 VL 64 IS 5 BP 758 EP 763 DI 10.1111/j.1751-1097.1996.tb01831.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VT662 UT WOS:A1996VT66200005 PM 8931372 ER PT J AU Matarasso, A Elias, AC Elias, RL AF Matarasso, A Elias, AC Elias, RL TI Labial incompetence: A marker for progressive bone resorption in silastic chin augmentation SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID IMPLANTS; GENIOPLASTY; MENTOPLASTY; PROPLAST AB Bone erosion below silicone rubber implants is a well-known sequela, occurring in a majority of patients undergoing augmentation genioplasty. It is generally considered to be self-limiting and with minimal adverse consequences. However, if bone erosion progresses to the extent to which teeth are jeopardized or alterations in sensibility of the mental nerve occur, removal of the implant is indicated. Osteoplastic genioplasty may be required to restore aesthetic contour to the chin and to avoid functional anomalies that may occur from explantation. A number of factors have been identified that contribute to this phenomenon; however, speculation regarding its etiology has not acknowledged the functional aberration of a tensed mentalis muscle. A study of six patients with aesthetically positioned and appropriately sized Silastic implants revealed a correlation between preoperative baseline labial incompetence and mentalis muscle hyperactivity and progressive bony erosion. One patient had grade II erosion and four patients had grade III erosion, one with the exposure of dental roots. The sixth patient with mentalis muscle strain, subsequent to attempts to contain her lower denture, also had severe resorption. Such findings suggest that attention should be paid to an alternative approach in microgenic patients presenting with lip strain, since labial incompetence appears to be a reliable marker for ongoing mandibular resorption following Silastic augmentation. Furthermore, since most patients are asymptomatic until significant erosion occurs or are satisfied and do not return, in those individuals with labial incompetence who have already had Silastic chin implants, consideration should be given to routine follow-up examination and radiographs. C1 ALBERT EINSTEIN COLL MED,DIV PLAST SURG,NEW YORK,NY. MANHATTAN EYE EAR & THROAT HOSP,NEW YORK,NY 10021. MT SINAI HOSP,DEPT ORAL & MAXILLOFACIAL SURG,NEW YORK,NY 10029. MASSACHUSETTS GEN HOSP,DIV ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02114. NR 28 TC 30 Z9 30 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD NOV PY 1996 VL 98 IS 6 BP 1007 EP 1014 DI 10.1097/00006534-199611000-00012 PG 8 WC Surgery SC Surgery GA VQ891 UT WOS:A1996VQ89100012 PM 8911470 ER PT J AU Engelman, A AF Engelman, A TI Biochemical characterization of recombinant equine infectious anemia virus integrase SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID ESCHERICHIA-COLI; TYPE-1 INTEGRASE; VIRAL-DNA; RNA-POLYMERASE; PROTEIN; INVITRO; EXPRESSION; CLEAVAGE AB The integrase from equine infectious anemia virus (EIAV) was expressed in Escherichia coli as a polyhistidine fusion protein. The protein was purified under native and denaturing conditions using one-step nickel-affinity chromatography. The purified denatured protein was refolded in the presence of detergent. In vitro 3' processing and DNA strand transfer activities were analyzed under Mg2+- and Mn2+-dependent reaction conditions. Both protein preparations were similarly active. Only one viral DNA end was efficiently integrated during Mn2+- and Mg2+-dependent DNA strand transfer. Water was the predominant nucleophile for Mg2+- and Mn2+-dependent 3' processing activity. The results underscore functional similarities between EIAV integrase and the previously characterized HIV-1 enzyme. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. RP Engelman, A (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV HUMAN RETROVIROL, 44 BINNEY ST, BOSTON, MA 02115 USA. FU PHS HHS [P30 A128691] NR 29 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 EI 1096-0279 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD NOV PY 1996 VL 8 IS 3 BP 299 EP 304 DI 10.1006/prep.1996.0104 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA VT837 UT WOS:A1996VT83700004 PM 8936591 ER PT J AU Johnson, BA Jasinski, DR Galloway, GP Kranzler, H Weinreib, R Anton, RF Mason, BJ Bohn, MJ Pettinati, HM Rawson, R Clyde, C AF Johnson, BA Jasinski, DR Galloway, GP Kranzler, H Weinreib, R Anton, RF Mason, BJ Bohn, MJ Pettinati, HM Rawson, R Clyde, C TI Ritanserin in the treatment of alcohol dependence - A multi center clinical trial SO PSYCHOPHARMACOLOGY LA English DT Article DE serotonin; (5-HT); ritanserin; 5-HT2 antagonist; alcoholism; clinical trial; multi-center; pharmacotherapy; humans ID CARBOHYDRATE-DEFICIENT TRANSFERRIN; PLACEBO-CONTROLLED TRIAL; VOLUNTARY ETHANOL-CONSUMPTION; COPING SKILLS; INTERACTIONAL THERAPIES; CONSUMMATORY BEHAVIORS; MATCHING ALCOHOLICS; RECEPTOR ANTAGONIST; 5-HT2 ANTAGONIST; SOCIAL DRINKERS AB Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled study to determine the safety and efficacy of the 5-HT2 receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1 week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received weekly individual sessions of manual-guided cognitive-behavioral therapy, Comparing the single-blind period with endpoint, there was approximately a 33% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in drinks/drinking day; and a 37% diminution in. alcohol craving for all treatment groups, All treatment groups experienced a beneficial clinical outcome as assessed by the Clinical Global Impression Scale, There was, however. no significant difference between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome, Subjects were of relatively high social functioning at baseline, and this did not change significantly during treatment, Treatment groups did not differ significantly on either medication compliance or reported adverse events, Ritanserin treatment was associated with a dose-related prolongation of subjects' QTc interval recording on the electrocardiogram, These results suggest that alcohol dependent subjects can show marked clinical improvement within a structured alcohol treatment program, These findings do not support an important role for ritanserin in the treatment of alcohol dependence. C1 FRANCIS SCOTT KEY MED CTR,BALTIMORE,MD 21224. HAIGHT ASHBURY FREE CLIN INC,SAN FRANCISCO,CA 94117. UNIV CONNECTICUT,CTR HLTH,DEPT PSYCHIAT,ALCOHOL RES CTR,FARMINGTON,CT 06003. UNIV PENN,TREATMENT RES CTR,PHILADELPHIA,PA 19104. MED UNIV S CAROLINA,DEPT PSYCHIAT,CHARLESTON,SC 29424. UNIV MIAMI,SCH MED,ALCOHOL DISORDERS RES UNIT,MIAMI,FL 33136. UNIV WISCONSIN,SCH MED,DEPT PSYCHIAT,MADISON,WI 53705. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. MATRIX CTR,LOS ANGELES,CA 90025. JANSSEN RES FDN,TITUSVILLE,NJ 08560. RP Johnson, BA (reprint author), UNIV TEXAS,HLTH SCI CTR,CLIN LAB,1300 MOURSUND,HOUSTON,TX 77030, USA. RI Mason, Barbara/P-6604-2016 NR 71 TC 65 Z9 65 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 1996 VL 128 IS 2 BP 206 EP 215 DI 10.1007/s002130050126 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VU304 UT WOS:A1996VU30400010 PM 8956382 ER PT J AU Worthington, J Fava, M Agustin, C Alpert, J Nierenberg, AA Pava, JA Rosenbaum, JF AF Worthington, J Fava, M Agustin, C Alpert, J Nierenberg, AA Pava, JA Rosenbaum, JF TI Consumption of alcohol, nicotine, and caffeine among depressed outpatients - Relationship with response to treatment SO PSYCHOSOMATICS LA English DT Article; Proceedings Paper CT 1994 Annual Meeting of the Academy-of-Psychosomatic-Medicine CY NOV 17-20, 1994 CL PHOENIX, AZ SP Acad Psychosomat Med ID PSYCHIATRIC-DISORDERS; MAJOR DEPRESSION; SMOKING; PREVALENCE; DEPENDENCE; POPULATION; PROGRAM; ILLNESS; COFFEE AB The authors present findings from the first investigation of the use of alcohol, nicotine, and caffeine in nonsubstance-abusing outpatients with major depressive disorder. The patients (N = 94) were assessed for their intake of alcohol, nicotine, and caffeine, and then treated openly for 8 weeks with 20 mg/day of fluoxetine. The degree of alcohol consumption at baseline was a significant predictor of poorer response to the antidepressant. This relationship remained significant even after adjusting for severity of depression at baseline. Even moderate levels of alcohol consumption appear to negatively affect pharmacologic treatment in depressed outpatients. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Worthington, J (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS RES PROGRAM,15 PARKMAN ST,BOSTON,MA 02114, USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01 MH-48483-03] NR 24 TC 44 Z9 44 U1 2 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 1996 VL 37 IS 6 BP 518 EP 522 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA VQ011 UT WOS:A1996VQ01100004 PM 8942202 ER PT J AU Greenberg, DB AF Greenberg, DB TI Handbook of functional gastrointestinal disorders - Olden,KW SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Greenberg, DB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 1996 VL 37 IS 6 BP 568 EP 569 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA VQ011 UT WOS:A1996VQ01100010 ER PT J AU Greenberg, DB AF Greenberg, DB TI Essential psychopharmacology: Neuroscientific basis and practical applications - Stahl,SM SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Greenberg, DB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 1996 VL 37 IS 6 BP 569 EP 570 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA VQ011 UT WOS:A1996VQ01100011 ER PT J AU Vatnitsky, S Siebers, J Miller, D Moyers, M Schaefer, M Jones, D Vynckier, S Hayakawa, Y Delacroix, S Isacsson, U Medin, J Kacperek, A Lomax, A Coray, A Kluge, H Heese, J Verhey, L Daftari, I Gall, K Lam, G Beck, T Hartmann, G AF Vatnitsky, S Siebers, J Miller, D Moyers, M Schaefer, M Jones, D Vynckier, S Hayakawa, Y Delacroix, S Isacsson, U Medin, J Kacperek, A Lomax, A Coray, A Kluge, H Heese, J Verhey, L Daftari, I Gall, K Lam, G Beck, T Hartmann, G TI Proton dosimetry intercomparison SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE proton dosimetry; intercomparison; inter-institutional uniformity ID BEAM; CODE AB Background and purpose: Methods for determining absorbed dose in clinical proton beams are based on dosimetry protocols provided by the AAPM and the ECHED. Both groups recommend the use of air-filled ionization chambers calibrated in terms of exposure or air kerma in a Co-60 beam when a calorimeter or Faraday cup dosimeter is not available. The set of input data used in the AAPM and the ECHED protocols, especially proton stopping powers and w-value is different. In order to verify inter-institutional uniformity of proton beam calibration, the AAPM and the ECHED recommend periodic dosimetry intercomparisons. In this paper we report the results of an international proton dosimetry intercomparison which was held at Loma Linda University Medical Center. The goal of the intercomparison was two-fold: first, to estimate the consistency of absorbed dose delivered to patients among the participating facilities, and second, to evaluate the differences in absorbed dose determination due to differences in Co-60-based ionization chamber calibration protocols. Materials and methods: Thirteen institutions participated in an international proton dosimetry intercomparison, The measurements were performed in a 15-cm square field at a depth of 10 cm in both an unmodulated beam (nominal accelerator energy of 250 MeV) and a 6-cm modulated beam (nominal accelerator energy of 155 MeV), and also in a circular field of diameter 2.6 cm at a depth of 1.14 cm in a beam with 2.4 cm modulation (nominal accelerator energy of 100 MeV). Results: The results of the intercomparison have shown that using ionization chambers with Co-60 calibration factors traceable to standard laboratories, and institution-specific conversion factors and dose protocols, the absorbed dose specified to the patient would fall within 3% of the mean value. A single measurement using an ionization chamber with a proton chamber factor determined with a Faraday cup calibration differed from the mean by 8%. Conclusion: The adoption of a single ionization chamber dosimetry protocol and uniform conversion factors will establish agreement on proton absorbed dose to approximately 1.5%, consistent with that which has been observed in high-energy photon and electron dosimetry. C1 NATL ACCELERATOR CTR,ZA-7131 FAURE,SOUTH AFRICA. UNIV CATHOLIQUE LOUVAIN,B-1348 LOUVAIN,BELGIUM. PROTON MED RES CTR,TSUKUBA,IBARAKI,JAPAN. PROTON THERAPY CTR ORSAY,ORSAY,FRANCE. UNIV HOSP,SVEDBERG LAB,UPPSALA,SWEDEN. CLATTERBRIDGE CTR ONCOL,CLATTERBRIDGE,ENGLAND. PAUL SCHERRER INST,VILLIGEN,SWITZERLAND. HAHN MEITNER INST BERLIN GMBH,D-1000 BERLIN,GERMANY. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV BRITISH COLUMBIA,TRIUMF,VANCOUVER,BC V5Z 1M9,CANADA. GERMAN CANC RES CTR,D-6900 HEIDELBERG,GERMANY. RP Vatnitsky, S (reprint author), LOMA LINDA UNIV,MED CTR,LOMA LINDA,CA 92350, USA. OI Kacperek, Andrzej/0000-0002-2434-2924 FU NCI NIH HHS [CA 31239] NR 24 TC 25 Z9 26 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD NOV PY 1996 VL 41 IS 2 BP 169 EP 177 DI 10.1016/S0167-8140(96)01800-2 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA WA119 UT WOS:A1996WA11900010 PM 9004361 ER PT J AU Ballantyne, JC Carr, DB Berkey, CS Chalmers, TC Mosteller, F AF Ballantyne, JC Carr, DB Berkey, CS Chalmers, TC Mosteller, F TI Comparative efficacy of epidural, subarachnoid, and intracerebroventricular opioids in patients with pain due to cancer SO REGIONAL ANESTHESIA LA English DT Article DE epidural opioid; subarachnoid opioid; intracerebroventricular opioid; cancer pain ID LONG-TERM TREATMENT; INTRAVENTRICULAR MORPHINE; INTRATHECAL MORPHINE; INTRACTABLE PAIN; CONTINUOUS INFUSION; META-ANALYSIS; NARCOTIC ANALGESIA; IMPLANTED PUMP; SYSTEM; INJECTION AB Background and Objectives. Although rarely used, intracerebroventricular opioid therapy (ICV) is an option for the control of intractable pain due to cancer when systemic treatments have failed. The aim of the present study is to use available data from published trials to compare ICV with the more common epidural (EPI) and subarachnoid (SA) opioid treatments in an attempt to establish the utility and safety of ICV. Methods. Because there are no published controlled trials comparing these routes of administration, the combined data from multiple uncontrolled trials were used, with differences between the treatments analyzed statistically. Trials assessing ICV (13 trials, 268 patients), EPI (29 trials, 909 patients) and SA (21 trials, 410 patients) in cancer patients were identified; data on analgesic efficacy common pharmacologic side effects, and complications were then extracted and the accumulated incidence data analyzed. Results. The findings (weighted means) indicated ICV to be at least as effective against pain as other neuraxial treatments, with 75% of ICV-treated patients obtaining excellent pain relief as compared with 72% of EPI- and 58% of SA-treated patients (not significant). The failure rate of both spinal treatments tended to be greater than that of ICV and was significantly higher in the case of EPI (P = .045). In general, persistent side effects appeared to be more of a problem with the spinal treatments, while transient symptoms occur more often with ICV. Persistent nausea, urinary retention, and pruritus all were more frequent with the two spinal treatments than with ICV, but transient nausea and respiratory depression occurred more often with ICV. Sedation and confusion appeared to occur more often with ICV than with spinal therapy, while constipation and headache were rarely encountered with ICV. There were no real differences in infectious complication rates among the three treatments (except for a lower rate of infection when an implanted pump was used), but technical problems such as catheter blockage, misplacement, or leakage tended to occur less often with ICV. Conclusions. Intracerebroventricular therapy appears to be at lease as effective against pain as other neuraxial treatments. The ICV technique is the only fixed system that is associated with fewer technical problems than the use of simple percutaneous epidural catheters (difference 9%, standard error of the difference 3.4). The present state of evidence indicates that ICV is a successful treatment for patients with intractable cancer pain and compares well with spinal opioid treatments in terms of efficacy, side effects, and complications. C1 MASSACHUSETTS GEN HOSP,MGH PAIN CTR,DEPT ANESTHESIOL,BOSTON,MA 02114. NR 68 TC 22 Z9 22 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0146-521X J9 REGION ANESTH JI Reg. Anesth. PD NOV-DEC PY 1996 VL 21 IS 6 BP 542 EP 556 PG 15 WC Anesthesiology SC Anesthesiology GA VW988 UT WOS:A1996VW98800008 PM 8956391 ER PT J AU Foust, RT AF Foust, RT TI Infection of a pancreatic pseudocyst due to Candida albicans SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID EARLY DIAGNOSIS; ABSCESS AB A 40-year-old man with diabetes mellitus, congestive heart failure, alcoholic cirrhosis, and chronic pancreatitis had an exacerbation of pancreatitis due to alcohol abuse, His condition deteriorated rapidly with development of apparent sepsis; cultures were negative, He slowly improved,vith multiple antibiotic therapy and total parenteral nutrition, Serial imaging of the pancreas revealed edematous pancreatitis that evolved initially into a phlegmon and later into multiple pseudocysts, Intermittent fever prompted computed-tomography-directed percutaneous aspiration of the largest pancreatic fluid collection, yielding purulent material that grew only Candida albicans, Subsequently, disseminated candidiasis developed. Despite therapy with amphotericin B and aggressive supportive care, the patient died from multiple organ system failure. C1 RALPH H JOHNSON VA MED CTR,CHARLESTON,SC. RP Foust, RT (reprint author), MED UNIV S CAROLINA,DIV GASTROENTEROL & HEPATOL,SUITE 916,CSB,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 30 TC 7 Z9 7 U1 0 U2 1 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD NOV PY 1996 VL 89 IS 11 BP 1104 EP 1107 DI 10.1097/00007611-199611000-00018 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA VR731 UT WOS:A1996VR73100018 PM 8903299 ER PT J AU Suwanwela, N Can, U Furie, KL Southern, JF Macdonald, NR Ogilvy, CS Hansen, CJ Buonanno, FS Abbott, WM Koroshetz, WJ Kistler, JP AF Suwanwela, N Can, U Furie, KL Southern, JF Macdonald, NR Ogilvy, CS Hansen, CJ Buonanno, FS Abbott, WM Koroshetz, WJ Kistler, JP TI Carotid Doppler ultrasound criteria for internal carotid artery stenosis based on residual lumen diameter calculated from en bloc carotid endarterectomy specimens SO STROKE LA English DT Article DE carotid endarterectomy; Doppler; pathology ID MAGNETIC-RESONANCE ANGIOGRAPHY; GROSS PATHOLOGY; SONOGRAPHY; CANDIDATES; TIME; ULTRASONOGRAPHY; ARTERIOGRAPHY; REAPPRAISAL; ISCHEMIA; EFFICACY AB Background and Purpose Carotid duplex ultrasound is widely used to screen patients for carotid endarterectomy and if combined with MR angiography and transcranial Doppler may be an alternative to conventional angiography in the preoperative assessment. We have examined the correlation between Doppler velocities and the residual lumen diameters of internal carotid arteries from surgical pathological specimens to establish Doppler criteria for residual lumen diameter independent of percent stenosis. Methods Ninety-one patients who underwent 99 carotid endarterectomies for internal carotid artery stenosis within 6 months of their carotid duplex ultrasound evaluation were studied. The endarterectomy specimens were removed en bloc, and the minimal residual lumen diameter was calculated by computer analysis. The sensitivity and specificity of the Doppler criteria for determining high-grade stenosis were calculated and receiver-operator curves generated. Results Peak systolic velocity (PSV), end-diastolic velocity (EDV), and carotid index (peak internal carotid artery velocity/common carotid artery velocity) correlated with the residual lumen diameter. PSV > 440 cm/s, EDV > 155 cm/s, or carotid index > 10 indicated a residual lumen diameter of less than or equal to 1.5 mm (specificity of 100% and sensitivity of 58%, 63%, and 30%, respectively). When these criteria were combined the sensitivity increased to 72%. A PSV > 200 cm/s combined with either an EDV > 140 cm/s or a carotid index > 4.5 has a sensitivity of 96% and a specificity of 61%. Conclusions Doppler criteria can be both specific and sensitive for detecting a significant stenosis, defined as a less than or equal to 1.5 mm residual lumen diameter. By adjustment of the velocity criteria, it can be 100% specific or a highly sensitive test (96%). C1 MASSACHUSETTS GEN HOSP,STROKE SERV,CEREBROVASC SECT,VASC LAB,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,VASC SURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PATHOL SERV,BOSTON,MA 02114. NR 44 TC 46 Z9 46 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 NOV PY 1996 VL 27 IS 11 BP 1965 EP 1969 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VQ163 UT WOS:A1996VQ16300006 PM 8898799 ER PT J AU Cramer, SC Robertson, RL Dooling, EC Scott, RM AF Cramer, SC Robertson, RL Dooling, EC Scott, RM TI Moyamoya and Down syndrome - Clinical and radiological features SO STROKE LA English DT Article DE Down syndrome; moyamoya disease; recovery; stroke ID DOWNS-SYNDROME; SURGICAL-TREATMENT; DISEASE; CHILDREN; ABNORMALITIES; ASSOCIATION; INFARCTION; STENOSIS; VESSELS; NEURONS AB Background and Purpose Moyamoya disease is a chronic occlusive cerebrovascular disorder characterized by progressive stenosis of the supraclinoid internal carotid artery, with the secondary development of enlarged basal collateral vessels. It may occur as a primary disease or as a syndrome in association with a variety of conditions, and its pathogenesis remains unexplained. There are relatively few reports describing the occurrence of moyamoya in Down syndrome. The aim of this study is to describe the clinical and radiological features of moyamoya syndrome associated with Down syndrome (MM-DS) and to explore theories of moyamoya pathogenesis in these patients. Methods Seven children with MM-DS underwent brain imaging, transfemoral angiography, and serial neurological exams. Neurological deficits, poststroke recovery, radiographic infarct characteristics, and angiographic abnormalities were reviewed. Results The clinical and radiological features of primary moyamoya disease overlap with those of MM-DS. Hemiplegia and aphasia were the most common presentations. Motor recovery was excellent in five of seven cases. Cerebral infarcts were superficial or deep and can occur in a watershed distribution. Angiography demonstrated involvement of the internal carotid artery and its branches bilaterally in all seven cases and the posterior cerebral arteries in four cases. Conclusions The clinical and radiological features of MM-DS overlap with primary moyamoya disease. We postulate that a protein encoded on chromosome 21 may be related to the pathogenesis of moyamoya disease. Although the neuronal substrate is abnormal in Down syndrome patients, recovery from hemiplegic stroke in patients with MM-DS is comparable to recovery in patients with primary moyamoya. C1 MASSACHUSETTS GEN HOSP,PEDIAT NEUROL UNIT,BOSTON,MA 02114. HARVARD UNIV,CHILDRENS HOSP,SCH MED,SERV RADIOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,NEUROSURG SERV,BOSTON,MA 02115. RP Cramer, SC (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,BIGELOW 1256,FRUIT ST,BOSTON,MA 02114, USA. OI Robertson, Richard/0000-0001-8811-4405 NR 49 TC 59 Z9 60 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 NOV PY 1996 VL 27 IS 11 BP 2131 EP 2135 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VQ163 UT WOS:A1996VQ16300041 PM 8898827 ER PT J AU Morris, ED Babich, JW Alpert, NM Bonab, AA Livni, E Weise, S Hsu, HB Christian, BT Madras, BK Fischman, AJ AF Morris, ED Babich, JW Alpert, NM Bonab, AA Livni, E Weise, S Hsu, HB Christian, BT Madras, BK Fischman, AJ TI Quantification of dopamine transporter density in monkeys by dynamic PET imaging of multiple injections of C-11-CFT SO SYNAPSE LA English DT Article DE mathematical model; displacement study; receptor occupancy; B'max; parameter estimates ID POSITRON EMISSION TOMOGRAPHY; COCAINE RECOGNITION SITES; PARKINSONS-DISEASE; BINDING-SITES; H-3 CFT; MPTP; INVIVO; BRAIN; WIN-35,428; RECEPTORS AB Idiopathic Parkinson's disease (PD) is characterized by loss of dopaminergic terminals in the basal ganglia. The cocaine analog, CFT (WIN 35,428), has been shown to bind selectively to the pre-synaptic dopamine transporters and thus represents an important probe for monitoring disease progression. In this study, we evaluated [C-11] labeled CFT as a PET ligand for the quantitative in vivo assay of dopamine transporter density in three normal rhesus monkeys (Macaca mulatta). One of the animals was studied after treatment with the neurotoxin, MPTP. Simulation studies demonstrated that a three injection protocol is necessary for quantitation of dopamine transporter density. The protocol consists of an initial high specific activity injection, a low specific activity ''displacement dose'' at 30 min, and a final high specific activity injection at similar to 90 min. Dynamic PET imaging and arterial blood sampling were started immediately before the first injection and continued for 2 h. Blood data were corrected for [C-11] labeled CFT metabolites. Compartmental models describing the dynamics of labeled and the unlabeled ligand explicitly were fitted to the PET and metabolite corrected blood data. Prior to MPTP treatment, modeling of the striatal data required a saturable receptor term and yielded mean estimates of: B'(max) = 113 pmol/g and K-D = 33 nM (n = 3). These values for B'(max) are in reasonable agreement with published values for [H-3] CFT binding in vitro. After multiple treatments with MPTP (0.6 mg/kg x 3), B'(max) in one of the animals was reduced from 122 to 10.2 pmol/g. K-D was relatively unaffected by MPTP treatment. These data provide additional basis for the use of [C-11] CFT in monitoring the progression of Parkinson's disease and other conditions that are associated with the loss of dopaminergic nerve terminals. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. FU NCI NIH HHS [T32 CA 09362]; NCRR NIH HHS [RR00168]; NINDS NIH HHS [NS30556] NR 29 TC 35 Z9 36 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 0887-4476 J9 SYNAPSE JI Synapse PD NOV PY 1996 VL 24 IS 3 BP 262 EP 272 DI 10.1002/(SICI)1098-2396(199611)24:3<262::AID-SYN9>3.0.CO;2-C PG 11 WC Neurosciences SC Neurosciences & Neurology GA VQ912 UT WOS:A1996VQ91200009 PM 8923667 ER PT J AU Hunter, AGW Cleveland, RH Blickman, JG Holmes, LB AF Hunter, AGW Cleveland, RH Blickman, JG Holmes, LB TI A study of level of lesion, associated malformations and sib occurrence risks in spina bifida SO TERATOLOGY LA English DT Article ID NEURAL-TUBE DEFECTS; ETIOLOGIC HETEROGENEITY; MULTISITE CLOSURE; NEURULATION; SEX AB Neural tube defects remain the most serious common birth defect and, despite considerable progress in understanding these malformations, the etiology of most cases remains unknown. It has been proposed that the cause may vary with the type and location of the malformation but, if these variables ave to be studied, a rigorous classification of cases is required. This has become more important as birth prevalence has fallen, mainly due to prenatal diagnosis and elective termination of pregnancy, and future studies will increasingly require collaboration between centres. In this study we have combined data from Ottawa, Ontario, and Boston, Massachusetts, in an attempt to examine the effect of level of spina bifida on sib occurrence rates and the rates of associated malformations, and to compare the level of lesion when determined radiographically with that recorded on the clinical chart, Malformations appeared to be more frequent with thoracic spina bifida and were more often associated with additional vertebral anomalies. Significant differences were found between the upper level of lesion recorded in the clinical file and that visible radiographically. Sib recurrences were too few for statistical comparison, but the data suggest a higher rate among sibs and more distant relatives of propositi with upper level lesions. There was not evidence to support a greater than expected concordance for level of lesion between sibs. (C) 1997 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,CHILDRENS SERV,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,TERATOL UNIT,BOSTON,MA 02114. RP Hunter, AGW (reprint author), CHILDRENS HOSP EASTERN ONTARIO,DEPT GENET,401 SMYTH RD,OTTAWA,ON K1H 8L1,CANADA. FU NHLBI NIH HHS [HO24560] NR 25 TC 14 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 0040-3709 J9 TERATOLOGY JI Teratology PD NOV PY 1996 VL 54 IS 5 BP 213 EP 218 DI 10.1002/(SICI)1096-9926(199611)54:5<213::AID-TERA1>3.0.CO;2-0 PG 6 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA WG679 UT WOS:A1996WG67900001 PM 9035342 ER PT J AU Salazar, M Granja, CB Selvakumar, A Fresia, B Alosco, S Dupont, B Yunis, EJ AF Salazar, M Granja, CB Selvakumar, A Fresia, B Alosco, S Dupont, B Yunis, EJ TI New HLA-DR haplotypes containing the DRB6 pseudogene SO TISSUE ANTIGENS LA English DT Article DE HLA; DR; DRB6 ID MOLECULAR CHARACTERIZATION; RECOMBINANT AB An unexpected probe reaction pattern was observed in two samples during HLA-DR typing by PCR-Sequence Specific Oligonucleotide Probes. In order to confirm the unusual typings, samples were analyzed by PCR-Sequence Specific Primers, cloning, and nucleotide sequencing of the second exon of the HLA-DRB-genes. The confirmed DR, DQ phenotype for one sample was DRB1*0701, DRB4*01, DRB5*0101, DRB6*0201, DQB*0602, DQB1*0202. The phenotype of other sample was DRB1*1602, DRB1*1302, DRB3*0301, DRB6*0101, DQB1*0501, DQB1*0502. The first sample has the novel combination of DRB1*0701 with DRB5*0101 and DRB6*0201. The second sample has either DRB6*0101 together with DRB1*1602 in absence of any DRB5 allele or DRB6*0101 together with DRB1*1302, DRB3*0301. We postulate that the most likely haplotype in sample #1 is DRB1*0701, DRB5*0101, DRB1*0602 which could have arisen from gene conversion. The most likely haplotype in sample #2, DRB1*1602, DRB6*0101, DQB1*0502 would have arisen from an homologous recombination event. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. SLOAN KETTERING INST CANC RES,NEW YORK,NY. RP Salazar, M (reprint author), AMER RED CROSS,NEW ENGLAND REG,180 RUSTCRAFT RD,DEDHAM,MA 02026, USA. NR 12 TC 3 Z9 3 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 NOV PY 1996 VL 48 IS 5 BP 575 EP 579 DI 10.1111/j.1399-0039.1996.tb02671.x PG 5 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA VY743 UT WOS:A1996VY74300008 PM 8988540 ER PT J AU Vamvakas, EC Carven, JH Hibberd, PL AF Vamvakas, EC Carven, JH Hibberd, PL TI Blood transfusion and infection after colorectal cancer surgery SO TRANSFUSION LA English DT Article ID POSTOPERATIVE SEPTIC COMPLICATIONS; DESIGN AFFECTS OUTCOMES; NOSOCOMIAL PNEUMONIA; AUTOLOGOUS BLOOD; IMMUNE FUNCTION; RISK-FACTORS; RECURRENCE; ASSOCIATION; THERAPY; METAANALYSIS AB Background: Many observational studies have described an association between perioperative transfusion and postoperative infection, Detection of such a relationship may depend on which variables are considered as potential confounders of the association under study. However, most reports have not considered risk factors for postoperative infection at specific sites as possible explanations for the observed relationship. Study Design and Methods: The records of 492 patients undergoing elective colorectal cancer resection at the Massachusetts General Hospital between January 1992 and December 1994 were reviewed. The probability of infection in association with transfusion was calculated with and without adjustment for the effects of chronic systemic illness, number of days with urinary catheter, endotracheal intubation, impaired consciousness, and specific risk factors for wound infection. Postoperative infection at any site and infections at specific sites were analyzed as separate outcomes. Results: After adjustment for the effects of the variables listed above, allogeneic transfusion was not associated with postoperative infection at any site (p = 0.407). Only a specific association of transfusion with wound infection could be detected. However, in an analysis that adjusted for the effects of only the 18 confounders considered by previous authors, transfusion was the most significant predictor of infection. In that analysis, the risk of postoperative infection Increased by 14 percent per unit of red cells transfused (p<0.001). Conclusion: The overall adverse relationship between transfusion and infection reported by previous observational studies may have been dire to an incomplete consideration of the variables that confound that association, This finding may help explain the disagreement between the conclusions of recent large, randomized, controlled trials (which failed to detect a deleterious transfusion effect) and the earlier observational studies. C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. RP Vamvakas, EC (reprint author), MASSACHUSETTS GEN HOSP,BLOOD TRANSFUS SERV,GRJ-224,GRAY BLDG,FRUIT ST,BOSTON,MA 02114, USA. NR 50 TC 69 Z9 70 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV-DEC PY 1996 VL 36 IS 11-12 BP 1000 EP 1008 DI 10.1046/j.1537-2995.1996.36111297091746.x PG 9 WC Hematology SC Hematology GA VU726 UT WOS:A1996VU72600013 PM 8937412 ER PT J AU Patti, ME Kahn, CR AF Patti, ME Kahn, CR TI Lessons from transgenic and knockout animals about noninsulin-dependent diabetes mellitus SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID INSULIN-RECEPTOR SUBSTRATE-1; ISLET AMYLOID POLYPEPTIDE; PANCREATIC BETA-CELLS; GLUCOSE-TRANSPORTER GLUT4; AMINO-ACID POLYMORPHISMS; SKELETAL-MUSCLES; YEAST HEXOKINASE; ADIPOSE-TISSUE; MICE; EXPRESSION AB The application of transgenic techniques to alter gene expression in vivo has provided new models to evaluate the role of specific genes in the complex pathogenesis of noninsulin-dependent diabetes mellitus (NIDDM). In this review we summarize methods used to create transgenic animals and highlight results from those models which have contributed to our understanding of the overall pathophysiology of NIDDM. Transgenic animal models have clearly demonstrated the requirement for normal insulin action in skeletal muscle, adipose tissue, and liver as well as normal insulin secretion by the pancreatic p-cell, in the maintenance of glucose homeostasis. In addition, these data confirm that isolated defects in single critical genes, including the insulin receptor IRS-1, and glucokinase, may play a role in the development of some types of insulin resistance and NIDDM. However, it is likely that multiple additive defects, both genetic and acquired are required to produce the full clinical syndrome typical of more common forms of NIDDM. (C) 1996, Elsevier Science Inc. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02215 USA. RP Patti, ME (reprint author), JOSLIN DIABET CTR, DIV RES, 1 JOSLIN PL, BOSTON, MA 02215 USA. NR 64 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD NOV PY 1996 VL 7 IS 9 BP 311 EP 319 DI 10.1016/S1043-2760(96)00154-3 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VV464 UT WOS:A1996VV46400001 PM 18406764 ER PT J AU Tootell, RBH Dale, AM Sereno, MI Malach, R AF Tootell, RBH Dale, AM Sereno, MI Malach, R TI New images from human visual cortex SO TRENDS IN NEUROSCIENCES LA English DT Review ID POSITRON-EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; OCULAR DOMINANCE COLUMNS; HUMAN BRAIN; MACAQUE MONKEY; CEREBRAL-ACHROMATOPSIA; SENSORY STIMULATION; OCCIPITAL CORTEX; CORTICAL AREAS; COLOR-CENTER AB Recent developments in imaging and histology have greatly clarified our understanding of the nature and organization of human visual cortex. More than ten human cortical visual areas can now be differentiated, compared with the approximately 30 areas described in macaque monkeys. Most human areas and columns described so far appear quite similar to those in macaque but distinctive species differences also exist. Imaging studies suggest two general information-processing streams (parietal and temporal) in human visual cortex, as proposed in macaque. Several human areas ave both motion- and direction-selective, and a progression of motion-processing steps can be inferred from the imaging data. Human visual areas for recognizing form are less well defined but the evidence again suggests a progression of information-processing steps and areas, beginning posterior to the human middle temporal area (or V5), and extending inferiorly then anteriorly. This is consistent with findings from macaque, and with human clinical reports. C1 UNIV CALIF SAN DIEGO, DEPT COGNIT SCI, SAN DIEGO, CA 92093 USA. WEIZMANN INST SCI, DEPT NEUROBIOL, IL-76100 REHOVOT, ISRAEL. RP Tootell, RBH (reprint author), MASSACHUSETTS GEN HOSP, NUCL MAGNET RESONANCE CTR, 149 13TH ST, CHARLESTOWN, MA 02129 USA. RI Dale, Anders/A-5180-2010; Sereno, Martin/F-7657-2012 OI Sereno, Martin/0000-0002-7598-7829 NR 99 TC 252 Z9 253 U1 1 U2 15 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD NOV PY 1996 VL 19 IS 11 BP 481 EP 489 DI 10.1016/S0166-2236(96)10053-9 PG 9 WC Neurosciences SC Neurosciences & Neurology GA VR301 UT WOS:A1996VR30100013 PM 8931274 ER PT J AU Kibel, AS Krithivas, K Shamel, LB Kantoff, PW DeWolf, WC AF Kibel, AS Krithivas, K Shamel, LB Kantoff, PW DeWolf, WC TI Constitutive expression of high levels of prostate-specific antigen in the absence of prostate carcinoma SO UROLOGY LA English DT Article ID TRANSITION ZONE BIOPSIES; MESSENGER-RNA; SERUM; CANCER; MEN; VALUES; ALPHA-1-ANTICHYMOTRYPSIN; DENSITY; DISEASE; MARKERS AB Objectives. To identify distinguishing serologic features in patients with stable marked elevation in prostate-specific antigen (PSA) and multiple negative biopsies. Methods. The study population consisted of 7 patients with a stable PSA level of greater than 20 ng/mL (average 27.0), followed for at least 54 months (average 56), and with two or more negative prostatic biopsies including transition zone biopsies. The PSA density (PSAD), rate of change in PSA, reverse transcriptase/polymerase chain reaction (RT/PCR), and free/total PSA were obtained. Results. Rate of change in PSA level was stable (0.18+/-1.2 ng/mL/yr), suggesting that there was no occult cancer; PSAD was high (0.34+/-0.5 ng/mL/cc), indicating that prostate size was not the sole cause of the elevation. The RT/PCR was negative in 6 of 7 patients, further decreasing the likelihood of an occult malignancy. Free versus total PSA was not consistent, averaging 16.8%, but with a range of 6% to 34%. Conclusions. Novel PSA tests were not found to be useful in this cohort of patients with multiple negative biopsies and PSA elevations greater than 20 ng/mL. Additional studies with larger sample size are required to confirm this finding. Copyright 1996 by Elsevier Science Inc. C1 BETH ISRAEL HOSP,DIV UROL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. HYBRITECH INC,DEPT RES & DEV,SAN DIEGO,CA. NR 31 TC 6 Z9 6 U1 1 U2 1 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD NOV PY 1996 VL 48 IS 5 BP 741 EP 746 DI 10.1016/S0090-4295(96)00235-X PG 6 WC Urology & Nephrology SC Urology & Nephrology GA VR748 UT WOS:A1996VR74800017 PM 8911518 ER PT J AU Gritsch, HA Sykes, M AF Gritsch, HA Sykes, M TI Host marrow has a competitive advantage that limits donor hematopoietic repopulation in mixed xenogeneic chimeras SO XENOTRANSPLANTATION LA English DT Article DE bone marrow transplantation; SCID mice; tolerance; hematopoiesis; hematopoietic competition ID NONLETHAL PREPARATIVE REGIMEN; COMBINED IMMUNE-DEFICIENCY; MONOCLONAL-ANTIBODIES; SCID MICE; NATURAL ANTIBODIES; CELLS; TOLERANCE; TRANSPLANTATION; BARRIER; DIFFERENTIATION AB In mixed xenogeneic (rat/mouse] chimeras, in which both donor and host hematopoietic cells coexist, donor hematopoiesis eventually declines, despite apparent immunological tolerance of the host to the donor. To explain this observation, we hypothesized that donor hematopoietic cells might have a competitive disadvantage in a xenogeneic environment. Since SCID (severe combined immunodeficient) bone marrow cells (BMC) are unable to produce functional B and T lymphocytes, they might compete for myeloid but not lymphocytic reconstitution of the animals, whereas marrow from the normal congenic strain, C.B-17, would compete for repopulation of both lineages. We therefore evaluated the capacity of SCID and C.B-17 mouse marrow to inhibit repopulation by rat BMC in irradiated SCID mouse recipients. Nine weeks after administration of T-cell depleted (TCD) F344 rat BMC alone to 3 Gy-irradiated SCID mice, rat cells of both the myeloid and the lymphoid lineages were readily detectable among peripheral blood leukocytes. Rat plus SCID mouse BMC reconstitution resulted in a marked reduction in rat myeloid repopulation, without affecting rat lymphoid repopulation. Rat plus TCD normal C.B-17 mouse BMC, on the other hand, completely inhibited repopulation of all rat lineages by 9 weeks. Since mouse marrow inhibited only the repopulation by rat cells of the lineages that the mouse marrow was itself capable of generating, we conclude that physiologic factors, such as species specificity or selectivity of cytokines, adhesion molecules, and other molecules important for hematopoiesis, provide a competitive advantage to host marrow over xenogeneic hematopoietic cells. This physiologic barrier must be overcome in addition to immunologic barriers if bone marrow transplantation (BMT) is to provide a feasible approach to inducing xenograft tolerance. In addition, we describe the development of a chronic graft-vs.-host-disease (GVHD)-like syndrome in SCID mouse recipients of TCD rat marrow. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. NR 36 TC 33 Z9 34 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 1996 VL 3 IS 4 BP 312 EP 320 DI 10.1111/j.1399-3089.1996.tb00153.x PG 9 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA VZ453 UT WOS:A1996VZ45300005 ER PT J AU Rosen, FS AF Rosen, FS TI Exquisite specificity: The monoclonal antibody revolution - Cambrosio,A, Keating,P SO NATURE LA English DT Book Review RP Rosen, FS (reprint author), CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD OCT 31 PY 1996 VL 383 IS 6603 BP 777 EP 777 DI 10.1038/383777a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VQ144 UT WOS:A1996VQ14400043 ER PT J AU Reiser, H Stadecker, MJ AF Reiser, H Stadecker, MJ TI Mechanisms of disease - Costimulatory B7 molecules in the pathogenesis of infectious and autoimmune diseases SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID T-CELL ACTIVATION; IN-VITRO; CD28-MEDIATED COSTIMULATION; MYCOBACTERIAL INFECTION; MURINE-B7 ANTIGEN; ADDITIONAL LIGAND; IMMUNE-RESPONSE; LYMPHOCYTES-T; CTLA-4; EXPRESSION C1 TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. FU NIAID NIH HHS [AI-18919, AI-33679, AI-35287] NR 70 TC 186 Z9 194 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 OCT 31 PY 1996 VL 335 IS 18 BP 1369 EP 1377 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA VP484 UT WOS:A1996VP48400007 PM 8857022 ER PT J AU McGovern, BA Miller, SW Flieder, DB AF McGovern, BA Miller, SW Flieder, DB TI A 50-year-old woman with cardiac disease, an electronic pacemaker, and cardiac arrest in ventricular fibrillation - Sarcoidosis involving the heart, lungs, peribronchial lymph nodes, liver, and spleen. Arrhythmogenic right ventricular dysplasia. Lipomatous hypertrophy of the atrial septum SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GIANT-CELL MYOCARDITIS; NECROPSY PATIENTS; FABRYS-DISEASE; CARDIOMYOPATHY; AMYLOIDOSIS; FEATURES; DYSFUNCTION; DIAGNOSIS; UTILITY; SYSTEM C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP McGovern, BA (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC ARRHYTHMIA SERV,BOSTON,MA 02114, USA. NR 48 TC 2 Z9 2 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 31 PY 1996 VL 335 IS 18 BP 1378 EP 1386 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA VP484 UT WOS:A1996VP48400008 ER PT J AU Andersen, J Goetghebeur, E Ryan, L AF Andersen, J Goetghebeur, E Ryan, L TI Missing cause of death information in the analysis of survival data SO STATISTICS IN MEDICINE LA English DT Article ID COMPETING RISKS; FAILURE AB Goetghebeur and Ryan proposed a method for proportional hazards analyses of competing risks failure-time data when the failure type is missing for some cases. This paper evaluates the properties of the method using data from a clinical trial in Hodgkin's disease. We generated several patterns of missingness in the cause of death in 'pseudo-studies' derived from the study database. We found that the proposed method provided regression coefficients and inferences that were less biased than those from other methods over an increasing percentage of missingness in the failure type when missingness is random, when it depends on an important covariate, when it depends on failure type, and when it depends on follow-up time. We present suggestions for study design with planned missingness in the failure type. C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. UNIV LIMBURG,MENS,NL-6200 MD MAASTRICHT,NETHERLANDS. RP Andersen, J (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NCI NIH HHS [CA61072] NR 10 TC 16 Z9 16 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 30 PY 1996 VL 15 IS 20 BP 2191 EP 2201 DI 10.1002/(SICI)1097-0258(19961030)15:20<2191::AID-SIM358>3.0.CO;2-D PG 11 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA VL323 UT WOS:A1996VL32300007 PM 8910963 ER PT J AU Shioda, T Fenner, MH Isselbacher, KJ AF Shioda, T Fenner, MH Isselbacher, KJ TI msg1, A novel melanocyte-specific gene, encodes a nuclear protein and is associated with pigmentation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE differential display; melanoma; 5'-rapid amplification of cDNA ends ID TUMOR PROGRESSION; DIFFERENTIAL DISPLAY; MALIGNANT-MELANOMA; MURINE MELANOCYTES; PRECURSOR LESIONS; RAS MUTATIONS; TRANSCRIPTION; EXPRESSION; CELLS; MICROPHTHALMIA AB Messenger RNA transcripts of the highly pigmented murine melanoma B16-F1 cells were compared with those from their weakly pigmented derivative B16-F10 cells by differential display. A novel gene called msg1 (melanocyte-specific gene) was found to be expressed at high levels in B16-F1 cells but at low levels in B16-F10 cells. Expression of msg1 was undetectable in the amelanotic g1735 murine melanoma cells. The pigmented murine melanocyte cell line melan-a expressed msg1, as did pigmented primary cultures of murine and human melanocytes; however, seven amelanotic or very weakly pigmented human melanoma cell lines were negative. Transformation of murine melanocytes by transfection with v-Ha-ras or Ela was accompanied by depigmentation and led to complete loss of msg1 expression. The normal tissue distribution of msg1 mRNA transcripts in adult mice was confined to melanocytes and testis. Murine msg1 and human MSG1 genes encode a predicted protein of 27 kDa with 75% overall amino acid identity and 96% identity within the C-terminal acidic domain of 54 amino acids. This C-terminal domain was conserved with 76% amino acid identity in another protein product of a novel human gene, MRG1 (msg1-related gene), isolated from normal human melanocyte cDNA by 5'-rapid amplification of cDNA ends based on the homology to msg1. The msg1 protein was localized to the melanocyte nucleus by immunofluorescence cytochemistry. We conclude that msg1 encodes a nuclear protein, is melanocyte-specific, and appears to be lost in depigmented melanoma cells. RP Shioda, T (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,LAB TUMOR BIOL,CHARLESTOWN,MA 02129, USA. RI Fenner, Martin/A-7225-2008 OI Fenner, Martin/0000-0003-1419-2405 NR 44 TC 69 Z9 74 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 OCT 29 PY 1996 VL 93 IS 22 BP 12298 EP 12303 DI 10.1073/pnas.93.22.12298 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VP937 UT WOS:A1996VP93700046 PM 8901575 ER PT J AU Velloso, LA Folli, F Sun, XJ White, MF Saad, MJA Kahn, CR AF Velloso, LA Folli, F Sun, XJ White, MF Saad, MJA Kahn, CR TI Cross-talk between the insulin and angiotensin signaling systems SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SMOOTH-MUSCLE CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; RECEPTOR SUBSTRATE-1; TYROSINE PHOSPHORYLATION; PROTEIN-KINASE; STIMULATION; ACTIVATION; ASSOCIATION; GROWTH; HEART AB Angiotensin II (AII), acting via its G-protein linked receptor, is an important regulator of cardiac, vascular, and renal function. Following injection of AII into rats, we find that there is also a rapid tyrosine phosphorylation of the major insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) in the heart. This phenomenon appears to involve JAK2 tyrosine kinase, which associates with the AT1 receptor and IRS-1/IRS-2 after AII stimulation. AII-induced phosphorylation leads to binding of phosphatidylinositol 3-kinase (PI 3-kinase) to IRS-1 and IRS-2; however, in contrast to other ligands, AII injection results in an acute inhibition of both basal and insulin-stimulated PI 3-kinase activity. The latter occurs without any reduction in insulin receptor or IRS phosphorylation or in the interaction of the p85 and p110 subunits of PI 3-kinase with each other or with IRS-1/IRS-2. These effects of AII are inhibited by AT1 receptor antagonists. Thus, there is direct cross-talk between insulin and AII signaling pathways at the level of both tyrosine phosphorylation and PI 3-kinase activation. These interactions may play an important role in the association of insulin resistance, hypertension, and cardiovascular disease. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HOSP SAN RAFFAELE,DEPT MED 1,I-30132 MILAN,ITALY. RP Velloso, LA (reprint author), UNIV CAMPINAS,UNICAMP,CELLULAR & MOL BIOL LAB,BR-13081 CAMPINAS,BRAZIL. OI folli, franco/0000-0001-9824-5222 FU NIDDK NIH HHS [DK 33201, DK 38712] NR 45 TC 283 Z9 299 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 29 PY 1996 VL 93 IS 22 BP 12490 EP 12495 DI 10.1073/pnas.93.22.12490 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VP937 UT WOS:A1996VP93700080 PM 8901609 ER PT J AU Vreugdenhil, M Bruehl, C Voskuyl, RA Kang, JX Leaf, A Wadman, WJ AF Vreugdenhil, M Bruehl, C Voskuyl, RA Kang, JX Leaf, A Wadman, WJ TI Polyunsaturated fatty acids modulate sodium and calcium currents in CA1 neurons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE n-3; omega-3 polyunsaturated fatty acids; ion channels; anticonvulsant ID RAT CARDIAC MYOCYTES; LONG-CHAIN; DOCOSAHEXAENOIC ACID; ARACHIDONIC-ACID; DEPENDENT BLOCK; ION CHANNELS; DRUGS; THRESHOLD; ISCHEMIA; BRAIN AB Recent evidence indicates that long-chain polyunsaturated fatty acids (PUFAs) can prevent cardiac arrhythmias by a reduction of cardiomyocyte excitability. This was shown to be due to a modulation of the voltage-dependent inactivation of both sodium (I-Na) and calcium (I-Ca) currents. To establish whether PUFAs also regulate neuronal excitability, the effects of PUFAs on I-Na and I-Ca were assessed in CA1 neurons freshly isolated from the rat hippocampus. Extracellular application of PUFAs produced a concentration-dependent shift of the voltage dependence of inactivation of both I-Na and I-Ca to more hyperpolarized potentials. Consequently, they accelerated the inactivation acid retarded the recovery from inactivation. The EC(50) for the shift of the I-Na, steady-state inactivation curve was 2.1 +/- 0.4 mu M for docosahexaenoic acid (DHA) and 4 +/- 0.4 mu M for eicosapentaenoic acid (EPA). The EC(50) for the shift on the I-Ca inactivation curve was 2.1 +/- 0.4 for DHA and > 15 mu M for EPA. Additionally, DHA and EPA suppressed both I-Na and I-Ca amplitude at concentrations > 10 mu M. PUFAs did not affect the voltage dependence of activation. The monounsaturated oleic acid and the saturated palmitic acid were virtually ineffective. The combined effects of the PUFAs on I-Na and I-Ca may reduce neuronal excitability and may exert anticonvulsive effects ira vivo. C1 UNIV AMSTERDAM,INST NEUROBIOL,NL-1098 SM AMSTERDAM,NETHERLANDS. LEIDEN UNIV,DEPT PHYSIOL,NL-2300 RC LEIDEN,NETHERLANDS. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BROCKTON W ROXBURY VET AFFAIRS MED CTR,DEPT MED,BOSTON,MA 02115. FU NIDDK NIH HHS [DK38165] NR 32 TC 191 Z9 193 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 29 PY 1996 VL 93 IS 22 BP 12559 EP 12563 DI 10.1073/pnas.93.22.12559 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VP937 UT WOS:A1996VP93700092 PM 8901621 ER PT J AU Natowicz, MR Wang, Y AF Natowicz, MR Wang, Y TI Plasma hyaluronidase activity in mucolipidoses II and III: Marked differences from other lysosomal enzymes SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE lysosomal enzymes; mucolipidosis; hyaluronidase ID CELL DISEASE; HEXOSAMINIDASE; LYMPHOBLASTS; FIBROBLASTS; DEFICIENCY; LIVER AB A nearly pathognomonic finding of the lysosomal storage disorders mucolipidoses II and III is the marked increase of plasma lysosomal enzyme activities, The genetic lesion in ML II and III causes defective function of the enzyme UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase. Defective function of this enzyme results in deficient phosphorylation of lysosomal enzyme asparagine-linked oligosaccharides and a consequent misrouting of many newly synthesized lysosomal enzymes, These enzymes are secreted from cells instead of being targeted to lysosomes, with resultant marked elevations of multiple lysosomal enzyme activities in plasma. We report here that plasma hyaluronidase activity, an endoglycosidase of presumably lysosomal origin, is not increased in the plasma from individuals with mucolipidoses II and III, unlike most lysosomal enzymes, Our data suggest the possibility that hyaluronidase is not targeted to lysosomes by a lysosomal enzyme phosphosmannosyl recognition mechanism. Alternatively, hyaluronidase activity may not be present in the cell type(s) responsible for the lysosomal enzyme hypersecretion in mucolipidoses II and III which, along with its deficiency in fibroblasts and leukocytes, would constitute an unusual tissue distribution of activity for a soluble lysosomal enzyme. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Natowicz, MR (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV MED GENET,200 TRAPELO RD,WALTHAM,MA 02254, USA. NR 40 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 28 PY 1996 VL 65 IS 3 BP 209 EP 212 DI 10.1002/(SICI)1096-8628(19961028)65:3<209::AID-AJMG7>3.0.CO;2-K PG 4 WC Genetics & Heredity SC Genetics & Heredity GA VR056 UT WOS:A1996VR05600007 PM 9240745 ER PT J AU Singer, PA Cooper, DS Daniels, GH Ladenson, PW Greenspan, FS Levy, EG Braverman, LE Clark, OH McDougall, IR Ain, KV Dorfman, SG AF Singer, PA Cooper, DS Daniels, GH Ladenson, PW Greenspan, FS Levy, EG Braverman, LE Clark, OH McDougall, IR Ain, KV Dorfman, SG TI Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID FOLLOW-UP; SUPPRESSIVE THERAPY; SERUM THYROGLOBULIN; MEDICAL THERAPY; CARCINOMA; PAPILLARY; IMPACT; MANAGEMENT AB A set of minimum clinical guidelines for use by primary care physicians in the evaluation and management of patients with thyroid nodules or thyroid cancer was developed by consensus by an Ii-member Standards of Care Committee (the authors of the article) of the American Thyroid Association, New York, NY. The participants were selected by the committee chairman and by the president of the American Thyroid Association based on their clinical experience. The committee members represented different geographic areas within the United States, to reflect different practice patterns. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information. Each committee participant was initially assigned to write a section of the document and to submit it to the committee chairman, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. Several of the committee members further revised and refined the document, which was then submitted to the entire membership of the American Thyroid Association for written comments and suggestions, many of which were incorporated into a final draft document, which was reviewed and approved by the Executive Council of the American Thyroid Association. C1 UNIV SO CALIF,SCH MED,DIV ENDOCRINOL DIABET & HYPERTENS,LOS ANGELES,CA. JOHNS HOPKINS UNIV,SCH MED,DIV ENDOCRINOL,BALTIMORE,MD. MT SINAI HOSP,DIV ENDOCRINOL,BALTIMORE,MD. MASSACHUSETTS GEN HOSP,THYROID UNIT,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,SCH MED,DIV ENDOCRINOL,SAN FRANCISCO,CA. UNIV MIAMI,SCH MED,DIV ENDOCRINOL,MIAMI,FL. UNIV MASSACHUSETTS,SCH MED,DIV ENDOCRINOL,WORCESTER,MA. UNIV CALIF SAN FRANCISCO,MT ZION MED CTR,SCH MED,DEPT SURG,SAN FRANCISCO,CA 94120. STANFORD UNIV,MED CTR,SCH MED,DIV NUCL MED,STANFORD,CA 94305. UNIV KENTUCKY,DIV ENDOCRINOL,LEXINGTON,KY. ENDOCRINE ASSOCIATES DALLAS,DALLAS,TX. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 21 TC 286 Z9 293 U1 0 U2 8 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 OCT 28 PY 1996 VL 156 IS 19 BP 2165 EP 2172 DI 10.1001/archinte.156.19.2165 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VN939 UT WOS:A1996VN93900002 PM 8885814 ER PT J AU Hasley, PB Albaum, MN Li, YH Fuhrman, CR Britton, CA Marrie, TJ Singer, DE Coley, CM Kapoor, WN Fine, MJ AF Hasley, PB Albaum, MN Li, YH Fuhrman, CR Britton, CA Marrie, TJ Singer, DE Coley, CM Kapoor, WN Fine, MJ TI Do pulmonary radiographic findings at presentation predict mortality in patients with community-acquired pneumonia SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BACTEREMIA; FAILURE AB Background: Previous studies have reported conflicting results on whether pulmonary radiographic findings predict mortality for patients with community-acquired pneumonia (CAP). Objective: To determine whether pulmonary radiographic findings at presentation are independently associated with 30-day mortality in patients with suspected CAP. Methods: This study was conducted as part of the Pneumonia Patient Outcomes Research Team multicenter, prospective cohort study of ambulatory and hospitalized patients with clinical and radiographic evidence of CAP. For each patient with CAP, a structured data form was completed by a panel of radiologists to evaluate the radiographic pattern of infiltrate, number of lobes involved, presence of pleural effusion, and 8 other radiographic characteristics. Cox proportional hazards models were used to evaluate the independent association between radiographic findings and 30-day mortality, while controlling for patient demographic, clinical, and laboratory characteristics with a known association with this outcome. Results: Of 2287 patients enrolled in the Pneumonia Patient Outcomes Research Team cohort study, 1906 patients (83.3%) had a pulmonary radiographic infiltrate confirmed by the radiology panel. Overall, 30-day mortality in this cohort was 4.9%. Univariate regression analyses demonstrated the following radiographic characteristics to be significantly associated with 30-day mortality: (1) bilateral pleural effusions (risk ratio [RR], 7.0; 95% confidence interval [CI], 3.9-12.6); (2) a pleural effusion of moderate or greater size (RR, 3.4; 95% CI, 1.4-8.4); (3) 2 or more lobes involved with infiltrate (RR, 2.5; 95% CI, 1.6-3.8); (4) bilateral infiltrate (RR, 2.8; 95% CI, 1.9-4.2); (5) bronchopneumonia (RR, 1.6; 95% CI, 1.0-2.7); and (6) air bronchograms (RR, 0.5; 95% CI, 0.2-0.9), Multivariate analysis of radiographic features and other clinical characteristics showed the presence of bilateral pleural effusions (RR, 2.8; 95% CI, 1.4-5.8) was independently associated with mortality. Conclusions: In patients with CAP, the presence of bilateral pleural effusions is an independent predictor of short-term mortality. This finding, which is available at presentation, can help guide physicians' assessment of prognosis in CAP. C1 UNIV PITTSBURGH,DIV GEN INTERNAL MED,PITTSBURGH,PA. UNIV PITTSBURGH,DEPT BIOSTAT,PITTSBURGH,PA 15261. UNIV PITTSBURGH,DEPT RADIOL,PITTSBURGH,PA 15260. VICTORIA GEN HOSP,DEPT MED,HALIFAX,NS B3H 2Y9,CANADA. VICTORIA GEN HOSP,DEPT MICROBIOL,HALIFAX,NS B3H 2Y9,CANADA. DALHOUSIE UNIV,HALIFAX,NS,CANADA. MASSACHUSETTS GEN HOSP,DEPT MED,GEN INTERNAL MED UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU AHRQ HHS [R01 HS 06468] NR 28 TC 75 Z9 77 U1 0 U2 3 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 OCT 28 PY 1996 VL 156 IS 19 BP 2206 EP 2212 DI 10.1001/archinte.156.19.2206 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA VN939 UT WOS:A1996VN93900007 PM 8885819 ER PT J AU Fuchs, CS Colditz, GA Stampfer, MJ Giovannucci, EL Hunter, DJ Rimm, EB Willett, WC Speizer, FE AF Fuchs, CS Colditz, GA Stampfer, MJ Giovannucci, EL Hunter, DJ Rimm, EB Willett, WC Speizer, FE TI A prospective study of cigarette smoking and the risk of pancreatic cancer SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; PAST MEDICAL HISTORY; ALCOHOL-CONSUMPTION; DIABETES-MELLITUS; TOBACCO; COFFEE; DISEASE; REPRODUCIBILITY; WOMEN; DIET AB Objectives: To prospectively examine the excess incidence of pancreatic cancer among cigarette smokers and to examine the influence of smoking cessation on the risk of pancreatic cancer. Methods: We obtained data on cigarette smoking and other risk factors for pancreatic cancer from 118 339 women aged 30 to 55 years and 49 428 men aged 40 to 75 years who were without diagnosed cancer. During the 2 116 229 persons-years of follow-up, pancreatic cancer was diagnosed in 186 participants. Results: The multivariate relative risk of pancreatic cancer for current smokers was 2.5 (95% confidence interval, 1.7-3.6). A significant, positive trend in risk with increasing pack-years of smoking was observed (P for trend=.004), although this association was confined to cigarette consumption within the past 15 years. Compared with participants who continued to smoke, former smokers had a 48% reduction in pancreatic cancer risk within 2 years of quitting. Ultimately, the relative risk of pancreatic cancer among former smokers approached that for never smokers after less than 10 years of smoking cessation. Overall, the proportion of pancreatic cancers attributable to cigarette smelting was 25%. Conclusions: Cigarette smoking is associated with an increased risk of pancreatic cancer. The rapid reduction in risk associated with quitting suggests that smelting cessation could eliminate 25% of the 27 000 deaths from pancreatic cancer occurring annually in the United States. C1 BRIGHAM & WOMENS HOSP,DEPT MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP Fuchs, CS (reprint author), DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA40935, CA55075, CA66385] NR 37 TC 181 Z9 184 U1 1 U2 3 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 OCT 28 PY 1996 VL 156 IS 19 BP 2255 EP 2260 DI 10.1001/archinte.156.19.2255 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VN939 UT WOS:A1996VN93900014 PM 8885826 ER PT J AU Bhide, PG AF Bhide, PG TI Cell cycle kinetics in the embryonic mouse corpus striatum SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE ganglionic eminence; neurogenesis; cerebral cortex; basal ganglia ID HAMSTER CRICETULUS-GRISEUS; CENTRAL NERVOUS-SYSTEM; MURINE CEREBRAL WALL; NEURON ORIGIN; GERMINAL ZONE; RAT STRIATUM; FOREBRAIN; NEUROGENESIS; TIME; PROLIFERATION AB Cells of the corpus striatum arise from the lateral ganglionic eminence of the telencephalic neuroepithelium. In mice, the length of the cell cycle and that of its component phases were estimated, and the interkinetic nuclear migratory pattern was characterized for lateral ganglionic progenitors on embryonic day 11 and 12 to gain insights into striatal cytogenetic process. An S-phase labeling paradigm using bromodeoxyuridine was employed. To assess regional variation in proliferative patterns, rostral, middle and caudal levels of the ganglionic neuroepithelium were examined separately. The pattern of interkinetic nuclear migration and the duration of G1-, G2-, and M-phases at the rostral and middle levels differed from those at the caudal level. The length of the cell cycle and that of the G1-phase increased during the interval embryonic day 11 to 12, especially at the rostral and middle levels. During the same interval, a sizable secondary proliferative population emerged at all three levels. Two principal conclusions are drawn: Progenitors at the different rostrocaudal levels are heterogeneous with regard to the pattern of cellular proliferation, and ganglionic progenitors are in advance of the cerebral cortical progenitors based on the relative size of the secondary proliferative population and the magnitude of cytokinetic parameters. Thus, proliferative behavior distinguishes progenitor populations at different rostrocaudal levels within the lateral ganglionic neuroepithelium and across the ganglionic and cerebral cortical domains of the telencephalic neuroepithelium. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. OI Bhide, Pradeep/0000-0003-4236-9415 FU PHS HHS [NINOS 30657] NR 53 TC 57 Z9 57 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD OCT 28 PY 1996 VL 374 IS 4 BP 506 EP 522 PG 17 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VP559 UT WOS:A1996VP55900003 PM 8910732 ER PT J AU Yuan, ZM Huang, YY Fan, MM Sawyers, C Kharbanda, S Kufe, D AF Yuan, ZM Huang, YY Fan, MM Sawyers, C Kharbanda, S Kufe, D TI Genotoxic drugs induce interaction of the c-Abl tyrosine kinase and the tumor suppressor protein p53 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-CYCLE ARREST; 1-BETA-D-ARABINOFURANOSYLCYTOSINE INCORPORATION; DNA; BINDING; PHOSPHORYLATION; GROWTH; ONCOPROTEIN; ACTIVATION; ELONGATION; INHIBITION AB The function of the c-Abl protein tyrosine kinase is unknown. The present studies demonstrate that the antimetabolite 1-beta-D-arabinofuranosylcytosine (ara-C) induces binding of c-Abl and p53. Ara-C treatment of cells that express wild type or a dominant negative, kinase-inactive c-Abl(K-R) was associated with formation of c-Abl-p53 complexes and increased expression of the cyclin dependent kinase (Cdk) inhibitor p21. However, down-regulation of Cdk2 by ara-C was found in cells expressing wild type c-Abl and not in cells expressing c-Abl(K-R) or those deficient in p53. Similar findings were obtained following treatment of cells with the alkylating agent methyl methanesulfonate (RIMS). Cells that express the c-Abl dominant negative or are null for c-Abl exhibited partial abrogation of Cdk2 down-regulation and G1 arrest in response to RIMS exposure, Cells lacking the c-abl gene also responded to ara-C and RIMS with increases in p53 levels and induction of p21. These findings indicate that the cellular response to certain genotoxic drugs involves binding of c-Abl to p53 and down-regulation of Cdk2 by a c-Abl kinase/p53-dependent mechanism. C1 UNIV CALIF LOS ANGELES,INST MOL BIOL,DEPT MED,LOS ANGELES,CA 90095. RP Yuan, ZM (reprint author), HARVARD UNIV,SCH MED,DIV CANC PHARMACOL,DANA FARBER CANC INST,BOSTON,MA 02115, USA. RI Sawyers, Charles/G-5327-2016 FU NCI NIH HHS [CA29431] NR 33 TC 62 Z9 62 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 OCT 25 PY 1996 VL 271 IS 43 BP 26457 EP 26460 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP233 UT WOS:A1996VP23300004 PM 8900110 ER PT J AU Bergwitz, C Gardella, TJ Flannery, MR Potts, JT Kronenberg, HM Goldring, SR Juppner, H AF Bergwitz, C Gardella, TJ Flannery, MR Potts, JT Kronenberg, HM Goldring, SR Juppner, H TI Full activation of chimeric receptors by hybrids between parathyroid hormone and calcitonin - Evidence for a common pattern of ligand-receptor interaction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PEPTIDE RECEPTOR; EXPRESSION CLONING; MOLECULAR-CLONING; HUMORAL HYPERCALCEMIA; SECRETIN RECEPTOR; SALMON-CALCITONIN; BINDING; GLUCAGON; GENE; MUTAGENESIS AB Calcitonin (CT) and parathyroid hormone (PTH), whose receptors belong to the same family of G protein-coupled receptors, share no amino acid sequence homology and selectively activate either CT or PTH receptors. We now show, however, that reciprocal hybrid ligands (CT/PTH and PTH/CT), which do not activate the ''wild-type'' receptors, activate PTH/CT and CT/PTH receptor chimeras, respectively, Our findings indicate that PTH and CT share a similar architecture with at least two functional, receptor-specific domains, These domains are sufficiently independent to permit synthetic hybrid ligands to efficiently activate appropriate receptor chimeras. Therefore, both ligands follow, despite their very different primary sequences, a common pattern of ligand-receptor interaction. C1 MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, DEPT MED, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, ARTHRITIS UNIT, DEPT MED, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CHILDRENS SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RI Fitzsimons, Chris/B-4171-2012 FU NIDDK NIH HHS [DK11794-28] NR 43 TC 124 Z9 125 U1 0 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 25 PY 1996 VL 271 IS 43 BP 26469 EP 26472 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP233 UT WOS:A1996VP23300007 PM 8900113 ER PT J AU Liu, Y Arshavsky, VY Ruoho, AE AF Liu, Y Arshavsky, VY Ruoho, AE TI Interaction sites of the COOH-terminal region of the gamma subunit of cGMP phosphodiesterase with the GTP-bound alpha subunit of transducin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLIC-GMP PHOSPHODIESTERASE; ROD OUTER SEGMENTS; AMINO-ACID-SEQUENCE; G-PROTEIN; INHIBITORY SUBUNIT; SYNTHETIC PEPTIDES; BINDING PROTEIN; ACTIVATION MECHANISM; STRUCTURAL-ANALYSIS; CATALYTIC SUBUNITS AB In photoreceptor cells, visual transduction occurs through photoexcitation of rhodopsin, GTP activation of the alpha subunit of transducin, and interaction between GTP-bound transducin alpha subunit and the inhibitory gamma subunit of phosphodiesterase. The gamma subunit of phosphodiesterase, in turn, accelerates the hydrolysis of GTP on the alpha subunit if transducin. Within the COOH-terminal residues (46-87) of the phosphodiesterase gamma subunit, Trp-70 has been implicated in phosphodiesterase activation, transducin alpha subunit-phosphodiesterase gamma subunit, interaction, and the GTP hydrolysis accelerating activity. We have derivatized the phosphodiesterase gamma subunit with a reversible photoactivatable reagent, [I-125]N-[(3-iodo-4-azidophenylpropionamido-S-(2-thiopyridyl)] cysteine ([I-125]ACTP), at cysteine (Cys-68). A light-dependent, cross-linked complex of guanosine 5'-(gamma-thio)-triphosphate-bound transducin alpha subunit and ACTP-derivatized phosphodiesterase gamma subunit formed after photolysis of a 1:1 stoichiometric complex of the two proteins. The specificity of complex formation between the transducin alpha subunit and the phosphodiesterase gamma subunit was demonstrated by specific protection by the C68A mutant of the phosphodiesterase gamma subunit. The cross-linked complex was treated with beta-mercaptoethanol to transfer the I-125 photomoiety from the phosphodiesterase gamma subunit to the transducin alpha subunit. Combined techniques involving electrophoresis, chemical and enzymatic cleavage, and chemical and radiosequencing were based to identify photoinsertion sites on the alpha(3) and alpha(4)/beta(6) regions of the transducin alpha subunit. Three photo-labeled residues, His-244 (alpha(3) helix), Met-308, and Arg-310 (alpha(4)/beta(6) interface), were specifically identified as photoinsertion sites. Utilizing the crystal structure coordinates of the GTP-bound transducin alpha subunit and molecular modeling, we conclude that Cys-68 of the phosphodiesterase gamma subunit is located at a position between the exposed face of the alpha(3) and alpha(4), helices of the transducin alpha subunit. We propose that the phosphodiesterase gamma subunit interacts with GTP-bound transducin alpha subunit at multiple sites in which the cysteine 68 to tryptophan 70 sequence of the phosphodiesterase gamma subunit, which is critical for GTP hydrolysis accelerating activity, interacts in the alpha(3)/alpha(4)/beta(6) region of GTP-bound transducin alpha subunit. C1 UNIV WISCONSIN,SCH MED,DEPT PHARMACOL,MADISON,WI 53706. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02114. FU NEI NIH HHS [EY-10336]; NIGMS NIH HHS [GM33138] NR 56 TC 27 Z9 27 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 OCT 25 PY 1996 VL 271 IS 43 BP 26900 EP 26907 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP233 UT WOS:A1996VP23300068 PM 8900174 ER PT J AU Resnick, D Chatterton, JE Schwartz, K Slayter, H Krieger, M AF Resnick, D Chatterton, JE Schwartz, K Slayter, H Krieger, M TI Structure of class A macrophage scavenger receptors - Electron microscopic study of flexible, multidomain, fibrous proteins and determination of the disulfide bond pattern of the scavenger receptor cysteine-rich domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIGAND-BINDING; MACROMOLECULES; CONTAINS; EXPRESSION; CLONING; GENE AB Structures of secreted forms of the human type I and II class A macrophage scavenger receptors were studied using biochemical and biophysical methods. Proteolytic analysis was used to determine the intramolecular disulfide bonds in the type I-specific scavenger receptor cysteine-rich (SRCR) domain: Cys(2)-Cys(7), Cys(3)-Cys(8), and Cys(5)-Cys(6). This pattern is likely to be shared by the highly homologous domains in the many other members of the SRCR domain superfamily. Electron microscopy using rotary shadowing and negative staining showed that the type I and II receptors are extended molecules whose contour lengths are similar to 440 Angstrom. They comprised two adjacent fibrous segments, an alpha-helical coiled-coil (similar to 230 Angstrom, including a contribution from the N-terminal spacer domain) and a collagenous triple helix (similar to 210 Angstrom). The type I molecules also contained a C-terminal globular structure (similar to 58 x 76 Angstrom) composed of three SRCR domains. The fibrous domains were joined by an extremely flexible hinge. The angle between these domains varied from 0 to 180 degrees and depended on the conditions of sample preparation. Unexpectedly, at physiologic pH, the prevalent angle seen using rotary shadowing was 0 degrees, resulting in a structure that is significantly more compact than previously suggested. The apparent juxtaposition of the fibrous domains at neutral pH provides a frame-work for future structure-function studies of these unusual multiligand receptors. C1 MIT,DEPT BIOL,CAMBRIDGE,MA 02139. ARRIS PHARMACEUT CORP,S SAN FRANCISCO,CA 94080. DANA FARBER CANC INST,BOSTON,MA 02115. FU NHLBI NIH HHS [HL 52212, HL 33014, HL 41484] NR 33 TC 69 Z9 71 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 OCT 25 PY 1996 VL 271 IS 43 BP 26924 EP 26930 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP233 UT WOS:A1996VP23300071 PM 8900177 ER PT J AU Saavedra, JE Southan, GJ Davies, KM Lundell, A Markou, C Hanson, SR Adrie, C Hurford, WE Zapol, WM Keefer, LK AF Saavedra, JE Southan, GJ Davies, KM Lundell, A Markou, C Hanson, SR Adrie, C Hurford, WE Zapol, WM Keefer, LK TI Localizing antithrombotic and vasodilatory activity with a novel, ultrafast nitric oxide donor SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SODIUM-NITRITE; THROMBOSIS; DELIVERY; ACIDS; MICE; RATS AB Reaction of nitric oxide (NO) with L-proline in methanolic sodium methoxide yields a diazeniumdiolate product, C5H7N3O4Na2 . CH3OH (PROLI/NO), that can be stabilized in basic solution but that dissociates to proline (1 mol) and NO (2 mol) with a half-life of only 1.8 s at pH 7.4 and 37 degrees C. This kinetic behavior has allowed the generation of highly localized antiplatelet and vasodilatory effects. By infusing solutions containing 4 mu M PROLI/NO in 0.1 M sodium hydroxide at the rate of 1 nmol . min(-1) immediately upstream from a polyester vascular graft in the unheparinized baboon circulatory system, for example, platelet deposition at the normally thrombogenic graft surface was substantially reduced relative to controls receiving only 0.1 M sodium hydroxide. In a second study, infusion of PROLI/NO into the right atrium of sheep with induced pulmonary hypertension selectively dilated the lung vasculature, dose-dependently reducing the pulmonary arterial pressure by as much as 9 mmHg with no observable effect on the systemic arterial pressure at an infusion rate of up to 24 nmol . kg(-1). min(-1). PROLI/NO could also be formulated as an insoluble polymer blend that released NO smoothly for prolonged periods. The results suggest that localized delivery of diazeniumdiolates such as PROLI/NO which generate NO with extreme rapidity on entering the blood stream may hold considerable promise for inhibition of thrombus formation, selective dilation of the vasculature, and other research and clinical applications. C1 NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. GEORGE MASON UNIV,DEPT CHEM,FAIRFAX,VA 22030. EMORY UNIV,DIV HEMATOL,ATLANTA,GA 30322. EMORY UNIV,YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322. MASSACHUSETTS GEN HOSP,DEPT ANAESTHESIA,BOSTON,MA 02114. RI Hurford, William/G-6386-2013; Keefer, Larry/N-3247-2014 OI Hurford, William/0000-0003-1201-0313; Keefer, Larry/0000-0001-7489-9555 FU NHLBI NIH HHS [HL-31469, HL-42397, HL-48667] NR 23 TC 109 Z9 110 U1 0 U2 10 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 OCT 25 PY 1996 VL 39 IS 22 BP 4361 EP 4365 DI 10.1021/jm960616s PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VP247 UT WOS:A1996VP24700004 PM 8893830 ER PT J AU Li, J Smolyar, A SunderPlassmann, R Reinherz, EL AF Li, J Smolyar, A SunderPlassmann, R Reinherz, EL TI Ligand-induced conformational change within the CD2 ectodomain accompanies receptor clustering: Implication for molecular lattice formation SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE conformational change; domain reorientation; Ig superfamily; CD2; epitope mapping ID T-CELL ACTIVATION; MAJOR HISTOCOMPATIBILITY COMPLEX; FUNCTION-ASSOCIATED ANTIGEN-3; IMMUNODEFICIENCY-VIRUS GP120; HUMAN LYMPHOCYTES-T; ERYTHROCYTE RECEPTOR; CRYSTAL-STRUCTURE; MONOCLONAL-ANTIBODIES; CLASS-II; ADHESION DOMAIN AB CD2 mediates interaction between T cells and their cognate partners through its CD58-binding membrane-distal adhesion domain (D1) facilitating T cell receptor (TCR) triggering. A neoepitope defined by anti-CD2R monoclonal antibodies (mAbs) has suggested structural alteration within the CD2 ectodomain during T cell activation. Here, we map CD2R to the flexible CD2 linker region between D1 and the membrane-proximal extracellular domain (D2) and show that exposure of this conformational site is independent of temperature and metabolic energy. Co-ligation of CD2 and CD58 molecules on opposing cells within a conjugate pair induces CD2R and redistributes CD2 to the region of cell-cell contact. These CD2R(+) molecules, in contrast to the CD2R(-) molecules, are tightly clustered on the T cell surface. Hence, a ligand-mediated increase in the D1-D2 interdomain angle apparently exposes CD2R, facilitates packing of CD2 molecules in a clustered array and is linked to CD2-mediated adhesion and activation events. Conformational alteration of this type may be generally important in ordered lattice formation involving surface receptors. (C) 1996 Academic Press Limited C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIAID NIH HHS [AI 21226] NR 86 TC 27 Z9 27 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 25 PY 1996 VL 263 IS 2 BP 209 EP 226 DI 10.1006/jmbi.1996.0570 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP739 UT WOS:A1996VP73900011 PM 8913302 ER PT J AU Blumenthal, D Epstein, AM AF Blumenthal, D Epstein, AM TI Quality of health care .6. The role of physicians in the future of quality management SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RP Blumenthal, D (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 21 TC 103 Z9 105 U1 0 U2 2 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 OCT 24 PY 1996 VL 335 IS 17 BP 1328 EP 1331 DI 10.1056/NEJM199610243351721 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA VN594 UT WOS:A1996VN59400031 PM 8857015 ER PT J AU Aveline, BM Kochevar, IE Redmond, RW AF Aveline, BM Kochevar, IE Redmond, RW TI Photochemistry of the nonspecific hydroxyl radical generator, N-hydroxypyridine-2(1H)-thione SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID LASER FLASH-PHOTOLYSIS; PULSE-RADIOLYSIS; PHOTOPHYSICAL PROPERTIES; AQUEOUS-SOLUTIONS; ENERGY-TRANSFER; IRON CHELATORS; RATE CONSTANTS; CELL-LINES; TRIPLET; DERIVATIVES AB The photochemistry of N-hydroxypyridine-2(1H)-thione (N-HPT) has been investigated in aqueous and organic solvents using laser flash photolysis (lambda(exc) = 308 or 355 nn). Independent of the environment, UV excitation of N-HPT causes homolytic N-O bond cleavage, which leads to formation of the 2-pyridylthiyl (PyS(.)) and hydroxyl((OH)-O-.) radicals. In aqueous media, this process occurs efficiently from both the anionic and neutral forms (Phi(N-O) approximate to 0.20-0.30). In addition to N-O bond scission, N-HPT undergoes other primary photoprocesses which are pH-dependent. At pH = 7, photoionization (Phi(e-) = 0.09 (lambda(exc) = 308 nm) and 0.05 (lambda(exc) = 355 nm)) of the anionic form generates the hydrated electron as well as the semioxidized radical of N-HPT. Fast rearrangement of the latter species produces the N-oxy-2-pyridylthiyl radical. At pH = 2, where the uncharged structure predominates, formation of an excited triplet state (E(T) greater than or equal to 59.5 kcal mol(-1)) is observed (Phi(T) greater than or equal to 0.05 using lambda(exc) = 355 nm) but photoionization does not take place. The neutral form of N-HPT displays similar photochemical behavior in organic solvents, generating (OH)-O-., PyS(.), and the triplet state (Phi(N-O) = 0.30-0.45 and Phi(T) = 0.03-0.05 using lambda(exc) = 355 nm). In nonpolar, aprotic media, the subsequent reaction of PyS(.) with the thiol tautomer of N-HPT leads to the formation of an unsymmetric disulfide radical. Reactivities of the different transient species toward potential scavengers have also been investigated. The results obtained show that the simultaneous generation of several highly reactive intermediates is a major drawback in the use of N-HPT as a clean and simple photolytic source of (OH)-O-.. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. NR 46 TC 48 Z9 48 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 23 PY 1996 VL 118 IS 42 BP 10113 EP 10123 DI 10.1021/ja961988t PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA VN850 UT WOS:A1996VN85000013 ER PT J AU Aveline, BM Kochevar, IE Redmond, RW AF Aveline, BM Kochevar, IE Redmond, RW TI Photochemistry of N-hydroxy-2(1H)-pyridone, a more selective source of hydroxyl radicals than N-hydroxypyridine-2(1H)-thione SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID BOND-DISSOCIATION ENERGIES; ELECTRON-SPIN RESONANCE; N-H BONDS; AQUEOUS-SOLUTIONS; PULSE-RADIOLYSIS; CENTERED RADICALS; PHENOXYL RADICALS; DERIVATIVES; REACTIVITY; N-HYDROXY-2-THIOPYRIDONE AB The primary and subsequent photochemistry of N-hydroxy-2(1H)-pyridone (N-HP) has been investigated in aqueous and nonaqueous media by laser flash photolysis (lambda(exc) = 308 nn). In organic solvents, as well as in buffers at pH less than or equal to 7, the initial photochemistry of N-HP consists of homolytic N-O bond cleavage lending to the formation of the 2-pyridyloxyl (PyO(.)) and hydroxyl ((OH)-O-.) radicals, the quantum yield (Phi(N-O) = Phi(OH)) varying from 0.25 to 0.6, depending on the solvent. Quenching experiments have demonstrated that PyO(.) is relatively unreactive and is removed mainly via a bimolecular radical reaction. In highly basic aqueous media, N-HP exists in the anionic form and is much less photolabile. At pH = 10, in addition to a low yield of N-O bond cleavage (Phi(N-O) = 0.037), N-HP undergoes photoionization, but solvated electron production was found to be very inefficient (Phi(e)(-) = 0.003). Thus, under biologically relevant conditions, N-HP has a much simpler photochemical behavior than that of the closely related N-hydroxypyridine-2(1H)-thione (N-HPT) and may be more useful as a specific generator of hydroxyl radicals in chemical and biological systems. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. NR 51 TC 30 Z9 30 U1 3 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 23 PY 1996 VL 118 IS 42 BP 10124 EP 10133 DI 10.1021/ja961989l PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA VN850 UT WOS:A1996VN85000014 ER PT J AU Jones, GS Elmaleh, DR Strauss, HW Fischman, AJ AF Jones, GS Elmaleh, DR Strauss, HW Fischman, AJ TI 7,10-bis(2-mercapto-2-methyl)propyl-7,10-diazapalmitic acid: A novel, N2S2 ligand for technetium-99m SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID TC-99M COMPLEXES; FATTY-ACID; RADIOPHARMACEUTICALS; BIODISTRIBUTION; ANALOGS AB 7,10-Bis(2-mercapto-2-methyl)propyl-7,10 acid (7) was synthesized and evaluated as a new ligand for technetium-99m (Tc-99m). The title fatty acid analog, an achiral bis(aminoethanethiol) derivative in which the amines are tertiary, gave a stable complex with Tc-99m. The biodistribution of Tc-99m-labeled 7 in rats is reported. Copyright (C) 1996 Elsevier Science Ltd. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 14 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD OCT 22 PY 1996 VL 6 IS 20 BP 2399 EP 2404 DI 10.1016/0960-894X(96)00440-4 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA VQ515 UT WOS:A1996VQ51500006 ER PT J AU Kramm, CM Rainov, NG SenaEsteves, M Barnett, FH Chase, M Herrlinger, U Pechan, PA Chiocca, EA Breakefield, XO AF Kramm, CM Rainov, NG SenaEsteves, M Barnett, FH Chase, M Herrlinger, U Pechan, PA Chiocca, EA Breakefield, XO TI Long-term survival in a rodent model of disseminated brain tumors by combined intrathecal delivery of herpes vectors and ganciclovir treatment SO HUMAN GENE THERAPY LA English DT Article ID SIMPLEX VIRUS; GENE-THERAPY; MUTANT AB Brain tumors that have disseminated into cerebrospinal fluid (CSF) pathways are an unresolved therapeutic problem, especially in pediatric neurooncology. Here a gene therapy approach using the herpes simplex virus type 1 thymidine kinase (HSV-TK)/ganciclovir (GCV) paradigm was tested using an HSV vector in a rodent model of disseminated central nervous system tumors. 9L-gliosarcoma cells were implanted simultaneously into the brain and the CSF of syngeneic rats. Five days later, resulting intracerebral and leptomeningeal tumors were treated by intrathecal injection of a replication-conditional HSV vector. This vector was defective for the ribonucleotide reductase gene, but contained an intact HSV-tk gene. Systemic GCV treatment was started 2 days after vector application and continued for 14 days. Tumor-free, long-term survival (LTS) was achieved in 90% of the animals treated with this combined therapeutic approach, whereas only 30% LTS was found in animals that had received the vector alone and 10% LTS in untreated animals. This therapeutic response probably involves oncolytic, on-site replication of the vector, activation of GCV by a HSV-TK, and a strong immune response both to the vector and to 9L cells. Apparent vector-related mortality was observed in 20% of animals without subsequent GCV therapy, but no vector-related mortality was found when the animals were treated with GCV after vector application. Given the successful outcome of this experimental treatment and the apparent potential of GCV to control HSV-related toxicity, intrathecal application of HSV vectors combined with GCV treatment may be a promising approach for treatment of disseminated brain tumors. C1 MASSACHUSETTS GEN HOSP EAST,CTR NEUROSCI,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02129. UNIV DUSSELDORF,CHILDRENS HOSP,D-4000 DUSSELDORF,GERMANY. UNIV HALLE WITTENBERG,DEPT NEUROSURG,HALLE,GERMANY. BRIGHAM & WOMENS HOSP,CHILDRENS HOSP,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02129. FU NINDS NIH HHS [NS24279] NR 17 TC 48 Z9 48 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT 20 PY 1996 VL 7 IS 16 BP 1989 EP 1994 DI 10.1089/hum.1996.7.16-1989 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD327 UT WOS:A1996WD32700008 PM 8930659 ER PT J AU Pechan, PA Fotaki, M Thompson, RL Dunn, R Chase, M Chiocca, EA Breakefield, XO AF Pechan, PA Fotaki, M Thompson, RL Dunn, R Chase, M Chiocca, EA Breakefield, XO TI A novel 'piggyback' packaging system for herpes simplex virus amplicon vectors SO HUMAN GENE THERAPY LA English DT Article ID IMMEDIATE-EARLY PROTEINS; GENE DELIVERY; TYPE-1; EXPRESSION; NEURONS; MUTANT; THYMIDINE; PROMOTER; CELLS; THERAPY AB Recombinant and amplicon vectors derived from herpes simplex virus type 1 (HSV-1) have proven to be an efficient means of gene delivery to cells in culture and in vivo, In this study, a system was developed to make propagation of the amplicon vector and helper virus mutually dependent on each other, in a 'piggyback' fashion, This combined system supports maintenance and enrichment of the amplicon vector when propagating stocks, while allowing the helper virus to serve as a recombinant vector in its own right, Amplicons bearing a gene essential for HSV-1 replication, IE3, as well as the Escherichia coli lacZ marker gene, were propagated using a mutant virus (d120) deleted in the same essential gene, Vector stocks could be propagated in Vero cells and other cultured cells not transfected with the IE3 gene with markedly delayed cytopathic effects, as compared to wild-type virus. Relatively high titers of amplicon vectors (6 x 10(7) infectious units/ml) were achieved with this piggyback system in Vero cells, with an apparent ratio of amplicon vector: helper virus of up of 5:1 under some conditions; however, recombinant wild-type virus was also generated, Injection of these stocks into experimental gliomas in rodent brain revealed gene delivery to tumor cells mediated by both amplicon vectors (lacZ) and helper virus (HSV-thymidine kinase), with no apparent neuropathology of normal brain, This basic piggyback vector model is amenable to modifications to promote conditional propagation of vectors in vivo and to allow incorporation of multiple transgene elements into both the amplicon and recombinant helper virus vectors. C1 HARVARD UNIV, SCH MED,MASSACHUSETTS GEN HOSP EAST,DEPT NEUROL, NEUROSCI PROGRAM, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED,MASSACHUSETTS GEN HOSP EAST, DEPT NEUROSURG,NEUROSCI PROGRAM, BOSTON, MA 02129 USA. MONTREAL GEN HOSP, RES INST, CTR RES NEUROSCI, MONTREAL, PQ H3G 1A4, CANADA. UNIV CINCINNATI, MED CTR, DEPT MOL GENET BIOCHEM & MICROBIOL, CINCINNATI, OH 45267 USA. FU NINDS NIH HHS [NS24279] NR 39 TC 24 Z9 24 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT 20 PY 1996 VL 7 IS 16 BP 2003 EP 2013 DI 10.1089/hum.1996.7.16-2003 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD327 UT WOS:A1996WD32700010 PM 8930661 ER PT J AU Nakamuta, M Chang, BHJ Zsigmond, E Kobayashi, K Lei, H Ishida, BY Oka, K Li, E Chan, L AF Nakamuta, M Chang, BHJ Zsigmond, E Kobayashi, K Lei, H Ishida, BY Oka, K Li, E Chan, L TI Complete phenotypic characterization of apobec-1 knockout mice with a wild-type genetic background and a human apolipoprotein B transgenic: Background, and restoration of apolipoprotein B mRNA editing by somatic gene transfer of apobec-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOW-DENSITY LIPOPROTEINS; HUMAN ADENOVIRUS TYPE-5; MESSENGER-RNA; MOLECULAR-CLONING; PROTEIN; EXPRESSION; MOUSE; B-48; REGION; B-100 AB We have produced gene knockout mice by targeted disruption of the apobec-1 gene. As recently reported by Hirano et al. (Hirano, K.-I., Young, S. G., Farese, R. V., Jr., Ng, J., Sande, E., Warburton, C., Powell-Braxton, L. M., and Davidson, N. O. (1996) J. Biol. Chem. 271, 9887-9890), these animals do not edit apolipoprotein (ape) B mRNA or produce apoB-48. In this study we have performed a detailed analysis of the lipoprotein phenotypic effects of apobec-1 gene disruption that were not examined in the previous study. We first analyzed the plasma lipoproteins in knockout animals with a wild-type genetic background. Although there was no difference in plasma cholesterol between apobec-1(-/-), (+/-) (+/+) mice, there Or was a marked (176%) increase in plasma apoB-100, from 1.8 +/- 1.2 mg/dl in apobec-1(+/+) mice to 2.7 +/- 0.6 mg/dl in apobec-1(+/-) and 5.0 +/- 1.4 mg/dl in apobec-1(-/-) mice. Plasma apoE was similar in these animals. By fast protein liquid chromatography (FPLC) analysis, there was a significant decrease in plasma high density lipoprotein (HDL) cholesterol in apobec-1(-/-) mice. We further fractionated the plasma lipoproteins into d < 1.006, 1.006-1.02, 1.02-1.05, 1.05-1.08, 1.08-1.10, and 1.10-1.21 g/ml classes, and found a marked (30-40%) reduction in the cholesterol and protein content in the (d 1.08-1.10 and 1.10-1.21) HDL fractions, corroborating the FPLC data. SDS-gel analysis revealed an absence of apoB-48, an increase in apoB-100 in the very low density Lipoprotein (VLDL) and low density lipoprotein (LDL) fractions, and a small decrease in apoA-I in the HDL fractions in the apobec-1(-/-) samples. We next raised the basal plasma apoB levels in the apobec-1(-/-) animals by crossbreeding them with human apoB transgenic (TgB) mice. The plasma apoB-100 was 3-fold higher in apobec-1(-/-)/TgB(+/-) mice (26.6 +/- 18.3 mg/dl) than in apobec-1(+/+)/TgB(+/-) mice (9.8 +/- 3.9 mg/dl, p < 0.05). The apobec-1(-/-)/TgB(+/-) mice had a plasma cholesterol levels of 170 +/- 28 mg/dl and triglyceride levels of 106 +/- 31 mg/dl, which are 80% and 58% higher, respectively, than the corresponding values of 94 +/- 21 mg/dl and 67 +/- 11 mg/dl in apobec(+/+)/TgB(+/-) mice. By FPLC, the apobec-1(-/-)/TgB(+/-) animals developed markedly elevated plasma LDL cholesterol (518.5 +/- 329.5 mu g/ml) that is 373% that of apobec-1(+/+)/TgB(+/-) mice (139.0 +/- 87.0 mu g/ml) (p < 0.05). The elevated plasma triglyceride was accounted for mainly by a 97% increase in VLDL triglyceride in the apobec-1(-/-)/TgB(+/-) mice. We conclude that apobec-1(-/-) animals have a distinctive lipoprotein phenotype characterized by significant hyperapoB-100 and HDL deficiency in mice with a wild-type genetic background. Furthermore, the abolition of apoB mRNA editing elevates plasma total cholesterol and LDL cholesterol in apobec-1(-/-) animals with a TgB background. Finally, to exclude the possibility that absence of apoB mRNA editing was a secondary effect of chronic Apobec-1 deficiency, we treated apobec-1(-/-) mice with a replication-defective mouse Apobec-1 adenoviral vector and found that we could acutely restore apoB mRNA editing in the Liver. These experiments indicate that Apobec-1 is an essential component of the apoB mRNA editing machinery and absence of editing in the knockout animals is a direct consequence of the absence of functional Apobec-1. C1 BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. CHILDRENS NUTR RES CTR,USDA ARS,HOUSTON,TX 77030. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. RP Nakamuta, M (reprint author), BAYLOR COLL MED,DEPT CELL BIOL,1 BAYLOR PLAZA,HOUSTON,TX 77030, USA. FU NHLBI NIH HHS [HL16512, HL56668, HL51586] NR 34 TC 64 Z9 65 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 OCT 18 PY 1996 VL 271 IS 42 BP 25981 EP 25988 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VN180 UT WOS:A1996VN18000041 PM 8824235 ER PT J AU Ricketts, WA Rose, DW Shoelson, S Olefsky, JM AF Ricketts, WA Rose, DW Shoelson, S Olefsky, JM TI Functional roles of the Shc phosphotyrosine binding and Src homology 2 domains in insulin and epidermal growth factor signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE PHOSPHORYLATION; RECEPTOR SUBSTRATE-1; PROTEIN SHC; PTB DOMAIN; NPXY MOTIF; ASSOCIATION; ACTIVATION; PATHWAY; SITES; RAS AB Shc is involved in the activation of Ras in response to many growth factors. Shc contains two phosphotyrosine binding domains, an Src homology 2 (SH2) domain in the carboxyl terminus of the protein and a phosphotyrosine binding (PTB) domain in the amino terminus. Since functional roles for these two domains have not been established, we microinjected glutathione S-transferase fusion proteins of either the Shc PTB or SH2 domains into fibroblasts expressing insulin and epidermal growth factor receptors and measured their effects on DNA synthesis. We found that the Shc PTB was necessary for insulin-induced mitogenic signaling, whereas the SH2 domain was not. In contrast, for epidermal growth factor signaling, the Shc SH2 was functionally more important. These differential modes of signal transduction may be an important factor in determining the specificity of the response of a cell to external stimuli. C1 UNIV CALIF SAN DIEGO,DEPT MED,DIV ENDOCRINOL & METAB,LA JOLLA,CA 92093. VET ADM RES SERV,SAN DIEGO,CA. UNIV CALIF SAN DIEGO,BIOMED SCI GRAD PROGRAM,SAN DIEGO,CA 92103. WHITTIER DIABET PROGRAM,LA JOLLA,CA 92093. JOSLIN DIABET CTR,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 33651] NR 28 TC 41 Z9 41 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 18 PY 1996 VL 271 IS 42 BP 26165 EP 26169 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VN180 UT WOS:A1996VN18000068 PM 8824262 ER PT J AU DeGiorgio, R Su, D Peter, D Edwards, RH Brecha, NC Sternini, C AF DeGiorgio, R Su, D Peter, D Edwards, RH Brecha, NC Sternini, C TI Vesicular monoamine transporter 2 expression in enteric neurons and enterochromaffin-like cells of the rat SO NEUROSCIENCE LETTERS LA English DT Article DE biogenic amines; histamine; serotonin; amine-handling neurons; digestive tract ID NERVOUS-SYSTEM; 5-HYDROXYTRYPTAMINE-LIKE IMMUNOREACTIVITY; SMALL-INTESTINE; GUINEA-PIG; PRECURSORS; PANCREAS AB The cellular localization of the vesicular monoamine transporter 2 (VMAT2) in the rat digestive tract was investigated with immunohistochemistry. VMAT2-immunoreactivity (IR) was localized to neurons and fibers of enteric and pancreatic ganglia, to processes supplying the gut wail, the pancreas and blood vessels, and to enterochromaffin-like (ECL) cells in the gastric corpus, which contained calbindin-IR. Few VMAT2-IR cells were also found in the gastric antrum, but they did not contain gastrin-IR. VMAT2-IR was expressed in extrinsic sympathetic fibers as demonstrated by the elimination of a portion of VMAT2-IR processes by sympathectomy. The VMAT2-IR pattern is consistent with the overall distribution of biogenic amine cell groups in the digestive tract. Our results provide further evidence that VMAT2 is the vesicular amine transporter responsible for accumulation of monoamines into secretory vesicles of monoaminergic neurons and ECL cells. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROBIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT IMMUNOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL & BIOL CHEM,LOS ANGELES,CA 90024. RP DeGiorgio, R (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CURE,DIGEST DIS RES CTR,11301 WILSHIRE BLVD,BLDG 115,LOS ANGELES,CA 90073, USA. OI De Giorgio, Roberto/0000-0003-0867-5873 FU NIDDK NIH HHS [DK41301] NR 16 TC 26 Z9 26 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 18 PY 1996 VL 217 IS 2-3 BP 77 EP 80 DI 10.1016/0304-3940(96)13051-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA VQ398 UT WOS:A1996VQ39800002 PM 8916076 ER PT J AU Narula, J Haider, N Virmani, R DiSalvo, TG Kolodgie, FD Hajjar, RJ Schmidt, U Semigran, MJ Dec, GW Khaw, BA AF Narula, J Haider, N Virmani, R DiSalvo, TG Kolodgie, FD Hajjar, RJ Schmidt, U Semigran, MJ Dec, GW Khaw, BA TI Apoptosis in myocytes in end-stage heart failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PROGRAMMED CELL-DEATH; PRESSURE-OVERLOAD; DNA FRAGMENTATION; IMMATURE THYMOCYTES; HYPERTROPHY; EXPRESSION; PROTEIN; IDENTIFICATION; CARDIOMYOCYTES; PROTOONCOGENE AB Background Heart failure can result from a variety of causes, including ischemic, hypertensive, toxic, and inflammatory heart disease. However, the cellular mechanisms responsible for the progressive deterioration of myocardial function observed in heart failure remain unclear and may result from apoptosis (programmed cell death). Methods We examined seven explanted hearts obtained during cardiac transplantation for evidence of apoptosis, All seven patients had severe chronic heart failure: four had idiopathic dilated cardiomyopathy, and three had ischemic cardiomyopathy, DNA fragmentation (an indicator of apoptosis) was identified histochemically by in situ end-labeling as well as by agarose-gel electrophoresis of end-labeled DNA. Myocardial tissues obtained from four patients who had had a myocardial infarction one to two days previously were used as positive controls, and heart tissues obtained from Sour persons who died in motor vehicle accidents were used as negative controls for the end-labeling studies. Results Hearts from all four patients with idiopathic dilated cardiomyopathy and from one of the three patients with ischemic cardiomyopathy had histochemical evidence of DNA fragmentation, All four myocardial samples from patients with dilated cardiomyopathy also demonstrated DNA laddering, a characteristic of apoptosis, whereas this was not seen in any of the samples from patients with ischemic cardiomyopathy. Histologic evidence of apoptosis was also observed in the central necrotic zone of acute myocardial infarcts, but not in myocardium remote from the infarcted zone. Rare isolated apoptotic myocytes were seen in the myocardium from the four persons who died in motor vehicle accidents. Conclusions Loss of myocytes due to apoptosis occurs in patients with end-stage cardiomyopathy and may contribute to progressive myocardial dysfunction. (C) 1996, Massachusetts Medical Society. C1 NORTHEASTERN UNIV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. NR 40 TC 1005 Z9 1046 U1 2 U2 16 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 OCT 17 PY 1996 VL 335 IS 16 BP 1182 EP 1189 DI 10.1056/NEJM199610173351603 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VN401 UT WOS:A1996VN40100003 PM 8815940 ER PT J AU Jenkins, TD Nakagawa, H Rustgi, AK AF Jenkins, TD Nakagawa, H Rustgi, AK TI The association of Epstein-Barr virus DNA with esophageal squamous cell carcinoma SO ONCOGENE LA English DT Article DE Epstein-Barr virus; esophageal cancer; genomic sequence ID LYMPHOEPITHELIOMA-LIKE CARCINOMA; NASOPHARYNGEAL CARCINOMA; GASTRIC ADENOCARCINOMA; HUMAN PAPILLOMAVIRUS; RAS MUTATIONS; CYCLIN D1; EXPRESSION; GENE; CANCER; AMPLIFICATION AB The Epstein-Barr virus (EBV), a member of the herpesviruses, is a double stranded 170 kilobase DNA virus important in many human benign and malignant conditions. It has been implicated in the pathogenesis of proliferative diseases of lymphocytes and tumors of epithelial derivation. The etiology and pathogenesis of esophageal squamous cell carcinoma (ESCC) is thought to involve a combination of genetic and environmental events which lead to epithelial cell transformation. The aim of this study was to determine whether an association exists between EBV and ESCC. DNA was extracted from 16 human ESCC cell lines and microdissected tumor specimens from 60 patients. The polymerase chain reaction was used to amplify a 400 base pair fragment corresponding to the BamHIW fragment repeat sequence of EBV. Southern blotting, utilizing an oligonucleotide probe specific for the BamH1W sequence, was used to confirm positive results and increase sensitivity of detection. 5/60 tumor samples and 1/16 ESCC cell Lines were positive for the EBV sequence. Positive tumor samples were estimated to contain one copy of EBV per 20 cellular genomes. Given the role of EBV in other tumors of epithelial derivation, it is possible that EBV may contribute to the molecular pathogenesis of ESCC. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HEMATOL ONCOL UNIT,BOSTON,MA 02114. FU NIDDK NIH HHS [T2DK07191D21, DK40561] NR 38 TC 20 Z9 22 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 17 PY 1996 VL 13 IS 8 BP 1809 EP 1813 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VM887 UT WOS:A1996VM88700027 PM 8895528 ER PT J AU Hayes, DF Bast, RC Desch, CE Fritsche, H Kemeny, NE Jessup, JM Locker, GY MacDonald, JS Mennel, RG Norton, L Ravdin, P Taube, S Winn, RJ AF Hayes, DF Bast, RC Desch, CE Fritsche, H Kemeny, NE Jessup, JM Locker, GY MacDonald, JS Mennel, RG Norton, L Ravdin, P Taube, S Winn, RJ TI Tumor marker utility grading system: A framework to evaluate clinical utility of tumor markers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NEGATIVE BREAST-CANCER; C-ERBB-2 ANTIGEN LEVELS; DNA FLOW-CYTOMETRY; CELL LUNG-CANCER; ESTROGEN-RECEPTOR; PRACTICE GUIDELINES; OVARIAN-CANCER; SUSCEPTIBILITY GENE; PROGNOSTIC FACTORS; SUPPRESSOR GENE AB Introduction of tumor markers into routine clinical practice has been poorly controlled, with few criteria or guidelines as to how such markers should be used. We propose a Tumor Marker Utility Grading System (TMUGS) to evaluate the clinical utility of tumor markers and to establish an investigational agenda for evaluation of new tumor markers, A Tumor Marker Utility Grading Worksheet has been designed. The initial portion of this worksheet is used to clarify the precise characteristics of the marker in question. These characteristics include the marker designation, the molecule and/or substance and the relevant alteration from normalcy, the assay format and reagents, the specimen type, and the neoplastic disease for which the marker is being evaluated, To determine the clinical utility of each marker, one of several potential uses must be designated, including risk assessment, screening, differential diagnosis, prognosis, and monitoring clinical course, For each of these uses, associations between marker assay results and expected biologic process and end paints must be determined, However, knowledge of tumor marker data should contribute to a decision in practice that results in a more favorable clinical outcome for the patient, including increased overall survival, increased disease-free survival, improvement in quality of life, or reduction in cost of care. Semiquantitative utility scales have been developed for each end point, The only markers recommended for use in routine clinical practice are those that are assigned utility scores of ''++'' or ''+++'' on a 6-point scale (ranging from 0 to +++) in the categories relative to more favorable clinical outcomes, Each utility score assignment should be supported by documentation of the level of evidence used to evaluate the marker, TMUGS sill establish a standardized analytic technique to evaluate clinical utility of known and future tumor markers. It should result in improved patient outcomes and more cost-efficient investigation and application of tumor markers. C1 DANA FARBER CANC INST,BREAST EVALUAT CTR,BOSTON,MA 02115. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,MASSEY CANC CTR,RICHMOND,VA 23298. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. NORTHWESTERN UNIV,EVANSTON HOSP,EVANSTON,IL 60201. TEMPLE UNIV,CTR CANC,PHILADELPHIA,PA 19122. TEXAS ONCOL,DALLAS,TX. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. NCI,CANC DIAG BRANCH,DIV CANC BIOL DIAG & CTR,BETHESDA,MD. RI Bast, Robert/E-6585-2011; Ain, Kenneth/A-5179-2012 OI Bast, Robert/0000-0003-4621-8462; Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [CA64057] NR 66 TC 465 Z9 483 U1 0 U2 23 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 OCT 16 PY 1996 VL 88 IS 20 BP 1456 EP 1466 DI 10.1093/jnci/88.20.1456 PG 11 WC Oncology SC Oncology GA VM256 UT WOS:A1996VM25600012 PM 8841020 ER PT J AU Nierenberg, AA Pava, JA Clancy, K Rosenbaum, JF Fava, M AF Nierenberg, AA Pava, JA Clancy, K Rosenbaum, JF Fava, M TI Are neurovegetative symptoms stable in relapsing or recurrent atypical depressive episodes? SO BIOLOGICAL PSYCHIATRY LA English DT Article DE depression; atypical features; neurovegetative symptoms; recurrence; relapse; stability ID PHENELZINE; IMIPRAMINE; PLACEBO AB Few data exist that assess the presence of reversed and positive neurovegetative symptoms through successive depressive episodes, To assess the stability of depressive symptoms across episodes, we studied 74 outpatients with atypical unipolar major depression, diagnosed by the Structured Clinical Interview for DSM-III-R, before response to fluoxetine treatment and again after relapse on either fluoxetine or placebo, Patients were assessed at baseline with the Atypical Depression Diagnosis Scale and at baseline and during follow-lip with the 17-item Hamilton Racing Scale for Depression, Thirty-two (43%) of responders had a relapse or recurrence, 21 (66%) of whom had a predominance of reversed of positive neurovegetative symptoms at baseline, Nine of 10 (90%) patients with reversed symptoms at baseline had the same symptoms when they relapsed; seven of 11 (64%) of those with positive symptoms at baseline had positive symptoms again (kappa 0.557), Overall, five of 21 (24%) had changes in their disturbances in sleep, appetite, or weight when they relapsed This study supports the relative stability of neurovegetative symptoms in atypical depression across episodes. RP Nierenberg, AA (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPRESS RES PROGRAM,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114, USA. NR 17 TC 25 Z9 25 U1 0 U2 0 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 OCT 15 PY 1996 VL 40 IS 8 BP 691 EP 696 DI 10.1016/0006-3223(96)00029-7 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VL694 UT WOS:A1996VL69400001 PM 8894060 ER PT J AU Harvey, PD Davidson, M White, L Keefe, RSE Hirschowitz, J Mohs, RC Davis, KL AF Harvey, PD Davidson, M White, L Keefe, RSE Hirschowitz, J Mohs, RC Davis, KL TI Empirical evaluation of the factorial structure of clinical symptoms in schizophrenia: Effects of typical neuroleptics on the brief psychiatric rating scale SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; neuroleptic; Brief Psychiatric Rating Scale ID NEGATIVE SYMPTOMS; MODEL AB There has been little investigation of the effect of neuroleptic medication on the structure of symptoms in schizophrenia, In this study, 135 male schizophrenic patients were rated with the Brief Psychiatric Rating Scale (BPRS) after 4 weeks of treatment with typical neuroleptic medication and after 2 weeks free of neuroleptics, with the order of assessment varying across patients, Confirmatory factor analyses (CFA) found that there were no differences in symptom structure across medication status and no differences in the structure of symptoms in treatment responders and nonresponders, The typical 5-factor BPRS model fit the data poorly and the fit improved considerably through deletion of items measuring symptoms not associated with schizophrenia, suggesting that some of the symptoms that contribute to a total BPRS score may be adding primarily error variance, Although the sample size in this study is limited, the results suggest that using total BPRS scores to measure severity of schizophrenic symptoms should be reconsidered. C1 BRONX VET ADM MED CTR,PSYCHIAT SERV,BRONX,NY. RP Harvey, PD (reprint author), MT SINAI SCH MED,DEPT PSYCHIAT,BOX 1229,NEW YORK,NY 10029, USA. NR 22 TC 34 Z9 34 U1 1 U2 2 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 OCT 15 PY 1996 VL 40 IS 8 BP 755 EP 760 DI 10.1016/0006-3223(95)00486-6 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VL694 UT WOS:A1996VL69400009 PM 8894068 ER PT J AU Cooke, KR Kobzik, L Martin, TR Brewer, J Delmonte, J Crawford, JM Ferrara, JLM AF Cooke, KR Kobzik, L Martin, TR Brewer, J Delmonte, J Crawford, JM Ferrara, JLM TI An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation .1. The roles of minor H antigens and endotoxin SO BLOOD LA English DT Article ID VERSUS-HOST DISEASE; TUMOR-NECROSIS-FACTOR; RESPIRATORY-DISTRESS SYNDROME; DIFFUSE ALVEOLAR HEMORRHAGE; FACTOR-ALPHA; INTERSTITIAL PNEUMONITIS; LETHAL GRAFT; TNF-ALPHA; HISTOCOMPATIBILITY BARRIERS; MAJOR COMPLICATIONS AB Idiopathic pneumonia syndrome (IPS) refers to diffuse, noninfectious pneumonia that occurs after allogeneic bone marrow transplantation (BMT). We have developed a model of IFS using a well-characterized murine BMT system (B10.BR --> CBA) in which lung injury after BMT can be induced by minor histocompatibility (H) antigenic differences between donor and host. Lung pathology and broncho-alveolar lavage (BAL) fluid were analyzed in transplant recipients before and after both syngeneic and allogeneic BMT. At 2 weeks after BMT, no specific pathologic abnormalities were noted; at 6 weeks, both pneumonitis and mononuclear cell infiltration around vessels and bronchioles were observed only in mice receiving allogeneic BMT, This injury was associated with elevated BAL fluid levels of endotoxin (lipopolysaccharide [LPS]), neutrophils, and tumor necrosis factor alpha. No pathologic organisms were isolated from the respiratory tract of any animal. We also tested the role of endotoxin in the development of this injury. Injection of LPS 6 weeks after transplantation caused profound lung injury only in mice with moderate graft-versus-host disease; dramatic increases in BAL neutrophils and tumor necrosis factor alpha were observed, with alveolar hemorrhage occurring in 4 of 12 of these mice but in no other group. We conclude that (1) this murine BMT system is a potentially useful model of clinical IPS; (2) minor H differences between donor and recipient can be important stimuli in the pathogenesis of IPS; and (3) endotoxin in BAL fluid is associated with lung injury, and excess endotoxin can cause the development of alveolar hemorrhage in this model. (C) 1996 by The American Society of Hematology. C1 CHILDRENS HOSP,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV RESP,BOSTON,MA 02115. RP Cooke, KR (reprint author), DANA FARBER CANC INST,DIV PEDIAT ONCOL,D1638,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 39542]; NHLBI NIH HHS [HL55162]; NIAID NIH HHS [AI 30018] NR 55 TC 471 Z9 529 U1 1 U2 7 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 OCT 15 PY 1996 VL 88 IS 8 BP 3230 EP 3239 PG 10 WC Hematology SC Hematology GA VN595 UT WOS:A1996VN59500049 PM 8963063 ER PT J AU Renshaw, AA Henske, EP Loughlin, KR Shapiro, C Weinberg, DS AF Renshaw, AA Henske, EP Loughlin, KR Shapiro, C Weinberg, DS TI Aggressive variants of chromophobe renal cell carcinoma SO CANCER LA English DT Article DE renal cell carcinoma; chromophobe; prognosis; pathology; ploidy AB BACKGROUND. Chromophobe renal cell carcinoma (RCC) is a distinctive subtype of RCC with a more favorable prognosis than clear cell RCC. We describe the pathologic features of 23 solitary cases and 2 cases with coexistent papillary RCCs, 7 of which developed metastases. METHODS. Cases were retrieved from the pathology files of our institutions. Clinical follow-up was obtained from the medical records. DNA analysis was performed on Feulgen-stained slides using image analysis. RESULTS. Twenty-five cases were identified. All cases had characteristic pathologic features, including diffuse cytoplasmic reactivity for Hale's colloidal iron. DNA ploidy analysis of ten cases revealed a diploid pattern in five, a hyperdiploid pattern in four, and a hypodiploid pattern in one, Follow-up was available for 20 cases, and metastases developed in 7 (from 4 to 120 months after surgery). In 5 of these cases, the tumors were solitary and more than 8 cm in greatest dimension and metastases developed in the liver. In both cases with papillary RCCs in the same kidney, metastases developed in the lung, although which tumor metastasized is unknown. CONCLUSIONS. Despite the overall favorable prognosis for chromophobe RCC, large tumors and those with coexistent papillary RCCs may produce in metastases. (C) 1996 American Cancer Society. C1 HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,DIV EXPT MED & HEMATOL ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,DEPT UROL,BOSTON,MA. DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. RP Renshaw, AA (reprint author), HARVARD UNIV,DEPT PATHOL,BRIGHAM & WOMENS HOSP,SCH MED,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 24 TC 84 Z9 86 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 OCT 15 PY 1996 VL 78 IS 8 BP 1756 EP 1761 DI 10.1002/(SICI)1097-0142(19961015)78:8<1756::AID-CNCR16>3.0.CO;2-X PG 6 WC Oncology SC Oncology GA VL244 UT WOS:A1996VL24400016 PM 8859189 ER PT J AU Hajjar, RJ Kang, JX Gwathmey, JK Rosenzweig, A AF Hajjar, RJ Kang, JX Gwathmey, JK Rosenzweig, A TI Physiological effects of adenoviral gene transfer of sarcoplasmic reticulum calcium ATPase in isolated rat myocytes SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 2 Z9 2 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 89 EP 89 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900088 ER PT J AU Stevenson, WG Friedman, PL Kocovic, DZ Sager, PA Saxon, LA Pavri, BB AF Stevenson, WG Friedman, PL Kocovic, DZ Sager, PA Saxon, LA Pavri, BB TI Radiofrequency catheter ablation for sustained ventricular tachycardia after myocardial infarction SO CIRCULATION LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HOSP UNIV PENN,PHILADELPHIA,PA 19104. UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 121 EP 121 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900120 ER PT J AU Mela, D Schwammenthal, E Pratola, C Torp, H Pedini, I Alboni, P Levine, RA AF Mela, D Schwammenthal, E Pratola, C Torp, H Pedini, I Alboni, P Levine, RA TI An objective technique for applying the PISA method to quantitate mitral regurgitation: Initial clinical studies using the digital flow map. SO CIRCULATION LA English DT Meeting Abstract C1 OSPED CIVILE,CENTO,ITALY. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. DEPT BIOENGN,TRONDHEIM,NORWAY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 417 EP 417 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900416 ER PT J AU Cannistra, LB Davidoff, R Picard, MH OMalley, CJ Dempsey, A Balady, GJ AF Cannistra, LB Davidoff, R Picard, MH OMalley, CJ Dempsey, A Balady, GJ TI Does exercise training after myocardial SO CIRCULATION LA English DT Meeting Abstract C1 BROWN UNIV,MEM HOSP RHODE ISL,PAWTUCKET,RI 02860. BOSTON UNIV,MED CTR,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 435 EP 435 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900434 ER PT J AU Skopicki, HA Weissman, NJ Rose, GA Abraham, SA Gewirtz, H Picard, MH AF Skopicki, HA Weissman, NJ Rose, GA Abraham, SA Gewirtz, H Picard, MH TI B-blockade inhibits the ability of DSE to detect ischemia but does not affect the assessment of myocardial viability SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 475 EP 475 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900474 ER PT J AU Mathier, MA Lozano, P Cai, Q Kudej, RK Shannon, RP AF Mathier, MA Lozano, P Cai, Q Kudej, RK Shannon, RP TI Cocaine produces increased myocardial oxygen demand but impaired coronary blood flow responses in conscious dogs with pacing induced cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 809 EP 809 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900807 ER PT J AU Cai, Q Lozano, P Mathier, MA Shannon, RP AF Cai, Q Lozano, P Mathier, MA Shannon, RP TI Impaired beta adrenergic responsiveness is associated with excessive myocardial oxygen requirements in conscious dogs with pacing induced heart failure SO CIRCULATION LA English DT Meeting Abstract C1 NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 813 EP 813 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900811 ER PT J AU Hill, JS Davis, RC Yang, D Wen, J Philo, JS Poon, PH Schumaker, VN Kempner, ES Wong, H AF Hill, JS Davis, RC Yang, D Wen, J Philo, JS Poon, PH Schumaker, VN Kempner, ES Wong, H TI Human hepatic lipase subunit structure determination SO CIRCULATION LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NIAMS,BETHESDA,MD. AMGEN INC,THOUSAND OAKS,CA 91320. NR 0 TC 0 Z9 0 U1 4 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 884 EP 884 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900882 ER PT J AU Hill, JS Davis, RC Yang, D Nikazy, J Scholz, MC AF Hill, JS Davis, RC Yang, D Nikazy, J Scholz, MC TI A molecular biology-based approach to examine lipoprotein lipase subunit orientation SO CIRCULATION LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 885 EP 885 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900883 ER PT J AU BenZeev, O BriquetLaugier, V Doolittle, MH AF BenZeev, O BriquetLaugier, V Doolittle, MH TI Lec 23 and cld: Mutations affecting two enzymes of the lipase gene family SO CIRCULATION LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 886 EP 886 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900884 ER PT J AU Laugier, VB BenZeev, O Doolittle, MH AF Laugier, VB BenZeev, O Doolittle, MH TI Lipoprotein lipase is misfolded in combined lipase deficiency SO CIRCULATION LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 887 EP 887 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900885 ER PT J AU Moroi, M Gold, HK Yasuda, T Fishman, MC Huang, PL AF Moroi, M Gold, HK Yasuda, T Fishman, MC Huang, PL TI Mice mutant in endothelial nitric oxide synthase: Vessel growth and response to injury SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 890 EP 890 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900888 ER PT J AU Hajjar, RJ Kang, JX Rosenzweig, A AF Hajjar, RJ Kang, JX Rosenzweig, A TI Effects of adenoviral gene transfer of phospholamban on intracellular calcium homeostasis in isolated myocytes SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 922 EP 922 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900920 ER PT J AU Stafford, RS Saglam, D Blumenthal, D AF Stafford, RS Saglam, D Blumenthal, D TI Low rates of angiotensin-converting enzyme inhibitor use in congestive heart failure SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1127 EP 1127 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901124 ER PT J AU Bienkowska, J Cruz, MA Handin, RI Liddington, RC AF Bienkowska, J Cruz, MA Handin, RI Liddington, RC TI Crystal structure of the von Willebrand factor A3 domain. SO CIRCULATION LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV LEICESTER,LEICESTER,LEICS,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1266 EP 1266 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901263 ER PT J AU Hornberger, LK Benacerraf, BR AF Hornberger, LK Benacerraf, BR TI Blood flow velocities in the 10 to 20 weeks gestational age fetus. Observations in normal and diabetic pregnancies. SO CIRCULATION LA English DT Meeting Abstract C1 CHILDRENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1383 EP 1383 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901380 ER PT J AU Hornberger, LK Mattitau, A Colan, SD Benacerraf, BR AF Hornberger, LK Mattitau, A Colan, SD Benacerraf, BR TI Ventricular and great artery growth in the 10-20 week gestational fetus. SO CIRCULATION LA English DT Meeting Abstract C1 CHILDRENS HOSP,BOSTON,MA. KAPLAN HOSP,IL-76100 REHOVOT,ISRAEL. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1384 EP 1384 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901381 ER PT J AU Harrell, LC Hashimoto, H Boucher, CA Palacios, IF AF Harrell, LC Hashimoto, H Boucher, CA Palacios, IF TI Lesion morphology is no longer a predictor of major events following coronary intervention in the new device era SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 1 Z9 1 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1453 EP 1453 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901449 ER PT J AU Schmidt, U Hajjar, RJ Carles, M Gwathmey, JK AF Schmidt, U Hajjar, RJ Carles, M Gwathmey, JK TI Reduced phosphorylation level of phospholamban in human heart failure SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1479 EP 1479 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901475 ER PT J AU Brezinski, ME Tearney, GJ Boppart, SA Bouma, BE Swanson, EA Southern, JF Fujimoto, JG AF Brezinski, ME Tearney, GJ Boppart, SA Bouma, BE Swanson, EA Southern, JF Fujimoto, JG TI High speed catheter based OCT imaging of coronary microstructure SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MIT,CAMBRIDGE,MA 02139. RI Boppart, Stephen/C-7338-2009 NR 0 TC 3 Z9 3 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1494 EP 1494 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901490 ER PT J AU Pigazzi, A Folli, F Heydrich, S Loscalzo, J AF Pigazzi, A Folli, F Heydrich, S Loscalzo, J TI Nitric oxide inhibits thrombin induced phosphoinositide 3-kinase activity in human platelets SO CIRCULATION LA English DT Meeting Abstract C1 BOSTON UNIV,BOSTON,MA 02215. JOSLIN DIABET CTR,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1573 EP 1573 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901569 ER PT J AU Skopicki, HA Lyons, GE Guo, K Schirm, S Walsh, K AF Skopicki, HA Lyons, GE Guo, K Schirm, S Walsh, K TI Embryonic expression of a growth-arrest homoeobox gene in cardiac, smooth and skeletal muscle SO CIRCULATION LA English DT Meeting Abstract C1 ST ELIZABETH HOSP,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BERLEX BIOSCI,RICHWOOD,CA. UNIV WISCONSIN,SCH MED,MADISON,WI. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1735 EP 1735 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901730 ER PT J AU Han, XQ Valenzuela, D Huang, P Mende, U Neer, EJ Fishman, MC AF Han, XQ Valenzuela, D Huang, P Mende, U Neer, EJ Fishman, MC TI Elimination of the G protein G(alpha o) subunit by targeted mutation in the mouse attenuates the muscarinic regulation of the ventricular L-type Ca2+ current SO CIRCULATION LA English DT Meeting Abstract C1 DIV CARDIOVASC,BOSTON,MA. HARVARD UNIV,WOMENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIOVASC RES CTR,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1786 EP 1786 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901781 ER PT J AU Billman, GE Leaf, A AF Billman, GE Leaf, A TI Purified omega-3 fatty acids prevent ventricular fibrillation induced by myocardial ischemia SO CIRCULATION LA English DT Meeting Abstract C1 OHIO STATE UNIV,COLUMBUS,OH 43210. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1788 EP 1788 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901783 ER PT J AU Thompson, JT Rackley, MR Menick, DR Cooper, G OBrien, TX Johnson, RH AF Thompson, JT Rackley, MR Menick, DR Cooper, G OBrien, TX Johnson, RH TI Analysis of cytochrome C transcription in right ventricular overload and hypertrophically stimulated cardiomyocytes. SO CIRCULATION LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,GAZES CARDIAC RES INST,RALPH H JOHNSON VAMC,CHARLESTON,SC 29425. MED UNIV S CAROLINA,GAZES CARDIAC RES INST,CHARLESTON,SC 29425. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1797 EP 1797 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901792 ER PT J AU Sato, N Vatner, SF Shen, YT Kudej, RK Uechi, M Asai, K Ghaleh, B Mirsky, I Patrick, TA Shannon, RP Vatner, DE AF Sato, N Vatner, SF Shen, YT Kudej, RK Uechi, M Asai, K Ghaleh, B Mirsky, I Patrick, TA Shannon, RP Vatner, DE TI Chronic ventricular denervation attenuates the decline in cardiac function in conscious dogs during the progression of heart failure SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,SOUTHBOROUGH,MA 01772. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1819 EP 1819 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901814 ER PT J AU Otsuji, Y Jiang, L Gilon, D Roy, MJ Weyman, AE AF Otsuji, Y Jiang, L Gilon, D Roy, MJ Weyman, AE TI Reduced diastolic valve opening is flow-independent in patients with incomplete mitral leaflet closure: Evidence for mitral valve tethering SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1836 EP 1836 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901831 ER PT J AU Sweeney, MO Guy, ML McGovern, B Garan, H Ruskin, JN AF Sweeney, MO Guy, ML McGovern, B Garan, H Ruskin, JN TI Success of implantable cardioverter-defibrillator antitachycardia pacing algorithms for spontaneous sustained ventricular tachycardia is not dependent on local bipolar electrogram morphology SO CIRCULATION LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1868 EP 1868 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901863 ER PT J AU Leaf, DA Kleinman, MT Hamilton, M Barslow, TJ AF Leaf, DA Kleinman, MT Hamilton, M Barslow, TJ TI The exercise-induced oxidative stress paradox: The effects of physical exercise training SO CIRCULATION LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. UNIV CALIF IRVINE,IRVINE,CA 92717. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1899 EP 1899 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901894 ER PT J AU Adrie, C Bloch, KD Moreno, PR Hurford, WE Guerrero, JL Holt, R Zapol, WM Gold, HK Semigran, MJ AF Adrie, C Bloch, KD Moreno, PR Hurford, WE Guerrero, JL Holt, R Zapol, WM Gold, HK Semigran, MJ TI Inhaled nitric oxide increases coronary artery patency after thrombolysis SO CIRCULATION LA English DT Article DE nitric oxide; thrombolysis; thrombus ID PLATELET THROMBUS FORMATION; BLEEDING-TIME PROLONGATION; CYCLIC-GMP; ANIMAL-MODELS; AGGREGATION; REOCCLUSION; ACTIVATION; VASOCONSTRICTION; PEROXYNITRITE; PATHOGENESIS AB Background Nitric oxide (NO) and nitrosovasodilators that release NO inhibit platelet aggregation. The antithrombotic effect of intravenously infused nitrosovasodilators is usually accompanied by systemic vasodilation. Inhaled NO is a pulmonary vasodilator that does not produce systemic hemodynamic effects. This study examines the antithrombotic effect of inhaled NO in a canine model of platelet-mediated coronary artery reocclusion after thrombolysis. Methods and Results In 25 anesthetized dogs, a segment of the left anterior descending coronary artery was traumatized and a high-grade stenosis created. Thrombus was injected at this site, and tissue plasminogen activator was administered, producing cyclic flow variations (CFVs) in 24 of 25 dogs. CFV frequency was unchanged in dogs not breathing NO but decreased by 35+/-9% (P<.05) and 53+/-7% (P<.01) while dogs breathed 20 and 80 parts per million (ppm) NO, respectively. The coronary artery patency ratio (fraction of time during which the coronary artery was patent; CAPR) was unchanged in dogs not treated with NO but increased from 51+/-7% to 64+/-8% while breathing 20 ppm NO (P<.01) and from 49+/-3% to 75+/-7% while breathing 80 ppm NO (P<.01). The increased CAPR during 80 ppm NO administration persisted during a 45-minute posttreatment period (70+/-7%, P<.05 versus baseline). NO inhalation did not change systemic hemodynamics. In a pharmacological model of coronary vasoconstriction, inhaled NO did not reverse the effect of the thromboxane A(2) agonist U-46619. In vitro ADP-induced platelet aggregation was inhibited by NO gas. Conclusions Inhaled NO at concentrations of 20 and 80 ppm increases coronary patency and decreases CFV frequency in a canine model of platelet-mediated coronary reocclusion after thrombolysis without producing systemic hemodynamic effects. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,CARDIOVASC RES CTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI Hurford, William/G-6386-2013; Guerrero, Jorge/I-3666-2015 OI Hurford, William/0000-0003-1201-0313; Guerrero, Jorge/0000-0003-4315-7318 FU NHLBI NIH HHS [HL-42397, HL-45895] NR 40 TC 44 Z9 44 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 OCT 15 PY 1996 VL 94 IS 8 BP 1919 EP 1926 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VM393 UT WOS:A1996VM39300023 PM 8873669 ER PT J AU Mahjoub, ZA Eagle, KA Smith, CAJ Gold, MR OGara, PT Paul, SD AF Mahjoub, ZA Eagle, KA Smith, CAJ Gold, MR OGara, PT Paul, SD TI Clinical decision making for the cost-effective evaluation of patients with unexplained syncope: Role of Noninvasive testing SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV MICHIGAN,MED CTR,ANN ARBOR,MI. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1941 EP 1941 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901936 ER PT J AU Song, JK Handschumacher, MD Gilon, D Solheim, J Fontaine, AA Yoganathan, AP Levine, RA AF Song, JK Handschumacher, MD Gilon, D Solheim, J Fontaine, AA Yoganathan, AP Levine, RA TI Improved proximal flow rate calculation using 3D reconstruction of digital Doppler velocities and a control volume approach SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. GEORGIA INST TECHNOL,ATLANTA,GA 30332. SANTIN ENGN,PEABODY,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1951 EP 1951 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901946 ER PT J AU Jiang, L Handschumacher, MD Lee, MY Otsuji, Y Gilon, D Guerrero, JL Caldwell, A Weyman, AE Levine, RA AF Jiang, L Handschumacher, MD Lee, MY Otsuji, Y Gilon, D Guerrero, JL Caldwell, A Weyman, AE Levine, RA TI Three-dimensional echocardiographic analysis of the mechanism of incomplete mitral leaflet closure SO CIRCULATION LA English DT Meeting Abstract C1 UNIV NEBRASKA,MED CTR,OMAHA,NE. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1953 EP 1953 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901948 ER PT J AU Chung, IM Reidy, MA Schwartz, SM Wight, TN Gold, HK AF Chung, IM Reidy, MA Schwartz, SM Wight, TN Gold, HK TI Enhanced extracellular matrix synthesis may be important for restenosis of arteries after stent deployment. SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2034 EP 2034 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902029 ER PT J AU Vatner, DE Sato, N Uechi, M Asai, K Ishikawa, Y AF Vatner, DE Sato, N Uechi, M Asai, K Ishikawa, Y TI Mechanisms of milrinone desensitization in heart failure SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2102 EP 2102 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902097 ER PT J AU Lozano, P Mathier, MA Cai, Q Browne, R Kudej, RK Shannon, RP AF Lozano, P Mathier, MA Cai, Q Browne, R Kudej, RK Shannon, RP TI Dynamic alterations in perfusion-contraction matching during chronic rapid pacing in conscious dogs SO CIRCULATION LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2104 EP 2104 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902099 ER PT J AU Pclidori, MC Beal, MF Koroshetz, W Rordorf, G Frei, B AF Pclidori, MC Beal, MF Koroshetz, W Rordorf, G Frei, B TI Increased lipid peroxidation in patients with cortical stroke SO CIRCULATION LA English DT Meeting Abstract C1 BOSTON UNIV,SCH MED,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2284 EP 2284 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902279 ER PT J AU Durante, W Liao, L Peyton, KJ Schafer, AI AF Durante, W Liao, L Peyton, KJ Schafer, AI TI Lysophosphatidylcholine stimulates the transport of cationic amino acids and their metabolism to growth stimulatory polyamines in vascular smooth muscle cells. SO CIRCULATION LA English DT Meeting Abstract C1 HOUSTON VA MED CTR,HOUSTON,TX. BAYLOR COLL MED,HOUSTON,TX 77030. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2350 EP 2350 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902345 ER PT J AU Pombo, CM Bonventre, JV Kyriakis, JM Force, T AF Pombo, CM Bonventre, JV Kyriakis, JM Force, T TI Activation of a human Ste20 homolog by oxidant stress and ATP depletion defines a novel stress response pathway SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2389 EP 2389 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902384 ER PT J AU Murray, DR Prabhu, SD Freeman, GL AF Murray, DR Prabhu, SD Freeman, GL TI Detrimental effect of L-NAME on mechanical restitution in closed-chest dogs SO CIRCULATION LA English DT Meeting Abstract C1 UTHSC,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2448 EP 2448 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902443 ER PT J AU Keller, MW AF Keller, MW TI Adenosine metabolites are responsible for mast cell degranulation and arteriolar constriction during reperfusion of ischemic skeletal muscle SO CIRCULATION LA English DT Meeting Abstract C1 UNIV COLORADO,HLTH SCI CTR,DENVER,CO. DENVER VET AFFAIRS HOSP,DENVER,CO. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2485 EP 2485 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902479 ER PT J AU Mele, E Rodriguez, AE Peyregne, E Boullon, F Santaera, O Balino, NP Palacios, I AF Mele, E Rodriguez, AE Peyregne, E Boullon, F Santaera, O Balino, NP Palacios, I TI Final follow up of Argentine randomized trial coronary angioplasty vs bypass surgery in multivessel disease (ERACI): Clinical outcome and cost analysis SO CIRCULATION LA English DT Meeting Abstract C1 ANCHORENA HOSP,BUENOS AIRES,DF,ARGENTINA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2542 EP 2542 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902535 ER PT J AU Baruch, L ODwyer, P Patacsil, P Stern, EH Chockalingam, S Eng, C Javed, MT AF Baruch, L ODwyer, P Patacsil, P Stern, EH Chockalingam, S Eng, C Javed, MT TI Thrombogenic milieu of atrial flutter and atrial fibrillation: Similar or different? A transesophageal echocardiographic study before and after cardioversion. SO CIRCULATION LA English DT Meeting Abstract C1 BRONX VET ADM MED CTR,BRONX,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2662 EP 2662 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902654 ER PT J AU Lin, LF Oeun, S Houng, AK Reed, GL AF Lin, LF Oeun, S Houng, AK Reed, GL TI Residues in streptokinase that are necessary for the catalytic processing of plasminogen by the activator complex. SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2686 EP 2686 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902678 ER PT J AU Butte, A Houng, AK Jang, IK Reed, GL AF Butte, A Houng, AK Jang, IK Reed, GL TI Specific inhibition of alpha 2-antiplasmin improves thrombolysis by tissue plasminogen activator in experimental pulmonary embolism SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2692 EP 2692 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902684 ER PT J AU Boppart, SA Tearney, GJ Bouma, BE Brezinski, ME Fujimoto, JG AF Boppart, SA Tearney, GJ Bouma, BE Brezinski, ME Fujimoto, JG TI Noninvasive in vivo assessment of developing cardiovascular morphology and function using high-speed optical coherence tomography SO CIRCULATION LA English DT Meeting Abstract C1 MIT,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI Boppart, Stephen/C-7338-2009 NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2828 EP 2828 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902820 ER PT J AU Foster, GP Otsuji, Y Guerrero, JL Levine, RA AF Foster, GP Otsuji, Y Guerrero, JL Levine, RA TI Noninvasive quantitation of the regurgitant orifice area in aortic regurgitation using the continuity equation: In vivo validation in a canine model SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI Guerrero, Jorge/I-3666-2015 OI Guerrero, Jorge/0000-0003-4315-7318 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2880 EP 2880 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902872 ER PT J AU Laurie, A Shroyer, W MaWhinney, S Warner, BA Hammermeister, KE Grover, FL AF Laurie, A Shroyer, W MaWhinney, S Warner, BA Hammermeister, KE Grover, FL TI No relationship between coronary artery bypass procedure volume and hospital length of stay SO CIRCULATION LA English DT Meeting Abstract C1 DENVER VA MED CTR,DENVER,CO. RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2964 EP 2964 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902956 ER PT J AU Filippov, G Bloch, DB Bloch, KD AF Filippov, G Bloch, DB Bloch, KD TI Nitric oxide decreases stability of mRNAs encoding soluble guanylate cyclase subunits SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3050 EP 3050 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903042 ER PT J AU ODonnell, MJ White, LT Doumen, C Yu, X LaNoue, KF Lewandowski, ED AF ODonnell, MJ White, LT Doumen, C Yu, X LaNoue, KF Lewandowski, ED TI Altered enzyme-substrate affinity in the Kreb's cycle at low pH as shown by carbon-13 NMR: Combined studies of metabolic flux in mitochondria and intact hearts SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV PENN,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3199 EP 3199 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903189 ER PT J AU Cigarroa, JE Ferrell, MA Collen, DJ Leinbach, RC AF Cigarroa, JE Ferrell, MA Collen, DJ Leinbach, RC TI Enhanced endogenous coronary thrombolysis during acute myocardial infarction following selective platelet receptor blockade with ReoPro SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3235 EP 3235 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903225 ER PT J AU Wong, M Cohen, I Taylor, R Baruch, L Perry, G Deedwania, PC Lopez, B Jay, CN AF Wong, M Cohen, I Taylor, R Baruch, L Perry, G Deedwania, PC Lopez, B Jay, CN TI Felodipine as adjunctive therapy in failing hearts improves ventricular emptying. V-HeFT III: Echocardiographic sub-study SO CIRCULATION LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3252 EP 3252 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903242 ER PT J AU Sweeney, MO Guy, ML McGovern, B Garan, H Ruskin, JN Stevenson, WG AF Sweeney, MO Guy, ML McGovern, B Garan, H Ruskin, JN Stevenson, WG TI Natural history of spontaneous sustained monomorphic ventricular tachycardia in coronary disease revealed by local bipolar electrograms retrieved from implantable cardioverter-defibrillators SO CIRCULATION LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3321 EP 3321 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903311 ER PT J AU Houng, AK Fitzgerald, M Reed, GL AF Houng, AK Fitzgerald, M Reed, GL TI Identification and molecular cloning of PSTP: A novel platelet secretory transport protein SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3395 EP 3395 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903385 ER PT J AU Narula, J Elmaleh, D Petrov, A Babich, J Fischman, AJ Khaw, BA AF Narula, J Elmaleh, D Petrov, A Babich, J Fischman, AJ Khaw, BA TI Noninvasive recognition of the smooth muscle cell synthetic phenotype in experimental atherosclerotic lesions: Targeting the purinoceptor upregulation or be neoantigen expression SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NORTHEASTERN UNIV,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3429 EP 3429 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903419 ER PT J AU Rollins, BJ Fallon, JT Rossikhina, M Zhang, YJ Nemerson, Y Taubman, MB AF Rollins, BJ Fallon, JT Rossikhina, M Zhang, YJ Nemerson, Y Taubman, MB TI Monocyte chemoattractant protein induces tissue factor in human aortic smooth muscle cells. SO CIRCULATION LA English DT Meeting Abstract C1 MT SINAI SCH MED,NEW YORK,NY. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3477 EP 3477 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903467 ER PT J AU Fogel, R Smith, C Laposata, M Johnson, SM Waltman, AC Thompson, BT Hales, CA AF Fogel, R Smith, C Laposata, M Johnson, SM Waltman, AC Thompson, BT Hales, CA TI Plasma D-Dimer in the diagnosis of pulmonary embolism SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3490 EP 3490 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903480 ER PT J AU Skopicki, H Abraham, S Fischman, A Alpert, N Gewirtz, H AF Skopicki, H Abraham, S Fischman, A Alpert, N Gewirtz, H TI PET measurement of myocardial blood flow responses to high dose dobutamine in patients with ischemic heart disease. SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3531 EP 3531 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903521 ER PT J AU Paul, SD Lambrew, CT Rogers, WJ Fifer, MA AF Paul, SD Lambrew, CT Rogers, WJ Fifer, MA TI A study of 118,276 patients with acute myocardial infarction in the United States in 1995: Less aggressive care, worse prognosis, and longer hospital length of stay for diabetics SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3576 EP 3576 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903566 ER PT J AU He, SQ Fontaine, AA Schwammenthal, E Yoganathan, AP AF He, SQ Fontaine, AA Schwammenthal, E Yoganathan, AP TI The mechanism of functional mitral regurgitation: The area of leaflet tenting predicts regurgitation better than the linear coaptation distance SO CIRCULATION LA English DT Meeting Abstract C1 GEORGIA INST TECHNOL,ATLANTA,GA 30332. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3612 EP 3612 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903603 ER PT J AU Dow, CJ Devour, L Gordon, L Guerrero, JL Gold, HK AF Dow, CJ Devour, L Gordon, L Guerrero, JL Gold, HK TI Successful use of a novel percutaneous aspiration thrombectomy catheter in coronary arteries SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HEART TECHNOL,REDMOND,WA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3616 EP 3616 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903607 ER PT J AU Murcia, AM Fallon, JT Fuster, V AF Murcia, AM Fallon, JT Fuster, V TI Smooth muscle cell proliferation does not account for restenosis in diabetic patients SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MT SINAI MED CTR,NEW YORK,NY 10029. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3628 EP 3628 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903619 ER PT J AU Gerszten, RE Rosenzweig, A AF Gerszten, RE Rosenzweig, A TI Adenoviral co-expression of VCAM-1 and MCP-1 in bovine aortic endothelial cells in vitro SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3705 EP 3705 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903696 ER PT J AU Tyler, RC Muramatsu, M Hepler, LK Abman, SH Stelzner, TJ Rodman, DM Bloch, KM McMurtry, IF AF Tyler, RC Muramatsu, M Hepler, LK Abman, SH Stelzner, TJ Rodman, DM Bloch, KM McMurtry, IF TI Variability in endothelial nitric oxide synthase gene expression in hypoxic, monocrotaline, and fawn hooded hypertensive rat lungs SO CIRCULATION LA English DT Meeting Abstract C1 UNIV COLORADO,HLTH SCI CTR,DENVER,CO. MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3783 EP 3783 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903774 ER PT J AU Hammermeister, KE Sethi, GK Henderson, WG Rahimtoola, S AF Hammermeister, KE Sethi, GK Henderson, WG Rahimtoola, S TI Comparison of outcomes 16 years after randomization to valve replacement with a bioprosthetic or mechanical prosthetic valve SO CIRCULATION LA English DT Meeting Abstract C1 DENVER VA MED CTR,DENVER,CO. TUCSON VA MED CTR,TUCSON,AZ. UNIV SO CALIF,LOS ANGELES,CA. EDWARD HINES VET ADM MED CTR,HINES,IL 60141. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3798 EP 3798 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903789 ER PT J AU Brezinski, ME Tearney, GJ Boppart, SA Weissman, N Bouma, BE Southern, JF Swanson, EA Fujimoto, JG AF Brezinski, ME Tearney, GJ Boppart, SA Weissman, N Bouma, BE Southern, JF Swanson, EA Fujimoto, JG TI Comparison of catheter based OCT imaging with high frequency ultrasound SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. GEORGETOWN UNIV,WASHINGTON,DC. MIT,CAMBRIDGE,MA 02139. RI Boppart, Stephen/C-7338-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3818 EP 3818 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903809 ER PT J AU Carles, M Schmidt, U Hajjar, RJ Narula, J Gwathmey, JK Khaw, BA AF Carles, M Schmidt, U Hajjar, RJ Narula, J Gwathmey, JK Khaw, BA TI The role of anti-SERCA2a antibody in the induction of experimental myocarditis: Characterization of the immunopathogenic epitope SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. NORTHEASTERN UNIV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3845 EP 3845 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903836 ER PT J AU Jelicks, L Li, CS Etgen, A Nordin, C Siri, F AF Jelicks, L Li, CS Etgen, A Nordin, C Siri, F TI Inverse relation between dihydropyridine binding and intracellular free sodium in hypertrophied guinea pig hearts. SO CIRCULATION LA English DT Meeting Abstract C1 ALBERT EINSTEIN COLL MED,BRONX,NY 10467. BRONX VET ADM MED CTR,BRONX,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3873 EP 3873 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903864 ER PT J AU Lawson, CA Stern, DM Rollins, BJ Yan, SD Pinsky, DJ AF Lawson, CA Stern, DM Rollins, BJ Yan, SD Pinsky, DJ TI Oxygen deprivation as a stimulus for thrombosis: The critical role of MCP-1 and tissue factor in vivo SO CIRCULATION LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. COLUMBIA UNIV,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 4062 EP 4062 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11904053 ER PT J AU Shatos, MA Doherty, JM Garabedian, HD Gold, HK AF Shatos, MA Doherty, JM Garabedian, HD Gold, HK TI ReoPro, antiplatelet antibody, enhances fibrinolytic potential of cultured arterial microvascular cells SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV VERMONT,COLL MED,BURLINGTON,VT 05405. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 4105 EP 4105 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11904096 ER PT J AU Stafford, RS Saglam, D Blumenthal, D AF Stafford, RS Saglam, D Blumenthal, D TI National patterns of medication treatment in hypertension SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 4198 EP 4198 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11904189 ER PT J AU Mullen, MP Schwartz, ML Fernandes, SM Liberthson, RR Perry, SB Landzberg, MJ AF Mullen, MP Schwartz, ML Fernandes, SM Liberthson, RR Perry, SB Landzberg, MJ TI Coronary artery abnormalities in anomalous left coronary artery from the pulmonary artery SO CIRCULATION LA English DT Meeting Abstract C1 BOSTON ADULT CONGENITAL HEART SERV,BOSTON,MA. CHILDRENS HOSP,BOSTON,MA. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 4206 EP 4206 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11904197 ER PT J AU Vonderheide, RH Kuter, DJ Thadhani, R AF Vonderheide, RH Kuter, DJ Thadhani, R TI Association of thrombocytopenia and use of intra-aortic balloon pump SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 4297 EP 4297 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11904288 ER PT J AU Wang, TC Koh, TJ Varro, A Cahill, RJ Dangler, CA Fox, JG Dockray, GJ AF Wang, TC Koh, TJ Varro, A Cahill, RJ Dangler, CA Fox, JG Dockray, GJ TI Processing and proliferative effects of human progastrin in transgenic mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE gastrin gene expression; transgenic mice; progastrin processing; growth factor; colon cancer ID GASTRIN RECEPTOR ANTAGONIST; CARCINOMA CELL-LINES; BINDING PROTEIN; PANCREATIC GASTRIN; INSULINOMA CELLS; RAT PANCREAS; HUMAN-COLON; EXPRESSION; GROWTH; GENE AB Incompletely processed gastrins have been postulated to play a role in growth of the gastrointestinal tract, but few studies have examined the effects of progastrin on mucosal proliferation in vivo, Human gastrin gene expression and progastrin processing were therefore studied in transgenic mice containing a human gastrin (hGAS) minigene, and compared to processing in mice bearing an insulin gastrin (INS-GAS) transgene that overexpresses amidated gastrin. Progastrin processing was studied using region-specific antisera and radioimmunoassays, biosynthetic labeling, immunoprecipitation, and HPLC, Proliferative effects due to overexpression of processed and unprocessed gastrin in INS-GAS and hGAS mice, respectively, were determined using routine histology and BrdU incorporation, The pancreatic islets of INS-GAS mice were able to produce carboxyamidated G-17, resulting in a twofold elevation of serum amidated gastrin, marked thickening of the oxyntic mucosa, and an increased BrdU labeling index (LI) of the gastric body. In contrast, livers of adult hGAS mice expressed abundant human gastrin mRNA and human progastrin but were unable to process this peptide to the mature amidated form, resulting in markedly elevated serum progastrin levels and normal amidated gastrin levels, Nevertheless, there was a marked increase in the BrdU labeling index of the colon in hGAS mice (LI 7.46+/-1.90%), as well as in INS-GAS mice (LI 6.16+/-1.17%), compared to age-matched, wild type control mice (LI 4.01+/-0.98%, P < 0.05). These studies suggest that incompletely processed gastrin precursors may contribute to colonic mucosal proliferation in vivo. C1 UNIV LIVERPOOL,PHYSIOL LAB,LIVERPOOL L69 3BX,MERSEYSIDE,ENGLAND. MIT,DIV COMPARAT MED,CAMBRIDGE,MA 02139. RP Wang, TC (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,DEPT MED,GRJ 724,32 FRUIT ST,BOSTON,MA 02114, USA. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 FU NIDDK NIH HHS [R01 DK-48077]; Wellcome Trust NR 58 TC 226 Z9 228 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT 15 PY 1996 VL 98 IS 8 BP 1918 EP 1929 DI 10.1172/JCI118993 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VN973 UT WOS:A1996VN97300029 PM 8878444 ER PT J AU Russell, GJ Parker, CM Sood, A Mizoguchi, E Ebert, EC Bhan, AK Brenner, MB AF Russell, GJ Parker, CM Sood, A Mizoguchi, E Ebert, EC Bhan, AK Brenner, MB TI p126 (CDw101), a costimulatory molecule preferentially expressed on mucosal T lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTESTINAL INTRAEPITHELIAL LYMPHOCYTES; LEUKOCYTE SURFACE PROTEIN; LYMPHOID-CELL LINES; EPITHELIAL-CELLS; PROLIFERATIVE RESPONSES; MONOCLONAL-ANTIBODY; RECEPTOR; LEUKEMIA; ESTABLISHMENT; ANTIGEN AB Intestinal mucosal lymphocytes are defined by their anatomic location within the epithelium (intraepithelial lymphocytes), the interstitium between the epithelial basement membrane and the underlying muscularis mucosa (lamina propria lymphocytes), or in organized lymphoid tissues (Peyer's patches), Although intestinal intraepithelial lymphocytes have a distinct localization, their function has not been determined. To define cell surface proteins that are involved in intestinal intraepithelial lymphocyte localization or function, cultured human mucosal lymphocytes were used as immunogens to develop mAbs that react predominantly with this cell population in an immunohistochemical screening assay, Three mAbs were selected that subsequently were found by biochemical analysis to identify a 200-kDa homodimeric polypeptide on 88 to 98% of CD3(+) mucosal lymphocytes but only 18 +/- 13% of PBLs, Expression on granulocytes and monocytes was also observed, This polypeptide has been termed p126 based on its SDS-PAGE-determined M(r) under reducing conditions, Cleveland digest maps demonstrated similarity between the p126 and CDw101 polypeptides, Determined amino acid sequence analysis of the purified p126 polypeptide revealed that it is the protein product of the recently identified V7 gene, which has structural similarities to members of the Ig gene superfamily, Two of the anti-p126 mAbs were costimulatory with suboptimal concentrations of anti-CD3 mAb inducing proliferation of cultured intestinal intraepithelial lymphocytes, Thus, we conclude that p126 is CDw101 encoded by a gene that predicts a seven-Ig domain chain-like structure, It has restricted expression predominantly on mucosal T lymphocytes and appears to have a costimulatory function of special relevance for CD28(-) T cells and for mucosal lymphocytes. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV RHEUMATOL & IMMUNOL,BOSTON,MA 02115. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT MED,NEW BRUNSWICK,NJ 08903. RP Russell, GJ (reprint author), HARVARD UNIV,SCH MED,PROGRAM PEDIAT GASTROENTEROL & NUTR,250 LONGWOOD AVE,ROOM 507,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK33506, KO8DK02010, DK43351] NR 47 TC 22 Z9 22 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 OCT 15 PY 1996 VL 157 IS 8 BP 3366 EP 3374 PG 9 WC Immunology SC Immunology GA VP226 UT WOS:A1996VP22600022 PM 8871633 ER PT J AU Vidal, SM Pinner, E Lepage, P Gauthier, S Gros, P AF Vidal, SM Pinner, E Lepage, P Gauthier, S Gros, P TI Natural resistance to intracellular infections - Nramp1 encodes a membrane phosphoglycoprotein absent in macrophages from susceptible (Nramp1(D169)) mouse strains SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYCOBACTERIUM-BOVIS BCG; PHENOTYPIC-EXPRESSION; HOST-RESISTANCE; GENETIC-CONTROL; PROTEIN; IDENTIFICATION; SEQUENCE; GLYCOPROTEINS; PARASITES; FAMILY AB The mouse Nramp1 gene (Bcg/lty/Lsh) controls innate defense to infection with intracellular parasites such as Mycobacterium, Salmonella, and Leishmania. Sequence analysis of Nramp1 predicts a hydrophobic, membrane-associated protein expressed exclusively in monocyte/macrophage lineages, A single G169D substitution within the fourth predicted transmembrane domain of Nramp1 is associated with susceptibility to infection (Bcg(s)) in inbred mouse strains, To initiate the biochemical characterization of the Nramp1 protein and to analyze the molecular basis of susceptibility associated with the Nramp1(D169) allelel oligopeptides derived from Nramp1 and two fusion proteins containing the first 54 and the last 35 residues of Nramp1 were used to raise specific anti-Nramp1 antisera, In addition, a c-Myc epitope (EQKLISEEDL) was introduced in-frame at the C terminus of Nramp1 to follow its expression in a yeast heterologous system. Western analysis of crude membrane fractions from yeast demonstrated that Nramp1 is indeed an integral membrane protein (resistant to urea extraction), In resident Bcg(r) (129sv, Nramp1(G169)) macrophages, one of the anti-Nramp1 antisera identified by immunoprecipitation a protein of 90,000 to 100,000 apparent m.w. that was absent in macrophages from knockout mice bearing a null mutation at Nramp1, The Nramp1 protein could be metabolically labeled with orthophosphate and was sensitive to glycosylase treatment, verifying that Nramp1 is an integral membrane phosphoglycoprotein, Parallel analysis of macrophage extracts from Bcg(s) mouse strains (C57BL6/J and BALB/c, Nramp1(D169)) failed to detect mature Nramp1 protein in these cells, suggesting that the G169D mutation at Nramp1 prevents proper maturation or membrane integration of the protein, resulting in its rapid degradation. C1 MCGILL UNIV, DEPT BIOCHEM, MONTREAL, PQ H3G 1Y6, CANADA. MONTREAL GEN HOSP, MCGILL CTR STUDY HOST RESISTANCE, MONTREAL, PQ, CANADA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT CELL BIOL, BOSTON, MA 02115 USA. FU NIAID NIH HHS [1RO1AI35237-01] NR 51 TC 166 Z9 170 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1996 VL 157 IS 8 BP 3559 EP 3568 PG 10 WC Immunology SC Immunology GA VP226 UT WOS:A1996VP22600045 PM 8871656 ER PT J AU Kelly, K AF Kelly, K TI Reversing asthma: A drug-free approach - Firshein,RN SO LIBRARY JOURNAL LA English DT Book Review RP Kelly, K (reprint author), MASSACHUSETTS GEN HOSP,TRENDWELL LIB,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 SN 0363-0277 J9 LIBR J JI Libr. J. PD OCT 15 PY 1996 VL 121 IS 17 BP 84 EP 84 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA VN323 UT WOS:A1996VN32300187 ER PT J AU Castillo, L Beaumier, L Ajami, AM Young, VR AF Castillo, L Beaumier, L Ajami, AM Young, VR TI Whole body nitric oxide synthesis in healthy men determined from [N-15]arginine-to-[N-15]citrulline labeling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID L-ARGININE; DEPENDENT VASODILATION; INTRAVENOUS TRACER; PLASMA ARGININE; ADULT MAN; KINETICS; NITRATE; METABOLISM; ISOTOPE; HUMANS AB The rates of whole body nitric oxide (NO) synthesis, plasma arginine flux, and de novo arginine synthesis and their relationships to urea production, were examined in a total of seven healthy adults receiving an L-amino acid diet for 6 days. NO synthesis was estimated by the rate of conversion of the [N-15]guanidino nitrogen of arginine to plasma [N-15]ureido citrulline and compared with that based on urinary nitrite (NO2-)/nitrate (NO3-) excretion. Six subjects received on dietary day 7, a 24-hr (12-hr fed/12-hr fasted) primed, constant, intravenous infusion of L-[guanidino-N-15(2)]arginine and [C-13]urea. A similar investigation was repeated with three of these subjects, plus an additional subject, in which they received L-[ureido-C-13] citrulline, to determine plasma citrulline fluxes. The estimated rates (mean +/- SD) of NO synthesis over a period of 24 hr averaged 0.96 +/- 0.1 mu mol . kg(-1). hr(-1) and 0.95 +/- 0.1 mu mol . kg(-1). hr(-1), for the [N-15]citrulline and the nitrite/nitrate methods, respectively. About 15% of the plasma arginine turnover was associated with urea formation and 1.2% with NO formation. De novo arginine synthesis averaged 9.2 +/- 1.4 mu mol . kg(-1). hr(-1), indicating that approximate to 11% of the plasma arginine flux originates via conversion of plasma citrulline to arginine. Thus, the fraction of the plasma arginine flux associated with NO and also urea synthesis in healthy humans is small, although the plasma arginine compartment serves as a significant precursor pool (54%) for whole body NO formation. This tracer model should be useful for exploring these metabolic relationships in vivo, under specific pathophysiologic states where the L-arginine-NO pathway might he altered. C1 MIT, CLIN RES CTR, CAMBRIDGE, MA 02139 USA. SHRINERS BURNS INST, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. MASS TRACE INC, WOBURN, MA 01801 USA. RP Castillo, L (reprint author), MIT, HUMAN NUTR LAB, CAMBRIDGE, MA 02139 USA. FU NCRR NIH HHS [RR80]; NIDDK NIH HHS [DK 15856]; NIGMS NIH HHS [GM 02700] NR 29 TC 149 Z9 150 U1 0 U2 4 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 OCT 15 PY 1996 VL 93 IS 21 BP 11460 EP 11465 DI 10.1073/pnas.93.21.11460 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100031 PM 8876157 ER PT J AU Hanstein, B Eckner, R DiRenzo, J Halachmi, S Liu, H Searcy, B Kurokawa, R Brown, M AF Hanstein, B Eckner, R DiRenzo, J Halachmi, S Liu, H Searcy, B Kurokawa, R Brown, M TI p300 is a component of an estrogen receptor coactivator complex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE transcription; steroid hormone; estrogen receptor-associated protein ID NUCLEAR-PROTEIN CBP; TRANSCRIPTIONAL ADAPTER; HORMONE RECEPTOR; ACTIVATION; KINASE; SUPERFAMILY; MEDIATOR; CREB AB The estrogen receptor (ER) is a ligand-dependent transcription factor that regulates expression of target genes in response to estrogen in concert with other cellular signaling pathways. This suggests that the mechanism by which ER transmits an activating signal to the general transcription machinery may include factors that integrate these diverse signals. We have previously characterized the estrogen receptor-associated protein, ERAP160, as a factor that complexes with ER in an agonist-dependent manner. We have now found that the transcriptional coactivator p300 associates with agonist bound ER and augments ligand-dependent activation by ER. Our studies show that an ER coactivator complex involves a direct hormone-dependent interaction between ER and ERAP160, resulting in the recruitment of p300. In addition, antibodies directed against the cloned steroid receptor coactivator 1 (SRC1) recognize ERAP160. The known role of p300 in multiple signal transduction pathways, including those involving the second messenger cAMP, suggests p300 functions as a point of integration between ER and these other pathways. C1 DANA FARBER CANC INST,DEPT NEOPLAST DIS MECHANISMS,BOSTON,MA 02115. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [CA57374] NR 25 TC 302 Z9 304 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 OCT 15 PY 1996 VL 93 IS 21 BP 11540 EP 11545 DI 10.1073/pnas.93.21.11540 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100045 PM 8876171 ER PT J AU Sheng, S Carey, J Seftor, EA Dias, L Hendrix, MJC Sager, R AF Sheng, S Carey, J Seftor, EA Dias, L Hendrix, MJC Sager, R TI Maspin acts at the cell membrane to inhibit invasion and motility of mammary and prostatic cancer cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE serpin; tumor suppressor; ruffling; video microscopy ID PLASMINOGEN-ACTIVATOR INHIBITOR-2; PRIMARY BREAST-CANCER; EPITHELIAL-CELLS; SCATTER FACTOR; EXTRACELLULAR-MATRIX; UROKINASE RECEPTOR; SIGNAL SEQUENCE; STRESS FIBERS; MIGRATION; EXPRESSION AB Maspin, a novel serine protease inhibitor (serpin), inhibits tumor invasion and metastasis of mammary carcinoma. We show here that recombinant maspin protein blocks the motility of these carcinoma cells in culture over 12 h, as demonstrated by time-lapse video microscopy. Lamellopodia are withdrawn but ruffling continues. Both exogenous recombinant maspin and maspin expressed by tumor transfectants exhibit inhibitory effects on cell motility and cell invasion as shown in modified Boyden chamber assays. In addition, three prostatic cancer cell lines treated with recombinant maspin exhibited similar inhibition of both invasion and motility, suggesting a similar mode of maspin action in these two glandular epithelial cancers. When mammary carcinoma cells were treated with recombinant maspin, the protein was shown by immunostaining to bind specifically to the cell surface, suggesting that maspin activity is membrane associated. When pretreated with antimaspin antibody, maspin loses its inhibitory effects on both invasion and motility. However, when maspin is added to these cells preceding antibody treatment, the activity of maspin is no longer inhibited by subsequent addition of the antibody. It is concluded therefore that the inhibition of invasion and motility by maspin is initially localized to the cell surface. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC GENET,BOSTON,MA 02115. UNIV IOWA,DEPT ANAT,COLL MED,IOWA CANC CTR,IOWA CITY,IA 52242. FU NCI NIH HHS [CA59702, CA61253] NR 56 TC 296 Z9 306 U1 1 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 OCT 15 PY 1996 VL 93 IS 21 BP 11669 EP 11674 DI 10.1073/pnas.93.21.11669 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100068 PM 8876194 ER PT J AU Xia, K Mukhopadhyay, NK Inhorn, RC Barber, DL Rose, PE Lee, RS Narsimhan, RP DAndrea, AD Griffin, JD Roberts, TM AF Xia, K Mukhopadhyay, NK Inhorn, RC Barber, DL Rose, PE Lee, RS Narsimhan, RP DAndrea, AD Griffin, JD Roberts, TM TI The cytokine-activated tyrosine kinase JAK2 activates Raf-1 in a p21(ras)-dependent manner SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE signal transduction; baculovirus; mammalian cells; oncogenes ID GAMMA SIGNAL-TRANSDUCTION; INTERFERON-GAMMA; ERYTHROPOIETIN RECEPTOR; PLASMA-MEMBRANE; PROTEIN-KINASE; CELL LINE; PHOSPHORYLATION; TRANSCRIPTION; REQUIREMENT; ALPHA/BETA AB JAK2, a member of the Janus kinase superfamily was found to interact functionally with Raf-1, a central component of the ras/mitogen-activated protein kinase signal transduction pathway. Interferon-gamma and several other cytokines that are known to activate JAK2 kinase were also found to stimulate Raf-1 kinase activity toward MEK-1 in mammalian cells. In the baculovirus coexpression system, Raf-1 was activated by JAK2 in the presence of p21(ras). Under these conditions, a ternary complex of p21(ras), JAK2, and Raf-1 was observed. In contrast, in the absence of p21(ras), coexpression of JAK2 and Raf-1 resulted in an overall decrease in the Raf-1 kinase activity. In addition, JAK2 phosphorylated Raf-1 at sites different from those phosphorylated by pp60(v-src). In mammalian cells treated with either erythropoietin or interferon-gamma, a small fraction of Raf-1 coimmunoprecipitated with JAK2 in lysates of cells in which JAK2 was activated as judged by its state of tyrosine phosphorylation. Taken together, these data suggest that JAK2 and p21(ras) cooperate to activate Raf-1. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA36167, CA43803]; NIDDK NIH HHS [DK43889] NR 31 TC 69 Z9 69 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 OCT 15 PY 1996 VL 93 IS 21 BP 11681 EP 11686 DI 10.1073/pnas.93.21.11681 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100070 PM 8876196 ER PT J AU Hall, KT Boumsell, L Schultze, JL Boussiotis, VA Dorfman, DM Cardoso, AA Bensussan, A Nadler, LM Freeman, GJ AF Hall, KT Boumsell, L Schultze, JL Boussiotis, VA Dorfman, DM Cardoso, AA Bensussan, A Nadler, LM Freeman, GJ TI Human CD100, a novel leukocyte semaphorin that promotes B-cell aggregation and differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE germinal center; T cell; CD23 ID MOLECULAR-CLONING; EXPRESSION; ANTIGEN; CD40; ACTIVATION; RECEPTOR; LIGAND; COLLAPSIN; MEMBER AB Herein we describe the molecular characterization of the human leukocyte activation antigen CD100 and identify it as the first semaphorin, to our knowledge, in the immune system. Semaphorins have recently been described as neuronal chemorepellants that direct pioneering neurons during nervous system development. In this study we demonstrate that CD100 induces B cells to aggregate and improves their viability in vitro. We show that CD100 modifies CD40-CD40L B-cell signaling by augmenting B-cell aggregation and survival and down-regulating CD23 expression. Thus, these results suggest that semaphorins as exemplified by CD100 also play a functional role in the immune system. C1 HARVARD UNIV,SCH MED,DEPT MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HOP ST LOUIS,INSERM U93,F-75675 PARIS 10,FRANCE. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. RI Schultze, Joachim/D-7794-2011; Bensussan, Armand/E-5434-2017 OI Schultze, Joachim/0000-0003-2812-9853; FU NCI NIH HHS [CA40216-11]; NIAID NIH HHS [AI35225-03] NR 25 TC 187 Z9 199 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 OCT 15 PY 1996 VL 93 IS 21 BP 11780 EP 11785 DI 10.1073/pnas.93.21.11780 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100088 PM 8876214 ER PT J AU Mazzaccaro, RJ Gedde, M Jensen, ER vanSanten, HM Ploegh, HL Rock, KL Bloom, BR AF Mazzaccaro, RJ Gedde, M Jensen, ER vanSanten, HM Ploegh, HL Rock, KL Bloom, BR TI Major histocompatibility class I presentation of soluble antigen facilitated by Mycobacterium tuberculosis infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COMPLEX CLASS-I; LISTERIA-MONOCYTOGENES; T-CELLS; EXOGENOUS ANTIGENS; INTERFERON-GAMMA; MHC MOLECULES; MACROPHAGES; PHAGOSOME; GROWTH; PHAGOCYTOSIS AB Cell-mediated immune responses are essential for protection against many intraceIluIar pathogens. For Mycobacterium tuberculosis (MTB), protection requires the activity of T cells that recognize antigens presented in the context of both major histocompatibility complex (MHC) class II and I molecules. Since MHC class I presentation generally requires antigen to be localized to the cytoplasmic compartment of antigen-presenting cells, it remains unclear how pathogens that reside primarily within endocytic vesicles of infected macrophages, such as MTB, can elicit specific MHC class I-restricted T cells. A mechanism is described for virulent MTB that allows soluble antigens ordinarily unable to enter the cytoplasm, such as ovalbumin, to be presented through the MHC class I pathway to T cells. The mechanism is selective for MHC class I presentation, since MTB infection inhibited MHC class II presentation of ovalbumin. The MHC class I presentation requires the tubercle bacilli to be viable, and it is dependent upon the transporter associated with antigen processing (TAP), which translocates antigenic peptides from the cytoplasm into the endoplasmic reticulum. The process is mimicked by Listeria monocytogenes and soluble listeriolysin, a pore-forming hemolysin derived from it, suggesting that virulent MTB may have evolved a comparable mechanism that allows molecules in a vacuolar compartment to enter the cytoplasmic presentation pathway for the generation of protective MHC class I-restricted T cells. C1 ALBERT EINSTEIN COLL MED,DEPT MICROBIOL & IMMUNOL,BRONX,NY 10461. ALBERT EINSTEIN COLL MED,HOWARD HUGHES MED INST,BRONX,NY 10461. UNIV PENN,SCH MED,DEPT MICROBIOL,PHILADELPHIA,PA 19104. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90095. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RI van Santen, Hisse Martien/E-8103-2013 FU NIAID NIH HHS [AI25545, AI07118] NR 38 TC 122 Z9 124 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 OCT 15 PY 1996 VL 93 IS 21 BP 11786 EP 11791 DI 10.1073/pnas.93.21.11786 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100089 PM 8876215 ER PT J AU Yamaguchi, N Plant, C Biancone, L Bachovchin, W McCluskey, R Andres, G AF Yamaguchi, N Plant, C Biancone, L Bachovchin, W McCluskey, R Andres, G TI In vivo modulation of CD26 (dipeptidyl peptidase IV) in the mouse - Effects of polyreactive and monoreactive antibodies SO TRANSPLANTATION LA English DT Article ID THYMOCYTE-ACTIVATING MOLECULE; PASSIVE HEYMANN NEPHRITIS; NATURAL ANTIBODIES; AMINOPEPTIDASE-IV; MEMBRANOUS GLOMERULONEPHRITIS; LYMPHOCYTE SURFACE; MEDIATED INJURY; IMMUNE-COMPLEXES; PROXIMAL TUBULES; DEFICIENT RATS AB We previously reported that intravenous injections in rabbits or guinea pigs of divalent antibodies to purified protein or carbohydrate antigens located mainly on endothelial cells induce acute pulmonary edema, which is often lethal. Surviving animals develop resistance to the injurious effect of subsequent injection of antibodies (adaptation), associated with shedding of antigen-antibody complexes from endothelial cells. In the present study, we investigated and compared in mice the effects of 3-day multiple injections of two different rabbit antibody (IgG) preparations against antigens expressed mainly at the surface of epithelial cells. The first preparation contained antibodies to a single transmembrane protein, CD26 (dipeptidyl peptidase IV [DPP IV]) (monoreactive anti-DPP IV IgG); the second contained antibodies against multiple antigens of the renal tubular brush border (BE), including DPP IV (polyreactive anti-BB IgG). Both IgG preparations caused loss of DPP IV from the organs studied, as shown by reduction in enzyme activity in tissue homogenates and by immunofluorescence microscopy, which showed loss of DPP IV from cell surface. However, the monoreactive anti-DPP IV IgG induced considerably greater reduction than polyreactive anti-BE IgG. Loss of DPP IV from the cell surface probably occurred by shedding of immune complexes into vascular and extravascular fluids, including bile and urine. The results may have relevance to hyperacute rejection of xenografts, as from pigs to primates. Since human natural antibodies that bind to porcine cells are polyreactive, a new prophylactic strategy for hyperacute rejection might be based on down-regulation of the major xenogeneic antigen, alpha-galactosyl, by injecting donor animals with monoreactive alpha-galactosyl antibodies before transplantation. C1 MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT PATHOL,CHARLESTOWN,MA. TUFTS UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02111. FU NIAID NIH HHS [AI-52251]; NIDDK NIH HHS [DK-36807] NR 100 TC 7 Z9 7 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 15 PY 1996 VL 62 IS 7 BP 973 EP 985 DI 10.1097/00007890-199610150-00017 PG 13 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA VN109 UT WOS:A1996VN10900017 PM 8878393 ER PT J AU Wang, LX Cardin, S Martinez, V Tache, Y AF Wang, LX Cardin, S Martinez, V Tache, Y TI Intracerebroventricular CRF inhibits cold restraint-induced c-fos expression in the dorsal motor nucleus of the vagus and gastric erosions in rats SO BRAIN RESEARCH LA English DT Article DE fos; cold; CRF; dorsal motor nucleus of the vagus; raphe pallidus; gastric erosion; central amygdala; nucleus tractus solitarius; paraventricular nucleus of the hypothalamus ID CORTICOTROPIN-RELEASING FACTOR; SYMPATHETIC PREGANGLIONIC NEURONS; VAGAL COMPLEX; RAPHE PALLIDUS; PARAVENTRICULAR NUCLEUS; LESION FORMATION; SOLITARY TRACT; SPINAL-CORD; CARDIOVASCULAR-RESPONSES; ADRENAL MEDULLARY AB Acute exposure to cold-restraint induces vagal-dependent gastric erosions associated with activation of neurons in the dorsal motor nucleus of the vagus (DMN) in rats. The influence of intracerebroventricular (i.c.v.) injection of corticotropin-releasing factor (CRF) (10 mu g) on c-fos expression in the brain and gastric erosions induced by 3 h cold-restraint was investigated in conscious rats. In cold-restraint exposed rats, CRF injected i.c.v. inhibited gastric erosions and the number of Fos positive neurons in the DMN by 93 and 72%, respectively. while Fos labelling in the nucleus tractus solitarius (NTS) was as increased by 5-fold compared with vehicle group. c-fos expression was also induced in the central amygdala by i.c.v. CRF, unlike the vehicle-injected group exposed to cold-restraint, c-fos expression induced by cold-restraint in the raphe pallidus (Rpa) and paraventricular nucleus of the hypothalamus was not altered by i.c.v. CRF. These data indicate that central CRF-induced gastric protection results from the inhibition of DMN neuronal activity enhanced by cold-restraint. CRF action on DMN neurons may be related to the increase in the NTS and central amygdala inputs leading to inhibition of DMN neurons rather than to the decrease in the excitatory input from the caudal raphe projections to the DMN. C1 UNIV CALIF LOS ANGELES,INST BRAIN RES,LOS ANGELES,CA 90073. RP Wang, LX (reprint author), UNIV CALIF LOS ANGELES,W LOS ANGELES VET ADM MED CTR,DEPT MED,CURE,DIGEST DIS RES CTR,LOS ANGELES,CA 90073, USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-33061]; NIMH NIH HHS [MH-00663] NR 58 TC 45 Z9 48 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 14 PY 1996 VL 736 IS 1-2 BP 44 EP 53 DI 10.1016/0006-8993(96)00726-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA VR613 UT WOS:A1996VR61300006 PM 8930307 ER PT J AU Salgia, R Pisick, E Sattler, M Li, JAL Uemura, N Wong, WK Burky, SA Hirai, H Chen, LP Griffin, JD AF Salgia, R Pisick, E Sattler, M Li, JAL Uemura, N Wong, WK Burky, SA Hirai, H Chen, LP Griffin, JD TI p130(CAS) forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; ACTIN-BINDING DOMAINS; TYROSINE PHOSPHORYLATION; V-CRK; SH3 DOMAINS; MOLECULAR-CLONING; C-ABL; ADHESION; KINASE; IDENTIFICATION AB The Philadelphia chromosome (Ph) translocation generates a chimeric tyrosine kinase oncogene, BCR/ABL, which causes chronic myelogenous leukemia (CML) and a type of acute lymphoblastic leukemia (ALL). In primary samples from virtually all patients with CML or Ph(+)ALL, the CRKL adapter protein is tyrosine phosphorylated and physically associated with p210(BCR/ABL). CRKL has one SH2 domain and two SH3 domains and is structurally related to c-CRK-II (CRK) and the v-Crk oncoprotein. We have previously shown that CRKL, but not the related adapter protein c-CRK, is tyrosine phosphorylated in cell lines transformed by BCR/ABL, and that CRKL binds to BCR/ABL through the CRKL-SH3 domains. Furthermore, the CRKL-SH2 domain has been shown to bind one or more cellular proteins, one of which is p120(CBL). Here we demonstrate that another cellular protein linked to BCR/ABL through the CRKL-SH2 domain is p130(CAS). p130(CAS) was found to be tyrosine phosphorylated and associated with CRKL in BCR/ABL expressing cell lines and in samples obtained from CML and ALL patients, but not in samples from controls. In both normal and BCR/ABL transformed cells, p130(CAS) was detected in focal adhesion-like structures, as was BCR/ABL. In normal cells, the focal adhesion proteins tensin, p125(FAK), and paxillin constitutively associated with p130(CAS). However, in BCR/ABL transformed cells, the interaction between p130(CAS) and tensin was disrupted, while the associations between p130(CAS), p125(FAK) and paxillin were unaffected. These results suggest that the BCR/ABL oncogene could alter the function of p130(CAS) in at least three ways: tyrosine phosphorylation, inducing constitutive binding of CRKL to a domain in p130(CAS) containing Tyr-X-X-Pro moths (substrate domain), and disrupting the normal interaction of p130(CAS) with the focal adhesion protein tensin. These alterations in the structure of signaling proteins in focal adhesion Like structures could contribute to the known adhesion abnormalities in CML cells. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV TOKYO,DEPT INTERNAL MED 3,BUNKYO KU,TOKYO 113,JAPAN. OI Li, Jian-Liang/0000-0002-6487-081X FU NCI NIH HHS [CA36167, CA60821] NR 45 TC 103 Z9 104 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 OCT 11 PY 1996 VL 271 IS 41 BP 25198 EP 25203 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VL693 UT WOS:A1996VL69300022 PM 8810278 ER PT J AU Bunnell, SC Henry, PA Kolluri, R Kirchhausen, T Rickles, RJ Berg, LJ AF Bunnell, SC Henry, PA Kolluri, R Kirchhausen, T Rickles, RJ Berg, LJ TI Identification of Itk/Tsk Src homology 3 domain ligands SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BRUTONS TYROSINE KINASE; X-LINKED AGAMMAGLOBULINEMIA; WISKOTT-ALDRICH SYNDROME; CELL ANTIGEN RECEPTOR; C-CBL PROTOONCOGENE; SH3 DOMAINS; T-CELLS; PROTEIN PRODUCT; K-PROTEIN; B-CELLS AB The tyrosine kinase Itk/Tsk is a T cell specific analog of Btk, the tyrosine kinase defective in the human immunodeficiency X-Linked agammaglobulinemia and in xid mice. T lymphocytes from Itk-deficient mice are refractory to mitogenic stimuli delivered through the T cell receptor (TCR). To gain insights into the biochemical role of Itk, the binding properties of the Itk SH3 domain were examined. An optimal Itk SH3 binding motif was derived by screening biased phage display libraries; peptides based on this motif bound with high affinity and selectivity to the Itk SH3 domain. Initial studies with T cell lysates indicated that the Itk SH3 domain bound Cbl, Fyn, and other tyrosine phosphoproteins from TCR-stimulated jurkat cells. Under conditions of increased detergent stringency Sam 68, Wiskott-Aldrich Syndrome protein, and hnRNP-K, but not Cbl and Fyn, were bound to the Itk SH3 domain. By examining the ability of different SH3 domains to interact with deletion variants of Sam 68 and WASP, we demonstrated that the Itk-SH3 domain and the SH3 domains of Src family kinases bind to overlapping but distinct sets of proline-rich regions in Sam 68 and WASP. C1 HARVARD UNIV,DEPT MOL & CELLULAR BIOL,CAMBRIDGE,MA 02138. ARIAD PHARMACEUT INC,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. FU NIAID NIH HHS [AI37584] NR 77 TC 140 Z9 140 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 OCT 11 PY 1996 VL 271 IS 41 BP 25646 EP 25656 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VL693 UT WOS:A1996VL69300085 PM 8810341 ER PT J AU Mashimo, H Wu, DC Podolsky, DK Fishman, MC AF Mashimo, H Wu, DC Podolsky, DK Fishman, MC TI Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor SO SCIENCE LA English DT Article ID PANCREATIC SPASMOLYTIC POLYPEPTIDE; EXPRESSION; PEPTIDES; CELLS; RAT; IDENTIFICATION; DISRUPTION; SECRETION; LETHALITY; TISSUES AB The mechanisms that maintain the epithelial integrity of the gastrointestinal tract remain largely undefined. The gene encoding intestinal trefoil factor (ITF), a protein secreted throughout the small intestine and colon, was rendered nonfunctional in mice by targeted disruption. Mice lacking ITF had impaired mucosal healing and died from extensive colitis after oral administration of dextran sulfate sodium, an agent that causes mild epithelial injury in wild-type mice. ITF-deficient mice manifested poor epithelial regeneration after injury. These findings reveal a central role for ITF in the maintenance and repair of the intestinal mucosa. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. FU NIDDK NIH HHS [P30DK43351, R01DK46906, T32DK07191] NR 27 TC 515 Z9 536 U1 2 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 11 PY 1996 VL 274 IS 5285 BP 262 EP 265 DI 10.1126/science.274.5285.262 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM671 UT WOS:A1996VM67100048 PM 8824194 ER PT J AU Kabelitz, D Marx, S Robertson, MJ Janssen, O AF Kabelitz, D Marx, S Robertson, MJ Janssen, O TI Rapid modulation of T lymphocyte surface antigens induced by Fas (CD95, APO-1) ligation SO CELLULAR IMMUNOLOGY LA English DT Article ID ACTIVATION-DRIVEN DEATH; PROGRAMMED CELL-DEATH; NODE HOMING RECEPTOR; INDUCED APOPTOSIS; MONOCLONAL-ANTIBODY; L-SELECTIN; MICE; LIGAND; EXPRESSION; INDUCTION AB Crosslinking the Fas (CD95, APO-1) antigen by mAb or Fas-ligand (Fas-L)-expressing cells triggers apoptosis. We have investigated the early consequences of Fas signaling on the expression of various cell surface antigens on T lymphocytes. Incubation of Fas-sensitive Jurkat (JM) cells with agonistic anti-Fas mAb induced rapid (within 4 hr) downmodulation of L-selectin (CD62L) and CD7 but not of CD3 or CD71. No modulation was observed on Fas-expressing but Fas-resistant JM variant 432.1. On PHA-activated, Fas-sensitive T cell blasts, anti-Fas mAb rapidly triggered downmodulation of a variety of antigens, including CD2, CD4, CD8, CD7, CD44, LFA1 alpha, LFA1 beta, and CD62L, but not CD3, CD25, or CD26. Most of these antigens were not downmodulated by either CD3 crosslinking (except CD3) or PMA treatment (except CD3, CD4, and CD62L). Comparable patterns of biphasic CD44, LFA1 alpha, and LFA1 beta expression were observed on CD4(+) and CD8(+) T cell blasts in response to Fas crosslinking. In these instances, downregulation occurred preferentially on cells undergoing rapid shrinkage. These results indicate that rapid downregulation of selected surface antigens is an early response of both normal and transformed T cells to Fas crosslinking. (C) 1996 Academic Press, Inc. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. RP Kabelitz, D (reprint author), PAUL EHRLICH INST,DEPT IMMUNOL,D-63225 LANGEN,GERMANY. RI Kabelitz, Dieter/A-2757-2010; Janssen, Ottmar/E-9735-2010 NR 41 TC 8 Z9 8 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT 10 PY 1996 VL 173 IS 1 BP 108 EP 115 DI 10.1006/cimm.1996.0256 PG 8 WC Cell Biology; Immunology SC Cell Biology; Immunology GA VN241 UT WOS:A1996VN24100012 PM 8871606 ER PT J AU Behar, O Golden, JA Mashimo, H Schoen, FJ Fishman, MC AF Behar, O Golden, JA Mashimo, H Schoen, FJ Fishman, MC TI Semaphorin III Is needed for normal patterning and growth of nerves, bones and heart SO NATURE LA English DT Article ID SPINAL-CORD; CONE GUIDANCE; GENE; FAMILY; EXPRESSION; COLLAPSIN; MEMBER AB THE expression patterns of the recently discovered family of semaphorin genes suggests that they have widespread roles in embryonic development(1-9). Some seem to guide neuronal growth cones, but otherwise their functions are unknown(2,10-12). Semaphorin III is a membrane-associated secreted protein with a developmentally dynamic pattern of expression, including particular domains of the nervous system, the borders of developing bones, and the heart(6,7). In vitro, semaphorin III causes growth-cone collapse, and repels cutaneous sensory axons from the ventral spinal cord(2,11). Mutants in the Drosophila gene semaII, which encodes a related semaphorin, die after eclosion, but no responsible abnormality is evident(3). We have generated mice mutant in the semaIII gene by homologous recombination. Here we show that in the mutants, some sensory axons project into inappropriate regions of the spinal cord where semaIII is normally expressed. The cerebral cortex of hymozygous mutant mice shows a paucity of neuropil and abnormally oriented neuronal processes, especially of the large pyramidal neurons. Certain embryonic bones and cartilaginous structures develop abnormally, with vertebral fusions and partial rib duplications. The few mice that survive more than a few days postnatally manifest pronounced and selective hypertrophy of the right ventricle of the heart and dilation of the right atrium. Thus, semaphorin III might serve as a signal that restrains growth in several developing organs. C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 22 TC 421 Z9 428 U1 1 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD OCT 10 PY 1996 VL 383 IS 6600 BP 525 EP 528 DI 10.1038/383525a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VL755 UT WOS:A1996VL75500050 PM 8849723 ER PT J AU Blumenthal, D AF Blumenthal, D TI Quality of health care .4. The origins of the quality-of-care debate SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PHYSICIANS; OUTCOMES RP Blumenthal, D (reprint author), MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,50 STANIFORD ST,BOSTON,MA 02114, USA. NR 39 TC 111 Z9 111 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 OCT 10 PY 1996 VL 335 IS 15 BP 1146 EP 1149 DI 10.1056/NEJM199610103351511 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA VN399 UT WOS:A1996VN39900011 PM 8813048 ER PT J AU Bosch, I Croop, J AF Bosch, I Croop, J TI P-glycoprotein multidrug resistance and cancer SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review ID MDR1 GENE-EXPRESSION; MULTIPLE-DRUG-RESISTANCE; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ADVANCED BREAST-CANCER; RENAL-CELL CARCINOMA; HUMAN COLON-CARCINOMA; HAMSTER OVARY CELLS; PHASE-I/II TRIAL; LIPOSOME-ENCAPSULATED DOXORUBICIN C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. NR 350 TC 89 Z9 95 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD OCT 9 PY 1996 VL 1288 IS 2 BP F37 EP F54 DI 10.1016/0304-419X(96)00022-4 PG 18 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA VP007 UT WOS:A1996VP00700003 PM 8876632 ER PT J AU Green, J AF Green, J TI Stem cells, lineage and plasticity of the differentiated state: A one-day symposium sponsored by Massachusetts General Hospital, Harvard Cutaneous Biology Research Center, held Friday, May 17, 1996 SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Editorial Material DE stem cell; differentiation; pluiripotency; cell fate; lineage; plasticity C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RP Green, J (reprint author), HARVARD UNIV,SCH MED,DIV MOL GENET,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD OCT 9 PY 1996 VL 1288 IS 2 BP R9 EP R11 DI 10.1016/0304-419X(96)00026-1 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA VP007 UT WOS:A1996VP00700006 ER PT J AU Seddon, JM Willett, WC Speizer, FE Hankinson, SE AF Seddon, JM Willett, WC Speizer, FE Hankinson, SE TI A prospective study of cigarette smoking and age-related macular degeneration in women SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID VITAMIN-C; PLASMA; RISK; SMOKERS; HEART; EYE AB Objective.-To evaluate the relationship between cigarette smoking acid incidence of age-related macular degeneration (AMD) among women. Design.-Prospective cohort study with 12 years of follow-up (1980 to 1992), in which information on smoking habits was updated every 2 years. Setting.-Eleven states throughout the United States. Participants.-A total of 31 843 registered nurses enrolled in the Nurses' Health Study who were aged 50 to 59 years in 1980 and did not report a diagnosis of cancer or AMD at the beginning of the study. Additional women entered the analytic cohort as they reached 50 years of age. Main Outcome Measure.-Incidence of AMD with visual loss. Results.-During 556 338 person-years of follow-up, 215 women were newly diagnosed as having AMD. After adjusting for other risk factors for AMD, women who currently smoked 25 or more cigarettes per day had a relative risk (RR) of AMD of 2.4 (95% confidence interval [CI], 1.4-4.0) compared with women who never smoked. Past smokers of this amount also had a 2-fold increased risk (RR=2.0; 95% CI, 1.2-3.4) relative to never smokers. Compared with current smokers, little reduction in risk was suggested even after quitting smoking for 15 or more years. Risk of AMD also increased with an increasing number of pack-years smoked (P for trend <.001); among women who smoked for 65 or more pack-years, the risk was 2.4 times the risk of never smokers (95% CI, 1.5-3.8). Analyses of dry and exudative types of AMD and other alternative definitions of AMD revealed similar results, Conclusions.-Cigarette smoking is an independent and avoidable risk factor for AMD among women. Because AMD is the most common cause of severe visual impairment among the elderly and treatment is not available or is ineffective for most patients, reducing the risk of this disease is another important reason to avoid smoking. C1 BRIGHAM & WOMENS HOSP,DEPT MED,CHANNING LAB,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT OPHTHALMOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. RP Seddon, JM (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,EPIDEMIOL UNIT,243 CHARLES ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 40356]; NEI NIH HHS [EY 09611] NR 25 TC 302 Z9 307 U1 4 U2 26 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 OCT 9 PY 1996 VL 276 IS 14 BP 1141 EP 1146 DI 10.1001/jama.276.14.1141 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VL332 UT WOS:A1996VL33200023 PM 8827966 ER PT J AU Doyle, KM CluetteBrown, JE Dube, DM Bernhardt, TG Morse, CR Laposata, M AF Doyle, KM CluetteBrown, JE Dube, DM Bernhardt, TG Morse, CR Laposata, M TI Fatty acid ethyl esters in the blood as markers for ethanol intake SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ALCOHOL-CONSUMPTION; METABOLISM; SERUM; ABUSE AB Objective.-To determine the clinical utility of farcy acid ethyl esters (FAEEs) in the blood as a short-term confirmatory marker for ethanol intake and a longer-term marker for ethanol intake after ethanol is no longer detectable. Design.-Single-center controlled clinical trial and a blinded comparison involving 48 blood samples that were positive, negative, or equivocal for blood ethanol. Participants.-Seven healthy subjects (4 men and 3 women, aged 21 to 23 years) participated in the clinical trial. Blood samples from participants for the blinded comparison portion of the study were numbered from 1 to 48 and not identified by name. Intervention.-The 7 healthy subjects ingested a known amount of ethanol at a fixed rate. The concentration of FAEEs in the blood alter ethanol intake was determined for a period of up to 24 hours. There was no intervention in the blinded comparison study. Main Outcome Measures.-In the clinical trial, a pharmacokinetic analysis of FAEE concentration in the blood after ethanol intake was completed for 7 individuals whose blood ethanol level was elevated from 25 to 35 mmol/L. In the blinded comparison, the 48 blood samples that were positive, negative, or equivocal for blood ethanol were analyzed for FAEE concentration. Results.-In the clinical trial, the disappearance of FAEEs from the blood followed a decay curve that initially resembled the decay curve for blood ethanol. However, because of a very slow secondary elimination phase, the FAEEs were found to persist in the blood for at least 24 hours after ethanol intake was completed, In the blinded comparison, all 20 samples that were positive for ethanol were positive for FAEEs, 7 of 7 samples equivocal for ethanol were positive for FAEEs, and 21 of 21 negative samples for ethanol were negative for FAEEs. Conclusions.-Serum concentration of FAEEs can serve as an excellent shortterm confirmatory test for ethanol intake as well as a longer-term marker of ethanol ingestion. Measurement of FAEEs in the blood may be a more sensitive indicator of ethanol ingestion than the measurement of blood ethanol. C1 MASSACHUSETTS GEN HOSP, DIV CLIN LABS, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. NR 23 TC 81 Z9 83 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 OCT 9 PY 1996 VL 276 IS 14 BP 1152 EP 1156 DI 10.1001/jama.276.14.1152 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA VL332 UT WOS:A1996VL33200025 PM 8827968 ER PT J AU Bartzokis, G Nuechterlein, KH Marder, SR Mintz, J Dery, K Laack, K AF Bartzokis, G Nuechterlein, KH Marder, SR Mintz, J Dery, K Laack, K TI Age at illness onset and left temporal lobe length in males with schizophrenia SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE magnetic resonance imaging (mri); schizophrenia; temporal lobe length; illness onset ID STRUCTURAL BRAIN CHANGES; LONG-TERM COURSE; HEAD CIRCUMFERENCE; NATURAL-HISTORY; LIMBIC SYSTEM; BASAL GANGLIA; POST-MORTEM; VOLUME; SUBTYPES; ABNORMALITIES AB Post-mortem data suggest that in schizophrenia, temporal lobe length may be associated with age at illness onset. We used sagittal magnetic resonance images standardly acquired in reference to a coronal pilot image to obtain linear measurements of the left hemisphere in 38 male schizophrenic patients early in the course of their illness and 21 matched normal controls. In addition to temporal lobe and anterior temporal lobe (anterior to the anterior commissure) lengths, measurements of maximal brain and skull lengths were also obtained. The data show that differences in temporal lobe length between patients and normal controls are primarily due to significant differences between the groups in the global measures of brain and skull lengths. However, within the patient group, a significant association between temporal lobe length and age at onset of psychosis was observed. The same association was observed when the anterior part of the temporal lobe was measured separately. These associations remained significant after controlling for multiple variables such as subject height and brain and skull lengths. Further statistical evaluations showed that the temporal lobe was significantly shorter among the subgroup of schizophrenics whose illness began before the age of 23. The data suggest that temporal lobe length may be a useful variable for investigating the biological heterogeneity of schizophrenia and highlight important technical issues regarding current efforts to measure the volumes of temporal lobe structures. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA 90074. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,DEPT RADIOL,TORRANCE,CA 90509. RP Bartzokis, G (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,11301 WILSHIRE BLVD,MAIL CODE B-151H,LOS ANGELES,CA 90073, USA. RI Bartzokis, George/K-2409-2013 NR 45 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD OCT 7 PY 1996 VL 67 IS 3 BP 189 EP 201 DI 10.1016/0925-4927(96)02894-6 PG 13 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VQ760 UT WOS:A1996VQ76000003 PM 8912958 ER PT J AU Eming, SA Yarmush, ML Morgan, JR AF Eming, SA Yarmush, ML Morgan, JR TI Enhanced function of cultured epithelium by genetic modification: Cell-based synthesis and delivery of growth factors SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article; Proceedings Paper CT Biochemical Engineering IX - Interdisciplinary Foundations for Creating New Biotechnology CY MAY 21-26, 1995 CL DAVOS, SWITZERLAND DE tissue engineering; gene therapy; artificial skin; wound-healing growth factors; growth factor delivery ID HUMAN EPIDERMAL-CELLS; HUMAN KERATINOCYTES; FULL-THICKNESS; FACTOR-ALPHA; BURN WOUNDS; SKIN; EXPRESSION; THERAPY; TISSUE; ALLOGRAFTS AB Skin substitutes, containing cultured keratinocytes of the epidermis (autologous or allogeneic cells), have been used in the treatment of severe burns and other defects of the skin such as chronic ulcers. Our goal is to enhance the functions of the cells used in these skin substitutes by genetic modification. We propose to develop a genetically modified skin graft which would function as a cell-based vehicle for the local synthesis and delivery of wound-healing growth factors. Using retroviral-mediated gene transfer, we have introduced stable copies of the genes encoding platelet-derived growth factor (PDGF-A) or insulin-like growth factor-1 (IGF-1) into cultured human diploid keratinocytes. After stable integration of these genes, the cells secreted significant levels of these growth factors, 744 ng and 502 ng/10(7) cells/24 h for PDGF-A and IGF-1, respectively. The modified cells were grown to confluence, detached as a multicell-layered epithelial sheet, and transplanted to athymic mice. Seven days after transplantation, grafts secreting PDGF-A or IGF-1 differentiated into a stratified epithelium comparable to unmodified cells. Most importantly, the newly synthesized connective tissue layer subjacent to the PDGF-A-modified grafts was significantly thicker and showed an increase in cellularity, vascularity, type I collagen, and fibronectin deposition when compared to control grafts of unmodified cells or grafts expressing IGF-1. These results demonstrated that the function of the cells of a skin substitute can be enhanced by genetic modification and show that PDGF-A secretion from these cells can mediate changes to the cellular, vascular, and extracellular matrix composition of the adjacent dermal tissue. Moreover, these results suggest that a cell-based method for growth factor synthesis and delivery may be a useful approach to promoting tissue repair. (C) 1996 John Wiley & Sons, Inc. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURN INST,SURG SERV,BOSTON,MA 02114. RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ. OI Morgan, Jeffrey/0000-0002-7546-3443 NR 37 TC 9 Z9 9 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD OCT 5 PY 1996 VL 52 IS 1 BP 15 EP 23 DI 10.1002/(SICI)1097-0290(19961005)52:1<15::AID-BIT2>3.0.CO;2-1 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA VH413 UT WOS:A1996VH41300003 PM 18629848 ER PT J AU Calias, P Galanopoulos, T Maxwell, M Khayat, A Graves, D Antoniades, HN dAlarcao, M AF Calias, P Galanopoulos, T Maxwell, M Khayat, A Graves, D Antoniades, HN dAlarcao, M TI Synthesis of inositol 2-phosphate-quercetin conjugates SO CARBOHYDRATE RESEARCH LA English DT Article DE inositol phosphates; quercetin; solubilized flavonoid conjugates ID QUERCETIN; CELLS AB The antiproliferative flavonoid, quercetin, is limited in its pharmacological utility by its low water solubility. In this paper, we describe the synthesis of two quercetin analogues prepared by linking the hydroxyl group at the 3- or 5-position of the flavonoid to the 1-hydroxyl group of myo-inositol-2-phosphate via a succinate diester linkage, The resulting conjugates were found to have dramatically enhanced water solubility relative to quercetin; the 5-linked quercetin analogue 2 had a water solubility of > 300 mg/mL at 20 degrees C, Comparison of the in vitro cytotoxicity and antiproliferative activity of conjugate 2 with those of quercetin toward cultured human colon adenocarcinoma (SW480) and human glioblastoma (U87MG) cells indicated that this modification of quercetin does not significantly diminish its activity in these assays. (C) 1996 Elsevier Science Ltd. C1 TUFTS UNIV,DEPT CHEM,MEDFORD,MA 02155. BOSTON UNIV,SCH DENT MED,DIV ORAL BIOL,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,SERV NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NR 16 TC 18 Z9 19 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD OCT 4 PY 1996 VL 292 BP 83 EP 90 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA VK403 UT WOS:A1996VK40300008 PM 8870239 ER PT J AU Koepp, DM Silver, PA AF Koepp, DM Silver, PA TI A GTPase controlling nuclear trafficking: Running the right way or walking RANdomly? SO CELL LA English DT Review ID PROTEIN IMPORT; RNA EXPORT; BINDING; RAN/TC4; TRANSLOCATION; DISSOCIATION; INHIBITION C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP Koepp, DM (reprint author), HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115, USA. NR 18 TC 143 Z9 144 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 4 PY 1996 VL 87 IS 1 BP 1 EP 4 DI 10.1016/S0092-8674(00)81315-X PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VL695 UT WOS:A1996VL69500001 PM 8858141 ER PT J AU Kyriakis, JM Avruch, J AF Kyriakis, JM Avruch, J TI Sounding the alarm: Protein kinase cascades activated by stress and inflammation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID SIGNAL-TRANSDUCTION PATHWAY; AMINO-TERMINAL KINASES; HEAT-SHOCK PROTEINS; C-JUN; MAPKAP KINASE-2; PHOSPHORYLATION; IDENTIFICATION; THREONINE; YEAST; JNK AB Eukaryotic cells respond to extracellular stimuli by recruiting signal transduction pathways, many of which employ protein Ser/Thr kinases of the ERK(1) family. The ubiquity of ERKs and their upstream activators, the MEKs, in signal transduction was first appreciated from studies of yeast (1, 2). Although a 54-kDa rat liver c-Jun kinase (SAPK-p54 alpha 1) with properties similar to the Ras-regulated MAPKs had been characterized (3-5), the physiologic roles and regulation of this and related mammalian enzymes have emerged only recently. Molecular cloning of the SAPKs and p38s, together with the paradigms derived from the ''classical'' MAPKs and work in lower eukaryotes has enabled rapid elucidation of the regulation and cellular functions of these newer mammalian ERK pathways. Although architecturally homologous to the Ras/MAPK pathway, the SAPK and p38 pathways are not activated primarily by mitogens but by cellular stresses and inflammatory cytokines, which stimuli result in growth arrest, apoptosis, or activation of immune and reticuloendothelial cells. C1 MASSACHUSETTS GEN HOSP,DIABET RES LABS,MED SERV,DIABET UNIT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,CHARLESTOWN,MA 02129. NR 78 TC 919 Z9 938 U1 1 U2 22 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 OCT 4 PY 1996 VL 271 IS 40 BP 24313 EP 24316 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM674 UT WOS:A1996VM67400001 PM 8798679 ER PT J AU Cahill, CM Waterman, WR Xie, Y Auron, PE Calderwood, SK AF Cahill, CM Waterman, WR Xie, Y Auron, PE Calderwood, SK TI Transcriptional repression of the prointerleukin 1 beta gene by heat shock factor 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NECROSIS-FACTOR-ALPHA; EXPRESSION; INTERLEUKIN-1; CELLS; BINDING; LIPOPOLYSACCHARIDE; TRANSDUCTION; TEMPERATURE; ACTIVATION; SEQUENCE AB Heat shock factor 1 activates the promoters of heat shock genes at elevated temperatures through its interaction with heat shock elements. We have examined a new role for heat shock factor 1 in the repression of the prointerluekin 1 beta gene in human monocytes responding to stimulation with lipopolysaccharide. Both exposure to elevated temperatures and heat-independent heat shock factor 1 expression repressed the transcription of the prointerleukin 1 beta gene, and repression was strictly dependent on an intact consensus heat shock element in the prointerleukin 1 beta promoter to which heat shock factor 1 bound. This is the first demonstration of heat shock factor 1 as a transcriptional repressor and suggests a role for the factor in the counter-regulation of cytokine gene transcription. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA47407, CA50642]; NIAID NIH HHS [AI27850] NR 28 TC 142 Z9 151 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 4 PY 1996 VL 271 IS 40 BP 24874 EP 24879 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM674 UT WOS:A1996VM67400086 PM 8926278 ER PT J AU LeeFruman, KK Collins, TL Burakoff, SJ AF LeeFruman, KK Collins, TL Burakoff, SJ TI Role of the Lck Src homology 2 and 3 domains in protein tyrosine phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELL RECEPTOR; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; CROSS-LINKING; KINASE P56LCK; LYMPHOCYTES-T; ZETA-CHAIN; CD4 RECEPTOR; SH3 DOMAINS; ACTIVATION AB Many protein tyrosine phosphorylation events that occur as a result of T cell receptor (TCR) stimulation are enhanced when CD4 is co-cross-linked with the TCR, and this increased phosphorylation is thought to be a mechanism by which T cell functions are augmented by CD4. Such enhanced tyrosine phosphorylation was originally attributed to the kinase activity of the CD4-associated tyrosine kinase Lck. However, it has been shown that CD4-associated Lck lacking the catalytic domain can enhance T cell functions, suggesting that the noncatalytic domains of Lck are also important in CD4 signaling. Using T cells expressing various CD4-Lck chimeric molecules, we assessed the role of different Lck domains in early T cell signaling, Following TCR-CD4 co-cross-linking, cells expressing a CD4-Lck full-length chimera showed enhanced tyrosine phosphorylation of many cellular proteins in a CD4-dependent manner. Surprisingly, cells expressing a CD4 Lck chimera lacking the catalytic domain (termed CD4-N32) also showed enhanced phosphorylation. This enhancement of phosphorylation required both the Src homology 2 (SH2) and SH3 domains of Lck, Lck has been postulated to dimerize through the SH2 and SH3 domains. In this way CD4-N32 may interact with endogenous Lck, and although it lacks intrinsic kinase activity, it may be capable of enhancing phosphorylation through the associated full-length Lck. Consistent with this model, when CD4-Lck chimeric molecules were expressed in J.CaM1.6 cells lacking endogenous Lck, CD4-N32 failed to enhance tyrosine phosphorylation. Moreover, a Lck SH2 and SH3 domain fragment expressed as a glutathione S-transferase fusion protein associated with Lck when incubated with activated Jurkat T cell lysates, suggesting that the SH2 and SH3 domains of Lck can associate with endogenous full-length Lck upon activation, Thus, our data suggest that dimerization is an important mechanism of Lck function in T cell activation. C1 HARVARD UNIV,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02215. HARVARD UNIV,DIV MED SCI,COMM IMMUNOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02215. FU NIAID NIH HHS [AI17258] NR 57 TC 20 Z9 20 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 OCT 4 PY 1996 VL 271 IS 40 BP 25003 EP 25010 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM674 UT WOS:A1996VM67400105 PM 8798782 ER PT J AU Dasgupta, A Takahashi, K Cutler, M Tanabe, KK AF Dasgupta, A Takahashi, K Cutler, M Tanabe, KK TI O-linked glycosylation modifies CD44 adhesion to hyaluronate in colon carcinoma cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HOMING RECEPTOR CD44; SPLICE VARIANTS; DIFFERENTIAL EXPRESSION; COLORIMETRIC ASSAY; BREAST-CANCER; ACID BINDING; ISOFORMS; GROWTH; TUMORS; EXON AB CD44 alternative splicing patterns differ between normal and malignant tissue, and accordingly, modulation of CD44 splicing has received the most attention in studies that have examined the role of CD44 in tumor progression. Many investigators have examined functional differences between individual CD44 alternative splice variants. However, specific CD44 isoforms function uniquely depending on the type of cell on which they are expressed, thereby suggesting that additional tissue-specific mechanisms regulate CD44 function. To the present study we have demonstrated that colon carcinoma cells modify CD44 with O-linked glycosyl groups, and blockade of this glycosylation enhances their CD44-mediated adhesion to hyaluronate. This enhancement is attributable principally to CD44H (CD44s) rather than high molecular weight CD44 variants. Use of site-directed mutant CD44H cDNA transfectants demonstrated that CD44 O-linked glycosylation modulates interaction between hyaluronate and the B loop domain of CD44. The influence of glycosylation on CD44 function in colon carcinoma cells is specific to the presence of O-linked sugars; inhibition of N-linked glycosylation had minimal influence on CDU function. These findings indicate that O-linked glycosylation may be as important as alternative splicing in the regulation of CD44 function and the broad spectrum of biological processes attributed to it, including normal development, tumor metastases, and lymphocyte function. (C) 1996 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,DIV SURG ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV MED ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NCI NIH HHS [CA64454]; NIDDK NIH HHS [DK43351] NR 40 TC 31 Z9 32 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 3 PY 1996 VL 227 IS 1 BP 110 EP 117 DI 10.1006/bbrc.1996.1475 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VL840 UT WOS:A1996VL84000018 PM 8858111 ER PT J AU Natowicz, MR Short, MP Wang, Y Dickersin, GR Gebhardt, MC Rosenthal, DI Sims, KB Rosenberg, AE AF Natowicz, MR Short, MP Wang, Y Dickersin, GR Gebhardt, MC Rosenthal, DI Sims, KB Rosenberg, AE TI Clinical and biochemical manifestations of hyaluronidase deficiency SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID THIN-LAYER CHROMATOGRAPHY; DISEASE; RECEPTOR; OLIGOSACCHARIDES; INTERNALIZATION; FIBROBLASTS; DEGRADATION; DIAGNOSIS; BINDING C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORTHOPED SURG,BOSTON,MA 02114. RP Natowicz, MR (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV MED GENET,200 TRAPELO RD,WALTHAM,MA 02254, USA. NR 31 TC 79 Z9 83 U1 0 U2 2 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 OCT 3 PY 1996 VL 335 IS 14 BP 1029 EP 1033 DI 10.1056/NEJM199610033351405 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA VL459 UT WOS:A1996VL45900005 PM 8793927 ER PT J AU Seltzer, SE Holman, BL Thrall, JH Bramson, RT Poller, W AF Seltzer, SE Holman, BL Thrall, JH Bramson, RT Poller, W TI Academic radiology in a networked environment SO ACADEMIC RADIOLOGY LA English DT Article ID CARE C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,PARTNERS HEALTHCARE,BOSTON,MA 02115. PITTSBURGH RADIOL ASSOCIATES,PITTSBURGH,PA. RP Seltzer, SE (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RADIOL,PARTNERS HEALTHCARE,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 11 TC 3 Z9 3 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 1996 VL 3 IS 10 BP 865 EP 872 DI 10.1016/S1076-6332(96)80280-7 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VQ221 UT WOS:A1996VQ22100010 PM 8923907 ER PT J AU Rubio, A Steinberg, K Figlewicz, DA MacDonald, ME Greenamyre, T Hamill, R Shoulson, I Powers, JM AF Rubio, A Steinberg, K Figlewicz, DA MacDonald, ME Greenamyre, T Hamill, R Shoulson, I Powers, JM TI Coexistence of Huntington's disease and familial amyotrophic lateral sclerosis: Case presentation SO ACTA NEUROPATHOLOGICA LA English DT Article DE amyotrophic lateral sclerosis; Huntington's disease; superoxide dismutase; heavy neurofilament subunit gene ID HEAVY NEUROFILAMENT SUBUNIT; SUPEROXIDE-DISMUTASE GENE; DEMENTIA; PARKINSONISM; GLUTAMATE; DISORDERS; BRAIN AB We present the clinical, molecular genetic and neuropathological findings of an sl-year-old man with concurrent Huntington's disease (HD) and familial amyotrophic lateral sclerosis (FALS). His mother had been diagnosed clinically as having ALS. There was no known family history of HD, but a maternal uncle had died in a chronic care psychiatric hospital. The diagnosis of HD in the patient was suspected at age 66, after 8 years of personality change, hallucinations, agitation, cognitive decline and choreoathetosis. No symptoms of motor neuron disease were noticed at that time, but progressive weakness developed later. Postmortem examination revealed cerebral atrophy, marked atrophy of basal ganglia (grade 3), and atrophy of brain stem and spinal cord. The neostriatum displayed massive neuronal loss and gliosis. The neocortex showed changes characterisitic of Alzheimer's disease. Pathological lesions also included loss of neurons and gliosis in the anterior hems, Clarke's columns and the hypoglossal nuclei; degeneration of the lateral corticospinal tracts, dorsal spinocerebellar tracts and fasciculus gracilis; and rare Bunina bodies and ubiquitin-positive filamentous skeins in motor-neuron perikarya. Molecular analysis demonstrated chromosome 4p16.3 expansion of trinucleotide repeats characteristic of HD. Analysis of Cu,Zn superoxide dismutase gene and heavy neurofilament subunit gene failed to demonstrate mutations. The concurrence of HD and FALS in our patient and three previously reported cases did not appear to be associated with cosegregation in other family members. C1 UNIV ROCHESTER,DEPT NEUROL,ROCHESTER,NY 14642. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. EMORY UNIV,DEPT NEUROL,ATLANTA,GA 30322. UNIV VERMONT,DEPT NEUROL,BURLINGTON,VT 05405. RP Rubio, A (reprint author), UNIV ROCHESTER,DEPT PATHOL,ROCHESTER,NY 14642, USA. RI Greenamyre, J. Timothy/B-4049-2011; OI Greenamyre, J. Timothy/0000-0003-3468-7878 FU NIA NIH HHS [AG08665] NR 41 TC 20 Z9 20 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD OCT PY 1996 VL 92 IS 4 BP 421 EP 427 PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA VH517 UT WOS:A1996VH51700014 PM 8891076 ER PT J AU BlackSchaffer, WS Young, RH Harris, NL AF BlackSchaffer, WS Young, RH Harris, NL TI Subspecialization of surgical pathology at the Massachusetts General Hospital SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article AB The anatomic pathology unit of the Massachusetts General Hospital (MGH) serves both the MGH (an 862-bed general hospital generating about 39,000 surgical accessions and 33,500 gynecologic and 8,500 nongynecologic cytology accessions annually) and the Massachusetts Eye and Ear Infirmary (MEEI, a 52-bed specialty hospital generating about 6,500 surgical accessions and 1,000 nongynecologic cytology accessions annually); the unit has 25 full-time equivalent (ME) staff pathologists and pathology fellows providing its diagnostic services, On July 1, 1995, diagnostic specimen signout in this unit was changed to a system of complete subspecialization. The historical context and rationale for this change and the process of its implementation are presented, with a preliminary evaluation of its effects, including the impact on pathology staff, fellows, and residents. In addition, a mechanism for evaluation of equity and efficiency of pathologist work is presented, together with some discussion of the limitations of its accuracy. The authors conclude that to date the change has achieved many of its expected effects and that the process has worked smoothly. Further experience will clarify the overall results of the change. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 2 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 1996 VL 106 IS 4 SU 1 BP S33 EP S42 PG 10 WC Pathology SC Pathology GA VL945 UT WOS:A1996VL94500007 PM 8853054 ER PT J AU Islam, M Paul, RV AF Islam, M Paul, RV TI Correction of metabolic alkalosis by potassium chloride in ectopic adrenocorticotropic hormone syndrome SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE hypokalemia; metabolic alkalosis; adrenocorticotropic hormone; 11-beta hydroxysteroid dehydrogenase ID 11-BETA-HYDROXYSTEROID DEHYDROGENASE-DEFICIENCY; APPARENT MINERALOCORTICOID EXCESS; DEPENDENT CUSHINGS-SYNDROME; CORTISOL; HYPERTENSION; DEPLETION AB A 57-year-old white man presented with metabolic alkalosis, hypokalemia (pH 7.58, HCO3 >50 mEq/L, serum K 1.8 mEq/L) and hypertension, The initial evaluation was significant for markedly elevated serum cortisol and adrenocorticotropic hormone (ACTH) level; neither hormone showed circadian rhythm or suppression with high-dose dexamethasone. Perihilar and supraclavicular masses were found to consist of undifferentiated small cell carcinoma, Ectopic ACTH syndrome was diagnosed, In spite of progressively rising hormone levels (ACTH, 723 pg/dL; and cortisol, 212 mu g/dL), his severe metabolic alkalosis was largely corrected by aggressive treatment with potassium chloride alone, Possible mechanisms of these clinical findings are discussed. (C) 1996 by the National Kidney Foundation, Inc. C1 MED UNIV S CAROLINA,DIV NEPHROL,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. NR 26 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 1996 VL 28 IS 4 BP 610 EP 613 DI 10.1016/S0272-6386(96)90475-8 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA VL786 UT WOS:A1996VL78600020 PM 8840954 ER PT J AU Arkin, MS Rubin, PAD Bilyk, JR Buchbinder, B AF Arkin, MS Rubin, PAD Bilyk, JR Buchbinder, B TI Anterior chiasmal optic nerve avulsion SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE eyes, injuries; eyes, magnetic resonance; nerves, optic (II); optic chiasm ID EVULSION; TRAUMA AB In a case of traumatic avulsion of the optic nerve at the anterior chiasm, MR imaging provided highly specific images of the injury site, including the absence of the optic nerve within the optic canal and the point of transection at the anterior portion of the chiasm, This was confirmed clinically and histopathologically, MR imaging should be considered in cases of suspected chiasmal injury. C1 MASSACHUSETTS EYE & EAR INFIRM,OPHTHALM PLAST & ORBITAL SURG SERV,DEPT OPHTHALMOL,BOSTON,MA 02114. WILLS EYE HOSP & RES INST,OCULOPLAST & ORBITAL SURG SERV,PHILADELPHIA,PA. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA. NR 17 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 1996 VL 17 IS 9 BP 1777 EP 1781 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA VM685 UT WOS:A1996VM68500030 PM 8896637 ER PT J AU Sobeilian, M Markomichelakis, N Foster, CS AF Sobeilian, M Markomichelakis, N Foster, CS TI Intermediate uveitis and retinal vasculitis as manifestations of cat scratch disease SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To study the ocular manifestations of systemic Rochalimaea infection. METHODS: We examined a healthy 21-year old woman who had floaters in both eyes, A bilateral mild vitreitis and multiple foci of retinal vasculitis were found; during the ensuing two weeks, exudates appeared over the inferior pars plana. The patient owned five kittens but had no history of cat bites or scratches. Serum levels of antibodies to Rochalimaea were elevated. RESULT: The retinal vasculitis and vitreitis resolved after three weeks of therapy with ciprofloxacin hydrochloride without concomitant antiinflammatory therapy. CONCLUSION: Rochalimaea infection should be considered in the differential diagnosis of intermediate uveitis and retinal vasculitis. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. SHAHID BEHESHTI UNIV MED SCI,LABBAFINEJAD MED CTR,DEPT OPHTHALMOL,TEHRAN,IRAN. NR 5 TC 0 Z9 1 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 OCT PY 1996 VL 122 IS 4 BP 582 EP 584 PG 3 WC Ophthalmology SC Ophthalmology GA VK702 UT WOS:A1996VK70200021 ER PT J AU Fini, ME Parks, WC Rinehart, WB Girard, MT Matsubara, M Cook, JR WestMays, JA Sadow, PM Burgeson, RE Jeffrey, JJ Raizman, MB Krueger, RR Zieske, JD AF Fini, ME Parks, WC Rinehart, WB Girard, MT Matsubara, M Cook, JR WestMays, JA Sadow, PM Burgeson, RE Jeffrey, JJ Raizman, MB Krueger, RR Zieske, JD TI Role of matrix metalloproteinases in failure to re-epithelialize after corneal injury SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID COLLAGENOLYTIC GELATINOLYTIC METALLOPROTEINASES; COLLAGENASE EXPRESSION; FIBROBLAST COLLAGENASE; 92-KD GELATINASE; CHRONIC WOUNDS; ULCERATION; CELLS; CLONING; EOSINOPHILS; INHIBITION AB Delayed re-epithelialization of the cornea after injury usually precedes stromal ulceration, Previous findings using a rat thermal injury model suggested that re-epithelialization is impeded by products of resident corneal cells, which destroy adhesive structures at the basement membrane zone, In this study, we provide additional evidence for this concept, failure to re-epithelialize was found to correlate with an increase in the amounts of gelatinolytic matrix metalloproteinases present in the rat cornea. One of these gelatinases, gelatinase B, is synthesized by the resident corneal cells, and inhibition of its synthesis correlated with inhibition of basement membrane dissolution. The matrix metalloproteinases collagenase and stromelysin are also synthesized by resident corneal cells in thermally injured corneas of rabbits, but the timing of bulk enzyme synthesis correlated more closely with deposition of repair tissue in the strong than with failure to re-epithelialize. Nevertheless, in human corneas with repair defects, gelatinase B and collagenase are synthesized by cells in the basal layer of the epithelium directly adjacent to the basement membrane, suggesting that both could participate in dissolution of this structure, Importantly, treatment of thermally injured corneas with a synthetic inhibitor of matrix metalloproteinases significantly improved basement membrane integrity, These data support the concept that over-expression of matrix metalloproteinases by resident corneal cells impedes re-epithelialization after some types of corneal injury. C1 TUFTS UNIV,SCH MED,BOSTON,MA 02111. WASHINGTON UNIV,SCH MED,DEPT MED DERMATOL,ST LOUIS,MO. WASHINGTON UNIV,SCH MED,DEPT CELL BIOL,ST LOUIS,MO. MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,DEPT DERMATOL,CHARLESTOWN,MA. ALBANY MED COLL,DEPT MED,ALBANY,NY 12208. ALBANY MED COLL,DEPT BIOCHEM,ALBANY,NY 12208. ALBANY MED COLL,DEPT MOL BIOL,ALBANY,NY 12208. ALBANY MED COLL,DEPT PHARMACOL & TOXICOL,ALBANY,NY 12208. ST LOUIS UNIV,DEPT OPHTHALMOL,ST LOUIS,MO 63103. HARVARD UNIV,SCH MED,SCHEPENS EYE RES INST,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. RP Fini, ME (reprint author), TUFTS UNIV NEW ENGLAND MED CTR,VIS RES LABS,DEPT OPHTHALMOL,750 WASHINGTON ST,BOX 450,BOSTON,MA 02111, USA. FU NEI NIH HHS [EY08408, EY09828]; NIAMS NIH HHS [AR42981] NR 49 TC 147 Z9 151 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 OCT PY 1996 VL 149 IS 4 BP 1287 EP 1302 PG 16 WC Pathology SC Pathology GA VM314 UT WOS:A1996VM31400021 PM 8863676 ER PT J AU Olsen, WA Lloyd, M Korsmo, H He, YZ AF Olsen, WA Lloyd, M Korsmo, H He, YZ TI Regulation of sucrase and lactase in Caco-2 cells: Relationship to nuclear factors SIF-1 and NF-LPH-1 SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE sucrase-isomaltase; lactase-phlorizin hydrolase; developmental regulation; transcription factors ID PHLORHIZIN HYDROLASE; INTESTINAL LACTASE; ISOMALTASE GENE; MESSENGER-RNA; EXPRESSION; PROMOTER; PROTEINS; TRANSCRIPTION; INTERACTS; BINDING AB Recent studies suggest the importance of two transcription factors, Cdx-2 and NF-LPH-1, in the regulation of sucrase-isomaltase (SI) and lactase-phlorizin hydrolase (LPH) gene expression, respectively. Cdx-2 accounts for the tissue specificity of sucrase expression (16), and NF-LPH-1 varies with postnatal changes in lactase activity, suggesting a role in its developmental regulation (22). We used electrophoretic mobility shift assays to study the relationship of Cdx-2 and NF-LPH-1 to SI and LPH gene expression in Caco-2 cells to provide evidence regarding the role of these factors in the development of sucrase and lactase with cellular differentiation. We found that Cdx-2 levels correlated with SI expression and that NF-LPH-1 did not correlate with LPH expression. These studies suggest a role for Cdx-2 but not for NF-LPH-1 in the development of carbohydrase expression in these cells. C1 UNIV WISCONSIN, DEPT MED, MADISON, WI 53706 USA. RP Olsen, WA (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR, MED SERV, GASTROENTEROL RES LAB, 2500 OVERLOOK TERRACE, MADISON, WI 53705 USA. FU NIDDK NIH HHS [R-29-DK-45785] NR 22 TC 20 Z9 20 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD OCT PY 1996 VL 271 IS 4 BP G707 EP G713 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA VN420 UT WOS:A1996VN42000023 PM 8897892 ER PT J AU Ma, JY Meng, W Ayata, C Huang, PL Fishman, MC Moskowitz, MA AF Ma, JY Meng, W Ayata, C Huang, PL Fishman, MC Moskowitz, MA TI L-NNA-sensitive regional cerebral blood flow augmentation during hypercapnia in type III NOS mutant mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE nitric oxide; knockout mice ID NITRIC-OXIDE SYNTHASE; RATS; ENDOTHELIUM; INHIBITION; RESPONSES; ARGININE; LACKING; GENE AB The effect of N-G-nitro-L-arginine (L-NNA) on regional cerebral blood flow (rCBF) response to hypercapnia (5% CO2 inhalation) was studied in urethan-anesthetized wild-type (SV-129) and type III nitric oxide (NO) synthase (NOS)-deficient mice, using laser-Doppler flowmetry and the closed cranial window technique. Resting rCBF during normocapnia decreased by similar to 25% after L-NNA superfusion in wild-type mice only (n = 18), suggesting a role for type III NOS in baseline blood flow. Hypercapnia augmented rCBP similar to 50% in both wild-type and type III NOS mutant mice. L-NNA superfusion (1 mM) inhibited this increase by similar to 60% in both strains. Hence, synthesis of NO by the constitutively expressed type I NOS contributes to blood flow augmentation during hypercapnia. C1 MASSACHUSETTS GEN HOSP, STROKE & NEUROVASC REGULAT LAB, DEPT NEUROSURG & NEUROL, CARDIOVASC RES CTR, CHARLESTOWN, MA 02129 USA. MASSACHUSETTS GEN HOSP, DEPT MED, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, SCH MED, CHARLESTOWN, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 NR 24 TC 37 Z9 37 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 1996 VL 271 IS 4 BP H1717 EP H1719 PG 3 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA VN411 UT WOS:A1996VN41100053 ER PT J AU Bergeron, M Mayers, P Brown, D AF Bergeron, M Mayers, P Brown, D TI Specific effect of maleate on an apical membrane glycoprotein (gp330) in proximal tubule of rat kidneys SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE Fanconi syndrome; immunofluorescence; immunogold; dipeptidyl peptidase IV; lectins ID EXPERIMENTAL FANCONI SYNDROME; LIPOPROTEIN RECEPTOR FAMILY; HEYMANN NEPHRITIS; BRUSH-BORDER; MALEIC-ACID; ALPHA-2-MACROGLOBULIN RECEPTOR; SODIUM-MALEATE; TRANSPORT; PROTEIN; ULTRASTRUCTURE AB Maleate treatment of rats induces transport defects similar to those seen in the Fanconi syndrome (glycosuria, aminoaciduria, phosphaturia, proteinuria, etc.) and causes an accumulation of apical vesicles in proximal tubule epithelial cells. Because the apical membrane glycoprotein, gp330, is a receptor associated with the apical endocytotic and recycling apparatus in these cells, we examined the effect of maleate on the distribution of this protein and other brush border markers. Rats received sodium maleate (400 mg/kg ip) and were killed at various times between 45 min and 3 h; kidneys were perfusion fixed with paraformaldehyde-lysine-periodate before processing for immunofluorescence and immunoelectron microscopy. In control rats, staining with a polyclonal or monoclonal gp330 antibody showed a uniform distribution on the brush border and in coated pits of all proximal tubule cells. In the S3 segments, the immunofluorescence labeling of the microvilli was generally uniform but-at times showed spike labeling, suggesting that gp330 sheds easily from the apical membrane. After maleate treatment, the staining intensity of the brush border was decreased in all proximal tubule segments, and cytoplasmic streaks as well as an intense vacuolar staining were seen. In the S3 segment, a remarkable mosaic pattern of staining was observed, with the brush border of some cells being completely negative, while adjacent cells showed an apparently normal staining pattern. These results were confirmed at the electron microscope level, using the protein A-gold technique. Maleate had no effect on the distribution or staining intensity of four other blush border markers, dipeptidyl peptidase IV, and various lectins (Helix pomatia lectin, peanut lectin, elderberry bark lectin). The urinary excretion of gp330 occurs in normal rats and was already increased as early as 1 h after maleate injection and remained at a twofold increment between 6 and 24 h. These data suggest that the generalized membrane transport derangement seen in this experimental Fanconi syndrome could occur via a specific effect on gp330, which seems to block endocytosis and the recycling apparatus at the late endosome level and inhibits the formation of new dense apical tubules. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, RENAL UNIT, BOSTON, MA 02129 USA. RP Bergeron, M (reprint author), UNIV MONTREAL, FAC MED, DEPT PHYSIOL, CP 6128, SUCC CTRVILLE, MONTREAL, PQ H3C 3J7, CANADA. FU NIDDK NIH HHS [DK-42956] NR 53 TC 21 Z9 21 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD OCT PY 1996 VL 271 IS 4 BP F908 EP F916 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA VL765 UT WOS:A1996VL76500017 PM 8898022 ER PT J AU Emmons, C AF Emmons, C TI Halide transport patterns of apical anion exchange in rabbit cortical collecting duct intercalated cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE transepithelial acid-base transport; bicarbonate secretion; apical anion exchanger ID CHLORIDE-BICARBONATE EXCHANGE; INTRACELLULAR PH; FUNCTIONAL-CHARACTERIZATION; TUBULE; SYSTEMS; CL AB To investigate halide selectivity patterns of cortical collecting duct (CCD) intercalated cells (ICs), intracellular pH (pH(i)) was measured in perfused rabbit outer CCD ICs in Na+-free, HCO3--buffered, 115 mM Cl- solutions. Apical anion exchange activity was measured as the dpH(i)/dt after lumen Cl- replacement with gluconate. The perfusate was randomly changed to equimolar Br-, F-, or I-. Addition of Br- to the lumen in place of gluconate caused a brisk acidification similar to that with Cl- return. The acidification rate with I- replacement was only similar to 25% of that seen with Cl- readdition, and F- substitution resulted in a small alkalinization. In a separate protocol, each halide was substituted for lumen Cl-. Replacement of lumen Cl- with Br- resulted in intracellular acidification, whereas F- substitution caused an increase in pH(i) similar to that with gluconate. A slower rate of alkalinization was seen with I-. Separate tubules were perfused and bathed in Cl--free gluconate solutions for 10 min, and then either Cl- or Br- was returned to the lumen. Similar rates of acidification were found with either Cl- or Br- return. Taken together, the results show that, at a halide concentration of 115 mM, the halide selectivity transport pattern of the apical anion exchanger of CCD ICs is Cl- = Br- > I- > F-. C1 UNIV CALIF LOS ANGELES, SCH MED, W LOS ANGELES VET AFFAIRS MED CTR, RES SERV, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, W LOS ANGELES VET AFFAIRS MED CTR, MED SERV, LOS ANGELES, CA 90073 USA. NR 27 TC 5 Z9 5 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD OCT PY 1996 VL 271 IS 4 BP F799 EP F805 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA VL765 UT WOS:A1996VL76500004 PM 8898009 ER PT J AU Riccardi, D Lee, WS Lee, KC Segre, GV Brown, EM Hebert, SC AF Riccardi, D Lee, WS Lee, KC Segre, GV Brown, EM Hebert, SC TI Localization of the extracellular Ca2+-sensing receptor and PTH/PTHrP receptor in rat kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE reverse transcriptase polymerase chain reaction; microdissected nephron segments; in situ hybridization ID THICK ASCENDING LIMB; FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; NEONATAL SEVERE HYPERPARATHYROIDISM; PARATHYROID-HORMONE; MG2+ TRANSPORT; MOUSE KIDNEY; HENLES LOOP; CALCIUM; EXPRESSION; CLONING AB Using a strategy based on homology to the bovine parathyroid Ca2+-sensing receptor previously identified by us (5), we have recently isolated an extracellular, G protein-coupled Ca2+/polyvalent cation-sensing receptor, RaKCaR (22), from rat kidney. The localization and physiological role(s) of this receptor in the kidney are not well understood. In the present study, we assessed the distribution of mRNAs for RaKCaR and the parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor along the rat nephron by in situ hybridization and reverse transcriptase-polymerase chain reaction of microdissected nephron segments. Our results show that transcripts for both receptors coexpress at glomeruli, proximal convoluted tubule, proximal straight tubule, cortical thick ascending limb, distal convoluted tubule, and cortical collecting duct. In addition, RaKCaR (but not PTH/PTHrP receptor) transcripts were found in the medullary thick ascending limb and outer medullary and inner medullary collecting ducts. These findings raise the possibility of roles for RaKCaR not only in the regulation of divalent mineral reabsorption but also in water reabsorption and urinary concentration. Taken together, our results provide new insights in understanding the effects of hypercalcemia on hormone-stimulated salt and water transport. C1 BRIGHAM & WOMENS HOSP, DIV RENAL, LAB MOL PHYSIOL & BIOPHYS, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, DEPT MED, ENDOCRINE HYPERTENS UNIT, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED,MASSACHUSETTS GEN HOSP,DEPT MED, ENDOCRINE UNIT, BOSTON, MA 02115 USA. RI Riccardi, Daniela/A-4674-2010 OI Riccardi, Daniela/0000-0002-7322-3163 FU NIDDK NIH HHS [DK-47237, DK-48330] NR 30 TC 177 Z9 178 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD OCT PY 1996 VL 271 IS 4 BP F951 EP F956 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA VL765 UT WOS:A1996VL76500022 PM 8898027 ER PT J AU Solomon, DA Ristow, WR Keller, MB Kane, JM Gelenberg, AJ Rosenbaum, JF Warshaw, MG AF Solomon, DA Ristow, WR Keller, MB Kane, JM Gelenberg, AJ Rosenbaum, JF Warshaw, MG TI Serum lithium levels and psychosocial function in patients with bipolar I disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SOCIAL RESOURCES; FOLLOW-UP; STANDARD; MANIA AB Objective: This study compared the effect of two different serum lithium levels on the psychosocial functioning of patients with bipolar I disorder. Method: Ninety patients with bipolar I disorder were enrolled in a prospective, double-blind maintenance trial of lithium. The patients were randomly assigned to treatment with doses of lithium adjusted to achieve a serum lithium concentration of either 0.8 to 1.0 mmol/liter (standard) or 0.4 to 0.6 mmol/liter (low). The Longitudinal Interval Follow-Up Evaluation was used to assess psychosocial functioning in the areas of work, interpersonal relationships, and global functioning. All observed values were analyzed with a mixed-effects analysis of covariance. Independent variables included treatment group (low or standard lithium serum level), relapse status, socioeconomic status, time from random treatment assignment to assessment, termination oi protocol before or after relapse, length of remission before random treatment assignment, polarity of the last mood episode before random treatment assignment, and number of mood episodes in the 3 years before random treatment assignment. Results: Relapse was associated with large negative effects on psychosocial functioning. Patients in higher socioeconomic brackets had better psychosocial functioning than did those in lower brackets. Patients receiving lithium doses that achieved standard serum levels had better psychosocial functioning than those receiving doses that achieved low serum levels; this effect was partially but not wholly mediated through relapse prevention. Conclusions: For patients with bipolar I disorder, standard serum lithium levels may enhance psychosocial functioning, above and beyond the effects of relapse prevention. C1 HILLSIDE HOSP,LONG ISL JEWISH MED CTR,NEW YORK,NY. ALBERT EINSTEIN COLL MED,NEW YORK,NY. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIMH NIH HHS [R01 MH025478] NR 22 TC 36 Z9 36 U1 2 U2 4 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 OCT PY 1996 VL 153 IS 10 BP 1301 EP 1307 PG 7 WC Psychiatry SC Psychiatry GA VK833 UT WOS:A1996VK83300010 PM 8831438 ER PT J AU Fava, M Alpert, JE Borus, JS Nierenberg, AA Pava, JA Rosenbaum, JF AF Fava, M Alpert, JE Borus, JS Nierenberg, AA Pava, JA Rosenbaum, JF TI Patterns of personality disorder comorbidity in early-onset versus late-onset major depression SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 148th Annual Meeting of the American-Psychiatric-Association CY MAY 20-25, 1995 CL MIAMI BEACH, FL SP Amer Psychiat Assoc ID PSYCHIATRIC-DISORDERS; ADOLESCENTS; CHILDREN; OUTPATIENTS; CHILDHOOD; ANXIETY; ADULTS AB Objective: This study tested the hypothesis that in a population of adult outpatients with major depression, those with an early onset of depression would have a greater prevalence of personality disorders than those with a late onset of depression. Method: The 404 subjects weve patients participating in depression treatment studies at the Massachusetts General Hospital. They were administered the Structured Clinical Interview for DSM-III-R-Patient Version to assess the current presence of major depression and the age at onset of the initial depressive episode. The subjects were then divided into two groups: those with early onset (before 18 years of age) and those with late onset (at age 18 or later). The prevalence of personality disorders was determined through use of the physician-rated Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) and the patient-rated Personality Diagnostic Questionnaire-Revised (PDQ-R). Results: The patients with early onset of major depression had a significantly higher prevalence of avoidant, histrionic, narcissistic, and borderline personality disorders according to the SCID-II. The PDQ-R scores indicated that avoidant, dependent, passive-aggressive, histrionic, narcissistic, borderline, and antisocial personality disorders were significantly more prevalent among the patients with early onset of major depression. Conclusions: Overall, the results are consistent with the view that early-onset depressive illness is distinguished from late-onset major depression by more frequent association with persistent disturbances in behaviors and attitudes. RP Fava, M (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS CLIN & RES PROGRAM,WACC 815,BOSTON,MA 02114, USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [MH-48483] NR 21 TC 98 Z9 99 U1 0 U2 4 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 OCT PY 1996 VL 153 IS 10 BP 1308 EP 1312 PG 5 WC Psychiatry SC Psychiatry GA VK833 UT WOS:A1996VK83300011 PM 8831439 ER PT J AU Hauser, R Daskalakis, C Christiani, DC AF Hauser, R Daskalakis, C Christiani, DC TI A regression approach to the analysis of serial peak flow among fuel oil ash exposed workers SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID EXPIRATORY FLOW; OZONE; ADAPTATION; WELDERS AB We investigated the association between exposure to fuel oil ash and acute airway obstruction in 31 boilermakers and 31 utility workers during the overhaul of a large oil-fired boiler. Air flow was assessed with self-recorded serial peak expiratory flow rate measurements (PEFR) using a mini-Wright meter. Exposure to thoracic particulates with an aerodynamic diameter of 10 mu m or smaller (PM(10)) was assessed using personal sampling devices and detailed work diaries. All subjects were male, with an average age of 43 yr, and an average of 18 yr at their current trade. Average PM(10) exposure on work days was 2.75 mg/m(3) for boilermakers and 0.57 mg/m(3) for utility workers. Three daily PEFR measurements (start-of-shift, end-of-shift, and bed-time) were analyzed simultaneously, using Huber linear regression. After adjustment for job title, welder status, age, height, smoking, and weld-years, for each mg/m(3) increase in PM(10), the estimated decline in PEFR was 13.2 L/min (p = 0.008) for end-of-shift, 9.9 L/min (p = 0.045) for bed-time, and 6.6 L/min (p = 0.26) for start-of-shift of the following day. This decline of the exposure effect over the 24-h period that follows was statistically significant (p = 0.004). No other factors were found to significantly modify the effect of exposure. Our results suggest that occupational exposure to fuel oil ash is associated with significant acute decrements in peak flow. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,OCCUPAT HLTH PROGRAM,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. FU NIEHS NIH HHS [ES05947, ES07069, ES00002] NR 15 TC 14 Z9 15 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT PY 1996 VL 154 IS 4 BP 974 EP 980 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA VN221 UT WOS:A1996VN22100025 PM 8887594 ER PT J AU Fan, KT Whitman, GJ Chew, FS AF Fan, KT Whitman, GJ Chew, FS TI Pulmonary zygomycosis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CLINICAL SPECTRUM C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT RADIOL,HOUSTON,TX 77030. NR 4 TC 2 Z9 3 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 1996 VL 167 IS 4 BP 946 EP 946 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VJ684 UT WOS:A1996VJ68400027 PM 8819389 ER PT J AU Willett, CG Daly, WJ Warshaw, AL AF Willett, CG Daly, WJ Warshaw, AL TI CA 19-9 is an index of response to neoadjunctive chemoradiation therapy in pancreatic cancer SO AMERICAN JOURNAL OF SURGERY LA English DT Article ID CARCINOMA AB PURPOSE: This Study examines the changes of serum levels of CA 19-9 in patients with pancreatic cancer following neoadjuvant irradiation and chemotherapy to define the potential role of this tumor marker in preoperative management of these patients, MATERIALS AND METHODS: Serum CA 19-9 levels were measured in 42 patients before receiving external beam irradiation with concurrent 5-fluorouracil in preparation for laparotomy and Whipple procedure or intraoperative irradiation (IORT). The CA 19-9 levels were determined again after irradiation, and changes were correlated with findings of restaging computed tomography (CT) scan and laparotomy, RESULTS: Following preoperative irradiation, 10 patients (24%) experienced an increase in CA 19-9 levels whereas 29 patients (69%) showed a decrease in CA 19-9, There was no change in the CA 19-9 levels of 3 patients (7%) after treatment, Of the 10 patients with increased CA 19-9 levels after irradiation, 9 (90%) had developed distant metastases or local tumor progression as determined by restaging CT scan or at laparotomy. In contrast, only 6 of 29 patients (21%) with declining CA 19-9 levels after irradiation demonstrated metastases or local tumor progression on restaging CT scan or at laparotomy. The correlation of CA 19-9 increase or decrease with disease progression or control, respectively, was statistically significant (P = 0.009), CONCLUSIONS: Serum CA 19-9 levels may rise or fall during neoadjuvant therapy, A rising CA 19-9 reliably indicates cancer progression while a falling CA 19-9 connotes disease control in the majority of patients, In developing strategies for application of neoadjuvant therapy for pancreatic cancer, monitoring of CA 19-9 appears most useful for the identification of patients who manifest progressive tumor growth and metastasis in spite of this treatment. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT GEN SURG,BOSTON,MA 02115. NR 6 TC 46 Z9 51 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD OCT PY 1996 VL 172 IS 4 BP 350 EP 352 DI 10.1016/S0002-9610(97)89547-5 PG 3 WC Surgery SC Surgery GA VM043 UT WOS:A1996VM04300012 PM 8873528 ER PT J AU Young, RH Oliva, E Garcia, JAS Bhan, AK Clement, PB AF Young, RH Oliva, E Garcia, JAS Bhan, AK Clement, PB TI Urethral caruncle with atypical stromal cells simulating lymphoma or sarcoma - A distinctive pseudoneoplastic lesion of females - A report of six cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE urethra; caruncle; atypical cells; pseudotumor ID FIBROEPITHELIAL POLYPS; VAGINAL POLYPS; GENITAL-TRACT; GIANT-CELLS; BENIGN; EXPRESSION; BLADDER; CERVIX AB Six urethral caruncles in women aged 32 to 82 (average, 56) years contained atypical stromal cells raising concern for a neoplasm. The atypical cells varied from spindled to round, the latter predominating, and typically had scant cytoplasm. A minority of the cells were binucleated or multinucleated and often had prominent nucleoli. A single mitotic figure was found in the atypical cells in one case. The atypical cells were characteristically present in an edematous background containing numerous inflammatory cells and were focally crowded together in five cases. The differential diagnosis in these cases included a florid reactive proliferation of lymphoid cells, but immunohistochemical stains failed to support a lymphoid nature for the atypical cells and also helped to exclude malignant lymphoma, the neoplasm most often simulated, Because of the invariable additional component of atypical spindle cells resembling those described in the stroma of the lower female genital tract and in polyps in a variety of sites, the round cells likely represent a variant of this atypical mesenchymal cell, Similar round mesenchymal cells have also been documented in the gastrointestinal tract, especially the stomach. Immunohistochemical stains in this series showed them to be positive for vimentin in four of four cases and for alpha smooth-muscle actin in two of four cases. The prominence of atypical round stromal cells in these cases appears to be a distinctive feature of some urethral caruncles. The presence of these cells should not lead to misinterpretation of the lesion as a neoplastic process. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,CAMBRIDGE,MA 02138. HOSP TXAGORRITXU,DEPT PATHOL,VITORIA,SPAIN. VANCOUVER HOSP & HLTH SCI CTR,DEPT PATHOL,VANCOUVER,BC V5Z 1M9,CANADA. UNIV BRITISH COLUMBIA,VANCOUVER,BC V5Z 1M9,CANADA. RP Young, RH (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,FRUIT ST,BOSTON,MA 02114, USA. NR 30 TC 10 Z9 10 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 OCT PY 1996 VL 20 IS 10 BP 1190 EP 1195 DI 10.1097/00000478-199610000-00003 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA VJ668 UT WOS:A1996VJ66800003 PM 8827024 ER PT J AU Imamura, SI Adams, JC AF Imamura, SI Adams, JC TI Immunolocalization of peptide 19 and other calcium-binding proteins in the guinea pig cochlea SO ANATOMY AND EMBRYOLOGY LA English DT Article DE calbindin; calretinin; calmodulin; organ of Corti; spiral ganglion ID OUTER HAIR-CELLS; INNER-EAR; IMMUNOHISTOCHEMICAL LOCALIZATION; IMMUNOCYTOCHEMICAL DETECTION; SUBSURFACE CISTERNAE; ORGAN; RAT; NEURONS; CORTI; CAT AB Calcium ions are known to play critical roles in a variety of cochlear functions. The distributions of a number of calcium binding proteins that regulate calcium ion levels within the cochlea have previously been described. In this report we extend and refine previous reports of the distribution of immunostaining for calmodulin, calbindin, and calretinin and show for the first time the distribution for peptide 19. There were longitudinal and radial gradients of immunostaining for peptide 19 within outer hair cells that appeared to match previously described gradients of efferent innervation of these cells. Gradients of immunostaining for calbindin within outer hair cells were in the opposite directions, which suggests that levels of this protein are correlated with afferent innervation density and perhaps the abundance of subsurface cisternae. No gradients were seen in the distributions of cells stained for calmodulin and calretinin, which included sensory cells and supporting cells respectively. All ganglion cells were stained for calmodulin but the other proteins appeared to be present in limited ganglion cell subpopulations. In addition to staining of sensorineural elements, anitsera to all compounds but peptide 19 showed immunostaining of cells within the lateral wall and the spiral limbus. The results suggest that the proteins under study are involved in a wide variety of calcium-regulated functions within the cochlea. Knowledge of the unique distribution of each of the compounds should facilitate further studies of their roles in cochlear function. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. YAMANASHI MED UNIV,DEPT OTOLARYNGOL,YAMANASHI,JAPAN. FU NIDCD NIH HHS [DC00269] NR 56 TC 22 Z9 23 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-2061 J9 ANAT EMBRYOL JI Anat. Embryol. PD OCT PY 1996 VL 194 IS 4 BP 407 EP 418 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA VL582 UT WOS:A1996VL58200011 PM 8896705 ER PT J AU Pasternak, RC Brown, LE Stone, PH Silverman, DI Gibson, CM Sacks, FM AF Pasternak, RC Brown, LE Stone, PH Silverman, DI Gibson, CM Sacks, FM TI Effect of combination therapy with lipid-reducing drugs in patients with coronary heart disease and ''normal'' cholesterol levels - A randomized, placebo-controlled trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE coronary disease; cholesterol; drug therapy, combination; hyperlipidemia; anticholesterolemic agents ID ACUTE-RENAL-FAILURE; HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; RECIPIENT RECEIVING LOVASTATIN; HIGH-DENSITY-LIPOPROTEIN; ARTERY DISEASE; MODERATE HYPERCHOLESTEROLEMIA; NORMOCHOLESTEROLEMIC PATIENTS; COMBINED HYPERLIPIDEMIA; ANGIOGRAPHIC TRIALS; NICOTINIC-ACID AB Background: Combination drug therapy has been shown to decrease cholesterol levels in hyperlipidemic patients. However, its efficacy has not been well studied in patients previously considered to be normolipidemic, many of whom are now candidates for this therapy. Objective: To determine the efficacy and tolerability of multidrug therapy designed to improve low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels. in patients with coronary heart disease and average lipid levels. Design: Randomized, placebo-controlled, 2.5-year trial comparing patients receiving usual care with patients receiving stepped-care drug therapy. Intervention: Stepped-care therapy (pravastatin, nicotinic acid, cholestyramine, and gemfibrozil) to decrease total cholesterol levels to less than 4.1 mmol/L (160 mg/dL) and the ratio of LDL cholesterol to HDL cholesterol to less than 2.0. Setting: 2 academic, urban, tertiary care hospitals. Patients: 91 patients (80 men and 11 women) with coronary heart disease, a mean age of 60 years, total cholesterol levels less than 6.4 mmol/L (250 mg/dL) at baseline, and ratios of total cholesterol to HDL cholesterol greater than 4.0 at baseline. Measurements: Easting serum lipoprotein profile, fasting apolipoprotein levels, and frequency of adverse effects. Patients were assessed every 6 weeks during drug titration and every 3 months thereafter. Results: Mean lipid levels at baseline were as follows: total cholesterol, 5.5 mmol/L (214 mg/dL); LDL cholesterol, 3.6 mmol/L (140 mg/dL); HDL cholesterol, 1.1 mmol/L (42 mg/dL); and triglycerides, 1.8 mmol/L (159 mg/dL). With pravastatin, changes in levels from baseline were -22% for total cholesterol, -32% for LDL cholesterol, +8% for HDL cholesterol, and -15% for triglycerides (P < 0.001 for all comparisons). With the addition of 1.5 g of nicotinic acid, additional changes were -6% for total cholesterol (P < 0.002), -11% for LDL cholesterol, +8% for HDL cholesterol, and -10% for triglycerides (P < 0.001 for all comparisons). With 2.25 to 3 g of nicotinic acid, these changes were - 7% for total cholesterol (P = 0.007), -14% for LDL cholesterol (P < 0.001), +6% for HDL cholesterol (P = 002), and -13% for triglycerides (P = 0.03). With cholestyramine, total cholesterol and LDL cholesterol levels were unchanged compared with the previous step; the change in HDL cholesterol level was -8% (P = 0.03); and the change in triglyceride level was +46% (P < 0.001). With gemfibrozil, total cholesterol level was unchanged; the additional change in LDL cholesterol level was +12% (P = 0.09); the change in HDL cholesterol level was +12% (P = 0.03); and the change in triglyceride level was -37% (P < 0.001). Apolipoprotein B levels decreased by 25% overall (P < 0.001); lipoprotein(a) levels did not change significantly. Adverse effects were primarily attributable to nicotinic acid or cholestyramine. In 18 of the 35 patients (50%) whose baseline LDL cholesterol levels were greater than 3.35 mmol/L (130 mg/dL), pravastatin decreased LDL cholesterol levels to 2.6 mmol/L (100 mg/dL) or less by 6 weeks; 70% of patients needed combination therapy to reach this National Cholesterol Education Program goal during the 2.5 years of the study. Adding nicotinic acid to pravastatin produced LDL cholesterol levels of 2.6 mmol/L or less in 15 more of these 35 patients, so that 94% (n = 33) of the patients receiving these two drugs reached this goal. Conclusions: To reach current goals for LDL cholesterol levels, most normolipidemic patients with coronary heart disease iri this study needed combination therapy. Pravastatin with nicotinic acid and pravastatin with gemfibrozil are well-tolerated combinations that can maintain target LDL cholesterol levels, decrease triglyceride levels, and increase HDL cholesterol levels. Adding resin to these combinations produced no further benefit. C1 BRIGHAM & WOMENS HOSP, DIV CARDIOVASC, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. BETH ISRAEL HOSP, BOSTON, MA 02215 USA. MASSACHUSETTS GEN HOSP, CARDIAC UNIT, BOSTON, MA 02114 USA. FU NCRR NIH HHS [M01 RR02635]; NHLBI NIH HHS [HL34980] NR 47 TC 55 Z9 55 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 1 PY 1996 VL 125 IS 7 BP 529 EP + PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VJ653 UT WOS:A1996VJ65300001 PM 8815751 ER PT J AU King, GL AF King, GL TI The role of hyperglycaemia and hyperinsulinaemia in causing vascular dysfunction in diabetes SO ANNALS OF MEDICINE LA English DT Article DE growth factors; insulin resistance; protein kinase C; vascular cells ID PROTEIN-KINASE-C; SMOOTH-MUSCLE CELLS; GLUCOSE; INSULIN; COMPLICATIONS; ACTIVATION; MELLITUS; IDENTIFICATION; ABNORMALITIES; PATHOGENESIS AB Hyperglycaemia and insulin abnormality are the causes of all vascular diseases in diabetes. Recent studies have narrowed down the pathways by which hyperglycaemia can cause the various complications observed in the vasculature. Insulin resistance and hyperinsulinaemia have been associated with cardiovascular disease. New ideas are presented on how selective insulin resistance of the vasculature may be responsible for the increased incidence of hypertension and cardiovascular disease. C1 BRIGHAM & WOMENS HOSP, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. RP King, GL (reprint author), JOSLIN DIABET CTR, 1 JOSLIN PL, BOSTON, MA 02215 USA. FU NEI NIH HHS [EY5110, EY9178]; NIDDK NIH HHS [DK36433] NR 36 TC 43 Z9 46 U1 0 U2 0 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0785-3890 J9 ANN MED JI Ann. Med. PD OCT PY 1996 VL 28 IS 5 BP 427 EP 432 DI 10.3109/07853899608999103 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VT416 UT WOS:A1996VT41600008 PM 8949974 ER PT J AU Vechio, JD Bruijn, LI Xu, ZS Brown, RH Cleveland, DW AF Vechio, JD Bruijn, LI Xu, ZS Brown, RH Cleveland, DW TI Sequence variants in human neurofilament proteins: Absence of linkage to familial amyotrophic lateral sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID MOTOR-NEURON DISEASE; POLYMORPHISM ANALYSIS; SCIATIC-NERVE; MOUSE MODEL; SUBUNIT; GENE; MICE; EXPRESSION; MUTATIONS; PATHOLOGY AB Neurofilaments, assembled from NF-L (68 kd), NF-M (95 kd), and NF-H (115 kd), are the most abundant structural components in large myelinated axons, particularly those of motor neurons. Aberrant neurofilament accumulation in cell bodies and axons of motor neurons is a prominent pathological feature of several motor neuron diseases, including sporadic and familial amyotrophic lateral sclerosis (ALS). Transgenic methods have proved in mice that mutation in or increased expression of neurofilament subunits can be primary causes of motor neuron disease that mimics the neurofilamentous pathology often reported in human disease. To examine whether mutation in neurofilament subunits causes or predisposes to ALS, we used single-strand conformation polymorphism coupled with DNA sequencing to search for mutations in the entirety of the human NF-L, NF-M, and NF-H genes from 100 familial ALS patients known not to carry mutations in superoxide dismutase 1 (SOD1), as well as from 75 sporadic ALS patients. Six polypeptide sequence variants were identified in rod and tail domains of NF-L, NF-M, or NF-H. However, all were found at comparable frequency in DNAs from normal individuals and no variant cosegregated with familial disease. Two deletions found previously in NF-H genes of sporadic ALS patients were not seen in this group of familial or sporadic ALS patients. C1 UNIV CALIF SAN DIEGO,LUDWIG INST CANC RES,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT NEUROSCI,LA JOLLA,CA 92093. WORCESTER FDN EXPT BIOL INC,SHREWSBURY,MA 01545. MASSACHUSETTS GEN HOSP,DAY LAB NEUROMUSCULAR RES,BOSTON,MA. FU NIA NIH HHS [AG 12922-01]; NINDS NIH HHS [NS 31248-03, NS 27036-07] NR 40 TC 63 Z9 64 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 1996 VL 40 IS 4 BP 603 EP 610 DI 10.1002/ana.410400410 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VN903 UT WOS:A1996VN90300009 PM 8871580 ER PT J AU Morris, AK Valley, AW AF Morris, AK Valley, AW TI Overview of the management of AIDS-related Kaposi's sarcoma SO ANNALS OF PHARMACOTHERAPY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY-SYNDROME; COLONY-STIMULATING FACTOR; RECOMBINANT INTERFERON-ALPHA; LEUKOCYTE-A INTERFERON; PHASE-II; INTRALESIONAL VINBLASTINE; LIPOSOMAL DAUNORUBICIN; STAGING CRITERIA; BETA-INTERFERON AB OBJECTIVE: To review the epidemiology, pathogenesis, clinical presentation, diagnosis, and staging of Kaposi's sarcoma (KS), as well as the current role of local and systemic therapies in the management of AIDS-related KS (AIDS-KS). DATA SOURCES AND STUDY SELECTION: MEDLINE and CANCERLIT searches of the English-language medical literature were conducted. Emphasis was placed on studies published since the onset of the AIDS epidemic in the early 1980s. A manual review of selected bibliographies was also completed, DATA SYNTHESIS: AIDS-KS is a disease with a heterogeneous presentation that affects approximately 20% of patients with AIDS. Although the proportion of AIDS patients developing this disease during the course of their illness is declining, the actual number of AIDS-KS cases is increasing. The etiology of AIDS-KS is not clear, but a sexually transmitted cofactor has been implicated. Recent reports demonstrate that a herpes-like virus may be responsible for the development of KS in patients with and without AIDS. Furthermore, the cellular origin of KS has not been identified and questions remain about whether KS represents a true malignancy. The system used in staging patients with AIDS-KS has changed dramatically since initial therapeutic trials were conducted, this may account for observed differences in outcome among trials. The immunologic status of patients is now included as part of the staging system, since it has prognostic significance, Since specific therapy for AIDS-KS is not curative and does not prolong survival, it should be directed at improving patient cosmesis and palliation of disease-related symptoms. Local therapy, such as radiation, cryotherapy, and intralesional chemotherapy, is recommended for the management of limited disease, Systemic interferon alfa or chemotherapy is indicated for disseminated disease. Interferon alfa is useful in patients with predominantly mucocutaneous disease and is most effective in patients with good prognostic factors, such as absence of B symptoms, no history of opportunistic infections, and a CD4 count of more than 200 cells/mm(3). Interferon alfa alone or in combination with zidovudine produces responses in approximately 30% of AIDS-KS patients with good prognostic factors. Single-agent or combination chemotherapy is indicated for rapidly progressive or advanced AIDS-KS. Commonly used agents include doxorubicin, daunorubicin, bleomycin, vincristine, and vinblastine. Responses can be expected in at least 50% of patients treated with single-agent or combination chemotherapy. However, many patients are unable to tolerate the toxicity associated with systemic AIDS-KS therapy. Future research will focus on therapies that target the underlying pathogenesis of this disease. CONCLUSIONS: The optimal therapy for patients with AIDS-KS has not been determined. Treatment is appropriately directed at palliation of disease-related symptoms as no therapy has been unequivocally proven to impact survival. Local therapies should be used in the management of localized disease, while systemic therapy is appropriate for disseminated disease. Interferon alfa is useful in patients with primarily mucocutaneous disease or asymptomatic visceral involvement, Chemotherapy is indicated in patients who have rapidly progressive or advanced disease. Therapy must be individualized according to the patient's disease course and other patient-specific factors. C1 UNIV TEXAS,HLTH SCI CTR,CLIN PHARM PROGRAM,SAN ANTONIO,TX. RP Morris, AK (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,BOX 1111,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 81 TC 18 Z9 18 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD OCT PY 1996 VL 30 IS 10 BP 1150 EP 1163 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VL133 UT WOS:A1996VL13300015 PM 8893123 ER PT J AU Colby, C Stoukides, CA Spitzer, TR AF Colby, C Stoukides, CA Spitzer, TR TI Antithymocyte immunoglobulin in severe aplastic anemia and bone marrow transplantation SO ANNALS OF PHARMACOTHERAPY LA English DT Article ID ANTI-THYMOCYTE GLOBULIN; SAA WORKING PARTY; HEMATOPOIETIC GROWTH-FACTORS; COLONY-STIMULATING FACTOR; COMPARING CYCLOSPORINE-A; ANTILYMPHOCYTE GLOBULIN; IMMUNOSUPPRESSIVE THERAPY; TRANSFUSED PATIENTS; INTERFERON-GAMMA; RANDOMIZED TRIAL AB OBJECTIVE: To review antithymocyte immunoglobulin (ATG) and its current role in the treatment of severe aplastic anemia (SAA), focusing on ATG in immunosuppressive therapy compared with bone marrow transplantation (BMT). DATA SOURCES: A MEDLINE search (1966 to 1996) of English-language literature and human subjects pertaining to ATG and BMT therapy in SAA was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. DATA SYNTHESIS: The hallmark of SAA is pancytopenia and bone marrow hypoplasia. Although the etiology in a majority of cases remains unknown, current data implicate an immune-mediated destruction of stem cells. ATG is a potent immunosuppressive agent and has emerged as an important therapy for patients with SAA. The exact mechanism of immunosuppressive action is not fully understood, although ATG appears to disrupt cell-mediated immune responses resulting in inhibition or altered T-cell function. Numerous trials have evaluated the use of ATG both as monotherapy and in combination with other immunosuppressive agents. Treatment with ATG in SAA has demonstrated a 40-70% response rate. Data suggest that intensive immunosuppressive therapy with ATG in combination with cyclosporine may provide the optimal immunosuppressive treatment. Questions still remain concerning complications and long-term survival of the patients. Although more than a 2-year follow-up shows a decline in mortality, a plateau in the survival curve was not achieved. BMT is a potential treatment for SAA. Although there is a high initial mortality due to treatment-related toxicities, successful marrow engraftment provides a cure for SAA. Many patients (75-90%) experience long-term survival after allogenic BMT. Age, donor availability, and severity of disease limit the number of eligible patients. CONCLUSIONS: Due to excellent results with BMT, it has become the therapy of choice for selected patients with SAA. For patients who are not eligible for BMT, intensive immunosuppressive therapy with ATG and cyclosporine is recommended. Further study to better understand the pathogenesis of SAA and prevent treatment-related complications is essential to provide the best care to all patients. C1 MED OUTCOMES MANAGEMENT,FOXBORO,MA. RP Colby, C (reprint author), MASSACHUSETTS GEN HOSP,BONE MARROW TRANSPLANT PROGRAM,FND 625,55 FRUIT ST,BOSTON,MA 02114, USA. NR 76 TC 3 Z9 3 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD OCT PY 1996 VL 30 IS 10 BP 1164 EP 1174 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VL133 UT WOS:A1996VL13300016 PM 8893124 ER PT J AU Schnitzer, JJ Hedrick, HL Pacheco, BA Losty, PD Ryan, DP Doody, DP Donahoe, PK AF Schnitzer, JJ Hedrick, HL Pacheco, BA Losty, PD Ryan, DP Doody, DP Donahoe, PK TI Prenatal glucocorticoid therapy reverses pulmonary immaturity in congenital diaphragmatic hernia in fetal sheep SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 116th Annual Meeting of the American-Surgical-Association CY APR 18-20, 1996 CL PHOENIX, AZ SP Amer Surg Assoc ID THYROTROPIN-RELEASING-HORMONE; RESPIRATORY-DISTRESS SYNDROME; PREMATURE-INFANTS; DEXAMETHASONE THERAPY; LUNG MATURATION; HYPOPLASIA; SEVERITY; DISEASE; REPAIR; GROWTH AB Objective To assess the feasibility of conducting clinical trials of prenatal steroid therapy for congenital diaphragmatic hernia (CDH) in humans, the authors tested whether prenatal glucocorticoid, currently the standard treatment to minimize respiratory distress syndrome in premature infants, might improve the pulmonary immaturity in severe CDH in a large animal model. Summary Background Data The authors have used the nitrofen-induced rat model of CDH, which demonstrates immature lungs by biochemical, morphometric, and molecular biologic criteria. They also have shown that the lethally immature lungs of the full-term CDH rats can be improved by biochemical, morphometric, physiologic, and molecular criteria by treating the mothers with parenteral steroids at doses extrapolated from the current therapy used to accelerate lung development of premature human babies. Methods During a 3-year period in 88 fetal sheep, 1) left-sided diaphragmatic hernias were created surgically at varying gestational ages (day 78-90; term=142-145 days) and size to maximize severity (n=45), 2) placement and design of indwelling fetal intravenous catheters were optimized (n=13), and 3) timing and dosage of cortisol administration were determined (n=17). As a result, diaphragmatic hernias were created on day 80, intravenous catheters were placed on day 120, and twice-daily intravenous cortisol injections (n=8) or saline as the control (n=5) were administered (days 133-135). Lambs were delivered on day 136 via cesarean section to avoid steroid-induced abortion; vascular access was obtained, and the fetuses were ventilated at standard settings. Physiologic data were collected, and lungs were harvested for biochemical and histologic analysis. Results Significant improvements were measured in postductal arterial oxygen pressure ([PaO2] 38+/-6 mmHg after cortisol therapy compared with 20+/-3 mmHg for saline controls; p=0.002) and in dynamic compliance (0.42+/-0.05 mL/cm H2O vs. 0.29+/-0.01 mL/cm H2O; p=0.01). Lung glycogen levels in the right lung of the cortisol group were significantly better than controls (4.6+/-mg/g lung vs. 6.8+/-0.4 mg/g; p=0.002), as were protein/DNA levels (8.3+/-0.9 mg/mg vs. 14.5+/-2.9 mg/mg; p <0.05). Striking morphologic maturation of airway architecture was observed in the treated lungs. Conclusions Prenatal glucocorticoids correct the pulmonary immaturity of fetal sheep with CDH by physiologic, biochemical, and histologic criteria. These data, combined with previous small animal studies, have prompted the authors to initiate a prospective phase I/II clinical trial to examine the efficacy of prenatal glucocorticoids to improve the maturation of hypoplastic lungs associated with CDH. C1 MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP Schnitzer, JJ (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT SURG SERV,32 FRUIT ST,WRN 1121,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA09535]; NHLBI NIH HHS [HL03132] NR 47 TC 56 Z9 57 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD OCT PY 1996 VL 224 IS 4 BP 430 EP 437 DI 10.1097/00000658-199610000-00002 PG 8 WC Surgery SC Surgery GA VL760 UT WOS:A1996VL76000009 PM 8857848 ER PT J AU Fischer, CP Bode, BP Souba, WW AF Fischer, CP Bode, BP Souba, WW TI A sarcoma-derived protein regulates hepatocyte metabolism via autocrine production of tumor necrosis factor-alpha SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 116th Annual Meeting of the American-Surgical-Association CY APR 18-20, 1996 CL PHOENIX, AZ SP Amer Surg Assoc ID FACTOR CACHECTIN; SKELETAL-MUSCLE; CANCER CACHEXIA; RATS; INFLAMMATION; BREAKDOWN; MEDIATORS AB Objective The effects of conditioned media from the methylcholanthrene (MCA) fibrosarcoma on hepatocyte albumin production and amino acid transport were studied. The authors characterized a factor responsible for the observed effects and investigated the role of tumor necrosis factor-alpha (TNF-alpha) in these events. Summary Background Data Cancer cachexia is mediated in part by TNF-alpha. However, few tumors secrete TNF-alpha, implicating host production of this cytokine in response to as yet uncharacterized tumor-derived factors. Autocrine production of TNF-alpha recently has been described as a potent mechanism for orchestrating hepatic metabolism. Methods Conditioned media from the MCA fibrosarcoma was incubated with isolated primary rat hepatocytes. Albumin production and TNF-alpha production by hepatocytes was measured by enzyme-linked immunosorbent assay and amino acid transport assayed by tritium (H-3)-labeled amino acid uptake. Dialysis membranes ranging from 3 kD to 100 kD were used to determine the size of the factor/factors responsible for the observed effects. Results Conditioned media from the MCA fibrosarcoma contained no TNF-alpha whereas treatment of primary rat hepatocytes with the conditioned media resulted in a 53-fold increase in TNF-alpha production by hepatocytes compared with control. Treatment of hepatocytes with MCA fibrosarcoma-conditioned media resulted in decreases in hepatic albumin production of 46%, 61%, and 42% over 3 days of treatment, and these effects were reversible by the addition of antibody to TNF-alpha. Treatment of hepatocytes with MCA fibrosarcoma conditioned media resulted in increases in hepatocyte amino acid transport via inductions of System N (1.87 fold) and System A(1.93 fold). These effects were partially abrogated by the addition of antibody to TNF-alpha. Dialysis experiments determined the molecular weight of the factor or factors responsible for the observed effects to be greater than 100 kD. The effects of the MCA fibrosarcoma conditioned media were abolished by both trypsin treatment and heat inactivation, indicating the protein nature of the factor being studied. Conclusions A tumor-derived protein has been isolated from the MCA fibrosarcoma. The protein inhibits hepatocyte albumin production and increases amino acid transport in vitro via the autocrine production of TNF-alpha. C1 MASSACHUSETTS GEN HOSP,DIV SURG ONCOL,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA57690]; NIDDK NIH HHS [DK40561] NR 25 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD OCT PY 1996 VL 224 IS 4 BP 476 EP 483 DI 10.1097/00000658-199610000-00006 PG 8 WC Surgery SC Surgery GA VL760 UT WOS:A1996VL76000037 PM 8857852 ER PT J AU Hilgenberg, AD Akins, CW Logan, DL Vlahakes, GJ Buckley, MJ Madsen, JC Torchiana, DF AF Hilgenberg, AD Akins, CW Logan, DL Vlahakes, GJ Buckley, MJ Madsen, JC Torchiana, DF TI Composite aortic root replacement with direct coronary artery implantation SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 29-31, 1996 CL ORLANDO, FL SP Soc Thorac Surgeons ID ASCENDING AORTA; GRAFT REPLACEMENT; VALVE; REIMPLANTATION; EXPERIENCE; OPERATIONS; APROTININ; REPAIR AB Background. Composite aortic root replacement is accepted treatment for aneurysms of the ascending aorta involving the root with aortic valve regurgitation, but controversy continues regarding the best technique of operation. We excise the aneurysm, implant a composite valve graft, directly attach the coronary arteries to the aortic graft, and make the distal anastomosis to the divided aorta. Methods. We reviewed the records and collected complete follow-up data on 110 consecutive patients having composite aortic root replacement with this technique from 1979 to 1995. Results. Average age was 54 years. Marfan's syndrome was present in 22 patients, acute dissections in 26, chronic dissections in 11, and active endocarditis in 13. Operative characteristics were: 25 emergency procedures, 33 urgent procedures, 52 elective procedures, 24 reoperations, and 19 with coronary artery bypass grafting. Hospital death occurred in 8 patients (7.3%). Multivariate predictors of hospital death were postoperative renal failure and acute dissection. Actuarial survival was 70% at 10 years (standard error, 5%). Multivariate predictors of total mortality were porcine valve, Bork-Shiley valve, preoperative stroke, reoperation on a composite valve graft, and coronary artery bypass grafting. Only 3 patients required late reoperation, all for valve dysfunction. Actuarial freedom from reoperation on the aortic root was 97.3% (standard error, 1.9%) at 10 years. Late echocardiograms in 47 patients showed no anastomotic aneurysms. Conclusions. Composite aortic root replacement with direct coronary implantation is effective and durable treatment for a variety of aortic pathologic conditions in elective and emergency situations. RP Hilgenberg, AD (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC SURG UNIT,WARREN 1120,BOSTON,MA 02114, USA. NR 19 TC 33 Z9 33 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 OCT PY 1996 VL 62 IS 4 BP 1090 EP 1095 DI 10.1016/0003-4975(96)00487-0 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA VK874 UT WOS:A1996VK87400038 PM 8823094 ER PT J AU Canver, CC Nichols, RD Cooler, SD Heisey, DM Murray, EL Kroncke, GM AF Canver, CC Nichols, RD Cooler, SD Heisey, DM Murray, EL Kroncke, GM TI Influence of increasing age on long-term survival after coronary artery bypass grafting SO ANNALS OF THORACIC SURGERY LA English DT Article ID SURGERY; OLDER; MORBIDITY; MORTALITY; OCTOGENARIANS AB Background. Despite the steady increase in the number of elderly patients undergoing coronary artery bypass grafting (CABG), skepticism still exists as to whether this operation is justified in older people with a reduced life expectancy. The purpose of this study was to examine the effects of increasing age on outcome after CABG. Methods. A retrospective chart review was performed on 1,689 consecutive veterans of the United States Armed Forces undergoing isolated primary CABG from January 1972 through December 1994. For better comparison, they were arbitrarily divided by age into three groups: group I, 50 years of age or less (n = 213), group II, between 51 and 70 years of age (n = 1,258), and group III, more than 70 years of age (n = 218). Long-term survival for each group was compared to that of their age-matched population derived from Wisconsin life tables. Results. The preoperative ejection fraction was comparable in all three groups (p = 0.114). The patients older than 70 years of age had received more grafts per operation than the patients 50 years of age and younger (3.7 versus 3.3) (p = 0.0001). Although the aortic cross-clamp time was prolonged with advanced age (p = 0.0002), the cardiopulmonary perfusion time was shortest in elderly patients (p = 0.0001). The early (30-day) mortality for the entire study population was 1.3%. There was a linear correlation between increasing age and early (30-day) mortality: group I, 0.5% (1/213); group II, 1.0% (13/1,258); and group III, 3.2% (7/218). The overall 10-year actuarial survival for all patients was 67%. The 10-year survival was diminished with increasing age (p = 0.0001): 74% for group I, 68% for group II, and 47% for group III. Comparative analysis of the three groups with their age-matched counterparts demonstrated an age-related survival after CABG. In group I, reduced survival was evident 4 years after the CABG: the 10-year survival in group I was 74.2%, and the survival of their age-matched population was 93.4% (confidence interval, 67% to 81.9%). In group II a survival difference was obvious 8 years after CABG: 10-year survival of 67.5% versus 75.1% in their age-matched population (confidence interval, 64.8% to 71.6%). In the elderly group of patients, no survival difference was noted: 10-year survival of 42.7% versus 45.9% of the age-matched population (confidence interval, 29.8% to 64.6%). Conclusions. An acceptable early mortality and long-term survival equal to those seen for an age-matched elderly population are sound outcome measures that support the justification of CABG in older patients irrespective of age. C1 UNIV WISCONSIN,SCH MED,WILLIAM S MIDDLETON MEM VET HOSP,SECT CARDIOTHORAC SURG,MADISON,WI 53706. NR 17 TC 27 Z9 29 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 OCT PY 1996 VL 62 IS 4 BP 1123 EP 1127 DI 10.1016/0003-4975(96)00446-8 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA VK874 UT WOS:A1996VK87400044 PM 8823100 ER PT J AU Anaissie, EJ Paetznick, VL Ensign, LG EspinelIngroff, A Galgiani, JN Hitchcock, CA LaRocco, M Patterson, T Pfaller, MA Rex, JH Rinaldi, MG AF Anaissie, EJ Paetznick, VL Ensign, LG EspinelIngroff, A Galgiani, JN Hitchcock, CA LaRocco, M Patterson, T Pfaller, MA Rex, JH Rinaldi, MG TI Microdilution antifungal susceptibility testing of Candida albicans and Cryptococcus neoformans with and without agitation: An eight-center collaborative study SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID BROTH MACRODILUTION; AMPHOTERICIN-B; MULTICENTER EVALUATION; IN-VITRO; FLUCONAZOLE; YEASTS; AGENTS AB The growth patterns observed in the trailing wells when fluconazole is being tested may give rise to readings that suggest resistance or increased MICs for known susceptible strains. We conducted a multicenter study to evaluate the intralaboratory and interlaboratory reproducibilities of a method that uses agitation to disperse these types of growth. Ten strains of Candida albicans and five strains of Cryptococcus neoformans were tested against fluconazole, flucytosine, and amphotericin B by using a microdilution adaptation of the proposed reference method of the National Committee for Clinical Laboratory Standards for yeasts (M27-T). The endpoint criterion used before agitation was consistent with the M27-T recommendation, while a criterion of 50% or more reduction of growth compared with the control was used after agitation, The results of this study showed that use of agitation and the modified endpoint criterion both improved intralaboratory and inter-laboratory agreement and increased the frequency of interpretable MICs, The MICs obtained by this method were comparable to those obtained by the broth macrodilution M27-T method. Like M27-T, this method was not able to definitely distinguish amphotericin B-susceptible from -resistant strains, although the MICs for the resistant strains were consistently higher than those for the susceptible ones. The findings imply that agitation should be seriously considered when antifungal agents, particularly fluconazole, are tested in a microdilution format. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOMATH,HOUSTON,TX 77030. ST LUKES EPISCOPAL HOSP,DEPT PATHOL,HOUSTON,TX 77030. UNIV TEXAS,SCH MED,CTR INFECT DIS,HOUSTON,TX 77030. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DIV INFECT DIS,RICHMOND,VA 23298. UNIV ARIZONA,MED SERV 111,VA MED CTR,TUCSON,AZ 85723. UNIV ARIZONA,DEPT MED,TUCSON,AZ 85723. PFIZER LTD,SANDWICH,KENT,ENGLAND. YALE UNIV,SCH MED,DEPT MED,INFECT DIS SECT,NEW HAVEN,CT 06510. UNIV IOWA,COLL MED,DEPT PATHOL,IOWA CITY,IA 52242. UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY MEM VET HOSP,LAB SERV 113,DEPT PATHOL,SAN ANTONIO,TX 78284. RP Anaissie, EJ (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,INFECT DIS SECT,BOX 47,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. FU NCI NIH HHS [CA 16672] NR 20 TC 22 Z9 22 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 OCT PY 1996 VL 40 IS 10 BP 2387 EP 2391 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA VK835 UT WOS:A1996VK83500030 PM 8891149 ER PT J AU Arahal, DR Dewhirst, FE Paster, BJ Volcani, BE Ventosa, A AF Arahal, DR Dewhirst, FE Paster, BJ Volcani, BE Ventosa, A TI Phylogenetic analyses of some extremely halophilic archaea isolated from dead sea water, determined on the basis of their 16S rRNA sequences SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID RIBOSOMAL-RNA GENE; NUCLEOTIDE-SEQUENCE; SP-NOV; HALOBACTERIUM-SODOMENSE; HALOARCULA-MARISMORTUI; NUMERICAL TAXONOMY; ENCODING GENES; ARCHAEBACTERIUM; NATRONOBACTERIUM; MICROORGANISMS AB Twenty-two extremely halophilic aerobic archaeal strains were isolated from enrichments prepared from Dead Sea water samples collected 57 years ago, The isolates were phenotypically clustered into five different groups, and a representative from each group was chosen for further study, Almost the entire sequences of the 16S rRNA genes of these representatives, and of Haloarcula hispanica ATCC 33960, were determined to establish their phylogenetic positions, The sequences of these strains were compared to previously published sequences of 27 reference halophilic archaea (members of the family Halobacteriaceae) and two other archaea, Methanobacterium formicicum DSM 1312 and Methanospirillum hungatei DSM 864, Phylogenetic analysis using approximately 1,400 base comparisons of 16S rRNA-encoding gene sequences demonstrated that the five isolates clustered closely to species belonging to three different genera-Haloferax, Halobacterium, and Haloarcula. Strains E1 and E8 were closely related and identified as members of the species Haloferax volcanii, and strain E12 was closely related and identified as a member of the species Halobacterium salinarum. However, strains E2 and E11 clustered in the Haloarcula branch with Haloarcula hispanica as the closest relative at 98.9 and 98.8% similarity, respectively, Strains E2 and E11 could represent two new species of the genus Haloarcula, However, because strains of these two new species were isolated from a single source, they will not be named until additional strains are isolated from other sources and fully characterized. C1 UNIV SEVILLA,FAC FARM,DEPT MICROBIOL & PARASITOL,SEVILLE 41012,SPAIN. FORSYTH DENT CTR,DEPT MOL GENET,BOSTON,MA 02115. UNIV CALIF SAN DIEGO,SCRIPPS INST OCEANOG,DIV MARINE BIOL RES,LA JOLLA,CA 92093. RI Arahal, David R./A-9344-2008 OI Arahal, David R./0000-0002-8926-9801 FU NIDCR NIH HHS [DE-08303, DE-10374] NR 49 TC 59 Z9 67 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 1996 VL 62 IS 10 BP 3779 EP 3786 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA VK372 UT WOS:A1996VK37200036 PM 8837434 ER PT J AU Sadhwani, A Schomacker, KT Tearney, GJ Nishioka, NS AF Sadhwani, A Schomacker, KT Tearney, GJ Nishioka, NS TI Determination of teflon thickness with laser speckle .1. Potential for burn depth diagnosis SO APPLIED OPTICS LA English DT Article DE burn diagnosis; laser speckle; tissue phantoms; speckle decorrelation time; Brownian motion ID BLOOD-FLOW; OPTICAL-PROPERTIES; TURBID MEDIA; FLUORESCENCE; ULTRASOUND; SCATTERING; PATTERNS; INJURY; NM AB A quantitative method for determining the depth of burn eschar would aid surgeons in determining whether to excise and subsequently graft a burn wound. We hypothesize that tissue viability could be assessed by an analysis of the spatial modulation of near-field laser speckle by flowing blood. A feasibility study of the technique was performed with two-layer tissue phantoms used to simulate a burn wound. A sheet of polytetrafluoroethylene (PTFE) was used to simulate nonperfused burn eschar, and tissue perfusion within deeper layers was represented by Brownian motion from a scattering solution. A low-power He-Ne laser was focused onto the target, and the resulting speckle image was captured with a CCD camera and stored on a computer for further processing. The diameter of the speckle pattern was found to be directly proportional to the thickness of the overlying layer. These data suggest that the thickness of PTFE can be determined to +/-100-mu m accuracy with 95% confidence and may be suitable for burn depth detection in vivo. (C) 1996 Optical Society of America C1 HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. RP Sadhwani, A (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. NR 33 TC 41 Z9 41 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 SN 0003-6935 J9 APPL OPTICS JI Appl. Optics PD OCT 1 PY 1996 VL 35 IS 28 BP 5727 EP 5735 DI 10.1364/AO.35.005727 PG 9 WC Optics SC Optics GA VJ501 UT WOS:A1996VJ50100037 PM 21127582 ER PT J AU Rosenberg, RN Richter, RW Risser, RC Taubman, K PradoFarmer, I Ebalo, E Posey, J Kingfisher, D Dean, D Weiner, MF Svetlik, D Adams, P Honig, LS Cullum, CM Schaefer, FV Schellenberg, GD AF Rosenberg, RN Richter, RW Risser, RC Taubman, K PradoFarmer, I Ebalo, E Posey, J Kingfisher, D Dean, D Weiner, MF Svetlik, D Adams, P Honig, LS Cullum, CM Schaefer, FV Schellenberg, GD TI Genetic factors for the development of Alzheimer disease in the Cherokee Indian SO ARCHIVES OF NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E POLYMORPHISM; TYPE-4 ALLELE; FREQUENCIES; POPULATIONS; EPSILON-4; DEMENTIA AB Objective: To study the relationship between the genetic degree of Cherokee ancestry, the apolipoprotein E *E4 (APOE*E4) allele type, and the development of Alzheimer disease (AD) in individuals from the Cherokee Nation who reside in northeastern Oklahoma. Setting: Alzheimer disease center satellite clinic and university departments of neurology, psychiatry, and academic computing. Design: Standardized dementia evaluations based on criteria from the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association were performed on 26 patients aged 65 years or older to establish a diagnosis of AD. Twenty-six control subjects were recruited and similarly assessed. The APOE allele type determinations were obtained on all patients and control subjects. Appropriate statistical analyses were used to compare the genetic degree of Cherokee ancestry, the APOE allele type, and the development of AD. Results: The data indicated that as the genetic degree of Cherokee Indian ancestry increased, the representation of AD decreased. The 9 patients with AD with a greater than 50% genetic degree of Cherokee ancestry constituted 35% of the group with AD. The 17 remaining patients with AD who were less than 50% Cherokee constituted 65% of the group with AD. In contrast, 17 (65%) of the control subjects were more than 50% Cherokee; only 9 (35%) were less than 50% Cherokee. These percentages of AD were not changed by the *E4 allele. This inverse relationship between the genetic degree of Cherokee ancestry and AD, independent of the APOE*E4 allele status, diminished with increasing age, suggesting an age-related protective effect of being Cherokee. For a decrease of 10% in Cherokee ancestry, the odds of developing AD are estimated to be 9.00 times greater at age 65 years but only 1.34 times greater at age 80 years. Conclusions: A greater genetic degree of Cherokee ancestry reduces the risk of developing AD and, thus, seems protective. This protective genetic factor is independent of APOE allele type and diminishes with age. C1 UNIV TEXAS,SW MED CTR,DEPT PSYCHIAT,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,ACAD COMP CTR,DALLAS,TX 75235. ST JOHNS HOSP,ALZHEIMERS DIS RES UNIT,TULSA,OK. UNIV OKLAHOMA,COLL MED,TULSA,OK 74136. CHEROKEE NAT,HLTH SERV DIV,TAHLEQUAH,OK. HA CHAPMAN INST MED GENET,TULSA,OK. UNIV WASHINGTON,MED CTR,SEATTLE,WA 98195. VET AFFAIRS PUGET SOUND HLTH CARE SYST,GERONTOL SERV,SEATTLE,WA. RP Rosenberg, RN (reprint author), UNIV TEXAS,SW MED CTR,DEPT NEUROL,5323 HARRY HINES BLVD,DALLAS,TX 75235, USA. OI Weiner, Myron/0000-0001-5682-4410 FU NIA NIH HHS [AGP30 12300] NR 21 TC 31 Z9 31 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD OCT PY 1996 VL 53 IS 10 BP 997 EP 1000 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA VM031 UT WOS:A1996VM03100011 PM 8859062 ER PT J AU Aiello, LP AF Aiello, LP TI Vascular endothelial growth factor and the eye - Past, present, and future SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID PROLIFERATIVE DIABETIC-RETINOPATHY; PERMEABILITY FACTOR; RETINAL NEOVASCULARIZATION; CELLS; MODEL RP Aiello, LP (reprint author), BEETHAM EYE INST,JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 22 TC 20 Z9 21 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 1996 VL 114 IS 10 BP 1252 EP 1254 PG 3 WC Ophthalmology SC Ophthalmology GA VL781 UT WOS:A1996VL78100017 PM 8859087 ER PT J AU Branigan, PJ Gerard, HC Hudson, AP Schumacher, HR AF Branigan, PJ Gerard, HC Hudson, AP Schumacher, HR TI Comparison of synovial tissue and synovial fluid as the source of nucleic acids for detection of Chlamydia trachomatis by polymerase chain reaction SO ARTHRITIS AND RHEUMATISM LA English DT Article ID REITERS-SYNDROME; ARTHRITIS; INFECTION; DISEASE; DNA; IDENTIFICATION; ANTIGEN; JOINTS AB Objective. Difficulties in detecting Chlamydia trachomatis in human joints by polymerase chain reaction (PCR) may be related to whether synovial tissue or synovial fluid (SF) is used as the source of DNA in PCR amplification. In this study, a new PCR assay was developed and used to compare chlamydial DNA in paired samples of SF and synovial tissue front patients with arthritis. Methods. The PCR assay targeted the ribosomal RNA operons, which are present in 2 copies on the C trachomatis chromosome. DNA from several relevant bacteria and chlamydial serovars was used for testing this screening system. The detection of chlamydial DNA in nucleic acid preparations from matched samples of SF and synovial tissue was compared by PCR assay. Samples were obtained from 55 patients, including patients with reactive arthritis, Reiter's syndrome, and other arthropathies. Results. Testing of the PCR screening system confirmed it to be highly specific and sensitive. Use of this assay to screen DNA from SF and synovial tissue samples showed that 29 (53%) of 55 synovial tissue preparations were positive for chlamydial DNA, but only 16 (29%) of the matched SF samples from these 29 patients were similarly positive. Five (9%) of 55 SF samples, but not their tissue counterparts, were positive for chlamydial DNA by PCR. Conclusion. Detection of chlamydial DNA in the joints of patients by PCR give positive results more often when synovial tissue rather than SF is the source of target nucleic acids. Although synovial tissue is the source of choice for the most reliable determination of chlamydia in the joint, both synovial tissue and SF should be assayed if possible. C1 MED COLL PENN & HAHNEMANN UNIV,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19129. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,ARTHRIT & IMMUNOL CTR,PHILADELPHIA,PA. OI Branigan, Patrick/0000-0001-9741-9067 FU NIAMS NIH HHS [AR-42541] NR 33 TC 85 Z9 87 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 1996 VL 39 IS 10 BP 1740 EP 1746 DI 10.1002/art.1780391018 PG 7 WC Rheumatology SC Rheumatology GA VL140 UT WOS:A1996VL14000017 PM 8843866 ER PT J AU Spiro, RG Yasumoto, Y Bhoyroo, V AF Spiro, RG Yasumoto, Y Bhoyroo, V TI Characterization of a rat liver Golgi sulphotransferase responsible for the 6-0-sulphation of N-acetylglucosamine residues in beta-linkage to mannose: Role in assembly of sialyl-galactosyl-N-acetylglucosamine 6-sulphate sequence of N-linked oligosaccharides SO BIOCHEMICAL JOURNAL LA English DT Article ID PORCINE ZONA-PELLUCIDA; ALPHA-D-MANNOSIDASE; CARBOHYDRATE CHAINS; GLYCOPROTEIN HORMONES; SULFATE; UNITS; CELLS; GALACTOSYLTRANSFERASE; IDENTIFICATION; THYROGLOBULIN AB Rat liver Golgi membranes were found to contain an enzyme that can transfer sulphate from 3'-phosphoadenosine 5'-phosphosulphate (PAPS) to C-6 of the terminal GlcNAc in beta-linkage to mannose and has properties indicating that it is involved in the synthesis of the NeuAc alpha 2-3(6)Gal beta 1-4GlcNAc(6-SO4) sequences observed in the N-linked carbohydrate units of various glycoproteins. Assays performed with [S-35]PAPS (K-m 0.67 mu M) and GlcNAc beta 1-6Man alpha 1-O-Me (GnMaMe) acceptor (K-m 0.71 mM) indicated that the sulphotransferase had a pH optimum of approx. 7.0 and is markedly stimulated by Mn2+ ions (maximum approx. 15 mM) and Triton X-100 (0.05-0.1 %). Hydrazine/nitrous acid/NaBH4 treatment of the S-35-labelled product yielded radiolabelled 2,5-anhydromannitol(6-SO4). The sulphated GnMaMe product of the GlcNAc-6-O-sulphotransferase could be galactosylated by a rat liver Golgi enzyme that was shown to have the same properties as the UDP-Gal:GlcNAc beta-1,4-galactosyltransferase from bovine milk, Competition studies performed with GlcNAc and GlcNAc-6-SO4 furthermore indicated that the same liver enzyme acted on both accepters to produce Gal beta 1-4GlcNAc and Gal beta 1-4GlcNAc(6-SO4) with K-m values of 1.04 and 1.68 mM respectively. Because the sulphated N-acetyl-lactosamine could in turn serve as an acceptor for rat liver sialyltransferase, it seems that this enzyme, together with the Golgi galactosyltransferase and the GlcNAc-6-O-sulphotransferase, could act in concert in assembling the NeuAc alpha 2-3(6)Gal beta 1-4GlcNAc(6-SO4) branches of complex N-linked oligosaccharides. C1 HARVARD UNIV, SCH MED, DEPT MED, JOSLIN DIABET CTR, BOSTON, MA 02215 USA. RP HARVARD UNIV, SCH MED, DEPT BIOL CHEM, JOSLIN DIABET CTR, 1 JOSLIN PL, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [DK 17477] NR 30 TC 42 Z9 43 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD OCT 1 PY 1996 VL 319 BP 209 EP 216 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM963 UT WOS:A1996VM96300032 PM 8870671 ER PT J AU Tedlow, JR Fava, M Uebelacker, LA Alpert, JE Nierenberg, AA Rosenbaum, JF AF Tedlow, JR Fava, M Uebelacker, LA Alpert, JE Nierenberg, AA Rosenbaum, JF TI Are study dropouts different from completers? SO BIOLOGICAL PSYCHIATRY LA English DT Article DE dropouts; completers; differences; fluoxetine; depression ID DEPRESSION; PAROXETINE; IMIPRAMINE; PLACEBO RP Tedlow, JR (reprint author), MASSACHUSETTS GEN HOSP,DEPRESS RES PROGRAM,CLIN PSYCHOPHARMACOL UNIT,WAC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01 MH48483-01] NR 19 TC 24 Z9 24 U1 0 U2 1 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 OCT 1 PY 1996 VL 40 IS 7 BP 668 EP 670 DI 10.1016/0006-3223(96)00204-1 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VJ929 UT WOS:A1996VJ92900016 PM 8886303 ER PT J AU Zhao, S Consoli, U Arceci, R Pfeifer, J Dalton, WS Andreeff, M AF Zhao, S Consoli, U Arceci, R Pfeifer, J Dalton, WS Andreeff, M TI Semi-automated PCR method for quantitating MDR1 expression SO BIOTECHNIQUES LA English DT Article ID POLYMERASE CHAIN-REACTION; MULTIDRUG-RESISTANT PHENOTYPE; BONE-MARROW CELLS; P-GLYCOPROTEIN; GENE-EXPRESSION; ACUTE-LEUKEMIA; MESSENGER-RNA; BLOOD AB The MDR1 gene is involved in drug resistance in many hematopoietic and solid tumors. The Quantitative PCR system 5000(TM)(QPCR-5000; Perkin-Elmer) is a new instillment system that uses electrochemiluminescence to automatically quantitate polymerase chain reaction (PCR) products. A comparative study between radioactively labeled PCR (P-32-PCR) and QPCR was performed to analyze the MDR1 gene expression in the drug-resistant (Doxorubicin) cell lines Dox40, Dox6, the parental cell line 8226/S, CEM Dox1 and three acute myeloid leukemia (AML) patient samples. Using the Dox40 and Dox6 resistant cell lines, we coilzpared the sensitivities of QPCR and P-32-PCR. A strong signal was obtained from QPCR at 20 to 25 cycles (which is in the linear range for quantitation), while a weak signal was obtained using P-32-PCR at the same cycle number: Dilution experiments gave better precision with the QPCR than with the radioactive method. AML samples were studied with the MDRI-specific MAbs MRK16 and 4E3, and the efflux function was analyzed using Rh-123 retention in the absence or presence of verapamil. The three samples showed high (D = 0.79), medium (D = 0.52) and negative (D = 0.08) p-glycoprotein (P-gp) levels and correlated with efflux function. The MDR1/beta 2-M mRNA ratios for P-32-PCR were 0.41, 0.40 and 0.12, respectively, and were 0.127, 0.097 and 0.028, respectively, for QPCR. There were significant differences between the samples with high and medium P-gp levels comparing the two methods. Very low levels of MDR1 in CEM Dox1 cells could be detected only by QPCR. In conclusion, QPCR was Sound to be more reproducible, accurate and sensitive than P-32-PCR. C1 UNIV TEXAS, MD ANDERSON CANC CTR, DEPT HEMATOL, HOUSTON, TX 77030 USA. DANA FARBER CANC CTR, BOSTON, MA USA. PERKIN ELMER CORP, APPL BIOSYST DIV, FOSTER CITY, CA USA. UNIV ARIZONA, TUCSON, AZ USA. FU NCI NIH HHS [CA57639, CA41305, CA55164] NR 14 TC 20 Z9 21 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD OCT PY 1996 VL 21 IS 4 BP 726 EP 731 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VL405 UT WOS:A1996VL40500027 PM 8891227 ER PT J AU Liu, PC Leong, T Quam, L Billadeau, D Kay, NE Greipp, P Kyle, RA Oken, MM VanNess, B AF Liu, PC Leong, T Quam, L Billadeau, D Kay, NE Greipp, P Kyle, RA Oken, MM VanNess, B TI Activating mutations of N- and K-ras in multiple myeloma show different clinical associations: Analysis of the Eastern Cooperative Oncology Group phase III trial SO BLOOD LA English DT Article ID POLYMERASE CHAIN-REACTION; PLASMA-CELL DYSCRASIAS; ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; GENE-MUTATIONS; LYMPHOID MALIGNANCIES; SIGNAL-TRANSDUCTION; ONCOGENE MUTATIONS; POINT MUTATIONS; C-MYC AB Mutations of members of the ras family are among the most common oncogene mutations found in multiple myeloma (MM). We have examined the mutational status of the N- and K-ras genes at codons 12, 13, and 61 in 160 newly diagnosed MM patients enrolled on the Eastern Cooperative Oncology Group (ECOG) phase III clinical trial E9486. The total incidence of ms mutations was found to be 39% of the samples analyzed. Five patients showed evidence of more than one mutation. We obtained 22 marrow samples from patients at the time of disease progression or relapse, for whom a ms mutation was identified at diagnosis. In all cases, the res mutation of the disease progression sample was identical to that found at diagnosis. In contrast, three of 25 patients who did not show any ms mutation at diagnosis acquired a res mutation at the time of disease progression. No significant association was observed between any ras mutation and stage of disease, beta(2)-microglobulin levels. labeling index, or protein type. The mean tumor burden and median survival for patients with mutations of N-ras was indistinguishable from patients with no ras mutations. However, patients with K-ras mutations had a significantly higher mean bone marrow tumor burden at diagnosis than patients with no ras mutations (57% v 36%, P <.02); and the median survival of patients with a K-ras mutation was significantly shorter (2.0 v 3.7 years, P <.02). To determine if the status of ms mutations could affect treatment response, we examined patient survival on the three treatment arms of E9486. Although the presence of a ms mutation in the multidrug treatment, VBMCP alone, showed a marginal significance, neither the VBMCP, nor the addition of interferon-cr showed statistically significant survival differences between mutant and wildtype ms status. Interestingly, there appeared to be a statistically significant difference in survival of patients treated with VBMCP and alternating high doses of cyclophosphamide + prednisone. Patients with ras mutations had a median survival of 2.1 years; patients with wildtype ras had a median survival of 4.0 years (P <.01). (C) 1996 by The American Society of Hematology. C1 UNIV MINNESOTA,INST HUMAN GENET,MINNEAPOLIS,MN 55455. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV KENTUCKY,LEXINGTON,KY. MAYO CLIN,ROCHESTER,MN. VIRGINIA PIPER CANC INST,MINNEAPOLIS,MN. FU NCI NIH HHS [CA15947, CA19853, CA32218] NR 38 TC 140 Z9 142 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 1996 VL 88 IS 7 BP 2699 EP 2706 PG 8 WC Hematology SC Hematology GA VK747 UT WOS:A1996VK74700038 PM 8839865 ER PT J AU Guillemot, JC Kruskal, BA Adra, CN Zhu, SC Ko, JL Burch, P Nocka, K Seetoo, K Simons, E Lim, B AF Guillemot, JC Kruskal, BA Adra, CN Zhu, SC Ko, JL Burch, P Nocka, K Seetoo, K Simons, E Lim, B TI Targeted disruption of guanosine diphosphate-dissociation inhibitor for rho-related proteins, GDID4: Normal hematopoietic differentiation but subtle defect in superoxide production by macrophages derived from in vitro embryonal stem cell differentiation SO BLOOD LA English DT Article ID GTP-BINDING PROTEIN; NEUTROPHIL NADPH OXIDASE; RESPIRATORY BURST OXIDASE; ACTIN STRESS FIBERS; MAST-CELLS; MOLECULAR-CLONING; CDC42 GTPASES; ES CELLS; RAC; ACTIVATION AB The Rho subfamily of small guanosine triphosphate (GTP)-binding proteins, through their role in cytoskeletal organization, is involved in diverse cellular functions, including cell motility and morphologic changes during differentiation. pac also has a special role in the production of superoxide, a key component in phagocytic antimicrobial function, Guanosine diphosphate (GDP)-dissociation inhibitors (GDIs) belong to one of three classes of proteins that regulate the critical cycling of GTP-binding proteins between the inactive and active states, Two homologous GDIs for the Rho subfamily have been identified. GDID4 is preferentially expressed in hematopoietic cells, while RhoGDI is ubiquitously expressed, Whether different physiologic functions are subserved by the two GDIs is unknown, We have derived embryonal stem (ES) cells with targeted disruption of both alleles of the GDID4 gene and examined hematopoiesis and phagocytic functions of macrophages derived from in vitro ES-cell differentiation. GDID4(-/-) ES cells develop like wildtype cells into colonies that contain heterogeneous populations of progenitor cells and differentiated erythromyeloid cells. GDID4(-/-) cells express no GDID4 protein, but have normal levels of RhoGDI, GDID4-/- macrophages phagocytose yeasts and antibody-opsonized erythrocytes as effectively as wild-type macrophages. However, a slight but consistent reduction in their capacity to generate superoxide was observed, which suggests new insight into the cellular role of GDID4, The minimal phenotypic effect of a loss of function of GDID4 also indicates a significant redundancy of function between GDIDC and RhoGDI, Their functional repertoire may be better revealed by a disruption of both genes, The use of hematopoietic cells derived in vitro from genotypically altered ES cells avoids the difficulties inherent in generating knockout animals and is a useful complementary approach for evaluating the gene function. (C) 1996 by The American Society of Hematology. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA. CHILDRENS HOSP,DIV INFECT DIS,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV BOSTON HOSP,DEPT BIOCHEM,BOSTON,MA 02118. CYTOMED INC,CAMBRIDGE,MA. FU NIDDK NIH HHS [DK47636, DK31056] NR 50 TC 27 Z9 27 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 OCT 1 PY 1996 VL 88 IS 7 BP 2722 EP 2731 PG 10 WC Hematology SC Hematology GA VK747 UT WOS:A1996VK74700041 PM 8839868 ER PT J AU Freedman, AS Gribben, JG Neuberg, D Mauch, P Soiffer, RJ Anderson, KC Pandite, L Robertson, MJ Kroon, M Ritz, J Nadler, LM AF Freedman, AS Gribben, JG Neuberg, D Mauch, P Soiffer, RJ Anderson, KC Pandite, L Robertson, MJ Kroon, M Ritz, J Nadler, LM TI High-dose therapy and autologous bone marrow transplantation in patients with follicular lymphoma during first remission SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; POLYMERASE CHAIN-REACTION; B-CELL LYMPHOMA; PERIPHERAL-BLOOD; MYELODYSPLASTIC SYNDROME; T(14-18)-POSITIVE CELLS; BCL-2 TRANSLOCATION; RESIDUAL CELLS; RELAPSE; AMPLIFICATION AB We report the results of a study in previously untreated advanced stage patients with follicular lymphoma (FL) who underwent uniform induction chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) followed by myeloablative therapy and anti-B-cell monoclonal antibody purged autologous bone marrow transplantation (ABMT). Eighty-three patients with previously untreated, low-grade FL were enrolled. After CHOP induction, only 36% achieved complete remission (CR) and 77 patients underwent ABMT, Before BM harvest, 70 patients had a known t(14;18), as determined by polymerase chain reaction (PCR), and all remained PCR positive in the BM at harvest, After ABMT, the disease-free survival (DFS) and overall survival are estimated to be 63% and 89% at 3 years, respectively, with a median follow-up of 45 months, Patients whose BM was PCR negative after purging experienced significantly longer freedom from recurrence (FFR) than those whose BM remained PCR positive (P = .0006), Continued PCR negativity in follow-up BM samples was also strongly predictive of continued CR, This study suggests that a subset of patients with advanced FL may experience prolonged clinical and molecular remissions following high-dose ablative therapy, although longer follow up will be necessary to determine potential impact on overall survival. (C) 1996 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES & BIOSTAT,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT RADIAT THERAPY,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA34183, CA66996] NR 38 TC 193 Z9 197 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 OCT 1 PY 1996 VL 88 IS 7 BP 2780 EP 2786 PG 7 WC Hematology SC Hematology GA VK747 UT WOS:A1996VK74700049 PM 8839876 ER PT J AU Lipton, SA AF Lipton, SA TI Similarity of neuronal cell injury and death in AIDS dementia and focal cerebral ischemia: Potential treatment with NMDA open-channel blockers and nitric oxide-related species SO BRAIN PATHOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; METHYL-D-ASPARTATE; CENTRAL-NERVOUS-SYSTEM; RECEPTOR-MEDIATED NEUROTOXICITY; TUMOR-NECROSIS-FACTOR; HIV COAT PROTEIN; VASOACTIVE-INTESTINAL-PEPTIDE; PLATELET-ACTIVATING-FACTOR; PRIMARY CORTICAL CULTURES; ARACHIDONIC-ACID AB Using in vitro models, our laboratory in collaboration with those of Pierluigi Nicotera (University of Konstanz, Germany) and Stan Orrenius (Karolinska Institute) has recently shown that fulminant insults to the nervous system from excitotoxins or free radicals result in neuronal cell death from necrosis, while more subtle insults result in delayed apoptosis. Over the past dozen or so years, mounting evidence has suggested that excitotoxins, such as glutamate, result in neuronal cell death after stroke. More recent evidence has suggested that in addition to necrotic cell death in the ischemic core, a number of neurons may also undergo apoptosis. Thus, the hypothesis that intense injury leads to necrosis while mild insult (perhaps in the penumbra) leads to apoptosis may hold in focal cerebral ischemia. Another neurological malady with mounting evidence for a pathogenesis that is mediated at least in part by excitotoxins is HIV-1-associated cognitive/motor complex (originally termed the AIDS Dementia Complex and, for convenience, designated here AIDS dementia). AIDS dementia appears to be associated with several neuropathological abnormalities, including giant cell formation by microglia, astrogliosis, and neuronal injury or loss. Recently, neuronal and other cell injury in AIDS brains has been shown to result in apoptotic-like cell death. How can HIV-1 result in neuronal damage if neurons themselves are only rarely, if ever, infected by the virus? Experiments from several different laboratories, including our group in collaboration with that of Howard Gendelman (University of Nebraska Medical Center), have lent support to the existence of HIV- and immune-related toxins in a variety of in vitro and in vivo paradigms. In one recently defined pathway to neuronal injury, HIV-infected macrophages/microglia as well as macrophages activated by HIV-1 envelope protein gp120 appear to secrete excitants/neurotoxins. These substances may include arachidonic acid, platelet-activating factor, free radicals (NO . and O-2(.-)), glutamate, quinoIinate, cysteine, cytokines (TNF-alpha, IL1-beta, IL-6), amines, and as yet unidentified factors emanating from stimulated macrophages and possibly reactive astrocytes. A final common pathway for neuronal susceptibility appears to be operative, similar to that observed in stroke and several neurodegenerative diseases. This mechanism involves excessive activation of N-methyl-D-aspartate (NMDA) receptor-operated channels, with resultant excessive influx of Ca2+ and the generation of free radicals, leading to neuronal damage. With the very recent development of clinically-tolerated NMDA antagonists, as discussed here, there is hope for future pharmacological intervention. C1 BETH ISRAEL HOSP,DEPT NEUROL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. RP Lipton, SA (reprint author), CHILDRENS HOSP,MOL & CELLULAR NEUROSCI LAB,ENDERS BLDG,SUITE 361,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 117 TC 77 Z9 79 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI ZURICH PA ISN JOURNAL PO BOX, CH-8033 ZURICH, SWITZERLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD OCT PY 1996 VL 6 IS 4 BP 507 EP 517 DI 10.1111/j.1750-3639.1996.tb00879.x PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA VQ897 UT WOS:A1996VQ89700014 PM 8944320 ER PT J AU Goff, BA Blake, J Bamberg, MP Hasan, T AF Goff, BA Blake, J Bamberg, MP Hasan, T TI Treatment of ovarian cancer with photodynamic therapy and immunoconjugates in a murine ovarian cancer model SO BRITISH JOURNAL OF CANCER LA English DT Article DE ovarian photodynamic therapy; OC125; photoimmunotherapy; immunoconjugate; chlorin ID MONOCLONAL-ANTIBODY; PHASE-I; CARCINOMA; TUMORS; PHOTOIMMUNOTHERAPY; RADIOIMMUNOTHERAPY; PHOTOSENSITIZERS; BIODISTRIBUTION; TOXICITY; ASCITES AB In photodynamic therapy (PDT), photosensitisers accumulate somewhat preferentially in malignant tissues; photoactivation with appropriate wavelength of light releases toxic molecular species which lead to tumour tissue death. In order to target ovarian cancer with increased specificity, a chlorin-based photosensitiser (chlorin e(6) monoethylendiamine monoamide) was conjugated to OC125. a monoclonal antibody recognising an antigen expressed in 80% of non-mucinous ovarian cancers. In previous work, this immunoconjugate (IC) was shown to be selectively phototoxic to cancer cells from ovarian cancer patients ex vivo and to localise preferentially in ovarian cancer tissue in vivo. In this study we report results from iii vivo phototoxicology and photodynamic treatment studies using this IC in a murine model for ovarian cancer. A comparison of single vs multiple treatments was also made. For in vivo experimentation. Balb C nude mice were injected with 30 x 10(6) NIH:OVCAR 3 cancer cells to create an ascitic tumour model. Animals were then given intraperitoneal injections of the immunoconjugate (0.5 mg kg(-1)). Twenty-four hours later the intraperitoneal surfaces were exposed to 656 nm light from an argon-ion pumped-dye laser (50 mW, 656 nm), using a cylindrical diffusing tip fibre. The overall treatment was given either once or multiply. No animals died from treatment complications. Twenty-four hours following one and three PDT treatments. the percentage of viable tumour cells in the ascites of the treated animals analysed ex who was 34% and 5% of control for one and three treatments respectively. With respect to survival, all control mice (n=18) died between 30 and 50 days. However, for those treated three times (n=10): 40% were still alive after 50 days, and for those treated four times (n=12) 58% were alive after 50 days. Evaluation with log-rank test revealed a significant survival with intraperitoneal PDT compared with controls (P=0.0006). These preliminary results suggest that PDT with an OC125 immunoconjugate may be an effective therapy for the management of advanced ovarian cancer. Clinical application of this therapy needs to be further optimised and may require multiple treatments, similar to fractionated radiation therapy and cyclic chemotherapy, in order to control malignant disease with acceptable toxicity to normal tissue. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED EEL224,BOSTON,MA 02114. HARVARD UNIV,SCH MED,VINCENT MEM GYNECOL ONCOL DIV,MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 30 TC 65 Z9 68 U1 0 U2 6 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD OCT PY 1996 VL 74 IS 8 BP 1194 EP 1198 DI 10.1038/bjc.1996.516 PG 5 WC Oncology SC Oncology GA VM367 UT WOS:A1996VM36700007 PM 8883404 ER PT J AU Dellian, M Helmlinger, G Yuan, F Jain, RK AF Dellian, M Helmlinger, G Yuan, F Jain, RK TI Fluorescence ratio imaging of interstitial pH in solid tumours: Effect of glucose on spatial and temporal gradients SO BRITISH JOURNAL OF CANCER LA English DT Article DE interstitium; pH gradient; fluorescence ratio imaging ID MAGNETIC-RESONANCE SPECTROSCOPY; BLOOD-FLOW; NONINVASIVE MEASUREMENT; EXTRACELLULAR PH; SCID MICE; OXYGEN; TUMORS; TISSUES; INVIVO; MICROENVIRONMENT AB Tumour pH plays a significant role in cancer treatment. However, because of the limitations of the current measurement techniques, spatially and temporally resolved pH data, obtained non-invasively in solid rumours. are not available. Fluorescence ratio imaging microscopy (FRIM) has been used previously For noninvasive, dynamic evaluation of pH in neoplastic tissue in vivo (Martin GR, Jain RK 1994, Cancer Res., 54, 5670-5674). However, owing to problems associated with quantitative fluorescence in thick biological tissues, these studies were limited to thin (50 mu m) rumours. We, therefore, adapted the FRIM technique for pH determination in thick (approximate to 2 mm) solid rumours in vivo using a pinhole illumination-optical sectioning (PIOS) method. Results show that (1) steep interstitial pH gradients (5 mu m resolution), with different spatial patterns, exist between tumour blood vessels. (2) pH decreased by an average of 0.10 pH units over a distance of 40 mu m away from the blood Vessel wall, and by 0.33 pH units over a 70 mu m distance; (3) the maximum pH drop, defined as the pH difference between the intervessel midpoint and the vessel wall, was positively correlated with the intervessel distance; (4) 45 min following a systemic glucose injection (6 g kg(-1) i.v.), interstitial pH gradients were shifted to lower pH values by an average of 0.15 pH units, while the spatial gradient (slope) was maintained. when compared with preglucose values. This pH decrease was not accompanied by significant changes in local blood flow, pH gradients returned to near-baseline values 90 min after glucose injection; (5) interstitial tumour pH before hyperglycaemia. and the glucose-induced pH drop strongly depended on the local vessel density. and (6) sodium bicarbonate treatment. either acute (1 M, 0.119 ml h(-1) for 3 h i.v.) or chronic (1% in drinking water for 8 days), did not significantly change interstitial tumour pH. Modified FRIM may be combined with other optical methods (e.g. phosphorescence quenching) to evaluate non-invasively the spatial and temporal characteristics of extracellular pH, intracellular pH and pO(2) in solid tumours. This will offer unique information about tumour metabolism and its modification by treatment modalities used in different cancer therapies. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114. RI Yuan, Fan/A-1287-2011 FU NCI NIH HHS [R35-CA-56591] NR 40 TC 55 Z9 56 U1 1 U2 12 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD OCT PY 1996 VL 74 IS 8 BP 1206 EP 1215 DI 10.1038/bjc.1996.518 PG 10 WC Oncology SC Oncology GA VM367 UT WOS:A1996VM36700009 PM 8883406 ER PT J AU Gentili, A Masih, S Yao, L Seeger, LL AF Gentili, A Masih, S Yao, L Seeger, LL TI Foot axes and angles SO BRITISH JOURNAL OF RADIOLOGY LA English DT Review AB Using radiographs and diagrams, this article reviews the most commonly used axes and angles of the foot, including: longitudinal axis of the rearfoot, collum tall axis, talocalcaneal angle, cuboid abduction angle, longitudinal axis of the lesser tarsus, lesser tarsus angle, talonavicular angle, longitudinal axis of the metatarsus, forefoot adductus angle, metatarsus adductus angle, first intermetatarsal angle, hallux valgus angle, proximal and distal articular set angles, and hallux interphalangeal angle, plane of support, collum tall axis, talar declination angle, calcaneal inclination axis, lateral talocalcaneal angle, first metatarsal declination axis and calcaneal inclination angle. C1 UNIV CALIF LOS ANGELES,SCH MED,CTR HLTH SCI,DEPT RADIOL SCI,LOS ANGELES,CA 90095. RP Gentili, A (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. RI Gentili, Amilcare/G-1238-2013 OI Gentili, Amilcare/0000-0002-5623-7512 NR 5 TC 28 Z9 28 U1 0 U2 2 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON, ENGLAND W1N 4AT SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD OCT PY 1996 VL 69 IS 826 BP 968 EP 974 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VM782 UT WOS:A1996VM78200016 PM 9038535 ER PT J AU Nixon, AJ Schnitt, SJ Gelman, R Gage, I Bornstein, B Hetelekidis, S Recht, A Silver, B Harris, JR Connolly, JL AF Nixon, AJ Schnitt, SJ Gelman, R Gage, I Bornstein, B Hetelekidis, S Recht, A Silver, B Harris, JR Connolly, JL TI Relationship of tumor grade to other pathologic features and to treatment outcome of patients with early stage breast carcinoma treated with breast-conserving therapy SO CANCER LA English DT Article DE histologic grade; breast-conserving treatment; breast neoplasms; radiation therapy; local recurrence ID PRIMARY RADIATION-THERAPY; INSTITUT-GUSTAVE-ROUSSY; LYMPH-NODE METASTASIS; PROGNOSTIC FACTORS; LOCAL RECURRENCE; HISTOLOGIC GRADE; FOLLOW-UP; CANCER; RADIOTHERAPY; SURGERY AB BACKGROUND. Although histologic grade has previously been described as a predictor of distant failure, it is uncertain whether histologic grade should be used to decide which patients should undergo axillary lymph node dissection and whether grade should be considered as a selection factor for breast-conserving therapy. METHODS. The authors retrospectively analyzed data from 1081 patients with American Joint Committee on Cancer Stage I or II infiltrating ductal carcinoma treated with breast-conserving therapy at the Joint Center for Radiation Therapy between 1970 and 1986. All patients had pathology slides reviewed by one of two study pathologists. Using the Elston modification of the Bloom-Richardson grading system, patients were divided by histologic grade into 3 groups (219 with Grade I, 482 with Grade II, and 380 with Grade III). The median follow-up time for 716 survivors was 134 months. The incidence of various pathologic features was examined with respect to histologic grade. In addition, the 10-year crude rates of failure (by first site) were examined as they related to grade. A polychotomous logistic regression model was used to determine the effect of grade on local and distant failure. RESULTS. High grade tumors tended to be larger, to exhibit more mononuclear cellular reaction and necrosis, and were more likely to be estrogen receptor negative. Patients with high grade tumors were also younger than those with lower grade tumors. The incidence of an extensive intraductal component and lymphatic vessel invasion did not vary significantly by histologic grade. The incidence of pathologic lymph node metastases also did not vary by grade, even when stratified by tumor size. In both univariable and multivariable analyses, the 10-year crude rate of local recurrence was not related to histologic grade (P = 0.44). Distant recurrence rates, however, were significantly higher as grade increased (P = 0.002). CONCLUSIONS. Higher histologic grade predicted an increased incidence of distant recurrence, but not a greater likelihood of axillary lymph node metastases or local recurrence after breast-conserving therapy. The authors conclude that grade should not be used to make decisions regarding local management. (C) 1996 American Cancer Society. C1 BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP Nixon, AJ (reprint author), HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,DEPT RADIAT ONCOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 23 TC 42 Z9 43 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 OCT 1 PY 1996 VL 78 IS 7 BP 1426 EP 1431 DI 10.1002/(SICI)1097-0142(19961001)78:7<1426::AID-CNCR8>3.3.CO;2-L PG 6 WC Oncology SC Oncology GA VJ536 UT WOS:A1996VJ53600008 PM 8839547 ER PT J AU Teicher, BA Holden, SA Goff, DA Wright, JE Tretyakov, O Ayash, LJ AF Teicher, BA Holden, SA Goff, DA Wright, JE Tretyakov, O Ayash, LJ TI Antitumor efficacy and pharmacokinetic analysis of 4-hydroperoxycyclophosphamide in comparison with cyclophosphamide +/-hepatic enzyme effectors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE 4-hydroperoxycyclophosphamide; oxazaphosphorines; cytochrome P-450 inducers ID CELL SENSITIZER ETANIDAZOLE; PHASE-I; FLUOSOL-DA; MAMMARY-CARCINOMA; TUMOR OXYGENATION; CIMETIDINE; ENHANCEMENT; METABOLISM; MELPHALAN; CARBOGEN AB 4-Hydroperoxycyclophosphamide is an oxazaphosphorine which is readily converted without enzymatic involvement to 4-hydroxycyclophosphamide a key intermediate in the antitumor activity of this class of drugs. The efficacy of 4-hydroperoxycyclophosphamide as a systemically administered antitumor drug was examined in mice bearing EMT-6 mammary carcinoma and in rats bearing 13762 mammary carcinoma in comparison with other oxazaphosphorines. 4-Hydroperoxycyclophosphamide was a more potent tumor cell killing agent than cyclophosphamide or ifosfamide in animals bearing the EMT-6 tumor. There were no significant differences in the toxicity to bone marrow amongst the three oxazaphosphorines. 4-Hydroperoxycyclophosphamide (90 mg/kg) on days 7, 9 and 11 produced 11.5 days of tumor growth delay compared with 10.4 days and 7.1 days for cyclophosphamide (150 mg/kg) and ifosfamide (150 mg/kg) administered on the same schedule, respectively. 4-Hydroperoxycyclophosphamide was tolerated at 90 mg/kg daily for 5 days and at 75 mg/kg twice daily for 4 days producing tumor growth delays of 14.4 days and 16.6 days, respectively. In rats bearing 13762 tumors, 4-hydroperoxycyclophosphamide (90 mg/kg) on days 8, 10 and 12 produced a tumor growth delay of 14.5 days compared with 8.9 days for cyclophosphamide (100 mg/kg) administered on the same schedule. Treatment of 13762 tumor-bearing rats with phenobarbital, pentobarbital or etanidazole increased the tumor growth delay produced by cyclophosphamide while treatment with cimetidine decreased the tumor growth delay produced by cyclophosphamide but not significantly. Administration of 4-hydroperoxycyclophosphamide (90 mg/kg) produced blood concentrations of 4-hydroxycyclophosphamide three-fold higher than those produced by administration of cyclophosphamide (100 mg/kg) at 15 min after drug injection. Treatment with phenobarbital or pentobarbital increased 4-hydroxycyclophosphamide blood concentration while pretreatment with cimetidine decreased 4-hydroxycyclophosphamide blood concentration from cyclophosphamide. 4-Hydroperoxycyclophosphamide is an effective antitumor agent worthy of further investigation. RP Teicher, BA (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 41 TC 6 Z9 6 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD OCT PY 1996 VL 38 IS 6 BP 553 EP 560 DI 10.1007/s002800050526 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA VH541 UT WOS:A1996VH54100011 PM 8823498 ER PT J AU Clinton, SK Emenhiser, C Schwartz, SJ Bostwick, DG Williams, AW Moore, BJ Erdman, JW AF Clinton, SK Emenhiser, C Schwartz, SJ Bostwick, DG Williams, AW Moore, BJ Erdman, JW TI cis-trans lycopene isomers, carotenoids, and retinol in the human prostate SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SINGLET MOLECULAR-OXYGEN; DIETARY BETA-CAROTENE; VITAMIN-A; CANCER RISK; EPIDEMIOLOGIC EVIDENCE; GEOMETRICAL-ISOMERS; ALPHA-CAROTENE; HUMAN SERUM; ACID; PREVENTION AB An evaluation of the Health Professionals Follow-Up Study has detected a lower prostate cancer risk associated with the greater consumption of tomatoes and related food products, Tomatoes are the primary dietary source of lycopene, a non-provitamin A carotenoid with potent antioxidant activity, Our goal was to define the concentrations of lycopene, other carotenoids, and retinol in paired benign and malignant prostate tissue from 25 men, ages 53 to 74, undergoing prostatectomy for localized prostate cancer, The concentrations of specific carotenoids in the benign and malignant prostate tissue from the same subject are highly correlated, Lycopene and all-trans beta-carotene are the predominant carotenoids observed, with means +/- SE of 0.80 +/- 0.08 nmol/g and 0.54 +/- 0.09, respectively, Lycopene concentrations range from 0 to 2.58 nmol/g, and all-trans beta-carotene concentrations range from 0.09 to 1.70 nmol/g, The 9-cis beta-carotene isomer, alpha-carotene, lutein, alpha-cryptoxanthin, zeaxanthin, and beta-cryptoxanthin are consistently detectable in prostate tissue, No significant correlations between the concentration of lycopene and the concentrations of any other carotenoid are observed, In contrast, strong correlations between prostate beta-carotene and alpha-carotene are noted (correlation coefficient, 0.88; P < 0.0001), as are correlations between several other carotenoid pairs, which reflects their similar dietary origins, Mean vitamin A concentration in the prostate is 1.52 nmol/g, with a range of 0.71 to 3.30 nmol/g, We further evaluated tomato-based food products, serum, and prostate tissue for the presence of geometric lycopene isomers using high-performance liquid chromatography with a polymeric C-30 reversed phase column, All-trans lycopene accounts for 79 to 91% and cis lycopene isomers for 9 to 21% of total lycopene in tomatoes, tomato paste, and tomato soup, Lycopene concentrations in the serum of men range between 0.60 and 1.9 nmol/ml, with 27 to 42% all-trans lycopene and 58 to 73% cis-isomers distributed among 12 to 13 peaks, depending upon their chromatographic resolution, In striking contrast with foods, all-trans lycopene accounts for only 12 to 21% and cis isomers for 79 to 88% of total lycopene in benign or malignant prostate tissues, cis Isomers of lycopene within the prostate are distributed among 14 to 18 peaks, We conclude that a diverse array of carotenoids are found in the human prostate with significant intra-individual variation, The presence of lycopene in the prostate at concentrations that are biologically active in laboratory studies supports the hypothesis that lycopene may have direct effects within the prostate and contribute to the reduced prostate cancer risk associated with the consumption of tomato-based foods, The future identification and characterization of geometric lycopene isomers may lead to the development of novel agents for chemoprevention studies. C1 N CAROLINA STATE UNIV,COLL AGR & LIFE SCI,DEPT FOOD SCI,RALEIGH,NC 27695. MAYO CLIN,DEPT LAB MED & PATHOL,ROCHESTER,MN 55905. UNIV ILLINOIS,DEPT FOOD SCI,DIV NUTR SCI,URBANA,IL 61820. RP Clinton, SK (reprint author), HARVARD UNIV,DANA FARBER CANC INST,SCH MED,DANA BLDG,ROOM 1740,44 BINNEY ST,BOSTON,MA 02115, USA. OI Schwartz, Steven/0000-0002-1427-5780 FU NCI NIH HHS [KO7 CA01680] NR 80 TC 318 Z9 334 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 1996 VL 5 IS 10 BP 823 EP 833 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VM565 UT WOS:A1996VM56500009 PM 8896894 ER PT J AU Alpan, RS Zhang, M Pardee, AB AF Alpan, RS Zhang, M Pardee, AB TI Cell cycle-dependent expression of TAP1, TAP2, and HLA-B27 messenger RNAs in a human breast cancer cell line SO CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; CLASS-I MOLECULES; DIFFERENTIAL DISPLAY; ANTIGEN PRESENTATION; TUMOR; TRANSPORTER; PROTEASOME; INDUCTION; DEFICIENT; PROTEIN AB Tumor cells are generally poorly responsive to immunotherapy. The results presented here suggest that antigen presentation of somatic tumor cells may be diminished greatly in quiescence and may be determined in part by growth regulation. Peptides produced by proteasomes are transported into the endoplasmic reticulum by transporter proteins TAP-1 and TAP-2, where they bind and stabilize MHC class I molecules required for antigenic presentation on the cell surface, TAP-1 and TAP-2 mRNAs were undetectable in quiescent, serum-deprived human breast cancer cells (21PT). They appeared 10 h after serum induction, near the G(1)-S boundary. In contrast, HLA-B27 mRNA was biphasically up-regulated. These mRNAs were significantly down-regulated in most tissues that contain mainly terminally differentiated, nonproliferating cells. All of the investigated breast cancer cell lines showed lower expression levels of these mRNAs than did the corresponding normal cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC PHAMACOL,DIV CANC GENET,BOSTON,MA 02115. FU NIGMS NIH HHS [GM24571] NR 29 TC 24 Z9 25 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 OCT 1 PY 1996 VL 56 IS 19 BP 4358 EP 4361 PG 4 WC Oncology SC Oncology GA VK307 UT WOS:A1996VK30700016 PM 8813124 ER PT J AU Kazachkov, Y Khaoustov, V Yoffe, B Solomon, H Klintmalm, GBG Tabor, E AF Kazachkov, Y Khaoustov, V Yoffe, B Solomon, H Klintmalm, GBG Tabor, E TI P53 Abnormalities in hepatocellular carcinoma from United States patients: Analysis of all 11 exons SO CARCINOGENESIS LA English DT Article ID HEPATITIS-B VIRUS; NITRIC-OXIDE; CODON 249; GENE; MUTATION; DNA; ONCOGENES; CELLS AB Mutations of the tumor suppressor gene p53 have been found in hepatocellular carcinomas (HCCs) from many countries where HCC is common, but p53 mutations detected by direct sequencing in HCCs from the United States (where HCC is uncommon) have been reported only rarely. p53 Exons 1 to 11 were analyzed by polymerase chain reaction, single-strand conformation polymorphism analysis, and direct sequencing in HCCs from 12 patients from the United States and in adjacent non-tumorous liver from 10 of them, Abnormalities of the p53 gene were found in five of the 12 tumors, including mutations in exon 4 (one patient), exon 5 (one patient) and exon 8 (three patients). In all 12 tumors, a normal conformation of exon 7 was found; in five of these HCCs the absence of mutations was confirmed by direct sequencing, Thus, the mutations of p53 codon 249 that have frequently been found in HCCs from endemic areas apparently do not play a role in most HCCs in the United States, Since the mutations in codon 249 are thought to be due to aflatoxin ingestion, the data suggest that factors other than aflatoxin may be responsible for the p53 abnormalities in the patients from the USA. C1 US FDA,CTR BIOL EVALUAT & RES HFM310,ROCKVILLE,MD 20852. BAYLOR COLL MED,VA MED CTR,HOUSTON,TX 77030. BAYLOR UNIV,MED CTR,DALLAS,TX. NR 28 TC 25 Z9 26 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1996 VL 17 IS 10 BP 2207 EP 2212 DI 10.1093/carcin/17.10.2207 PG 6 WC Oncology SC Oncology GA VM805 UT WOS:A1996VM80500016 PM 8895490 ER PT J AU Tashkin, DP Kleerup, EC Koyal, SN Marques, JA Goldman, MD AF Tashkin, DP Kleerup, EC Koyal, SN Marques, JA Goldman, MD TI Acute effects of inhaled and IV cocaine on airway dynamics SO CHEST LA English DT Article DE airway resistance; bronchomotor tone; cocaine base; cocaine HCl ID PULMONARY COMPLICATIONS; CRACK; ABUSE; HUMANS; BASE; PYROLYSIS; LIDOCAINE; SMOKERS; ASTHMA AB Background: Wheezing has been reported by 32% of habitual smokers of crack cocaine, and several cases of crack-related acute exacerbations of asthma have been reported. Study objective: To compare the acute effects of physiologically active doses of smoked cocaine base and IV cocaine hydrochloride (HCl), a subphysiologic dose of cocaine base (smoked ''placebo''), and IV saline solution placebo on bronchomotor tone, subjective level of intoxication, and cardiovascular responses in healthy habitual crack users. Design: A single-blind crossover study in which the order of route of administration (inhaled vs IV) was random but placebo always preceded the active drug. Subjects: Fourteen healthy, nonasthmatic current crack-smoking subjects, 34 to 48, years of age, with a history of previous IV cocaine use (1 to 12 times per lifetime). Methods: Heart rate, BP, self-rated level of intoxication (scale of 0 to 10), and measurements of airway resistance (Raw) and specific airway conductance (SGaw) were recorded during separate sessions before and 3 to 5, 10, 15, and 30 min after administration of smoked cocaine base (38.5+/-2.3 [SEM] mg), smoked placebo (2.3+/-0.9 mg cocaine base), IV cocaine HCl (30.0+/-2.0 mg), and IV placebo (saline solution). Results: Both smoked active cocaine and IV cocaine HCl caused comparable, significant (p<0.05) peak levels of acute intoxication (6.7+/-0.7 and 7.3+/-0.8, respectively) and increases in heart rate from baseline (29.6+/-2.9% and 21.4+/-3.7%, respectively, at 5 min), However, only smoked active cocaine caused significant decreases from baseline in SGaw (25.4+/-6.3% at 5 min), in contrast to nonsignificant changes after IV cocaine HCl (5.6+/-7.0% increase) and smoked placebo (10.2+/-6.0% decrease). Conclusions: Smoked cocaine base, but not systemically administered cocaine HCl, causes acute bronchoconstriction that is probably mediated by local airway irritation and could account for reports of crack-induced wheezing and asthma attacks in nonasthmatic and asthmatic individuals, respectively. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Tashkin, DP (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,ROOM 32-176,CHS,10833 LE CONTE AVE,LOS ANGELES,CA 90024, USA. OI Marques, Agostinho/0000-0002-4227-2093 FU NIDA NIH HHS [R01 DA008254, R01 DA08254] NR 36 TC 28 Z9 30 U1 1 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD OCT PY 1996 VL 110 IS 4 BP 904 EP 910 DI 10.1378/chest.110.4.904 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA VN269 UT WOS:A1996VN26900012 PM 8874243 ER PT J AU Famularo, R Fenton, T Kinscherff, R Augustyn, M AF Famularo, R Fenton, T Kinscherff, R Augustyn, M TI Psychiatric comorbidity in childhood post traumatic stress disorder SO CHILD ABUSE & NEGLECT LA English DT Article DE child abuse and neglect; child maltreatment; post traumatic stress disorder (PTSD); the diagnostic interview for children and adolescents; suicide ID NATURAL DISASTER; COMBAT EXPOSURE; VETERANS; CHILDREN; MALTREATMENT; BEHAVIOR; VICTIMS AB Objective : The purpose of this study was to examine the psychiatric comorbidity between children presenting with Post Traumatic Stress Disorder (PTSD) and traumatized children not developing this disorder. Design: One-hundred and seventeen severely maltreated children were examined for evidence of PTSD. Analyses probed for diagnostic relationships between PTSD and other formal diagnoses on The Diagnostic Interview for Children and Adolescents, Revised Version (DICA-C-R). Participants: All children presented before a juvenile/family court due to severe child maltreatment and psychological trauma. These children had been ordered removed from parental custody due to the trauma suffered by the child. For the purposes of analyses, this entire group of maltreated and traumatized children were dichotomized into a PTSD group and a non PTSD group. Thirty-five percent (41 of 117) of the children met strict DICA criteria for PTSD. Measurements: The children were examined by means of a structured clinical interview, The Diagnostic Interview for Children and Adolescents, revised version (DICA-Child-R), along with a more general psychiatric interview. The DICA-Child-R responses provided the only determination of whether the children met formal PTSD criteria. Data gathering on the sample also included a comprehensive review of risk factors for the development of PTSD, including demographics, and type(s) of trauma suffered. Results: Findings revealed that the PTSD diagnosis was significantly correlated with: 1. Attention deficit hyperactivity disorder (ADHD) 2. Other anxiety disorders 3. Brief psychotic disorder or psychotic disorder NOS 4. The presence of suicidal ideation. 5. A trend toward mood disorders. There were no differences between the two samples on measures of age, race, and family income. Conclusions: Pediatric PTSD is a severe psychiatric disorder. In this study, PTSD was statistically related to other formal psychiatric diagnoses. The investigators attended to the issues relating to true comorbidity versus inaccuratediagnosis secondary to symptom overlap between different conditions. Applying strict criteria, the results suggest that the presence of PTSD in children confers a substantial likelihood of other formal diagnoses. Moreover, the symptom of suicidal ideation was overrepresented among PTSD subjects. Given these additional conditions, more extensive evaluation and specialized, multi-modal treatment should be considered in children presenting with PTSD. C1 FRANCISCAN CHILDRENS HOSP,DEPT PEDIAT,BOSTON,MA. BOSTON UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT CHILD PSYCHIAT,BOSTON,MA 02118. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT LAW & PSYCHIAT,BOSTON,MA 02114. BOSTON UNIV,BOSTON CITY HOSP,SCH MED,DEPT PEDIAT,DIV DEV & BEHAV PEDIAT,BOSTON,MA 02118. RP Famularo, R (reprint author), MASSACHUSSETTS DEPT MENTAL HLTH,BOSTON JUVENILE COURT CLIN,ROOM 210,NEW COURT HOUSE,BOSTON,MA 02108, USA. NR 31 TC 87 Z9 88 U1 4 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD OCT PY 1996 VL 20 IS 10 BP 953 EP 961 DI 10.1016/0145-2134(96)00084-1 PG 9 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA VH438 UT WOS:A1996VH43800007 PM 8902292 ER PT J AU Kang, JX Leaf, A AF Kang, JX Leaf, A TI Antiarrhythmic effects of polyunsaturated fatty acids - Recent studies SO CIRCULATION LA English DT Article ID RAT CARDIAC MYOCYTES; SMOOTH-MUSCLE CELLS; ARACHIDONIC-ACID; LONG-CHAIN; VENTRICULAR-FIBRILLATION; POTASSIUM CHANNELS; LOCAL-ANESTHETICS; SODIUM-CHANNELS; DIETARY-INTAKE; K+ CHANNELS C1 MASSACHUSETTS GEN HOSP, DEPT MED, BOSTON, MA 02114 USA. BROCKTON W ROXBURY VET AFFAIRS MED CTR, DEPT MED, BOSTON, MA USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. FU NIDDK NIH HHS [DK38165] NR 52 TC 158 Z9 166 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 1 PY 1996 VL 94 IS 7 BP 1774 EP 1780 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VJ979 UT WOS:A1996VJ97900043 PM 8840874 ER PT J AU Lipsky, BA Baker, CA AF Lipsky, BA Baker, CA TI Improving the appropriateness of vancomycin usage in a VA Medical Center. SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 0 Z9 0 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 OCT PY 1996 VL 23 IS 4 BP 40 EP 40 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VN246 UT WOS:A1996VN24600088 ER PT J AU Devincenzo, JP Montana, JB Murthy, GGK Skornik, WA Brain, JD Mciver, J AF Devincenzo, JP Montana, JB Murthy, GGK Skornik, WA Brain, JD Mciver, J TI Aerosolized respiratory syncytial virus (RSV) antibody treatment of RSV infected cotton rats. SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,BOSTON,MA 02115. MASSACHUSETTS BIOL LAB,BOSTON,MA. NR 0 TC 0 Z9 0 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 OCT PY 1996 VL 23 IS 4 BP 101 EP 101 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VN246 UT WOS:A1996VN24600148 ER PT J AU Hanlon, MM Dupuy, DE Keel, SB Gebhardt, MC AF Hanlon, MM Dupuy, DE Keel, SB Gebhardt, MC TI Symptomatic forearm mass in a 48-year-old man SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PAROSTEAL LIPOMA C1 MASSACHUSETTS GEN HOSP,ORTHOPEAD SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CONNECT TISSUE ONCOL CTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 10 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 1996 IS 331 BP 308 EP & PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA VP347 UT WOS:A1996VP34700043 PM 8895654 ER PT J AU Litz, BT Roemer, L AF Litz, BT Roemer, L TI Post-traumatic stress disorder: An overview SO CLINICAL PSYCHOLOGY & PSYCHOTHERAPY LA English DT Editorial Material ID VIETNAM COMBAT VETERANS; BORDERLINE PERSONALITY-DISORDER; GENERAL-POPULATION; URBAN-POPULATION; ASSAULT VICTIMS; NATIONAL SAMPLE; SOCIAL SUPPORT; YOUNG-ADULTS; SEXUAL ABUSE; RAPE VICTIMS AB This introductory paper for the Special Series on Post-traumatic Stress Disorder (PTSD) provides an overview of the psychological literature on chronic PTSD. We describe the symptoms of PTSD, the common associated features of the disorder, and common themes in the clinical presentation of traumatized individuals. Epidemiological studies are reviewed that reveal the widespread occurrence of potentially traumatizing events and the prevalence of PTSD among traumatized populations. We next provide an overview of psychological assessment procedures. This is followed by a description of three psychological theories of PTSD that have received a good deal of attention along with their implications for treatment. Two of the most widely applied treatments of PTSD are next reviewed in some detail: direct therapeutic exposure therapy and stress management approaches. Finally, we introduce the six papers that follow in the series in the context of a brief discussion of directions for future research in the field of chronic PTSD. C1 TUFTS UNIV,SCH MED,MEDFORD,MA 02155. RP Litz, BT (reprint author), BOSTON DEPT VET AFFAIRS MED CTR,NATL CTR PTSD 116B2,150 S HUNGTINGTON AVE,BOSTON,MA 02130, USA. OI Roemer, Lizabeth/0000-0002-2453-5435 NR 113 TC 10 Z9 11 U1 2 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1063-3995 J9 CLIN PSYCHOL PSYCHOT JI Clin. Psychol. Psychother. PD OCT PY 1996 VL 3 IS 3 BP 153 EP 168 PG 16 WC Psychology, Clinical SC Psychology GA VQ902 UT WOS:A1996VQ90200001 ER PT J AU Delmonice, FL Cosimi, AB AF Delmonice, FL Cosimi, AB TI Anti-CD4 monoclonal antibody therapy SO CLINICAL TRANSPLANTATION LA English DT Article DE monoclonal antibodies; anti-CD4; tolerance ID RENAL-ALLOGRAFT RECIPIENTS; T-CELLS; TRANSPLANTATION; REJECTION; INDUCTION; SUBSETS; ANTIGEN; CD4 AB Because they can be selected to target only cells which are crucial for rejection, monoclonal antibodies (mAbs) offer enormous potential for specific manipulation of the immune response. Interest in the clinical potential of anti-CD4 mAbs has been heightened by the demonstration, in experimental models, that such therapy can produce long-term donor-specific non-responsiveness. Early clinical trials using two murine anti-CD4 mAbs (BL4 and mT-151) were discouraging, with over 50% of recipients suffering early rejection episodes. Another murine preparation, OKT4A, was initially found to prolong allograft survival in non-human primates. Limited clinical trials revealed that this mAb was well tolerated, that most recipients produced an antimurine response, and that only 26% of patients suffered rejection episodes during the first 3 post-operative months. Another murine preparation, Max.16H5, has been reported to reverse late onset acute rejection episodes as effectively as, but more safely than, conventional immunosuppression. More recent interest has focused upon humanized recombinants of these earlier murine anti-CD4 preparations. cMT-412, has been studied in recipients of heart or heart-lung allografts. These patients were observed to have less frequent and markedly delayed rejection episodes, fewer infectious complications, and better overall survival than that observed in an ATG-treated control group. Further studies are thus being undertaken. A CDR grafted IgG4 preparation of OKT4A has also been studied. This molecule (OKTcdr4a) contains only 8% of the parent murine sequence while retaining the binding affinity of OKT4A for the human CD4 antigen. In a pilot trial, biopsy-proven reversible rejection episodes were observed in 2/11 (18%) of renal allograft recipients. There were no allograft failures and no antibody response to the mAb. These and other trials emphasize the intense interest in immunosuppressive regimens incorporating anti-CD4 mAbs as well as the difficulties encountered in defining optimal protocols. Nevertheless, the impressive results observed in rodent and non-human primate models suggest that these agents are likely to play an important role in future immunosuppressive protocols, particularly those designed to induce tolerance. RP Delmonice, FL (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT UNIT,BOSTON,MA 02114, USA. NR 20 TC 7 Z9 7 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD OCT PY 1996 VL 10 IS 5 BP 397 EP 403 PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA VR371 UT WOS:A1996VR37100001 PM 8930451 ER PT J AU Russotti, G Brieva, TA Toner, M Yarmush, ML AF Russotti, G Brieva, TA Toner, M Yarmush, ML TI Induction of tolerance to hypothermia by previous heat shock using human fibroblasts in culture SO CRYOBIOLOGY LA English DT Article ID CHINESE-HAMSTER CELLS; LIVER PRESERVATION; OVARY CELLS; UW SOLUTION; COLD DENATURATION; MAMMALIAN-CELLS; GENE-EXPRESSION; PROTEINS; THERMOTOLERANCE; HYPERTHERMIA AB The technique of organ preservation is limited by the amount of time which organs can be hypothermically stored. A potential method to effectively extend reliable storage limes involves the conditioning of cells to better withstand hypothermia by previous exposure to a less severe stress. Using human fibroblasts in culture, we have demonstrated that such an approach may be feasible. Subjecting human diploid IMR-90 fibroblasts to 5 h 42.5 degrees C heat shock was found to improve cell survival more than 10-fold to subsequent 4 degrees C hypothermic exposure. The prior heat shock resulted in the increased synthesis of heat shock proteins (HSPs), the absolute concentrations of which were measured by an assay which utilized sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting techniques. Both the degree of cold tolerance conferred upon IMR-90 cells and the levels of HSP70 and HSP27 were dependent upon initial heat shock duration. Induced cold tolerance was found to be reversible; longer recovery times at 37 degrees C following heat shock resulted in a loss of this cold-tolerant state as well as a disappearance of HSPs. The fact that the degree of cold tolerance and HSP concentrations showed similar trends with respect to both heat shock time at 42.5 degrees C and subsequent recovery time at 37 degrees C suggests that these proteins may be intimately involved in the induction of cold tolerance. (C) 1996 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,CTR ENGN & MED,BOSTON,MA 02114. RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114. SHRINERS BURNS INST,BOSTON,MA 02114. FU NIDDK NIH HHS [DK43371]; NIGMS NIH HHS [GM-08339] NR 59 TC 26 Z9 27 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 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD OCT PY 1996 VL 33 IS 5 BP 567 EP 580 DI 10.1006/cryo.1996.0060 PG 14 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA VQ074 UT WOS:A1996VQ07400009 PM 8893514 ER PT J AU Shuster, TA Martin, F Nagy, AK AF Shuster, TA Martin, F Nagy, AK TI Zinc causes an apparent increase in rhodopsin phosphorylation SO CURRENT EYE RESEARCH LA English DT Article DE rhodopsin; rhodopsin phosphorylation; zinc; rhodopsin kinase; rod outer segment; bovine (cattle) ID ROD OUTER SEGMENTS; PROTEIN-KINASE-C; LIGHT-DEPENDENT PHOSPHORYLATION; PHOTORECEPTOR MEMBRANES; DISK MEMBRANES; BINDING; DEPHOSPHORYLATION; COPPER AB Purpose. Rhodopsin is a zinc-binding protein. We investigated the effect of low concentrations of zinc on the initial phosphorylation of rhodopsin. Methods. Dark-adapted bovine rod outer segments (ROS) were incubated with (gamma(32)P)ATP and 5 mM magnesium in the presence and absence of micromolar amounts of zinc. The ROS were exposed to light to initiate phosphorylation under conditions which allow only limited initial phosphorylation. Results. We found that zinc enhanced the rhodopsin phosphorylation apparent on autoradiographies by several fold. Phosphorylation reactions conducted in the presence of potent phospho-opsin phosphatase inhibitors show a comparable zinc-enhanced phosphorylation of rhodopsin. Under our reaction conditions, ROS membranes also appear more red upon initial exposure to light when zinc is present. Conclusions. Zinc can increase initial rhodopsin phosphorylation, apparently acting at the substrate rhodopsin and not at relevant phosphatases or rhodopsin kinase. How zinc binding to rhodopsin might increase its ability to serve as a substrate for phosphorylation is under investigation. C1 UNIV CALIF LOS ANGELES,MED CTR,DEPT NEUROL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Shuster, TA (reprint author), CALIF STATE UNIV LONG BEACH,DEPT SCI BIOL,1250 BELLFLOWER BLVD,LONG BEACH,CA 90840, USA. FU NEI NIH HHS [R15 EY10612] NR 34 TC 16 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD OCT PY 1996 VL 15 IS 10 BP 1019 EP 1024 DI 10.3109/02713689609017650 PG 6 WC Ophthalmology SC Ophthalmology GA VL889 UT WOS:A1996VL88900005 PM 8921240 ER PT J AU Sachs, DH AF Sachs, DH TI Transplantation SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material RP Sachs, DH (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,MGH E,BLDG 149-9019,BOSTON,MA 02129, USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 1996 VL 8 IS 5 BP 671 EP 673 DI 10.1016/S0952-7915(96)80084-7 PG 3 WC Immunology SC Immunology GA VL883 UT WOS:A1996VL88300011 PM 8939733 ER PT J AU Auchincloss, H Sultan, H AF Auchincloss, H Sultan, H TI Antigen processing and presentation in transplantation SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID T-CELL RECOGNITION; SKIN-GRAFT REJECTION; HISTOCOMPATIBILITY COMPLEX PEPTIDES; LYMPHOCYTES IN-VIVO; II-DEFICIENT MICE; ALLOGRAFT-REJECTION; CARDIAC ALLOGRAFTS; PRESENTING CELLS; MHC ANTIGENS; MECHANISMS AB For many years the direct stimulation of T cells in response to donor MHC antigens expressed on donor antigen-presenting cells has been the focus of transplantation immunology. Indirect recognition in response to peptides of donor antigens presented by self MHC molecules on recipient antigen-presenting cells has not generally been considered an important feature of graft rejection. Recent evidence suggests that indirect responses may be more important than previously considered and the new emphasis on indirect pathways in allograft rejection has raised new issues, many of which are unresolved. RP Auchincloss, H (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG & TRANSPLANTAT,WHITE 510B,FRUIT ST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL 18646, HL 36372]; NIAID NIH HHS [AI-38397] NR 52 TC 95 Z9 97 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 1996 VL 8 IS 5 BP 681 EP 687 DI 10.1016/S0952-7915(96)80086-0 PG 7 WC Immunology SC Immunology GA VL883 UT WOS:A1996VL88300013 PM 8902394 ER PT J AU Sykes, M AF Sykes, M TI Chimerism and central tolerance SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID NONLETHAL PREPARATIVE REGIMEN; COLONY-STIMULATING FACTOR; ALLOGENEIC BONE-MARROW; MATURE T-CELLS; TRANSPLANTATION TOLERANCE; INTRATHYMIC INOCULATION; ALLOGRAFT TOLERANCE; PROGENITOR CELLS; MIXED CHIMERISM; CLONAL ANERGY AB With adequate depletion or inactivation of the pre-existing immune system and establishment of conditions permitting donor hematopoietic stem cell engraftment, a robust state of central deletional tolerance to allogeneic or xenogeneic donors can be induced. Advances have been made in the ability to achieve this permissive state without toxic, myeloablative conditioning, thus bringing this approach closer to clinical application. RP Sykes, M (reprint author), MASSACHUSETTS GEN HOSP EAST,TRANSPLANATAT BIOL RES CTR,BONE MARROW TRANSPLANTAT SECT,BOSTON,MA 02129, USA. NR 84 TC 75 Z9 75 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 1996 VL 8 IS 5 BP 694 EP 703 DI 10.1016/S0952-7915(96)80088-4 PG 10 WC Immunology SC Immunology GA VL883 UT WOS:A1996VL88300015 PM 8902396 ER PT J AU Sheng, M Kim, E AF Sheng, M Kim, E TI Ion channel associated proteins SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; HETEROMULTIMERIC K+ CHANNELS; BETA-SUBUNIT; GLYCINE RECEPTOR; SUBCELLULAR-LOCALIZATION; CENTRAL NEURONS; NMDA RECEPTOR; ACETYLCHOLINE-RECEPTOR; GLUTAMATE RECEPTORS; CALCIUM CHANNELS AB Neuronal ion channels are directly associated in vivo with a wide variety of proteins. New classes of channel-associated proteins have been identified recently, including the PSD-95/SAP90 family of channel-clustering molecules acid components of the synaptic vesicle release machinery. Recent findings suggest that non-pore-forming subunits of ion channels may also have cell biological functions independent of their effects on channel electrophysiological properties. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. RP Sheng, M (reprint author), HOWARD HUGHES MED INST,50 BLOSSOM ST,BOSTON,MA 02114, USA. RI Kim, Eunjoon/C-1566-2011 NR 63 TC 102 Z9 103 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD OCT PY 1996 VL 6 IS 5 BP 602 EP 608 DI 10.1016/S0959-4388(96)80091-2 PG 7 WC Neurosciences SC Neurosciences & Neurology GA VR586 UT WOS:A1996VR58600005 PM 8937823 ER PT J AU MacDonald, ME Gusella, JF AF MacDonald, ME Gusella, JF TI Huntington's disease: Translating a CAG repeat into a pathogenic mechanism SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID GENE HOMOLOG HDH; EMBRYONIC LETHALITY; PROTEIN; BRAIN; EXPRESSION; EXPANSION; INACTIVATION; LOCALIZATION; NEURONS; PRODUCT AB The specific pattern of neuronal cell death in Huntington's disease (HD) is triggered by an abnormal version of the huntingtin protein, which is produced by translation of the HD gene defect, an expanded CAG repeat in a novel 4p16.3 gene. The extended amino-terminal polyglutamine segment may act via the protein's inherent activity, increasing ii or decreasing it in a graded fashion, or, alternatively, it may confer the ability to interact with a completely different set of cellular pathways, focusing attention on the HD protein's normal and abnormal physiological functions. RP MacDonald, ME (reprint author), MASSACHUSETTS GEN HOSP EAST,MOL NEUROGENET UNIT,BLDG 149,ROOM 6115,CHARLESTOWN,MA 02129, USA. NR 45 TC 73 Z9 74 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD OCT PY 1996 VL 6 IS 5 BP 638 EP 643 DI 10.1016/S0959-4388(96)80097-3 PG 6 WC Neurosciences SC Neurosciences & Neurology GA VR586 UT WOS:A1996VR58600011 PM 8937828 ER PT J AU Beal, MF AF Beal, MF TI Mitochondria, free radicals, and neurodegeneration SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; SUPEROXIDE-DISMUTASE GENE; ALZHEIMERS-DISEASE; TRANSGENIC MICE; PROTEIN; DEGENERATION; NEUROTOXICITY; SPECTROSCOPY; ACTIVATION; IMPAIRMENT AB A central role for defective mitochondrial energy production, and the resulting increased levels of free radicals, in the pathogenesis of various neurodegenerative diseases is gaining increasing acceptance. Defects in energy metabolism may contribute to both excitotoxicity and oxidative damage. Evidence implicating energy defects in neurodegenerative diseases comes from similarities to known mitochondrial disorders, including delayed and variable age of onset, slow progression, and symmetric degeneration of circumscribed groups of neurons. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Beal, MF (reprint author), MASSACHUSETTS GEN HOSP,NEUROCHEM LAB,NEUROL SERV,WRN 408,32 FRUIT ST,BOSTON,MA 02114, USA. FU NIA NIH HHS [AG05134]; NINDS NIH HHS [NS16367, NS31579] NR 45 TC 327 Z9 341 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD OCT PY 1996 VL 6 IS 5 BP 661 EP 666 DI 10.1016/S0959-4388(96)80100-0 PG 6 WC Neurosciences SC Neurosciences & Neurology GA VR586 UT WOS:A1996VR58600014 PM 8937831 ER PT J AU Li, VW Baden, HP Kvedar, JC AF Li, VW Baden, HP Kvedar, JC TI Loose anagen syndrome and loose anagen hair SO DERMATOLOGIC CLINICS LA English DT Article ID HUMAN SKIN; FOLLICLE; EXPRESSION; EPIDERMIS; CELLS; BULGE AB Loose anagen syndrome, or loose anagen hair, is a recently described condition of unknown etiology that may be under-recognized. The typical patient is a child with sparse fine hair that can easily be pulled out. The diagnosis is confirmed by microscopic examination of firmly pulled hairs, many of which are in the anagen phase but lacking an inner and outer root sheath and demonstrating a ruffled cuticle. Some presentations of alopecia areata may be confused With this condition, but the pull test analysis serves to differentiate them. A variety of theories have been postulated to explain the pathophysiology of loose anagen syndrome. In some cases, there is an autosomal dominant pattern of inheritance. In most cases, this condition spontaneously improves with age. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT DERMATOL,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. NR 28 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 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD OCT PY 1996 VL 14 IS 4 BP 745 EP & DI 10.1016/S0733-8635(05)70401-0 PG 8 WC Dermatology SC Dermatology GA VJ549 UT WOS:A1996VJ54900021 PM 9238333 ER PT J AU Lei, H Oh, SP Okano, M Juttermann, R Goss, KA Jaenisch, R Li, E AF Lei, H Oh, SP Okano, M Juttermann, R Goss, KA Jaenisch, R Li, E TI De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells SO DEVELOPMENT LA English DT Article DE DNA ccytosine methyltransferase; de novo methylation; genomic imprinting; X-inactivation; gene targeting; embryonic stem cells ID DENOVO METHYLATION; RETROVIRAL GENOMES; XIST GENE; H19 GENE; EXPRESSION; BINDING; EMBRYOGENESIS; DOMAIN AB It has been a controversial issue as to how many DNA cytosine methyltransferase mammalian cells have and whether de novo methylation and maintenance methylation activities are encoded by a single gene or two different genes, To address these questions, we have generated a null mutation of the only known mammalian DNA methyltransferase gene through homologous recombination in mouse embryonic stem cells and found that the development of the homozygous embryos is arrested prior to the 8-somite stage, Surprisingly, the null mutant embryonic stem cells are viable and contain low but stable levels of methyl cytosine and methyltransferase activity, suggesting the existence of a second DNA methyltransferase in mammalian cells, Further studies indicate that de novo methylation activity is not impaired by the mutation as integrated provirus DNA in MoMuLV-infected homozygous embryonic stem cells become methylated at a similar rate as in wild-type cells. Differentiation of mutant cells results in further reduction of methyl cytosine levels, consistent with the de novo methylation activity being down regulated in differentiated cells, These results provide the first evidence that an independently encoded DNA methyltransferase is present in mammalian cells which is capable of de novo methylating cellular and viral DNA in vivo. C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. MIT,WHITEHEAD INST BIOMED RES,DEPT BIOL,CAMBRIDGE 02124,ENGLAND. FU NCI NIH HHS [R35-CA44339]; NICHD NIH HHS [F32 HD07945-01]; NIGMS NIH HHS [GM52106] NR 44 TC 517 Z9 531 U1 1 U2 9 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 OCT PY 1996 VL 122 IS 10 BP 3195 EP 3205 PG 11 WC Developmental Biology SC Developmental Biology GA VP653 UT WOS:A1996VP65300023 PM 8898232 ER PT J AU Frykberg, RG Veves, A AF Frykberg, RG Veves, A TI Diabetic foot infections SO DIABETES-METABOLISM REVIEWS LA English DT Article ID LOWER-EXTREMITY INFECTIONS; PERIPHERAL VASCULAR-DISEASE; SKIN-STRUCTURE INFECTIONS; DOUBLE-BLIND; NEUROPATHIC ULCERATION; GROWTH-FACTOR; OSTEOMYELITIS; MELLITUS; ULCERS; AMPUTATION RP Frykberg, RG (reprint author), HARVARD UNIV,SCH MED,DEACONESS JOSLIN FOOT CTR,1 DEACONESS RD,BOSTON,MA 02215, USA. NR 93 TC 24 Z9 26 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0742-4221 J9 DIABETES METAB REV JI Diabetes-Metab. Rev. PD OCT PY 1996 VL 12 IS 3 BP 255 EP 270 DI 10.1002/(SICI)1099-0895(199610)12:3<255::AID-DMR167>3.0.CO;2-8 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VW073 UT WOS:A1996VW07300006 PM 8959388 ER PT J AU Oishi, AJ Inoue, Y Souba, WW Sarr, MG AF Oishi, AJ Inoue, Y Souba, WW Sarr, MG TI Alterations in carrier-mediated glutamine transport after a model of canine jejunal autotransplantation SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE glutamine transport; small bowel transplantation; absorption; amino acid absorption; amino acid transport ID INTESTINAL TRANSPLANTATION; IN-VIVO; JEJUNOILEUM; ENDOTOXEMIA; SEPSIS AB The effects of small bowel transplantation (SBTx) on absorptive function are unknown. Preliminary experiments showed a decrease in absorption of glutamine. Our aim was to determine mechanisms of decreased ileal transport of glutamine utilizing a model of intestinal autotransplantation. Seven dogs were studied before and after a model of jejunoileal autotransplantation. In vivo absorption experiments were performed before and two and eight weeks postoperatively with an electrolyte solution containing glutamine (20 mM). In vitro glutamine transport was studied using brush-border membrane vesicles (BBMV) prepared from ileal mucosa obtained from six other dogs and compared to a controls. In vivo net absorptive flux of glutamine decreased at two weeks but returned toward baseline by eight weeks (P = 0.06). Transport of glutamine into BBMVs was decreased at two weeks and remained decreased at eight weeks. K-max(Na+), a measure of carrier affinity was unchanged but V-max(Na+), a function of the number of transporter was decreased at two and eight weeks. Glucose transport was unchanged. It is concluded that jejunoileal autotransplantation decreases ileal absorption of glutamine by a decrease in carrier-mediated transport of glutamine. C1 MAYO CLIN & MAYO FDN,GASTROENTEROL UNIT,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,DEPT SURG,ROCHESTER,MN 55905. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA. FU NCI NIH HHS [CA45327]; NIDDK NIH HHS [DK39337] NR 25 TC 16 Z9 16 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 1996 VL 41 IS 10 BP 1915 EP 1924 DI 10.1007/BF02093590 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VN432 UT WOS:A1996VN43200002 PM 8888701 ER PT J AU Sun, L Liu, AP Georgopoulos, K AF Sun, L Liu, AP Georgopoulos, K TI Zinc finger-mediated protein interactions modulate Ikaros activity, a molecular control of lymphocyte development SO EMBO JOURNAL LA English DT Article DE dimerization; dominant negative; Ikaros; lymphocyte proliferation; zinc finger ID DNA-BINDING PROTEINS; TRANSCRIPTION FACTOR; ACTIVATION DOMAINS; SELF-ASSOCIATION; GENE; RETINOBLASTOMA; DIMERIZATION; SP1; SPECIFICITY; RECOGNITION AB The Ikaros gene, an essential regulator of lymphocyte differentiation, encodes, by means of differential splicing, protein isoforms with a distinct number of kruppel-type zinc fingers organized in two domains, Deletion of the N-terminal zinc finger domain responsible for the sequence-specific DNA binding of the Ikaros proteins results in an early and complete arrest in lymphocyte development in homozygous mutant mice, In sharp contrast, heterozygotes reliably develop T cell leukemias and lymphomas, Here we show that the C-terminal zinc finger domain present in all of the Ikaros wild-type and mutant isoforms is responsible for their stable interactions off DNA and plays a pivotal role in determining their overall activity, Mutations in the C-terminal zinc fingers which ablate Ikaros protein interactions have a dramatic effect on the ability of these proteins to bind DNA and activate transcription, Therefore, interactions between Ikaros isoforms with an intact DNA binding domain are essential for their function, In contrast, interactions between isoforms with and without a DNA binding domain result in Ikaros complexes that do not bind DNA and, as a consequence, cannot activate transcription, Dominant-negative Ikaros isoforms are generated in smaller amounts by the wild-type Ikaros gene but are also produced exclusively by the N-terminally deleted Ikaros locus, Given these data, we propose that interactions between Ikaros isoforms are essential for normal progression through the lymphoid pathways, Mutations in the Ikaros gene that prevent Ikaros protein interactions or which change the relative ratio of DNA to non-DNA binding isoforms have profound effects in both lymphoid specification and homeostasis. RP Sun, L (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BLDG 149,13TH ST,CHARLESTOWN,MA 02129, USA. FU NIAID NIH HHS [R)1-AI33062 02] NR 34 TC 260 Z9 265 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 1 PY 1996 VL 15 IS 19 BP 5358 EP 5369 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VN178 UT WOS:A1996VN17800025 PM 8895580 ER PT J AU Shalev, A SiegristKaiser, CA Yen, PM Wahli, W Burger, AG Chin, WW Meier, CA AF Shalev, A SiegristKaiser, CA Yen, PM Wahli, W Burger, AG Chin, WW Meier, CA TI The peroxisome proliferator-activated receptor alpha is a phosphoprotein: Regulation by insulin. SO ENDOCRINOLOGY LA English DT Article ID STEROID-HORMONE RECEPTORS; RETINOID-X RECEPTOR; PHOSPHORYLATION; HETERODIMERS; LIGAND; GAMMA; J(2) AB Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily implicated in adipocyte differentiation The observations that PPAR alpha is a regulator of hepatic lipid metabolism and that the insulin-sensitizing thiazolidinediones are ligands for PPAR gamma suggest that cross-talk might exist between insulin signaling and PPAR activity, possibly through insulin-induced PPAR phosphorylation. Immunoprecipitation of endogenous PPAR alpha from primary rat adipocytes prelabeled with [P-32]-orthophosphate and pretreated for 2 h with vanadate and okadaic acid demonstrated for the first time that PPAR alpha is a phosphoprotein in vive. Treatment with insulin induced a time-dependent increase in PPAR phosphorylation showing a 3-fold increase after 30 min. Insulin also increased the phosphorylation of human PPAR alpha expressed in CV-1 cells. These changes in phosphorylation were paralleled by enhanced transcriptional activity of PPAR alpha and gamma. Transfection studies in CV-1 cells and HepG2 cells revealed a nearly 2-fold increase of PPAR activity in the presence of insulin. In contrast, insulin had no effect on the transcriptional activity of transfected thyroid hormone receptor in CV-1 cells, suggesting a PPAR-specific effect. Thus, insulin stimulates PPAR alpha phosphorylation and enhances the transcriptional activity of PPAR, suggesting that the transcriptional activity of this nuclear hormone receptor might be modulated by insulin-mediated phosphorylation. C1 HARVARD UNIV, DIV GENET,DEPT MED,MED SCH,BRIGHAM & WOMENS HOSP, BOSTON, MA 02115 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DIV ENDOCRINE, BOSTON, MA 02114 USA. UNIV HOSP GENEVA, UNITE THYROIDE, CH-1211 GENEVA, SWITZERLAND. UNIV HOSP GENEVA, DEPT MED, MED CLIN 2, CH-1211 GENEVA, SWITZERLAND. UNIV LAUSANNE, INST BIOL ANIM, CH-1015 LAUSANNE, SWITZERLAND. RI Wahli, Walter/B-1398-2009 OI Wahli, Walter/0000-0002-5966-9089 NR 17 TC 146 Z9 152 U1 0 U2 6 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 OCT PY 1996 VL 137 IS 10 BP 4499 EP 4502 DI 10.1210/en.137.10.4499 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VN288 UT WOS:A1996VN28800056 PM 8828512 ER PT J AU Reif, JS Hatch, MC Bracken, M Holmes, LB Schwetz, BA Singer, PC AF Reif, JS Hatch, MC Bracken, M Holmes, LB Schwetz, BA Singer, PC TI Reproductive and developmental effects of disinfection by-products in drinking water SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE birth defects; chlorination; drinking water; epidemiology; low birth weight; prematurity; reproduction; teratogens; trihalomethanes ID NEURAL-TUBE DEFECTS; PREGNANCY OUTCOMES; DELAYED CONCEPTION; TAP WATER; CONSUMPTION; ASSOCIATION; EXPOSURE; INFANTS AB Recent epidemiologic studies have reported associations between the consumption of chlorinated drinking water and reproductive and development effects. Here we review the available epidemiologic data, assess the hazard potential posed by exposure to disinfection by-products, identify critical data gaps, and offer recommendations for further research. The epidemiologic evidence supporting associations between exposure to water disinfection by-products (DBPs) and adverse pregnancy outcomes is sparse, and positive findings should be interpreted cautiously. The methods used during the early stages of research in this area have been diverse. Variability in exposure assessment and endpoints makes it difficult to synthesize or combine the available data. Exposure misclassification and unmeasured confounding may have lead to bias in risk estimation. Future studies of reproductive outcome and exposure to chlorinated water should use improved methods for exposure assessment to 1) assure selection of appropriate exposure markets, 2) assess seasonal and annual fluctuations in DBPs, 3) assess variability within the distribution system, and 4) assess exposure through multiple routes such as bathing and showering, as well as consumption. Population-based studies should be conducted to evaluate male and female fertility, conception delay, growth retardation, and specific birth defects. The reproductive and development effects of exposure to DBPs could be efficiently explored in ongoing investigations by incorporating valid exposure markers and relevant questionnaire information. Future studies should make use of naturally occurring variability in the concentrations of DBPs and may incorporate biomarkers of exposure and effect in their design. Epidemiologic investigations should be conducted in parallel with laboratory-based and animal studies in a coordinated, multidisciplinary approach. C1 COLORADO STATE UNIV,DEPT ENVIRONM HLTH,FT COLLINS,CO 80523. COLUMBIA UNIV,DIV EPIDEMIOL,NEW YORK,NY 10032. YALE UNIV,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. MASSACHUSETTS GEN HOSP,GENET & TERATOL UNIT,BOSTON,MA 02114. NIEHS,ENVIRONM TOXCIOL PROGRAM,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT ENVIRONM SCI & ENGN,CHAPEL HILL,NC 27599. NR 26 TC 64 Z9 64 U1 0 U2 6 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1996 VL 104 IS 10 BP 1056 EP 1061 DI 10.2307/3433117 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA VR978 UT WOS:A1996VR97800018 PM 8930546 ER PT J AU MeyerRosberg, K Scott, DR Rex, D Melchers, K Sachs, G AF MeyerRosberg, K Scott, DR Rex, D Melchers, K Sachs, G TI The effect of environmental pH on the proton motive force of Helicobacter pylori SO GASTROENTEROLOGY LA English DT Article ID HYDROGEN-ION CONCENTRATION; PEPTIC-ULCER DISEASE; ESCHERICHIA-COLI; CAMPYLOBACTER-PYLORI; GNOTOBIOTIC PIGLETS; MEMBRANE-VESICLES; ACID-SECRETION; MUCUS LAYER; UREASE; OMEPRAZOLE AB Background & Aims: Responses of the proton motive farce (the driving force for protons) in Helicobacter pylori to varying medium pH may explain gastric colonization. The aim of this study was to determine the effect of external pH (pH(out)) on the proton motive force, the sum of the pH gradient, and the potential difference across the bacterial membrane. Methods: Intracellular pH (pH(in)) was measured by bis-carboxyethyl-carboxyfluorescein fluorescence and transmembrane potential difference (PD) by fluorescent quenching of 3,3'-dipropyl thiadicarbocyanine iodide at differing pH(out) and was correlated with survival, Results: PD was -131 +/- 0.36 mV (n = 3), and pH(in) was about 8.4 at loading pH(out) 7.0. PD increased as pH(out) was increased from 4.0 to 8.0, giving a constant proton motive force of about -220 mV. Outside these limits, PD collapsed irreversibly to zero, Addition of 5 mmol/l urea to weak buffer at pH 3.0 or 3.5 prevented irreversible collapse of PD by elevation of pH(out) caused by NH3 production, Urea addition to weak buffer at pH 7.0 collapsed the PD as urease activity increased the pH(out) to about 8.4, Survival was also limited to this range of pH(out). Conclusions: H. pylori survives over the range of pH(out) where it maintains a proton motive force. The effect of urease activity on pH(out), while allowing gastric survival in acidic media, may limit survival in nonacidic media. C1 W LOS ANGELES VA MED CTR,DEPT PHYSIOL & MED,LOS ANGELES,CA 90073. BYK GULDEN LOMBERG GMBH,D-7750 CONSTANCE,GERMANY. FU NIDDK NIH HHS [DK40615, DK41301] NR 46 TC 136 Z9 136 U1 1 U2 10 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 OCT PY 1996 VL 111 IS 4 BP 886 EP 900 DI 10.1016/S0016-5085(96)70056-2 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL248 UT WOS:A1996VL24800005 PM 8831583 ER PT J AU Abboud, PAC Malet, PF Berlin, JA Staroscik, R Cabana, MD Clarke, JR Shea, JA Schwartz, JS Williams, SV AF Abboud, PAC Malet, PF Berlin, JA Staroscik, R Cabana, MD Clarke, JR Shea, JA Schwartz, JS Williams, SV TI Predictors of common bile duct stones prior to cholecystectomy: A meta-analysis SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID ENDOSCOPIC RETROGRADE CHOLANGIOGRAPHY; LAPAROSCOPIC CHOLECYSTECTOMY; OPERATIVE CHOLANGIOGRAPHY; INTRAOPERATIVE CHOLANGIOGRAPHY; DIAGNOSTIC-TEST; SELECTIVE CHOLANGIOGRAPHY; ELECTIVE CHOLECYSTECTOMY; ALKALINE-PHOSPHATASE; MANAGEMENT; CHOLEDOCHOLITHIASIS AB Background: The decision of whether or not to investigate for common bile duct stones before cholecystectomy utilizes clinical, laboratory, and radiologic information (indicators). There is tremendous individual variation among clinicians in the criteria used for making this decision. Our aim was to perform a meta-analysis of published data to estimate the performance characteristics of the most commonly used preoperative indicators of common bile duct stones. Methods: Using predetermined exclusion criteria, we selected articles from a MEDLINE search and bibliographic review. Weighted averages were used to determine summary sensitivity, specificity, and positive and negative likelihood ratios for each indicator for stones. Results: From 2221 citations identified, 22 studies met inclusion criteria. The 10 indicators examined were reported in a common fashion in three or more articles, and could be assessed preoperatively. Seven exhibited a specificity greater than 90%. Indicators with positive likelihood ratios of 10 or above were cholangitis, preoperative jaundice, and ultrasound evidence of common bile duct stones. Positive likelihood ratios for dilated common bile duct on ultrasound, hyperbilirubinemia, and jaundice ranged from almost 4 to almost 7, Elevated levels of alkaline phosphatase, pancreatitis, cholecystitis, and hyperamylasemia exhibited positive likelihood ratios of less than 3. Conclusions: This meta-analysis has identified indicators for duct stones and ranked them according to likelihood ratios. These findings can be applied as guidelines for whether to investigate for duct stones before cholecystectomy. C1 UNIV PENN,DIV GEN INTERNAL MED,PHILADELPHIA,PA 19104. UNIV PENN,DIV GASTROENTEROL,PHILADELPHIA,PA. UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. MED COLL PENN & HAHNEMANN UNIV,DEPT SURG,PHILADELPHIA,PA 19129. VET AFFAIRS MED CTR,PHILADELPHIA,PA. FU AHRQ HHS [HS06481] NR 75 TC 139 Z9 145 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 1996 VL 44 IS 4 BP 450 EP 457 DI 10.1016/S0016-5107(96)70098-6 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VN676 UT WOS:A1996VN67600017 PM 8905367 ER PT J AU Eckner, R Yao, TP Oldread, E Livingston, DM AF Eckner, R Yao, TP Oldread, E Livingston, DM TI Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation SO GENES & DEVELOPMENT LA English DT Article DE p300/CBP; myogenesis; B-cell differentiation ID HEAVY-CHAIN ENHANCER; CREATINE-KINASE GENE; 5 E1A PROTEINS; TRANSCRIPTION FACTOR; DNA-BINDING; MYOGENIC DIFFERENTIATION; SKELETAL-MUSCLE; NUCLEAR FACTOR; MYC HOMOLOGY; MYOD AB Differentiation of skeletal muscle cells and B lymphocytes is regulated by basic helix-loop-helix (bHLH) proteins. Both differentiation programs are inhibited by the adenovirus E1A oncoprotein. Analysis of E1A mutants has implicated two of its cellular-binding proteins, p300 and CBP, in controlling certain aspects of differentiation. We find that p300 can cooperate with tissue-specific bHLH proteins in activating target genes and requires only the bHLH domain of such proteins to stimulate E box-directed transcription. Importantly, the ability of bHLH proteins to activate transcription correlates with the presence of p300/CBP in E box-dependent DNA-binding complexes, because both phenomena require at least two adjacent E-box motifs. Microinjection of p300/CBP antibodies into myoblasts blocks terminal differentiation, cell fusion, and transcriptional activity of myogenic bHLH proteins. These results suggest that the function of p300/CBP is essential for the execution of key aspects of cellular differentiation. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 65 TC 302 Z9 302 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 OCT 1 PY 1996 VL 10 IS 19 BP 2478 EP 2490 DI 10.1101/gad.10.19.2478 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA VM254 UT WOS:A1996VM25400009 PM 8843199 ER PT J AU Duronio, RJ Brook, A Dyson, N OFarrell, PH AF Duronio, RJ Brook, A Dyson, N OFarrell, PH TI E2F-induced S phase requires cyclin E SO GENES & DEVELOPMENT LA English DT Article DE Drosophila; E2F; cyclin E; S phase; cell cycle ID TRANSCRIPTION FACTOR E2F; CELL-CYCLE; RETINOBLASTOMA PROTEIN; DROSOPHILA EMBRYOGENESIS; DNA-REPLICATION; SACCHAROMYCES-CEREVISIAE; GROWTH-REGULATION; GENE PROMOTER; DEVELOPMENTAL CONTROL; DEPENDENT KINASES AB Both the heterodimeric transcription factor, E2F, and the G(1) cyclin, cyclin E, are required for the G(1)-S transition at the start of the metazoan cell cycle. It has been established that cyclin E can act as an upstream activator of E2F. In addition to this action, we show here that cyclin E has an essential role in DNA replication distinct from activating E2F. We have created transgenic Drosophila capable of inducible, ectopic production of E2F activity. Simultaneous overexpression of both Drosophila E2F subunits, dE2F and dDP, in embryos stimulated the expression of multiple E2F-target genes including cycIin E, and also caused the initiation of S phase. Mutation of cycIin E prevented the initiation of S phase after overexpression of dE2E/dDP without affecting induction of target gene expression. Thus, E2F-directed transcription cannot bypass loss of cyclin E in Drosophila embryos. C1 MASSACHUSETTS GEN HOSP,CTR CANC,ONCOL MOL LAB,CHARLESTOWN,MA 02129. RP Duronio, RJ (reprint author), UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143, USA. OI O'Farrell, Patrick/0000-0003-0011-2734 FU NIGMS NIH HHS [R01 GM037193] NR 86 TC 93 Z9 93 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT 1 PY 1996 VL 10 IS 19 BP 2505 EP 2513 DI 10.1101/gad.10.19.2505 PG 9 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA VM254 UT WOS:A1996VM25400011 PM 8843201 ER PT J AU Haarer, BK Corbett, A Kweon, Y Petzold, AS Silver, P Brown, SS AF Haarer, BK Corbett, A Kweon, Y Petzold, AS Silver, P Brown, SS TI SEC3 mutations are synthetically lethal with profilin mutations and cause defects in diploid-specific bud-site selection SO GENETICS LA English DT Article ID YEAST SECRETORY PATHWAY; SACCHAROMYCES-CEREVISIAE; ACTIN CYTOSKELETON; CELL-CYCLE; IMMUNOFLUORESCENCE LOCALIZATION; INTERNALIZATION STEP; BUDDING PATTERN; GENE ENCODES; IDENTIFY 2; PROTEIN AB Replacement of the wild-type yeast profilin gene (PFY1) with a mutated form (pfy1-111) that has codon 72 changed to encode glutamate rather than arginine results in defects similar to, but less severe than, those that result from complete deletion of the profilin gene. We have used a colony color-sectoring assay to identify mutations that cause pfy1-111, but not wild-type, cells to be inviable. These profilin Synthetic lethal (psl) mutations result in various degrees of abnormal growth, morphology, and temperature sensitivity in PFY1 cells. We have examined psl1 strains in the most detail. interestingly, these strains display a diploid-specific defect in bud-site selection; haploid strains bud normally, while homozygous diploid strains show a dramatic increase in random budding. We discovered that PSL1 is the late secretory gene, SEC3, and have found that mutations in several other late secretory genes are also synthetically lethal with pfy1-111. Our results are likely to reflect an interdependence between the actin cytoskeleton and secretory processes in directing cell polarity and growth. Moreover, they indicate that the secretory pathway is especially crucial for maintaining budding polarity in diploids. C1 UNIV MICHIGAN, DEPT ANAT & CELL BIOL, ANN ARBOR, MI 48109 USA. UNIV TEXAS, INST MOL & CELLULAR BIOL, AUSTIN, TX 78712 USA. DANA FARBER CANC INST, BOSTON, MA 02115 USA. RP UNIV TEXAS, DEPT ZOOL, PATTERSON LABS 219, DIV BIOL SCI, AUSTIN, TX 78712 USA. FU NCRR NIH HHS [MO1 RR-00042] NR 55 TC 47 Z9 50 U1 0 U2 1 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD OCT PY 1996 VL 144 IS 2 BP 495 EP 510 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA VK261 UT WOS:A1996VK26100006 PM 8889515 ER PT J AU McHorney, CA AF McHorney, CA TI Measuring and monitoring general health status in elderly persons: Practical and methodological issues in using the SF-36 health survey SO GERONTOLOGIST LA English DT Article DE health status assessment; quality-of-life assessment; methodological considerations; practical considerations; SF-36 Survey ID SURVEY QUESTIONNAIRE; OLDER ADULTS; PHYSICAL FUNCTION; OUTCOME MEASURE; MEDICAL-CARE; ILL PATIENTS; DATA QUALITY; VALIDITY; RELIABILITY; POPULATION AB In the last eight years, there has been a notable increase in the number of gerontological studies that use traditional measures of functional status in tandem with generic health status measures. This article describes practical and methodological issues in using generic measures of health status with elderly persons. One of the generic instruments used to illustrate these issues is the SF-36 Health Survey. Selection of generic measures for use in gerontological research or cross-age life-course studies involves choosing the right horse for the right course, and multiple considerations must be weighed. Of equal importance to practical and psychometric considerations is the correspondence between the conceptual framework of the investigation and the conceptualization of health embodied in candidate measurement tools. C1 UNIV WISCONSIN, SCH MED, DEPT MED, MADISON, WI USA. UNIV WISCONSIN, SCH MED, DEPT PREVENT MED, MADISON, WI USA. RP McHorney, CA (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR, HLTH SERV RES & DEV PROGRAM, 2500 OVERLOOK TERRACE, MADISON, WI 53705 USA. NR 74 TC 129 Z9 130 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 1996 VL 36 IS 5 BP 571 EP 583 PG 13 WC Gerontology SC Geriatrics & Gerontology GA WE321 UT WOS:A1996WE32100003 PM 8942101 ER PT J AU Wiederschain, G Koul, O Bovin, N Nifantev, N McCluer, R AF Wiederschain, G Koul, O Bovin, N Nifantev, N McCluer, R TI Expression of alpha-L-fucosyltransferase, alpha-L-fucosidase and alpha/beta-D-galactosidases in developing rat brain SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DEPT BIOMED SCI,WALTHAM,MA 02254. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RUSSIAN ACAD SCI,INST BIOORGAN CHEM,MOSCOW 117901,RUSSIA. RUSSIAN ACAD SCI,ND ZELINSKII ORGAN CHEM INST,MOSCOW 117901,RUSSIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1996 VL 6 IS 7 BP 1111 EP 1111 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT565 UT WOS:A1996VT56500179 ER PT J AU SajdelSulkowska, EM Chou, D McCluer, RH AF SajdelSulkowska, EM Chou, D McCluer, RH TI alpha 1,3-fucosyltransferase expression in rat cerebellar astrocytes and granule cells. SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DEPT BIOMED SCI,WALTHAM,MA 02254. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1996 VL 6 IS 7 BP 1113 EP 1113 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT565 UT WOS:A1996VT56500182 ER PT J AU Pouyani, T Seed, B AF Pouyani, T Seed, B TI Structural and functional studies of P-selectin/ligand interactions SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1996 VL 6 IS 7 BP 1203 EP 1203 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT565 UT WOS:A1996VT56500190 ER PT J AU Cannistra, SA Swanson, L Strobel, T AF Cannistra, SA Swanson, L Strobel, T TI In vivo inhibition of CD44 prevents peritoneal implantation of ovarian cancer cells. SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1996 VL 6 IS 7 BP K4 EP K4 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT565 UT WOS:A1996VT56500067 ER PT J AU Kasper, DL Finberg, RW Tzianabos, AO AF Kasper, DL Finberg, RW Tzianabos, AO TI Polysaccharides modulate T cell-dependent control of abscess induction SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,DANA FARBER CANC INST,DIV INFECT DIS,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1996 VL 6 IS 7 BP L3 EP L3 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT565 UT WOS:A1996VT56500071 ER PT J AU Schorge, JO Molpus, KL Goodman, A Nikrui, N Fuller, AF AF Schorge, JO Molpus, KL Goodman, A Nikrui, N Fuller, AF TI The effect of postsurgical therapy on stage III endometrial carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article ID PARAAORTIC LYMPHADENECTOMY; CYCLOPHOSPHAMIDE PAC; PROGNOSTIC FACTORS; RADIATION-THERAPY; UTERINE CORPUS; RISK-FACTORS; DOXORUBICIN; CANCER; ADENOCARCINOMA; CISPLATIN AB The records of 86 pathologic stage III endometrial carcinoma patients treated at Massachusetts General Hospital between 1974 and 1992 were retrospectively reviewed to identify predictors of poor outcome and to determine the effect of postsurgical therapy on recurrence and survival, Patients underwent TAH/BSO with selective lymphadenectomy and peritoneal washings, Cases prior to 1988 were retrospectively restaged using the FIGO surgical staging criteria, Postoperatively, patients received individualized regimens of EBRT (external beam radiotherapy), brachytherapy, and cytotoxic or hormonal chemotherapy, The 5-year survival and 5-year disease-free survival (DFS) for all patients were 54 and 44%, respectively, Forty-two percent of stage IIIA/B patients recurred in a median time of 14 months, Fifty-four percent of stage IIIC patients recurred in a median time of 16 months, Of patients who recurred, 90% stage IIIA/B and 71% stage IIIC patients recurred at extrapelvic sites, Age greater than 70, high-grade lesions, and fallopian tube metastases were predictive of poor outcome in stage IIIA/B by multivariate analysis, Vascular invasion was the only poor prognostic factor identified by multivariate analysis in stage IIIC disease. No benefit from pelvic EBRT in stage IIIA/B could be identified, Stage IIIC patients had increased DFS and a trend for increased survival with pelvic EBRT. Chemotherapy did not improve survival in either group. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,VINCENT MEM GYNCOL ONCOL SERV,BOSTON,MA 02114. NR 28 TC 56 Z9 58 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 1996 VL 63 IS 1 BP 34 EP 39 DI 10.1006/gyno.1996.0274 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA VP424 UT WOS:A1996VP42400008 PM 8898165 ER PT J AU Janco, RL Maclean, WE Perrin, JM Gortmaker, SL AF Janco, RL Maclean, WE Perrin, JM Gortmaker, SL TI A prospective study of patterns of bleeding in boys with haemophilia SO HAEMOPHILIA LA English DT Article DE haemarthrosis; patterns; prospective; joints; trauma ID HEMOPHILIA AB To describe the patterns of bleeding and clotting factor concentrate use in boys with haemophilia over a 6-month period, daily diary records of bleeding, factor use, levels of physical activity, chore performance and school attendance were collected from parents of 96 males between 4 and 17 rears of age with haemophilia A or B followed at six comprehensive haemophilia treatment centres in Massachusetts, Rhode Island and Tennessee. 14 243 person days were available for analysis. The sample cohort averaged approximately nine bleeding episodes (1.5 per months), almost two-thirds of which were haemarthroses. 44% of bleeds were associated with injury and the average duration was 1.4 days. New bleeding episodes were significantly more likely to begin on weekdays (Monday-Thursday) than on weekends (Friday-Sunday). Boys with more severe disease had significantly more bleeding episodes and a higher frequency of haemarthroses. Boys with the most severe disease were also more likely to have joints involved when they bled and to have more spontaneous bleedings without apparent preceding trauma. Bleeding was associated with increased school absence, decreased levels of physical activity and decreased rates of household task performance. Relatively high rates of bleeding associated with trauma suggest the need for preventive interventions. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CHILDRENS SERV,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT BEHAV SCI,BOSTON,MA 02115. RP Janco, RL (reprint author), VANDERBILT UNIV,SCH MED,DEPT PEDIAT,2220 PIERCE AVE,517 MRB2,NASHVILLE,TN 37232, USA. RI MacLean, William/H-1387-2013 NR 9 TC 8 Z9 8 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD OCT PY 1996 VL 2 IS 4 BP 202 EP 206 DI 10.1111/j.1365-2516.1996.tb00137.x PG 5 WC Hematology SC Hematology GA VR409 UT WOS:A1996VR40900004 PM 27214357 ER PT J AU Shekelle, PG Schriger, DL AF Shekelle, PG Schriger, DL TI Evaluating the use of the appropriateness method in the agency for health care policy and research clinical practice guideline development process SO HEALTH SERVICES RESEARCH LA English DT Article DE practice guidelines; appropriateness; group process AB Objective. To assess the feasibility of the appropriateness method in the Agency for Health Care Policy and Research (AHCPR) Clinical Practice Guideline Development process, and to compare the results of the appropriateness method with those obtained using evidence tables and an informal consensus method. Setting. AHCPR Low Back Problems Clinical Practice Guideline. Design. Two different group process methods with the same panel of experts were used in observational comparison of results of and satisfaction with guideline development. Data Collection. Practice guideline statements were created for topics using the conventional AHCPR method; then six months later new guideline statements for four topics were created using the appropriateness method. Panelist satisfaction with each process and resulting set of guideline statements was assessed. Principal Findings. Results of the appropriateness method for TENS, discography, and traction showed no disagreement among panel members and no appropriate indications for their use in the patient scenarios considered. These results are qualitatively similar to the guideline statements produced using evidence tables and informal consensus. Clinical practice guideline statements about electro-diagnostics created from appropriateness ratings were much more clinically specific than those created using evidence tables and informal consensus. Neither informal consensus building nor the appropriateness method was clearly preferred by a majority of panelists. Conclusions. It is feasible to use the appropriateness method in the AHCPR Clinical Practice Guideline Development process, and in some instances it produces more clinically specific guideline statements than does informal consensus. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,EMERGENCY CTR,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. RP Shekelle, PG (reprint author), RAND CORP,1700 MAIN ST,POB 2138,SANTA MONICA,CA 90407, USA. OI Schriger, David/0000-0003-0242-1127 NR 11 TC 25 Z9 26 U1 0 U2 0 PU HEALTH ADMINISTRATION PRESS PI MELROSE PARK PA C/O FOUNDATION AMER COLL HEALTHCARE EXECUTIVES 1951 CORNELL AVE, MELROSE PARK, IL 60160 SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 1996 VL 31 IS 4 BP 453 EP 468 PG 16 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA VN722 UT WOS:A1996VN72200005 PM 8885858 ER PT J AU Scadden, DT AF Scadden, DT TI Hematologic disorders and growth factor support in HIV infection SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; COLONY-STIMULATING FACTOR; THROMBOTIC THROMBOCYTOPENIC PURPURA; IMMUNE-DEFICIENCY-SYNDROME; RECOMBINANT-HUMAN-ERYTHROPOIETIN; AIDS-RELATED COMPLEX; HEMATOPOIETIC PROGENITOR CELLS; BONE-MARROW EXAMINATION; NON-HODGKINS-LYMPHOMA; PROTEIN-S DEFICIENCY AB During the course of HIV disease a broad spectrum of hematologic disorders develop including abnormalities in blood cell generation, survival, and function. Alterations in coagulation parameters may evolve associated with disruption of immunoglobulin or factor production. This article reviews the manifestations and pathophysiology of these abnormalities and discusses the role for growth factor support. C1 HARVARD UNIV, SCH MED, DEPT MED, CAMBRIDGE, MA 02138 USA. RP Scadden, DT (reprint author), MASSACHUSETTS GEN HOSP, 13TH ST, CNY7, ROOM 7214, BLDG 149, BOSTON, MA 02129 USA. NR 100 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 1996 VL 10 IS 5 BP 1149 EP + DI 10.1016/S0889-8588(05)70390-7 PG 0 WC Oncology; Hematology SC Oncology; Hematology GA VG731 UT WOS:A1996VG73100012 PM 8880202 ER PT J AU Bucher, NLR StieglitzJoseph, K Radner, B Franco, E Boyce, FM AF Bucher, NLR StieglitzJoseph, K Radner, B Franco, E Boyce, FM TI Efficient of gene transfer by a baculovirus vector into primary cultures of adult rat hepatocytes depends on their proliferative state. SO HEPATOLOGY LA English DT Meeting Abstract C1 BOSTON UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 38 EP 38 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500039 ER PT J AU Perrillo, R Rakela, J Martin, P Levy, G Schiff, E Wright, T Dienstag, J Gish, R Villeneuve, J Caldwell, S Brown, N Self, P AF Perrillo, R Rakela, J Martin, P Levy, G Schiff, E Wright, T Dienstag, J Gish, R Villeneuve, J Caldwell, S Brown, N Self, P TI Lamivudine for hepatitis B after liver transplantation (OLT). SO HEPATOLOGY LA English DT Meeting Abstract C1 ALTON OCHSNER MED FDN & OCHSNER CLIN,NEW ORLEANS,LA 70121. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. TORONTO HOSP,TORONTO,ON M5T 2S8,CANADA. UNIV MIAMI,CORAL GABLES,FL 33124. UCSF,SAN FRANCISCO,CA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CA PAC MED CTR,SAN FRANCISCO,CA. HOSP ST LUC,MONTREAL,PQ,CANADA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 223 EP 223 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500222 ER PT J AU Dienstag, JL Schiff, ER Mitchell, M Gitlin, N Lissoos, T Condreay, L Garrett, L Rubin, M Brown, N AF Dienstag, JL Schiff, ER Mitchell, M Gitlin, N Lissoos, T Condreay, L Garrett, L Rubin, M Brown, N TI Extended lamivudine retreatment for chronic hepatitis B. SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV MIAMI,MIAMI,FL 33152. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. GREATER BALTIMORE MED CTR,BALTIMORE,MD. EMORY UNIV,ATLANTA,GA 30322. UNIV WASHINGTON,ST LOUIS,MO. GLAXO WELLCOME INC,RES TRIANGLE PK,NC 27709. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 245 EP 245 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500245 ER PT J AU Li, JS Tong, SP Wands, JR AF Li, JS Tong, SP Wands, JR TI A binding partner for duck hepatitis B virus pre-S protein with selective expression in viral infectible tissues. SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,MOL HEPATOL LAB,CTR CANC,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 381 EP 381 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500381 ER PT J AU Scaglioni, PP Melegari, MM Yoon, SK Wands, JR AF Scaglioni, PP Melegari, MM Yoon, SK Wands, JR TI Post-transcriptional regulation of HBV replication by the precore protein: Potential use as a novel antiviral agent. SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,MOL HEPATOL LAB,CTR CANC,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 383 EP 383 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500382 ER PT J AU Tsuji, N Dyson, MR Cuervo, JH Abedi, JK Murray, K Takahashi, H AF Tsuji, N Dyson, MR Cuervo, JH Abedi, JK Murray, K Takahashi, H TI Inhibition of hepatitis B virus production in transfected hepatoma cells. SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV EDINBURGH,INST CELL & MOL BIOL,EDINBURGH,MIDLOTHIAN,SCOTLAND. BIOGEN INC,CAMBRIDGE,MA 02142. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 385 EP 385 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500385 ER PT J AU Eto, T Takahashi, H AF Eto, T Takahashi, H TI Amplified antiviral effect against hepatitis B virus by targeted interferon beta with asialoglycoprotein moiety. SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 390 EP 390 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500391 ER EF