FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Begum, NA Coker, A Shibuta, K Swanson, RS Chen, LB Mori, M Barnard, GF AF Begum, NA Coker, A Shibuta, K Swanson, RS Chen, LB Mori, M Barnard, GF TI Loss of hIRH mRNA expression from premalignant adenomas and malignant cell lines SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MESSENGER-RNA; HEPATOCELLULAR-CARCINOMA; DIFFERENTIAL DISPLAY; MOLECULAR-CLONING; GENE-EXPRESSION; COLON-CARCINOMA; INTERLEUKIN-8 AB We recently isolated from differential displays and subsequently cloned a human alpha-intercrine (hIRH) whose mRNA is reduced in human hepatocellular carcinomas. We now report that on Northern blots its mRNA is absent from premalignant colonic adenomas and from all of 27 human malignant cell lints (including breast, cervix, colon, duodenal, gastric, leukemia, liver, lung, melanoma, and pancreatic lines). hIRH mRNA was present in most normal human and mouse tissues and fibroblast derived cell lines but absent from leukocytes and brain. Two mRNA signals, at similar to 2 Kb and similar to 3.5 Kb, had variation in signal strength or size between tissues and species. (C) 1996 Academic Press. C1 UNIV MASSACHUSETTS,MED CTR,DEPT MED,WORCESTER,MA 01655. UNIV MASSACHUSETTS,MED CTR,DEPT SURG,WORCESTER,MA 01655. KYUSHU UNIV,MED INST BIOREGULAT,BEPPU,OITA,JAPAN. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02138. RI Mori, Masaki/A-4501-2011 NR 17 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 24 PY 1996 VL 229 IS 3 BP 864 EP 868 DI 10.1006/bbrc.1996.1893 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WA822 UT WOS:A1996WA82200028 PM 8954985 ER PT J AU Lin, LF Oeun, S Houng, A Reed, GL AF Lin, LF Oeun, S Houng, A Reed, GL TI Mutation of lysines in a plasminogen binding region of streptokinase identifies residues important for generating a functional activator complex SO BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 68th Annual Meeting of the American-Heart-Association CY NOV 13-16, 1995 CL ANAHEIM, CA SP Amer Heart Assoc ID MONOCLONAL-ANTIBODY; MECHANISM; FRAGMENTS; PROTEINS; SYSTEMS; SITE; DNA AB Through a unique but poorly understood mechanism, streptokinase (SK) interacts with human plasminogen to generate an ''activator complex'' that efficiently cleaves substrate plasminogen molecules. Previous studies have suggested that lysine residues in SK may play a role in the binding and function of the activator complex. To investigate this hypothesis, 10 different lysine residues in the plasminogen binding region of SK were altered to construct 8 recombinant (r) SK mutants. Only one double mutant, rSK(K256,257A) (replacing Lys with Ala at residues 256 and 257), showed a statistically significant reduction (63%) in binding affinity for Glu-plasminogen. This mutant also displayed a lagtime in the appearance of maximal activity, and modest impairments (2-5-fold) in kinetic parameters for amidolytic and plasminogen activator activity compared to rSK. In contrast, another mutant, rSK(K332,334A), formed an activator complex with profound and nearly selective defects in the catalytic processing of substrate plasminogen molecules. When compared to rSK in kinetic assays of plasminogen activation, the rSK(K332,334A) mutant formed an activator complex that bound substrate plasminogens normally (normal K-m), but its ability to activate or cleave these molecules (k(cat)) was reduced by 34-fold. In contrast, in amidolytic assays, the kinetic parameters of rSK(K332,334A) showed only minor differences (< 2-fold) from rSK. Similarly, the binding affinity of this mutant to human Glu-plasminogen was indistinguishable from rSK [(2.6 +/- 0.8) x 10(9) vs (2.4 +/- 0.2) x 10(9) M(-1), respectively]. In summary, these experiments have identified lysine residues in a plasminogen binding region of SK which appear to be necessary for normal high-affinity binding to plasminogen, and for the efficient catalytic processing of substrate plasminogen molecules by the activator complex. C1 HARVARD UNIV,SCH PUBL HLTH,CARDIOVASC BIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-02348] NR 37 TC 27 Z9 28 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 24 PY 1996 VL 35 IS 51 BP 16879 EP 16885 DI 10.1021/bi961531w PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA602 UT WOS:A1996WA60200057 PM 8988027 ER PT J AU Cheatham, B Volchuk, A Kahn, CR Wang, L Rhodes, CJ Klip, A AF Cheatham, B Volchuk, A Kahn, CR Wang, L Rhodes, CJ Klip, A TI Insulin-stimulated translocation of GLUT4 glucose transporters requires SNARE-complex proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RAT SKELETAL-MUSCLE; 3T3-L1 ADIPOCYTES; TETANUS-TOXIN; BOTULINAL NEUROTOXINS; CONTAINING VESICLES; CELL-SURFACE; MEMBRANE; CELLUBREVIN; FUSION; EXPRESSION AB A major physiological role of insulin is the regulation of glucose uptake Into skeletal and cardiac muscle and adipose tissue, mediated by an insulin-stimulated translocation of GLUT4 glucose transporters from an intracellular vesicular pool to the plasma membrane. This process is similar to the regulated docking and fusion of vesicles in neuroendocrine cells, a process that involves SNARE-complex proteins, Recently, several SNARE proteins were found in adipocytes: vesicle-associated membrane protein (VAMP-2), its related homologue cellubrevin, and syntaxin-4. In this report we show that treatment of permeabilized 3T3-L1 adipocytes with botulinum neurotoxin D, which selectively cleaves VAMP-2 and cellubrevin, inhibited the ability of insulin to stimulate translocation of GLUT4 vesicles to the plasma membrane, Furthermore, treatment of the permeabilized adipocytes with glutathione S-transferase fusion proteins encoding soluble forms of VAMP-2 or syntaxin-4 also effectively blocked insulin-regulated GLUT4 translocation, These results provide evidence of a functional role for SNARE-complex proteins in insulin-stimulated glucose uptake and suggest that adipocytes utilize a mechanism of regulating vesicle docking and fusion analogous to that found in neuroendocrine tissues. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. HOSP SICK CHILDREN,DIV CELL BIOL,TORONTO,ON M5G 1X8,CANADA. RP Cheatham, B (reprint author), JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK-33201, DK-47919, 5 P30 DK-36836, P30 DK036836, R01 DK033201, R01 DK047919] NR 32 TC 141 Z9 143 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 DEC 24 PY 1996 VL 93 IS 26 BP 15169 EP 15173 DI 10.1073/pnas.93.26.15169 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC204 UT WOS:A1996WC20400034 PM 8986782 ER PT J AU GrayBablin, J Zalvide, J Fox, MP Knickerbocker, CJ DeCaprio, JA Keyomarsi, K AF GrayBablin, J Zalvide, J Fox, MP Knickerbocker, CJ DeCaprio, JA Keyomarsi, K TI Cyclin E, a redundant cyclin in breast cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell cycle; retinoblastoma; p16; redundancy ID RETINOBLASTOMA-SUSCEPTIBILITY GENE; CELL-CYCLE; DEPENDENT KINASES; SUPPRESSOR GENES; EPITHELIAL-CELLS; PROTEIN; EXPRESSION; PRODUCT; P16(INK4); PROGRESSION AB Cyclin E is an important regulator of cell cycle progression that together with cyclin-dependent kinase (cdk) 2 is crucial for the G(1)/S transition during the mammalian cell cycle, Previously, we showed that severe overexpression of cyclin E protein in tumor cells and tissues results in the appearance of lower molecular weight isoforms of cyclin E, which together with cdk2 can form a kinase complex active throughout the cell cycle. In this study, we report that one of the substrates of this constitutively active cyclin E/cdk2 complex is retinoblastoma susceptibility gene product (pRb) in populations of breast cancer cells and tissues that also overexpress p16, In these tumor cells and tissues, we show that the expression of p16 and pRb is not mutually exclusive, Overexpression of p16 in these cells results in sequestering of cdk4 and cdk6, rendering cyclin D1/cdk complexes inactive, However, pRb appears to be phosphorylated throughout the cell cycle following an initial lag, revealing a time course similar to phosphorylation of glutathione S-transferase retinoblastoma by cyclin E immunoprecipitates prepared from these synchronized cells. Hence, cyclin E kinase complexes can function redundantly and replace the loss of cyclin D-dependent kinase complexes that functionally inactivate pRb. In addition, the constitutively overexpressed cyclin E is also the predominant cyclin found in p107/E2F complexes throughout the tumor, but not the normal, cell cycle. These observations suggest that overexpression of cyclin E in tumor cells, which also overexpress p16, can bypass the cyclin D/cdk4-cdk6/p16/pRb feedback loop, providing yet another mechanism by which tumors can gain a growth advantage. C1 NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,DIV MOL MED,LAB DIAGNOST ONCOL,ALBANY,NY 12201. DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA 02146. NR 58 TC 101 Z9 102 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 DEC 24 PY 1996 VL 93 IS 26 BP 15215 EP 15220 DI 10.1073/pnas.93.26.15215 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC204 UT WOS:A1996WC20400042 PM 8986790 ER PT J AU Kovacs, CS Lanske, B Hunzelman, JL Guo, J Karaplis, AC Kronenberg, HM AF Kovacs, CS Lanske, B Hunzelman, JL Guo, J Karaplis, AC Kronenberg, HM TI Parathyroid hormone-related peptide (PTHrP) regulates fetal-placental calcium transport through a receptor distinct from the PTH/PTHrP receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT 10th Congress of the International-Society-for-Endocrinology CY JUN 12-15, 1996 CL SAN FRANCISCO, CA SP Int Soc Endocrinol ID BASAL PLASMA-MEMBRANES; VITAMIN-D; SKELETAL DEVELOPMENT; MINERAL-CONTENT; MESSENGER-RNA; RAT PLACENTA; PROTEIN; EXPRESSION; MAGNESIUM; TROPHOBLAST AB To determine the role of PTHrP in fetal calcium metabolism, blood calcium was measured in mice homozygous (HOM) for deletion of the PTHrP gene. On day 18.5 of gestation, ionized calcium and the maternal-fetal calcium gradient were significantly reduced in HOM PTHrP-ablated fetuses compared with that of their littermates. To assess the placental contribution to the effect of PTHrP, Ca-45 and Cr-51-EDTA (as a blood diffusional marker) were administered by intracardiac injection to pregnant, heterozygous dams on day 17.5 of gestation, Five minutes after the injection, whole fetal Ca-45 accumulation was significantly decreased in HOM PTHrP-ablated fetuses compared with that of their littermates, Next, two fetuses from each litter were injected in utero with fragments of PTHrP, PTH, or diluent 1 h before administering Ca-45 and Cr-51 for the dam. PTHrP-(1-86) and PTHrP-(67-86) significantly increased relative Ca-45 accumulation in HOM PTHrP-ablated fetuses, but PTHrP(1-34), PTH-(1-84), and the diluent had no effect, Finally, similar studies were performed on fetal mice that lacked the PTH/PTHrP receptor gene, Ionized calcium was significantly reduced in HOM PTH/PTHrP receptor-ablated fetuses, However, 5 min after maternal injection of Ca-45 and Cr-51, relative accumulation of Ca-45 was significantly increased in these fetuses, It was concluded that PTHrP is an important regulator of fetal blood calcium and placental calcium transport, In addition, the bioactivity of PTHrP for placental calcium transport is specified by a mid-molecular region that does not use the PTH/PTHrP receptor. C1 MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. OI Kovacs, Christopher/0000-0002-5219-9993 FU NIDDK NIH HHS [DK 47038] NR 41 TC 155 Z9 159 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 DEC 24 PY 1996 VL 93 IS 26 BP 15233 EP 15238 DI 10.1073/pnas.93.26.15233 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC204 UT WOS:A1996WC20400045 PM 8986793 ER PT J AU Kim, SS Chen, YM OLeary, E Witzgall, R Vidal, M Bonventre, JV AF Kim, SS Chen, YM OLeary, E Witzgall, R Vidal, M Bonventre, JV TI A novel member of the RING finger family, KRIP-1, associates with the KRAB-A transcriptional repressor domain of zinc finger proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE transcription factors; Kid-1; ZNF2; coiled-coil motif; TIF1; PHD domain ID ACTIVATION; IDENTIFICATION; RECOGNITION; EXPRESSION; SUBFAMILY; YEAST; CELLS AB The Kruppel-associated box A (KRAB-A) domain is an evolutionarily conserved transcriptional repressor domain present in approximately one-third of zinc finger proteins of the Cys(2)-His(2) type. Using the yeast two-hybrid system, we report the isolation of a cDNA encoding a novel murine protein, KRAB-A interacting protein 1 (KRIP-1) that physically interacts with the KRAB-A region. KRIP-1 is a member of the RBCC subfamily of the RING finger, or Cys(3)HisCys(4), family of zinc binding proteins whose other members are known to play important roles in differentiation, oncogenesis, and signal transduction. The KRIP-1 protein has high homology to TIF1, a putative modulator of ligand-dependent activation function of nuclear receptors. A 3.5-kb mRNA for KRIP-1 is ubiquitously expressed among all adult mouse tissues studied. When a GAL4-KRIP-1 fusion protein is expressed in COS cells with a chloramphenicol acetyltransferase reporter construct with five GAL4 binding sites, there is dose-dependent repression of transcription. Thus, KRIP-1 interacts with the KRAB-A region of C2H2 zinc finger proteins and may mediate or modulate KRAB-A transcriptional repressor activity. C1 MASSACHUSETTS GEN HOSP,MED SERV,RENAL UNIT,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 39773, P01 DK038452, R37 DK039773, DK 38452, R01 DK039773]; NINDS NIH HHS [P50 NS010828, P01 NS010828, F32 NS010828, NS 10828] NR 31 TC 224 Z9 236 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 DEC 24 PY 1996 VL 93 IS 26 BP 15299 EP 15304 DI 10.1073/pnas.93.26.15299 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC204 UT WOS:A1996WC20400058 PM 8986806 ER PT J AU Leister, RT Ausubel, FM Katagiri, F AF Leister, RT Ausubel, FM Katagiri, F TI Molecular recognition of pathogen attack occurs inside of plant cells in plant disease resistance specified by the Arabidopsis genes RPS2 and RPM1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LEUCINE-RICH REPEATS; SYRINGAE PV GLYCINEA; AVIRULENCE GENES; IDENTIFICATION; THALIANA; EXPRESSION; SEQUENCES; SECRETION; HOMOLOGS; PROTEINS AB The Arabidopsis thaliana disease resistance genes RPS2 and RPM1 belong to a class of plant disease resistance genes that encode proteins that contain an N-terminal tripartite nucleotide binding site (NBS) and a C-terminal tandem array of leucine-rich repeats, RPS2 and RPM1 confer resistance to strains of the bacterial phytopathogen Pseudomonas syringae carrying the avirulence genes avl Rpt2 and avrB, respectively, in these gene-for-gene relationships, it has been proposed that pathogen avirulence genes generate specific ligands that are recognized by cognate receptors encoded by the corresponding plant resistance genes, To test this hypothesis, it is crucial to know the site of the potential molecular recognition. Mutational analysis of RPS2 protein and in vitro translation/translocation studies indicated that RPS2 protein is localized in the plant cytoplasm. To determine whether avirulence gene products themselves are the ligands for resistance proteins, we expressed the avrRpt2 and avrB genes directly in plant cells using a novel quantitative transient expression assay, and found that expression of avrRpt2 and avrB elicited a resistance response in plants carrying the corresponding resistance genes, This observation indicates that no bacterial factors other than the avirulence gene products are required for the specific resistance response as long as the avirulence gene products are correctly localized. We propose that molecular recognition of P. syringae in RPS2- and RPM1-specified resistance occurs inside of plant cells. C1 UNIV MARYLAND,DEPT SCI BIOL,BALTIMORE,MD 21250. MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. FU PHS HHS [48707] NR 33 TC 127 Z9 132 U1 1 U2 9 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 DEC 24 PY 1996 VL 93 IS 26 BP 15497 EP 15502 DI 10.1073/pnas.93.26.15497 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC204 UT WOS:A1996WC20400092 PM 8986840 ER PT J AU Biere, AL Ostaszewski, B Stimson, ER Hyman, BT Maggio, JE Selkoe, DJ AF Biere, AL Ostaszewski, B Stimson, ER Hyman, BT Maggio, JE Selkoe, DJ TI Amyloid beta-peptide is transported on lipoproteins and albumin in human plasma SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BLOOD-BRAIN-BARRIER; HUMAN APOLIPOPROTEIN-E; ISOFORM-SPECIFIC BINDING; ONSET ALZHEIMER-DISEASE; CEREBROSPINAL-FLUID; ENDOGENOUS ALBUMIN; PROTEIN-PRECURSOR; SENILE PLAQUES; SOLUBLE FORM; E GENOTYPE AB The amyloid beta-peptide (A beta) is the major constituent of neuritic plaques in Alzheimer's disease and occurs as a soluble 40-42-residue peptide in cerebrospinal fluid and blood of both normal and AD subjects. It is unclear whether A beta, once it is secreted by cells, remains free in biological fluids or is associated with other proteins and thus transported and metabolized with them. Such knowledge of the normal fate of A beta is a prerequisite for understanding the changes that may lead to the pathological aggregation of soluble A beta in vivo, the possible influence of certain extracellular proteins, particularly apolipoprotein E, on plaque formation, and the pharmacology of putative A beta-lowering drugs. To address the question of A beta distribution in human biological fluids, we incubated fresh human plasma from 38 subjects with physiological concentrations (0.5-0.7 nM) of radioiodinated A beta(1-40) and seven plasma samples with A beta(1-42). Lipoproteins and lipid-free proteins were separated and analyzed for bound iodinated A beta(1-40). We found that up to 5% of A beta added to plasma is bound to selected lipoproteins: very low density, low density, and high density, but not lipoprotein(a). The large majority (approximate to 89%), however, is bound to albumin, and very little A beta is free. A beta distribution in plasma was not significantly influenced by apolipoprotein E genotype. We conclude that A beta is normally bound to and transported by albumin and specific lipoproteins in human plasma under physiological conditions. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,CTR NEUROL DIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL49552]; NIA NIH HHS [AG12749] NR 69 TC 187 Z9 190 U1 1 U2 16 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 DEC 20 PY 1996 VL 271 IS 51 BP 32916 EP 32922 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VZ373 UT WOS:A1996VZ37300068 PM 8955133 ER PT J AU Moratalla, R Vallejo, M Elibol, B Graybiel, AM AF Moratalla, R Vallejo, M Elibol, B Graybiel, AM TI D1-class dopamine receptors influence cocaine-induced persistent expression of Fos-related proteins in striatum SO NEUROREPORT LA English DT Article DE behavioral sensitization; cocaine; dopamine receptors; Fra; Fos; FosB; immediate-early gene; JunB; striatum ID MESSENGER-RNA; C-FOS; DYNORPHIN EXPRESSION; RAT STRIATUM; INDUCTION; AMPHETAMINE; BRAIN; SENSITIZATION; GENE AB CHRONIC intermittent exposure to psychomotor stimulants induces in the striatum the expression of Fos-related proteins (Fras) that persist after the end of drug treatment. We carried out experiments to determine whether such Fras ('chronic Fras') require dopamine D1-class receptor function for their persistent expression in the striatum. We chronically administered cocaine to rats in a behavioral sensitization protocol and blocked D1-class receptors with SCH23390 before a final cocaine challenge. Western blotting and immunohistochemical analyses indicate that Fras persistently expressed in response to chronic treatment include proteins of two types: those that have become independent of D1-class dopamine receptor activation and those that remain dependent on D1-class receptors for their expression following drug challenge. C1 MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,REPROD ENDOCRINE UNIT,BOSTON,MA. HACETTEPE UNIV,TIP FAK,ANKARA,TURKEY. RI Moratalla, Rosario/H-9280-2015 OI Moratalla, Rosario/0000-0002-7623-8010 FU NIDA NIH HHS [5R01 DA08037] NR 21 TC 41 Z9 41 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 20 PY 1996 VL 8 IS 1 BP 1 EP 5 DI 10.1097/00001756-199612200-00001 PG 5 WC Neurosciences SC Neurosciences & Neurology GA WX339 UT WOS:A1996WX33900002 PM 9051741 ER PT J AU Maynard, KI Chen, D Arango, PM Ogilvy, CS AF Maynard, KI Chen, D Arango, PM Ogilvy, CS TI Nitric oxide produced during ischemia improves functional recovery in the rabbit retina SO NEUROREPORT LA English DT Article DE central nervous system; ischemia; neuroprotection; nitric oxide; retina ID FOCAL CEREBRAL-ISCHEMIA; SYNTHASE; INHIBITION; NEURONS; ENDOTHELIUM; ARGININE; CELLS; CGMP; CNS AB We examined the effect of modulating endogenous nitric oxide (NO) production on the recovery of neuronal in which blood temporary ischemia using a preparation is not a factor. Inhibition of function from tem nitric oxide synthase (NOS) during ischemia with L-NA (100 mu mol(-1)) resulted in worse functional recovery compared to D-NA (100 mu moll(-1))-treated control retinas (p<0.01). In contrast, addition of L-Arg (1000 mu mol(-1)) during ischemia, resulted in a concentration-dependent functional improvement (p<0.05). These results show that inhibition of constitutive NOS is detrimental, whilst the enhancement of endogenous NO a production improves the recovery of neuronal function during a period of temporary ischemia in the isolated retina, (an in vitro avascular model of the CNS). Thus, independent of its effects on the vasculature, NO production during temporary ischemia protects neurons from irreversible function damage. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Maynard, KI (reprint author), MASSACHUSETTS GEN HOSP,NEUROPHYSIOL LAB,NEUROSURG SERV,EDWARDS 414,32 FRUIT ST,BOSTON,MA 02114, USA. FU NINDS NIH HHS [NS-01732] NR 25 TC 17 Z9 18 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 20 PY 1996 VL 8 IS 1 BP 81 EP 85 DI 10.1097/00001756-199612200-00017 PG 5 WC Neurosciences SC Neurosciences & Neurology GA WX339 UT WOS:A1996WX33900018 PM 9051757 ER PT J AU Weaver, DR Reppert, SM AF Weaver, DR Reppert, SM TI The Mel(1a) melatonin receptor gene is expressed in human suprachiasmatic nuclei SO NEUROREPORT LA English DT Article DE circadian rhythms; melatonin; melatonin receptors; suprachiasmatic nucleus ID SYRIAN-HAMSTERS; BRAIN; ENTRAINMENT; RESPONSES; CLOCK AB THE pineal hormone melatonin influences circadian rhythmicity in many vertebrate species. The circadian effects of melatonin in humans have led to its use to treat jet lag and circadian-based sleep disorders. Melatonin is thought to influence circadian rhythmicity by acting in the suprachiasmatic nuclei (SCN). The recent cloning of two melatonin receptor subtypes with high affinity for melatonin allows molecular analysis of melatonin receptors in human SCN. We report that Mel(1a) receptor mRNA is detectable in neonatal human SCN by in situ hybridization. Mel(1b) and melatonin-related receptor mRNAs were not detected. The presence of Mel(1a) receptor mRNA in human SCN supports the hypothesis that the Mel(1a) receptor is responsible for the circadian effects of melatonin in humans. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. RP Weaver, DR (reprint author), MASSACHUSETTS GEN HOSP,LAB DEV CHRONOBIOL,SERV PEDIAT,BOSTON,MA 02114, USA. OI Weaver, David/0000-0001-7941-6719 FU NICHD NIH HHS [HD 14227, N01-HD-1-3138] NR 22 TC 88 Z9 99 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 DEC 20 PY 1996 VL 8 IS 1 BP 109 EP 112 DI 10.1097/00001756-199612200-00022 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WX339 UT WOS:A1996WX33900023 PM 9051762 ER PT J AU Hu, ED Kim, JB Sarraf, P Spiegelman, BM AF Hu, ED Kim, JB Sarraf, P Spiegelman, BM TI Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPAR gamma SO SCIENCE LA English DT Article ID EPIDERMAL GROWTH-FACTOR; ACTIVATED PROTEIN-KINASE; ADIPOSE-TISSUE DEVELOPMENT; TUMOR NECROSIS FACTOR; MYELIN BASIC-PROTEIN; ADIPOCYTE DIFFERENTIATION; SUBSTRATE RECOGNITION; 3T3-L1 ADIPOCYTES; INSULIN-RECEPTORS; ESTROGEN-RECEPTOR AB Adipocyte differentiation is an important component of obesity and other metabolic diseases. This process is strongly inhibited by many mitogens and oncogenes. Several growth factors that inhibit fat cell differentiation caused mitogen-activated protein (MAP) kinase-mediated phosphorylation of the dominant adipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPAR gamma) and reduction of its transcriptional activity. Expression of PPAR gamma with a nonphosphorylatable mutation at this site (serine-112) yielded cells with increased sensitivity to ligand-induced adipogenesis and resistance to inhibition of differentiation by mitogens. These results indicate that covalent modification of PPAR gamma by serum and growth factors is a major regulator of the balance between cell growth and differentiation in the adipose cell lineage. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. FU NIDDK NIH HHS [R37DK31405] NR 52 TC 777 Z9 794 U1 2 U2 21 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 20 PY 1996 VL 274 IS 5295 BP 2100 EP 2103 DI 10.1126/science.274.5295.2100 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY974 UT WOS:A1996VY97400055 PM 8953045 ER PT J AU Masland, RH AF Masland, RH TI Consequences of retinal color coding for cortical color decoding - Response SO SCIENCE LA English DT Article ID DISTINCT RP Masland, RH (reprint author), MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 20 PY 1996 VL 274 IS 5295 BP 2119 EP 2119 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY974 UT WOS:A1996VY97400061 ER PT J AU Tormey, DC Gray, R Falkson, HC AF Tormey, DC Gray, R Falkson, HC TI Postchemotherapy adjuvant tamoxifen therapy beyond five years in patients with lymph node-positive breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID LONG-TERM TAMOXIFEN; TRIAL AB Background: Data from a pilot study published in 1984 suggested that tamoxifen administration (as adjuvant hormonal therapy) for more than 5 years after initial breast cancer surgery might have therapeutic benefit. Purpose: A randomized trial was performed to assess the efficacy of maintaining tamoxifen therapy beyond 5 years in women with axillary lymph node-positive breast cancer who had been treated with surgery followed by 1 year of chemotherapy and 5 years of tamoxifen. Methods: One hundred ninety-four women (87 postmenopausal and 107 premenopausal) enrolled in two concurrent Eastern Cooperative Oncology Group adjuvant trials (E4181 for postmenopausal patients and E5181 for premenopausal patients) were randomly assigned to continued tamoxifen therapy or observation. Data for 193 women (87 postmenopausal and 108 premenopausal) were available for analysis. Median follow-up being 8.0 years. The major analyses measured events from the time of randomization until relapse or death; these include time-to-relapse analyses, with new opposite-breast cancers counted as treatment failures, and survival analyses. Time-to-relapse comparisons and survival comparisons for women in the two treatment groups were made by use of the Kaplan-Meier method and the log rank test. Reported P values are two-sided. Results: Five years after the randomization , no statistically significant differences were noted in either time to relapse or survival between women continuing to receive tamoxifen and those on observation. Eighty-five percent of the women receiving tamoxifen were disease free at this time compared with 73% of those on observation (P=.10); survival was 86% for those continuing to receive tamoxifen and 89% for those on observation (P=.52). Differences in the time to relapse and survival between premenopausal and postmenopausal women assigned to the two treatment groups were also not statistically significant (time to relapse: P=.38 and P=.16 for premenopausal and postmenopausal patients, respectively; survival: P=.18 and P=.72 for premenopausal and postmenopausal patients, respectively). There was an indication that women with estrogen receptor-positive tumors may experience a longer time to relapse with continued tamoxifen therapy (P=.014); however, the survival difference for this subgroup was not statistically significant (P=.81). The toxicity patterns in the two treatment groups were similar. Conclusions and Implications: Our results suggest that further evaluation of adjuvant tamoxifen therapy beyond 5 years in women with axillary lymph node-positive, estrogen receptor-positive breast cancer who have also been treated with adjuvant chemotherapy would be appropriate. C1 DANA FARBER CANC INST,BOSTON,MA 02115. UNIV PRETORIA,ZA-0002 PRETORIA,SOUTH AFRICA. RP Tormey, DC (reprint author), AMC CANC RES CTR,1600 PIERCE ST,DENVER,CO 80214, USA. FU NCI NIH HHS [CA21076, CA21692, CA23318] NR 13 TC 117 Z9 122 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 18 PY 1996 VL 88 IS 24 BP 1828 EP 1833 DI 10.1093/jnci/88.24.1828 PG 6 WC Oncology SC Oncology GA VY199 UT WOS:A1996VY19900011 PM 8961972 ER PT J AU Pollack, AE Fink, JS AF Pollack, AE Fink, JS TI Synergistic interaction between an adenosine antagonist and a D-1 dopamine agonist on rotational behavior and striatal c-Fos induction in 6-hydroxydopamine-lesioned rats SO BRAIN RESEARCH LA English DT Article DE adenosine receptor A(2); striatum; DMPX; SKF38393; dopamine receptor D-1; c-Fos ID GENE-EXPRESSION; STRIATONIGRAL NEURONS; STRIATOPALLIDAL NEURONS; SELECTIVE LESION; RECEPTORS; D2; D1; LOCALIZATION; RELEASE; BRAIN AB The interaction between adenosine and D-1 dopamine systems in regulating motor behavior and striatal c-Fos expression was examined in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions. These results were compared to the synergistic interaction between D-1 and D-2 dopamine systems in 6-OHDA rats. Coadministration of the adenosine antagonist 3,7-dimethyl-1-propargylxanthine (DMPX: 10 mg/kg) and the D-1 dopamine agonist SKF38393 (0.5 mg/kg) to 6-OHDA-lesioned rats produced significant contralateral rotation and c-Fos expression in the ipsilateral striatum compared to 6-OHDA rats treated with either drug alone. However, the regional pattern of striatal c-Fos activation following treatment of 6-OHDA rats with SKF38393 and DMPX was different from the dorsolateral pattern of striatal c-Fos induction observed after coadministration of D-1 and D-2 dopamine agonists (SKF38393: 0.5 mg/kg + quinpirole: 0.05 mg/kg). These data are consistent with a functional interaction between D-1 dopamine and adenosine systems in the striatum, but suggest that activation of different subsets of striatal neurons underlie the behavioral synergy observed following combined adenosine antagonist-D-1 dopamine agonist and combined D-1 dopamine agonist-D-2 dopamine agonist treatment. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOL NEUROBIOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. FU NIDA NIH HHS [DA07496, T32-DA07282]; NINDS NIH HHS [NS31579] NR 40 TC 55 Z9 55 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 DEC 16 PY 1996 VL 743 IS 1-2 BP 124 EP 130 DI 10.1016/S0006-8993(96)01036-0 PG 7 WC Neurosciences SC Neurosciences & Neurology GA WC373 UT WOS:A1996WC37300017 PM 9017239 ER PT J AU Abascal, VM Moreno, PR Rodriguez, L Monterroso, VM Palacios, IF Weyman, AE Davidoff, R AF Abascal, VM Moreno, PR Rodriguez, L Monterroso, VM Palacios, IF Weyman, AE Davidoff, R TI Comparison of the usefulness of Doppler pressure half-time in mitral stenosis in patients <65 and >=65 years of age SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR COMPLIANCE; ECHOCARDIOGRAPHIC DETERMINATION; VALVE AREA; VALVOTOMY; DISEASE AB Doppler pressure half-time is a reliable method for estimating mitral valve area when net left atrial and ventricular compliance remain stable. The accuracy of Doppler pressure half-time in estimating mitral valve area in older patients is unknown. We studied 80 patients (65 women and 15 men, aged 56+/-14 years) with cardiac catheterization and echocardiography. Mitral valve area was calculated using the Gorlin formula and by the Doppler pressure half-time method. Patients were stratified into those aged <65 years (n=57), and those aged greater than or equal to 65 years (n=23). The discordance between pressure half-time and Gorlin-derived mitral valve area wets assessed and related to multiple clinical, echocardiographic, and hemodynamic variables. The difference between pressure half-time and Gorlin-derived mitral valve area was greater in the older than inthe younger patient (0.34+/-0.30 vs 0.15+/-0.27 cm(2), =0.009) bur the older group had smaller mitral valve areas by the Gorlin method (0.72+/-0.18 vs 0.89+/-0.32 cm(2), p=0.02) and lower cardiac output. The difference between pressure half-time and Gorlin remained greater in the group of older patients (0.32+/-0.30 vs 0.19+/-0.22 cm(2), p=0.04), even when the analysis was restricted to patients with similar mitral valve area (<1 cm(2) by the Gorlin method). Using multivariate analysis, age greater than or equal to 65 years remained the only significant predictor of the discrepancy between pressure half-time and Gorlin mitral valve area. Thus, when compared with Gorlin-derived mitral valve area, pressure half-time overestimated valve area in older patients, and this technique for estimating mitral valve area should be used with caution in patients greater than or equal to 65 years of age. (C) 1996 by Excerpta Medica, Inc. C1 BOSTON UNIV HOSP,MED CTR,EVANS MEM DEPT CLIN RES,BOSTON,MA 02218. BOSTON UNIV HOSP,MED CTR,DIV CARDIOL,BOSTON,MA 02218. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,BOSTON,MA. NR 22 TC 10 Z9 10 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 15 PY 1996 VL 78 IS 12 BP 1390 EP 1393 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VX770 UT WOS:A1996VX77000011 PM 8970412 ER PT J AU Iqbal, J Hudson, AP AF Iqbal, J Hudson, AP TI An in vitro transcription assay for yeast mitochondria using organellar lysates SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID INVITRO TRANSCRIPTION; STRINGENT RESPONSE; RNA-POLYMERASE; SIGMA-FACTORS; DNA AB The nuclear gene NUC1 encodes the major mitochondrial (mt) ribonuclease in the yeast Saccharomyces cerevisiae. We describe an in vitro mt transcription assay system based on lysates of purified mitochondria from a petite (rho(-), mt deletion mutant) yeast strain in which NUC1 has been insertionally inactivated. Control in vitro run-on transcription assays using intact mitochondria demonstrate that the rate of incorporation of labeled precursor into mt RNA is identical in organelles from the nuc1 rho(-) mutant and its otherwise isochromosomal NUC1 parent strain. Brij-35 lysates of mitochondria from the nuc1 strain incorporate precursor into mt RNA at nearly the same rate as do intact organelles hom that strain, while similar mt lysates from NUC1 cells show no such incorporation. Other control studies show that mt lysates from the nucl strain retain functional mt cAMP-dependent protein kinase and other critical activities. When the cloned template DNA encoding the yeast mt 21S rRNA gene, which is not retained in the nuc1 rho(-) strain, is added to mt lysates from that strain, transcripts are produced from the template under standard assay conditions. (C) 1996 Academic Press, Inc C1 DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. ALLEGHENY UNIV HLTH SCI,MCP HAHNEMANN SCH MED,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19129. NR 19 TC 4 Z9 4 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD DEC 15 PY 1996 VL 243 IS 2 BP 270 EP 276 DI 10.1006/abio.1996.0516 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WA791 UT WOS:A1996WA79100010 PM 8954560 ER PT J AU Sagoo, JK Fruman, DA Wesselborg, S Walsh, CT Bierer, BE AF Sagoo, JK Fruman, DA Wesselborg, S Walsh, CT Bierer, BE TI Competitive inhibition of calcineurin phosphatase activity by its autoinhibitory domain SO BIOCHEMICAL JOURNAL LA English DT Article ID CYCLOPHILIN-CYCLOSPORINE-A; PROTEIN PHOSPHATASE; CATALYTIC SUBUNIT; COMPLEX; ACTIVATION; DEPHOSPHORYLATION; IDENTIFICATION; CALMODULIN; ENZYME AB Carcineurin (protein phosphatase 2B), a calmodulin and calcium-dependent serine/threonine phosphatase, appears to be regulated by a C-terminal autoinhibitory domain. A 25 amino acid peptide derived from this domain inhibits calcineurin phosphatase activity in vitro. Here we show that a 97 amino acid fragment of the calcineurin A alpha C-terminus is approx. 8-fold more potent than the shorter peptide in calcineurin inhibition experiments. Mutation of an evolutionarily conserved Asp to Asn, previously shown to disrupt calcium-dependent signalling and calcineurin regulation in T-lymphocytes, greatly reduced inhibition by the autoinhibitory domain in vitro. Kinetic analysis of wild-type and mutated autoinhibitory domains show that both are competitive inhibitors of calcineurin phosphatase activity with K-i values of 5.0+/-0.2 mu M and 36.0+/-3.7 mu M respectively. This suggests intrasteric regulation of calcineurin, with the autoinhibitory domains interacting at the active site of the enzyme. The competitive behaviour of the autoinhibitory domains contrasts with the mechanism of calcineurin inhibition by immunosuppressant-immunophilin complexes, which have been shown to bind to calcineurin at a region removed from the active site. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI 32514] NR 26 TC 31 Z9 32 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 15 PY 1996 VL 320 BP 879 EP 884 PN 3 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VZ868 UT WOS:A1996VZ86800024 PM 9003375 ER PT J AU Bridges, KR Barabino, GD Brugnara, C Cho, MR Christoph, GW Dover, G Ewenstein, BM Golan, DE Guttmann, CRG Hofrichter, J Mulkern, RV Zhang, B Eaton, WA AF Bridges, KR Barabino, GD Brugnara, C Cho, MR Christoph, GW Dover, G Ewenstein, BM Golan, DE Guttmann, CRG Hofrichter, J Mulkern, RV Zhang, B Eaton, WA TI A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy SO BLOOD LA English DT Article ID VASCULAR ENDOTHELIAL-CELLS; HEMOGLOBIN-F PRODUCTION; GLOBIN GENE-CLUSTER; RED-BLOOD-CELLS; S GELATION; DELAY TIME; ANEMIA; DISEASE; POLYMERIZATION; KINETICS AB During 24 weeks of hydroxyurea treatment, we monitored red blood cell (RBC) parameters in three patients with sickle cell disease, including F-cell and F-reticulocyte profiles, distributions of delay times for intracellular polymerization, sickle erythrocyte adherence to human umbilical vein endothelial cells in a laminar flow chamber, RBC phthalate density profiles, mean corpuscular hemoglobin concentration and cation content, reticulocyte mean corpuscular hemoglobin concentration, H-1-nuclear magnetic resonance transverse relaxation rates of packed RBCs, and plasma membrane lateral and rotational mobilities of band 3 and glycophorins. Hydroxyurea increases the fraction of cells with sufficiently long delay times to escape the microcirculation before polymerization begins. Furthermore, high pretreatment adherence to human umbilical vein endothelial cells of sickle RBCs decreased to normal after only 2 weeks of hydroxyurea treatment, preceding the increase in fetal hemoglobin levels. The lower adhesion of sickle RBCs to endothelium would facilitate escape from the microcirculation before polymerization begins. Hydroxyurea shifted several biochemical and biophysical parameters of sickle erythrocytes toward values observed with hemoglobin SC disease, suggesting that hydroxyurea moderates sickle cell disease toward the milder, but still clinically significant, hemoglobin SC disease. The 50% reduction in sickle crises documented in the Multicenter Study of Hydroxyurea in Sickle Cell Disease is consistent with this degree of erythrocyte improvement. This is a US government work. There are no restrictions on its use. C1 BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT PATHOL,BOSTON,MA. CHILDRENS HOSP,DEPT LAB MED,BOSTON,MA. CHILDRENS HOSP,DEPT RADIOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MOL PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA. NORTHEASTERN UNIV,DEPT CHEM ENGN,BOSTON,MA 02115. JOHNS HOPKINS UNIV HOSP,PEDIAT HEMATOL DIV,BALTIMORE,MD 21205. NIDDK,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. RP Bridges, KR (reprint author), BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,DEPT MED,221 LONGWOOD AVE,LMRC 620,BOSTON,MA 02115, USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 FU NHLBI NIH HHS [HL28028, HL15157, HL32854] NR 48 TC 115 Z9 117 U1 0 U2 6 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 DEC 15 PY 1996 VL 88 IS 12 BP 4701 EP 4710 PG 10 WC Hematology SC Hematology GA VZ305 UT WOS:A1996VZ30500034 PM 8977264 ER PT J AU Cohen, SA AF Cohen, SA TI Immunocytochemical localization of rH1 sodium channel in adult rat heart atria and ventricle - Presence in terminal intercalated disks SO CIRCULATION LA English DT Article DE sodium channels; ion channels; immunohistochemistry; intercalated disk; conduction ID LONG QT SYNDROME; SKELETAL-MUSCLE; NA+ CHANNEL; FUNCTIONAL EXPRESSION; CARDIAC-ARRHYTHMIA; PROTEIN; ANTIBODIES AB Background Of the five sodium channel subtypes expressed in cardiac tissues, the rat (rH1) and human (hH1) isoforms are thought to be the predominant subtypes on the basis of heterologous expression studies. In this study, subtype-specific antibodies and immunocytochemistry were used to confirm protein expression and to localize rH1 protein in cardiac tissues. Methods and Results Subtype-specific antibodies immunolabeled adult rat heart tissue in a manner identical to that obtained with subtype-nonselective antibodies. All antibodies specifically bound to the surface and t-tubular systems of atrial and ventricular muscle cells. Cytoplasmic labeling, reflecting nascent sodium channels or cytoplasmic stores of sodium channel protein, was apparent. Most notably, all antibodies also specifically labeled the subset of intercalated disks located at the ends but not the sides of adjacent ventricular muscle cells. Conclusions rH1 is the predominant subtype expressed on rat atrial and ventricular muscle cells. rH1 protein localization in surface and t-tubular membranes is consistent with its proposed role in coordinating membrane depolarization along the length and deep within cardiac muscle cells. rH1 protein localization in terminal intercalated disks suggests that sodium channels may also act as a localized voltage-dependent current amplifier, raising the safety margin for conduction; they also may contribute to anisotropic or saltatory conduction in cardiac tissues. These electrophysiological properties would be particularly important under conditions of altered channel function resulting from ion channel gene defects (eg, long QT syndrome), antiarrhythmic drug therapy, ischemia, or other heart diseases by influencing the electrophysiological substrate for ventricular tachyarrhythmias. C1 UNIV PENN,SCH MED,DEPT MED,DIV CARDIOL,PHILADELPHIA,PA 19104. RP Cohen, SA (reprint author), VET AFFAIRS MED CTR,MED SERV,CARDIOL SECT 111C,UNIV & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. NR 18 TC 96 Z9 96 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 DEC 15 PY 1996 VL 94 IS 12 BP 3083 EP 3086 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VY746 UT WOS:A1996VY74600011 PM 8989112 ER PT J AU Moreno, PR Bernardi, VH LopezCuellar, J Murcia, AM Palacios, IF Gold, HK Mehran, R Sharma, SK Nemerson, Y Fuster, V Fallon, JT AF Moreno, PR Bernardi, VH LopezCuellar, J Murcia, AM Palacios, IF Gold, HK Mehran, R Sharma, SK Nemerson, Y Fuster, V Fallon, JT TI Macrophages, smooth muscle cells, and tissue factor in unstable angina - Implications for cell-mediated thrombogenicity in acute coronary syndromes SO CIRCULATION LA English DT Article; Proceedings Paper CT 45th Annual Scientific Session of the American-College-of-Cardiology Meeting CY MAR 24-28, 1996 CL ORLANDO, FL SP Amer Coll Cardiol DE atherosclerosis; coronary disease; thrombosis leukocytes ID PLAQUE RUPTURE; ATHEROSCLEROTIC PLAQUES; MYOCARDIAL-INFARCTION; FACTOR EXPRESSION; PROTEIN; EROSION; GROWTH; SITE AB Background Macrophage expression of tissue factor may be responsible for coronary thrombogenicity in patients with plaque rupture. In patients without plaque rupture, smooth muscle cells may be the thrombogenic substrate. This study was designed to identify the cellular correlations of tissue factor in patients with unstable angina. Methods and Results Tissue from 50 coronary specimens (1560 pieces) from patients with unstable angina and 15 specimens from patients with stable angina were analyzed. Total and segmental areas (in square millimeters) were identified with trichrome staining. Macrophages, smooth muscle cells, and tissue factor were identified by immunostaining. Tissue factor content was larger in unstable angina (42+/-3%) than in stable angina (18+/-4) (P=.0001). Macrophage content was also larger in unstable angina (16+/-2%) than in stable angina (5+/-2%) (P=.002). The percentage of tissue factor located in cellular areas was larger in coronary samples from patients with unstable angina (67+/-8%) than in samples from patients with stable angina (40+/-5%) (P=.00007). Multiple linear stepwise regression analysis showed that coronary tissue factor content correlated significantly (r=.83, P<.0001) with macrophage and smooth muscle cell areas only in tissue from patients with unstable angina, with a strong relationship between tissue factor content and macrophages in the atheromatous gruel (r=.98, P<.0001). Conclusions Tissue factor content is increased in unstable angina and correlates with areas of macrophages and smooth muscle cells, suggesting a cell-mediated thrombogenicity in patients with acute coronary syndromes. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,BOSTON,MA. MT SINAI SCH MED,CARDIOVASC INST,NEW YORK,NY. RI Fuster, Valentin/H-4319-2015; OI Fuster, Valentin/0000-0002-9043-9986; Sharma, Sanjeev Kumar/0000-0002-3273-0708 NR 31 TC 292 Z9 298 U1 1 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 15 PY 1996 VL 94 IS 12 BP 3090 EP 3097 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VY746 UT WOS:A1996VY74600013 PM 8989114 ER PT J AU Moreno, PR Bernardi, VH LopezCuellar, J Newell, JB McMellon, C Gold, HK Palacios, IF Fuster, V Fallon, JT AF Moreno, PR Bernardi, VH LopezCuellar, J Newell, JB McMellon, C Gold, HK Palacios, IF Fuster, V Fallon, JT TI Macrophage infiltration predicts restenosis after coronary intervention in patients with unstable angina SO CIRCULATION LA English DT Article; Proceedings Paper CT 68th Annual Scientific Sessions of the American-Heart-Association CY NOV 13-16, 1995 CL ANAHEIM, CA SP Amer Heart Assoc, Brazilian Natl Res Council, Sao Paolo, CNR DE atherosclerosis; angioplasty; coronary disease; leukocytes ID ATHEROSCLEROSIS; ANGIOPLASTY; RABBIT; ATHERECTOMY; LESIONS; INJURY; METALLOPROTEINASES; CLASSIFICATION; MIGRATION; CASCADE AB Background Restenosis remains the major limitation of percutaneous coronary revascularization. Macrophages release cy tokines, metalloproteinases, and growth factors that may induce smooth muscle cell migration and proliferation. We tested the hypothesis that primary lesions that develop restenosis after coronary atherectomy have more macrophages and smooth muscle cells than primary lesions that do not develop restenosis. Methods and Results Fifty patients with unstable angina were identified. Total and segmental areas were quantified on trichrome-stained sections of coronary atherectomy tissue. Macrophages and smooth muscle cells were identified by immunohistochemical staining. Restenosis, defined as >50% stenosis diameter by quantitative cineangiography, was present in 30 patients. The other 20 patients (<50% stenosis) constitute the ''no restenosis'' group. The percentages of smooth muscle cell areas were similar in specimens from patients with and without restenosis (57+/-5% and 52+/-6%) (P=NS). However, macrophage-rich areas were larger in plaque tissue from patients with restenosis (20.4+/-2%) than in tissue from patients without restenosis (9.3+/-2%) (P=.0007). Multiple stepwise logistic regression analysis identified macrophages as the only independent predictor for restenosis (P=.006). Conclusions Macrophages are increased in coronary atherectomy tissue from primary lesions that develop restenosis. suggesting a possible role for macrophages in the restenotic process after percutaneous coronary intervention. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,BOSTON,MA. MT SINAI SCH MED,CARDIOVASC INST,NEW YORK,NY. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 31 TC 143 Z9 150 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 DEC 15 PY 1996 VL 94 IS 12 BP 3098 EP 3102 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VY746 UT WOS:A1996VY74600014 PM 8989115 ER PT J AU Curhan, GC Willett, WC Rimm, EB Spiegelman, D Ascherio, AL Stampfer, MJ AF Curhan, GC Willett, WC Rimm, EB Spiegelman, D Ascherio, AL Stampfer, MJ TI Birth weight and adult hypertension, diabetes mellitus, and obesity in US men SO CIRCULATION LA English DT Article DE hypertension; diabetes mellitus; birth weight; obesity; epidemiology ID IMPAIRED GLUCOSE-TOLERANCE; FETAL; LIFE; RISK; GROWTH; WOMEN; AGE AB Background Low birth weight has been associated with several chronic diseases in adults, including hypertension, diabetes mellitus, and obesity. Further study of these diseases in a large cohort with information on a wide variety of risk factors is essential to determine more precisely the risks associated with birth weight. Methods and Results We examined the relation between birth weight and cumulative incidence of adult hypertension, incidence of non-insulin-dependent diabetes mellitus, and prevalence of obesity in a cohort of 22 846 US men (Health Professionals Follow-up Study). Birth weights, medical histories, family histories, and other factors were collected by biennial mailed questionnaires. Logistic regression was used to examine the association between birth weight and these chronic adult diseases. Low birth weight was associated with an increased risk of hypertension and diabetes; high birth weight was associated with an increased risk of obesity. Compared with men in the referent birth weight category (7.0 to 8.4 lb), men who weighed <5.5 lb had an age-adjusted odds ratio for hypertension of 1.26 (95% confidence interval [CI], 1.11 to 1.44) and for diabetes mellitus of 1.75 (95% CI, 1.21 to 2.54). There was no material change after controlling for adult body mass index and parental histories of hypertension and diabetes mellitus. Compared with men in the referent group, the age-adjusted odds ratio of being in the highest versus the lowest quintile of adult body mass index for men with birth weight greater than or equal to 10.0 lb was 2.08 (95% CI, 1.73 to 2.50). Conclusions These findings support the hypothesis that early life exposures, for which birth weight is a marker, are associated with several chronic diseases in adulthood. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,CHANNING LAB,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Curhan, GC (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-55075]; NHLBI NIH HHS [HL-35464]; NIDDK NIH HHS [DK-45362] NR 19 TC 547 Z9 563 U1 0 U2 22 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 15 PY 1996 VL 94 IS 12 BP 3246 EP 3250 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VY746 UT WOS:A1996VY74600035 PM 8989136 ER PT J AU Corbett, A Ferrigno, P Henry, M Kahana, J Koepp, D Lee, M Nguyen, L Schlenstedt, G Seedorf, M Shen, E Taura, T Wong, D Silver, P AF Corbett, A Ferrigno, P Henry, M Kahana, J Koepp, D Lee, M Nguyen, L Schlenstedt, G Seedorf, M Shen, E Taura, T Wong, D Silver, P TI Genetic analysis of macromolecular transport across the nuclear envelope SO EXPERIMENTAL CELL RESEARCH LA English DT Article; Proceedings Paper CT Nobel Symposium on The Functional Organization of the Eukaryotic Cell Nucleus CY SEP 03-06, 1996 CL SALTSJOBADEN, SWEDEN ID GTPASE-ACTIVATING PROTEIN; MESSENGER-RNA EXPORT; SACCHAROMYCES-CEREVISIAE; BINDING-PROTEIN; PORE COMPLEX; CHROMOSOME CONDENSATION; LOCALIZATION SEQUENCES; YEAST NUCLEOPORIN; RAN/TC4 HOMOLOG; IMPORT AB Numerous factors that promote movement of macromolecules in and out of the nucleus have now been identified. These include both soluble cytoplasmic and nucleoplasmic proteins and proteins of the nuclear pore complex (NPC). Genetic analyses of the nuclear transport process in the model organism, the budding yeast Saccharomyces cerevisiae, have revealed remarkable conservation of all of these factors. In addition, important clues as to how these factors promote the unique bidirectional movement across the NPC have emerged from studies of yeast. We summarize the characterization and genetic interactions of the soluble transport factors and present data to illustrate how genetic experiments can be used to further define the import and export pathways. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. NR 54 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD DEC 15 PY 1996 VL 229 IS 2 BP 212 EP 216 DI 10.1006/excr.1996.0362 PG 5 WC Oncology; Cell Biology SC Oncology; Cell Biology GA WD564 UT WOS:A1996WD56400008 PM 8986600 ER PT J AU Krinzman, SJ DeSanctis, GT Cernadas, M Mark, D Wang, YS Listman, J Kobzik, L Donovan, C Nassr, K Katona, I Christiani, DC Perkins, DL Finn, PW AF Krinzman, SJ DeSanctis, GT Cernadas, M Mark, D Wang, YS Listman, J Kobzik, L Donovan, C Nassr, K Katona, I Christiani, DC Perkins, DL Finn, PW TI Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE T cells; asthma; costimulation; airway hyperresponsiveness; murine ID BRONCHOALVEOLAR LAVAGE; ACTIVATION; CTLA-4; ASTHMA; INDUCTION; MICE; RESPONSIVENESS; METHACHOLINE; EXPRESSION; HISTAMINE AB Activation of naive T cells requires at least two signals. In addition to the web characterized interaction of the T cell antigen receptor with the antigen/MHC expressed on an antigen-presenting cell, T cell activation also requires costimulation by a second set of signals. The best characterized costimulatory receptor is CD28, which binds to a family of B7 ligands expressed on antigen-presenting cells. In asthma, although activated T cells play a role in the initiation and maintenance of airway inflammation, the importance of T cell costimulation in bronchial hyperresponsiveness had not been characterized. Therefore, we tested the hypothesis that inhibition of the CD28:B7 costimulatory pathway would abrogate airway hyperresponsiveness. Our results show that blockade of costimulation with CTLA4-Ig, a fusion protein known to prevent costimulation by blocking CD28:B7 interactions, inhibits airway hyperresponsiveness, inflammatory infiltration, expansion of thoracic lymphocytes, and allergen-specific responsiveness of thoracic T cells in this murine model of allergic asthma. C1 BRIGHAM & WOMENS HOSP,DIV PULM,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV RENAL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DIV PULM,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,DEPT PEDIAT & MED,BETHESDA,MD 20814. HARVARD UNIV,SCH MED,BETH ISRAEL HOSP,DIV PULM,CAMBRIDGE,MA 02138. FU NHLBI NIH HHS [HL-36110]; NIAID NIH HHS [AI-31517]; NIEHS NIH HHS [ES-106568] NR 33 TC 117 Z9 121 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC 15 PY 1996 VL 98 IS 12 BP 2693 EP 2699 DI 10.1172/JCI119093 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VZ318 UT WOS:A1996VZ31800007 PM 8981913 ER PT J AU Benn, SI Whitsitt, JS Broadley, KN Nanney, LB Perkins, D He, L Patel, M Morgen, JR Swain, WF Davidson, JM AF Benn, SI Whitsitt, JS Broadley, KN Nanney, LB Perkins, D He, L Patel, M Morgen, JR Swain, WF Davidson, JM TI Particle-mediated gene transfer with transforming growth factor-beta 1 cDNAs enhances wound repair in rat skin SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE gene therapy; wound healing; transforming growth factor-beta; gene gun; skin ID ADENOASSOCIATED VIRUS VECTOR; BETA-BINDING-PROTEIN; SMOOTH-MUSCLE CELLS; IN-VIVO; EXTRACELLULAR-MATRIX; SKELETAL-MUSCLE; EXPRESSION; INVIVO; DNA; GROWTH-FACTOR-BETA-1 AB Based on preliminary but variable results with direct DNA transfer into wounds, we evaluated in vivo gene transfer by particle-mediated DNA delivery to rat skin to determine whether overexpression of TGF-beta 1 at the site of skin incisions would result in a significant improvement in repair. Optimization of the method with viral promoter-luciferase reporter constructs indicated that expression of luciferase activity persisted up to 5 d and was promoter, pressure, and site dependent (ventral >dorsal). Using cytomegalovirus (CMV)-driven human alpha-antitrypsin, transgene expression was immunolocalized within keratinocytes of the stratum granulosum at 24 h. We measured tensile strength of skin incisions at 11-21 d in both normal and diabetic rats transfected with TGF-beta 1 expression vectors at surgery. Native murine TGF-beta 1 under an SV40 promoter produced positive effects, while wound strengthening was more pronounced in diabetic animals using a CMV-driven construct, Transfection of rat skin with constitutively active, mutant porcine TGF-beta 1 under the control of the CMV and Moloney murine leukemia virus promoters significantly increased tensile strength up to 80% for 14-21 d after surgery. Transfection 24 h before surgery was more effective. Particle-mediated gene delivery can be used to deliver viral promoter-cytokine expression constructs into rat skin in a safe, efficient, and reproducible fashion, The extent of wound repair, as evidenced by enhanced tensile strength, can be markedly improved in tissues transfected with TGF-beta 1 expression constructs. C1 VANDERBILT UNIV,SCH MED,DEPT PATHOL,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,DEPT PEDIAT,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,DEPT PLAST SURG,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,DEPT CELL BIOL,NASHVILLE,TN 37232. DEPT VET AFFAIRS MED CTR,RES SERV,NASHVILLE,TN 37212. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02139. SHRINERS BURNS INST,BOSTON,MA 02139. AGRACETUS INC,MIDDLETON,WI 53562. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NIA NIH HHS [AG-06528]; NIAMS NIH HHS [AR-41943] NR 53 TC 89 Z9 89 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC 15 PY 1996 VL 98 IS 12 BP 2894 EP 2902 DI 10.1172/JCI119118 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VZ318 UT WOS:A1996VZ31800032 PM 8981938 ER PT J AU Huang, M Sharma, S Mao, JT Dubinett, SM AF Huang, M Sharma, S Mao, JT Dubinett, SM TI Non-small cell lung cancer-derived soluble mediators and prostaglandin E(2) enhance peripheral blood lymphocyte IL-10 transcription and protein production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; CLASS-I EXPRESSION; T-CELLS; IMMUNE-RESPONSE; TNF-ALPHA; CYTOKINE PRODUCTION; TYROSINE KINASE; DOWN-REGULATION; MESSENGER-RNA; CARCINOMA AB Studies suggest that IL-10 may contribute to tumor-associated immunosuppression, In the current study we evaluated the capacity of human non-small cell lung cancer (NSCLC) cell lines to induce PBL IL-10 production, We observed a 10- to 100-fold increase in human PBL IL-10 production following exposure to NSCLC cell supernatants. The tumor-induced increase in PBL IL-10 production was partially blocked by pretreatment of the tumors with the PC inhibitor indomethacin, NSCLC lines were found to constitutively produce PCE(2). Exogenous PGE(2) also induced PBL IL-10 production in a dose- and time-dependent manner, Both PCE, and NSCLC supernatant-induced PBL IL-10 production were due to an increase in the IL-10 mRNA transcriptional rate, To evaluate the significance of tumor-induced lymphocyte IL-10 production, the capacity of PBL to produce IFN-gamma during culture in tumor supernatants was assessed in the presence of specific anti-IL-10 mAb, We found enhanced PBL IFN-gamma production following anti-IL-10 treatment, These in vitro studies imply that NSCLC-induced PBL IL-10 production may serve to shift the Th1/Th2 cytokine axis at the tumor site and thus inhibit cell-mediated anti-tumor immune responses, These findings identify a mechanism by which lung cancer cells may escape host immune surveillance, We conclude that NSCLC-derived soluble mediators, including PGs, may play an immunoregulatory role through induction of lymphocyte IL-10 production, C1 UNIV CALIF LOS ANGELES,SCH MED,JOHNSON COMPREHENS CANC CTR,W LOS ANGELES VET ADM MED CTR,LOS ANGELES,CA 90073. FU NCI NIH HHS [CA09120]; NHLBI NIH HHS [HL07014] NR 70 TC 131 Z9 138 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1996 VL 157 IS 12 BP 5512 EP 5520 PG 9 WC Immunology SC Immunology GA VX026 UT WOS:A1996VX02600037 PM 8955201 ER PT J AU Montefiori, DC Baba, TW Li, A Bilska, M Ruprecht, RM AF Montefiori, DC Baba, TW Li, A Bilska, M Ruprecht, RM TI Neutralizing and infection-enhancing antibody responses do not correlate with the differential pathogenicity of SIVmac239 Delta 3 in adult and infant rhesus monkeys SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; SEROPOSITIVE INDIVIDUALS; MONOCLONAL-ANTIBODIES; MUCOSAL INFECTION; IMMUNE-RESPONSES; ATTENUATED SIV; NEF GENE; MACAQUES; VACCINE; TYPE-1 AB Variants of SIV containing a deletion in the nef gene are attenuated in adult macaques, where they provide protection from challenge with pathogenic SIV, but the mechanism of protection remains unknown, One of these attenuated variants carrying deletions in nef, vpr, and NRE (SIVmac239 Delta 3) was recently found to be pathogenic in infant macaques exposed to the virus at birth, We investigated whether inadequate or inappropriate antiviral humoral immune responses could explain why this virus causes disease in infant macaques, Plasma samples from four infants infected with SIVmac251 and five infants and two adults infected with SIVmac239 Delta 3 were evaluated for neutralizing Abs to a laboratory-passaged stock of SIVmac251, an animal challenge stock of SIVmac239/nef-open, and a stock of SIVmac239 Delta 3 to which animals were exposed, Plasma samples were evaluated further for complement-mediated Ah-dependent enhancement (C'-ADE) of SIVmac239/nef-open in vitro, High-titer neutralizing Abs to SIVmac251 were detected in plasma samples from adults and most infants within 3 to 5 wk of infection with either virus, Neutralizing Abs to SIVmac239/nef-open and SIVmac239 Gamma 3 developed more slowly, being undetectable before 23 to 63 wk of infection, Timing, magnitude, and breadth of neutralizing Ab responses did not correlate with progression to disease or lack thereof and gave no indication of an impaired humoral immune response in infants, Furthermore, C'-ADE was detected equally in plasma samples from adults and infants, The results indicate that infection with SIVmac239 Delta 3 causes disease in infant macaques despite their mounting of antiviral humoral immune responses comparable to those of adults. C1 TUFTS UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,LAB VIRAL PATHOGENESIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP Montefiori, DC (reprint author), DUKE UNIV,MED CTR,CTR AIDS RES,DEPT SURG,BOX 2926,DURHAM,NC 27710, USA. FU NIAID NIH HHS [AI35533, AI32330]; PHS HHS [6S-1649] NR 53 TC 71 Z9 72 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 DEC 15 PY 1996 VL 157 IS 12 BP 5528 EP 5535 PG 8 WC Immunology SC Immunology GA VX026 UT WOS:A1996VX02600039 PM 8955203 ER PT J AU Farokhzad, OO Shelley, CS Arnaout, MA AF Farokhzad, OO Shelley, CS Arnaout, MA TI Induction of the CD11b gene during activation of the monocytic cell line U937 requires a novel nuclear factor MS-2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; TRANSCRIPTION FACTOR PU.1; MYELOID CELLS; FACTOR-RECEPTOR; CHAIN GENE; NF-M; GRANULOCYTIC DIFFERENTIATION; HUMAN PROINTERLEUKIN-1-BETA; REGULATED EXPRESSION; PROMOTER SEQUENCES AB The differentiation of myeloid precursors into mature myelomonocytic cells is characterized by the induction of the gene encoding the beta(2) integrin CD11b. The transcription factors Sp1 and PU.1 prime the CD11b promoter, but the nature of the factors responsible for its inducible expression are unknown. In addition to the CD11b gene, the homologous genes encoding CD11a and CD11c also exhibit inducible expression during myeloid differentiation. Therefore, we compared the nucleotide sequences of the CD11a, CD11b, and CD11c gene promoters to identify common elements that might contribute to inducible expression. This analysis identified one such element repeated four times within the CD11b promoter. Mutation of these elements indicated that two, MS-2 beta and MS-2 gamma, are critical to the induction of the CD11b gene during differentiation of the pro-monocytic cell line U937. Electrophoretic mobility shift assays indicate that MS-2 beta and MS-2 gamma interact with nuclear factors that are induced during U937 differentiation. These factors are detected at the time the CD11b promoter is activated. The molecular mass of these factors is approximately 28 kDa, and their DNA binding characteristics are indistinguishable from those of the novel nuclear factor MS-2. Taken together, our data indicate that MS-2 mediates induction of the CD11b gene as cells of the monocytic lineage mature. The presence of multiple potential binding sites for MS-2 in the promoter regions of a wide range of genes expressed in mature myeloid cells suggests this factor plays a general role in myeloid differentiation. C1 MASSACHUSETTS GEN HOSP,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,RENAL UNIT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,RENAL UNIT,CHARLESTOWN,MA 02129. HARVARD UNIV,DEPT MED,CHARLESTOWN,MA 02129. FU NIDDK NIH HHS [R29 DK50779-01, 2PO1 DK28465-06] NR 77 TC 19 Z9 19 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1996 VL 157 IS 12 BP 5597 EP 5605 PG 9 WC Immunology SC Immunology GA VX026 UT WOS:A1996VX02600048 PM 8955212 ER PT J AU Stoddart, JH Jasuja, RR Sikorski, MA vonAndrian, UH Mier, JW AF Stoddart, JH Jasuja, RR Sikorski, MA vonAndrian, UH Mier, JW TI Protease-resistant L-selectin mutants - Down-modulation by cross-linking but not cellular activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEUKOCYTE ADHESION MOLECULE-1; MEMBRANE-PROXIMAL CLEAVAGE; HIGH ENDOTHELIAL VENULES; HUMAN NEUTROPHILS; CHROMOSOMAL LOCALIZATION; CHEMOTACTIC FACTORS; SURFACE MOLECULE; HOMING RECEPTORS; PROTEINS; INVITRO AB The adhesion molecule L-selectin (CD62L) is rapidly shed from the plasma membrane during leukocyte activation as a result of proteolytic cleavage between Lys(321) and Ser(322) within the extracellular domain, L-selectin is also down-modulated from the surface in response to cross-linking, possibly through a similar mechanism. To further characterize the mechanism of downmodulation, several L-selectin mutants were generated and transfected into COS cells, Wild-type L-selectin as well as mutants with one or two amino acid substitutions at the cleavage site were nearly quantitatively shed into the culture supernatant. However, mutants in which a nine-amino acid stretch that included the protease-sensitive site was either deleted or replaced with a polyglycine spacer or a comparable region of E-selectin were retained on the cell surface and not detected in the supernatant, These results are consistent with other reports describing protease resistant L-selectin mutants. We also demonstrate that when expressed in L1-2 pre-B cells, the L-selectin nine-amino acid deletion mutant (321del.9), but not wild-type L-selectin, is resistant to down-regulation induced by PMA. However, both wild-type and mutant 321del.9 are completely lost from the cell surface in response to cross-linking with an L-selectin Ab. PMA-induced- but not L-selectin cross-linking-induced down-modulation was inhibited by staurosporine. These data are consistent with the idea that the L-selectin protease(s) can tolerate minor structural alterations at the cleavage site, and that L-selectin down-modulation can be induced by more than one mechanism, at least one of which (cross-linking) is protein kinase C independent. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,TUPPER RES INST,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,DIV HEMATOL ONCOL,BOSTON,MA 02111. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RI von Andrian, Ulrich/A-5775-2008 FU NCI NIH HHS [CA 43950] NR 37 TC 25 Z9 26 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 DEC 15 PY 1996 VL 157 IS 12 BP 5653 EP 5659 PG 7 WC Immunology SC Immunology GA VX026 UT WOS:A1996VX02600054 PM 8955218 ER PT J AU Cramer, KS Angelucci, A Hahm, JO Bogdanov, MB Sur, M AF Cramer, KS Angelucci, A Hahm, JO Bogdanov, MB Sur, M TI A role for nitric oxide in the development of the ferret retinogeniculate projection SO JOURNAL OF NEUROSCIENCE LA English DT Article DE diffusible messenger; visual system; lateral geniculate nucleus (LGN); pattern formation; eye-specific layers; ON/OFF sublaminae; neuronal activity ID LONG-TERM POTENTIATION; LATERAL GENICULATE-NUCLEUS; NEURONAL NADPH DIAPHORASE; NMDA RECEPTORS; RETINOTECTAL PROJECTION; SYNAPTIC POTENTIATION; POSTNATAL-DEVELOPMENT; TRANSPORTED PROTEINS; REACTION-PRODUCT; VISUAL-SYSTEM AB The ferret retinogeniculate projection segregates into eye-specific layers during the first postnatal week and into ON/OFF sublaminae, which receive inputs from either on-center or off-center retinal ganglion cells, during the third and fourth postnatal weeks. The restriction of retinogeniculate axon arbors into eye-specific layers appears to depend on action potential activity (Shatz and Stryker, 1988) but does not require activation of NMDA receptors (Smetters et al., 1994). The formation of ON/OFF sublaminae is also activity-dependent and is disrupted by in vivo blockade of NMDA receptors (Hahm et al., 1991). To investigate a possible mechanism whereby blockade of postsynaptic NMDA receptors in the lateral geniculate nucleus (LGN) results in changes in the size and position of presynaptic axon arbors, we tested the role of the diffusible messenger nitric oxide (NO) in the development of the retinogeniculate pathway. We found previously that NO synthase (NOS) is transiently expressed in LGN cells during the refinement of retinogeniculate projections (Cramer et al., 1995). In this study, treatment with N-G-nitro-L-arginine (L-NoArg), an arginine analog that inhibits NOS, during the third and fourth postnatal weeks resulted in an overall pattern of sublamination that was significantly reduced compared with normal and control animals. Single retinogeniculate axon arbors were located in the middle of eye-specific layers rather than toward the inner or outer half as in normal or control animals. The effect of NOS inhibition was not a consequence of the hypertensive effect of L-NoArg, In contrast to the effect of L-NoArg on the formation of ON/OFF sublaminae, treatment with L-NoArg during the first postnatal week did not disrupt the formation of eye-specific layers, Biochemical assays indicated significant inhibition of NOS during both treatment periods. These data suggest that NO acts together with NMDA receptors in activity-dependent refinement of connections during a specific phase of retinogeniculate development. C1 GEORGETOWN UNIV, MED CTR, DEPT NEUROSURG, WASHINGTON, DC 20007 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. RP Cramer, KS (reprint author), MIT, DEPT BRAIN & COGNIT SCI, E25-235, CAMBRIDGE, MA 02139 USA. FU NEI NIH HHS [EY07023, EY11512] NR 66 TC 116 Z9 118 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 15 PY 1996 VL 16 IS 24 BP 7995 EP 8004 PG 10 WC Neurosciences SC Neurosciences & Neurology GA VW945 UT WOS:A1996VW94500020 PM 8987826 ER PT J AU Lee, JT Jaenisch, R AF Lee, JT Jaenisch, R TI A method for high efficiency YAC lipofection into murine embryonic stem cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID YEAST ARTIFICIAL CHROMOSOME; TRANSGENIC MICE; GENE; EXPRESSION; HEAVY AB We describe a modified protocol for introducing yeast artificial chromosomes (YACs) into murine embryonic stem (ES) cells by lipofection. With a decreased DNA:cell ratio, increased concentration of condensing agents and altered culture conditions, this protocol reduces the requirement for YAC DNA to a few micrograms, improves the recovery of neomycin-resistant ES colonies and increases the yield of clones containing both flanking vector markers and insert, These modifications enable generation of sufficient 'intact' transgenic clones for biological analysis with a single experiment. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. RP Lee, JT (reprint author), MIT,DEPT BIOL,WHITEHEAD INST BIOMED RES,9 CAMBRIDGE CTR,CAMBRIDGE,MA 02138, USA. FU NCI NIH HHS [R35-CA44339] NR 10 TC 15 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 15 PY 1996 VL 24 IS 24 BP 5054 EP 5055 DI 10.1093/nar/24.24.5054 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA462 UT WOS:A1996WA46200031 PM 9016681 ER PT J AU Shekelle, PG AF Shekelle, PG TI Spinal manipulation for low back pain: An 2860 updated systematic review of randomized clinical trials - Point of view SO SPINE LA English DT Editorial Material C1 RAND CORP,SANTA MONICA,CA. RP Shekelle, PG (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,SANTA MONICA,CA, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-2436 J9 SPINE JI SPINE PD DEC 15 PY 1996 VL 21 IS 24 BP 2872 EP 2872 DI 10.1097/00007632-199612150-00014 PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA WB802 UT WOS:A1996WB80200014 ER PT J AU Atlas, SJ Deyo, RA Patrick, DL Convery, K Keller, RB Singer, DE AF Atlas, SJ Deyo, RA Patrick, DL Convery, K Keller, RB Singer, DE TI The Quebec Task Force classification for spinal disorders and the severity, treatment, and outcomes of sciatica and lumbar spinal stenosis SO SPINE LA English DT Article DE classification; cohort study; diagnosis; low back pain; lumbar disc surgery; lumbar spinal stenosis; natural history; outcomes research; prognosis; sciatica ID LOW-BACK-PAIN; DISABILITY; HISTORY AB Study Design. A prospective cohort study of patients in Maine with sciatica and lumbar spinal stenosis treated surgically and nonsurgically. Summary of Background Data. In 1987, the Quebec Task Force on Spinal Disorders proposed a diagnostic classification to help make clinical decisions, evaluate quality of care, assess prognosis, and conduct research. Objectives. To assess the Quebec Task Force classification's ability to stratify patients according to severity and treatment al baseline, and to assess changes over time in health-related quality of life, including symptoms, functional status, and disability. Methods. Five hundred sixteen patients participating in the Maine Lumbar Spine Study who completed baseline and 1-year follow-up evaluations were classified successfully according to the Quebec Task Force classification. Patient characteristics and treatments were compared across Quebec Task Force classification categories. Changes in health-related quality of life over 1 year were assessed according to Quebec Task Force classification category and type of treatment. Results. Among patients with sciatica (n = 370), higher Quebec Task Force classification categories (from 2, pain radiating to the proximal extremity, to 6, sciatica with evidence of nerve root compression) were associated with increased severity of symptoms at baseline. There was no association between Quebec Task Force classification and baseline functional status. Quebec Task Force classification was associated strongly with the likelihood of receiving surgical treatment (P less than or equal to 0.005). Among patients with sciatica treated nonsurgically, improvement at 1 year in back-specific and generic physical function increased with higher Quebec Task Force classification category (P less than or equal to 0.05). Only a nonsignificant trend was observed for surgically treated patients. Patients with lumbar spinal stenosis (Quebec Task Force classification 7, n = 131) had baseline features and outcomes distinct from patients with sciatica. Conclusions. For patients with sciatica, the Quebec Task Force classification was-highly associated with the severity of symptoms and the probability of subsequent surgical treatment. Nonsurgically treated patients in Quebec Task Force classification categories reflecting nerve root compression had greater improvement than those with pain symptoms alone. Among surgical patients, the Quebec Task Force classification was not associated with Outcome. These results provide validation for the classification and its wider adoption. Nonetheless, improved diagnostic classifications are needed to predict outcomes better in patients with sciatica who undergo surgery. C1 MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GEN INTERNAL MED UNIT,MED SERV,BOSTON,MA. UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. MAINE MED ASSESSMENT FDN,MANCHESTER,ME. RP Atlas, SJ (reprint author), MASSACHUSETTS GEN HOSP,MED PRACTICES EVALUAT CTR,50 STANIFORD ST,BOSTON,MA 02114, USA. FU AHRQ HHS [HS-06344, HS-08194] NR 17 TC 95 Z9 95 U1 1 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-2436 J9 SPINE JI SPINE PD DEC 15 PY 1996 VL 21 IS 24 BP 2885 EP 2892 DI 10.1097/00007632-199612150-00020 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA WB802 UT WOS:A1996WB80200020 PM 9112713 ER PT J AU Jagodzinski, PP Wustner, J Kmieciak, D Wasik, TJ Fertala, A Sieron, AL Takahashi, I Tsuji, T Mimura, T Fung, MS Gorny, MK Kloczewiak, M Kaneko, Y Kozbor, D AF Jagodzinski, PP Wustner, J Kmieciak, D Wasik, TJ Fertala, A Sieron, AL Takahashi, I Tsuji, T Mimura, T Fung, MS Gorny, MK Kloczewiak, M Kaneko, Y Kozbor, D TI Role of the V2, V3, and CD4-binding domains of GP120 in curdlan sulfate neutralization sensitivity of HIV-1 during infection of T lymphocytes SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; TYPE-1 NEUTRALIZATION; GLYCOPROTEIN GP120; EPITOPE EXPOSURE; DEXTRAN SULFATE; ENVELOPE GP120; BINDING; MECHANISM; LOOP AB A sulfated polysaccharide, curdlan sulfate (CRDS) with 1,3-beta-D-glucan as a main chain, inhibits HIV-1 infection of human peripheral blood lymphocytes (PBLs) by binding to the V3 region of gp120. We previously showed that T cell (T)-tropic HIV-1 isolates are over 10-fold more sensitive to neutralization by CRDS than macrophage (MT)-tropic viruses, which posseses a relatively less charged amino acid composition in the vs sequence. To analyze the interaction of CRDS with V3 and its association with neutralization sensitivity or HIV-1 isolates, we examined the effect or CRDS on the binding of neutralizing antibodies to monomeric and oligomeric gp120 mutants of T- and MT-tropic HIV-I clones in which the V3 loop was either deleted or substituted by V3 of another isolate. Our results showed that the presence and the amino acid composition of the V3 loop appears to determine the extent of interaction of CRDS with the V2 and CD4-binding regions on native gp120 monomers; however, the positive charge of vs has less effect on this interaction on oligomeric gp120. Furthermore, our results established that only the CRDS-induced masking of V3 on oligomeric gp120 appears to be associated with the anti-HIV-1 activity of CRDS in vitro. Our findings underline the usefulnes of CRDS for understanding the structural constraints on gp120 that drive the transition from MT- to T-tropic isolates in vivo and enable the Virus to use multiple fusion cofactors. (C) 1996 Academic Press, Inc. C1 THOMAS JEFFERSON UNIV,DEPT MICROBIOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,DEPT BIOCHEM & MOL BIOL,PHILADELPHIA,PA 19107. AJINOMOTO CO INC,CHUO KU,TOKYO 104,JAPAN. TANOX BIOSYST INC,HOUSTON,TX 77025. NYU,SCH MED,DEPT PATHOL,NEW YORK,NY 10016. NYU,SCH MED,CTR AIDS RES,NEW YORK,NY 10016. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02114. K MARCINKOWSKI UNIV,SCH MED SCI,DEPT PHYSIOL CHEM,POZNAN,POLAND. RI Sieron, Aleksander/G-1700-2013 FU NICHD NIH HHS [HD 27107] NR 35 TC 23 Z9 24 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 15 PY 1996 VL 226 IS 2 BP 217 EP 227 DI 10.1006/viro.1996.0649 PG 11 WC Virology SC Virology GA VZ463 UT WOS:A1996VZ46300009 PM 8955041 ER PT J AU Fuchs, CS AF Fuchs, CS TI Progress in rectal cancer SO LANCET LA English DT Article ID ADJUVANT THERAPY RP Fuchs, CS (reprint author), DANA FARBER CANC INST,DEPT MED ONCOL,BOSTON,MA 02115, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD DEC 14 PY 1996 VL 348 IS 9042 BP 1600 EP 1600 DI 10.1016/S0140-6736(05)65687-5 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VX876 UT WOS:A1996VX87600002 PM 8961983 ER PT J AU Soncin, F Calderwood, SK AF Soncin, F Calderwood, SK TI Reciprocal effects of pro-inflammatory stimuli and anti-inflammatory drugs on the activity of heat shock factor-1 in human monocytes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SEQUENCE; PROTEIN; BINDING; EXPRESSION; ACTIVATION; ASPIRIN; CELLS; GENE AB Heat shock factor-1 (HSF-1), the transcriptional activator of heat shock genes has recently been shown to play a role in the repression of acute phase genes. We have further explored the role of HSF-1 in inflammatory processes in human monocytes. HSF-1 was activated in these cells by a wide range of classes of non-steroidal antiinflammatory drugs (NSAIDs) while being strongly repressed by pro-inflammatory stimuli. The experiments indicate reciprocal regulation of the acute phase and heat shock responses and suggest a novel target for the NSAID family of drugs. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RI SONCIN, Fabrice/A-1475-2009; OI Soncin, Fabrice/0000-0001-6312-0673 FU NCI NIH HHS [CA 31303, CA 506421] NR 14 TC 22 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 13 PY 1996 VL 229 IS 2 BP 479 EP 484 DI 10.1006/bbrc.1996.1829 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VZ799 UT WOS:A1996VZ79900019 PM 8954923 ER PT J AU Son, H Hawkins, RD Martin, K Kiebler, M Huang, PL Fishman, MC Kandel, ER AF Son, H Hawkins, RD Martin, K Kiebler, M Huang, PL Fishman, MC Kandel, ER TI Long-term potentiation is reduced in mice that are doubly mutant in endothelial and neuronal nitric oxide synthase SO CELL LA English DT Article ID PLATELET-ACTIVATING-FACTOR; HIPPOCAMPAL PYRAMIDAL CELLS; RAT HIPPOCAMPUS; SYNAPTIC TRANSMISSION; RETROGRADE MESSENGER; INHIBITORS; ENHANCEMENT; SYNAPSES; SLICES; CA1 AB Nitric oxide (NO) has been implicated in hippocampal long-term potentiation (LTP), but LTP is normal in mice with a targeted mutation in the neuronal form of NO synthase (nNOS(-)). LTP was also normal in mice with a targeted mutation in endothelial NOS (eNOS(-)), but LTP in stratum radiatum of CA1 was significantly reduced in doubly mutant mice (nNOS(-)/eNOS(-)). By contrast, LTP in stratum oriens was normal in the doubly mutant mice. These results provide the first genetic evidence that NOS is involved in LTP in stratum radiatum and suggest that the neuronal and endothelial forms can compensate for each other in mice with a single mutation. They further suggest that there is also a NOS-independent component of LTP in stratum radiatum and that LTP in stratum oriens is largely NOS independent. C1 COLUMBIA UNIV,COLL PHYS & SURG,CTR NEUROBIOL & BEHAV,NEW YORK,NY 10032. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. RP Son, H (reprint author), COLUMBIA UNIV,COLL PHYS & SURG,HOWARD HUGHES MED INST,NEW YORK,NY 10032, USA. FU NIMH NIH HHS [MH50733]; NINDS NIH HHS [NS10828, NS33335] NR 41 TC 325 Z9 337 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 13 PY 1996 VL 87 IS 6 BP 1015 EP 1023 DI 10.1016/S0092-8674(00)81796-1 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VY447 UT WOS:A1996VY44700007 PM 8978606 ER PT J AU Cayrol, C Flemington, E AF Cayrol, C Flemington, E TI G(0)/G(1), growth arrest mediated by a region encompassing the basic leucine zipper (bZIP) domain of the Epstein-Barr virus transactivator Zta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLIN-DEPENDENT KINASES; DNA-BINDING; DIMERIZATION DOMAIN; ACTIVATION DOMAIN; BZLF1 PROTEIN; PROMOTER DNA; DIFFERENTIATION; CELLS; EXPRESSION; INHIBITOR AB The Epstein-Barr virus (EBV) immediate early transactivator Zta is a basic leucine zipper (bZIP) transcription factor that causes G(0)/G(1) cell cycle arrest through induction of the tumor suppressor protein, p53, and the cyclin-dependent kinase inhibitors, p21 and p27 (Cayrol, C., and Flemington, E. K. (1996) EMBO J. 15, 2748-2759). Here, we report a genetic analysis of Zta-mediated G(0)/G(1) growth arrest and p21 induction. The majority of the Zta transactivation domain can be deleted (Z Delta 1-128) without significantly affecting the ability of Zta to elicit growth arrest. A larger amino-terminal deletion (Z Delta 1-167) abrogates the ability of Zta to inhibit proliferation, mapping the growth-inhibitory domain to a carboxyl-terminal region encompassing the bZIP domain (amino acids 128-245), The integrity of the bZIP domain is required for growth suppression since a two-amino acid mutant which is defective for homodimerization, fails to induce cell cycle arrest. Western blot analysis of p21 expression in cells expressing Zta mutants reveals that the ability of Zta mutants to cause G(0)/G(1) growth arrest is intimately related to their capacity to induce p21 expression. Together, these data demonstrate that a carboxyl-terminal region of Zta that includes the bZIP domain is sufficient to mediate G(0)/G(1) growth arrest and p21 induction. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA 02115. RI CAYROL, Corinne/C-2106-2011 FU NCI NIH HHS [CA47554]; NIGMS NIH HHS [R29 GM48045] NR 32 TC 52 Z9 53 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 DEC 13 PY 1996 VL 271 IS 50 BP 31799 EP 31802 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VY340 UT WOS:A1996VY34000010 PM 8943219 ER PT J AU Huang, LE Arany, Z Livingston, DM Bunn, HF AF Huang, LE Arany, Z Livingston, DM Bunn, HF TI Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its alpha subunit SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING ACTIVITY; NF-KAPPA-B; HUMAN ERYTHROPOIETIN GENE; SIGNAL-TRANSDUCTION PATHWAY; ARYL-HYDROCARBON RECEPTOR; LACTATE-DEHYDROGENASE-A; RESPONSE ELEMENTS; ACTIVITY INVITRO; CAROTID-BODY; FACTOR-I AB Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that is critical for hypoxic induction of a number of physiologically important genes, We present evidence that regulation of HIF-1 activity is primarily determined by the stability of the HLF-1 alpha protein, Both HIF-1 alpha and HIF-1 beta mRNAs were constitutively expressed in HeLa and Hep3B cells with no significant induction by hypoxia, However, the HIF-1 alpha protein was barely detectable in normoxic cells, even when HLF-1 alpha was overexpressed, but was highly induced in hypoxic cells, whereas HIF-1 beta protein levels remained constant, regardless of pO(2). Hypoxia-induced HIF-1 binding as well as the HIF-1 alpha protein were rapidly and drastically decreased in vivo following an abrupt increase to normal oxygen tension, Moreover, short pre-exposure of cells to hydrogen peroxide selectively prevented hypoxia-induced HIF-1 binding via blocking accumulation of HIF-1 alpha protein, whereas treatment of hypoxic cell extracts with H2O2 had no effect on HIF-1 binding. These observations suggest that an intact redox-dependent signaling pathway is required for destabilization of the RIF-la protein, In hypoxic cell extracts, HIF-1 DNA binding was reversibly abolished by sulfhydryl oxidation, Furthermore, the addition of reduced thioredoxin to cell extracts enhanced HIF-1 DNA binding, Consistent with these results, overexpression of thioredoxin and Ref-1 significantly potentiated hypoxia-induced expression of a reporter construct containing the wild-type HIF-1 binding site, These experiments indicate that activation of HIF-1 involves redox-dependent stabilization of HIF-1 alpha protein. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL ONCOL,LMRC 2,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NIDDK NIH HHS [DK09365-01, R01-DK41234] NR 51 TC 810 Z9 841 U1 2 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 DEC 13 PY 1996 VL 271 IS 50 BP 32253 EP 32259 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VY340 UT WOS:A1996VY34000075 PM 8943284 ER PT J AU Sheen, J AF Sheen, J TI Ca2+-dependent protein kinases and stress signal transduction in plants SO SCIENCE LA English DT Article ID STOMATAL GUARD-CELLS; ABSCISIC-ACID; ARABIDOPSIS-THALIANA; GENE-EXPRESSION; MOLECULAR RESPONSES; PROMOTER ACTIVITY; SEED MATURATION; LOW-TEMPERATURE; OSMOTIC-STRESS; SALT STRESS AB Stress responses in plants involve changes in the transcription of specific genes. The constitutively active mutants of two related Ca2+-dependent protein kinases (CDPK1 and CDPK1a) activate a stress-inducible promoter, bypassing stress signals. Six other plant protein kinases, including two distinct CDPKs, fail to mimic this stress signaling, The activation is abolished by a CDPK1 mutation in the kinase domain and diminished by a constitutively active protein phosphatase 2C that is capable of blocking responses to the stress hormone abscisic acid. A variety of functions are mediated by different CDPKs. CDPK1 and CDPK1a may be positive regulators controlling stress signal transduction in plants. C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. RP Sheen, J (reprint author), HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114, USA. NR 65 TC 382 Z9 432 U1 1 U2 17 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 13 PY 1996 VL 274 IS 5294 BP 1900 EP 1902 DI 10.1126/science.274.5294.1900 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY200 UT WOS:A1996VY20000041 PM 8943201 ER PT J AU Bartlett, JD Simmer, JP Xue, J Margolis, HC Moreno, EC AF Bartlett, JD Simmer, JP Xue, J Margolis, HC Moreno, EC TI Molecular cloning and mRNA tissue distribution of a novel matrix metalloproteinase isolated from porcine enamel organ SO GENE LA English DT Article DE alternative polyadenylation sites; homology screening; mineralized tissue; RT-PCR ID BREAST CARCINOMAS; BOVINE ENAMEL; CDNA SEQUENCE; COLLAGENASE; EXPRESSION; CELLS; GENE; IDENTIFICATION; FIBROBLASTS; MACROPHAGES AB A cDNA encoding a novel matrix metalloproteinase (MMP) was isolated from a porcine enamel organ-specific cDNA library. Multiple tissue northern blot analysis revealed the presence of two mRNA transcripts which were expressed only in the enamel organ. The transcripts were 1968 bp or 3420 bp in length and resulted from the utilization of alternative polyadenylation sites. The open reading frame of the cloned mRNA encodes a protein composed of 483 amino acids. The MMP has a predicted molecular mass of 54.1 kDa, which is similar to that of the stromelysins or collagenases, although it is not a member of either of these two classes of MMPs. A motif analysis revealed that the cloned MMP does not contain a consensus hemopexin-like domain because it lacks a critical tryptophan and proline residue at the appropriate positions. Since the cloned MMP is a new member of the MMP gene family and its expression appears limited to the enamel organ, we have named it enamelysin. C1 UNIV TEXAS,DEPT PEDIAT DENT,SAN ANTONIO,TX 78284. RP Bartlett, JD (reprint author), FORSYTH DENT CTR,DEPT BIOMINERALIZAT,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-03781] NR 28 TC 154 Z9 168 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 12 PY 1996 VL 183 IS 1-2 BP 123 EP 128 DI 10.1016/S0378-1119(96)00525-2 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA VZ989 UT WOS:A1996VZ98900018 PM 8996096 ER PT J AU Hortobagyi, GN Theriault, RL Porter, L Blayney, D Lipton, A Sinoff, C Wheeler, H Simeone, JF Seaman, J Knight, RD Heffernan, M Reitsma, DJ AF Hortobagyi, GN Theriault, RL Porter, L Blayney, D Lipton, A Sinoff, C Wheeler, H Simeone, JF Seaman, J Knight, RD Heffernan, M Reitsma, DJ TI Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MITOMYCIN-C; PHASE-II; CHEMOTHERAPY; CARCINOMA; ONCOLOGY; 5-FLUOROURACIL; MITOXANTRONE; DOXORUBICIN; THERAPY; QUALITY AB Background Bisphosphonates such as pamidronate disodium inhibit osteoclast-induced bone resorption associated with cancer that has metastasized to bone. Methods Women with stage IV breast cancer who were receiving cytotoxic chemotherapy and had at least one lytic bone lesion were given either placebo or pamidronate (90 mg) as a two-hour intravenous infusion monthly for 12 cycles. Skeletal complications, including pathologic fractures, the need for radiation to bone or bone surgery, spinal cord compression, and hypercalcemia (a serum calcium concentration above 12 mg per deciliter [3.0 mmol per liter] or elevated to any degree and requiring treatment), were assessed monthly. Bone pain, use of analgesic drugs, performance status, and quality of life were assessed throughout the trial. Results The efficacy of treatment was evaluated in 380 of 382 randomized patients, 185 receiving pamidronate and 195 receiving placebo. The median time to the occurrence of the first skeletal complication was greater in the pamidronate group than in the placebo group (13.1 vs. 7.0 months, P=0.005), and the proportion of patients in whom any skeletal complication occurred was lower (43 percent vs. 56 percent, P=0.008). There was significantly less increase in bone pain (P=0.046) and deterioration of performance status (P=0.027) in the pamidronate group than in the placebo group. Pamidronate was well tolerated. Conclusions Monthly infusions of pamidronate as a supplement to chemotherapy can protect against skeletal complications in women with stage IV breast cancer who have osteolytic bone metastases. (C) 1996, Massachusetts Medical Society. C1 ST THOMAS HOSP,ST THOMAS MED GRP,NASHVILLE,TN. ST VINCENT HOSP & MED CTR,LOS ANGELES,CA. MILTON S HERSHEY MED CTR,HERSHEY,PA. NE ONTARIO REG CANC CTR,SUDBURY,ON,CANADA. ROYAL N SHORE HOSP,DEPT CLIN ONCOL,ST LEONARDS,NSW 2065,AUSTRALIA. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. CIBA GEIGY PHARMACEUT CORP,SUMMIT,NJ. RP Hortobagyi, GN (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BREAST MED ONCOL,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 27 TC 690 Z9 702 U1 3 U2 12 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 DEC 12 PY 1996 VL 335 IS 24 BP 1785 EP 1791 DI 10.1056/NEJM199612123352401 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA VW683 UT WOS:A1996VW68300001 PM 8965890 ER PT J AU Lipsitz, SR Fitzmaurice, GM Sleeper, L Zhao, LP AF Lipsitz, SR Fitzmaurice, GM Sleeper, L Zhao, LP TI Estimating the joint distribution of repeated binary responses: Some small sample results SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE Bahadur representation; correlated binary data; marginal model; simulation ID LONGITUDINAL DATA-ANALYSIS AB The joint distribution of repeated binary observations is multinomial, and can be specified using a representation first suggested by Bahadur (in: H. Solomon (Ed.) Studies in item analysis and prediction (Stanford University Press, Stanford, 1961)), and later by Cox (Appl. Statist., 21 (1972) 113-120). Using the Bahadur representation, the marginal probabilities of success can be related to a set of covariates using the logistic link function, or any other suitable link function. If only the marginal parameters are of interest, then these can be estimated using the generalized estimating equations approach proposed by Liang and Zeger (Biometrica (1986)). However, often the joint probabilities are of scientific interest. For example, we may have interest in the probability of success on any of the repeated measures. This ''union'' probability can be specified in terms of the joint probabilities between the repealed measures, which can be expressed as functions of the marginal probabilities and the 2nd and higher-order correlations. We present the results of a simulation study designed to evaluate the small sample properties of several methods of estimating the parameters of the Bahadur model. C1 DANA FARBER CANC INST,DEPT BIOSTAT & EPIDEMIOL,BOSTON,MA 02115. UNIV HAWAII,CANC RES CTR HAWAII,PROGRAM EPIDEMIOL,HONOLULU,HI 96813. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. NR 8 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD DEC 11 PY 1996 VL 23 IS 2 BP 219 EP 227 DI 10.1016/S0167-9473(96)00031-X PG 9 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA VZ700 UT WOS:A1996VZ70000002 ER PT J AU Takahara, PM Frederick, CA Lippard, SJ AF Takahara, PM Frederick, CA Lippard, SJ TI Crystal structure of the anticancer drug cisplatin bound to duplex DNA SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID IRREGULAR NUCLEIC-ACIDS; DOUBLE-STRANDED DNA; FREE R-VALUE; MOLECULAR-STRUCTURE; MAJOR ADDUCT; A-DNA; ANGSTROM RESOLUTION; HYDROGEN-BONDS; BENT DNA; CIS-DIAMMINEDICHLOROPLATINUM(II) AB The X-ray crystal structure of d(CCTCTG*G*TCTCC). d(GGAGACCAGAGG), where G*G* represents the major adduct of the antitumor drug cisplatin on a duplex DNA dodecamer, was solved to a resolution of 2.6 Angstrom (R = 0.203, R-free = 0.245). The molecule crystallizes in the space group P1, with unit cell dimensions a = 31.27 Angstrom, b = 35.46 Angstrom, c = 47.01 Angstrom, alpha = 79.81 degrees; beta = 84.75 degrees, gamma = 82.79 degrees, and Z = 2. Two molecules in the asymmetric unit are related by a local two-fold symmetry axis and have very similar structures. The duplexes are bent significantly, each having a 26 degrees roll toward the major groove at the site of the platinum intrastrand cross-link. The platinum atom binds to the N7 atoms of adjacent guanine residues, compacting the major groove and widening and flattening the minor groove. Because of the shallow roll, the platinum atom is displaced from the planes of the guanine bases by similar to 1 Angstrom and is considerably strained. The overall structure of the cisplatin-modified duplex, contains an unusual juxtaposition of A-like and B-like helical segments. This bent structure is accommodated by an interesting and novel packing arrangement in the crystal. One end of each duplex packs end-to-end with another, as in crystal structures of B-DNA, whereas the other end packs into the minor groove of an adjacent molecule, much like A-DNA crystal packing. An unusual backbone-to-backbone packing interaction involving several CH ... C hydrogen bonds was also observed. The widened minor groove and the bend caused by platinum binding resembles the DNA component of the structure of the HMG domains of SRY bound to its recognition site DNA. This similarity suggests how HMG-domain proteins might recognize cisplatin-DNA adducts. C1 MIT,DEPT CHEM,CAMBRIDGE,MA 02139. DANA FARBER CANC INST,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. NR 59 TC 350 Z9 351 U1 3 U2 28 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 DEC 11 PY 1996 VL 118 IS 49 BP 12309 EP 12321 DI 10.1021/ja9625079 PG 13 WC Chemistry, Multidisciplinary SC Chemistry GA VX654 UT WOS:A1996VX65400008 ER PT J AU Munshi, HG Burks, DJ Joyal, JL White, MF Sacks, DB AF Munshi, HG Burks, DJ Joyal, JL White, MF Sacks, DB TI Ca2+ regulates calmodulin binding to IQ motifs in IRS-1 SO BIOCHEMISTRY LA English DT Article ID INSULIN-STIMULATED PHOSPHORYLATION; RECEPTOR SUBSTRATE IRS-1; SIGNALING COMPLEXES; INTACT-CELLS; FREE CALCIUM; PROTEIN; DOMAIN; RECOGNITION; TRIFLUOPERAZINE; ADIPOCYTES AB IRS-proteins couple the receptors for insulin and various cytokines to signalling proteins containing Src homology 2 (SH2) domains. Here we demonstrate that calmodulin, a mediator of Ca2+-dependent physiological processes, associates with IRS-1 in a phosphotyrosine-independent manner. IRS-1 coimmunoprecipitated with calmodulin from lysates of Chinese hamster ovary cells expressing IRS-1. The interaction was modulated by Ca2+, and calmodulin binding to IRS-1 was enhanced by increasing intracellular Ca2+ with A23187. In contrast, trifluoperazine, a cell-permeable calmodulin antagonist, decreased binding of calmodulin to IRS-1. Insulin stimulated tyrosine phosphorylation of IRS-1, but did not significantly alter the interaction between calmodulin and IRS-1. IQ-like motifs occur between residues 106-126 and 839-859 of IRS-1. Synthetic peptides based on these sequences inhibited the association between IRS-1 and calmodulin. These data demonstrate that calmodulin binds to IRS-1 in intact cells in a Ca2+-regulated manner, providing a molecular link between the signalling pathways. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. OI Sacks, David/0000-0003-3100-0735 FU NIDDK NIH HHS [DK09062, DK 38712, DK 43808] NR 48 TC 39 Z9 39 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 10 PY 1996 VL 35 IS 49 BP 15883 EP 15889 DI 10.1021/bi962107y PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VX510 UT WOS:A1996VX51000032 PM 8961953 ER PT J AU McCormick, RJ Badalian, T Fisher, DE AF McCormick, RJ Badalian, T Fisher, DE TI The leucine zipper may induce electrophoretic mobility anomalies without DNA bending SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Myc; transcription; chromatin ID HELIX-LOOP-HELIX; CRYSTAL-STRUCTURE; OPPOSITE ORIENTATIONS; B/HLH/Z DOMAIN; TRANSCRIPTION; FOS; JUN; RECOGNITION; BINDING; MYC AB Numerous proteins bend DNA upon binding, a phenomenon of potential significance for regulation of gene expression and chromatin. DNA bending is commonly predicted from the presence of electrophoretic mobility anomalies in protein-DNA complexes. However, as compared with electrophoretic methods, several DNA binding oncoprotein families do not display comparable evidence of DNA bends in x-ray structural studies. Herein, circularization kinetics and affinity measurements with prebent DNA templates were employed to assess bending and DNA structural preferences for Max and other basic helix-loop-helix/leucine zipper proteins. In this way, proteins in the Myc/Max basic helix-loop-helix/leucine zipper family were found not to bend DNA in solution but to actually stabilize DNA in an unbent configuration that resists circularization. The mobility anomaly was found to be induced by the leucine zipper protein motif, rather than structural distortions of DNA. Thus rigid protein domain structures may induce anomalous electrophoretic mobility. Moreover, the energetic preference of non-DNA bending proteins for unbent templates suggests mechanisms whereby chromatin structure may regulate transcription. C1 DANA FARBER CANC INST,BOSTON,MA 02115. FU NIAMS NIH HHS [R01 AR043369, AR43369] NR 29 TC 22 Z9 22 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 DEC 10 PY 1996 VL 93 IS 25 BP 14434 EP 14439 DI 10.1073/pnas.93.25.14434 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY448 UT WOS:A1996VY44800046 PM 8962069 ER PT J AU Tyagi, S Bhol, K Natarajan, K LivirRallatos, C Foster, CS Ahmed, AR AF Tyagi, S Bhol, K Natarajan, K LivirRallatos, C Foster, CS Ahmed, AR TI Ocular cicatricial pemphigoid antigen: Partial sequence and biochemical characterization SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ALPHA-6-BETA-4 INTEGRIN; BASEMENT-MEMBRANE; CELL-LINES; AUTOANTIBODIES; HEMIDESMOSOMES; PROTEIN; DISTINCT; SUBUNIT; ASSOCIATION; ANTIBODIES AB Ocular cicatricial pemphigoid (OCP) is an autoimmune disease that affects mainly conjunctiva and other squamous epithelia, OCP is histologically characterized by a separation of the epithelium from underlying tissues within the basement membrane zone, Immunopathological studies demonstrate the deposition of anti-basement membrane zone autoantibodies in vivo. Purified IgG from sera of patients with active OCP identified a cDNA clone from a human keratinocyte cDNA library that had complete homology with the cytoplasmic domain of beta 4-integrin, The sera recognized a 205-kDa protein in human epidermal, human conjunctiva, and tumor cell lysates that was identified as beta 4-integrin by its reaction with polyclonal and monoclonal antibodies to human beta 4-integrin. Sera from patients with bullous pemphigoid. pemphigus vulgaris, and cicatricial pemphigoid-like diseases did not recognize the 205-kDa protein, indicating the specificity of the binding, These data strongly implicate a role for human beta 4-integrin in the pathogenesis of OCP, It should be emphasized that multiple antigens in the basement membrane zone of squamous epithelia may serve as targets for a wide spectrum of autoantibodies observed in vesiculobullous diseases, Molecular definition of these autoantigens will facilitate the classification and characterization of subsets of cicatricial pemphigoid and help distinguishing them from bullous pemphigoid, This study highlights the function and importance of beta 4-integrin in maintaining the attachment of epithelial cells to the basement membrane. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. FU NEI NIH HHS [EYO8378]; NIDCR NIH HHS [DEO9978] NR 42 TC 88 Z9 88 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 DEC 10 PY 1996 VL 93 IS 25 BP 14714 EP 14719 DI 10.1073/pnas.93.25.14714 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY448 UT WOS:A1996VY44800097 PM 8962120 ER PT J AU Nagasawa, T Nakajima, T Tachibana, K Iizasa, H Bleul, CC Yoshie, O Matsushima, K Yoshida, N Springer, TA Kishimoto, T AF Nagasawa, T Nakajima, T Tachibana, K Iizasa, H Bleul, CC Yoshie, O Matsushima, K Yoshida, N Springer, TA Kishimoto, T TI Molecular cloning and characterization of a murine pre-B-cell growth-stimulating factor stromal cell-derived factor 1 receptor, a murine homolog of the human immunodeficiency virus 1 entry coreceptor fusin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chemokine; B lymphopoiesis; bone marrow; myelopoiesis; cardiogenesis ID CHROMOSOMAL LOCALIZATION; GENE AB Pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 (PBSF/SDF-1) is a member of the CSC group of chemokines that is initially identified as a bone marrow stromal cell-derived factor and as a pre-B-cell stimulatory factor, Although most chemokines are thought to be inducible inflammatory mediators, PBSF/SDF-1 is essential for perinatal viability, B lymphopoiesis, bone marrow myelopoiesis, and cardiac ventricular septal formation, and it has chemotactic activities on resting lymphocytes and monocytes, In this paper, we hare isolated a cDNA that encodes a seven transmembrane-spanning-domain receptor, designated pre-B-cell-derived chemokine receptor (PB-CKR) from a murine pre-B-cell door, DW34. The deduced amino acid sequence has 90% identity with that of a HUMSTSR/fusin, a human immunodeficiency virus 1 (HIV-1) entry coreceptor, However, the second extracellular region has lower identity (67%) compared with HUMSTSR/fusin. PB-CKR is expressed during embryo genesis and in many organs and T cells of adult mice, Murine PBSF/SDF-1 induced an increase in intracellular free Ca2+ in DW35 cells and PB-CKR-transfected Chinese hamster ovary (CHO) cells, suggesting that PB-CKR is a functional receptor for murine PBSF/SDF-1. Murine PBSF/SDF-1 also induced Ca2+ influx in fusin-transfected CHO cells, On the other hand, considering previous results that HIV-1 does not enter murine T cells that expressed human CD4, PB-CKR may not support HIV-1 infection, Thus, PB-CKR HIV-1 will be an important tool for functional mapping of HIV-1 entry coreceptor fusin and for understanding the function of PBSF/SDF-1 further. C1 OSAKA UNIV,INST MOL & CELLULAR BIOL,SUITA,OSAKA 565,JAPAN. SHIONOGI INST MED SCI,SETTSU,OSAKA 566,JAPAN. UNIV TOKYO,GRAD SCH MED,DIV SOCIAL MED,DEPT MOL PREVENT MED,BUNKYO KU,TOKYO 113,JAPAN. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. OSAKA UNIV,SCH MED,DEPT MED 3,SUITA,OSAKA 565,JAPAN. RP Nagasawa, T (reprint author), OSAKA MED CTR MATERNAL & CHILD HLTH,RES INST,DEPT IMMUNOL,840 MURODO CHO,IZUMI,OSAKA 59002,JAPAN. RI Kishimoto, Tadamitsu/C-8470-2009; Iizasa, Hisashi/A-9821-2012 NR 24 TC 250 Z9 256 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 DEC 10 PY 1996 VL 93 IS 25 BP 14726 EP 14729 DI 10.1073/pnas.93.25.14726 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY448 UT WOS:A1996VY44800099 PM 8962122 ER PT J AU Yuan, F Chen, Y Dellian, M Safabakhsh, N Ferrara, N Jain, RK AF Yuan, F Chen, Y Dellian, M Safabakhsh, N Ferrara, N Jain, RK TI Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor vascular permeability factor antibody SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE angiogenesis; vascular obstruction ID HUMAN ADENOCARCINOMA LS174T; BLOOD-VESSEL GROWTH; HUMAN COLON-CANCER; MICROVASCULAR PERMEABILITY; SCID MICE; ANGIOGENESIS; INHIBITION; METASTASIS; EXPRESSION; TISSUE AB The hyperpermeability of tumor vessels to macromolecules, compared with normal vessels, is presumably due to vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) released by neoplastic and/or host cells, In addition, VEGF/VPF is a potent angiogenic factor, Removal of this growth factor may reduce the permeability and inhibit tumor angiogenesis. To test these hypotheses, we transplanted a human glioblastoma (U87), a human colon adenocarcinoma (LS174T), and a human melanoma (P-MEL) into two locations in immunodeficient mice: the cranial window and the dorsal skinfold chamber, The mice bearing vascularized tumors were treated with a bolus (0.2 ml) of either a neutralizing antibody (A4.6.1) (492 mu g/ml) against VEGF/VPF or PBS (control). We found that tumor vascular permeability to albumin in antibody-treated groups was lower than in the matched controls and that the effect of the antibody was time-dependent and influenced by the mode of injection, Tumor vascular permeability did not respond to i.p. injection of the antibody until 4 days posttreatment, However, the permeability was reduced within 6 h after i.v. injection of the same amount of antibody, In addition to the reduction in vascular permeability, the tumor vessels became smaller in diameter and less tortuous after antibody injections and eventually disappeared from the surface after four consecutive treatments in U87 tumors, These results demonstrate that tumor vascular permeability can be reduced by neutralization of endogenous VEGF/VPF and suggest that angiogenesis and the maintenance of integrity of tumor vessels require the presence of VEGF/VPF in the tissue microenvironment. The latter finding reveals a new mechanism of tumor vessel regression-i.e., blocking the interactions between VEGF/VPF and endothelial cells or inhibiting VEGF/VPF synthesis in solid tumors causes dramatic reduction in vessel diameter, which mag block the passage of blood elements and thus lead to vascular regression. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. GENENTECH INC,S SAN FRANCISCO,CA 94080. RP Yuan, F (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. RI Yuan, Fan/A-1287-2011 FU NCI NIH HHS [R35-CA-56591] NR 34 TC 487 Z9 501 U1 3 U2 19 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 DEC 10 PY 1996 VL 93 IS 25 BP 14765 EP 14770 DI 10.1073/pnas.93.25.14765 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY448 UT WOS:A1996VY44800106 PM 8962129 ER PT J AU Carroll, M Tomasson, MH Barker, GF Golub, TR Gilliland, DG AF Carroll, M Tomasson, MH Barker, GF Golub, TR Gilliland, DG TI The TEL platelet-derived growth factor beta receptor (PDGF beta R) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGF beta R kinase-dependent signaling pathways SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ETS GENE FAMILY; TYROSINE KINASE; INDEPENDENT ACTIVATION; PHOSPHOTYROSINE PHOSPHATASE; CHROMOSOMAL TRANSLOCATION; BINDING; ABL; SEQUENCES; ONCOGENE; C-ETS-1 AB The TEL/PDGF beta R fusion protein is the product of the t(5;12) translocation in patients with chronic myelomonocytic leukemia, The TEL/PDGF beta R is an unusual fusion of a putative transcription factor, TEL, to a receptor tyrosine kinase. The translocation fuses the amino terminus of TEL, containing the helix-loop-helix (HLH) domain, to the transmembrane and cytoplasmic domain of the PDGF beta R. We hypothesized that TEL/PDGF beta R self-association, mediated by the HLH domain of TEL, would lead to constitutive activation of the PDGF beta R tyrosine kinase domain and cellular transformation, Analysis of in vitro-translated TEL/PDGF beta R confirmed that the protein self associated and that self-association was abrogated by deletion of 51 aa within the TEL HLH domain. In vivo, TEL/PDGP beta R was detected as a 100-kDa protein that was constitutively phosphorylated on tyrosine and transformed the murine hematopoietic cell line Ba/F3 to interleukin 3 growth factor independence, Transformation of Ba/F3 cells required the HLH domain of TEL and the kinase activity of the PDGF beta R portion of the fusion protein. Immunoblotting demonstrated that TEL/PDGF beta R associated with multiple signaling molecules known to associate with the activated PDGF beta R, including phospholipase C gamma 1, SHP2, and phosphoinositol-3-kinase. TEL/PDGF beta R is a novel transforming protein that self-associates and activates PDGF beta R-dependent signaling pathways, Oligomerization of TEL/PDGF beta R that is dependent on the TEL HLH domain provides further evidence that the HLH domain, highly conserved among ETS family members, is a self-association motif. C1 BRIGHAM & WOMENS HOSP,HOWARD HUGHES MED INST,DIV HEMATOL & ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. FU NCI NIH HHS [P01CA66996-01, P01 CA066996]; NIDDK NIH HHS [P01 DK050654, P01DK50654-01] NR 28 TC 215 Z9 221 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 10 PY 1996 VL 93 IS 25 BP 14845 EP 14850 DI 10.1073/pnas.93.25.14845 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY448 UT WOS:A1996VY44800120 PM 8962143 ER PT J AU Buckner, RL Bandettini, PA OCraven, KM Savoy, RL Petersen, SE Raichle, ME Rosen, BR AF Buckner, RL Bandettini, PA OCraven, KM Savoy, RL Petersen, SE Raichle, ME Rosen, BR TI Detection of cortical activation during averaged single trials of a cognitive task using functional magnetic resonance imaging SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neuroimaging; single trial; language; prefrontal ID HUMAN BRAIN AB Functional neuroimaging studies in human subjects using positron emission tomograph or functional magnetic resonance imaging (fMRI) are typically conducted by collecting data over extended time periods that contain many similar trials of a task. Here methods for acquiring fMRI data from single trials of a cognitive task are reported, In experiment one, whole brain fMRI was used to reliably detect single-trial responses in a prefrontal region within single subjects. In experiment two, higher temporal sampling of a more limited spatial field Has used to measure temporal offsets between regions, Activation maps produced solely from the single-trial data were comparable to those produced from blocked runs. These findings suggest that single-trial paradigms a will be able to exploit the high temporal resolution of fMRI. Such paradigms will provide experimental flexibility and time-resolved data for individual brain regions on a trial-by-trial basis. C1 ROWLAND INST SCI INC,CAMBRIDGE,MA 02142. HARVARD UNIV,SCH MED,BOSTON,MA 02115. WASHINGTON UNIV,SCH MED,DEPT NEUROL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT NEUROSURG,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,MCDONNELL CTR STUDY HIGHER BRAIN FUNCT,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT RADIOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT ANAT & NEUROBIOL,ST LOUIS,MO 63110. RP Buckner, RL (reprint author), MASSACHUSETTS GEN HOSP,NUCL MAGNET RESONANCE CTR,DEPT RADIOL,13TH ST,BLDG 149,ROOM 2301,CHARLESTOWN,MA 02129, USA. RI Bandettini, Peter/F-5871-2012 FU NIA NIH HHS [AG-08377]; NIDA NIH HHS [P01 DA009467, P1DA09467] NR 23 TC 403 Z9 414 U1 5 U2 13 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 DEC 10 PY 1996 VL 93 IS 25 BP 14878 EP 14883 DI 10.1073/pnas.93.25.14878 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY448 UT WOS:A1996VY44800126 PM 8962149 ER PT J AU Strettoi, E Masland, RH AF Strettoi, E Masland, RH TI The number of unidentified amacrine cells in the mammalian retina SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE starburst; indoleamine; AII cells; anatomy; cortex ID LOCAL CIRCUIT NEURONS; MONKEY STRIATE CORTEX; GABA-LIKE IMMUNOREACTIVITY; RABBIT RETINA; CAT RETINA; ACCUMULATING NEURONS; CHOLINERGIC NEURONS; BIPOLAR CELLS; IDENTIFICATION; GLUTAMATE AB The three largest known populations of amacrine cells in the rabbit retina were stained with fluorescent probes in whole mounts and counted at a series of retinal eccentricities. The retinas were counterstained using a fluorescent DNA-binding molecule and the total number of nuclei in the inner nuclear layer were counted in confocal sections. From the total number of inner nuclear layer cells and the known fraction of them occupied by amacrine cells, the fraction of amacrine cells made up by the stained populations could be calculated. Starburst cells made up 3%, indoleamine-accumulating cells made up 4%, and AII cells made up 11% of all amacrine cells. By referring four smaller populations of amacrine cells to the number of indoleamine-accumulating cells, they were estimated to make up 4% of all amacrine cells. Thus, 78% of all amacrine cells in the rabbit's retina are known only from isolated examples, if at all. This proportion is similar in the retinas of the mouse, cat, and monkey. It is likely that a substantial fraction of the local circuit neurons present in other regions of the central nervous system are also invisible as populations to current techniques. C1 MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. RP Strettoi, E (reprint author), CNR,IST NEUROFISIOL,VIA SAN ZENO 51,I-56127 PISA,ITALY. FU NEI NIH HHS [EY01075] NR 44 TC 93 Z9 95 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 DEC 10 PY 1996 VL 93 IS 25 BP 14906 EP 14911 DI 10.1073/pnas.93.25.14906 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY448 UT WOS:A1996VY44800131 PM 8962154 ER PT J AU Stafford, RS Singer, DE AF Stafford, RS Singer, DE TI National patterns of warfarin use in atrial fibrillation SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ANTICOAGULATION; STROKE; PREVENTION; ASPIRIN; THERAPY AB Background: Despite consensus that patients with atrial fibrillation benefit from warfarin sodium anticoagulation, little is known about national trends and predictors of anticoagulant use. Methods: We analyzed 1062 visits by patients with atrial fibrillation to randomly selected office-based physicians included in the National Ambulatory Medical Care Surveys in 1980, 1981, 1985, and 1989 through 1993. Warfarin and aspirin use in these patients was extrapolated to national patterns and logistic regression was used to determine independent predictors. Results: Patients with atrial fibrillation made an estimated 1.3 (1980) to 3.1 (1992) million annual visits to physicians. Warfarin use in atrial fibrillation increased from 7% in 1980 and 1981 to 32% in 1992 and 1993 (P<.001 for trend). In 1992 and 1993, patients 80 years or older were significantly less likely to be taking warfarin (19%) compared with younger patients (36%), but showed similar rates of increase from 1980 and 1981 to 1992 and 1993. Tn 1992 and 1993, anticoagulation therapy was significantly more likely to be reported in visits to cardiologists (32%) and general internists (40%) compared with general and family practitioners (15%), but was similar in women (34%) and men (30%). Residents of the South (16%) had significantly lower rates of warfarin use than those in other regions of the United States (36%). Aspirin use increased from 3% to 10% (P=.001 for trend) and showed little overlap with warfarin use, Multiple logistic regression indicated that more recent year, residence outside the South, patient aged 65 to 74 years, and visits to cardiologists and internists increased the likelihood of warfarin use. Conclusions: Anticoagulant use for atrial fibrillation has increased dramatically. The substantial increase from 1989 and 1990 to 1992 and 1993 coincided with the publication of several randomized clinical trials reporting the benefits of warfarin. Although it is unrealistic to expect universal warfarin use, the 1992 and 1993 rate of 32% is probably suboptimal given the benefit of anticoagulation in preventing embolic strokes. The oldest patients, in whom warfarin may have its greatest benefit, appear to have the lowest rates of anticoagulant use. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. HARVARD UNIV, SCH PUBL HLTH, DEPT EPIDEMIOL, BOSTON, MA 02115 USA. RP Stafford, RS (reprint author), MASSACHUSETTS GEN HOSP, GEN INTERNAL MED UNIT, MED SERV, 50 STANIFORD ST, 9TH FLOOR, BOSTON, MA 02114 USA. FU PHS HHS [R01H S07892-01A2] NR 35 TC 168 Z9 171 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC 9 PY 1996 VL 156 IS 22 BP 2537 EP 2541 DI 10.1001/archinte.156.22.2537 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA VX013 UT WOS:A1996VX01300003 PM 8951296 ER PT J AU Salgia, R Avraham, S Pisick, E Li, JL Raja, S Greenfield, EA Sattler, M Avraham, H Griffin, JD AF Salgia, R Avraham, S Pisick, E Li, JL Raja, S Greenfield, EA Sattler, M Avraham, H Griffin, JD TI The related adhesion focal tyrosine kinase forms a complex with paxillin in hematopoietic cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION; PHOSPHORYLATION; BINDING; IDENTIFICATION; P210(BCR/ABL); PP125(FAK); ASSOCIATION; PROTEINS; PP125FAK; CLONING AB Related adhesion focal tyrosine kinase (RAFTK), also known as proline-rich tyrosine kinase 2 and cellular adhesion kinase beta, has been recently cloned and characterized as a member of the focal adhesion kinase (FAR) subfamily. RAFTK has an overall 48% amino acid homology to p125(FAK) and contains a kinase domain but lacks a transmembrane region, myristylation sites, and Src homology region 2 and 3 domains. By Northern blot analysis, RAFTK is expressed in myeloid, lymphoid, and megakaryocytic hematopoietic cells. Like p125(FAK), we found that RAFTK interacts with the focal adhesion protein paxillin. In the lymphoid cell line BaF3 and the myeloid cell Line 32Dc13, RAFTK coprecipitates with paxillin. Using in vitro binding assays, RAFTK and paxillin were shown to bind directly, through a segment of paxillin that required amino acids 100-227 and a domain in the C terminus of RAFTK. In vitro, RAFTK could phosphorylate paxillin on tyrosine residues, These results suggest that RAFTK, as well as p125(FAK), may be important in phosphotyrosine-signaling events within the focal adhesion. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DEACONESS HOSP,DIV HEMATOL & ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. OI Li, Jian-Liang/0000-0002-6487-081X FU NCI NIH HHS [CA60821]; NHLBI NIH HHS [HL51456, HL55445] NR 31 TC 126 Z9 129 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 DEC 6 PY 1996 VL 271 IS 49 BP 31222 EP 31226 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VW686 UT WOS:A1996VW68600035 PM 8940124 ER PT J AU Cryns, VL Bergeron, L Zhu, H Li, HL Yuan, JY AF Cryns, VL Bergeron, L Zhu, H Li, HL Yuan, JY TI Specific cleavage of alpha-fodrin during Fas- and tumor necrosis factor-induced apoptosis is mediated by an interleukin-1 beta-converting enzyme Ced-3 protease distinct from the poly(ADP-ribose) polymerase protease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEATH GENE CED-3; SMALL NUCLEAR RIBONUCLEOPROTEIN; PROGRAMMED CELL-DEATH; CONVERTING-ENZYME; CYSTEINE PROTEASE; IN-VITRO; IL-1-BETA-CONVERTING ENZYME; ICE/CED-3 PROTEASE; MULTIPLE PROTEASES; MAMMALIAN HOMOLOG AB Interleukin 1 beta-converting enzyme (ICE)/Ced-3 proteases play a critical role in apoptosis. One well characterized substrate of these proteases is the DNA repair enzyme poly(ADP-ribose) polymerase. We report here that alpha-fodrin, an abundant membrane-associated cytoskeletal protein, is cleaved rapidly and specifically during Fas- and tumor necrosis factor-induced apopto sis; this cleavage is mediated by an ICE/Ced-3 protease distinct from the poly(ADP-ribose) polymerase protease. Studies in cells treated with these apoptotic stimuli reveal that both fodrin and poly(ADP-ribose) polymerase proteolysis are inhibited by acetyl-Tyr-Val-Ala-Asp chloromethyl ketone and CrmA, specific inhibitors of ICE/Ced-3 proteases. However, fodrin proteolysis can be distinguished from poly(ADP-ribose) polymerase prote olysis by its relative insensitivity to acetyl-Asp-Glu-Val-Asp aldehyde (DEVD-CHO), a selective inhibitor of a subset of ICE/Ced-3 proteases that includes CPP32. DEVD-CHO protects cells from Fas induced apoptosis but does not prevent fodrin proteolysis, indicating that cleavage of this protein can be uncoupled from apoptotic cell, death. Moreover, purified fodrin is cleaved in vitro by CPP32 (but not by ICE) into fragments of the same size observed in vivo during apoptosis. These findings suggest that fodrin proteolysis in vivo may reflect the activity of multiple ICE/Ced-3 proteases whose partial sensitivity to DEVD-CHO reflects a limited contribution from CPP32, or an ICE/Ced-3 protease less sensitive than CPP32 to DEVD-CHO inhibition. C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. FU NCI NIH HHS [K08-CA01752-03]; NIA NIH HHS [AG12859-01] NR 58 TC 181 Z9 182 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 6 PY 1996 VL 271 IS 49 BP 31277 EP 31282 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VW686 UT WOS:A1996VW68600043 PM 8940132 ER PT J AU Ilaria, RL VanEtten, RA AF Ilaria, RL VanEtten, RA TI P210 and P190(BCR/ABL) induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; HEMATOPOIETIC-CELL LINE; TRANSCRIPTION FACTOR; C-ABL; PHILADELPHIA-CHROMOSOME; KINASE-ACTIVITY; SH2 DOMAIN; ACTIVATION; PROTEIN; SIGNAL AB The products of the Philadelphia chromosome translocation, P210 and p190(BCR/ABL), are cytoplasmic protein tyrosine kinases that share the ability to transform hematopoietic cytokine-dependent cell lines to cytokine independence but differ in the spectrum of leukemia induced in vivo. We have analyzed the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways in hematopoietic cells transformed by Bcr/Abl, STAT5 and, to a lesser extent, STATs 1 and 3 were constitutively activated by tyrosine phosphorylation and induction of DNA binding activity in both P210 and p190(BCR/ABL)-transformed cells, but P190 differed in that it also prominently activated STAT6, There was low level tyrosine phosphorylation of JAKs 1, 2, and 3 in Bcr/Abl-transformed cells, but no detectable complex formation with Bcr/Abl, and activation of STAT5 by P210 was not blocked by two different dominant-negative JAK mutants, These results suggest that P210 and p190(BCR/ABL) directly activate specific STAT family members and may help explain their overlapping yet distinct roles in leukemogenesis. C1 HARVARD UNIV,SCH MED,DEPT GENET,CTR BLOOD RES,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. FU NHLBI NIH HHS [K08HL03310-01] NR 46 TC 342 Z9 349 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 DEC 6 PY 1996 VL 271 IS 49 BP 31704 EP 31710 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VW686 UT WOS:A1996VW68600104 PM 8940193 ER PT J AU Blumenthal, D Campbell, EG Causino, N Louis, KS AF Blumenthal, D Campbell, EG Causino, N Louis, KS TI Participation of life-science faculty in research relationships with industry SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article AB Background Recent research on academic-industrial research relationships in the life sciences has examined their frequency, benefits, risks, and evolution from the standpoint of industrial sponsors of research. We collected information on the extent and effects of academic-industrial research relationships from the standpoint of faculty members who participate in them. Methods We used a mailed questionnaire to collect data between October 1994 and April 1995 from 2052 faculty members (of 3169 eligible respondents; response rate, 65 percent) in the life sciences at the 50 U.S. universities receiving the most research funding from the National Institutes of Health. Results Twenty-eight percent of the respondents received research support from industry. Faculty members receiving industrial funds had more peer-reviewed articles published in the previous three years, participated in more administrative activities in their institutions or disciplines, and were more commercially active than faculty members without such funding. However, faculty members receiving more than two thirds of their research support from industry were less academically productive than those receiving a lower level of industrial support, and their articles were less influential than those by researchers with no industrial support. Faculty members with industrial support were significantly more likely than those without industrial support to report that trade secrets had resulted from their work (14.5 percent vs. 4.7 percent, P<0.001) and that they had taken commercial considerations into account when choosing research topics (35 percent vs. 14 percent, P<0.001). Conclusions Faculty members with industrial research support are at least as productive academically as those without such support and are more productive commercially. However, faculty members who have research relationships with industry are more likely to restrict their communication with colleagues, and high levels of industrial support may be associated with less academic activity without evidence of proportional increases in commercial productivity. (C) 1996, Massachusetts Medical Society. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. UNIV MINNESOTA,COLL EDUC,MINNEAPOLIS,MN 55455. RP Blumenthal, D (reprint author), MASSACHUSETTS GEN HOSP,DIV GEN INTERNAL MED,HLTH POLICY RES & DEV UNIT,50 STANIFORD ST,BOSTON,MA 02114, USA. FU NHGRI NIH HHS [HG00724-01] NR 6 TC 216 Z9 219 U1 1 U2 9 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 DEC 5 PY 1996 VL 335 IS 23 BP 1734 EP 1739 DI 10.1056/NEJM199612053352305 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VW795 UT WOS:A1996VW79500005 PM 8929266 ER PT J AU Berkowitz, RS Goldstein, DP AF Berkowitz, RS Goldstein, DP TI Medical progress - Chorionic tumors SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID GESTATIONAL TROPHOBLASTIC DISEASE; PARTIAL HYDATIDIFORM MOLE; CENTRAL NERVOUS-SYSTEM; SINGLE-AGENT CHEMOTHERAPY; RISK-FACTORS; PROPHYLACTIC CHEMOTHERAPY; ACTINOMYCIN-D; PROGNOSTIC-SIGNIFICANCE; RESPIRATORY-FAILURE; NATURAL-HISTORY C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT OBSTET GYNECOL & REPROD BIOL,BOSTON,MA 02115. RP Berkowitz, RS (reprint author), BRIGHAM & WOMENS HOSP,DIV GYNECOL ONCOL,NEW ENGLAND TROPHOBLAST DIS CTR,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 100 TC 170 Z9 174 U1 0 U2 4 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 DEC 5 PY 1996 VL 335 IS 23 BP 1740 EP 1748 DI 10.1056/NEJM199612053352306 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA VW795 UT WOS:A1996VW79500006 PM 8929267 ER PT J AU Rosenberg, JE Lisle, DK Burwick, JA Ueki, K vonDeimling, A Mohrenweiser, HW Louis, DN AF Rosenberg, JE Lisle, DK Burwick, JA Ueki, K vonDeimling, A Mohrenweiser, HW Louis, DN TI Refined deletion mapping of the chromosome 19q glioma tumor suppressor gene to the D19S412-STD interval SO ONCOGENE LA English DT Article DE chromosome 19; D19S745; glioma; tumor suppressor gene ID REGION; ASTROCYTOMAS; CANDIDATE; 19Q13.3; MAP AB Allelic loss of chromsome 19q occurs frequently in malignant gliomas, suggesting the presence of a chromosome 19q glioma tumor suppressor gene, Deletion mapping studies have delineated a 3.5 Mb candidate region between D19S219 and HRC, Cloned sequences from the proximal 425 kb of this interval, however, have not shown tumor-specific alterations, To refine the location of the tumor suppressor gene further, we conducted loss of heterozygosity studies on 191 malignant gliomas using nine PCR-based polymorphisms, These included the previously identified and physically mapped markers D19S219, DM, D19S112, HRC and the recently physically mapped polymorphisms at D19S412, STD, D19S596 and GYS. In addition, we isolated a novel microsatellite polymorphism that maps 400 kb telomeric to D19S112, Oligodendroglial tumors showed frequent loss of heterozygosity in all grades, and typically displayed allelic loss at all studied markers, Astrocytomas, however, showed frequent loss primarily in anaplastic astrocytomas and displayed deletion breakpoints within the candidate region, Deletion mapping revealed a minimal region of overlap between D19S412 and STD, a distance of 900 kb, These data suggest that the D19S412-STD interval represents the most likely location for a chromsome 19q glioma tumor suppressor gene involved in astrocytoma, and perhaps oligodendroglioma, tumorigenesis. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,NEUROSURG SERV,MOL NEUROONCOL LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. UNIV HOSP,INST NEUROPATHOL,BONN,GERMANY. LAWRENCE LIVERMORE NATL LAB,CTR HUMAN GENOME,LIVERMORE,CA 94550. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X FU NCI NIH HHS [CA 57683, CA 69285] NR 16 TC 76 Z9 77 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 5 PY 1996 VL 13 IS 11 BP 2483 EP 2485 PG 3 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VX108 UT WOS:A1996VX10800023 PM 8957092 ER PT J AU Blumenthal, D AF Blumenthal, D TI Ethics issues in academic-industry relationships in the life sciences: The continuing debate SO ACADEMIC MEDICINE LA English DT Article; Proceedings Paper CT Working Symposium on Conflict of Interest in University-Industry Research Relationships CY OCT 30-31, 1995 CL CASE W RESERVE UNIV, CLEVELAND, OH HO CASE W RESERVE UNIV AB The author reviews in detail the status of academic-industry relationships (AIRs) in the life sciences from both ethical and empirical. perspectives, and identifies ethical issues that have been resolved and those that must still be debated. He summarizes by stating that ethical reasoning militates against the involvement of scientists and universities in those AIRs in which a financial conflict of interest on the part of life science investigators may affect the welfare of human subjects and trainees, Even in other types of AIRs, conflicts of interest have effects on professional decision making that could damage the integrity and productivity of life sciences research, especially scientists' withholding of data and their redirecting of research in more commercial directions. These effects could also help undermine public trust in and support of university researchers, Balanced against these worrisome effects are the benefits of AIRs in increasing some investigators' creativity and productivity, in encouraging technology transfer, and thus in promoting economic growth and public health. He concludes that more research is needed on the harms and benefits of AIRs, especially the development of better data on the effects of withholding data, and also on the economic and health benefits of AIRs and public attitudes toward issues of scientific research that involve possible conflicts of interest. More information on these questions would allow policymakers to make more realistic estimates of the gains and losses associated with AIRs. In the meantime, current information suggests that in general the conflicts of interest created by AIRs are real, consequential, but tolerable if managed carefully. Until more is known about the effects of AIRs, it is prudent for universities and faculty to participate at modest levels in such relationships and to monitor them carefully. This article is one of three in this issue of Academic Medicine that deal with issues of conflict of interest in university-industry research relationships. These articles are discussed in an overview that precedes them. C1 HEALTHCARE SYST,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RP Blumenthal, D (reprint author), MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,50 STANFORD ST,9TH FLOOR,BOSTON,MA 02114, USA. NR 14 TC 35 Z9 35 U1 0 U2 8 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD DEC PY 1996 VL 71 IS 12 BP 1291 EP 1296 DI 10.1097/00001888-199612000-00010 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA VZ142 UT WOS:A1996VZ14200012 PM 9114886 ER PT J AU Donovan, DM AF Donovan, DM TI Marlatt's classification of relapse precipitants: Is the Emperor still wearing clothes? SO ADDICTION LA English DT Article ID ALCOHOL AB The present paper provides comments on the series of papers dealing with the reliability and validity of Marlatt's taxonomy of relapse precipitants. The results of these papers suggest that thc degree of reliability and predictive validity of the original relapse taxonomy, as operationalized and employed in the present studies, is lower than would be hoped for. Both methodological factors in the studies and limitations in the taxonomy are discussed. While the original taxonomic system has provided a useful heuristic model and a guide for clinical intervention, it is recommended that it be modified to improve its utility in research and practice. A number of specific recommendations are provided for modifying the system C1 WASHINGTON UNIV,DEPT PSYCHIAT & BEHAV SCI,SEATTLE,WA 98105. VET AFFAIRS PUGET SOUND HLTH CARE SYST,ADDICT TREATMENT CTR,SEATTLE,WA. RP Donovan, DM (reprint author), WASHINGTON UNIV,INST ALCOHOL & DRUG ABUSE,3937 15TH AVE NE,SEATTLE,WA 98105, USA. NR 14 TC 13 Z9 13 U1 1 U2 3 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD DEC PY 1996 VL 91 SU S BP S131 EP S137 DI 10.1111/j.1360-0443.1996.tb02333.x PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA WC567 UT WOS:A1996WC56700012 PM 8997787 ER PT J AU Donovan, DM AF Donovan, DM TI Assessment issues and domains in the prediction of relapse SO ADDICTION LA English DT Article ID SITUATIONS; ALCOHOL AB The present paper provides a brief overview of methodological issues involved in the process of assessment related to the classification and prediction of relapse. These include conceptual and operational definitions of relapse, retrospective versus prospective assessment, attributional biases in recalling relapse events, single versus multiple determinants of relapse, static versus dynamic assessment models, and the necessary level of specificity involved in the assessment of relapse categories. Additionally, general domains representing distal personal characteristics, intermediate background variables and factors proximal in time to relapse situations are reviewed. Potential variables appropriate for assessment within each of these domains are described. It is concluded that relapse is best understood as a complex process having multiple and interactive determinants that vary in their temporal proximity from and their relative influence on relapse. An adequate assessment model must be sufficiently comprehensive to include theoretically relevant variables from each of the multiple domains and different levels of potential predictors. C1 WASHINGTON UNIV,DEPT PSYCHIAT & BEHAV SCI,SEATTLE,WA 98105. VET AFFAIRS PUGET SOUND HLTH CARE SYST,ADDICT TREATMENT CTR,SEATTLE,WA. RP Donovan, DM (reprint author), WASHINGTON UNIV,INST ALCOHOL & DRUG ABUSE,3937 15TH AVE NE,SEATTLE,WA 98105, USA. NR 22 TC 27 Z9 27 U1 2 U2 5 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD DEC PY 1996 VL 91 SU S BP S29 EP S36 DI 10.1111/j.1360-0443.1996.tb02325.x PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA WC567 UT WOS:A1996WC56700004 PM 8997779 ER PT J AU Dohmen, K Baraona, E Ishibashi, H Pozzato, G Moretti, M Matsunaga, C Fujimoto, K Lieber, CS AF Dohmen, K Baraona, E Ishibashi, H Pozzato, G Moretti, M Matsunaga, C Fujimoto, K Lieber, CS TI Ethnic differences in gastric sigma-alcohol dehydrogenase activity and ethanol first-pass metabolism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE stomach; alcohol dehydrogenase isozymes; firstpass metabolism; ethnic differences ID HUMAN-LIVER ALCOHOL; ALDEHYDE DEHYDROGENASES; 1ST-PASS METABOLISM; JAPANESE SUBJECTS; HUMAN STOMACH; ADH7 GENE; BLOOD; BIOAVAILABILITY; POLYMORPHISMS; PURIFICATION AB We assessed whether the low sigma-alcohol dehydrogenase (ADH) activity in Japanese (compared with Caucasians) affects the first-pass metabolism of ethanol. ADH isozyme activities were determined in endoscopic biopsies of the gastric corpus from 24 Japanese and 41 Caucasian men by starch gel electrophoresis and by comparing the reduction of m-nitrobenzaldehyde (a preferred substrate of sigma-ADH) with that of acetaldehyde (a preferred substrate of gamma-ADH) and the glutathione-dependent formaldehyde oxidation (a specific reaction of chi-ADH). Alcohol pharmacokinetics was compared in 10 Japanese and 10 Caucasians after administration of ethanol (300 mg/kg of body weight) intravenously or orally, using 5 and 40% oral solutions. Japanese exhibited lower sigma-ADH activity than Caucasians, with no difference in the other gastric isozymes. With 5% ethanol, first-pass metabolism was strikingly lower in Japanese than in Caucasions. Blood alcohol levels were similar because of the high elimination rate in Japanese due to the hepatic beta(2)-ADH variant. With 40% ethanol, the first-pass metabolism increased in both groups to comparable levels, suggesting an additional contribution by chi-ADH at high ethanol concentrations. These results indicate that sigma-ADH activity contributes significantly to gastric ethanol oxidation and its lower activity in Japanese is associated with lesser first-pass metabolism. C1 BRONX VET AFFAIRS MED CTR,CTR ALCOHOL RES & TREATMENT,NEW YORK,NY. MT SINAI SCH MED,NEW YORK,NY. KYUSHU UNIV,DEPT INTERNAL MED 1,FUKUOKA 812,JAPAN. UNIV TRIESTE,INST CLIN MED,TRIESTE,ITALY. SAGA MED SCH,DEPT INTERNAL MED,DIV GASTROENTEROL,SAGA,JAPAN. FU NIAAA NIH HHS [AA 03508, AA 07275] NR 34 TC 76 Z9 78 U1 0 U2 4 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 DEC PY 1996 VL 20 IS 9 BP 1569 EP 1576 DI 10.1111/j.1530-0277.1996.tb01701.x PG 8 WC Substance Abuse SC Substance Abuse GA VZ863 UT WOS:A1996VZ86300012 PM 8986205 ER PT J AU Sparano, JA Lipsitz, S Wadler, S Hansen, R Bushunow, PW Kirkwood, J Flynn, PJ Dutcher, JP Benson, AB AF Sparano, JA Lipsitz, S Wadler, S Hansen, R Bushunow, PW Kirkwood, J Flynn, PJ Dutcher, JP Benson, AB TI Phase II trial of prolonged continuous infusion of 5-fluorouracil and interferon-alpha in patients with advanced pancreatic cancer - Eastern Cooperative Oncology Group Protocol 3292 SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE pancreatic cancer; 5-fluorouracil; interferon-alpha; continuous infusion; therapy ID HIGH-DOSE LEUCOVORIN; PREVIOUSLY UNTREATED PATIENTS; ADVANCED ADENOCARCINOMA; COLORECTAL-CARCINOMA; FLUOROURACIL; COMBINATION; TOXICITY; THERAPY; ALFA-2A AB Evidence suggests that interferon-alpha (IFN-alpha) augments the antineoplastic activity of 5-fluorouracil (5-FU) in human adenocarcinoma cell lines in vitro and may enhance the efficacy of 5-FU in patients with advanced colorectal carcinoma. In addition, 5-FU may be more effective when given as a prolonged, continuous i.v. infusion (PCI). The Eastern Cooperative Oncology Group performed a Phase II trial of PCI 5-FU plus IFN-alpha in patients with advanced pancreatic carcinoma. Twenty-six patients with advanced, surgically incurable adenocarcinoma of the pancreas received PCI 5-FU (250 mg/m(2) daily for 28 days) in combination with IFN-alpha (5 x 10(6) IU/m(2) s.c. thrice weekly). Treatment cycles were repeated 14 days or longer after completion of the previous cycle. Treatment was interrupted prior to day 28 if intolerable toxicity developed, and the dose of 5-FU was reduced in subsequent cycles. Partial response occurred in two of 24 evaluable patients (8%; 95% confidence interval, 0-19%). The majority of the study group (88%) had liver metastases. Patients whose serum lactate dehydrogenase (LDH) was more than twofold elevated developed 5-FU-related toxicity significantly sooner than patients with smaller elevations in serum LDH (9 vs. 22 days, p = 0.003). A similar trend was observed for patients with a more than twofold elevation in serum glutamic-oxaloacetic transaminase (SGOT; 9 vs. 15 days; p = 0.07). In conclusion, PCI 5-FU plus IFN-alpha has minimal activity in patients with advanced pancreatic carcinoma, and elevated serum LDH and/or SGOT may be useful for predicting greater toxicity from 5-FU-based therapy in patients with liver metastases. C1 DANA FARBER CANC INST,BOSTON,MA 02115. MED COLL WISCONSIN,MILWAUKEE,WI 53226. UNIV ROCHESTER,CTR CANC,ROCHESTER,NY 14627. UNIV PITTSBURGH,PITTSBURGH,PA 15260. METRO MINNESOTA COMMUNITY CANC ONCOL PROGRAM,MINNEAPOLIS,MN. NORTHWESTERN UNIV,MED CTR,CHICAGO,IL 60611. RP Sparano, JA (reprint author), MONTEFIORE MED CTR,ALBERT EINSTEIN CANC CTR,111 E 210TH ST,BRONX,NY 10467, USA. FU NCI NIH HHS [CA 11083, CA 23318, CA 15958] NR 28 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD DEC PY 1996 VL 19 IS 6 BP 546 EP 551 DI 10.1097/00000421-199612000-00002 PG 6 WC Oncology SC Oncology GA VT716 UT WOS:A1996VT71600002 PM 8931668 ER PT J AU Katz, IR AF Katz, IR TI On the inseparability of mental and physical health in aged persons - Lessons from depression and medical comorbidity SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY FEB 17-20, 1995 CL CANCUN, MEXICO SP Amer Assoc Geriatr Psychiat ID HEMISPHERIC CEREBRAL INFARCTION; CORTICOTROPIN-RELEASING FACTOR; OBSTRUCTIVE PULMONARY-DISEASE; PROTEIN PLASMA-LEVELS; MAJOR DEPRESSION; ALZHEIMERS-DISEASE; LATE-LIFE; MYOCARDIAL-INFARCTION; PSYCHIATRIC MORBIDITY; REVERSIBLE DEMENTIA AB Recent research findings demonstrate that general medical and mental health are inseparable in older individuals. The medical consequences of depression can be summarized with the unifying hypothesis that depression interacts with medical or neurological illness to modify the course of disease and to amplify its associated effects. The medical causes of depression can be divided into specific mechanisms of certain diseases or medications and general mechanisms that may integrate effects of a number of the common chronic disorders of late life. The authors discuss two general hypotheses: One suggests that depression may be associated with subclinical cerebrovascular disease in older patients with cerebrovascular risk factors; the other suggests that depression occurring in association with various conditions may be related to cytokine-mediated ''sickness behavior.'' The research literature makes a compelling case for the need to address psychiatric-medical comorbidity in late life as a central issue in public policy and the design of health care systems. RP Katz, IR (reprint author), UNIV PENN,PHILADELPHIA VA MED CTR,DEPT PSYCHIAT,3600 MARKET ST,ROOM 812,PHILADELPHIA,PA 19104, USA. NR 124 TC 102 Z9 102 U1 7 U2 11 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD WIN PY 1996 VL 4 IS 1 BP 1 EP 16 PG 16 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA TL531 UT WOS:A1996TL53100001 ER PT J AU DeGasperi, R Sosa, MAG Sartorato, EL Battistini, S MacFarlane, H Gusella, JF Krivit, W Kolodny, EH AF DeGasperi, R Sosa, MAG Sartorato, EL Battistini, S MacFarlane, H Gusella, JF Krivit, W Kolodny, EH TI Molecular heterogeneity of late-onset forms of globoid-cell leukodystrophy SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID KRABBE DISEASE; HUMAN GALACTOCEREBROSIDASE; GALC GENE; LARGE DELETION; SPLICE-SITE; MUTATION; SUBSTITUTION; EXON; CDNA AB Globoid-cell leukodystrophy (GLD) is an autosomal recessive inherited disorder caused by the deficiency of galactocerebrosidase, the lysosomal enzyme responsible for the degradation of the myelin glycolipid galactocerebroside. Although the most common form of the disease is the classical infantile form (Krabbe disease), lateronset forms also have been described, We have analyzed the galactocerebrosidase gene in 17 patients (nine families) with late-onset GLD and in 1 patient with classical Krabbe disease. Half of the patients were heterozygous for the large gene deletion associated with the 502C-->T polymorphism, the most common mutation in infantile patients. Several novel mutations that result in deficient galactocerebrosidase activity were also identified in these patients. They include the missense mutations R63H, G95S, M101L, G268S, Y298C, and I234T; the nonsense mutation S7X; a one-base deletion (805delG); a mutation that interferes with the splicing of intron 1; and a 34-nt insertion in the RNA, caused by the aberrant splicing of intron 6. All of these genetic defects are clustered in the first 10 exons of the galactocerebrosidase gene and therefore affect the 50-kD subunit of the mature enzyme. Studies on the distribution and enzymatic activity of the polymorphic alleles 1637T/C (I546/T546) provided support for previous data that had indicated the existence of two galactocerebrosidase forms with different catalytic activities in the general population. Our data also indicate that the mutations occur preferentially in the ''low activity'' 1637C allele. C1 NYU,SCH MED,DEPT NEUROL,NEW YORK,NY. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. UNIV MINNESOTA,DEPT PEDIAT,MINNEAPOLIS,MN 55455. RI Battistini, Stefania/N-2596-2015 OI Battistini, Stefania/0000-0003-2887-7624 FU NINDS NIH HHS [NS 24279] NR 27 TC 51 Z9 52 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 DEC PY 1996 VL 59 IS 6 BP 1233 EP 1242 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA VV315 UT WOS:A1996VV31500009 PM 8940268 ER PT J AU Terrett, JA NewburyEcob, R Smith, NM Li, QY Garrett, C Cox, P Bonnet, D Lyonnet, S Munnich, A Buckler, AJ Brook, JD AF Terrett, JA NewburyEcob, R Smith, NM Li, QY Garrett, C Cox, P Bonnet, D Lyonnet, S Munnich, A Buckler, AJ Brook, JD TI A translocation at 12q2 refines the interval containing the holt-oram syndrome 1 gene SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SYNDROME MAPS; LONG ARM; CHROMOSOME-12; DNA AB A gene for Holt-Gram syndrome (HOS) has been previously mapped to chromosome 12q2 and designated HOS1. We have identified a HOS patient with a de novo chromosomal rearrangement involving 12q. Detailed cytogenetic analysis of this case reveals three breaks on 12q, and two of these are within the HOS1 interval. By using a combination of chromosome painting and FISH with YACs and cosmids, it has been possible to map these breakpoints within the critical HOS1 interval and thus provide a focus for HOS gene-identification efforts. C1 UNIV NOTTINGHAM,QUEENS MED CTR,DEPT GENET,NOTTINGHAM NG7 2UH,ENGLAND. CITY HOSP,CTR MED GENET,NOTTINGHAM NG5 1PB,ENGLAND. NORTHWICK PK HOSP & CLIN RES CTR,KENNEDY GALTON CTR,HARROW HA1 3UJ,MIDDX,ENGLAND. HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT PATHOL,LONDON,ENGLAND. DEPT PEDIAT,PARIS,FRANCE. HOP NECKER ENFANTS MALAD,INSERM,U393,UNITE RECH HANDICAPS GENET ENFANT,F-75743 PARIS,FRANCE. MASSACHUSETTS GEN HOSP,DEPT NEUROGENET,CHARLESTOWN,MA. OI Brook, John David/0000-0002-5946-6740 NR 13 TC 5 Z9 5 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 1996 VL 59 IS 6 BP 1337 EP 1341 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA VV315 UT WOS:A1996VV31500021 PM 8940280 ER PT J AU Rogus, JJ Krolewski, AS AF Rogus, JJ Krolewski, AS TI Using discordant sib pairs to map loci for qualitative traits with high sibling recurrence risk SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENETICALLY COMPLEX TRAITS; AFFECTED RELATIVE PAIRS; DIABETIC NEPHROPATHY; LINKAGE STRATEGIES; PREVALENCE AB A common approach for detecting genetic linkage using siblings is to collect affected sib pairs (ASPs) and to identify markers where allele sharing exceeds expectation. Alternatively, markers can be analyzed in discordant sih pairs (DSPs) for allele sharing below expectation. Relative to the ASP approach, according to Risch, the power of the DSP approach increases with sibling recurrence risk, the two approaches being equally effective at 50% recurrence risk. However, with many diseases associated with more moderate sibling recurrence risk, less emphasis has been placed on the use of DSPs and the development of the underlying theory. In this paper, we expand the work of Risch to provide a more general foundation for DSP studies, since power can be quite high under the appropriate conditions. For example, in some highly affected populations, such as the diabetes-prone Pima Indians, sibling recurrence risk can be very large and, thus, DSPs ideal. Similarly, as we show through simulation, DSPs are preferable for diabetic nephropathy due to a 70% recurrence rare among siblings with insulin-dependent diabetes mellitus. Following the diabetic nephropathy example, we consider more systematically the situations in which DSPs can provide an efficient alternative to ASPs. C1 HARVARD UNIV,SCH PUBL HLTH,PROGRAM POPULAT GENET,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RP Rogus, JJ (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,SECT EPIDEMIOL & GENET,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK41256] NR 17 TC 35 Z9 36 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 1996 VL 59 IS 6 BP 1376 EP 1381 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA VV315 UT WOS:A1996VV31500024 PM 8940283 ER PT J AU Merkel, PA Chang, YC Pierangeli, SS Convery, K Harris, EN Polisson, RP AF Merkel, PA Chang, YC Pierangeli, SS Convery, K Harris, EN Polisson, RP TI The prevalence and clinical associations of anticardiolipin antibodies in a large inception cohort of patients with connective tissue diseases SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID PRIMARY ANTIPHOSPHOLIPID SYNDROME; SYSTEMIC LUPUS-ERYTHEMATOSUS; PRIMARY SJOGRENS-SYNDROME; ANTI-CARDIOLIPIN ANTIBODIES; RHEUMATOID-ARTHRITIS; SCLEROSIS; MANIFESTATIONS; WORKSHOP; STANDARDIZATION; FEATURES AB PURPOSE: TO determine the prevalence and clinical associations of anticardiolipin antibodies (aCL) in a blinded, controlled study of patients with a variety of connective tissue diseases (CTD) using a standardized aCL testing system. PATIENTS AND METHODS: Anticardiolipin antibodies (IgG, IgM, and IgA) were measured by direct enzyme-linked immunosorbent assay (ELISA) in the baseline serum samples of patients enrolled in a Cooperative Study of Systematic Rheumatic Diseases (CSSRD), National Institutes of Health (NIH) supported, 5-year inception-cohort, prospective study of early rheumatic diseases: rheumatoid arthritis (RA, n = 70), systemic lupus erythematosus (SLE, n = 70), scleroderma (PSS, n = 45), myositis (PM/DM, n = 36), and early undifferentiated connective tissue disease (EUCTD, n = 165). Diagnosis was based on standardized criteria and determined at the last study visit. A nested group of patients with Sjogren's syndrome (SJ, n = 44) was also defined. Serum from 200 blood donors (BE) served as controls. Additional patients with known antiphospholipid syndrome (APS, n = 33) and ANCA-related renal vasculitis (ANCA, n = 52) were also studied. Laboratory personnel were blinded to sample diagnostic group. RESULTS: The prevalence of either IgG or IgM aCL among each diagnostic group was RA 15.7%, SLE 15.76%, PSS 6.7%, PM/DM 8.3%, EUCTD 9.1%, SJ 6.8%, ANCA 3.8%, and BE controls 4.0%. Prevalence of aCL was significantly different for both the RA and SLE groups versus BE controls (P < 0.01) but not among other diagnostic groups. Only 2 study patients had positive tests for IgA aCL (1 with PM/DM and 1 with EUCTD) versus 15% of APS with positive IgA aCL. Study patients positive for IgG or IgM aCL were significantly more likely to have hemolytic anemia or a positive serologic test for syphilis and less likely to have Raynaud's phenomenon. However, no associations were found between aCL positivity and thrombocytopenia, seizures, renal insufficiency, presence of a positive antinuclear antibody or rheumatoid factor, subcutaneous nodules or digital ulcers. CONCLUSIONS: Based on results from this large CSSRD inception cohort, anticardiolipin antibodies are present in approximately 16% of patients with RA or SLE but are less common in patients with PSS, PM/DM, EUCTD, SJ, and ANCA vasculitis, where their prevalence approaches that in the normal population. Few consistent clinical associations can be found among patients with CTD who are aCL positive. The complete diagnostic and prognostic importance and specificity of these antibodies remains to be fully determined. (C) 1996 by Excerpta Medica, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,MED PRACTICE EVALUAT CTR,BOSTON,MA 02114. UNIV LOUISVILLE,DEPT MED,DIV RHEUMATOL,LOUISVILLE,KY 40292. 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] NR 50 TC 104 Z9 111 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 1996 VL 101 IS 6 BP 576 EP 583 DI 10.1016/S0002-9343(96)00335-X PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WB602 UT WOS:A1996WB60200003 PM 9003103 ER PT J AU Henderson, MC Hunt, DK Williams, JW AF Henderson, MC Hunt, DK Williams, JW TI General internists influence students to choose primary care careers: The power of role modeling SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID MEDICAL-STUDENTS; SPECIALTY CHOICE; SCHOOL AB PURPOSE: TO determine whether medical students supervised by general internist attendings during the third-year medicine clerkship are more likely to choose primary care careers than students supervised by subspecialist attendings. METHODS: One hundred forty-four consecutive medical students rotating on the general medicine inpatient service during the 1993-1994 academic year were surveyed about their career choice and professional expectations, both at the beginning and end of the clerkship; an additional 50 students completed a post-clerkship survey only. The cohort of students was surveyed at graduation to determine stability of their career preferences. RESULTS: Both pre- and post-clerkship surveys were completed by 138 of 144 students (96%); post-clerkship surveys were completed by 181/194 (93%); and graduation surveys were completed by 137/188 (73%). Fifty-eight students (32%) designated primary care (general internal medicine, general pediatrics, or family practice) as their career choice post-clerkship; of these, 45 students (78%) also indicated a primary care career choice at graduation. Characteristics associated with choosing primary care post-clerkship were: low income expectation, desire to interact closely with patients, desire to contribute to society, low class rank, female gender, and high educational debt. Having a physician parent was negatively associated with choosing primary care. After controlling for important demographic, academic and attitudinal characteristics, increasing exposure to a general internist attending was associated with choosing primary care (OR = 5.1, comparing highest to lowest amount). Among students choosing primary care, exposure to a general internist attending was associated with choosing general internal medicine in a dose-dependent fashion (OR = 4.2, comparing highest to lowest amount). CONCLUSIONS: Although career choice is clearly related to personal characteristics such as socioeconomic background and humanistic qualities, a high degree of exposure to general internists during the medicine clerkship is associated with choosing primary care. Exposure of students interested in primary care to general internist attendings may also influence them to consider general internal medicine over family practice and pediatrics. (C) 1996 by Excerpta Medica, Inc. C1 AUDIE L MURPHY MEM VET ADM MED CTR,AMBULATORY CARE SECT,SAN ANTONIO,TX 78284. RP Henderson, MC (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GEN MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 18 TC 39 Z9 40 U1 0 U2 2 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 DEC PY 1996 VL 101 IS 6 BP 648 EP 653 DI 10.1016/S0002-9343(96)00334-8 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA WB602 UT WOS:A1996WB60200013 PM 9003113 ER PT J AU Han, DP Vine, AK Blodi, BA Elner, SG Johnson, MW Jessup, LM Khanderia, S Pierson, CL Willis, J McIver, F Stanley, S Sneed, SR Capone, A Aaberg, TM Lim, JI Sternberg, P Coffman, DS Moore, CN Gardner, SK Nolte, FS Fremstad, A Gibbs, D Gilman, J Swords, R Aguilar, HE Meredith, TA Lakhanpal, V Christian, FD Hood, MA Schwalbe, RS Billings, EE Buie, W Mallonee, JJ Millar, MA Verbeek, S Campochiaro, PA Palardy, CB Reynolds, L Dick, JD Cain, D DAmico, DJ Frederick, AR Morley, MG Pesavento, RD Puliafito, CA Topping, TM Finn, SM Raymond, LA Baker, AS Paton, B Evans, C Napoli, J Kiernan, C Makris, K McInnes, T Reidy, WT White, R Garfinkel, RA Pilkerton, AR Frantz, RA Abernathy, GB Barbaccia, JG Ensey, HR Ormes, CA Park, CH Caplan, J Russel, K Toma, R Packo, KH deBustros, S Flood, TP Glazer, L DeAlba, M Evanich, E Montwill, MA Rothman, JJ Ruderman, G Beard, M Landau, W Shen, MH Gordon, M Graff, S Kwiatkowski, K Pappas, L Bryant, D Doherty, D Morini, F Arredondo, L Garretson, BR Gerena, C Hunt, M Kinnaird, SM Neri, T Rice, TA Novak, MA Rwe, PS Jamieson, S Newberry, D Rech, GR Dul, MJ Kinser, L Strozewski, K ClarkRath, S DeLisio, M Dempsey, DL Kukula, D PinterSmith, A Rowe, PS SmithBrewer, S Ludwig, T Chambers, RB Davidorf, FH Taylor, CS Hale, KN Buesching, WJ Chaudhuri, C Cover, NJ Shortlidge, GR Keating, MJ Savage, SJ Andrzejewska, P Cornetet, S Milliron, JD Richmond, R Schneider, L Weisenberger, D Cantrill, HL Ramsay, RC Brallier, AB Johnson, TP Rossing, EE Knauth, KA Monahan, MM Oestreich, NW Clark, KF Glennen, AM Yarian, DL Green, SN Leff, SR Masciulli, L Lucido, MM Ludwig, EJ Marano, CL Peters, L Joho, K Volkert, DC Andersen, F Coffey, D Schlosser, A Honeywell, A Mames, RN Driebe, WT Stern, GA Francis, A Zam, ZS Cooper, R Gaskins, D Shamis, DJ Willingham, M Barker, K Rosa, H Friedman, SM Gardner, TW Blankenship, GW Coyle, CJ Bero, CJ Halas, C Schick, S Walker, J Cunningham, D Lambert, HM Clogston, PS Frady, PM Gardner, SN Osato, MS Carr, L Shigley, J Lopez, PF Chong, LP Frambach, DA Cisneros, L Padilla, M Yee, EM Nakamura, T Walonker, AF Morales, R Nichols, T Huete, ME Liggett, PE Ober, RR QuillenThomas, B Williams, M Barr, CC Bloom, SM Greene, PJ Whittington, GK Martin, ME Watson, G JenkinsCurry, B Gilkey, LA Huelsman, S Burton, TC Mieler, WF Pulido, JS Reeser, FH Newman, JL Werner, KA Pisarzewicz, PJ Reinerio, NA Walloch, MLK Wilmer, Z Laabs, J Picchiottino, R Phillips, J Wipplinger, W Abrams, GW Jurkiewicz, DT Leet, ML Mandel, P Metzger, K Suchla, L Zarling, D Balles, MW Ryan, EH Knobloch, WH Cook, SM Luke, DG Ferrieri, P Schiminsky, NM Genia, A Philiph, DA Stinson, EK Wright, LM McMichael, WC Mielke, SJ Ponwith, LJ Pavan, PR Pautler, SE Coats, ML Kirk, NM Millard, SM Castellano, FC Edwards, CR Marquardt, A McCormack, AJ McCormick, MT Renshaw, B Restuccia, A Campbell, M Christopher, N Garrett, LS Halkias, DG Hothersall, K MIckler, K Minnick, TS Burr, C Saxon, W Arcacha, MA Carlton, S Edison, SK Mallis, MJ Sayers, TL Sudds, TW Tiberia, RJ Wolabaugh, S Bradford, RH Parke, DW Wolf, TC Shofner, JM Tobey, LE Jensen, HG Sanchez, D Shofner, J Burris, R Drake, KK Grissom, KR Rowsey, JJ Wilkinson, CP Brown, GC Benson, WE Federman, JL Lucier, AC Maguire, JI Sarin, LK Shakin, EP Sivalingam, A Tasman, W Vander, JF Ward, N Weisbecker, CA Agnew, CL Lambert, R Tomer, T Carlson, K Franchine, G Serfass, MS Doft, BH Bergren, RL Lobes, LA Olsen, KR Rinkoff, JS Metz, DJ Leonard, MN Karenchak, LM Kowalski, RP Wellman, LA Wilcox, LA Campbell, AF Steinberg, DR Vagstad, GL Flook, KA Good, MM Keenen, BJ Mellinger, KA Margherio, RR Cox, MS Murphy, PL Trese, MT Werner, JC Williams, GA Manatrey, PE Prote, JL Lucarotti, R Martin, S Band, J Bostic, G Cumming, K Mitchell, B Regan, VS Bridges, C Cox, S Houston, G Johnson, J Streasik, P Wood, B Blumenkranz, MS Cayo, L Kaye, V Valenzuela, CL Orgel, IK Poliner, LS Tornambe, PE Cannon, SV Nielsen, JL Carlson, A Chan, P Drake, L Grim, M Peterson, C Borg, LA Gillyatt, J Beyer, C Hammer, ME Grizzard, WS Shannon, TL Traynom, JR Collado, MJ McManus, DW Sweeney, DE Adams, DH Watson, TT Antworth, MV Araos, JG Greenwald, MA Habib, M Myers, SK Ockers, KM Thibodeau, JA Watkins, B Nelsen, PT Rosenthal, JG Mintz, FV Biedenbach, M Leonardy, NJ Lawniczak, SM Bork, C Hageage, G Hunter, EB Marshall, MJ Roman, P Hill, R HOfbauer, T Lemanowicz, J Cupples, HP Guzman, GI Brodeur, RJ Yee, D Delaha, EC Geyer, SL Slovis, S Shields, WJ Lauber, S Michelitsch, K Barza, M Kassoff, A Watling, S Wilson, LA Buehler, JC McVay, J Kelsey, SF Wisniewski, SR Podobinski, GK Sillett, RL Groer, S Avery, B Belle, SH Boles, J Henry, L Shema, SJ TitusErnstoff, L Davis, M Magli, YL Hubbard, L Thomas, S Everett, DF Mowery, R Davis, K Azen, S Covey, P McCuen, B Packer, A Robbin, J AF Han, DP Vine, AK Blodi, BA Elner, SG Johnson, MW Jessup, LM Khanderia, S Pierson, CL Willis, J McIver, F Stanley, S Sneed, SR Capone, A Aaberg, TM Lim, JI Sternberg, P Coffman, DS Moore, CN Gardner, SK Nolte, FS Fremstad, A Gibbs, D Gilman, J Swords, R Aguilar, HE Meredith, TA Lakhanpal, V Christian, FD Hood, MA Schwalbe, RS Billings, EE Buie, W Mallonee, JJ Millar, MA Verbeek, S Campochiaro, PA Palardy, CB Reynolds, L Dick, JD Cain, D DAmico, DJ Frederick, AR Morley, MG Pesavento, RD Puliafito, CA Topping, TM Finn, SM Raymond, LA Baker, AS Paton, B Evans, C Napoli, J Kiernan, C Makris, K McInnes, T Reidy, WT White, R Garfinkel, RA Pilkerton, AR Frantz, RA Abernathy, GB Barbaccia, JG Ensey, HR Ormes, CA Park, CH Caplan, J Russel, K Toma, R Packo, KH deBustros, S Flood, TP Glazer, L DeAlba, M Evanich, E Montwill, MA Rothman, JJ Ruderman, G Beard, M Landau, W Shen, MH Gordon, M Graff, S Kwiatkowski, K Pappas, L Bryant, D Doherty, D Morini, F Arredondo, L Garretson, BR Gerena, C Hunt, M Kinnaird, SM Neri, T Rice, TA Novak, MA Rwe, PS Jamieson, S Newberry, D Rech, GR Dul, MJ Kinser, L Strozewski, K ClarkRath, S DeLisio, M Dempsey, DL Kukula, D PinterSmith, A Rowe, PS SmithBrewer, S Ludwig, T Chambers, RB Davidorf, FH Taylor, CS Hale, KN Buesching, WJ Chaudhuri, C Cover, NJ Shortlidge, GR Keating, MJ Savage, SJ Andrzejewska, P Cornetet, S Milliron, JD Richmond, R Schneider, L Weisenberger, D Cantrill, HL Ramsay, RC Brallier, AB Johnson, TP Rossing, EE Knauth, KA Monahan, MM Oestreich, NW Clark, KF Glennen, AM Yarian, DL Green, SN Leff, SR Masciulli, L Lucido, MM Ludwig, EJ Marano, CL Peters, L Joho, K Volkert, DC Andersen, F Coffey, D Schlosser, A Honeywell, A Mames, RN Driebe, WT Stern, GA Francis, A Zam, ZS Cooper, R Gaskins, D Shamis, DJ Willingham, M Barker, K Rosa, H Friedman, SM Gardner, TW Blankenship, GW Coyle, CJ Bero, CJ Halas, C Schick, S Walker, J Cunningham, D Lambert, HM Clogston, PS Frady, PM Gardner, SN Osato, MS Carr, L Shigley, J Lopez, PF Chong, LP Frambach, DA Cisneros, L Padilla, M Yee, EM Nakamura, T Walonker, AF Morales, R Nichols, T Huete, ME Liggett, PE Ober, RR QuillenThomas, B Williams, M Barr, CC Bloom, SM Greene, PJ Whittington, GK Martin, ME Watson, G JenkinsCurry, B Gilkey, LA Huelsman, S Burton, TC Mieler, WF Pulido, JS Reeser, FH Newman, JL Werner, KA Pisarzewicz, PJ Reinerio, NA Walloch, MLK Wilmer, Z Laabs, J Picchiottino, R Phillips, J Wipplinger, W Abrams, GW Jurkiewicz, DT Leet, ML Mandel, P Metzger, K Suchla, L Zarling, D Balles, MW Ryan, EH Knobloch, WH Cook, SM Luke, DG Ferrieri, P Schiminsky, NM Genia, A Philiph, DA Stinson, EK Wright, LM McMichael, WC Mielke, SJ Ponwith, LJ Pavan, PR Pautler, SE Coats, ML Kirk, NM Millard, SM Castellano, FC Edwards, CR Marquardt, A McCormack, AJ McCormick, MT Renshaw, B Restuccia, A Campbell, M Christopher, N Garrett, LS Halkias, DG Hothersall, K MIckler, K Minnick, TS Burr, C Saxon, W Arcacha, MA Carlton, S Edison, SK Mallis, MJ Sayers, TL Sudds, TW Tiberia, RJ Wolabaugh, S Bradford, RH Parke, DW Wolf, TC Shofner, JM Tobey, LE Jensen, HG Sanchez, D Shofner, J Burris, R Drake, KK Grissom, KR Rowsey, JJ Wilkinson, CP Brown, GC Benson, WE Federman, JL Lucier, AC Maguire, JI Sarin, LK Shakin, EP Sivalingam, A Tasman, W Vander, JF Ward, N Weisbecker, CA Agnew, CL Lambert, R Tomer, T Carlson, K Franchine, G Serfass, MS Doft, BH Bergren, RL Lobes, LA Olsen, KR Rinkoff, JS Metz, DJ Leonard, MN Karenchak, LM Kowalski, RP Wellman, LA Wilcox, LA Campbell, AF Steinberg, DR Vagstad, GL Flook, KA Good, MM Keenen, BJ Mellinger, KA Margherio, RR Cox, MS Murphy, PL Trese, MT Werner, JC Williams, GA Manatrey, PE Prote, JL Lucarotti, R Martin, S Band, J Bostic, G Cumming, K Mitchell, B Regan, VS Bridges, C Cox, S Houston, G Johnson, J Streasik, P Wood, B Blumenkranz, MS Cayo, L Kaye, V Valenzuela, CL Orgel, IK Poliner, LS Tornambe, PE Cannon, SV Nielsen, JL Carlson, A Chan, P Drake, L Grim, M Peterson, C Borg, LA Gillyatt, J Beyer, C Hammer, ME Grizzard, WS Shannon, TL Traynom, JR Collado, MJ McManus, DW Sweeney, DE Adams, DH Watson, TT Antworth, MV Araos, JG Greenwald, MA Habib, M Myers, SK Ockers, KM Thibodeau, JA Watkins, B Nelsen, PT Rosenthal, JG Mintz, FV Biedenbach, M Leonardy, NJ Lawniczak, SM Bork, C Hageage, G Hunter, EB Marshall, MJ Roman, P Hill, R HOfbauer, T Lemanowicz, J Cupples, HP Guzman, GI Brodeur, RJ Yee, D Delaha, EC Geyer, SL Slovis, S Shields, WJ Lauber, S Michelitsch, K Barza, M Kassoff, A Watling, S Wilson, LA Buehler, JC McVay, J Kelsey, SF Wisniewski, SR Podobinski, GK Sillett, RL Groer, S Avery, B Belle, SH Boles, J Henry, L Shema, SJ TitusErnstoff, L Davis, M Magli, YL Hubbard, L Thomas, S Everett, DF Mowery, R Davis, K Azen, S Covey, P McCuen, B Packer, A Robbin, J TI Microbiologic factors and visual outcome in the endophthalmitis vitrectomy study SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID STAPHYLOCOCCUS-EPIDERMIDIS ENDOPHTHALMITIS; COAGULASE-NEGATIVE STAPHYLOCOCCI; INFECTIOUS ENDOPHTHALMITIS; MANAGEMENT; SPECTRUM AB PURPOSE: To evaluate the relationship between microbiologic factors, effect of treatment, and visual outcome in the Endophthalmitis Vitrectomy Study. METHODS: Four hundred twenty patients were enrolled in the Endophthalmitis Vitrectomy Study between February 1990 and January 1994. Of these, 394 completed 9 to 12 months of follow-up. Patients presented with features of bacterial endophthalmitis within 6 weeks of cataract extraction or secondary intraocular lens implantation. The relations between visual outcome and the identity of infecting species, gram stain results, antibiotic susceptibilities, and presence of vitrectomy cassette growth were examined. RESULTS: Rates of achieving final visual acuity of 20/100 or better for the more common isolates were as follows: gram-positive, coagulase-negative micrococci, 84%; Staphylococcus aureus, 50%; streptococci, 30%; enterococci, 14%; and gram-negative organisms, 56%. A positive gram stain or infection with species other than gram-positive, coagulase-negative micrococci were significantly associated with poorer visual outcome (P <.001 for species group comparisons). However, presenting visual acuity was more powerful than microbiologic factors in predicting visual outcome and favorable response to vitrectomy. Bacterial growth from the vitrectomy cassette specimen had prognostic significance equivalent to growth from other intraocular sources. CONCLUSIONS: Visual prognosis was strongly associated with the type of infecting organism and gram stain positivity. However, visual acuity at initial presentation appeared to be more useful than microbiologic factors in predicting visual outcome and judging the value of immediate vitrectomy in acute bacterial endophthalmitis after cataract surgery. C1 UNIV MICHIGAN,ANN ARBOR,MI 48109. EMORY EYE CTR,ATLANTA,GA. UNIV MARYLAND,EYE ASSOCIATES,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,BALTIMORE,MD. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RETINA GRP WASHINGTON,CHEVY CHASE,MD. RUSH UNIV,INGALLS HOSP,CHICAGO,IL 60612. RETINA ASSOCIATES CLEVELAND INC,CLEVELAND,OH. OHIO STATE UNIV,COLUMBUS,OH 43210. UNIV MINNESOTA,EDINA,MN. RETINA VITREOUS CTR PA,EDISON,NJ. UNIV FLORIDA,GAINESVILLE,FL. PENN STATE UNIV,HERSHEY,PA 17033. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV SO CALIF,LOS ANGELES,CA. UNIV LOUISVILLE,KENTUCKY LIONS EYE RES INST,LOUISVILLE,KY 40292. MED COLL WISCONSIN,MILWAUKEE,WI 53226. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV S FLORIDA,TAMPA,FL. DEAN A MCGEE EYE INST,OKLAHOMA CITY,OK. THOMAS JEFFERSON UNIV,WILLS EYE HOSP,PHILADELPHIA,PA 19107. RETINA VITREOUS CONSULTANTS,PITTSBURGH,PA. ASSOCIATED RETINAL CONSULTANTS,ROYAL OAK,MI. RETINA CONSULTANTS,SAN DIEGO,CA. UNIV S FLORIDA,TAMPA,FL. RETINA CONSULTANTS NE OHIO,TOLEDO,OH. RETINA VITREOUS ASSOCIATES INC,TOLEDO,OH. GEORGETOWN UNIV,WASHINGTON,DC. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV WISCONSIN,MADISON,WI. NEI,PROGRAM OFF,BETHESDA,MD 20892. WASHINGTON UNIV,SAFETY & DATA MONITORING COMM,ST LOUIS,MO. UNIV SO CALIF,SAFETY & DATA MONITORING COMM,LOS ANGELES,CA 90089. CARNEGIE MELLON UNIV,SAFETY & DATA MONITORING COMM,PITTSBURGH,PA 15213. DUKE UNIV,CTR EYE,SAFETY & DATA MONITORING COMM,DURHAM,NC. UNIV ILLINOIS,SAFETY & DATA MONITORING COMM,CHICAGO,IL 60680. NIH,SAFETY & DATA MONITORING COMM,BETHESDA,MD 20892. UNIV PITTSBURGH,SAFETY & DATA MONITORING COMM,PITTSBURGH,PA. UNIV WISCONSIN,SAFETY & DATA MONITORING COMM,MADISON,WI 53706. RI Rice, Treva/D-1385-2009 NR 23 TC 119 Z9 125 U1 0 U2 9 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 DEC PY 1996 VL 122 IS 6 BP 830 EP 846 PG 17 WC Ophthalmology SC Ophthalmology GA VW758 UT WOS:A1996VW75800009 ER PT J AU Yu, YM Burke, JF Tompkins, RG Martin, R Young, VR AF Yu, YM Burke, JF Tompkins, RG Martin, R Young, VR TI Quantitative aspects of interorgan relationships among arginine and citrulline metabolism SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE tracers; arteriovenous difference; splanchnic region; kidney ID CHRONIC RENAL-INSUFFICIENCY; AMINO-ACID-METABOLISM; PLASMA ARGININE; NITRIC-OXIDE; WHOLE-BODY; INTRAVENOUS TRACER; LEUCINE KINETICS; SMALL-INTESTINE; BURN PATIENTS; LIVER AB The quantitative roles of the splanchnic region and the kidneys in whole body (WB) arginine and citrulline metabolism were assessed in postabsorptive mongrel dogs with primed constant intravenous infusions of [N-15(2)-guanidino, 5,5-H-2(2)]arginine and [C-13-ureido] citrulline or [C-13-guanidino]arginine and [N-15]urea tracers. Isotope and metabolite concentration balances of arginine and citrulline were measured across the gut, liver, splanchnic region, and kidneys, together with WB arginine and citrulline fluxes and urea production rate. The WB citrulline flux and rate of citrulline to arginine (C-A) conversion were 16 and 9.4 mu mol . kg(-1) . h(-1), respectively. Concentration balance of citrulline across kidneys was +8.2 mu mol . kg(-1) . h(-1), and metabolism of citrulline by kidneys was 8.7 mu mol kg(-1) . h(-1), which was derived about equally from intestine and liver. The appearance rate of citrulline-derived arginine in renal vein was 6.8 mu mol . kg(-1) . h(-1). These three separate estimates of C-A conversion within the kidneys were in good agreement, indicating 40% of blood C-A conversion occurring outside kidneys. These findings of interorgan metabolism are discussed in reference to the current knowledge derived largely from studies in laboratory rodents. C1 MASSACHUSETTS GEN HOSP, DEPT SURG, BOSTON, MA 02114 USA. MIT, HUMAN NUTR LAB, CAMBRIDGE, MA 02139 USA. NR 61 TC 42 Z9 42 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD DEC PY 1996 VL 271 IS 6 BP E1098 EP E1109 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA WA522 UT WOS:A1996WA52200021 ER PT J AU Simon, FR Fortune, J Iwahashi, M Gartung, C Wolkoff, A Sutherland, E AF Simon, FR Fortune, J Iwahashi, M Gartung, C Wolkoff, A Sutherland, E TI Ethinyl estradiol cholestasis involves alterations in expression of liver sinusoidal transporters SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE sodium-potassium-activated adenosinetriphosphatase; sodium-dependent bile acid transporter; organic anion transporter; fluidity; bile acids ID MEMBRANE LIPID FLUIDITY; RAT-LIVER; PLASMA-MEMBRANE; ECTO-ATPASE; BILE-ACID; INTRAHEPATIC CHOLESTASIS; TAUROCHOLATE TRANSPORT; HEPATOCYTES; CLONING; PROTEIN AB The mechanisms involved in ethinyl estradiol-induced cholestasis are controversial. Basal bile flow was reduced by ethinyl estradiol administration, with a half time (t(1/2)) of 12.5 +/- 0.6 h. In contrast, initial taurocholate uptake was not significantly reduced until 3 days to 59% of control and to 13 and 10% of control at 5 and 7 days, respectively. The t(1/2) was 4.3 +/- 0.1 days. These physiological changes were correlated with measurement of protein mass and steady-state mRNA for Na+-K+-adenosinetriphosphatase (Na+-K+-ATPase), Na+-dependent taurocholate transporter, organic anion transporters, and membrane lipid fluidity. Ethinyl estradiol significantly decreased Na+-K+-ATPase activity and membrane fluidity. However, neither Na+-K+-ATPase alpha-subunit nor beta-subunit mass was altered by ethinyl estradiol administration. In contrast, protein content of the Na+-dependent taurocholate transporter was significantly reduced to 21% of control (P < 0.001) at 5 days. The Na+-dependent taurocholate transporter was identified in sinusoidal membrane fractions as a doublet with a molecular size estimated to be 51 and 56 kDa. Although both bands were reduced with ethinyl estradiol treatment, the 56-kDa band was decreased more rapidly and to a greater extent than the 51-kDa band. The estimated t(1/2) of 4.8 +/- 0.6 days for the doublet was similar to that for Na+-dependent taurocholate uptake. The organic anion transporter protein mass was similarly reduced with time of ethinyl estradiol administration to 21% of control (P < 0.01) at 5 days. Ethinyl estradiol also rapidly decreased the steady-state mRNA levels of Na+-dependent and organic anion transporters to similar to 50% and 15% of control at 5 days, respectively. These studies indicate early generalized abnormalities of the sinusoidal membrane lipid fluidity, Na+-K+-ATPase activity, and bile acid transport protein content. C1 UNIV COLORADO, HLTH SCI CTR, DENVER VET AFFAIRS MED CTR, DENVER, CO 80262 USA. ALBERT EINSTEIN COLL MED, DEPT MED, BRONX, NY 10461 USA. ALBERT EINSTEIN COLL MED, MARION BESSIN LIVER RES CTR, BRONX, NY 10461 USA. YALE UNIV, SCH MED, DEPT MED, LIVER STUDY UNIT, NEW HAVEN, CT 06520 USA. RP Simon, FR (reprint author), UNIV COLORADO, HLTH SCI CTR, HEPATOBILIARY CTR, 4200 E 9TH AVE, B-145, DENVER, CO 80262 USA. NR 35 TC 145 Z9 146 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 DEC PY 1996 VL 271 IS 6 BP G1043 EP G1052 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA WA523 UT WOS:A1996WA52300014 ER PT J AU Kato, S Koide, M Cooper, G Zile, MR AF Kato, S Koide, M Cooper, G Zile, MR TI Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE osmolarity; diastole; stress; strain ID LEFT-VENTRICULAR HYPERTROPHY; DIASTOLIC DYSFUNCTION; MITRAL REGURGITATION; FIBRILLAR COLLAGEN; SKELETAL-MUSCLE; HEART-FAILURE; CALCIUM; MYOCYTES; CARDIOCYTES; MYOCARDIUM AB It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However. no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness. C1 MED UNIV S CAROLINA, DIV CARDIOL, DEPT MED, GAZES CARDIAC RES INST, CHARLESTON, SC 29425 USA. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR, CHARLESTON, SC 29401 USA. NR 31 TC 12 Z9 12 U1 0 U2 2 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 DEC PY 1996 VL 271 IS 6 BP H2575 EP H2583 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA WB840 UT WOS:A1996WB84000044 ER PT J AU Holzmann, A Bloch, KD Sanchez, LS Filippov, G Zapol, WM AF Holzmann, A Bloch, KD Sanchez, LS Filippov, G Zapol, WM TI Hyporesponsiveness to inhaled nitric oxide in isolated, perfused lungs from endotoxin-challenged rats SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE nitric oxide; phosphodiesterases; lipopolysaccharide ID RESPIRATORY-DISTRESS-SYNDROME; PULMONARY VASOCONSTRICTION; PHOSPHODIESTERASE; HYPERTENSION; RELAXATION; INFUSION AB Inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in patients with the adult respiratory distress syndrome (ARDS). Approximately 30% of ARDS patients fail to respond to iNO. Because sepsis syndrome often accompanies a decreased response to iNO, we investigated NO responsiveness in isolated, perfused lungs from rats exposed to lipopolysaccharide (LPS). Eighteen hours after intraperitoneal injection of 0.5 mg/kg LPS, rat lungs were isolated, perfused, and preconstricted with U-46619. Ventilation with 0.4, 4, and 40 parts per million by volume NO vasodilated LPS-pretreated lungs 75, 47, and 42% less than control lungs (P < 0.01 value differs at each concentration). The diminished vasodilatory response to iNO was associated with decreased NO-stimulated guanosine 3',5'-cyclic monophosphate (cGMP) release into the perfusate. Soluble guanylate cyclase activity did not differ in lung extracts from LPS-pretreated and control rats. LPS increased pulmonary cGMP-phosphodiesterase (PDE) activity by 40%. The PDE-sensitive cGMP analogue 8-bromoguanosine 3',5'-cyclic monophosphate vasodilated lungs from LPS-pretreated rats less than lungs from control rats. In contrast, the PDE-insensitive 8-para-chlorophenylthioguanosine 3',5'-cyclic monophosphate vasodilated lungs equally from both groups. After LPS challenge, the rat pulmonary vasculature becomes hyporesponsive to iNO. Hyporesponsiveness to iNO appears partly attributable to increased pulmonary cGMP-PDE activity. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT ANESTHESIA, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, CARDIOVASC RES CTR, BOSTON, MA 02114 USA. FU NHLBI NIH HHS [HL-45895, HL-42397] NR 25 TC 26 Z9 27 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 DEC PY 1996 VL 271 IS 6 BP L981 EP L986 PG 6 WC Physiology; Respiratory System SC Physiology; Respiratory System GA VZ650 UT WOS:A1996VZ65000014 PM 8997269 ER PT J AU Jackson, RM Parish, G Ho, YS AF Jackson, RM Parish, G Ho, YS TI Effects of hypoxia on expression of superoxide dismutases in cultured ATII cells and lung fibroblasts SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE alveolar epithelium; hypoxia ID MESSENGER-RNA LEVELS; II EPITHELIAL-CELLS; RAT LUNG; ANTIOXIDANT ENZYMES; HYPEROXIA; PROTEIN; PNEUMOCYTES; INDUCTION; EXPOSURE; GENE AB This study investigated whether hypoxia affected the expression of mitochondrial manganese-containing superoxide dismutase (Mn-SOD) and the cytosolic copper and zinc-containing superoxide dismutase (Cu,Zn-SOD) in alveolar type II epithelial (ATII) cells and lung fibroblasts. Cells were exposed in vitro to air (controls) or to 2.5% oxygen (hypoxia) for 24 h. Mn-SOD and Cu,Zn-SOD mRNA expression was measured by quantitative reverse transcriptase-polymerase chain reaction. Both Mn-SOD and Cu,Zn-SOD mRNA expression in ATII cells decreased significantly after 1 day in hypoxic conditions. The decrease in Mn-SOD mRNA (-69%) was greater than that in Cu,Zn-SOD mRNA (-48%). ATII cell surfactant protein A transcript expression remained constant. Mn-SOD (-52%) and Cu,Zn-SOD (-54%) mRNA expression decreased similarly in lung fibroblasts cultured during hypoxia. The half-life of the Mn-SOD mRNA measured in lung fibroblasts exposed to air or hypoxia for 24 h decreased significantly from 5.8 +/- 0.1 to 3.8 +/- 0.7 h (-34%). The half-life for the Cu,Zn-SOD decreased significantly from 4.0 +/- 0.3 to 2.4 +/- 0.1 h(-40%). Neither Mn-SOD nor Cu,Zn-SOD protein expression in ATII cells changed significantly during hypoxia. Hypoxia decreases expression of Mn-SOD and Cu,Zn-SOD mRNA in ATII cells and lung fibroblasts in part by decreasing stability of the mRNA transcripts. C1 BIRMINGHAM VET AFFAIRS MED CTR, BIRMINGHAM, AL 35223 USA. WAYNE STATE UNIV, INST CHEM TOXICOL, DETROIT, MI 48201 USA. RP Jackson, RM (reprint author), UNIV ALABAMA, DIV PULM & CRIT CARE MED, BIRMINGHAM, AL 35294 USA. FU NHLBI NIH HHS [HL-39147, HL-39585] NR 36 TC 37 Z9 37 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 DEC PY 1996 VL 271 IS 6 BP L955 EP L962 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA VZ650 UT WOS:A1996VZ65000011 PM 8997266 ER PT J AU YoshidaYoneda, E OLee, TJ Wei, JY Vigna, SR Tache, Y AF YoshidaYoneda, E OLee, TJ Wei, JY Vigna, SR Tache, Y TI Peripheral bombesin induces gastric vagal afferent activation in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE cholecystokinin; gastric distension; vagus; cholecystokinin antagonist; ICI-216140; desmethionine-bombesin antagonist; bombesin binding ID BINDING-SITES; GASTROINTESTINAL-TRACT; RECEPTOR ANTAGONIST; CHOLECYSTOKININ; BRAIN; CCK; RESPONSES; RELEASE; SATIETY; TRANSPORT AB Bombesin's influence on gastric vagal afferent discharge (GVAD) was studied in urethan-anesthetized rats. Vehicle and peptides were injected intravenously at 30-min intervals. Cholecystokinin (CCK; 300 pmol) and bombesin (300 pmol) increased ongoing multiunit GVAD by 153 +/- 59 and 162 +/- 37%, respectively; similar increases were induced by a second injection of bombesin and CCK. The bombesin antagonist, ICI-216140, prevented bombesin-induced increase in GVAD, whereas the CCK response was not influenced. The CCK-A receptor antagonist devazepide reduced the activation of GVAD induced by bombesin from 107 +/- 11 to 63 +/- 6%, while abolishing the CCK response. Devazepide given alone or in combination with ICI-216140 did not modify gastric distension (3 ml)-induced increase in GVAD. Of 22 single units that were activated by gastric load (4 ml), 17 and 20 units responded also to bombesin (620 pmol) and CCK (870 pmol), respectively. Of the nine units that did not respond to gastric load, eight had an increase in GVAD induced by both bombesin and CCK. There was no specific binding of I-125-labled [Tyr(4)] bombesin on cervical vagus, either intact or 24 h after ligation. These data suggest that intravenous bombesin-induced stimulation of GAVD is indirect and initially mediated through specific receptor activation influencing gastric smooth muscle and the release of CCK. C1 W LOS ANGELES VET AFFAIRS MED CTR, CTR ULCER RES & EDUC, DIGEST DIS RES CTR, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, BRAIN RES INST, LOS ANGELES, CA 90073 USA. DUKE UNIV, MED CTR, DEPT CELL BIOL, DURHAM, NC 27710 USA. NR 36 TC 26 Z9 26 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD DEC PY 1996 VL 271 IS 6 BP R1584 EP R1593 PG 10 WC Physiology SC Physiology GA WB876 UT WOS:A1996WB87600017 ER PT J AU Marder, SR Wirshing, WC Mintz, J McKenzie, J Johnston, K Eckman, TA Lebell, M Zimmerman, K Liberman, RP AF Marder, SR Wirshing, WC Mintz, J McKenzie, J Johnston, K Eckman, TA Lebell, M Zimmerman, K Liberman, RP TI Two-year outcome of social skills training and group psychotherapy for outpatients with schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MAINTENANCE CHEMOTHERAPY; FAMILY PSYCHOEDUCATION; AFTERCARE TREATMENT; RELAPSE; FLUPHENAZINE; ADJUSTMENT; TRIAL AB Objective: The authors evaluated the effectiveness of behaviorally oriented social skills training and supportive group therapy for improving the social adjustment of schizophrenic patients living in the community and for protecting them against psychotic relapse. Method: Eighty male outpatients with schizophrenia were stabilized with a low dose of fluphenazine decanoate (5 to 10 mg every 14 days), which was supplemented with oral fluphenazine (5 mg twice daily) or a placebo when they first met criteria for a prodromal period. (Half of the patients did so at some time during the study.) Patients were randomly assigned to receive either social skills training or supportive group therapy twice weekly for 6 months and then weekly for the next 18 months. Rates of Psychotic exacerbation were monitored, as were scores on the Social Adjustment Scale II. Results: There were significant main effects favoring social skills training over supportive group therapy on two of the six Social Adjustment Scale II cluster totals examined (personal well-being and total) and significant interactions between psychosocial treatment and drug treatment for three items (external family, social and leisure activities, and total). In each case, these interactions indicated that the advantage of social skills training over supportive group therapy was greatest when it was combined with active drug supplementation. Social skills training did not significantly decrease the risk of psychotic exacerbation in the full group, but an advantage was observed (post hoc) among patients who received placebo supplementation. Conclusions: These findings suggest that social skills training resulted in greater improvement in certain measures of social adjustment than supportive group therapy. The greatest improvement in social outcomes occurred when social skills training was combined with a pharmacological strategy of active drug supplementation at the time prodromal worsening of psychotic symptoms was first observed. However, these improvements were modest in absolute terms and confined to certain subgroups of patients. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. RP Marder, SR (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,BRENTWOOD DIV,PSYCHIAT SERV 116A,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. FU NIMH NIH HHS [MH-41573] NR 25 TC 136 Z9 137 U1 1 U2 10 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 1996 VL 153 IS 12 BP 1585 EP 1592 PG 8 WC Psychiatry SC Psychiatry GA VV491 UT WOS:A1996VV49100013 PM 8942455 ER PT J AU Goff, DC Tsai, GC Manoach, DS Flood, J Darby, DG Coyle, JT AF Goff, DC Tsai, GC Manoach, DS Flood, J Darby, DG Coyle, JT TI D-cycloserine added to clozapine for patients with schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 11-15, 1995 CL SAN JUAN, PR SP Amer Coll Neuropsychopharm ID NMDA RECEPTOR; GLYCINE; SITE AB Objective: The effects of D-cycloserine added to clozapine were assessed and compared with previous results for D-cycloserine plus conventional neuroleptics. Method: Ten schizophrenic outpatients receiving clozapine entered consecutive 2-week trials of placebo and D-cycloserine at 5, 15, 50, and 250 mg/day. Clinical evaluations were videotaped and scored by a rater blind to the sequence of assessments. Results: There was a significant dose effect of D-cycloserine on scores on the Scale for the mg dose produced a mean 21% increase in SANS score. The patients had significantly higher baseline serum glutamate concentrations than the patients receiving typical neuroleptics in the previous trial. Baseline glutamate level and change in glycine level significantly correlated with response of negative symptoms to 50-mg D-cycloserine. Conclusions: The improvement of negative symptoms with D-cycloserine previously observed in patients receiving typical neuroleptics did not occur in patients treated with clozapine. C1 HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. MASSACHUSETTS GEN HOSP,PSYCHOT DISORDERS PROGRAM,BOSTON,MA 02114. RP Goff, DC (reprint author), FREEDOM TRAIL CLIN,25 STANIFORD ST,BOSTON,MA 02114, USA. NR 16 TC 135 Z9 136 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 1996 VL 153 IS 12 BP 1628 EP 1630 PG 3 WC Psychiatry SC Psychiatry GA VV491 UT WOS:A1996VV49100021 PM 8942463 ER PT J AU Dupuy, DE Palmer, WE Rosenthal, DI AF Dupuy, DE Palmer, WE Rosenthal, DI TI Vertebral fluid collection associated with vertebral collapse SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID INTRAVERTEBRAL VACUUM CLEFT AB OBJECTIVE. Three elderly women with osteoporotic compression fractures of a vertebral body underwent MR imaging because of neurologic signs and symptoms. Atypical fluid collections were shown by MR imaging in all three patients. For histologic characterization of these vertebral fluid collections, CT-guided biopsies and aspirations were done for all three patients. CONCLUSION. After studying the clinical, histologic, and imaging features of these fluid collections associated with vertebral fracture, we suggest that they are most likely associated with underlying avascular necrosis. RP Dupuy, DE (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,ACC 515,POB 9657,15 PARKMAN ST,BOSTON,MA 02114, USA. OI Dupuy, Damian/0000-0003-0524-5982 NR 6 TC 38 Z9 41 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 DEC PY 1996 VL 167 IS 6 BP 1535 EP 1538 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VW769 UT WOS:A1996VW76900037 PM 8956592 ER PT J AU Rosol, MS Cohen, GL Halpern, EF Chew, FS Kattapuram, SV Palmer, WE Dupuy, DE Rosenthal, DI AF Rosol, MS Cohen, GL Halpern, EF Chew, FS Kattapuram, SV Palmer, WE Dupuy, DE Rosenthal, DI TI Vertebral morphometry derived from digital images SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID SPINE DEFORMITY; FRACTURES; DIMENSIONS; OSTEOPOROSIS; DIAGNOSIS; INDEX; AREA AB OBJECTIVE. We describe a method for capturing measurement data directly from digitized images using specialized software and high-resolution workstations. We have evaluated the reliability, accuracy, and reproducibility of this method in an international clinical trial involving vertebral morphometry. MATERIALS AND METHODS. Accuracy was determined using clinical radiographs measured with vernier calipers and a film phantom. Intra- and interobserver variabilities were assessed, and longitudinal reproducibility was evaluated. As part of the trial, spinal radiographs were collected from more than 200 international health care facilities and digitized at four screening centers. Digitized images were stored and sent to our central facility for morphometry and archiving. Timeliness and variability of the process were tracked. RESULTS. Relative accuracy was nearly 100%. Correlation with clinical measurements was high (r = .96; p < .05). The mean coefficient of variation for interobserver variability was 2%. Intraobserver variation was 3-5%. The coefficient of variation for longitudinal reproducibility ranged from 4% to 6%. After 9 months of operation, our trial included 9494 patients. Of approximately 36,000 radiographs, 98% passed quality review. Only 1% of vertebral levels were not measurable. Hardware and software problems were minimal. CONCLUSION. The use of digitized images for morphometry is accurate, reproducible, and convenient. When applied to a large-scale clinical trial, it offers unique advantages that may justify the cost and complexity that exceed those of conventional radiographs. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. OI Dupuy, Damian/0000-0003-0524-5982; Chew, Felix/0000-0003-2711-2013 NR 19 TC 12 Z9 14 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 DEC PY 1996 VL 167 IS 6 BP 1545 EP 1549 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VW769 UT WOS:A1996VW76900039 PM 8956594 ER PT J AU Eskey, CJ Whitman, GJ Chew, FS AF Eskey, CJ Whitman, GJ Chew, FS TI Invasive aspergillosis of the orbit SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material 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 3 TC 3 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 DEC PY 1996 VL 167 IS 6 BP 1588 EP 1588 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VW769 UT WOS:A1996VW76900048 PM 8956603 ER PT J AU Zeitels, SM AF Zeitels, SM TI Phonomicrosurgical treatment of early glottic cancer and carcinoma in situ SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 4th International Conference of the Society-of-the-Head-and-Neck-Surgeons CY JUL 28-AUG 01, 1996 CL TORONTO, CANADA SP Soc Head & Neck Surgeons ID LASER-SURGERY; CLINICAL-EXPERIENCE; MANAGEMENT; CO2-LASER; EXPOSURE; LARYNX AB BACKGROUND: In recent years, transoral resection of early glottic cancer has developed into a phonomicrosurgical approach that resulted from the convergence of microlaryngoscopic surgical technique theory with body cover mucosal wave theory of voice production. The vocal outcome from these procedures has improved by minimizing the deep resection margin and thereby maximizing the preservation of the vocal folds' normal layered microstructure (laminae propria and epithelium). Recurrence and cure rates from this narrow-margin approach were examined. METHODS: The phonomicrosurgical resection approach is composed of four basic procedures in which there is an increasing depth of resection to accommodate a narrow-field deep cancer margin. This approach was employed to treat 13 T1 cancers and 7 with carcinoma in situ (CIS). RESULTS: NO patients who underwent a cancer resection developed a recurrence. Minimum follow-up on these patients was 2 years and the mean follow-up was 42 months. In the group with CIS, 2 patients developed microinvasive carcinoma despite en bloc excision of the CIS, Both were successfully treated; 1 was resected transorally and the other underwent radiation therapy. CONCLUSIONS: This study indicates that the phonomicrosurgical approach, which incorporates a narrow deep cancer margin to enhance the postoperative vocal outcome, resulted in standard control and cure of early glottic neoplasia. (C) 1996 by Excerpta Medica, Inc. C1 HARVARD UNIV, SCH MED, DEPT OTOL & LARYNGOL, BOSTON, MA 02115 USA. VET AFFAIRS MED CTR, OTOLARYNGOL SECT, BOSTON, MA USA. RP Zeitels, SM (reprint author), MASSACHUSETTS EYE & EAR INFIRM, DEPT OTOLARYNGOL, 243 CHARLES ST, BOSTON, MA 02114 USA. NR 32 TC 42 Z9 45 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD DEC PY 1996 VL 172 IS 6 BP 704 EP 709 DI 10.1016/S0002-9610(96)00295-4 PG 6 WC Surgery SC Surgery GA WA356 UT WOS:A1996WA35600024 PM 8988684 ER PT J AU Young, RH Oliva, E AF Young, RH Oliva, E TI Transitional cell carcinomas of the urinary bladder that may be underdiagnosed - A report of four invasive cases exemplifying the homology between neoplastic and non-neoplastic transitional cell lesions SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE urinary bladder; transitional cell carcinoma; innocuous-appearing; homology ID TRACT AB Four unusual invasive transitional carcinomas of the urinary bladder arose in patients aged 70 to 85 years. One or more specimens from each case were misinterpreted as benign. The features that led to diagnostic confusion included nests and trabeculae composed of cells with relatively bland cytologic features and small tubules, medium-sized glands, or cysts that suggested nephrogenic adenoma, cystitis glandularis, or cystitis cystica. In three cases, elongated slit-like lumens or clefts that frequently branched were also present, and several tumors had nests with pointed projections from which neoplastic cells invaded into the adjacent stroma in an often inconspicuous manner. In addition to their unusual patterns and frequent deceptive cytologic features, the tumors were noteworthy because they often had cells with abundant eosinophilic cytoplasm. A variety of architectural features, specifically a disorderly distribution of the epithelial elements, their frequent packed arrangement, and their variation in size and shape, all spoke for a neoplastic interpretation in the current cases. Additionally, in most of these cases, small clusters of cells or individual cells of more conventional invasive carcinoma facilitated the interpretation. The results of the study of these four cases expand the spectrum of recently described peculiar features of transitional cell carcinoma of the urinary bladder. Several of the findings in these tumors exemplify the parallels that exist between nonneoplastic epithelial abnormalities and transitional cell carcinoma of the bladder. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Young, RH (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,FRUIT ST,BOSTON,MA 02114, USA. NR 10 TC 38 Z9 40 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 DEC PY 1996 VL 20 IS 12 BP 1448 EP 1454 DI 10.1097/00000478-199612000-00003 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA VV544 UT WOS:A1996VV54400003 PM 8944037 ER PT J AU Young, RH Bostwick, DG AF Young, RH Bostwick, DG TI Florid cystitis glandularis of intestinal type with mucin extravasation: A mimic of adenocarcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE urinary bladder; cystitis glandularis; intestinal variant; mucin extravasation; tumor-like lesion ID URINARY-BLADDER; TRACT; METAPLASIA; CARCINOMAS; UROTHELIUM AB Six florid examples of cystitis glandularis of intestinal type associated with focal mucin extravasation into the stroma are reported. Several of the cases caused major diagnostic difficulty with regard to their distinction from adenocarcinoma. Five patients had masses that simulated a bladder neoplasm. Patients ranged from 27 to 65 (average 46) years of age and complained of hematuria or irritative symptoms. Four patients were treated only by transurethral resection. One patient underwent partial cystectomy because of an erroneous diagnosis of adenocarcinoma and another total cystectomy because of a neurogenic bladder. Microscopic examination showed numerous glands lined by intestinal type epithelium, conforming to the appearance of the intestinal variant of cystitis glandularis. All cases had at least a minor component of typical cystitis glandularis, and it was prominent in four cases. All six cases had foci of basophilic mucin in the stroma, and this was prominent in four cases. Rounded aggregates of mucin were occasionally surrounded by compressed connective tissue cells, simulating mucinous cysts. In favor of a benign interpretation were the absence of epithelial cells in the extravasated mucin, the lack of atypicality of the cells lining the intestinal type glands in all but one case, a generally orderly distribution of the glands, and their lack of infiltration of the muscularis propria, although they abutted the latter in several cases. Follow-up from 2 to 14 years is available for three of the cases and has been uneventful, the longest follow-up being in the case diagnosed as adenocarcinoma. These cases illustrate the extent to which cystitis glandularis may mimic a neoplasm on gross evaluation and the propensity of mucin extravasation to cause diagnostic difficulty, a finding documented only rarely previously. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MAYO CLIN,ROCHESTER,MN. RP Young, RH (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114, USA. NR 36 TC 31 Z9 35 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 DEC PY 1996 VL 20 IS 12 BP 1462 EP 1468 DI 10.1097/00000478-199612000-00005 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA VV544 UT WOS:A1996VV54400005 PM 8944039 ER PT J AU Baum, HBA Biller, BMK Finkelstein, JS Cannistraro, KB Oppenheim, DS Schoenfeld, AD Michel, TH Wittink, H Klibanski, A AF Baum, HBA Biller, BMK Finkelstein, JS Cannistraro, KB Oppenheim, DS Schoenfeld, AD Michel, TH Wittink, H Klibanski, A TI Effects of physiologic growth hormone therapy on bone density and body composition in patients with adult-onset growth hormone deficiency - A randomized, placebo-controlled trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE somatotropin; bone density; body composition; insulin-like growth factor I ID X-RAY ABSORPTIOMETRY; CARDIOVASCULAR RISK-FACTORS; OSTEOBLAST-LIKE CELLS; MINERAL DENSITY; REPLACEMENT THERAPY; GH DEFICIENCY; FACTOR-I; METABOLISM; HEART; DISEASE AB Background: Patients with adult-onset growth hormone deficiency have reduced bone density and increased fat mass. Growth hormone at high doses may decrease body fat in these patients, but the effects of growth hormone at more physiologic doses on bone density and body composition have not been convincingly shown. Objective: To determine whether long-term growth hormone therapy at a dose adjusted to maintain normal insulin-like growth factor 1 (IGF-1) levels has clinical effects in patients with adult-onset growth hormone deficiency. Design: Randomized, placebo-controlled study. Setting: Tertiary referral center. Patients: 32 men with adult-onset growth hormone deficiency. intervention: Growth hormone (initial daily dose. 10 mu g/kg of body weight) or placebo for 18 months. The growth hormone dose was reduced by 25% if IGF-1 levels were elevated. Measurements: Body composition and bone mineral density of the lumbar spine, femoral neck, and proximal radius were measured by dual energy x-ray absorptiometry at 6-month intervals. Markers of bone turnover were also measured during the first 12 months of the study. Results: Growth hormone therapy increased bone mineral density in the lumbar spine by a mean (+/- SD) of 5.1% +/- 4.1% and bone mineral density in the femoral neck by 2.4% +/- 3.5%. in the growth hormone group, significant increases were seen in the following markers of bone turnover: osteocalcin (4.4 +/- 3.6 mg/L to 7.2 +/- 4.6 mg/L) and urinary pyridinoline (39.0 +/- 19.8 nmol/mmol of creatinine to 55.7 +/- 25.5 nmol/mmol of creatinine) and deoxypyridinoline (8.4 +/- 7.1 nmol/mmol of creatinine to 14.9 +/- 9.4 nmol/mmol of creatinine). Percentage of body fat in the growth hormone group decreased (from 31.9% +/- 6.5% to 28.3% +/- 7.0%), and lean body mass increased (from 59.0 +/- 8.5 kg to 61.5 +/- 6.9 kg). These changes were significant compared with corresponding changes in the placebo group (P < 0.01 for all comparisons). Conclusions: Growth hormone administered to men with adult-onset growth hormone deficiency at a dose adjusted according to serum IGF-1 levels increases bone density and stimulates bone turnover, decreases body fat and increases lean mass, and is associated with a low incidence of side effects. C1 MASSACHUSETTS GEN HOSP,NEUROENDOCRINE UNIT,BOSTON,MA 02114. MAINE MED CTR,PORTLAND,ME 04102. FU NCRR NIH HHS [RR01066]; NIDDK NIH HHS [DK08783] NR 34 TC 196 Z9 198 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 1 PY 1996 VL 125 IS 11 BP 883 EP & PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA VV541 UT WOS:A1996VV54100003 PM 8967668 ER PT J AU Ikeda, M Sharma, V Sumi, M Rogaeva, EA Poorkaj, P Sherrington, R Nee, L Tsuda, T Oda, N Watanabe, M Aoki, M Shoji, M Abe, K Itoyama, Y Hirai, S Schellenberg, GD Bird, TD StGeorgeHyslop, PH AF Ikeda, M Sharma, V Sumi, M Rogaeva, EA Poorkaj, P Sherrington, R Nee, L Tsuda, T Oda, N Watanabe, M Aoki, M Shoji, M Abe, K Itoyama, Y Hirai, S Schellenberg, GD Bird, TD StGeorgeHyslop, PH TI The clinical phenotype of two missense mutations in the presenilin I gene in Japanese patients SO ANNALS OF NEUROLOGY LA English DT Article ID FAMILIAL ALZHEIMERS-DISEASE; CHROMOSOME-14; LINKAGE; LOCUS; KINDREDS AB We report the clinical and neuropathologic phenotypes associated with two different missense mutations in the presenilin I (PS-I) gene in Japanese patients with early-onset familial Alzheimer's disease (FAD). In the AM/JPN1 pedigree a missense mutation (C-->T) was found at nucleotide 1102, which is predicted to cause an alanine-to-valine missense substitution at codon 260. In this family, the disease had a mean age of onset of 40.3 rears and an indolent course (range, 8-19 years). Neuropathologic studies in 3 members of this pedigree showed widespread senile plaques, neuro-fibrillary tangles, and neuronal loss, as well as abundant perivascular subpial amyloid deposits in the Virchow-Robin spaces and the presence of Pick-like intraneuronal inclusions in the dentate gyrus. In the second pedigree, transmitting a C-->T nucleotide substitution at position 1027, leading to the missense mutation of alanine to valine at codon 285, the disease had a later onset (mean, 51 years) but a more rapid course. Comparison of the disease phenotypes associated with other missense mutations in exon 9 of PS-I reveals no clinical or pathological phenotype, which uniquely distinguishes Alzheimer's disease associated with PS-I mutations from other forms of early-onset PAD, implying that direct mutation screening is required to identify these cases. C1 TORONTO HOSP,DEPT MED,TORONTO,ON M5T 2S8,CANADA. UNIV WASHINGTON,SCH MED,DEPT MED,SEATTLE,WA 98195. UNIV WASHINGTON,SCH MED,DEPT NEUROL,SEATTLE,WA 98195. VET AFFAIRS PUGET SOUND HLTH CARE SYST,CTR GERIATR RES EDUC & CLIN,SEATTLE,WA. VET AFFAIRS PUGET SOUND HLTH CARE SYST,NEUROL SECT,SEATTLE,WA. NINCDS,CLIN NEUROPHARMACOL SECT,BETHESDA,MD 20892. TOHOKU UNIV,SCH MED,DEPT NEUROL,MAEBASHI,GUMMA,JAPAN. TOHOKU UNIV,SCH MED,DEPT NEUROL,SENDAI,MIYAGI 980,JAPAN. ISHII HOSP NEUROSURG & OPHTHALMOL,DIV NEUROL & NEUROSURG,IWAKI,FUKUSHIMA,JAPAN. RP Ikeda, M (reprint author), UNIV TORONTO,CTR RES NEURODEGENERAT DIS,DEPT MED,DIV NEUROL,TANZ NEUROSCI BLDG,TORONTO,ON M5S 3H2,CANADA. FU NIA NIH HHS [AG0513C, R01-AG11762] NR 16 TC 39 Z9 40 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 1996 VL 40 IS 6 BP 912 EP 917 DI 10.1002/ana.410400614 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WE377 UT WOS:A1996WE37700013 PM 9007097 ER PT J AU Garrison, MW Anderson, DE Campbell, DM Carroll, KC Malone, CL Anderson, JD Hollis, RJ Pfaller, MA AF Garrison, MW Anderson, DE Campbell, DM Carroll, KC Malone, CL Anderson, JD Hollis, RJ Pfaller, MA TI Stenotrophomonas maltophilia: Emergence of multidrug-resistant strains during therapy and in an in vitro pharmacodynamic chamber model SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID XANTHOMONAS-MALTOPHILIA; PSEUDOMONAS-MALTOPHILIA; DISK DIFFUSION; BETA-LACTAMASE; SUSCEPTIBILITY; INFECTION; CIPROFLOXACIN; COLONIZATION; COMBINATIONS; AGENTS AB Emergence of Stenotrophomonas maltophilia as a nosocomial pathogen is becoming increasingly apparent. Pleiotropic resistance characterizes S. maltophilia. Furthermore, a slow growth rate and an increased mutation rate generate discordance between in vitro susceptibility testing and clinical outcome. Despite original susceptibility, drug-resistant strains of S. maltophilia are often recovered from patients receiving beta-lactams, quinolones, or aminoglycosides. Given the disparity among various in vitro susceptibility methods, this study incorporated a unique pharmacodynamic model to more accurately characterize the bacterial time-kill curves and mutation rates of four clinical isolates of S. maltophilia following exposure to simulated multidose regimens of ceftazidime, ciprofloxacin, gentamicin, and ticarcillin-clavulanate. Time-kill data demonstrated regrowth of S. maltophilia with all four agents. With the exception of ticarcillin-clavulanate, viable bacterial counts at the end of 24 h exceeded the starting inoculum. Ciprofloxacin only reduced bacterial counts by less than 1.0 log prior to rapid bacterial regrowth. Resistant mutant strains, identical to their parent strain by pulsed-field gel electrophoresis, were observed following exposure to each class of antibiotic. Mutant strains also had distinct susceptibility patterns. These data are consistent with previous reports which suggest that S. maltophilia, despite susceptibility data that imply that the organism is sensitive, develops multiple forms of resistance quickly and against several classes of antimicrobial agents. Standard in vitro susceptibility methods are not completely reliable for detecting resistant S. maltophilia strains; and therefore, interpretation of these results should be done with caution. In vivo studies are needed to determine optimal therapy against S. maltophilia infections. C1 SACRED HEART & DEACONESS MED CTR,SPOKANE,WA 99210. ASSOCIATED REG UNIV PATHOLOGISTS,SALT LAKE CITY,UT 84108. UNIV IOWA,COLL MED,IOWA CITY,IA 52242. RP Garrison, MW (reprint author), WASHINGTON STATE UNIV,COLL PHARM,601 W 1ST AVE,SPOKANE,WA 99204, USA. NR 30 TC 60 Z9 62 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 DEC PY 1996 VL 40 IS 12 BP 2859 EP 2864 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA VW221 UT WOS:A1996VW22100035 PM 9124855 ER PT J AU Sasaki, T Akutsu, N Nishiyama, T Burgeson, RE Nishiyama, T Nakajima, H AF Sasaki, T Akutsu, N Nishiyama, T Burgeson, RE Nishiyama, T Nakajima, H TI Type XII collagen in human skin: Studies on its localization with monoclonal antibodies SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE collagen; connective tissue disease; human skin; immunohistochemistry; monoclonal antibody ID COMPONENT C1 SHISEIDO RES CTR,LIFE SCI RES LABS,KANAZAWA KU,YOKOHAMA,KANAGAWA 236,JAPAN. MASSACHUSETTS GEN HOSP,MGH HARVARD CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Sasaki, T (reprint author), YOKOHAMA CITY UNIV,SCH MED,DEPT DERMATOL,KANAZAWA KU,3-9 FUKUURA,YOKOHAMA,KANAGAWA 236,JAPAN. RI Nishiyama, Toshio/C-5434-2013 NR 7 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD DEC PY 1996 VL 289 IS 1 BP 62 EP 64 DI 10.1007/s004030050156 PG 3 WC Dermatology SC Dermatology GA VZ016 UT WOS:A1996VZ01600013 PM 9017140 ER PT J AU Li, KK Cheney, ML Gliklich, RE August, M Caradonna, D AF Li, KK Cheney, ML Gliklich, RE August, M Caradonna, D TI Fixed mandibular implant after microvascular mandibular reconstruction SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID STAPLE BONE PLATE; OROMANDIBULAR RECONSTRUCTION; OSSEOINTEGRATED IMPLANTS; HYPERBARIC-OXYGEN; OSTEORADIONECROSIS; IRRADIATION; MANAGEMENT; RADIATION; FLAPS; HEAD AB Objective: To evaluate the use of fixed mandibular implants to retain dental prostheses after microvascular mandibular reconstruction. Design: Case series. Setting: Tertiary referral center. Patients: Eight patients with microvascular mandibular reconstruction after mandibular resection. Outcome Measures: Clinically noted functional results, serial radiographic evidence of fixed mandibular implant and mandibular integrity, and mandibular integrity, and complications encountered. Results: Eight of 8 fixed mandibular implants were successfully placed and remained stable. The follow-up period ranged from 10 to 21 months (mean, 14.3 months). Conclusion: The use of fixed mandibular implants to retain dental prostheses after microvascular mandibular reconstruction is a safe and effective treatment option. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,DIV FACIAL PLAST & RECONSTRUCT SURG,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH DENT MED,DEPT ORAL & MAXILLOFACIAL SURG,MASSACHUSETTS GEN HOSP,BOSTON,MA 02115. NR 32 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD DEC PY 1996 VL 122 IS 12 BP 1308 EP 1312 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA VX016 UT WOS:A1996VX01600004 PM 8956741 ER PT J AU Steindel, SJ Howanitz, PJ Renner, SW AF Steindel, SJ Howanitz, PJ Renner, SW TI Reasons for proficiency testing failures in clinical chemistry and blood gas analysis - A College of American Pathologists Q-Probes study in 665 laboratories SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PERFORMANCE AB Objective.-To determine the reasons for proficiency testing (PT) failures from 41 chemistry and blood gas analytes using data collected to benchmark performance. Design.-Self-administered survey requesting number of challenges by analyte encompassing nine PT events. When the challenge resulted in a self-defined failure, further information was requested concerning the magnitude of the failure (as a standard deviation index) and categorization of the type of failure into six major groups (Methodologic, Technical, Clerical, Survey, Unexplained, or Other) and then into subgroups. Participants.-Laboratories enrolled in the 1992 College of American Pathologists Q-Probes program. Main Outcome Measures.-Rate of PT failures and reasons for failure. Results.-Proficiency testing data from 670 489 challenges performed in 665 laboratories revealed 9268 (1.4%) unacceptable results. Failure types were distributed as follows: Methodologic, 33.5%; Technical, 17.4%; Clerical, 11.1%; Survey, 7.8%; Unexplained, 25.7%; and Other, 7.4%. Conclusions.-Individual analyte PT failure is a common event in the participating laboratories, but failures in successive or alternate events are rare. Analysis of the reasons for failed events indicates that most identified reasons occurred in either the Methodologic or Technical categories (50.9%). Analysis of the failure types suggested investigation pathways based on the magnitude of the failure that could reduce the 25.7% rate of unexplained failures. C1 UNIV CALIF LOS ANGELES,MED CTR,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90024. W LOS ANGELES VET ADM HOSP,LAB SERV,LOS ANGELES,CA. RP Steindel, SJ (reprint author), CTR DIS CONTROL & PREVENT,PUBL HLTH PRACTICE PROGRAM OFF,DIV LAB SYST,CHAMBLEE,GA 30341, USA. NR 19 TC 25 Z9 25 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 1996 VL 120 IS 12 BP 1094 EP 1101 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA WQ053 UT WOS:A1996WQ05300006 PM 15456173 ER PT J AU Clegg, DO Reda, DJ Weisman, MH Blackburn, WD Cush, JJ Cannon, GW Mahowald, ML Schumacher, HR Taylor, T BudimanMak, E Cohen, MR Vasey, FB Luggen, ME Mejias, E Silverman, SL Makkena, R Alepa, FP Buxbaum, J Haakenson, CM Ward, RH Manaster, BJ Anderson, RJ Ward, JR Henderson, WG AF Clegg, DO Reda, DJ Weisman, MH Blackburn, WD Cush, JJ Cannon, GW Mahowald, ML Schumacher, HR Taylor, T BudimanMak, E Cohen, MR Vasey, FB Luggen, ME Mejias, E Silverman, SL Makkena, R Alepa, FP Buxbaum, J Haakenson, CM Ward, RH Manaster, BJ Anderson, RJ Ward, JR Henderson, WG TI Comparison of sulfasalazine and placebo in the treatment of ankylosing spondylitis - A Department of Veterans Affairs cooperative study SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CLINICAL-TRIAL; SULPHASALAZINE; THERAPY; INDEX AB Objective. To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active ankylosing spondylitis (AS) that is not controlled with nonsteroidal antiinflammatory drug therapy. Methods. Two hundred sixty-four patients with AS were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on morning stiffness, back pain, and physician and patient global assessments. Results. While longitudinal analysis revealed a trend favoring SSZ in the middle of treatment, no difference was seen at the end of treatment. Response rates were 38.2% for SSZ and 36.1% for placebo (P = 0.73). The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). AS patients with associated peripheral arthritis showed improvement that favored SSZ (P = 0.02). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints. Conclusion. SSZ at a dosage of 2,000 mg/day does not seem to be more effective than placebo in the treatment of AS patients with chronic, longstanding disease. SSZ is well tolerated and may be more effective than placebo in the treatment of AS patients with peripheral joint involvement. This effect is more pronounced in treatment of the peripheral arthritis in this subgroup of AS patients. C1 HINES CSP COORDINATING CTR,HINES,IL. VAMC,SAN DIEGO,CA. VAMC,BIRMINGHAM,AL. VAMC,DALLAS,TX. VAMC,MINNEAPOLIS,MN. VAMC,PHILADELPHIA,PA. VAMC,WHITE RIVER JCT,VT. VAMC,HINES,IL. VAMC,MILWAUKEE,WI. VAMC,TAMPA,FL. VAMC,CINCINNATI,OH. VAMC,SAN JUAN,PR. VAMC,LOS ANGELES,CA. VAMC,NEW ORLEANS,LA. VAMC,TUCSON,AZ. VAMC,NEW YORK,NY. ALBUQUERQUE CSP CLIN RES PHARM COORDINATING CTR,ALBUQUERQUE,NM. UNIV ILLINOIS,CHICAGO,IL. UNIV UTAH,HLTH SCI CTR,SALT LAKE CITY,UT. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV IOWA,IOWA CITY,IA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. DEPT VET AFFAIRS,CENT OFF,BOSTON,MA. DEPT VA CENT OFF,WASHINGTON,DC. RP Clegg, DO (reprint author), VAMC,DIV RHEUMATOL,4B200-SOM,50 N MED DR,SALT LAKE CITY,UT 84132, USA. NR 21 TC 164 Z9 171 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 1996 VL 39 IS 12 BP 2004 EP 2012 DI 10.1002/art.1780391209 PG 9 WC Rheumatology SC Rheumatology GA VX901 UT WOS:A1996VX90100008 PM 8961905 ER PT J AU Clegg, DO Reda, DJ Mejias, E Cannon, GW Weisman, MH Taylor, T BudimanMak, E Blackburn, WD Vasey, FB Mahowald, ML Cush, JJ Schumacher, HR Silverman, SL Alepa, FP Luggen, ME Cohen, MR Makkena, R Haakenson, CM Ward, RH Manaster, BJ Anderson, RJ Ward, JR Henderson, WG AF Clegg, DO Reda, DJ Mejias, E Cannon, GW Weisman, MH Taylor, T BudimanMak, E Blackburn, WD Vasey, FB Mahowald, ML Cush, JJ Schumacher, HR Silverman, SL Alepa, FP Luggen, ME Cohen, MR Makkena, R Haakenson, CM Ward, RH Manaster, BJ Anderson, RJ Ward, JR Henderson, WG TI Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis - A Department of Veterans Affairs cooperative study SO ARTHRITIS AND RHEUMATISM LA English DT Article ID DOUBLE-BLIND; CONTROLLED TRIAL AB Objective. To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis (PsA) resistant to nonsteroidal antiinflammatory drug therapy. Methods. Two hundred twenty-one patients with PsA were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on joint pain/tenderness and swelling scores and physician and patient global assessments. Results. Longitudinal analysis revealed a trend favoring SSZ treatment (P = 0.13). At the end of treatment, response rates were 57.8% for SSZ compared with 44.6% for placebo (P = 0.05). The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints, including dyspepsia, nausea, vomiting, and diarrhea. Conclusion. SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with PsA. C1 HINES CSP COORDINATING CTR,HINES,IL. VAMC,SAN JUAN,PR. VAMC,SAN DIEGO,CA. VAMC,WHITE RIVER JCT,VT. VAMC,HINES,IL. VAMC,BIRMINGHAM,AL. VAMC,TAMPA,FL. VAMC,MINNEAPOLIS,MN. VAMC,DALLAS,TX. VAMC,PHILADELPHIA,PA. VAMC,LOS ANGELES,CA. VAMC,TUCSON,AZ. VAMC,CINCINNATI,OH. VAMC,MILWAUKEE,WI. VAMC,NEW ORLEANS,LA. ALBUQUERQUE CSP CLIN RES PHARM COORDINATING CTR,ALBUQUERQUE,NM. UNIV ILLINOIS,CHICAGO,IL. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV IOWA,IOWA CITY,IA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. DEPT VET AFFAIRS,CENT OFF,BOSTON,MA. DEPT VA CENT OFF,WASHINGTON,DC. UNIV UTAH,HLTH SCI CTR,SALT LAKE CITY,UT. RP Clegg, DO (reprint author), VAMC,DIV RHEUMATOL,4B200-SOM,50 N MED DR,SALT LAKE CITY,UT 84132, USA. NR 15 TC 273 Z9 283 U1 1 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 DEC PY 1996 VL 39 IS 12 BP 2013 EP 2020 DI 10.1002/art.1780391210 PG 8 WC Rheumatology SC Rheumatology GA VX901 UT WOS:A1996VX90100009 PM 8961906 ER PT J AU Clegg, DO Reda, DJ Weisman, MH Cush, JJ Vasey, FB Schumacher, HR BudimanMak, E Balestra, DJ Blackburn, WD Cannon, GW Inman, RD Alepa, FP Mejias, E Cohen, MR Makkena, R Mahowald, ML Higashida, J Silverman, SL Parhami, N Buxbaum, J Haakenson, CM Ward, RH Manaster, BJ Anderson, RJ Ward, JR Henderson, WG AF Clegg, DO Reda, DJ Weisman, MH Cush, JJ Vasey, FB Schumacher, HR BudimanMak, E Balestra, DJ Blackburn, WD Cannon, GW Inman, RD Alepa, FP Mejias, E Cohen, MR Makkena, R Mahowald, ML Higashida, J Silverman, SL Parhami, N Buxbaum, J Haakenson, CM Ward, RH Manaster, BJ Anderson, RJ Ward, JR Henderson, WG TI Comparison of sulfasalazine and placebo in the treatment of reactive arthritis (Reiter's syndrome) - A Department of Veterans Affairs cooperative study SO ARTHRITIS AND RHEUMATISM LA English DT Article AB Objective. To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective in the treatment of reactive arthritis (ReA) that has been unresponsive to nonsteroidal antiinflammatory drug (NSAID) therapy. Methods. One hundred thirty-four patients with ReA who had failed to respond to NSAIDs were recruited from 19 clinics, randomized (double-blind) to receive either SSZ or placebo, and followed up for 36 weeks. The definition of treatment response was based on joint pain/tenderness and swelling scores and physician and patient global assessments. Results. Longitudinal analysis revealed improvement in the patients taking SSZ compared with those taking placebo, which appeared at 4 weeks and continued through the trial (P = 0.02). At the end of treatment, response rates were 62.3% for SSZ treatment compared with 47.7% for placebo treatment. The Westergren, erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints. Conclusion. SSZ at a dosage of 2,000 mg/day is well tolerated and effective in patients with chronically active ReA. C1 HINES CSP COORDINATING CTR,HINES,IL. VAMC,SAN DIEGO,CA. VAMC,DALLAS,TX. VAMC,TAMPA,FL. VAMC,PHILADELPHIA,PA. VAMC,HINES,IL. VAMC,BIRMINGHAM,AL. UNIV TORONTO,TORONTO,ON,CANADA. VAMC,LOS ANGELES,CA. VAMC,SAN JUAN,PR. VAMC,MILWAUKEE,WI. VAMC,NEW ORLEANS,LA. VAMC,MINNEAPOLIS,MN. VAMC,MARTINEZ,CA. VAMC,ALBANY,NY. VAMC,NEW YORK,NY. ALBUQUERQUE CSP CLIN RES PHARM COORDINATING CTR,ALBUQUERQUE,NM. UNIV UTAH,HLTH SCI CTR,SALT LAKE CITY,UT. UNIV ILLINOIS,CHICAGO,IL. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV IOWA,IOWA CITY,IA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. DEPT VET AFFAIRS,CENT OFF,BOSTON,MA. DEPT VA CENT OFF,WASHINGTON,DC. RP Clegg, DO (reprint author), VAMC,DIV RHEUMATOL,4B200-SOM,50 N MED DR,SALT LAKE CITY,UT 84132, USA. NR 15 TC 82 Z9 87 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 1996 VL 39 IS 12 BP 2021 EP 2027 DI 10.1002/art.1780391211 PG 7 WC Rheumatology SC Rheumatology GA VX901 UT WOS:A1996VX90100010 PM 8961907 ER PT J AU Sussman, S Simon, TR Glynn, SM Stacy, AW AF Sussman, S Simon, TR Glynn, SM Stacy, AW TI What does ''high risk'' mean? A PsycINFO scan of the literature SO BEHAVIOR THERAPY LA English DT Article ID ADOLESCENTS; TRENDS AB Recent health research has emphasized the study of high risk variables without consensus regarding different meanings of the term high risk. We provide a categorization scheme for this concept that includes prediction of consequence variables from antecedent variables in different contexts. Different antecedent-consequence combinations (notions of high risk) across a variety of health research contexts are described based on a search of PsycINFO entries from 1985 to 1990. investigators apparently limit their notions of high risk by specific research areas. We discuss the potential usefulness of the category scheme for providing a conceptual framework which bridges different research domains, or at least reduces the likelihood of misuse of the term. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Sussman, S (reprint author), UNIV SO CALIF,INST HLTH PROMOT & DIS PREVENT RES,1540 ALCAZAR ST,CHP-209F,LOS ANGELES,CA 90033, USA. RI Stacy, Alan/G-5406-2016 NR 28 TC 4 Z9 5 U1 0 U2 0 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD WIN PY 1996 VL 27 IS 1 BP 53 EP 65 DI 10.1016/S0005-7894(96)80035-9 PG 13 WC Psychology, Clinical SC Psychology GA UG689 UT WOS:A1996UG68900006 ER PT J AU Hyman, SE AF Hyman, SE TI Addiction: Taking the brain seriously SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material AB Heyman's target article is an analytical tour de force, but it makes too hard a distinction between voluntary and riven behavior. It is more fruitful to think about brain and behavior as shifting, interacting ''agents,'' represented by multiple neural circuits. This has the virtue of better connecting behavioral analysis with wet neuroscience. C1 NIMH,ROCKVILLE,MD 20857. RP Hyman, SE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,LAB MOL & DEV NEUROSCI,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD DEC PY 1996 VL 19 IS 4 BP 582 EP & PG 0 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA WY849 UT WOS:A1996WY84900012 ER PT J AU Zhao, LP Lipsitz, S Lew, D AF Zhao, LP Lipsitz, S Lew, D TI Regression analysis with missing covariate data using estimating equations SO BIOMETRICS LA English DT Article DE estimating equations; generalized linear model; joint estimating equations; missing at random; missing completely at random; missing covariate data; weighted estimating equations ID 2-STAGE CASE-CONTROL; MODELS; DESIGNS AB In regression analysis, missing covariate data has been among the most common problems. Frequently, practitioners adopt the so-called complete-case analysis, i.e., performing the analysis on only a complete dataset after excluding records with missing covariates. Performing a complete-case analysis is convenient with existing statistical packages, but it may be inefficient since the observed outcomes and covariates on those records with missing covariates are not used. It can even give misleading statistical inference if missingness is not completely at random. This paper introduces a joint estimating equation (JEE) for regression analysis in the presence of missing observations on one covariate, which may be thought of as a method in a general framework for the missing covariate data problem proposed by Robins, Rotnitzky, and Zhao (1994, Journal of the American Statistical Association 89, 846-866). A generalization of JEE to more than one such covariate is discussed. The JEE is generally applicable to estimating regression coefficients from a regression model, including linear and logistic regression. Provided that the missing covariate data is either missing completely at random or missing at random (in addition to mild regularity conditions), estimates of regression coefficients from the JEE are consistent and have an asymptotic normal distribution. Simulation results show that the asymptotic distribution of estimated coefficients performs well in finite samples. Also shown through the simulation study is that the validity of JEE estimates depends on the correct specification of the probability function that characterizes the missing mechanism, suggesting a need for further research on how to robustify the estimation from making this nuisance assumption. Finally, the JEE is illustrated with an application from a case-control study of diet and thyroid cancer. C1 DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP Zhao, LP (reprint author), FRED HUTCHINSON CANC RES CTR,DIV PUBL HLTH SCI,1124 COLUMBIA ST,MP 381,SEATTLE,WA 98104, USA. FU NCI NIH HHS [CA 64046, CA 55670] NR 16 TC 55 Z9 57 U1 0 U2 7 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1996 VL 52 IS 4 BP 1165 EP 1182 DI 10.2307/2532833 PG 18 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA VX804 UT WOS:A1996VX80400001 PM 8962448 ER PT J AU Ibrahim, JG Ryan, LM AF Ibrahim, JG Ryan, LM TI Use of historical controls in time-adjusted trend tests for carcinogenicity SO BIOMETRICS LA English DT Article DE Dirichlet; Dirichlet-multinomial; log-rank; prior ID PROPORTIONS; INFORMATION AB We develop a method for incorporating historical control information into time-adjusted tests for dose effects in carcinogenicity studies. After discretizing the time scaler we use a multinomial distribution to model the number of animals dying with tumor in each interval and specify a Dirichlet prior distribution on the control tumor death rates in each interval. Data ti om past studies are used to estimate the parameters characterizing the prior. A score test derived from the resulting Dirichlet-multinomial generalizes the test of Tarone (1982, Biometrics 38, 215-220) and reduces, in the limit, to the log-rank test in the case of a diffuse prior. The methodology is illustrated with data from a study of the fire retardant 2,2-Bis(bromomethyl)-1,3-propanediol. C1 DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. RP Ibrahim, JG (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,44 BINNEY ST,BOSTON,MA 02115, USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 13 TC 15 Z9 16 U1 0 U2 2 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1996 VL 52 IS 4 BP 1478 EP 1485 DI 10.2307/2532862 PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA VX804 UT WOS:A1996VX80400030 PM 8962464 ER PT J AU Williams, P Ryan, L AF Williams, P Ryan, L TI Design of multiple binary outcome studies with intentionally missing data SO BIOMETRICS LA English DT Article DE clustered data; developmental toxicity; efficiency; generalized estimating equations; score test; teratology ID DEVELOPMENTAL TOXICITY; MAXIMUM-LIKELIHOOD; TESTS; RATS; MICE AB We discuss the design and analysis of studies involving multiple binary outcomes in which only a subset of these outcomes can be measured on each individual. Such studies with ''intentionally missing data'' may arise due to practical or economic constraints; several examples from toxicology serve as illustrations. A global test statistic based on generalized estimating equations is presented and evaluated under a variety of missingness patterns and correlation structures. Extensions of the global test statistic to allow for clustered data are also described, The relative efficiency of the global test statistic with missing data relative to that for complete data is investigated, both under a common dose effect alternative and when exposure has differential effects on the multiple endpoints. The implications of these efficiency calculations on study design are explored, and several recommendations are provided. C1 DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. RP Williams, P (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NCI NIH HHS [CA-48601] NR 13 TC 3 Z9 3 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1996 VL 52 IS 4 BP 1498 EP 1514 DI 10.2307/2532865 PG 17 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA VX804 UT WOS:A1996VX80400033 PM 8962465 ER PT J AU Lee, SJ Kim, K Tsiatis, AA AF Lee, SJ Kim, K Tsiatis, AA TI Repeated significance testing in longitudinal clinical trials SO BIOMETRIKA LA English DT Article DE error spending function; generalised estimating equation; group sequential; independent increments; repeated measures; score test; Wald test ID GENERALIZED LINEAR-MODELS; MULTIVARIATE OBSERVATIONS; SEQUENTIAL-METHODS; BOUNDARIES; PARAMETERS; DISCRETE AB When longitudinal clinical trials are monitored, multiplicity from repeated significance testing as well as from repeated measures has to be accounted for properly to control the overall type I error. This often involves a multidimensional integration procedure to compute group sequential boundaries. We establish an independent increments structure of sequentially computed test statistics based on the generalised estimating equations of Liang & Zeger (1986) for longitudinal data. This simplifies the computational procedure for group:sequential boundaries to one involving recursive one-dimensional integrations and allows the use of standard methodology for group sequential tests. We also apply the error spending function approach of Lan & DeMets (1983) by defining information fraction in this setting. C1 UNIV MICHIGAN, CTR COMPREHENS CANC, ANN ARBOR, MI 48109 USA. HARVARD UNIV, SCH PUBL HLTH, DEPT BIOSTAT, BOSTON, MA 02115 USA. RP Lee, SJ (reprint author), DANA FARBER CANC INST, DIV BIOSTAT, BOSTON, MA 02115 USA. NR 28 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 EI 1464-3510 J9 BIOMETRIKA JI Biometrika PD DEC PY 1996 VL 83 IS 4 BP 779 EP 789 DI 10.1093/biomet/83.4.779 PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA WE019 UT WOS:A1996WE01900005 ER PT J AU Lipsitz, SR Ibrahim, JG AF Lipsitz, SR Ibrahim, JG TI A conditional model for incomplete covariates in parametric regression models SO BIOMETRIKA LA English DT Article DE EM-algorithm; missing at random; non-monotone missing data ID RANDOMIZED PHASE-II; HEPATOCELLULAR-CARCINOMA AB Incomplete covariate data arise in many data sets. When the missing covariates are categorical, a useful technique for obtaining parameter estimates is the EM algorithm by the method of weights proposed in Ibrahim (1990). This method requires the estimation of many nuisance parameters for the distribution of the covariates. Unfortunately, in data sets when the percentage of missing data is high, and the missing covariate patterns are highly non-monotone, the estimates of the nuisance parameters can lead to highly unstable estimates of the parameters of interest. We propose a conditional model for the covariate distribution that has several modelling advantages for the E-step and provides a reduction in the number of nuisance parameters, thus providing more stable estimates in finite samples. We present a clinical trials example with six covariates, five of which have some missing values. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. RP Lipsitz, SR (reprint author), DANA FARBER CANC INST,DIV BIOSTAT,44 BINNEY ST,BOSTON,MA 02115, USA. NR 10 TC 74 Z9 74 U1 0 U2 3 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD DEC PY 1996 VL 83 IS 4 BP 916 EP 922 DI 10.1093/biomet/83.4.916 PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA WE019 UT WOS:A1996WE01900018 ER PT J AU Hiddemann, W Longo, DL Coiffier, B Fisher, RI Cabanillas, F Cavalli, F Nadler, LM DeVita, VT Lister, TA Armitage, JO AF Hiddemann, W Longo, DL Coiffier, B Fisher, RI Cabanillas, F Cavalli, F Nadler, LM DeVita, VT Lister, TA Armitage, JO TI Lymphoma classification - The gap between biology and clinical management is closing SO BLOOD LA English DT Editorial Material ID MANTLE CELL LYMPHOMA; NEOPLASMS C1 UNIV GOTTINGEN,DEPT HEMATOL ONCOL,D-3400 GOTTINGEN,GERMANY. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. CTR HOSP LYON SUD,DEPT HEMATOL,F-69310 PIERRE BENITE,FRANCE. LOYOLA UNIV,CTR CANC,DIV HEMATOL ONCOL,MAYWOOD,IL 60153. MD ANDERSON CANC CTR,DEPT HEMATOL,HOUSTON,TX 77030. OSPED SAN GIOVANNI BELLINZONA,DIV ONCOL,BELLINZONA,SWITZERLAND. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. YALE UNIV,CTR CANC,NEW HAVEN,CT. ST BARTHOLOMEWS HOSP,DEPT MED ONCOL,LONDON,ENGLAND. UNIV NEBRASKA,DEPT INTERNAL MED,OMAHA,NE. NR 15 TC 109 Z9 115 U1 1 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 DEC 1 PY 1996 VL 88 IS 11 BP 4085 EP 4089 PG 5 WC Hematology SC Hematology GA VV152 UT WOS:A1996VV15200001 PM 8943841 ER PT J AU Ku, H Hirayama, F Kato, T Miyazaki, H Aritomi, M Ota, Y DAndrea, AD Lyman, SD Ogawa, M AF Ku, H Hirayama, F Kato, T Miyazaki, H Aritomi, M Ota, Y DAndrea, AD Lyman, SD Ogawa, M TI Soluble thrombopoietin receptor (Mpl) and granulocyte colony-stimulating factor receptor directly stimulate proliferation of primitive hematopoietic progenitors of mice in synergy with steel factor or the ligand for Flt3/Mlk2 SO BLOOD LA English DT Article ID BLAST CELL COLONIES; MURINE LYMPHOHEMATOPOIETIC PROGENITORS; UMBILICAL-CORD BLOOD; MOLECULAR-CLONING; GROWTH-FACTOR; C-KIT; INTERLEUKIN-3-DEPENDENT PROLIFERATION; CHROMOSOMAL LOCALIZATION; ERYTHROPOIETIN RECEPTOR; SUPPORTS FORMATION AB In an effort to establish the specificity of the thrombopoietin (TPO) effects on murine multipotential progenitors, we tested the effects of soluble TPO receptor (sTPOR; sMpl) on multilineage colony formation that was supported by a combination of TPO and steel factor (SF). Surprisingly, sTPOR did not suppress colony formation from primitive progenitors, This led to the discovery that sTPOR synergizes with SF or Flt3/Flk2 ligand (FL) to support the formation of various types of hematopoietic colonies including multilineage colonies. The colonies supported by the combination of sTPOR and SF were capable of expressing both myeloid and B-lymphoid potentials. Studies using micromanipulation and serum-free culture showed that the effects of sTPOR and SF on the primitive progenitors are direct, not mediated by contaminating stromal cells, and not dependent on factors present in the serum. TPOR belongs to the cytokine receptor group that includes granulocyte colony-stimulating factor receptor (G-CSFR) and erythropoietin receptor (EPOR). Therefore, we tested the effects of sG-CSFR and sEPOR on primitive progenitors, sG-CSFR, but not sEPOR, was able to synergize with SF or FL in supporting the proliferation of primitive progenitors. The direct effects of the soluble receptors appear to be mediated through interactions with their respective membrane-bound receptors expressed on the primitive hematopoietic progenitors. (C) 1996 by The American Society of Hematology. C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. KIRIN BREWERY CO LTD,PHARMACEUT RES LAB,MAEBASHI,GUMMA 371,JAPAN. PROT ENGN RES INST,SUITA,OSAKA 565,JAPAN. IMMUNEX CORP,SEATTLE,WA. DANA FARBER CANC INST,BOSTON,MA 02115. FU NIDDK NIH HHS [DK32294, DK/HL48714] NR 51 TC 26 Z9 26 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1996 VL 88 IS 11 BP 4124 EP 4131 PG 8 WC Hematology SC Hematology GA VV152 UT WOS:A1996VV15200006 PM 8943846 ER PT J AU Ganju, RK Shpektor, RG Brenner, DG Shipp, MA AF Ganju, RK Shpektor, RG Brenner, DG Shipp, MA TI CD10/neutral endopeptidase 24.11 is phosphorylated by casein kinase II and coassociates with other phosphoproteins including the lyn src-related kinase SO BLOOD LA English DT Article ID PROTEIN-TYROSINE KINASES; EPIDERMAL GROWTH-FACTOR; BOMBESIN-LIKE PEPTIDES; NEUTRAL ENDOPEPTIDASE; MOLECULAR-CLONING; ANTIGEN RECEPTOR; CONVERTING ENZYME; HUMAN-NEUTROPHILS; CELL CARCINOMAS; ACTIVATION AB CD10/neutral endopeptidase 24.11 (NEP) regulates peptide-mediated proliferation of lymphoid progenitors and certain epithelial cells and is itself regulated by cellular proliferation. To further characterize mechanisms by which cell-surface signaling might regulate CD10/MEP expression, we determined whether CD10/NEP was phosphorylated and whether the enzyme co-associated with additional cellular phosphoproteins. The CD10/NEP cytoplasmic tail contains two consensus recognition sequences for casein kinase II (CKII), a serine and threonine kinase that increases in activity following peptide signaling. In standard in vitro kinase assays, CKII phosphorylated full-length recombinant CD10/NEP but did not phosphorylate a truncated CD10/NEP protein that lacked the transmembrane region and cytoplasmic tail. To determine whether CD10/NEP might interact with additional cellular phosphoproteins, in vitro kinase assays were performed on CD10/NEP immune complexes from Nalm-6 cells. Three additional tyrosine phosphoproteins of similar to 40 kD, similar to 56 kD, and similar to 75 kD were identified in the CD10/NEP immunoprecipitates. The similar to 56-kD CD10/NEP-associated phosphoprotein was immunoprecipitated with an anti-lyn antibody confirming its identity as the lyn src-related kinase. Taken together, these data indicate that CD10/NEP is itself phosphorylated by CKII and that CD10/NEP co-associates with additional tyrosine phosphoproteins including lyn. (C) 1996 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. KHEPRI PHARMACEUT INC,S SAN FRANCISCO,CA. NR 61 TC 35 Z9 35 U1 1 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 DEC 1 PY 1996 VL 88 IS 11 BP 4159 EP 4165 PG 7 WC Hematology SC Hematology GA VV152 UT WOS:A1996VV15200010 PM 8943850 ER PT J AU McLean, TW Ringold, S Neuberg, D Stegmaier, K Tantravahi, R Ritz, J Koeffler, HP Takeuchi, S Janssen, JWG Seriu, T Bartram, CR Sallan, SE Gilliland, DG Golub, TR AF McLean, TW Ringold, S Neuberg, D Stegmaier, K Tantravahi, R Ritz, J Koeffler, HP Takeuchi, S Janssen, JWG Seriu, T Bartram, CR Sallan, SE Gilliland, DG Golub, TR TI TEL/AML-1 dimerizes and is associated with a favorable outcome in childhood acute lymphoblastic leukemia SO BLOOD LA English DT Article ID POLYMERASE CHAIN-REACTION; ACUTE MYELOID-LEUKEMIA; AML1 GENE; TEL GENE; MYELOPROLIFERATIVE DISORDERS; TRANSCRIPTION FACTOR; FUSION; 12P13; TRANSLOCATION; REGION AB Polymerase chain reaction-based screening of childhood acute lymphoblastic leukemia (ALL) samples showed that a TEL/AML1 fusion transcript was detected in 27% of all cases, representing the most common known gene rearrangement in childhood cancer. The TEL/AML1 fusion results from a t(12;21)(p13:q22) chromosomal translocation, but was undetectable at the routine cytogenetic level. TEL/AML1-positive patients had exclusively B-lineage ALL, and most patients were between the ages of 2 and 9 years at diagnosis. Only 3/89 (3.4%) adult ALL patients were TEL/AML1-positive. Most importantly, TEL/AML1-positive children had a significantly lower rate of relapse compared with TEL/AML1-negative patients (0/22 v 16/54, P = .004). Co-immunoprecipitation experiments demonstrated that TEL/AML-1 formed homodimers in vitro, and heterodimerized with the normal TEL protein when the two proteins were expressed together, The elucidation of the precise mechanism of transformation by TEL/AML1 and the role of TEL/AML1 testing in the treatment of childhood ALL will require additional studies. (C) 1996 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. UNIV CALIF LOS ANGELES,SCH MED,CEDARS SINAI RES INST,DIV HEMATOL ONCOL,LOS ANGELES,CA. UNIV HEIDELBERG,INST HUMAN GENET,HEIDELBERG,GERMANY. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA 57261] NR 48 TC 252 Z9 253 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 DEC 1 PY 1996 VL 88 IS 11 BP 4252 EP 4258 PG 7 WC Hematology SC Hematology GA VV152 UT WOS:A1996VV15200021 PM 8943861 ER PT J AU Saban, J Zussman, MA Havey, R Pathwardhan, AG Schneider, GB King, D AF Saban, J Zussman, MA Havey, R Pathwardhan, AG Schneider, GB King, D TI Heterozygous oim mice exhibit a mild form of osteogenesis imperfecta SO BONE LA English DT Article DE osteogenesis imperfecta; oim mice; biomechanics; bones ID EMBRYONIC LETHAL MUTATION; ALPHA-1(I) COLLAGEN GENE; TRANSGENIC MICE; I COLLAGEN; RETROVIRUS; PHENOTYPE; INSERTION; COL1A1; MODEL AB The oim Strain of mice is one of several rodent models that exhibit an osteogenesis imperfecta (OI) phenotype, These mice have a mutation in the gene encoding alpha-2 chain of type I procollagen that prevents proper assembly of this propeptide with alpha-1 propeptides, Homozygous oim mice experience multiple bone fractures under standard laboratory animal housing conditions and are representative of moderate to severe forms of OI, Because fractures are not typically experienced by heterozygous oim mice, they have not been studied extensively, The present studies show that the organization of cortical bone is deficient in heterozygotes, exhibiting a morphology intermediate to specimens from homozygotes and wild-type mice, The biomechanical properties of femurs isolated from heterozygous oim mice are also intermediate to homozygotes and wild-type mice when tested in four-point bending, Although it is not possible to distinguish visually between heterozygous oim and wild-type mice, the quality and biomechanical properties of bone in heterozygotes is significantly reduced by twelve weeks of age, Heterozygous oim mice are useful as a model for a mild form of OI. (C) 1996 by Elsevier Science Inc. C1 FINCH UNIV HLTH SCI CHICAGO MED SCH,DEPT MICROBIOL & IMMUNOL,N CHICAGO,IL 60064. FINCH UNIV HLTH SCI CHICAGO MED SCH,DEPT MOL BIOL & PHARMACOL,N CHICAGO,IL 60064. FINCH UNIV HLTH SCI CHICAGO MED SCH,DEPT CELL BIOL & ANAT,N CHICAGO,IL 60064. LOYOLA UNIV,MED CTR,DEPT ORTHOPAED SURG,MAYWOOD,IL 60153. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,ORTHOPAED BIOMECH LAB,HINES,IL 60141. NR 21 TC 50 Z9 51 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 8756-3282 J9 BONE JI Bone PD DEC PY 1996 VL 19 IS 6 BP 575 EP 579 DI 10.1016/S8756-3282(96)00305-5 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VZ104 UT WOS:A1996VZ10400002 PM 8968022 ER PT J AU BenEliyahu, S Page, GG Shakhar, G Taylor, AN AF BenEliyahu, S Page, GG Shakhar, G Taylor, AN TI Increased susceptibility to metastasis during pro-oestrus/oestrus in rats: Possible role of oestradiol and natural killer cells SO BRITISH JOURNAL OF CANCER LA English DT Article DE oestrous cycle; menstrual cycle; immunity; oestradiol; MADB106 ID LARGE GRANULAR LYMPHOCYTES; OPERABLE BREAST-CANCER; MENSTRUAL-CYCLE; NK CELLS; PERIPHERAL-BLOOD; PREMENOPAUSAL WOMEN; MONOCLONAL-ANTIBODY; SURGICAL-TREATMENT; ESTROUS-STAGE; TUMOR-CELLS AB It has been suggested that tumour development and immunocompetence are affected by the menstrual and the oestrous cycle, and sex hormones have been shown to modulate lymphokine production, neuroendocrine activity and immunity. In this study, we assessed natural killer cell activity and host susceptibility to metastasis during the oestrous cycle in the Fisher 344 inbred rat strain. Females were inoculated intravenously with MADB106 tumour cells, a syngeneic mammary adenocarcinoma cell line that metastasises only to the lungs. The susceptibility to metastatic development of this tumour was found to be significantly higher during pro-oestrus and oestrus than during metoestrus and dioestrus. Two days of exposure to oestradiol benzoate caused similar effects in ovariectomised females, and a single administration of progesterone reduced this effect of oestradiol to a statistically non-significant level. The tumour was found to be negative for oestradiol receptors, and its in vitro proliferation rate was not affected by oestradiol or progesterone, suggesting that the effects of sex hormones on the metastatic process are not attributable to a direct effect on tumour cells. Because the metastatic process of MADB106 tumour cells is known, and confirmed here, to be highly controlled by large granular lymphocyte natural killer (LGL/NK) cell activity, we assessed their role in mediating the effects of the oestrous cycle. The number and activity levels of circulating blood LG/NK cells (NKR-Pl(+) bright) were studied. Findings indicated oestrous-dependent alterations in the number of LGL/NK cells and suggested a diminished NK activity per LGL/NK cell during pro-oestrus/oestrus, the same phases that were characterised by higher susceptibility to metastatic development. These findings provide the first empirical evidence for a causal relationship between a short-term exposure to elevated oestradiol/low progesterone levels and decreased resistance to tumour metastasis, and it is hypothesised that an alteration in LGL/NK cell activity underlies these effects. Homologies and relevance to clinical phenomena are discussed. C1 OHIO STATE UNIV,COLL NURSING,COLUMBUS,OH 43210. UNIV CALIF LOS ANGELES,DEPT NEUROBIOL,LOS ANGELES,CA 90095. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90095. RP BenEliyahu, S (reprint author), TEL AVIV UNIV,DEPT PSYCHOL,IL-69978 TEL AVIV,ISRAEL. FU NICHD NIH HHS [TS32 HD07228] NR 60 TC 38 Z9 38 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD DEC PY 1996 VL 74 IS 12 BP 1900 EP 1907 DI 10.1038/bjc.1996.651 PG 8 WC Oncology SC Oncology GA VX690 UT WOS:A1996VX69000007 PM 8980388 ER PT J AU Barnhill, RL Xiao, M Graves, D Antoniades, HN AF Barnhill, RL Xiao, M Graves, D Antoniades, HN TI Expression of platelet-derived growth factor (PDGF)-A, PDGF-B and the PDGF-alpha receptor, but not the PDGF-beta receptor, in human malignant melanoma in vivo SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID SIMIAN SARCOMA-VIRUS; TRANSFORMED-CELLS; TUMOR PROGRESSION; RNA EXPRESSION; MESSENGER-RNAS; V-SIS; TISSUE; MELANOCYTES; CARCINOMAS; PHENOTYPE AB There has been considerable interest in the potential role of growth factors in the initiation and development of cutaneous malignant melanoma (CMM). Platelet-derived growth factor (PDGF) has been shown to be secreted by melanoma cell lines and by metastatic melanoma in vivo. PDGF also has been reported to stimulate the development of tumour stroma and new blood vessels. We studied the expression of PDGF and its receptors by both immunohistochemistry (IHC) and in situ hybridization (ISH) in primary and metastatic melanoma and in normal skin specimens. Cryostat sections were incubated with S-35-labelled riboprobes and antibodies for PDGF-AA, PDGF-alpha receptor, PDGF-BB and PDGF-beta receptor, Both primary and metastatic melanoma exhibited significant expression of PDGF-AA, PDGF-BB and PDGF-alpha receptor by both IHC and ISH, compared with only background expression in normal skin, We did not observe expression of PDGF-beta receptor in melanoma. Our results suggest that PDGF may function as an autocrine growth factor, as well as an angiogenesis factor, in CMM tumour development. This expression of the PDGF-alpha receptor rather than the beta receptor may be unique among solid tumours. C1 HARVARD UNIV,SCH PUBL HLTH,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL & NUTR,BOSTON,MA 02115. BOSTON UNIV,SCH MED,DEPT ORAL BIOL,BOSTON,MA 02118. RP Barnhill, RL (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV DERMATOPATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE07559] NR 31 TC 66 Z9 67 U1 0 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD DEC PY 1996 VL 135 IS 6 BP 898 EP 904 DI 10.1046/j.1365-2133.1996.d01-1092.x PG 7 WC Dermatology SC Dermatology GA VX119 UT WOS:A1996VX11900005 PM 8977709 ER PT J AU Prostak, KS Lees, S AF Prostak, KS Lees, S TI Visualization of crystal-matrix structure. In situ demineralization of mineralized turkey leg tendon and bone SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE bone; apatite; collagen; demineralization; ultrastructure ID COLLAGEN FIBRILS; ELECTRON-MICROSCOPY; RAT BONE; SIALOPROTEIN; OSTEOPONTIN; PROTEINS AB A technique to correlate the ultrastructural distribution of mineral with its organic material in identical sections of mineralized turkey leg tendon (MTLT) and human bone was developed. Osmium or ethanol fixed tissues were processed for transmission electron microscopy (TEM). The mineralized tissues were photographed at high, intermediate, and low magnifications, making note of section features such as fibril geometry, colloidal gold distribution, or section artifacts for subsequent specimen realignment after demineralization. The specimen holder was removed from the microscope, the tissue section demineralized in situ with a drop of 1 N HCl, then stained with 2% aqueous vanadyl sulfate. The specimen holder was reinserted into the microscope, realigned with the aid of the section features previously noted, and rephotographed at identical magnification used for the mineralized sections. A one to one correspondence was apparent between the mineral and its demineralized crystal ''ghost'' in both MTLT and bone. The fine structural periodic banding seen in unmineralized collagen was not observed in areas that were fully mineralized before demineralization, indicating that the axial arrangement of the collagen molecules is altered significantly during mineralization. Regions that had contained extrafibrillar crystallites stained more intensely than the intrafibrillar regions, indicating that the noncollagenous material surrounded the collagen fibrils. The methodology described here may have utility in determining the spatial distribution of the noncollagenous proteins in bone. RP Prostak, KS (reprint author), FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02115, USA. FU NIA NIH HHS [AGO-2325] NR 17 TC 53 Z9 53 U1 1 U2 8 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD DEC PY 1996 VL 59 IS 6 BP 474 EP 479 DI 10.1007/BF00369213 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VV310 UT WOS:A1996VV31000011 PM 8939774 ER PT J AU DeFrank, JS Tang, W Powell, SN AF DeFrank, JS Tang, W Powell, SN TI p53-null Cells are more sensitive to ultraviolet light only in the presence of caffeine SO CANCER RESEARCH LA English DT Article ID REGULATED GADD45 PROTEIN; MUTANT P53 INCREASES; EXCISION-REPAIR; DNA-DAMAGE; RADIATION; UV; RADIOSENSITIZATION; CHECKPOINT; RESISTANCE; MUTATIONS AB We have shown previously that p53(-/-) fibroblasts show greater sensitization by caffeine to the Lethal effects of ionizing radiation compared with p53(+/+) cells. Recently published data have suggested a possible role of p53 in nucleotide excision repair: an association of p53 and xeroderma pigmentosum group B protein and a greater sensitivity to cisplatin of RKO cells transfected with the E6 protein of human papilloma virus (inactivating p53). We show that p53(+/+) and p53(-/-) cells have equal sensitivity to germicidal UV light (as with ionizing radiation). However, the introduction of 2 mM caffeine led to a sensitization enhancement ratio (at 10% survival) of 1.8 in p53(-/-) cells, but only 1.3 in wild-type (p53+/+) cells. Lower doses of caffeine had less effect, and 0.1 mM caffeine resulted in no detectable sensitization of either cell type to UV light in contrast to X-rays. The differential sensitivity of p53(-/-) cells to X-rays and caffeine was thought to be due to override of the G(2)-M block to cell cycle progression. In response to UV light, cells accumulate in S phase, and the magnitude of S-phase accumulation was observed to be greater in p53(-/-) cells. Caffeine had little effect on the cell cycle distribution in p53(+/+) cells. However, for p53(-/-) cells, a greater proportion mere in S phase after treatment with caffeine, and a complete loss of S-phase delay was observed after UV irradiation. In conclusion, the role of p53 in nucleotide excision repair appears to be of little significance for cell survival. Greater sensitization of p53(-/-) cells to caffeine could be mediated via override of S-phase delay. C1 HARVARD UNIV,DEPT RADIAT ONCOL,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. FU NCI NIH HHS [CA58985] NR 27 TC 39 Z9 41 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1996 VL 56 IS 23 BP 5365 EP 5368 PG 4 WC Oncology SC Oncology GA VV562 UT WOS:A1996VV56200012 PM 8968086 ER PT J AU Yu, JS SenaEsteves, M Paulus, W Breakefield, XO Reeves, SA AF Yu, JS SenaEsteves, M Paulus, W Breakefield, XO Reeves, SA TI Retroviral delivery and tetracycline-dependent expression of IL-1 beta-converting enzyme (ICE) in a rat glioma model provides controlled induction of apoptotic death in tumor cells SO CANCER RESEARCH LA English DT Article ID SUPPRESSOR GENES; CED-3; BRAIN; LINE; P53 AB Interleukin 1 beta-converting enzyme (ICE) is a member of a growing family of cysteine proteases shown to be a crucial component in the activation of a genetic program that leads to autonomous cell death in mammalian cells. In this study, a murine ICE-lacZ fusion gene was introduced into a novel retroviral vector designed to achieve regulated ectopic expression of a foreign gene in mammalian-cells. By delivering the ICE-lacZ gene within a retroviral vector and under the control of a tetracycline-regulated promoter, we were able to utilize the intrinsic cell death program of ICE as a means for tumoricidal therapy in a rat brain tumor model. Both in culture and in vivo suppression of ICE-lacZ expression was extremely tight in the presence of tetracycline, as determined by the lack of X-galactosidase-positive tumor cells and by cell viability. When tetracycline was withdrawn, ICE-lacZ gene expression was rapidly turned on and apoptosis-mediated cell death occurred in essentially all tumor cells. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,NEUROL SERV,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. FU NINDS NIH HHS [NS24279] NR 23 TC 60 Z9 65 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1996 VL 56 IS 23 BP 5423 EP 5427 PG 5 WC Oncology SC Oncology GA VV562 UT WOS:A1996VV56200022 PM 8968096 ER PT J AU McGhie, AI Weyman, A AF McGhie, AI Weyman, A TI Searching for hibernating myocardium - Time to reevaluate investigative strategies? SO CIRCULATION LA English DT Editorial Material DE editorials; hibernation, myocardial; myocardial viability; imaging ID LEFT-VENTRICULAR FUNCTION; CORONARY-ARTERY DISEASE; DOBUTAMINE ECHOCARDIOGRAPHY; VIABLE MYOCARDIUM; REVASCULARIZATION; TL-201; DYSFUNCTION; REINJECTION; IMPROVEMENT; VIABILITY C1 MASSACHUSETTS GEN HOSP,DEPT INTERNAL MED,CARDIAC UNIT,BOSTON,MA. RP McGhie, AI (reprint author), UNIV TEXAS,DEPT INTERNAL MED,MSB 1228,HOUSTON,TX 77030, USA. NR 16 TC 22 Z9 23 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 DEC 1 PY 1996 VL 94 IS 11 BP 2685 EP 2688 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VV274 UT WOS:A1996VV27400004 PM 8941087 ER PT J AU Gerszten, RE Luscinskas, FW Ding, HT Dichek, DA Stoolman, LM Gimbrone, MA Rosenzweig, A AF Gerszten, RE Luscinskas, FW Ding, HT Dichek, DA Stoolman, LM Gimbrone, MA Rosenzweig, A TI Adhesion of memory lymphocytes to vascular cell adhesion molecule-1-transduced human vascular endothelial cells under simulated physiological flow conditions in vitro SO CIRCULATION RESEARCH LA English DT Article DE adhesion; endothelium; atherosclerosis; lymphocyte; adenovirus ID INVIVO GENE-TRANSFER; LEUKOCYTE ADHESION; ATHEROSCLEROTIC PLAQUES; RECOMBINANT ADENOVIRUS; MODEL SYSTEM; E-SELECTIN; EXPRESSION; MOLECULE-1; ALPHA; DIVERSITY AB The accumulation of mononuclear leukocytes is an early and persistent finding in atherosclerotic plaques. These mononuclear leukocytes are mostly monocyte-derived, but up to 20% are lymphocytes, predominantly CD4(+) CD45RO(+) (memory) T cells. To evaluate the potential of adenovirus vectors for studies of mononuclear leukocyte recruitment in vitro, we studied the effects of adenovirus vectors per se on human umbilical vein endothelial cells (HUVECs), a well-characterized in vitro model of vascular endothelium. A recombinant adenovirus containing the seven-domain isoform of rabbit vascular cell adhesion molecule-1 (rVCAM-1) was constructed and used to study lymphocyte adhesion under defined laminar flow conditions in transduced HUVEC monolayers. No increase in basal HUVEC surface expression of the inducible endothelial adhesion molecules and markers of activation, E-selectin and VCAM-1, was noted across a broad range of multiplicity of infection. A modest dose-dependent increase in surface intercellular adhesion molecule-1 expression was detectable by flow cytometry at an MOI of >30 plaque-forming units per cell. Under defined laminar how from 1.5 to 0.5 dyne/cm(2), the adenovirus vector carrying r-VCAM-1 mediated stable adhesion of both a Jurkat T-cell line and primary human CD4(+) CD45RO(+) (memory)T cells. Monoclonal antibodies to alpha(4)-integrin or rVCAM-1 abolished adhesion, whereas monoclonal antibodies to CD18 or P-selectin had no effect. We conclude that adenoviral gene transfer is useful for studies of VCAM-1-dependent leukocyte adhesion in vitro and that endothelial expression of VCAM-1 alone, in the absence of overt endothelial cell activation, is sufficient under simulated physiological how conditions to support adhesion of memory T cells, the predominant lymphocyte subset in atherosclerotic plaque. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CHARLESTOWN,MA 02129. NHLBI,MOL HEMATOL BRANCH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,SAN FRANCISCO,CA 94141. UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109. BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV VASC RES,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-54202, HL-475646, HL-36028] NR 47 TC 54 Z9 56 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD DEC PY 1996 VL 79 IS 6 BP 1205 EP 1215 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA VV612 UT WOS:A1996VV61200016 PM 8943959 ER PT J AU Steel, BL Hassell, KL Rajagopalan, C Merritt, AA Parsons, T Braun, T Marlar, RA AF Steel, BL Hassell, KL Rajagopalan, C Merritt, AA Parsons, T Braun, T Marlar, RA TI Unique case of brothers with moderate factor XI deficiency and one with severe bleeding after surgery SO CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS LA English DT Article DE Factor XI; Amicar; bleeding ID PARTIAL THROMBOPLASTIN TIME; SENSITIVITY; REAGENTS AB Factor XI is the only contact factor whose deficiency may result in a bleeding diathesis. This case report describes two brothers with similar moderate factor XI deficiency (41% and 45%), but one brother had severe bleeding during invasive procedures whereas the other brother undergoing the same surgical procedure had no excessive bleeding. The bleeding in the first brother continued despite adequate factor XI levels; however, it was stopped only after EACA therapy. Also discussed is the importance of a sensitive aPTT reagent to the various factors and the role of the aPTT in predicting potential bleeding, since a normal aPTT was obtained prior to the first surgery. This case demonstrates that major bleeding can occur in heterozygous factor XI deficiency and the patient must be considered 'at risk' for potential bleeding and should be treated accordingly. C1 DENVER VA MED CTR,LAB SERV 113,DEPT PATHOL & LAB MED,DENVER,CO 80220. VET AFFAIRS MED CTR,DEPT MED,DENVER,CO 80220. UNIV COLORADO,HLTH SCI CTR,DEPT PATHOL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT MED,DIV HEMATOL ONCOL,DENVER,CO 80262. NR 17 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1076-0296 J9 CLIN APPL THROMB-HEM JI Clin. Appl. Thromb.-Hemost. PD WIN PY 1996 VL 2 IS 1 BP 14 EP 17 DI 10.1177/107602969600200104 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA TU308 UT WOS:A1996TU30800004 ER PT J AU Finegold, SM Wexler, HM AF Finegold, SM Wexler, HM TI Present status of therapy for anaerobic infections SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on New Fluoroquinolones and Anaerobic Infections CY NOV 05-09, 1995 CL SAN JUAN, PR ID BACTERIOLOGY AB Therapeutic approaches to anaerobic infections are changing. Debridement, drainage, and other surgical approaches remain extremely important. Resistance to antimicrobial agents currently used for treatment of anaerobic infections is increasing. However, promising new agents are being introduced. We review the current status of therapy for anaerobic infections and discuss the potential role of these new agents. We stress an empirical approach to therapy that is based on the usual infecting flora in various types of infections. C1 W LOS ANGELES VET AFFAIRS MED CTR,INFECT DIS SECT 111F,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. RP Finegold, SM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,INFECT DIS SECT 111F,MED SERV,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 9 TC 30 Z9 30 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 DEC PY 1996 VL 23 SU 1 BP S9 EP S14 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VW522 UT WOS:A1996VW52200003 PM 8953100 ER PT J AU Maloney, WJ Sychterz, C Bragdon, C McGovern, T Jasty, M Engh, CA Harris, WH AF Maloney, WJ Sychterz, C Bragdon, C McGovern, T Jasty, M Engh, CA Harris, WH TI Skeletal response to well fixed femoral components inserted with and without cement SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID HIP-REPLACEMENT; BONE; STRESS AB Previous studies evaluating femoral remodeling after total hip arthroplasty have used clinical radiographs and dual energy xray absorptiometry. Limitation of these techniques make it impossible to quantify the magnitude of bone loss in terms of cortical thinning and cortical bone area and bone mineral density changes, Femoral cortical bone remodeling after cemented and cementless replacement was quantified and possible determinants of bone remodeling in terms of clinical and radiographic variables were evaluated, Forty-eight anatomic specimen femora from 24 patients with unilateral cemented and cementless hip replacements were analyzed. Cortical thickness, cortical bone area, and bone mineral density was assessed in 4 quadrants at 5 discrete levels, The maximum cortical bone loss by level was at the middle section for the cemented femurs and at the midproximal and middle sections for the cementless femurs. However, if one examines individual quadrants, the proximal medial cortex still represents the specific region of maximal bone loss for both types of implant fixation. The posterior cortex had substantially more bone loss, even in the diaphyseal levels, than had been previously appreciated, A strong correlation was noted between the bone mineral density of the control femur and the percentage decrease of bone mineral density in the remodeled femur. Based on this data, it seems that the less dense the bone is before hip replacement surgery, the greater the extent of bone loss after total hip arthroplasty regardless of the fixation type. C1 ANDERSON ORTHOPAED RES INST,ARLINGTON,VA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Maloney, WJ (reprint author), UNIV WASHINGTON,SCH MED,DEPT ORTHOPAED SURG,1 BARNES HOSP PLAZA,SUITE 11300,ST LOUIS,MO 63110, USA. NR 20 TC 78 Z9 80 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 DEC PY 1996 IS 333 BP 15 EP 26 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA WA380 UT WOS:A1996WA38000003 PM 8981879 ER PT J AU Harris, WH AF Harris, WH TI Hybrid total hip replacement - Rationale and intermediate clinical results SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID IMPROVED CEMENTING TECHNIQUES; 10-YEAR FOLLOW-UP; BONE-CEMENT; SIMPLEX-P; ARTHROPLASTY; COMPONENTS; FIXATION; YOUNGER; FATIGUE; FAILURE AB The decade of the 1980s was considered by many hip surgeons to be the decade of cement versus cementless. An alternate approach was introduced in which the acetabular component used was cementless and the femoral component was fixed with cement. This has been called the hybrid total hip replacement. The rationale for this approach is presented and intermediate term results (average, 6.6-year followup) showed that among 65 consecutive standard hybrid total hip replacements in patients who had an average age of 61 years (range, 23-83 years) at the time of surgery, no femoral component was revised for aseptic loosening and no acetabular component was revised for aseptic loosening. Of the 130 components, 3 were removed in 2 patients. One patient had both components removed because of recurrent dislocation and 1 patient had the acetabular component revised because of failure of fixation of the polyethylene liner. The clinical results of this approach were excellent in the intermediate term and may have promise for the longterm. RP MASSACHUSETTS GEN HOSP, ORTHOPAED BIOMECH LAB, DEPT ORTHOPAED SURG, HIP & IMPLANT UNIT, GRJ 1126, BOSTON, MA 02114 USA. NR 72 TC 28 Z9 29 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 1996 IS 333 BP 155 EP 164 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA WA380 UT WOS:A1996WA38000015 PM 8981891 ER PT J AU Jasty, M Webster, W Harris, W AF Jasty, M Webster, W Harris, W TI Management of limb length inequality during total hip replacement SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article AB Significant limb length inequality is not an uncommon problem after total hip replacement, Preoperative measurement of limb Length inequality, preoperative planning with radiographic templates, and intraoperative correction with measurements of limb lengths before and after the insertion of the trial components using special calipers can reduce the incidence and magnitude of this problem. A review of 85 consecutive patients who had primary total hip arthroplasty in which these techniques were used by a single surgeon, showed that 43 had limb inequality preoperatively ranging from 0.5 to 7.25 cm, but only 14 (16%) had limb length inequality after surgery, Eleven limbs (13%) had been lengthened 0.5 to 1 cm compared with the contralateral limb, Of the 42 patients with equal limb lengths preoperatively, 3 had a lengthened limb postoperatively compared with their contralateral limb, Four patients were using lifts on the same side because the limb was too short, and 2 were using lifts on the other side because the limb was too long, None of the other patients complained about limb length inequality, The techniques described above are helpful in minimizing limb length inequality during total hip replacements. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Jasty, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,HIP & IMPLANT UNIT,ACC 533,BOSTON,MA 02114, USA. NR 11 TC 54 Z9 57 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 1996 IS 333 BP 165 EP 171 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA WA380 UT WOS:A1996WA38000016 PM 8981892 ER PT J AU Yao, L Lee, HY Gentili, A Shapiro, MM AF Yao, L Lee, HY Gentili, A Shapiro, MM TI Lateral down-sloping of the acromion: A useful MR sign? SO CLINICAL RADIOLOGY LA English DT Article AB Objective: The anterior acromion may appear to slope downward in a lateral direction on coronal-oblique magnetic resonance (MR) images of the shoulder. We sought to determine the significance of this finding as a marker of rotator cuff impingement. Patients and methods: MR studies of 58 subjects (26 with impingement, 32 with glenohumeral instability) were retrospectively analysed. Subjective down-sloping of the acromion was compared to standardized acromial measurements made on MR (acromial axis, width of the anterior acromion, and distance of the acromioclavicular joint from the superior glenoid) and clinical diagnosis. Results: Interobserver variance for lateral down-sloping was fair (kappa = 0.5). One reader's assessment of lateral down-sloping of the acromion correlated with standardized MR measurements. Subjective lateral down-sloping of the acromion did not, however, correlate with impingement. Conclusion: The subjective finding of a laterally down-sloping acromion on coronal-oblique MR images, while partially validated by standardized measurements, is aot predictive of impingement syndrome. C1 UNIV CALIF LOS ANGELES,DEPT ORTHOPAED SURG,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,W LOS ANGELES VET ADM HOSP,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,DEPT RADIOL SCI,DEPT RADIOL,LOS ANGELES,CA 90024. RI Gentili, Amilcare/G-1238-2013 OI Gentili, Amilcare/0000-0002-5623-7512 NR 10 TC 8 Z9 8 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 DEC PY 1996 VL 51 IS 12 BP 869 EP 872 DI 10.1016/S0009-9260(96)80085-7 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VY014 UT WOS:A1996VY01400009 PM 8972653 ER PT J AU Kluth, D Losty, PD Schnitzer, JJ Lambrecht, W Donahoe, PK AF Kluth, D Losty, PD Schnitzer, JJ Lambrecht, W Donahoe, PK TI Toward understanding the developmental anatomy of congenital diaphragmatic hernia SO CLINICS IN PERINATOLOGY LA English DT Article ID RATS AB The pathway of abnormal embryonic development leading to congenital diaphragmatic hernia (CDH) is incompletely understood. Using a nitrofen-induced model of left CDH in rats, sequential stages of development were analyzed by scanning electron microscopy. Abnormal development patterns were observed in the cells comprising the posthepatic mesenchymal plate and the adjacent liver. The septum transversum did not appear to be involved. In this article, the authors theorize that a disturbed ''balance of cell growth'' is responsible for the creation of the diaphragmatic defect. C1 UNIV HAMBURG,DEPT PEDIAT SURG,HAMBURG,GERMANY. UNIV LIVERPOOL,INST CHILD HLTH,LIVERPOOL L69 3BX,MERSEYSIDE,ENGLAND. MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LAB,BOSTON,MA 02114. NR 18 TC 15 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 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD DEC PY 1996 VL 23 IS 4 BP 655 EP & PG 16 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA VZ914 UT WOS:A1996VZ91400003 PM 8982562 ER PT J AU Spillmann, M Fava, M AF Spillmann, M Fava, M TI S-adenosylmethionine (ademetionine) in psychiatric disorders - Historical perspective and current status SO CNS DRUGS LA English DT Article ID ADENOSYL-L-METHIONINE; DOUBLE-BLIND; AFFECTIVE-ILLNESS; SWITCH MECHANISM; FOLIC-ACID; RAT-BRAIN; DEPRESSION; METABOLISM; ANTIDEPRESSANT; TRIAL AB S-Adenosylmethionine (SAMe; ademetionine) is a naturally occurring compound that is found in virtually all living organisms. It serves as a major source of methyl groups in the brain, donating these groups to molecules such as hormones, neurotransmitters, nucleic acids. proteins and phospholipids, and is of fundamental importance in a number of intracellular metabolic pathways. The most commonly reported effect of SAMe is mood elevation in depressed patients. A few, relatively small clinical studies have shown that parenteral SAMe is superior to placebo and at least as effective as standard antidepressants, perhaps with a relatively rapid onset of action. Furthermore, the addition of SAMe to standard antidepressants may shorten the time to treatment response compared with the use of antidepressants alone. There are also additional reports suggesting the usefulness of the compound in dementia. SAMe appears to be remarkably well tolerated and free of severe adverse effects. Further studies are needed to clearly establish the role that SAMe may play in the treatment of depressive disorders and dementia. RP Spillmann, M (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS CLIN & RES PROGRAM,WAC 815,BOSTON,MA 02114, USA. NR 85 TC 32 Z9 34 U1 0 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PD DEC PY 1996 VL 6 IS 6 BP 416 EP 425 DI 10.2165/00023210-199606060-00002 PG 10 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VY232 UT WOS:A1996VY23200002 ER PT J AU Kanwisher, N Chun, MM McDermott, J Ledden, PJ AF Kanwisher, N Chun, MM McDermott, J Ledden, PJ TI Functional imaging of human visual recognition SO COGNITIVE BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 9th Toyota Conference on the Brain and Mind CY DEC 05-08, 1995 CL MIKKABI, JAPAN SP Toyota DE visual recognition; human ID HUMAN EXTRASTRIATE CORTEX; POSITRON EMISSION TOMOGRAPHY; SELECTIVE ATTENTION; CORTICAL AREAS; TIME COURSE; OBJECT; FACE; WORDS; PET; INTERFERENCE C1 MASSACHUSETTS GEN HOSP,NMR CTR,CHARLESTOWN,MA 02129. RP Kanwisher, N (reprint author), HARVARD UNIV,DEPT PSYCHOL,33 KIRKLAND ST,CAMBRIDGE,MA 02138, USA. OI Chun, Marvin/0000-0003-1070-7993 NR 39 TC 166 Z9 167 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD DEC PY 1996 VL 5 IS 1-2 BP 55 EP 67 DI 10.1016/S0926-6410(96)00041-9 PG 13 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA WH807 UT WOS:A1996WH80700007 ER PT J AU Henning, KR Frueh, BC AF Henning, KR Frueh, BC TI Cognitive-behavioral treatment of incarcerated offenders - An evaluation of the Vermont Department of Corrections' cognitive self-change program SO CRIMINAL JUSTICE AND BEHAVIOR LA English DT Article ID SURVIVAL ANALYSIS; REHABILITATION; METAANALYSIS; ATTITUDES; VIOLENT; SEX AB Recidivism rates were compared in two groups of male offenders from a medium-security state prison. Offenders in the first group (n = 55) voluntarily participated in a cognitive-behavioral treatment program that addressed ''thinking errors'' related to criminal behavior. A second group of offenders (n = 141) from the same facility, who did not participate in the treatment program, served as a comparison group. A significant difference in recidivism was observed between the groups, with 50% of the offenders from the treatment group recidivating, compared to 70.8% of the comparison group. More favorable results for the program were observed when these data were subjected to survival analyses and implications. Practical limitations of the present study for the treatment of a general population of incarcerated offenders are discussed. C1 MED UNIV S CAROLINA,RALPH H JOHNSON VET ADM MED CTR,CHARLESTON,SC 29425. RP Henning, KR (reprint author), UNIV MEMPHIS,DEPT PSYCHOL,MEMPHIS,TN 38152, USA. NR 49 TC 41 Z9 41 U1 3 U2 14 PU SAGE SCIENCE PRESS PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0093-8548 J9 CRIM JUSTICE BEHAV JI Crim. Justice Behav. PD DEC PY 1996 VL 23 IS 4 BP 523 EP 541 DI 10.1177/0093854896023004001 PG 19 WC Psychology, Clinical; Criminology & Penology SC Psychology; Criminology & Penology GA VU357 UT WOS:A1996VU35700001 ER PT J AU Brun, RP Kim, JB Hu, E Altiok, S Spiegelman, BM AF Brun, RP Kim, JB Hu, E Altiok, S Spiegelman, BM TI Adipocyte differentiation: A transcriptional regulatory cascade SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID ENHANCER-BINDING-PROTEIN; BROWN ADIPOSE-TISSUE; PROLIFERATOR-ACTIVATED RECEPTORS; GENE-EXPRESSION; FATTY-ACIDS; 3T3-L1 PREADIPOCYTES; C/EBP-ALPHA; PPAR-GAMMA; CELLS; MICE AB The adipose cell is now known to play a complex role in energy homeostasis, energy storage and signaling to other tissues concerning the state of energy balance. The past few years have seen an explosive increase in our knowledge of the transcriptional basis of adipocyte differentiation. Factors such as peroxisome proliferator-activated receptor gamma, the CCAAT/enhancer binding protein family members, and adipocyte determination- and differentiation-dependent factor 1 play important regulatory roles in this process. Furthermore, these factors provide a focus for beginning to understand how various hormones and metabolites influence the development oi adipose tissue in vivo. RP Brun, RP (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT CELL BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 68 TC 124 Z9 128 U1 1 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD DEC PY 1996 VL 8 IS 6 BP 826 EP 832 DI 10.1016/S0955-0674(96)80084-6 PG 7 WC Cell Biology SC Cell Biology GA VU442 UT WOS:A1996VU44200010 PM 8939673 ER PT J AU Stemple, DL Driever, W AF Stemple, DL Driever, W TI Zebrafish: Tools for investigating cellular differentiation SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID EMBRYONIC ZEBRAFISH; NEURAL CREST; GENE; DROSOPHILA; POLARITY; PATTERN; MUSCLE; PROGENITORS; MUTATIONS; SYSTEM AB Two recent large-scale genetic screens in zebrafish have identified many mutations that affect differentiation in a variety oi organ systems, particularly the notochord, the neural crest and the blood. The combination of these newly identified mutations and well established embryological methods makes zebrafish uniquely suited among vertebrate experimental systems to simultaneously address the roles of specific genes and specific cell-cell interactions during differentiation. RP Stemple, DL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIOVASC RES CTR,149 13TH ST 4TH FLOOR,CHARLESTOWN,MA 02129, USA. NR 70 TC 11 Z9 11 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD DEC PY 1996 VL 8 IS 6 BP 858 EP 864 DI 10.1016/S0955-0674(96)80088-3 PG 7 WC Cell Biology SC Cell Biology GA VU442 UT WOS:A1996VU44200014 PM 8939671 ER PT J AU Hosler, BA Brown, RH AF Hosler, BA Brown, RH TI Superoxide dismutase and oxygen radical neurotoxicity SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; TRANSGENIC MICE; NEUROFILAMENT SUBUNIT; SUBSTANTIA-NIGRA; OXIDATIVE DAMAGE; ANIMAL-MODEL; MUTATIONS; PEROXYNITRITE; APOPTOSIS AB Although reactive oxygen species are natural metabolic products, they can be toxic to cells and are implicated in some neurodegenerative diseases. Cytosolic Cu,Zn superoxide dismutase normally defends against damage by reactive oxygen species; however, mutant forms of the enzyme might instead contribute to damage of motor neurons in some amyotrophic lateral sclerosis patients. Possible mechanisms of oxidative injury to neurons are discussed with reference to cytosolic Cu,Zn superoxide dismutase mutations and other factors which might enhance oxygen radical toxicity. C1 MASSACHUSETTS GEN HOSP EAST,NEUROL SERV,CECIL B DAY LAB NEUROMUSC RES,CHARLESTOWN,MA 02129. NR 49 TC 12 Z9 12 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 1996 VL 9 IS 6 BP 486 EP 491 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WC726 UT WOS:A1996WC72600016 PM 9007410 ER PT J AU Driever, W SolnicaKrezel, L Schier, AF Neuhauss, SCF Malicki, J Stemple, DL Stainier, DYR Zwartkruis, F Abdelilah, S Rangini, Z Belak, J Boggs, C AF Driever, W SolnicaKrezel, L Schier, AF Neuhauss, SCF Malicki, J Stemple, DL Stainier, DYR Zwartkruis, F Abdelilah, S Rangini, Z Belak, J Boggs, C TI A genetic screen for mutations affecting embryogenesis in zebrafish SO DEVELOPMENT LA English DT Article DE zebrafish Danio rerio; mutagenesis; genetic control; embryogenesis ID RECESSIVE LETHAL MUTATIONS; BRACHYDANIO-RERIO; INT-1 PROTOONCOGENE; SKELETAL-MUSCLE; NERVOUS-SYSTEM; FLOOR PLATE; MOUSE; INDUCTION; VERTEBRATE; LOCUS AB Systematic genome-wide mutagenesis screens for embryonic phenotypes have been instrumental in the understanding of invertebrate and plant development, Here, we report the results from the first application of such a large-scale genetic screening to vertebrate development. Male zebrafish were mutagenized with N-ethyl N-nitrosourea to induce mutations in spermatogonial cells at an average specific locus rate of one in 651 mutagenized genomes, Mutations were transmitted to the F-1 generation, and 2205 F-2 families were raised. F-3 embryos from sibling crosses within the F-2 families were screened for developmental abnormalities, A total of 2337 mutagenized genomes were analyzed, and 2383 mutations resulting in abnormal embryonic and early larval phenotypes were identified. The phenotypes of 695 mutants indicated involvement of the identified loci in specific aspects of embryogenesis. These mutations were maintained for further characterization and were classified into categories according to their phenotypes, The analyses and genetic complementation of mutations from several categories are reported in separate manuscripts, Mutations affecting pigmentation, motility, muscle and body shape have not been extensively analyzed and are listed here, A total of 331 mutations were tested for allelism within their respective categories, This defined 220 genetic loci with on average 1.5 alleles per locus. For about two-thirds of all loci only one allele was isolated, Therefore it is not possible to give a reliable estimate on the degree of saturation reached in our screen; however, the number of genes that can mutate to visible embryonic and early larval phenotypes in zebrafish is expected to be several-fold larger than the one for which we have observed mutant alleles during the screen. This screen demonstrates that mutations affecting a variety of developmental processes can be efficiently recovered from zebrafish. C1 HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. RP Driever, W (reprint author), MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,149 13TH ST,CHARLESTOWN,MA 02129, USA. RI malicki, jarema/G-8611-2014 FU NICHD NIH HHS [R01-HD29761] NR 65 TC 824 Z9 859 U1 4 U2 50 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 DEC PY 1996 VL 123 SI SI BP 37 EP 46 PG 10 WC Developmental Biology SC Developmental Biology GA WE748 UT WOS:A1996WE74800003 PM 9007227 ER PT J AU SolnicaKrezel, L Stemple, DL MountcastleShah, E Rangini, Z Neuhauss, SCF Malicki, J Schier, AF Stainier, DYR Zwartkruis, F Abdelilah, S Driever, W AF SolnicaKrezel, L Stemple, DL MountcastleShah, E Rangini, Z Neuhauss, SCF Malicki, J Schier, AF Stainier, DYR Zwartkruis, F Abdelilah, S Driever, W TI Mutations affecting cell fates and cellular rearrangements during gastrulation in zebrafish SO DEVELOPMENT LA English DT Article DE organizer; gastrulation; epiboly; convergence; extension; zebrafish; dorsoventral polarity ID CENTRAL-NERVOUS-SYSTEM; XENOPUS-LAEVIS; MUTANT EMBRYOS; AXIAL MESODERM; FLOOR PLATE; VERTEBRATE GASTRULATION; NOTOCHORD DEVELOPMENT; GOOSECOID EXPRESSION; NEURAL INDUCTION; BODY AXIS AB One of the major challenges of developmental biology is understanding the inductive and morphogenetic processes that shape the vertebrate embryo. In a large-scale genetic screen for zygotic effect, embryonic lethal mutations in zebrafish we have identified 25 mutations that affect specification of cell fates and/or cellular rearrangements during gastrulation, These mutations define at least 14 complementation groups, four of which correspond to previously identified genes, Phenotypic analysis of the ten novel loci revealed three groups of mutations causing distinct effects on cell fates in the gastrula, One group comprises mutations that lead to deficiencies in dorsal mesodermal fates and affect central nervous system patterning, Mutations from the second group affect formation of ventroposterior embryonic structures, We suggest that mutations in these two groups identify genes necessary for the formation, maintenance or function of the dorsal organizer and the ventral signaling pathway, respectively, Mutations in the third group affect primarily cellular rearrangements during gastrulation and have complex effects on cell fates in the embryo, This group, and to some extent mutations from the first two groups, affect the major morphogenetic processes, epiboly, convergence and extension, and tail morphogenesis. These mutations provide an approach to understanding the genetic control of gastrulation in vertebrates. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. RI malicki, jarema/G-8611-2014 FU NICHD NIH HHS [R01-HD29761] NR 92 TC 214 Z9 217 U1 1 U2 11 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 DEC PY 1996 VL 123 SI SI BP 67 EP 80 PG 14 WC Developmental Biology SC Developmental Biology GA WE748 UT WOS:A1996WE74800006 PM 9007230 ER PT J AU Stemple, DL SolnicaKrezel, L Zwartkruis, F Neuhauss, SCF Schier, AF Malicki, J Stainier, DYR Abdelilah, S Rangini, Z MountcastleShah, E Driever, W AF Stemple, DL SolnicaKrezel, L Zwartkruis, F Neuhauss, SCF Schier, AF Malicki, J Stainier, DYR Abdelilah, S Rangini, Z MountcastleShah, E Driever, W TI Mutations affecting development of the notochord in zebrafish SO DEVELOPMENT LA English DT Article DE zebrafish; notochord; floor plate; mesoderm; embryogenesis ID MOTOR-NEURON INDUCTION; TERMINAL CLEAVAGE PRODUCT; MOUSE EMBRYOS LACKING; FLOOR PLATE; SONIC HEDGEHOG; SCLEROTOME INDUCTION; TISSUE INTERACTIONS; AXIAL STRUCTURES; TAIL MUTATION; CHICK-EMBRYO AB The notochord is critical for the normal development of vertebrate embryos, It serves both as the major skeletal element of the embryo and as a signaling source for the establishment of pattern within the neurectoderm, the paraxial mesoderm and other tissues, In a large-scale systematic screen of mutations affecting embryogenesis in zebrafish we identified 65 mutations that fall into 29 complementation groups, each leading to a defect in the formation and/or maintenance of the notochord, These mutations produce phenotypic abnormalities at numerous stages of notochord development, thereby establishing a phenotypic pathway, which in turn suggests a genetic pathway for the development of the notochord, Perturbations within adjacent tissues in mutant embryos further indicate the importance of notochord-derived signals for patterning within the embryo and suggest that these mutations will yield additional insight into the cues that regulate these patterning processes. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. RI malicki, jarema/G-8611-2014 FU NICHD NIH HHS [R01 HD29761] NR 55 TC 140 Z9 141 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 0950-1991 J9 DEVELOPMENT JI Development PD DEC PY 1996 VL 123 SI SI BP 117 EP 128 PG 12 WC Developmental Biology SC Developmental Biology GA WE748 UT WOS:A1996WE74800010 PM 9007234 ER PT J AU Schier, AF Neuhauss, SCF Harvey, M Malicki, J SolnicaKrezel, L Stainier, DYR Zwartkruis, F Abdelilah, S Stemple, DL Rangini, Z Yang, H Driever, W AF Schier, AF Neuhauss, SCF Harvey, M Malicki, J SolnicaKrezel, L Stainier, DYR Zwartkruis, F Abdelilah, S Stemple, DL Rangini, Z Yang, H Driever, W TI Mutations affecting the development of the embryonic zebrafish brain SO DEVELOPMENT LA English DT Review DE zebrafish; brain; neuroectoderm; cyclopia; cerebellum; ventricle; neurogenesis; axonogenesis ID CENTRAL-NERVOUS-SYSTEM; FLOOR PLATE; POLARIZING ACTIVITY; VERTEBRATE DEVELOPMENT; SONIC-HEDGEHOG; NEURAL-TUBE; PAX GENES; HINDBRAIN DEVELOPMENT; SEGMENTATION MUTANT; INT-1 PROTOONCOGENE AB In a large scale mutagenesis screen for embryonic mutants in zebrafish, we have identified 63 mutations in 24 loci affecting the morphogenesis of the zebrafish brain, The expression of marker genes and the integrity of the axonal scaffold have been studied to investigate abnormalities in regionalization, neurogenesis and axonogenesis in the brain, Mutants can be broadly classified into two groups, one affecting regionalization along the anterior-posterior or dorsal-ventral axis, and the other affecting general features of brain morphology, The first group includes one locus that is required to generate the anlage of the midbrain-hindbrain boundary region at the beginning of somitogenesis. Four loci were identified that affect dorsal-ventral patterning of the brain, including the previously described cyclops locus, Mutant embryos of this class show a reduction of ventral neuroectodermal structures and variable fusion of the eyes, The second group includes a large class of mutations affecting the formation of brain ventricles. Analysis of this class reveals the requirement of a functional cardiovascular system for ventricle enlargement during embryogenesis. Mutations in one locus lead to the formation of supernumerary primary neurons, a reminiscent of neurogenic mutants in Other mutant phenotypes described here range from abnormalities in the fasciculation and outgrowth of axons to defects in the diameter of the neural tube. The identified loci establish the genetic foundation for a further analysis of the development of the zebrafish embryonic brain, phenotype Drosophila. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. RI malicki, jarema/G-8611-2014 FU NICHD NIH HHS [R01-HD29761] NR 121 TC 273 Z9 276 U1 2 U2 23 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 DEC PY 1996 VL 123 SI SI BP 165 EP 178 PG 14 WC Developmental Biology SC Developmental Biology GA WE748 UT WOS:A1996WE74800014 PM 9007238 ER PT J AU Abdelilah, S MountcastleShah, E Harvey, M SolnicaKrezel, L Schier, AF Stemple, DL Malicki, J Neuhauss, SCF Zwartkruis, F Stainier, DYR Rangini, Z Driever, W AF Abdelilah, S MountcastleShah, E Harvey, M SolnicaKrezel, L Schier, AF Stemple, DL Malicki, J Neuhauss, SCF Zwartkruis, F Stainier, DYR Rangini, Z Driever, W TI Mutations affecting neural survival in the zebrafish Danio rerio SO DEVELOPMENT LA English DT Article DE zebrafish; development; CNS; programmed cell death; degeneration ID PROGRAMMED CELL-DEATH; NERVE GROWTH-FACTOR; CAENORHABDITIS-ELEGANS; RECEPTOR GENE; C-ELEGANS; TARGETED DISRUPTION; DNA FRAGMENTATION; PRIMARY NEURONS; PROTEIN ISL-1; APOPTOSIS AB Programmed cell death is a prominent feature of normal animal development, During neurogenesis, naturally occurring cell death is a mechanism to eliminate neurons that fail to make appropriate connections, To prevent accidental cell death, mechanisms that trigger programmed cell death, as well as the genetic components of the cell death program, are tightly controlled. In a large-scale mutagenesis screen for embryonic lethal mutations in zebrafish Danio rerio we have found 481 mutations with a neural degeneration phenotype, Here, we present 50 mutations that fall into two classes (termed spacehead and fala-like) that are characterized by two main features: first, they appear to affect cell survival primarily within the neuroectodermal lineages during somitogenesis, and second, they show an altered brain morphology at or before 28 hours of development, Evidence for the specificity of cell death within the central nervous system comes from visual inspection of dying cells and analysis of DNA fragmentation, a process associated with apoptotic cell death. In mutants, the level of dying cells is significantly increased in brain and spinal cord, Furthermore, at the end of somitogenesis, the cell count of radial glia and trigeminal neurons is reduced in some mutants of the spacehead class. A variety of neurodegenerative disorders in mouse and humans have been associated with abnormal levels of programmed cell death within the central nervous system, The mutations presented here might provide a genetic framework to aid in the understanding of the etiology of degenerative and physiological disorders within the CNS and the activation of inappropriate programmed cell death. C1 MASSACHUSETTS GEN HOSP, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, SCH MED, CHARLESTOWN, MA 02129 USA. RI malicki, jarema/G-8611-2014 FU NICHD NIH HHS [R01-HD29761] NR 68 TC 61 Z9 61 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC PY 1996 VL 123 SI SI BP 217 EP 227 PG 11 WC Developmental Biology SC Developmental Biology GA WE748 UT WOS:A1996WE74800018 PM 9007242 ER PT J AU Malicki, J Neuhauss, SCF Schier, AF SolnicaKrezel, L Stemple, DL Stainier, DYR Abdelilah, S Zwartkruis, F Rangini, Z Driever, W AF Malicki, J Neuhauss, SCF Schier, AF SolnicaKrezel, L Stemple, DL Stainier, DYR Abdelilah, S Zwartkruis, F Rangini, Z Driever, W TI Mutations affecting development of the zebrafish retina SO DEVELOPMENT LA English DT Article DE retina; neurogenesis; zebrafish ID BRACHYDANIO-RERIO; NEURONAL DIFFERENTIATION; DROSOPHILA EYE; VISUAL-SYSTEM; BETA-SUBUNIT; EYELESS GENE; FLOOR PLATE; IN-VITRO; MOUSE; PIGMENTOSA AB In a large scale screen for genetic defects in zebrafish embryogenesis we identified 49 mutations affecting development of the retina, Based on analysis of living embryos as well as histological sections, we grouped the isolated mutations into six phenotypic categories, (1) Mutations in three loci result in a loss of wild-type laminar pattern of the neural retina, (2) Defects in four loci lead to an abnormal specification of the eye anlagen, Only one eye frequently forms in this class of mutants, (3) Seven loci predominantly affect development of the outer retinal layers, Mutants in this category display cell loss mainly in the photoreceptor cell layer. (4) Nine mutations cause retardation of eye growth without any other obvious abnormalities in the retina, (5) A group of twelve mutations is characterized by nonspecific retinal degeneration, (6) Four mutations display retinal degeneration associated with a pigmentation defect. Finally, two mutations, one with absence of the ventral retina and one with an eye-specific pigmentation defect, are not classified in any of the above groups, The identified mutations affect numerous aspects of eye development, including: specification of the eye anlage, growth rate of the optic cup, establishment of retinal stratification, specification or differentiation of retinal neurons and formation of the dorsoventral axis in the developing eye. C1 MASSACHUSETTS GEN HOSP, CARDIOVASC RES CTR, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, SCH MED, CHARLESTOWN, MA 02129 USA. RI malicki, jarema/G-8611-2014 FU NICHD NIH HHS [R01-HD29761] NR 71 TC 201 Z9 203 U1 0 U2 9 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC PY 1996 VL 123 SI SI BP 263 EP 273 PG 11 WC Developmental Biology SC Developmental Biology GA WE748 UT WOS:A1996WE74800022 PM 9007246 ER PT J AU Malicki, J Schier, AF SolnicaKrezel, L Stemple, DL Neuhauss, SCF Stainier, DYR Abdelilah, S Rangini, Z Zwartkruis, F Driever, W AF Malicki, J Schier, AF SolnicaKrezel, L Stemple, DL Neuhauss, SCF Stainier, DYR Abdelilah, S Rangini, Z Zwartkruis, F Driever, W TI Mutations affecting development of the zebrafish ear SO DEVELOPMENT LA English DT Article DE ear; patterning; zebrafish; quadro; little richard; golas; antytalent ID NEURAL CREST; INNER-EAR; TARGETED DISRUPTION; BRACHYDANIO-RERIO; GENE; EXPRESSION; DEFECTS; EMBRYOS; TUBE; KR AB In a large scale screen for genetic defects in zebrafish embryogenesis we identified mutations affecting several aspects of ear development, including: specification of the otic placode, growth of the otic vesicle (otocyst), otolith formation, morphogenesis of the semicircular canals and differentiation of the otic capsule, Here we report initial phenotypic and genetic characterization of 20 of these mutations defining 13 independent loci. Embryos mutant at the quadro locus display abnormal specification of the otic placode, As revealed by dlx-3 expression, the otic field in the mutant embryos is smaller or split into two fields, At later stages of development the ear of quadro mutants is frequently divided into two smaller, incomplete units, Four loci affect ear shape shortly after formation of the otic vesicle, All of them also display abnormal brain morphology, Mutations in five loci result in the absence of otolith formation; two of these also produce changes of ear morphology, Two loci, little richard and golas, affect morphology of the otic vesicle shortly before formation of the semicircular canals, In both cases the morphogenesis of the semicircular canals is disrupted, Finally, the antytalent locus is involved in late expansion of the ear structure, Analysis of mutations presented here vuill strengthen our understanding of vertebrate ear morphogenesis and provide novel entry points to its genetic analysis. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. RI malicki, jarema/G-8611-2014 FU NICHD NIH HHS [R01-HD29761] NR 48 TC 92 Z9 95 U1 0 U2 7 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 DEC PY 1996 VL 123 SI SI BP 275 EP 283 PG 9 WC Developmental Biology SC Developmental Biology GA WE748 UT WOS:A1996WE74800023 PM 9007247 ER PT J AU Stainier, DYR Fouquet, B Chen, JN Warren, KS Weinstein, BM Meiler, SE Mohideen, MAPK Neuhauss, SCF SolnicaKrezel, L Schier, AF Zwartkruis, F Stemple, DL Malicki, J Driever, W Fishman, MC AF Stainier, DYR Fouquet, B Chen, JN Warren, KS Weinstein, BM Meiler, SE Mohideen, MAPK Neuhauss, SCF SolnicaKrezel, L Schier, AF Zwartkruis, F Stemple, DL Malicki, J Driever, W Fishman, MC TI Mutations affecting the formation and function of the cardiovascular system in the zebrafish embryo SO DEVELOPMENT LA English DT Article DE heart; vasculature; zebrafish ID HEART DEVELOPMENT; MOUSE EMBRYOS; GENE; DROSOPHILA; TUBE; VERTEBRATES; MESODERM; TINMAN AB As part of a large-scale mutagenesis screen of the zebrafish genome, we have identified 58 mutations that affect the formation and function of the cardiovascular system, The cardiovascular system is particularly amenable for screening in the transparent zebrafish embryo because the heart and blood vessels are prominent and their function easily examined, We have classified the mutations affecting the heart into those that affect primarily either morphogenesis or function, Nine mutations clearly disrupt the formation of the heart, cloche deletes the endocardium, In cloche mutants, the myocardial layer forms in the absence of the endocardium but is dysmorphic and exhibits a weak contractility, Two loci, miles apart and bonnie and clyde, play a critical role in the fusion of the bilateral tubular primordia, Three mutations lead to an abnormally large heart and one to the formation of a diminutive, dysmorphic heart, We have found no mutation that deletes the myocardial cells altogether, but one, pandora, appears to eliminate the ventricle selectively. Seven mutations interfere with vascular integrity, as indicated by hemorrhage at particular sites, In terms of cardiac function, one large group exhibits a weak beat, In this group, five loci affect both chambers and seven a specific chamber (the atrium or ventricle). For example, the weak atrium mutation exhibits an atrium that becomes silent but has a normally beating ventricle, Seven mutations affect the rhythm of the heart causing, for example, a slow rate, a fibrillating pattern or an apparent block to conduction, In several other mutants, regurgitation of blood how from ventricle to atrium is the most prominent abnormality, due either to the absence of valves or to poor coordination between the chambers with regard to the timing of contraction, The mutations identified in this screen point to discrete and critical steps in the formation and function of the heart and vasculature. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RI malicki, jarema/G-8611-2014; OI Chen, Jau-Nian/0000-0001-8807-3607 FU NHLBI NIH HHS [R01-HL49579, T32-HL07208]; NICHD NIH HHS [R01-HD29761] NR 30 TC 367 Z9 374 U1 4 U2 39 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 DEC PY 1996 VL 123 SI SI BP 285 EP 292 PG 8 WC Developmental Biology SC Developmental Biology GA WE748 UT WOS:A1996WE74800024 PM 9007248 ER PT J AU Chen, JN Haffter, P Odenthal, J Vogelsang, E Brand, M vanEeden, FJM FurutaniSeiki, M Granato, M Hammerschmidt, M Heisenberg, CP Jiang, YJ Kane, DA Kelsh, RN Mullins, MC NussleinVolhard, C AF Chen, JN Haffter, P Odenthal, J Vogelsang, E Brand, M vanEeden, FJM FurutaniSeiki, M Granato, M Hammerschmidt, M Heisenberg, CP Jiang, YJ Kane, DA Kelsh, RN Mullins, MC NussleinVolhard, C TI Mutations affecting the cardiovascular system and other internal organs in zebrafish SO DEVELOPMENT LA English DT Article DE heart; circulation; cardiovascular system; intestine; liver; kidney; zebrafish ID RECEPTOR TYROSINE KINASE; TARGETED DISRUPTION; EMBRYONIC LETHALITY; MOUSE EMBRYOS; HEART TUBES; GENE; DEFECTS; DIFFERENTIATION; VASCULOGENESIS; DROSOPHILA AB In a screen for early developmental mutants of the zebrafish, we have identified mutations specifically affecting the internal organs, We identified 53 mutations affecting the cardiovascular system, Nine of them affect specific landmarks of heart morphogenesis. Mutations in four genes cause a failure in the fusion of the bilateral heart primordia, resulting in cardia bifida. In lonely atrium, no heart venticle is visible and the atrium is directly fused to the outflow tract. In the overlooped mutant, the relative position of the two heart chambers is distorted, The heart is enormously enlarged in the santa mutant, In two mutants, scotch tape and superglue, the cardiac jelly between the two layers of the heart is significantly reduced, We also identified a number of mutations affecting the function of the heart, The mutations affecting heart function can be subdivided into two groups, one affecting heart contraction and another affecting the rhythm of the heart beat. Among the contractility group of mutants are 5 with no heart beat at all and 15 with a reduced heart beat of one or both chambers, 6 mutations are in the rhythmicity group and specifically affect the beating pattern of the heart, Mutations in two genes, bypass and kurzschluss, cause specific defects in the circulatory system, In addition to the heart mutants, we identified 23 mutations affecting the integrity of the liver, the intestine or the kidney, In this report, we demonstrate that it is feasible to screen for genes specific for the patterning or function of certain internal organs in the zebrafish, The mutations presented here could serve as an entrypoint to the establishment of a genetic hierarchy underlying organogenesis. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MAX PLANCK INST ENTWICKLUNGSBIOL,D-72076 TUBINGEN,GERMANY. RP Chen, JN (reprint author), MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,149 13TH ST,CHARLESTOWN,MA 02129, USA. RI Kelsh, Robert/B-6445-2008; Van Eeden, Freek/E-6198-2010; Brand, Michael/A-5509-2010; Jiang, Yun-Jin/E-3995-2010; OI Kelsh, Robert/0000-0002-9381-0066; Brand, Michael/0000-0001-5711-6512; Jiang, Yun-Jin/0000-0003-0499-7306; Chen, Jau-Nian/0000-0001-8807-3607 FU NHLBI NIH HHS [R01-HL-49579] NR 42 TC 311 Z9 318 U1 3 U2 21 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 DEC PY 1996 VL 123 SI SI BP 293 EP 302 PG 10 WC Developmental Biology SC Developmental Biology GA WE748 UT WOS:A1996WE74800025 PM 9007249 ER PT J AU Weinstein, BM Schier, AF Abdelilah, S Malicki, J SolnicaKrezel, L Stemple, DL Stainier, DYR Zwartkruis, F Driever, W Fishman, MC AF Weinstein, BM Schier, AF Abdelilah, S Malicki, J SolnicaKrezel, L Stemple, DL Stainier, DYR Zwartkruis, F Driever, W Fishman, MC TI Hematopoietic mutations in the zebrafish SO DEVELOPMENT LA English DT Article DE primitive haematopoiesis; mutations; zebrafish ID ERYTHROID DEVELOPMENT; FANCONIS ANEMIA; MICE LACKING; STEM-CELLS; IN-VITRO; MOUSE; ATRANSFERRINEMIA; DIFFERENTIATION; GENE AB We have identified mutations that perturb the formation or differentiation of the first embryonic blood cells in the zebrafish embryo, These 'primitive' red blood cells originate in the intermediate cell mass of the trunk, a derivative of the dorsal lateral plate mesoderm. By transfusion of blood between embryos we demonstrate that this cohort of cells provides the embryo with all, or nearly all, of its blood cells until at least day 5 postfertilization, Larval lethal mutations generated by ENU mutagenesis affect different steps In the development of these cells, Some cause defects in precursor generation, others defects in differentiation, and others an increase in cellular photosensitivity. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RI malicki, jarema/G-8611-2014 FU NHLBI NIH HHS [R01-HL49579, T32-HL07208]; NICHD NIH HHS [R01-HD29761] NR 31 TC 162 Z9 167 U1 0 U2 3 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 DEC PY 1996 VL 123 SI SI BP 303 EP 309 PG 7 WC Developmental Biology SC Developmental Biology GA WE748 UT WOS:A1996WE74800026 PM 9007250 ER PT J AU Pack, M SolnicaKrezel, L Malicki, J Neuhauss, SCF Schier, AF Stemple, DL Driever, W Fishman, MC AF Pack, M SolnicaKrezel, L Malicki, J Neuhauss, SCF Schier, AF Stemple, DL Driever, W Fishman, MC TI Mutations affecting development of zebrafish digestive organs SO DEVELOPMENT LA English DT Article DE gut; intestine; liver; pancreas; zebrafish ID EMBRYONIC EXPRESSION; TARGETED DISRUPTION; CHICK-EMBRYO; MOUSE; GENE; CELLS; PANCREAS; MICE; GUT; DIFFERENTIATION AB The zebrafish gastrointestinal system matures in a manner akin to higher vertebrates, We describe nine mutations that perturb development of these organs. Normally, by the fourth day postfertilization the digestive organs are formed, the epithelial cells of the intestine are polarized and express digestive enzymes, the hepatocytes secrete bile, and the pancreatic islets and acini generate immunoreactive insulin and carboxypeptidase A, respectively. Seven mutations cause arrest of intestinal epithelial development after formation of the tube but before cell polarization is completed, These perturb different regions of the intestine. Six preferentially affect foregut, and one the hindgut, In one of the foregut mutations the esophagus does not form, Two mutations cause hepatic degeneration, The pancreas is affected in four mutants, all of which also perturb anterior intestine, The pancreatic exocrine cells are selectively affected in these four mutations, Exocrine precursor cells appear, as identified by GATA-5 expression, but do not differentiate and acini do not form, The pancreatic islets are spared, and endocrine cells mature and synthesize insulin, These gastrointestinal mutations may be informative with regard to patterning and crucial lineage decisions during organogenesis, and may be relevant to diabetes, congenital dysmorphogenesis and disorders of cell proliferation. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RI malicki, jarema/G-8611-2014 FU NHLBI NIH HHS [R01-HL49579]; NICHD NIH HHS [R01-HD29761]; NIDDK NIH HHS [K11-DK02157] NR 31 TC 146 Z9 148 U1 0 U2 13 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 DEC PY 1996 VL 123 SI SI BP 321 EP 328 PG 8 WC Developmental Biology SC Developmental Biology GA WE748 UT WOS:A1996WE74800028 PM 9007252 ER PT J AU Neuhauss, SCF SolnicaKrezel, L Schier, AF Zwartkruis, F Stemple, DL Malicki, J Abdelilah, S Stainier, DYR Driever, W AF Neuhauss, SCF SolnicaKrezel, L Schier, AF Zwartkruis, F Stemple, DL Malicki, J Abdelilah, S Stainier, DYR Driever, W TI Mutations affecting craniofacial development in zebrafish SO DEVELOPMENT LA English DT Article DE Danio rerio; craniofacial mutants; cartilage; pharyngeal arches ID CRANIAL NEURAL CREST; ORYZIAS-LATIPES TELEOSTEI; TGF-BETA-SUPERFAMILY; INNER-EAR; HOMEOTIC TRANSFORMATION; TRANSPOSED RHOMBOMERES; AGGRECAN GENE; EXPRESSION; CARTILAGE; SKELETAL AB In a large-scale screen for mutations affecting embryogenesis in zebrafish, we identified 48 mutations in 34 genetic loci specifically affecting craniofacial development, Mutants were analyzed for abnormalities in the cartilaginous head skeleton. Further, the expression of marker genes was studied to investigate potential abnormalities in mutant rhombencephalon, neural crest, and pharyngeal endoderm, The results suggest that the identified mutations affect three distinct aspects of craniofacial development. In one group, mutations affect the overall pattern of the craniofacial skeleton, suggesting that the genes are involved in the specification of these elements. Another large group of mutations affects differentiation and morphogenesis of cartilage, and may provide insight into the genetic control of chondrogenesis, The last group of mutations leads to the abnormal arrangement of skeletal elements and may uncover important tissue-tissue interactions underlying jaw development. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. RI malicki, jarema/G-8611-2014 FU NICHD NIH HHS [R01-HD29761] NR 55 TC 157 Z9 159 U1 0 U2 11 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 DEC PY 1996 VL 123 SI SI BP 357 EP 367 PG 11 WC Developmental Biology SC Developmental Biology GA WE748 UT WOS:A1996WE74800031 PM 9007255 ER PT J AU Knapik, EW Goodman, A Atkinson, OS Roberts, CT Shiozawa, M Sim, CU WekslerZangen, S Trolliet, MR Futrell, C Innes, BA Koike, G McLaughlin, MG Pierre, L Simon, JS Vilallonga, E Roy, M Chiang, PW Fishman, MC Driever, W Jacob, HJ AF Knapik, EW Goodman, A Atkinson, OS Roberts, CT Shiozawa, M Sim, CU WekslerZangen, S Trolliet, MR Futrell, C Innes, BA Koike, G McLaughlin, MG Pierre, L Simon, JS Vilallonga, E Roy, M Chiang, PW Fishman, MC Driever, W Jacob, HJ TI A reference cross DNA panel for zebrafish (Danio rerio) anchored with simple sequence length polymorphisms SO DEVELOPMENT LA English DT Article DE zebrafish; genetic map; reference cross ID GENETIC-LINKAGE MAP; RAT AB The ultimate informativeness of the zebrafish mutations described in this issue will rest in part on the ability to clone these genes. However, the genetic infrastructure required for the positional cloning in zebrafish is still in its infancy, Here we report a reference cross panel of DNA, consisting of 520 F-2 progeny (1040 meioses) that has been anchored to a zebrafish genetic linkage map by 102 simple sequence length polymorphisms, This reference cross DNA provides: (1) a panel of DNA from the cross that was used to construct the genetic linkage map, upon which polymorphic gene(s) and genetic markers can be mapped; (2) a fine order mapping tool, with a maximum resolution of 0.1 cM; and (3) a foundation for the development of a physical map (an ordered array of clones each containing a known portion of the genome), This reference cross DNA will serve as a resource enabling investigators to relate genes or genetic markers directly to a single genetic linkage map and avoid the problem of integrating different maps with different genetic markers, as must be currently done when using randomly amplified polymorphic DNA markers, or as has occurred with human genetic linkage maps. RP Knapik, EW (reprint author), MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,149 13TH ST,CHARLESTOWN,MA 02129, USA. RI Knapik, Ela/J-6172-2014 FU NHLBI NIH HHS [HL-49579, HL08968]; NICHD NIH HHS [HD29761] NR 18 TC 141 Z9 147 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 DEC PY 1996 VL 123 SI SI BP 451 EP 460 PG 10 WC Developmental Biology SC Developmental Biology GA WE748 UT WOS:A1996WE74800038 PM 9007262 ER PT J AU Chen, JN Fishman, MC AF Chen, JN Fishman, MC TI Zebrafish tinman homolog demarcates the heart field and initiates myocardial differentiation SO DEVELOPMENT LA English DT Article DE Nkx2.5; heart; zebrafish; myocardial differentiation; tinman ID HOMEOBOX-CONTAINING GENE; LEFT-RIGHT ASYMMETRY; DROSOPHILA; MESODERM; XENOPUS; NKX-2.5; SPECIFICATION; VERTEBRATES; EXPRESSION; FAMILY AB The fashioning of a vertebrate organ requires integration of decisions of cell fate by individual cells with those that regulate organotypic form. Logical candidates for this role, in an organ such as the heart, are genes that initiate the differentiation process leading to heart muscle and those that define the earliest embryonic heart field, but for neither class are genes defined. We cloned zebrafish Nkx2.5, a homolog of the tinman homeodomain gene needed for visceral and cardiac mesoderm formation in Drosophila. In the zebrafish, its expression is associated with cardiac precursor cells throughout development, even in the early gastrula, where the level of zebrafish Nkx2.5 is in a gradient which spatially matches the regional propensity of ventral-marginal cells to become heart. Overexpression of Nkx2.5 causes formation of disproportionally larger hearts in otherwise apparently normal embryos, Transplanted cell expressing high levels of Nkx2.5 express cardiac genes even in ectopic locales. Fibroblasts transfected with myc-tagged Nkx2.5 express cardiac genes, These effects require the homeodomain. Thus, Nkx2.5 appears to mark the earliest embryonic heart field and to be capable of initiating the cardiogenic differentiation program, Because ectopic cells or transfected fibroblasts do not beat, Nkx2.5 is likely to be but one step in the determination of cardiac myocyte cell fate, Its overexpression increases heart size, perhaps by bringing cells on the edge of the field to a threshold level for initiation of cardiac differentiation. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,CHARLESTOWN,MA 02129. OI Chen, Jau-Nian/0000-0001-8807-3607 FU NCRR NIH HHS [NIH RO1-RR08888]; NHLBI NIH HHS [NIH RO1-HL49579] NR 38 TC 229 Z9 234 U1 1 U2 12 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 DEC PY 1996 VL 122 IS 12 BP 3809 EP 3816 PG 8 WC Developmental Biology SC Developmental Biology GA WC554 UT WOS:A1996WC55400013 PM 9012502 ER PT J AU Block, NE Zhu, ZM Kachinsky, AM Dominov, JA Miller, JB AF Block, NE Zhu, ZM Kachinsky, AM Dominov, JA Miller, JB TI Acceleration of semitic myogenesis in embryos of myogenin promoter-MRF4 transgenic mice SO DEVELOPMENTAL DYNAMICS LA English DT Article DE MRF4; transgenic mice; somites; embryos; myogenin ID REGULATORY FACTOR PROTEINS; HEAVY-CHAIN ISOFORMS; SKELETAL-MUSCLE; TRANSCRIPTION FACTORS; ECTOPIC EXPRESSION; PAX-3 EXPRESSION; GENE-EXPRESSION; SONIC HEDGEHOG; MRF4 PROMOTER; CELL LINEAGES AB The four muscle regulatory factors (MRFs) of the MyoD family are expressed in distinct temporal and spatial patterns in developing somites. To examine MRF function and regulation in somites, we generated myogenin promoter-MRF4 transgenic mice in which MRF4 was expressed in rostral somites about a half day earlier than normal. We found that the transgene, which was expressed at about the same level as endogenous MRFs, did not noticeably alter developing or adult mice, whereas the rostral somites of transgenic embryos showed accelerated myocyte formation, as well as precocious expression of the endogenous MRF4 gene. In an individual transgenic somite, MRF4 was expressed in both presumptive myotomal (mesenchymal) and dermatomal (epithelial) cells. Transgenic dermatomal cells also contained myogenin, which is expressed early in myogenesis, but did not contain myosin, which is expressed late in myogenesis. In transgenic myotomal cells, in contrast, precocious expression of MRF4 accelerated late events in myogenesis, including myosin expression and striated myofibril formation. MRF function, therefore, appears to be differentially regulated in dermatomal and myotomal cells. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,NEUROMUSCULAR LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. NR 59 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 1996 VL 207 IS 4 BP 382 EP 394 DI 10.1002/(SICI)1097-0177(199612)207:4<382::AID-AJA3>3.0.CO;2-D PG 13 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA VV653 UT WOS:A1996VV65300003 PM 8950513 ER PT J AU Meredith, M Rabaglia, ME Corbett, JA Metz, SA AF Meredith, M Rabaglia, ME Corbett, JA Metz, SA TI Dual functional effects of interleukin-1 beta on purine nucleotides and insulin secretion in rat islets and INS-1 cells SO DIABETES LA English DT Article ID NITRIC-OXIDE PRODUCTION; MOUSE PANCREATIC-ISLETS; BETA-CELLS; GLUCOSE-CONCENTRATION; CYCLIC-GMP; LANGERHANS; METABOLISM; INHIBITION; RELEASE; DEPENDENCE AB Interleukin-1 beta (IL-1 beta) has been shown to inhibit glucose-induced insulin secretion from rat islets and purified beta-cells, primarily through the generation of nitric oxide (NO). However, the mechanisms by which NO exerts its effects remain unclear. To examine the role of purine nucleotides, we cultured intact rat islets or INS-1 (glucose-responsive transformed rat) beta-cells for 18 h in the presence or absence of IL-1 beta. In islets, the exposure to IL-1 beta (100 pmol/l) inhibited subsequent glucose-induced insulin secretion by 91% with no significant effect on insulin content or basal insulin release. IL-1 beta also diminished insulin secretion induced by pure mitochondrial fuels, 40 mmol/l K+, or a phorbol ester. Concomitantly, IL-1 beta significantly decreased islet ATP (-45%), GTP (-33%), ATP/ADP (-54%), and GTP/GDP (-46%). These effects mere totally reversed by provision of N-omega-nitro-L-arginine methyl ester (NAME) in arginine-free media that inhibited NO production. In contrast, in INS-1 cells, IL-1 beta (10 or 100 pmol/l) reduced both basal and glucose-induced insulin secretion by 50%, but insulin content was also reduced by 35%. Therefore, the INS-1 cells were still able to respond to glucose stimulation with a 1.8-2.0-fold increase in insulin release in either the presence or absence of IL-1 beta. Concomitantly, in INS-1 cells, IL-1 beta had no effect on ATP/ADP or GTP/GDP ratios, although it modestly decreased ATP (-25%) and GTP (-22%). As in islets, all effects of IL-1 beta in INS-1 cells were prevented by NAME. Thus, in rat islets, IL-1 beta (via the generation of NO) abolishes insulin exocytosis in association with large decreases in the ATP/ADP (and GTP/GDP) ratio, implying the impairment of mitochondrial function. Furthermore, IL-1 beta inhibits cytosolic synthesis of new purine nucleotides (via the salvage pathway), as assessed by a decrease in their specific activity after labeling with [H-3]hypoxanthine. In contrast, in INS-1 cells, IL-1 beta appears to impair cytosolic synthesis of purine nucleotides and insulin biosynthesis selectively (both possibly reflecting decreased glycolysis) with little direct effect on insulin exocytosis itself. C1 UNIV WISCONSIN,DIV ENDOCRINOL,MADISON,WI. UNIV WISCONSIN,DEPT MED,MADISON,WI. UNIV WISCONSIN HOSP & CLIN,WILLIAM S MIDDLETON MEM VET ADM HOSP,MADISON,WI 53792. ST LOUIS UNIV,SCH MED,DEPT BIOCHEM & MOL BIOL,ST LOUIS,MO 63104. FU NIDDK NIH HHS [DK37312] NR 43 TC 22 Z9 22 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1996 VL 45 IS 12 BP 1783 EP 1791 DI 10.2337/diabetes.45.12.1783 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VU836 UT WOS:A1996VU83600018 PM 8922366 ER PT J AU Warner, DC McCandless, RR DeNino, LA Cornell, JE Pugh, JA Marsh, GM AF Warner, DC McCandless, RR DeNino, LA Cornell, JE Pugh, JA Marsh, GM TI Costs of diabetes in Texas, 1992 SO DIABETES CARE LA English DT Article ID MELLITUS AB OBJECTIVE - To estimate direct and indirect costs of diabetes in Texas in 1992. RESEARCH DESIGN AND METHODS - For most direct medical costs, we relied on third party and provider billing databases, including Medicare, Medicaid, VA facilities, public hospitals, and others. The researchers identified people with diabetes in the respective databases, located all records of their care, and sorted records as clearly probably, or probably not attributable to diabetes on the basis of principal diagnoses. In most cases, costs were valued as allowable or paid charges. Some medical costs, such as private insurance, were estimated from national data and state surveys. Indirect costs included current short- and long-term disability costs and the discounted present value of future costs of mortality Disability estimates relied on National Health Interview Survey (NHIS) data and U.S. Department of Labor wage data applied to Texas. Mortality estimates were based on death certificates. RESULTS - Total costs clearly or probably attributable to diabetes among Texans in 1992 were estimated at $4.0 billion. Direct medical costs were similar to$1.6 billion. Indirect costs were estimated at $2.4 billion. The largest direct costs were paid by Medicare. Most indirect costs were from long-term disability. CONCLUSIONS - This study demonstrates methods for conducting cost of illness studies at the state level. In a state like Texas, with a large and growing Mexican-American population, estimation of current and future economic costs of diabetes is vital for development of strategies to minimize social and economic consequences of diabetes. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,MEXICAN AMER MED TREATMENT EFFECT RES CTR,SAN ANTONIO,TX 78284. S TEXAS VET HLTH CARE SYST,AUDIE L MURPHY DIV,SAN ANTONIO,TX. RP Warner, DC (reprint author), UNIV TEXAS,LYNDON B JOHNSON SCH PUBL AFFAIRS,PO DRAWER Y,AUSTIN,TX 78713, USA. OI Pugh, Jacqueline/0000-0003-4933-141X FU AHRQ HHS [1-U01-HS07397-04] NR 13 TC 22 Z9 22 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD DEC PY 1996 VL 19 IS 12 BP 1416 EP 1419 DI 10.2337/diacare.19.12.1416 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VU770 UT WOS:A1996VU77000019 PM 8941474 ER PT J AU Wang, QF Tilly, KI Tilly, JL Preffer, F Schneyer, AL Crowley, WF Sluss, PM AF Wang, QF Tilly, KI Tilly, JL Preffer, F Schneyer, AL Crowley, WF Sluss, PM TI Activin inhibits basal and androgen-stimulated proliferation and induces apoptosis in the human prostatic cancer cell line, LNCaP SO ENDOCRINOLOGY LA English DT Article ID SUPPRESSING PROTEIN FOLLISTATIN; RAT GRANULOSA-CELLS; FUNCTIONAL-ANALYSIS; GROWTH-FACTOR; BINDING PROTEIN; BETA-SUBUNIT; RECEPTOR; DEATH; MESODERM; XENOPUS AB LNCaP cells, derived from an androgen-sensitive cell line widely employed as an in vitro model of human prostate cancer, have been shown to express activin receptors. Activin is a local regulator of cellular growth, appears to play a key role in mesoderm induction and differentiation during development, and has been implicated in gonadal tumorigenesis. Follistatin, a monomeric glycoprotein that specifically binds and neutralizes activin, is often coexpressed with activin and, thus, modulates the autocrine/paracrine biological activity of this potent growth factor. We tested the hypothesis that LNCaP growth is modulated by the activin/follistatin system. Recombinant human activin A inhibited [H-3]thymidine incorporation in a dose-dependent fashion with an ED(50) of approximately 0.43+/-0.3 nM. Activin (0.1-3 nM) also inhibited dihydrotestosterone (DHT)-stimulated [H-3]thymidine incorporation in LNCaP cells. Similarly, recombinant human inhibin A inhibited LNCaP proliferation, but was only 1/100th as potent as activin. Furthermore, activin (3 nM) induced a 3-fold increase in the extent of labeling of low mol wt DNA fragments typical of apoptosis. Activin-induced apoptosis was also indicated by an increase in the number of cells with reduced DNA content, as measured by flow cytometry of activin-treated cells. Both activin-mediated inhibition of cell proliferation and induction of apoptosis could be completely blocked by recombinant human follistatin. Based upon these results using an in vitro model, we speculate that activin functions locally to oppose androgen-driven cell proliferation and, thus, is a key factor controlling prostate growth. Reduced activin biosynthesis, increased follistatin secretion, or signaling defects in the activin receptor system should be further investigated in future studies as potential mechanisms underlying enhanced androgen-independent growth of human prostate cancer cells. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED, VINCENT CTR REPROD BIOL,DEPT OBSTET & GYNECOL, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED, NATL COOPERAT PROGRAM INFERTIL RES,DEPT MED, BOSTON, MA 02114 USA. NR 74 TC 75 Z9 77 U1 0 U2 3 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 DEC PY 1996 VL 137 IS 12 BP 5476 EP 5483 DI 10.1210/en.137.12.5476 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VU351 UT WOS:A1996VU35100042 PM 8940374 ER PT J AU Aziz, N Brown, D Lee, WS NarayFejesToth, A AF Aziz, N Brown, D Lee, WS NarayFejesToth, A TI Aberrant 11 beta-hydroxysteroid dehydrogenase-1 activity in the cpk mouse: Implications for regulation by the Ke 6 gene SO ENDOCRINOLOGY LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; RAT-KIDNEY; CYSTIC-DISEASE; TARGET-CELLS; LOCALIZATION; MODEL; ALDOSTERONE; EXPRESSION; RECEPTOR AB Glucocorticoids have been used to create experimental polycystic kidney disease in rodents and to induce cysts in embryonic kidneys cultures. In addition, the plasma corticosterone levels are higher in a heritable murine model of polycystic kidney disease, cph mice, in the first postnatal week. Previously, we had shown that the 11 beta-hydroxysteroid dehydrogenase-1 (11 beta HSD-1) gene is down-regulated in the cph mice in a coordinated pattern with the Ke 6 gene. In this study, we measured the level of 11 beta HSD-1 activity in kidney and Liver tissues of cpk homozygote mice and found a reduction in its activity only in the kidney, not in the liver. The activity of the 11 beta HSD-1 enzyme appears to be tightly correlated to the level of Ke 6 protein in these tissues. We discuss the possibility that the activity of the 11 beta HSD-1 enzyme may be regulated by the Ke 6 enzyme. Ke 6 gene expression has been located to the outer stripe region of rodent kidneys, which is the same region of expression as that for the 11 beta HSD-1 gene. These results suggest that down-regulation of the Ke 6 gene may lead to elevated corticosterone levels, mediated through an inhibition of 11 beta HSD-1 activity. C1 HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA 02115 USA. HARVARD UNIV, SCH PUBL HLTH, CARDIOVASC BIOL LAB, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, RENAL UNIT, CHARLESTOWN, MA 02129 USA. DARTMOUTH COLL SCH MED, DEPT PHYSIOL, LEBANON, NH 03756 USA. RP Aziz, N (reprint author), CHILDRENS HOSP, DEPT MED, DIV NEPHROL, HUNNEWELL 3, 300 LONGWOOD AVE, BOSTON, MA 02115 USA. FU NIDDK NIH HHS [DK-48098] NR 34 TC 20 Z9 20 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1996 VL 137 IS 12 BP 5581 EP 5588 DI 10.1210/en.137.12.5581 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VU351 UT WOS:A1996VU35100056 PM 8940387 ER PT J AU Houser, CR Esclapez, M AF Houser, CR Esclapez, M TI Vulnerability and plasticity of the GABA system in the pilocarpine model of spontaneous recurrent seizures SO EPILEPSY RESEARCH LA English DT Article; Proceedings Paper CT 3rd Workshop on the Neurobiology of Epilepsy (WONOEP III) - Mechanisms of Chronic Models of Epilepsy CY AUG 29-SEP 02, 1995 CL KEWARRA BEACH, AUSTRALIA DE glutamate decarboxylase; GAD65; hippocampus; dentate gyrus; epilepsy; temporal lobe epilepsy ID TEMPORAL-LOBE EPILEPSY; GLUTAMIC-ACID DECARBOXYLASE; HIPPOCAMPAL DENTATE GYRUS; RAT FASCIA-DENTATA; GABAERGIC NEURONS; NEUROPEPTIDE-Y; GRANULE CELLS; KAINIC ACID; 2 FORMS; INTRAHIPPOCAMPAL KAINATE AB Several similarities exist between the alterations observed in the chronic pilocarpine model of recurrent seizures in the rat and those found in human temporal lobe epilepsy. The present studies are focused on changes in the GABA system in this model. Following the initial pilocarpine-induced seizures, a substantial loss of glutamic acid decarboxylase (GAD) mRNA-containing neurons has been found in the hilus of the dentate gyrus (Obenaus et al., J. Neurosci, 13 (1993) 4470-4485), and, recently, a loss of GAD mRNA-labeled neurons has also been found in stratum oriens of CA1. Yet numerous other GABA neurons remain within the hippocampal formation, and there appear to be multiple compensatory changes in these neurons. Labeling for GAD65 mRNA and associated protein is substantially increased in the remaining GABA neurons at 2-4 months after the initial seizure episode. Such increased labeling suggests that the remaining GABA neurons are part of a functional circuit and may be responding to the need for increased activity. Alterations also occur in at least one subunit of the GABA-A receptor. Labeling for the alpha 5 subunit mRNA is substantially decreased in CAI and CA2 of pilocarpine-treated rats during the chronic, seizure-prone period. These findings emphasize the complexity of changes in the GABA system and indicate a need for evaluating the functional consequences of each of the changes. The initial loss of specific groups of GABA neurons could be a critical first step in the gradual development of epileptiform activity. While many of the subsequent changes in the GABA system may be considered to be compensatory, significant deficits of GABAergic function could remain. C1 UNIV CALIF LOS ANGELES,DEPT NEUROBIOL,LOS ANGELES,CA 90095. W LOS ANGELES VET AFFAIRS MED CTR,WADSWORTH DIV,NEUROL SERV,COMPREHENS EPILEPSY PROGRAM,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,WADSWORTH DIV,RES SERV,COMPREHENS EPILEPSY PROGRAM,LOS ANGELES,CA 90073. RP Houser, CR (reprint author), UNIV CALIF LOS ANGELES,BRAIN RES INST,LOS ANGELES,CA 90095, USA. RI Esclapez, Monique/O-6509-2016 OI Esclapez, Monique/0000-0002-8558-1363 FU NINDS NIH HHS [NS21908] NR 59 TC 153 Z9 156 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 DEC PY 1996 VL 26 IS 1 BP 207 EP 218 DI 10.1016/S0920-1211(96)00054-X PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA VX953 UT WOS:A1996VX95300022 PM 8985701 ER PT J AU Teicher, BA Emi, Y Kakeji, Y Northey, D AF Teicher, BA Emi, Y Kakeji, Y Northey, D TI TNP-470/minocycline/cytotoxic therapy: A systems approach to cancer therapy SO EUROPEAN JOURNAL OF CANCER LA English DT Article ID ANGIOGENESIS INHIBITOR TNP-470; TUMOR STROMA GENERATION; ALKYLATING-AGENTS; BREAST-CANCER; MCF-7 CELLS; GROWTH; MINOCYCLINE; CARCINOMA; AGM-1470; INVIVO C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP Teicher, BA (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 51 TC 39 Z9 40 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD DEC PY 1996 VL 32A IS 14 BP 2461 EP 2466 DI 10.1016/S0959-8049(96)00380-2 PG 6 WC Oncology SC Oncology GA WE687 UT WOS:A1996WE68700010 PM 9059334 ER PT J AU Vawter, MP DillonCarter, O Tourtellotte, WW Carvey, P Freed, WJ AF Vawter, MP DillonCarter, O Tourtellotte, WW Carvey, P Freed, WJ TI TGF beta 1 and TGF beta 2 concentrations are elevated in Parkinson's disease in ventricular cerebrospinal fluid SO EXPERIMENTAL NEUROLOGY LA English DT Article ID GROWTH-FACTOR-BETA; BLOOD-BRAIN-BARRIER; MIDBRAIN DOPAMINERGIC-NEURONS; TGF-BETA; ALZHEIMERS-DISEASE; MULTIPLE-SCLEROSIS; NERVOUS-SYSTEM; DIFFERENTIAL EXPRESSION; TOTAL PROTEIN; FACTOR-BETA-1 AB Transforming growth factor (TGF)beta plays a role in injury repair in sites surrounding brain injury. The present study tested the hypothesis that TGF beta 1 and TGF beta 2 levels in the postmortem CSF of patients with neurodegenerative disorders would be elevated compared to those in normal subjects. Free TGF beta 1 and total TGF beta 2 were measured by ELISA in postmortem ventricular cerebrospinal fluid (vCSF) of patients with Parkinson's disease (n = 30), Alzheimer's disease (n = 30), multiple sclerosis (n = 15), and schizophrenia (n = 12) and of normal controls (n = 16). In addition, albumin, IgG, and total protein in vCSF were measured. Both TGF beta 1 and TGF beta 2 were significantly different between groups (P < 0.002 and P < 0.001, respectively). Parkinson's disease vCSF showed significant increases in both TGF beta 1 (P = 0.015) and TGF beta 2 (P = 0.012) compared to normal controls. There was a trend for TGF beta 2 to be elevated in Alzheimer's disease and multiple sclerosis vCSFs, which failed to achieve significance. There were no differences between controls and schizophrenics in TGF beta 1 or TGF beta 2. Alzheimer's disease vCSF showed a significant decrease in protein compared to all other groups, which was not related to blood-brain barrier permeability, age, or autolysis differences. Evidence is presented suggesting that some TGF beta 1 may leak into the vCSF from plasma, Autopsy vCSF levels of TGF beta isoforms were found to be distinctly different from those reported for human serum, especially for TGF beta 2, which is undetectable in plasma. These results indicate that further in vivo studies of TGF beta 2 in the CSF of Parkinson's disease patients are warranted to determine the relationship between clinical status, medication, and TGF beta 2 concentrations. (C) 1996 Academic Press, Inc. C1 W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. RP Vawter, MP (reprint author), NIMH,SECT PRECLIN NEUROSCI,NEUROPSYCHIAT BRANCH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032, USA. FU NIA NIH HHS [AG10161, AG09466] NR 50 TC 83 Z9 87 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 1996 VL 142 IS 2 BP 313 EP 322 DI 10.1006/exnr.1996.0200 PG 10 WC Neurosciences SC Neurosciences & Neurology GA VV613 UT WOS:A1996VV61300009 PM 8934562 ER PT J AU Reinecker, HC MacDermott, RP Mirau, S Dignass, A Podolsky, DK AF Reinecker, HC MacDermott, RP Mirau, S Dignass, A Podolsky, DK TI Intestinal epithelial cells both express and respond to interleukin 15 SO GASTROENTEROLOGY LA English DT Article ID IL-2 RECEPTOR; BETA-CHAIN; T-LYMPHOCYTES; GROWTH-FACTOR; CLONING; BINDING AB Background & Aims: Interleukin (IL)-15 exerts functional effects on lymphocytes similar to those of IL-2, IL-15 is expressed by nonlymphoid cells and may integrate these cells into classical immune responses, The aim of this study was to characterize the expression of IL-15 by intestinal epithelial cells and determine the functional roles of IL-15 within the mucosal immune system. Methods: Rat IL-15 was cloned from a rat jejunal library, Expression of IL-15 in rat and human intestinal epithelial cells was assessed by Northern and Western blotting, Tyrosine kinase activation in response to IL-15 in intestinal epithelial cells was determined by immunoprecipitation, Results: Rat and human intestinal epithelial cells express IL-15 messenger RNA, IL-15 activates Stat3 and stimulates the proliferation of intestinal epithelial cells, The relevance of the observations for intestinal epithelial cell function in vivo was supported by the demonstration of transcripts for IL-15 in primary human intestinal epithelial cells. Conclusions: IL-15 is expressed by intestinal epithelial cells and may be able to regulate intestinal epithelial cell function, These experiments suggest that IL-15 is an important mediator that could integrate intestinal epithelial cell function with the intestinal immune system. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,DEPT MED,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV ESSEN GESAMTHSCH,DEPT MED,D-4300 ESSEN,GERMANY. LAHEY CLIN FDN,BURLINGTON,MA. FU NIDDK NIH HHS [DK 21474, DK 41557, DK 43351] NR 23 TC 188 Z9 193 U1 0 U2 2 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 DEC PY 1996 VL 111 IS 6 BP 1706 EP 1713 DI 10.1016/S0016-5085(96)70036-7 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VW292 UT WOS:A1996VW29200038 PM 8942753 ER PT J AU Podolsky, DK AF Podolsky, DK TI Gastroenterology, research, and the American Gastroenterological Association: Today's investigation, tomorrow's practice SO GASTROENTEROLOGY LA English DT Article RP Podolsky, DK (reprint author), MASSACHUSETTS GEN HOSP,COMM RES,32 FRUIT ST GRJ719,BOSTON,MA 02114, USA. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 1996 VL 111 IS 6 BP 1753 EP 1757 DI 10.1016/S0016-5085(96)70041-0 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VW292 UT WOS:A1996VW29200042 PM 8942757 ER PT J AU Brodkin, KI Abrass, IB AF Brodkin, KI Abrass, IB TI Hypertension in the elderly SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Article ID HIGH BLOOD-PRESSURE; PLASMA-RENIN ACTIVITY; FRAMINGHAM; TRIAL; MORTALITY; MORBIDITY; WEIGHT C1 UNIV WASHINGTON,DEPT MED,DIV GERONTOL & GERIATR MED,SEATTLE,WA. RP Brodkin, KI (reprint author), VET AFFAIRS PUGET SOUND HLTH CARE SYST,CTR GERIATR RES EDUC & CLIN,SEATTLE,WA, USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC AGING PI SAN FRANCISCO PA 833 MARKET ST, STE 511, SAN FRANCISCO, CA 94103-1824 SN 0738-7806 J9 GENERATIONS JI Generations-J. Am. Soc. Aging PD WIN PY 1996 VL 20 IS 4 BP 28 EP 32 PG 5 WC Gerontology SC Geriatrics & Gerontology GA WC863 UT WOS:A1996WC86300007 ER PT J AU Hofmann, F Martelli, F Livingston, DM Wang, ZY AF Hofmann, F Martelli, F Livingston, DM Wang, ZY TI The retinoblastoma gene product protects E2F-1 from degradation by the ubiquitin-proteasome pathway SO GENES & DEVELOPMENT LA English DT Article DE E2F; pRb; cell-cycle control; ubiquitin-proteasome; protein degradation ID TRANSCRIPTION FACTOR E2F-1; CELL-CYCLE PROGRESSION; S-PHASE ENTRY; DOWNSTREAM TARGET; BINDING PROTEIN; EXPRESSION; PROMOTER; DNA; FAMILY; KINASE AB E2F-1 plays a crucial role in the regulation of cell-cycle progression at the G(1)-S transition. In keeping with the fact that, when overproduced, it is both an oncoprotein and a potent inducer of apoptosis, its transcriptional activity is subject to multiple controls. Among them are binding by the retinoblastoma gene product (pRb), activation by cdk3, and S-phase-dependent down-regulation of DNA-binding capacity by cyclin A-dependent kinase. Here we report that E2F-1 is actively degraded by the ubiquitin-proteasome pathway. Efficient degradation depends on the availability of selected E2F-1 sequences. Unphosphorylated pRb stabilized E2F-1, protecting it from in vivo degradation. pRb-mediated stabilization was not an indirect consequence of G(1) arrest, but rather depended on the ability of pRb to interact physically with E2F-1. Thus, in addition to binding E2F-1 and transforming it into a transcriptional repressor, pRb has another function, protection of E2F-1 from efficient degradation during a period when pRb/E2F complex formation is essential to regulating the cell cycle. In addition, there may be a specific mechanism for limiting free E2F-1 levels, failure of which could compromise cell survival and/or homeostasis. C1 DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Tang, Amy/L-3226-2016; OI Tang, Amy/0000-0002-5772-2878; Martelli, Fabio/0000-0002-8624-7738 NR 70 TC 200 Z9 200 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 1 PY 1996 VL 10 IS 23 BP 2949 EP 2959 DI 10.1101/gad.10.23.2949 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA VX613 UT WOS:A1996VX61300001 PM 8956996 ER PT J AU Ha, I Wightman, B Ruvkun, G AF Ha, I Wightman, B Ruvkun, G TI A bulged lin-4/lin-14 RNA duplex is sufficient for Caenorhabditis elegans lin-14 temporal gradient formation SO GENES & DEVELOPMENT LA English DT Article DE C, elegans; development; heterochronic; bulged RNA; translation; lin-14, lin-4; 3' UTR ID HETEROCHRONIC GENE LIN-14; 3' UNTRANSLATED REGION; C-ELEGANS; MESSENGER-RNA; ANTISENSE RNA; TRANSLATIONAL REGULATION; DEVELOPMENTAL SWITCH; PROTEIN INTERACTIONS; MAJOR GROOVE; BINDING AB The Caenorhabditis elegans heterochronic gene lin-14 generates a temporal gradient of the LIN-14 proteins to control stage-specific patterns of cell lineage during development. Down-regulation of LIN-14 is mediated by the lin-14 3' untranslated region (UTR), which bears seven sites that are complementary to the regulatory lin-4 RNA. Here we report molecular and genetic evidence that RNA duplexes between the lin-4 and lin-14 RNAs form in vivo and are necessary for LIN-14 temporal gradient generation, lin-4 RNA binds in vitro to a lin-14 mRNA bearing the seven lin-4 complementary sites but not to a lin-14 mRNA bearing point mutations in these sites. In vivo, the lin-4 complementary regions are necessary for lin-14 3' UTR-mediated temporal gradient formation. Based on lin-14 3' UTR sequence comparisons between C. elegans and C. briggsae, four of the seven lin-4/lin-14 RNA duplexes are predicted to bulge a lin-4 C residue, and three sites are predicted to form nonbulged RNA duplexes. Reporter genes bearing multimerized bulged C lin-4 binding sites show almost wild-type temporal gradient formation, whereas those bearing multimerized nonbulged lin-4 binding sites do not form a temporal gradient. Paradoxically, lin-4 RNA binds in vitro to nonbulged lin-14 RNA more avidly than to the bulged lin-14 RNA. This suggests that a specific secondary structure of lin-4/lin-14 RNA duplex that may be recognized by an accessory protein, rather than an RNA duplex per se, is required in vivo for the generation of the LIN-14 temporal gradient. C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. FU NIGMS NIH HHS [GM44619] NR 43 TC 155 Z9 161 U1 1 U2 5 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 DEC 1 PY 1996 VL 10 IS 23 BP 3041 EP 3050 DI 10.1101/gad.10.23.3041 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA VX613 UT WOS:A1996VX61300009 PM 8957004 ER PT J AU Missero, C DiCunto, F Kiyokawa, H Koff, A Dotto, GP AF Missero, C DiCunto, F Kiyokawa, H Koff, A Dotto, GP TI The absence of p21(Cip1/WAF1) alters keratinocyte growth and differentiation and promotes ras-tumor progression SO GENES & DEVELOPMENT LA English DT Article DE cell cycle; CDK inhibitors; tumor suppression; ras oncogene ID DEPENDENT KINASE INHIBITOR; CELL-CYCLE ARREST; P53 GENE DOSAGE; DNA-REPLICATION; MALIGNANT PROGRESSION; POTENTIAL MEDIATOR; PROTEIN-KINASE; IN-VIVO; P21; EXPRESSION AB p21(Cip1/WAF1) was the first cyclin-dependent kinase (CDK) inhibitor to be identified, as a mediator of p53 in DNA damage-induced growth arrest, cell senescence, and direct CDK regulation. p21 may also play an important role in differentiation-associated growth arrest, as its expression is augmented in many terminally differentiating cells. A general involvement of p21 in growth/differentiation control and tumor suppression has been questioned, as mice lacking p21 undergo a normal development, harbor no gross alterations in any of their organs, and exhibit no increase in spontaneous tumor development. However, a significant imbalance between growth and differentiation could be unmasked under conditions where normal homeostatic mechanisms are impaired. We report here that primary keratinocytes derived from p21 knockout mice, transformed with a ras oncogene, and injected subcutaneously into nude mice exhibit a very aggressive tumorigenic behavior, which is not observed with wild-type control keratinocytes nor with keratinocytes with a disruption of the closely related p27 gene. p21 knockout keratinocytes tested under well-defined in vitro conditions show a significantly increased proliferative potential, which is also observed but to a lesser extent with p27 knockout cells. More profound differences were found in the differentiation behavior of p21 versus p27 knockout keratinocytes, with p21 (but not p27) deficiency causing a drastic down-modulation of differentiation markers linked with the late stages of the keratinocyte terminal differentiation program. Thus, our results reveal a so far undetected role of p21 in tumor suppression, demonstrate that this function is specific as it cannot be attributed to the closely related p27 molecule, and point to an essential involvement of p21 in terminal differentiation control, which may account for its role in tumor suppression. C1 HARVARD UNIV,SCH MED,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129. MEM SLOAN KETTERING CANC CTR,PROGRAM MOL BIOL,NEW YORK,NY 10021. OI di cunto, ferdinando/0000-0001-9367-6357 FU NCI NIH HHS [CA16038]; NIAMS NIH HHS [AR39190] NR 57 TC 255 Z9 257 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 1 PY 1996 VL 10 IS 23 BP 3065 EP 3075 DI 10.1101/gad.10.23.3065 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA VX613 UT WOS:A1996VX61300011 PM 8957006 ER PT J AU Wood, TF Srivatsan, ES Chakrabarti, R Ma, GC Kuan, NK Samara, GJ Higgins, MJ Shows, TB Johnson, CL Wan, YJY Passaro, EP Sawicki, MP AF Wood, TF Srivatsan, ES Chakrabarti, R Ma, GC Kuan, NK Samara, GJ Higgins, MJ Shows, TB Johnson, CL Wan, YJY Passaro, EP Sawicki, MP TI A 1.5-megabase physical map encompassing the multiple endocrine neoplasia type-1 (MEN1) locus on chromosome 11q13 SO GENOMICS LA English DT Article ID CELL HYBRIDS; LONG ARM; GENE; REGION; MARKERS; TUMORS; DNA; HUMAN-CHROMOSOME-11; SUBLOCALIZATION; HETEROZYGOSITY AB Linkage analysis and loss of heterozygosity studies have shown that the gene responsible for the multiple endocrine neoplasia type-1 (MEN1) syndrome localizes to a small interval between D11S427 and D11S460 on chromosome 11q13. As an initial step to clone this tumor suppressor gene, our group is the first to map the MEN1 region physically using yeast artificial chromosome, bacterial artificial chromosome (BAG), and cosmid contigs. The 1.5-Mb high-resolution, contiguous map extends from PYGM to 300 kb telomeric of D11S460. Of this, the 1.2-Mb interval between PYGM and D11S460 is isolated in cosmids and BACs and will be useful for the development of genomic sequences and transcription maps of this important region. Nine new sequence-tagged sites (STS) ape also characterized from this region, The physical map and the STSs will be valuable tools for the cloning of the MEN1 gene. (C) 1996 Academic Press, Inc. C1 UNIV CALIF LOS ANGELES,SCH MED,W LOS ANGELES VET AFFAIRS MED CTR,DEPT SURG W112,LOS ANGELES,CA 90073. COLUMBIA UNIV,DEPT OTOLARYNGOL HEAD & NECK SURG,NEW YORK,NY 10032. ROSWELL PK CANC INST,DEPT HUMAN GENET,BUFFALO,NY 14263. ALBERTA CHILDRENS PROV GEN HOSP,CLIN GENET UNIT,CALGARY,AB T2T 5C7,CANADA. HARBOR UCLA MED CTR,DEPT PATHOL,TORRANCE,CA 90509. FU NHGRI NIH HHS [HG00359] NR 52 TC 21 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC 1 PY 1996 VL 38 IS 2 BP 166 EP 173 DI 10.1006/geno.1996.0612 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VY320 UT WOS:A1996VY32000008 PM 8954798 ER PT J AU Weng, S Spiro, RG AF Weng, S Spiro, RG TI Evaluation of the early processing routes of N-linked oligosaccharides of glycoproteins through the characterization of Man(8)GlcNAc(2) isomers: Evidence that endomannosidase functions in vivo in the absence of a glucosidase blockade SO GLYCOBIOLOGY LA English DT Article DE glycoprotein processing; endomannosidase; mannosidase; kifunensine; Man(8)GlcNAc(2) isomers ID ALPHA-D-MANNOSIDASE; LIVER GOLGI MEMBRANES; RAT-LIVER; ENDOPLASMIC-RETICULUM; BIOSYNTHESIS; PATHWAY; PURIFICATION; KIFUNENSINE; INHIBITORS; PROTEINS AB Since it has become apparent that the early processing of the N-linked oligosaccharides of glycoproteins can proceed by several routes, we undertook to determine whether the isomeric nature of Man(8)GlcNAc(2), which is the first intermediate with the potential for structural diversity, can provide information relating to the pathways utilized in various intact cultured cells as well as in the total membrane fraction derived from these cells (BW5147.3, HepG2, HL-60, F-9, and MDCK), With the use of kifunensine (KIF) to block processing by Golgi mannosidase I, it could be shown that a substantial amount of Man(8)GlcNAc(2) components in which the terminal mannose is missing in the alpha 1,3-linked and alpha 1,6-linked chain (isomers A and C, respectively) are produced, although in the absence of the inhibitor only the B-isomer, in which the mannose of the middle chain has been excised, was apparent, Our findings in vivo and in vitro suggest that the distinctive Man(8)GlcNAc(2) product of endomannosidase (isomer A) and of ER mannosidase II (isomer C) are not evident in the absence of KIF, since they are rapidly degraded by Golgi mannosidase I, which is located in an intracellular compartment distal to the other two enzymes and itself exclusively generates the Man(8)GlcNAc(2) isomer B. Investigations carried out in HepG2 cells indicated that glycoproteins with N-linked oligosaccharides whose processing has been blocked by KIF at the Man(8)GlcNAc(2) isomer A and C stage can nevertheless be effectively secreted, The observation that isomer A of Man(8)GlcNAc(2) is a specific product of endomannosidase action made it possible to demonstrate the action of this enzyme in vivo without employing a glucosidase blockade and to show that a substantial amount of the deglucosylation of N-linked oligosaccharides is carried out by this enzyme. C1 JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02215. FU NIDDK NIH HHS [DK 17477] NR 28 TC 24 Z9 24 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD DEC PY 1996 VL 6 IS 8 BP 861 EP 868 DI 10.1093/glycob/6.8.861 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA487 UT WOS:A1996WA48700012 PM 9023549 ER PT J AU Kim, RY Cooper, KL Kelly, LD AF Kim, RY Cooper, KL Kelly, LD TI Predictive factors for response to medical therapy in bacterial ulcerative keratitis SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID CONTACT-LENS WEAR; MICROBIAL KERATITIS; CORNEAL ULCERS; PREDISPOSING FACTORS; OCULAR MEDICATIONS; RISK AB Background: Fifty-four consecutive cases of culture-positive bacterial ulcerative keratitis presenting at a major university hospital were reviewed to identify factors predictive of response to medical therapy for bacterial ulcerative keratitis (BUK). Methods: Eleven patients (20%) failed medical therapy (defined as the need for surgical intervention or cyanoacry late gluing). Using multivariate logistic regression, the following variables were evaluated: (1) predisposing ocular factors (e.g., contact lens wear), (2) pre-existing ocular diseases, (3) ulcer size, and (4) the number of topical ocular medications used at the time of presentation. Results: We noted certain factors to be potentially predictive of medical therapy outcome. The average size of the ulcer at the time of presentation was 4.4+/-2.4 mm in the failure group but only 2.5+/-1.9 mm for the success group (P=0.027). In addition, patients in the medical failure group used more topical ocular medications at the time of presentation (P=0.0075). Further analysis of the individual topical ocular medications revealed that the use of corticosteroids was higher in the failure group (56% vs 12%, P=0.0005 by Fisher's exact test). Other factors such as patient age, the type of organism(s), and the time elapsed between the onset of symptoms and the beginning of definitive therapy were not statistically significant. Conclusion: In this population, ulcer size at the onset of antibacterial treatment and the use of certain ocular medications, specifically corticosteroids, were significant predictive factors for failure of medical therapy for BUK. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. STANFORD UNIV,MED CTR,DEPT OPHTHALMOL,STANFORD,CA 94305. NR 29 TC 7 Z9 8 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD DEC PY 1996 VL 234 IS 12 BP 731 EP 738 DI 10.1007/BF00189353 PG 8 WC Ophthalmology SC Ophthalmology GA WA425 UT WOS:A1996WA42500002 PM 8986444 ER PT J AU Navani, SS AlvaradoCabrero, I Young, RH Scully, RE AF Navani, SS AlvaradoCabrero, I Young, RH Scully, RE TI Endometrioid carcinoma of the fallopian tube: A clinicopathologic analysis of 26 cases SO GYNECOLOGIC ONCOLOGY LA English DT Article ID PROBABLE WOLFFIAN ORIGIN; ADNEXAL TUMOR; ADENOCARCINOMA; OVARY AB Twenty-six endometrioid adenocarcinomas of the fallopian tube that occurred in patients 37 to 85 (average 57) years of age are described, Most of the patients presented with symptoms related to a pelvic mass but nine tumors were incidental findings at the time of operation, All the neoplasms were unilateral, Eighteen tumors were Stage I, four Stage II, two Stage III, and two Stage IV, Two tumors were primary in the fimbriated end of the tube, On gross examination the typical appearance was that of a fusiform swelling of the tube which contained a predominantly intraluminal neoplasm up to 6 cm in greatest dimension, Six separate tumors were present in one case, Microscopic examination revealed that 14 tumors were typical endometrioid carcinomas with foci of squamous differentiation in 7 cases, spindle cells interpreted as epithelial cells in 4 cases, and a trabecular pattern in 1 case, One of these 14 tumors was composed almost exclusively of oxyphilic cells lining glands, Twelve tumors were characterized by a mostly solid proliferation of small closely packed cells punctured by numerous glands that varied from small to cystic, imparting a superficial resemblance to an adnexal tumor of probable Wolffian origin, Benign stromal osseous metaplasia was noted in two Wolffian-like and one typical endometrioid carcinoma, Five tumors were grade 1, 11 were grade 2, and 10 were grade 3. Follow-up information was available for 18 patients. Five with noninvasive Stage Ia-0 tumors (intraluminal, noninvasive masses) were without disease at 2 to 5 (average 3) years postoperatively, Two of three patients with Stage Ia1 tumors were alive without recurrence at 2 and 3 years postoperatively, One of two patients with Stage Ia2 disease for whom follow-up is available was alive without disease 1.5 years postoperatively and one died of other causes 11.2 years postoperatively, One patient with Stage Ic disease had recurrence of tumor at 2 years; four with Stage II disease were without disease at 1.5, 2, 3, and 8 years; one with Stage IIIa disease died with disease at 4 years; and one with Stage IV disease died with disease after 5 years, Two additional patients had fimbrial tumors [Stage I(f)]; one of them died with disease at 7 years, and the other was alive without disease at 8 years, This small series indicates that endometrioid carcinomas of the fallopian tube are characteristically noninvasive or only superficially invasive and have a generally favorable prognosis. This subtype of tubal carcinoma should be distinguished from the more common neoplasms of serous type and from those of various other cell types. (C) 1996 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114. NR 29 TC 33 Z9 34 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 DEC PY 1996 VL 63 IS 3 BP 371 EP 378 DI 10.1006/gyno.1996.0338 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA VY318 UT WOS:A1996VY31800015 PM 8946874 ER PT J AU Spunt, BS Deyo, RA Taylor, VM Leek, KM Goldberg, HI Mulley, AG AF Spunt, BS Deyo, RA Taylor, VM Leek, KM Goldberg, HI Mulley, AG TI An interactive videodisc program for low back pain patients SO HEALTH EDUCATION RESEARCH LA English DT Article; Proceedings Paper CT 122nd Annual Meeting of the American-Public-Health-Association CY OCT 29-NOV 04, 1994 CL WASHINGTON, DC SP Amer Public Hlth Assoc ID MEDICAL-CARE; EDUCATION; DISK; VIDEOTAPE; OUTCOMES AB Decisions about back pain treatment are often made in the presence of both physician and patient uncertainty. Therefore, we developed a computerized, interactive video program to help patients make informed decisions about undergoing low back surgery. Program development was guided by the shared decision-making model, a comprehensive literature synthesis, information from administrative databases, and focus groups of patients and physicians, Core segments are tailored to each patient's age and diagnosis; and include a narrative, excerpts from patient interviews, animated graphics illustrating spinal anatomy, and tabular summaries of the benefits and risks of both surgical and non-surgical treatment, As part of a multifocal information dissemination effort, interactive videodiscs were placed in five medical facilities in two Washington State counties, Patients (N = 239) who viewed the video program completed short evaluation forms, The majority rated the video's understandability (84%) and interest (64%) as very good or excellent, Most patients felt the amount of information provided was appropriate (75%) and over half (56%) believed the discussion of surgical versus non-surgical treatment was completely balanced, Fewer patients (17%) remained undecided about therapy after watching the program than before (29%). We conclude that interactive videodisc technology offers substantial promise as a means of involving patients in their own medical decision making. C1 UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98105. VET AFFAIRS MED CTR,NW HLTH SERV RES & DEV FIELD PROGRAM,SEATTLE,WA 98108. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. RP Spunt, BS (reprint author), UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98105, USA. FU AHRQ HHS [HS08194, HS06344] NR 24 TC 25 Z9 25 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD DEC PY 1996 VL 11 IS 4 BP 535 EP 541 DI 10.1093/her/11.4.535 PG 7 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA VZ609 UT WOS:A1996VZ60900014 PM 10163960 ER PT J AU Pedrozo, HA Schwartz, Z Luther, M Dean, DD Boyan, BD Wiederhold, ML AF Pedrozo, HA Schwartz, Z Luther, M Dean, DD Boyan, BD Wiederhold, ML TI A mechanism of adaptation to hypergravity in the statocyst of Aplysia californica SO HEARING RESEARCH LA English DT Article DE hypergravity; organ; calcification; Aplysia californica; gravity ID BONE; WEIGHTLESSNESS; MICROGRAVITY AB The gravity-sensing organ of Aplysia californica consists of bilaterally paired statocysts containing statoconia, which are granules composed of calcium carbonate crystals in an organic matrix. In early embryonic development, Aplysia contain a single granule called a statolith, and as the animal matures, statoconia production takes place. The objective of this study was to determine the effect of hypergravity on statoconia production and homeostasis and explore a possible physiologic mechanism for regulating this process. Embryonic Aplysia were exposed to normogravity or 3 x g or 5.7 x g and each day samples were analyzed for changes in statocyst, statolith, and body dimensions until they hatched. In addition, early metamorphosed Aplysia (developmental stages 7-10) were exposed to hypergravity (2 x g) for 3 weeks, and statoconia number and statocyst and statoconia volumes were determined. We also determined the effects of hypergravity on statoconia production and homeostasis in statocysts isolated from developmental stage 10 Aplysia. Since prior studies demonstrated that urease was important in the regulation of statocyst pH and statoconia formation, we also evaluated the effect of hypergravity on urease activity. The results show that hypergravity decreased statolith and body diameter in embryonic Aplysia in a magnitude-dependent fashion. In early metamorphosed Aplysia, hypergravity decreased statoconia number and volume. Similarly, there was an inhibition of statoconia production and a decrease in statoconia volume in isolated statocysts exposed to hypergravity in culture. Urease activity in statocysts decreased after exposure to hypergravity and was correlated with the decrease in statoconia production observed. In short, there was a decrease in statoconia production with exposure to hypergravity both in vivo and in vitro and a decrease in urease activity. It is concluded that exposure to hypergravity downregulates urease activity, resulting in a significant decrease in the formation of statoconia. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT ORTHOPAED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PERIODONT,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT OTOLARYNGOL HEAD & NECK SURG,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,DEPT PERIODONT,SAN ANTONIO,TX 78229. OI Dean, David/0000-0002-4512-9065 NR 48 TC 19 Z9 22 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD DEC 1 PY 1996 VL 102 IS 1-2 BP 51 EP 62 DI 10.1016/S0378-5955(96)00147-5 PG 12 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA VX780 UT WOS:A1996VX78000006 PM 8951450 ER PT J AU Oshima, J Yu, CE Piussan, C Klein, G Jabkowski, J Balci, S Miki, T Nakura, J Ogihara, T Ells, J Smith, MDC Melaragno, MI Fraccaro, M Scappaticci, S Matthews, J Ouais, S Jarzebowicz, A Schellenberg, GD Martin, GM AF Oshima, J Yu, CE Piussan, C Klein, G Jabkowski, J Balci, S Miki, T Nakura, J Ogihara, T Ells, J Smith, MDC Melaragno, MI Fraccaro, M Scappaticci, S Matthews, J Ouais, S Jarzebowicz, A Schellenberg, GD Martin, GM TI Homozygous and compound heterozygous mutations at the Werner syndrome locus SO HUMAN MOLECULAR GENETICS LA English DT Article ID EXCISION REPAIR GENE; RNA-POLYMERASE-II; XERODERMA-PIGMENTOSUM; DNA HELICASE; PUTATIVE HELICASES; MOLECULAR-BASIS; LIFE-SPAN; CELLS; TRANSCRIPTION; RECOMBINATION AB The Werner syndrome (WS) is a rare autosomal recessive progeroid disorder, The Werner syndrome gene (WRN) has recently been identified as a member of the helicase family, Four distinct mutations were previously reported in three Japanese and one Syrian WS pedigrees, The latter mutation was originally described as a 4 bp deletion spanning a spliced junction, It is now shown that this mutation results in a 4 bp deletion at the beginning of an exon, Nine new WRN mutations in 10 additional WS patients, both Japanese and Caucasian, are described, These include three compound heterozygotes (one Japanese and two Caucasian), The new mutations are located all across the coding region. C1 VET AFFAIRS PUGET SOUND HLTH CARE SYST,SEATTLE DIV,CTR GERIATR RES EDUC & CLIN,SEATTLE,WA. UNIV AMIENS,F-80054 AMIENS,FRANCE. KRANKENHAUS ELISABETHINEN,DERMATOL ABT ALLGEM OFFENTLICHE,A-239 LINZ,AUSTRIA. HACETTEPE UNIV,CHILDRENS HISPITAL,DEPT CLIN GENET,ANKARA,TURKEY. OSAKA UNIV,DEPT GERIATR MED,OSAKA 565,JAPAN. NELLIS AIR FORCE BASE HOSP,INTERNAL MED CLIN,LAS VEGAS,NV 89101. ESCOLA PAULISTA MED,DIV GENET,BR-04023 SAO PAULO,BRAZIL. UNIV PAVIA,I-27100 PAVIA,ITALY. GRP HLTH,FAIRFAX,VA 22039. DAMASCUS CITY HOSP,ENDOCRINOL SECT,DAMASCUS,SYRIA. RP Oshima, J (reprint author), UNIV WASHINGTON,DEPT PATHOL,BOX 357470,SEATTLE,WA 98195, USA. RI Melaragno, Maria/F-9013-2012; Smith, Marilia/C-4397-2012 OI Smith, Marilia/0000-0002-1441-1033 FU NIA NIH HHS [P1 AG08303, R37 AG08303, T32 AG00057] NR 42 TC 72 Z9 72 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC PY 1996 VL 5 IS 12 BP 1909 EP 1913 DI 10.1093/hmg/5.12.1909 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA VX747 UT WOS:A1996VX74700008 PM 8968742 ER PT J AU Ivanchuk, SM Myers, SM Eng, C Mulligan, LM AF Ivanchuk, SM Myers, SM Eng, C Mulligan, LM TI De novo mutation of GDNF, ligand for the RET/GDNFR-alpha receptor complex, in Hirschsprung disease SO HUMAN MOLECULAR GENETICS LA English DT Article ID RET PROTOONCOGENE; TYROSINE KINASE AB Hirschsprung disease (HSCR) is a common congenital abnormality characterized by absence of the enteric ganglia in the hind gut. In 10-40% of HSCR cases, mutations of the RET receptor tyrosine kinase have been found, The recent identification of a multimeric RET ligand/receptor complex suggested that mutations of genes encoding other components of this complex might also occur in HSCR. To investigate this role, we examined the gene for glial cell line-derived neurotrophic factor (GDNF), the circulating ligand of the RET receptor complex, for mutations in a panel of sporadic and familial HSCR. We identified GDNF sequence variants in 2/36 HSCR patients, The first of these was a conservative change which did not affect the GDNF protein sequence, The second variant was a de novo missense mutation in a family with no history of HSCR and without mutation of the RET gene, Thus, our data are consistent with a causative role for GDNF mutations in some HSCR cases. C1 QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. QUEENS UNIV,DEPT PAEDIAT,KINGSTON,ON K7L 3N6,CANADA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. NR 19 TC 91 Z9 95 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC PY 1996 VL 5 IS 12 BP 2023 EP 2026 DI 10.1093/hmg/5.12.2023 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA VX747 UT WOS:A1996VX74700024 PM 8968758 ER PT J AU Granter, SR Renshaw, AA Fletcher, CDM Bhan, AK Rosenberg, AE AF Granter, SR Renshaw, AA Fletcher, CDM Bhan, AK Rosenberg, AE TI CD99 reactivity in mesenchymal chondrosarcoma SO HUMAN PATHOLOGY LA English DT Article DE MIC2; O13; CDSS; immunohistochemistry; mesenchymal chondrosarcoma; Ewing's sarcoma; primitive neuroectodermal tumors ID CELL-SURFACE ANTIGEN; EWINGS-SARCOMA; IMMUNOHISTOCHEMICAL ANALYSIS; HISTOGENESIS; TUMORS; MIC2; BONE; P30/32(MIC2); OSTEOSARCOMA; EXPERIENCE AB CD99 reactivity has been reported to be a sensitive and specific marker for Ewing's sarcoma (ES) and primitive neuroectodermal tumor (PNET). However, within the group of ''small round blue cell tumors,'' the specificity has not been extensively examined. We investigated the immunoreactivity of mesenchymal chondrosarcoma to CD99 using the O13 antibody and found reactivity in 11 of 11 (100%) of cases, specifically in the ''small round blue cell'' component. All cases showed strong reactivity involving more than 50% of the small round blue cells with a distinct membrane pattern of staining. Staining was either absent or focal and weak in cartilaginous areas. We conclude that mesenchymal chondrosarcoma cannot be distinguished from ES/PNET on the basis of CD99 immunoreactivity. Copyright (C) 1996 by W.B. Saunders Company C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Granter, SR (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 22 TC 83 Z9 93 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD DEC PY 1996 VL 27 IS 12 BP 1273 EP 1276 DI 10.1016/S0046-8177(96)90336-6 PG 4 WC Pathology SC Pathology GA VX746 UT WOS:A1996VX74600006 PM 8958297 ER PT J AU Pogue, BW Hasan, T AF Pogue, BW Hasan, T TI Fluorophore quantitation in tissue-simulating media with confocal detection SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article ID LASER-INDUCED FLUORESCENCE; MODEL; LIGHT; SPECTROSCOPY; LOCALIZATION; SCATTERING; PHANTOMS; TUMORS; RATS; FLUX AB Fluorescence measurements from tissue are increasingly being used as a medical diagnostic procedure to assess tissue malignancy or tissue function, Unfortunately, the remitted fluorescent intensity measured from a tissue surface is not necessarily proportional to the fluorophore concentration because the light is altered by the tissue's intrinsic absorption and scattering properties, By measuring fluorescence from tissue volumes which are smaller than the average scattering length, the effects of the tissue's intrinsic absorption are diminished, Zn this study, experiments with tissue simulating phantoms are used, as well as Monte Carlo simulations of the experiment, to demonstrate the utility of point fluorescence detection for diagnostic measurements, Potential applications of this technique range from photosensitizer quantitation in vivo, pharmacokinetic measurements of fluorophore in different tissues, to any application where fluorophore quantification is required from a highly scattering medium. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. NR 32 TC 28 Z9 28 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD DEC PY 1996 VL 2 IS 4 BP 959 EP 964 DI 10.1109/2944.577322 PG 6 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA XD616 UT WOS:A1996XD61600021 ER PT J AU SchmidtErfurth, U Birngruber, R Hasan, T AF SchmidtErfurth, U Birngruber, R Hasan, T TI Photodynamic therapy in ocular vascular disease SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; RECEPTOR ACTIVITY; PLASMA-LIPOPROTEINS; SINGLET OXYGEN; CELLS-INVITRO; MURINE TUMOR; HEMATOPORPHYRIN; INVIVO; BENZOPORPHYRIN; RETINOBLASTOMA AB Photodynamic therapy (PDT) is a novel therapeutical approach which is noninvasive and potentially selective for neoplastic pathologies, Association of photosensitizers with low density lipoprotein (LDL) leads to direct targeting of the treated lesions with enhanced efficiency and selectivity. LDL-mediated PDT is particularly useful in the treatment of neovascular structures since LDL receptors are abundantly expressed on vascular endothelial cells, To evaluate the potential of selective photodynamic vasoocclusion in ocular neovascular disease a sequence of experiments was designed: Efficiency of the LDL-carrier was tested in vitro, the system was then transfered to an in vivo model demonstrating a vascularized neoplasm, Occlusion was successfully performed in experimentally induced neovascularization in the cornea, while selective photothrombosis of subretinal vasculature revealed lack of collateral damage, The experimental results were used to establish a first clinical trial for the use of PDT in age-related macular degeneration, one of the leading causes for blindness. C1 MED LASERZENTRUM LUBECK,D-23562 LUBECK,GERMANY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. RP SchmidtErfurth, U (reprint author), UNIV LUBECK,HOSP EYE,D-23538 LUBECK,GERMANY. RI Birngruber, Reginald/Q-2342-2016 NR 57 TC 5 Z9 5 U1 1 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD DEC PY 1996 VL 2 IS 4 BP 988 EP 996 DI 10.1109/2944.577328 PG 9 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA XD616 UT WOS:A1996XD61600025 ER PT J AU Ho, BKT Tsai, MJ Wei, J Ma, M Saipetch, P AF Ho, BKT Tsai, MJ Wei, J Ma, M Saipetch, P TI Video compression of coronary angiograms based on discrete wavelet transform with block classification SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article ID RADIOLOGICAL IMAGE COMPRESSION; FULL-FRAME; MOTION COMPENSATION; IMPLEMENTATION; MODULE; DESIGN; JPEG AB A new method of video compression for angiographic images has beers developed to achieve high compression ratio (similar to 20:1) while eliminating block artifacts which leads to loss of diagnostic accuracy. This method adopts motion picture experts group's (MPEG's) motion compensated prediction to takes advantage of frame to frame correlation. However, in contrast to MPEG, the error images arising from mismatches in the motion estimation are encoded bg discrete wavelet transform (DWT) rather than block discrete cosine transform (DCT). Furthermore, we developed a classification scheme which label each block in an image as intra, error, or background type and encode it accordingly. This hybrid coding can significantly improve the compression efficiency in certain cases. This method can be generalized for any dynamic image sequences applications sensitive to block artifacts. C1 UNIV CALIF LOS ANGELES, DEPT COMP SCI, LOS ANGELES, CA 90032 USA. ATRIUM TECHNOL CO LTD, BANGKOK, THAILAND. UNIV CALIF LOS ANGELES, DEPT ELECT ENGN, LOS ANGELES, CA 90032 USA. RP HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT RADIOL, WHT 292, BOSTON, MA 02114 USA. NR 50 TC 7 Z9 7 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD DEC PY 1996 VL 15 IS 6 BP 814 EP 823 DI 10.1109/42.544499 PG 10 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA VV634 UT WOS:A1996VV63400006 PM 18215961 ER PT J AU Wang, JH Nichogiannopoulou, A Wu, L Sun, L Sharpe, AH Bigby, M Georgopoulos, K AF Wang, JH Nichogiannopoulou, A Wu, L Sun, L Sharpe, AH Bigby, M Georgopoulos, K TI Selective defects in the development of the fetal and adult lymphoid system in mice with an Ikaros null mutation SO IMMUNITY LA English DT Article ID DENDRITIC EPIDERMAL-CELLS; HEMATOPOIETIC STEM-CELLS; NATURAL-KILLER-CELLS; DELTA-T-CELLS; MOUSE THYMUS; TRANSCRIPTION FACTOR; PRECURSOR CELLS; GENE; DIFFERENTIATION; THYMOCYTES AB Mice homozygous for an Ikaros null mutation display distinct defects in the development of fetal and adult lymphocytes. Fetal T lymphocytes, and fetal and adult B lymphocytes and their earliest progenitors are absent. Postnatally, hematopoietic stem cells give rise to thymocyte precursors that undergo aberrant differentiation into the CD4 lineage and clonal expansion. The lack of NK cells and some gamma delta T cell subsets and a large reduction in thymic dendritic APCs suggest that Ikaros is essential for establishing early branch points in the postnatal T cell pathway. The lymphoid defects detected in Ikaros null mice reveal critical molecular differences between fetal and postnatal hematopoietic progenitors that dictate their ability to give rise to T cells, These studies also establish Ikaros as a tumor suppressor gene acting during thymocyte differentiation, Phenotypic comparison of this null mutation with a severe dominant-negative Ikaros mutation identifies molecular redundancy in the postnatal hemo-lymphoid system. C1 WALTER & ELIZA HALL INST MED RES, MELBOURNE, VIC 3050, AUSTRALIA. HARVARD UNIV, SCH MED, BRIGHAM & WOMENS HOSP, DIV IMMUNOL RES, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BRIGHAM & WOMENS HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. RP Wang, JH (reprint author), HARVARD UNIV, SCH MED, MASSACHUSETTS GEN HOSP, CUTANEOUS BIOL RES CTR, CHARLESTOWN, MA 02129 USA. FU NCI NIH HHS [CA-06927]; PHS HHS [A1-26782] NR 45 TC 410 Z9 414 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 1996 VL 5 IS 6 BP 537 EP 549 DI 10.1016/S1074-7613(00)80269-1 PG 13 WC Immunology SC Immunology GA WA651 UT WOS:A1996WA65100005 PM 8986714 ER PT J AU Castro, JE Listman, JA Jacobson, BA Wang, YS Lopez, PA Ju, ST Finn, PW Perkins, DL AF Castro, JE Listman, JA Jacobson, BA Wang, YS Lopez, PA Ju, ST Finn, PW Perkins, DL TI Fas modulation of apoptosis during negative selection of thymocytes SO IMMUNITY LA English DT Article ID MRL-LPR/LPR MICE; IMMATURE CD4+8+ THYMOCYTES; PROGRAMMED CELL-DEATH; TUMOR-NECROSIS-FACTOR; MATURE T-CELLS; LPR MICE; CD4(+)CD8(+) THYMOCYTES; MONOCLONAL-ANTIBODIES; CD4+CD8+ THYMOCYTES; POSITIVE SELECTION AB A major mechanism maintaining immune tolerance is the deletion of potentially autoreactive thymocytes by apoptosis during development in the thymus, Previous reports suggest that apoptosis is induced by high avidity signals transduced via the T cell receptor; however, the role of signals transduced by other cell surface receptors during thymic selection remains poorly understood. Fas, a member of the TNF receptor family, has been shown to induce apoptosis in mature peripheral T cells; however, the effects of Fas on negative selection of thymocytes have not been previously detected. Using a sensitive terminal deoxynucleotidyl transferase method to detect apoptotic cells, we found that mutant Pas molecules in lpr mice decrease the sensitivity of thymocytes to T cell receptor-mediated apoptosis and that blockade of Fas-Fas ligand interactions in vivo can inhibit antigen-induced apoptosis of thymocytes in non-lpr mice. Thus, we have shown that Fas, in conjunction with antigen-specific signals, can modulate apoptosis during negative selection of thymocytes. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV PULM,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,LAB IMMUNOGENET & TRANSPLANTAT,RENAL DIV,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV RENAL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. BOSTON UNIV,MED CTR,DEPT MICROBIOL,BOSTON,MA 02118. BOSTON UNIV,MED CTR,DEPT MED,CTR ARTHRITIS,BOSTON,MA 02118. DANA FARBER CANC INST,CORE FLOW CYTOMETRY FACIL,BOSTON,MA 02115. RP Castro, JE (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV PULM,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI33100]; NIEHS NIH HHS [ES01065] NR 57 TC 116 Z9 117 U1 2 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 1996 VL 5 IS 6 BP 617 EP 627 DI 10.1016/S1074-7613(00)80275-7 PG 11 WC Immunology SC Immunology GA WA651 UT WOS:A1996WA65100011 PM 8986720 ER PT J AU Coxon, A Rieu, P Barkalow, FJ Askari, S Sharpe, AH vonAndrian, UH Arnaout, MA Mayadas, TN AF Coxon, A Rieu, P Barkalow, FJ Askari, S Sharpe, AH vonAndrian, UH Arnaout, MA Mayadas, TN TI A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosis: A homeostatic mechanism in inflammation SO IMMUNITY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; LEUKOCYTE ADHESION MOLECULES; PROGRAMMED CELL-DEATH; RECURRENT BACTERIAL-INFECTIONS; SELECTIN-DEFICIENT MICE; RESPIRATORY BURST; TYROSINE PHOSPHORYLATION; VITRONECTIN RECEPTOR; INHERITED DEFECT; CR3 CD11B/CD18 AB In mice selectively deficient in CD11b/CD18, a beta 2 integrin, chemoattractant-induced leukocyte adhesion to microvascular endothelium in vivo was reduced. Paradoxically, thioglycollate-induced neutrophil accumulation in the peritoneal cavity was increased and was associated with a significant delay in apoptosis of extravasated cells. The extravasated cells had a near absence of neutrophil phagocytosis and a reduction in oxygen free radical generation, which may contribute to the observed defect in apoptosis, This is supported by our in vitro studies, in which phagocytosis of opsonized particles by human neutrophils rapidly induced apoptosis that could be blocked with CD11b/CD18 antibodies, Reactive oxygen species are the intracellular link in this process: phagocytosis-induced apoptosis was blocked both in neutrophils treated with the flavoprotein inhibitor diphenylene iodonium and in neutrophils from patients with chronic granulomatous disease, which lack NADPH oxidase. Thus, CD11b/CD18 plays a novel and unsuspected homeostatic role in inflammation by accelerating the programmed elimination of extravasated neutrophils. C1 HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, CTR BLOOD RES, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED, LEUKOCYTE BIOL & INFLAMMAT PROGRAM,RENAL DIV, BOSTON, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008 FU NIDDK NIH HHS [DK-48549]; NINDS NIH HHS [NS33296]; PHS HHS [P0150305] NR 73 TC 444 Z9 447 U1 3 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD DEC PY 1996 VL 5 IS 6 BP 653 EP 666 DI 10.1016/S1074-7613(00)80278-2 PG 14 WC Immunology SC Immunology GA WA651 UT WOS:A1996WA65100014 PM 8986723 ER PT J AU Israel, EJ Wilsker, DF Hayes, KC Schoenfeld, D Simister, NE AF Israel, EJ Wilsker, DF Hayes, KC Schoenfeld, D Simister, NE TI Increased clearance of IgG in mice that lack beta(2)-microglobulin: Possible protective role of FcRn SO IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY THERAPY; IMMUNOGLOBULIN-G; RAT INTESTINE; HALF-LIVES; RECEPTOR; MHC; BINDING; COMPLEX; MOUSE; CELLS AB The mechanisms that regulate immunoglobulin G (IgG) catabolism are little understood. We have previously found unusually low IgG concentrations in sera of mice homozygous for a targeted disruption of the beta(2)-microglobulin gene. We therefore investigated whether this might result, at least in part, from increased clearance of IgG from the systemic circulation in mice lacking beta(2)-microglobulin. We compared the half-lives of radiolabelled mouse IgG1 injected intravenously into beta(2)-microglobulin(-/-) mice and wild-type or heterozygous siblings. The clearance of I-125-labelled IgG1 was strikingly more rapid in the mice lacking beta(2)-microglobulin. beta(2)-microglobulin(-/-) mice lack functional molecules of the MHC class I-related Fc receptor, FcRn. Some mutations in mouse IgG1 that increase its clearance have recently been shown to prevent binding to FcRn in the gut. To determine whether the slower degradation of immunoglobulin in mice with beta(2)- microglobulin correlated with the ability of the antibody to bind FcRn, we measured the clearance of chicken IgY, which does not bind this receptor. The I-125-labelled IgY was catabolized equally rapidly in beta(2)-microglobulin-deficient and wild-type mice. We compared the half-lives of the four subclasses of mouse IgG in beta(2)-microglobulin(-/-), (+/-), and (+/+) mice to determine whether the difference we had noted for IgG1 was peculiar to this subclass. The I-125-labelled IgG of all subclasses, with the possible exception of IgG2b, was degraded more rapidly in the beta(2)-microglobulin-deficient mice than in heterozygous or wild-type siblings. These data suggest that FcRn can protect IgG from degradation, and is therefore important in maintaining IgG levels in the circulation. C1 BRANDEIS UNIV,ROSENSTIEL BASIC MED SCI RES CTR,WALTHAM,MA 02254. BRANDEIS UNIV,DEPT BIOL,WALTHAM,MA 02254. MASSACHUSETTS GEN HOSP,DEPT MED,CTR BIOSTAT,BOSTON,MA 02114. RP Israel, EJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,VBK 107,BOSTON,MA 02114, USA. FU NICHD NIH HHS [HD00938, HD12437, HD31852] NR 47 TC 219 Z9 224 U1 0 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 1996 VL 89 IS 4 BP 573 EP 578 DI 10.1046/j.1365-2567.1996.d01-775.x PG 6 WC Immunology SC Immunology GA VY648 UT WOS:A1996VY64800016 PM 9014824 ER PT J AU Wood, K Sachs, DH AF Wood, K Sachs, DH TI Chimerism and transplantation tolerance: Cause and effect SO IMMUNOLOGY TODAY LA English DT Article ID BONE-MARROW TRANSPLANTATION; DONOR-TYPE MICROCHIMERISM; KIDNEY ALLOGRAFTS; DENDRITIC CELLS; ORGAN-TRANSPLANTATION; CARDIAC ALLOGRAFTS; T-CELLS; MIGRATION; RECIPIENTS; INDUCTION AB Evidence for persistence of donor leukocytes in recipients of long-term organ allografts has prompted the hypothesis that such microchimerism is not only essential to graft survival but that donor and host cells both play active roles. Here, Kathryn Wood and David Sachs caution that the jury is still out on whether such microchimerism is the cause or merely the consequence of long-term allografting. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. RP Wood, K (reprint author), UNIV OXFORD,JOHN RADCLIFFE HOSP,NUFFIELD DEPT SURG,OXFORD OX3 9DU,ENGLAND. NR 35 TC 140 Z9 143 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD DEC PY 1996 VL 17 IS 12 BP 584 EP 587 DI 10.1016/S0167-5699(96)10069-4 PG 4 WC Immunology SC Immunology GA WA035 UT WOS:A1996WA03500013 PM 8991291 ER PT J AU Worden, JW AF Worden, JW TI Dealing with grief - Introduction SO IN SESSION-PSYCHOTHERAPY IN PRACTICE LA English DT Editorial Material C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CAMBRIDGE,MA 02138. NR 0 TC 0 Z9 0 U1 1 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1077-2413 J9 IN SESSION-PSYCHOTH JI In Session-Psychother. Pract. PD WIN PY 1996 VL 2 IS 4 BP 1 EP 2 PG 2 WC Psychology, Clinical SC Psychology GA VT113 UT WOS:A1996VT11300001 ER PT J AU Worden, JW AF Worden, JW TI Tasks and mediators of mourning: A guideline for the mental health practitioner SO IN SESSION-PSYCHOTHERAPY IN PRACTICE LA English DT Article DE mourning; social mediators; personality factors AB Clinicians who work with bereaved individuals around grief issues need a way to understand tbe process of mourning. Generally, the mourning process can be conceptualized as involving either stages, phases, or tasks. In this article the author selects the task model and outlines the tasks of mourning as well as identifying 6 mediators of mourning that influence both the grief experience and duration of the bereavement course. This model is useful for working with both complicated and uncomplicated bereavement. (C) 1996 John Wiley & Sons, Inc. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CAMBRIDGE,MA 02138. NR 12 TC 6 Z9 6 U1 1 U2 5 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1077-2413 J9 IN SESSION-PSYCHOTH JI In Session-Psychother. Pract. PD WIN PY 1996 VL 2 IS 4 BP 73 EP 80 PG 8 WC Psychology, Clinical SC Psychology GA VT113 UT WOS:A1996VT11300007 ER PT J AU Winter, H Grand, R AF Winter, H Grand, R TI Medical therapy for children with inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Review ID DISTAL ULCERATIVE-COLITIS; CROHNS-DISEASE; CYCLOSPORINE-A; GROWTH FAILURE; ADOLESCENTS; CHILDHOOD; ENEMAS C1 CHILDRENS HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. TUFTS UNIV NEW ENGLAND MED CTR,DIV PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02111. RP Winter, H (reprint author), BOSTON MED CTR,DEPT PEDIAT GI & NUTR,801 ALBANY ST,S402,BOSTON,MA 02118, USA. NR 45 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD WIN PY 1996 VL 2 IS 4 BP 269 EP 275 DI 10.1002/ibd.3780020410 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VX311 UT WOS:A1996VX31100009 PM 23282595 ER PT J AU Sands, BE AF Sands, BE TI Taking aim at P SO INFLAMMATORY BOWEL DISEASES LA English DT Article RP Sands, BE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD WIN PY 1996 VL 2 IS 4 BP 310 EP 311 DI 10.1002/ibd.3780020416 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VX311 UT WOS:A1996VX31100015 PM 23282601 ER PT J AU Moro, O Tajima, M Lerner, EA AF Moro, O Tajima, M Lerner, EA TI Receptors for the vasodilator maxadilan are expressed on selected neural crest and smooth muscle-derived cells SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE G-protein coupled receptor; maxadilan; second messenger; CAMP; sandfly; leishmaniasis ID CYCLIC-AMP FORMATION; MACROPHAGE FUNCTION; PEPTIDE RECEPTORS; ADRENOMEDULLIN AB Maxadilan is a potent vasodilator peptide isolated from salivary glands of the blood feeding sand fly Lutzomyia longipalpis. The peptide relaxes rabbit aortic rings in an endothelium independent manner while elevating levels of cAMP and has been found to bind to membrane homogenates from brain, These studies on tissues have now been expanded with an examination of binding and signaling of maxadilan to a number of established cell lines and primary cultures, The data reveal that maxadilan binds to and stimulates the accumulation of cAMP in the rat pheochromocytoma line PC12 and the human neuroblastoma line NBfl. Accumulation of cAMP occurred in a transformed mouse pancreatic smooth muscle line (MILE) and primary rabbit aorta smooth muscle cells, The peptide did not bind to or induce cAMP formation in the rat thoracic aorta line L6. Scatchard analysis of binding to the PC12 and NBfl lines indicates that maxadilan binds to a single class of high-affinity receptors. Similar pharmacologic actions and possible structural homologies between maxadilan and calcitonin gene-related peptide (CGRP) suggested the possibility that they shared receptors. However, competition studies and comparative second messenger analysis reveal that maxadilan does not interact with receptors for CGRP, amylin or adrenomedullin and suggest that this peptide may bind to a novel receptor whose endogenous ligand remains unknown. Copyright (C) 1997 Elsevier Science Ltd. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. SHISEIDO LIFE SCI LAB,YOKOHAMA,KANAGAWA 236,JAPAN. FU NIAMS NIH HHS [R01 AR42005] NR 15 TC 11 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD DEC PY 1996 VL 26 IS 10 BP 1019 EP 1025 DI 10.1016/S0965-1748(96)00025-2 PG 7 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA WG403 UT WOS:A1996WG40300004 PM 9035385 ER PT J AU Bromley, B Benacerraf, BR AF Bromley, B Benacerraf, BR TI Acute reversal of oligohydramnios-polyhydramnios sequence in monochorionic twins SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE twin-to-twin transfusion; oligohydramnios; polyhydramnios ID TRANSFUSION SYNDROME; REMISSION; HYDROPS AB Two cases of monochorionic diamniotic twin gestation with severe oligohydramnios-polyhydramnios sequence ('stuck' twin) are described. In each of these cases there was a marked fluctuation in amniotic fluid volume and reversal of which twin was 'stuck'. The definitive identification of the twins was evident due to a discordant fetal malformations in each twin pair. Copyright (C) 1996 International Federation of Gynecology and Obstetrics. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNECOL & RADIOL,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. NR 6 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD DEC PY 1996 VL 55 IS 3 BP 281 EP 283 DI 10.1016/S0020-7292(96)02771-3 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA WA021 UT WOS:A1996WA02100011 PM 9003954 ER PT J AU Maxwell, M Galanopoulos, T Antoniades, HN AF Maxwell, M Galanopoulos, T Antoniades, HN TI Expression of cyclin D1 proto-oncogene mRNA in primary meningiomas may contribute to tumorigenesis SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE meningioma; cyclins; cell-cycle; tumorigenesis ID CELL NUCLEAR ANTIGEN; TUMOR PROGRESSION; MESSENGER-RNAS; GENE; CANCER; RECEPTORS; NEUROFIBROMATOSIS-2; AMPLIFICATION; RECURRENCE; DELETIONS AB Meningiomas are benign brain tumors thought to arise by multi-step tumorigenesis, involving both the activation of oncogenes and the loss of tumor suppressor genes. The cell cycle regulator proto-oncogene cyclin D1 has been implicated in the pathogenesis of several types of cancer. Northern blot analysis revealed expression of cyclin D1 mRNA in 8 (53%), and cyclin B mRNA in 12 of 14 (86%), primary meningiomas. Immunocytochemistry using an antibody specific for cyclin D1 showed strong positivity amongst meningeal cells in the same meningioma samples. No cyclin D1 mRNA was detected in a sample of normal pachymeninges. Cyclin B, which has not yet been linked to tumorigenesis and serves as a marker for cellular proliferation, was expressed in a higher proportion of meningioma samples. These data provide the first evidence for the overexpression of cyclin D1 and B mRNA and protein in primary human meningiomas, and are consistent with a proposed oncogenic role of cyclin D1 in tumorigenesis. Excessive levels of the cyclin D1 proto-oncogene may lead to deregulation of G1 control in a proportion of arachnoid cap cells leading to tumorigenesis. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02114. RP Maxwell, M (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,HOUSE MAIL,BOSTON,MA 02114, USA. NR 45 TC 1 Z9 1 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 DEC PY 1996 VL 9 IS 6 BP 1213 EP 1217 PG 5 WC Oncology SC Oncology GA VU549 UT WOS:A1996VU54900015 PM 21541630 ER PT J AU Chow, CYC Foster, CS AF Chow, CYC Foster, CS TI Mooren's ulcer SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID PENETRATING KERATOPLASTY; INFLAMMATORY DISEASE; CYCLOSPORINE-A; THERAPY; GRAFT AB Mooren's ulcer of the cornea, also known as chronic serpiginous ulcer and ulcus rodens, was first described by Bowman in 1849 [1]. Mooren, in 1867, published cases describing the disorder in detail and establishing it as a distinct clinical entity [1]. Mooren's ulcer is a painful, relentless, chronic ulcerative keratitis that begins peripherally and progresses circumferentially and centrally. It is, by definition, idiopathic, meaning that it occurs in the absence of any systemic disorder to which an ulcerative keratitis may be attributed. Its exact pathophysiology remains uncertain. Advances have been made in the management of this disorder, but a significant percentage of cases remain refractory to available therapies and result in severe visual morbidity. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. NR 54 TC 27 Z9 28 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 1 EP 13 DI 10.1097/00004397-199603610-00003 PG 13 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100002 PM 8778056 ER PT J AU Colby, K Dohlman, C AF Colby, K Dohlman, C TI Vernal keratoconjunctivitis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID CROMOLYN SODIUM; CONJUNCTIVITIS; CYCLOSPORINE; EFFICACY; ASPIRIN; THERAPY AB Vernal keratoconjunctivitis (VKC) is a bilateral, recurrent inflammatory disorder of the conjunctiva and cornea. Vernal comes from the Greek, meaning ''occurring in the spring,'' and aptly describes the usual seasonal predilection of VKC. Although generally believed to be a benign and self-limiting condition, VKC has the potential to produce serious visual consequences, not only as a result of the disease itself but also as a complication of its treatment. This chapter reviews the clinical and epidemiological features, pathogenesis, differential diagnosis, and treatment of this disorder. RP Colby, K (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL OPHTHALM EDUC,243 CHARLES ST,BOSTON,MA 02114, USA. NR 26 TC 11 Z9 12 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 15 EP 20 DI 10.1097/00004397-199603610-00004 PG 6 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100003 PM 8778061 ER PT J AU Gregory, JK Foster, CS AF Gregory, JK Foster, CS TI Peripheral ulcerative keratitis in the collagen vascular diseases SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; RELAPSING POLYCHONDRITIS; WEGENERS GRANULOMATOSIS; NECROTIZING SCLERITIS; CORNEAL AUTOIMMUNITY; ASSOCIATION; THERAPY AB Peripheral ulcerative keratitis (PUK) is a crescent-shaped destructive lesion of the juxtalimbal corneal stroma associated with an epithelial defect and stromal inflammatory cell infiltrate. PUK occurs in a variety of ocular and systemic conditions (Table). In one study of noninfectious PUK patients, approximately one-half of the cases occurred in patients with collagen vascular diseases, often as the disease's initial manifestation [1]. Patients with collagen vascular disease-related PUK often require aggressive systemic treatment to stop the relentless progression of corneal destruction. In these patients, PUK is viewed as the heralding of a systemic and possibly life-threatening vasculitis that requires systemic immunosuppressive therapy. RP Gregory, JK (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114, USA. NR 37 TC 11 Z9 13 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 21 EP 30 DI 10.1097/00004397-199603610-00005 PG 10 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100004 PM 8778066 ER PT J AU You, T PavanLangston, D AF You, T PavanLangston, D TI Immune reactions in corneal herpetic disease SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID KERATITIS; SIMPLEX AB The destructive effects of herpetic ocular involvement involve both the cytotoxic effects of the viral particles directly and a variety of immunological mechanisms that are activated even after the acute stage of infectious disease has passed. These so-called noninfectious immune reactions represent a host response to rid the body of an antigen that can never be completely eradicated. Herpes simplex virus (HSV) presents in several ways, including infectious epithelial keratitis and keratouveitis, and as several conditions that have a proposed immunological basis. In managing herpetic conditions, one should always consider these immune-based phenomena, as erroneous treatment directed only toward the virus can result in progressive injury to the eye. The clinical and experimental support for the immune response accompanying HSV keratitis is well established. These changes are classified on the basis of the structures involved. First, a low-grade immune response can be associated with epithelial basement membrane changes in epithelial trophic ulcers. Second, the stroma can involve several types of reactions, including stromal interstitial keratitis, Wessely immune rings, limbitis, and disciform keratitis. Third, an immunological basis is believed to be responsible for the endotheliitis that can accompany herpetic disease. Clearly, there are other forms of herpetic involvement that are, in part, immune-based, such as herpetic iridocyclitis, but this chapter is limited to those involving the cornea. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 31 EP 39 DI 10.1097/00004397-199603610-00006 PG 9 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100005 PM 8778067 ER PT J AU Nguyen, QD Foster, CS AF Nguyen, QD Foster, CS TI Cicatricial pemphigoid: Diagnosis and treatment SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID IMMUNOSUPPRESSIVE THERAPY; CONJUNCTIVA; IMMUNOFLUORESCENCE; AUTOANTIBODIES; ASSOCIATION; FEATURES; DISTINCT AB Cicatricial pemphigoid (CP) is a systemic autoimmune disease with both ocular and nonocular manifestations. CP, unlike bullous pemphigoid, produces scarring of the affected skin [1, 2]. It can lead to catastrophic ophthalmic consequences, such as bilateral blindness due to corneal scarring. CP also can be fatal when it produces strictures from scarring in the esophagus or in the trachea. Histopathological and immunopathological studies indicate a possible defect in immunoregulation [1]. It is critically important that the diagnosis be made early, with conjunctival biopsy and immunohistochemistry. Progression of the disease can be halted only through systemic chemotherapeutic strategies. Reconstructive surgery can be performed only after all inflammatory activities have been controlled with chemotherapy. RP Nguyen, QD (reprint author), HARVARD UNIV, MASSACHUSETTS EYE & EAR INFIRM, SCH MED, DEPT OPHTHALMOL, 243 CHARLES ST, BOSTON, MA 02114 USA. NR 52 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 41 EP 60 DI 10.1097/00004397-199603610-00007 PG 20 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100006 PM 8778068 ER PT J AU Chynn, EW Jakobiec, FA AF Chynn, EW Jakobiec, FA TI Cogan's syndrome: Ophthalmic, audiovestibular, and systemic manifestations and therapy SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID INTERSTITIAL KERATITIS; INVOLVEMENT; VASCULITIS AB Cogan's syndrome (CS) is a rare multisystem disease characterized by acute nonsyphilitic interstitial keratitis and audiovestibular dysfunction including neurosensory hearing loss, tinnitus, and vertigo. This disease was first recognized as a discrete clinical entity by David Cogan in 1945, when he reported a series of 4 patients with characteristic findings, although prior isolated reports can be found in the literature [1]. The systemic associations of CS were recognized early historically by both Cogan [2-4] and others [5-8]. The most important systemic manifestations include vasculitis and aortic insufficiency. The accurate diagnosis of CS assumes an importance disproportionate to its incidence, as early systemic steroid therapy may prevent permanent deafness, whereas systemic workup and management can prevent life-threatening complications. RP Chynn, EW (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 46 TC 31 Z9 33 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 61 EP 72 DI 10.1097/00004397-199603610-00008 PG 12 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100007 PM 8778069 ER PT J AU Legmann, A Foster, CS AF Legmann, A Foster, CS TI Noninfectious necrotizing scleritis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID IMMUNOSUPPRESSIVE THERAPY; SCLERAL DISEASE AB Anterior scleritis comprises approximately 94% of scleritis cases [1]. The classification system of Watson and coworkers [2, 3] for anterior scleritis (diffuse, nodular, necrotizing, and scleromalacia perforans) is useful to the clinician, as pronounced differences exist in each type's association with systemic disease and in its response to selected therapy. Fewer than 10% of patients progress from one type of scleritis to another [2]. Necrotizing scleritis is the specific subtype of anterior scleritis toward which the remainder of this chapter will be directed. RP Legmann, A (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 23 TC 3 Z9 3 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 73 EP 80 DI 10.1097/00004397-199603610-00009 PG 8 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100008 PM 8778070 ER PT J AU Kwon, YH Dreyer, EB AF Kwon, YH Dreyer, EB TI Inflammatory glaucomas SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID JUVENILE RHEUMATOID-ARTHRITIS; FUCHS HETEROCHROMIC IRIDOCYCLITIS; REFRACTORY GLAUCOMA; MITOMYCIN-C; TRABECULECTOMY; UVEITIS; 5-FLUOROURACIL; MANIFESTATIONS; APRACLONIDINE; SARCOIDOSIS AB Symptoms of ocular inflammation commonly include pain, photophobia, and tearing. Ocular examination may reveal conjunctival injection, ciliary flush, iridocyclitis, vitritis, retinitis, choroiditis, or papillitis. In addition, ocular inflammation can lead to keratopathy, peripheral anterior synechiae, posterior synechiae, cataract, chorioretinal atrophy, optic atrophy, and secondary glaucoma. RP Kwon, YH (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 55 TC 2 Z9 2 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 81 EP 89 DI 10.1097/00004397-199603610-00010 PG 9 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100009 PM 8778071 ER PT J AU Ceisler, EJ Foster, CS AF Ceisler, EJ Foster, CS TI Juvenile rheumatoid arthritis and uveitis: Minimizing the blinding complications SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID CARBONIC-ANHYDRASE INHIBITORS; INDUCED CHROMOSOME-DAMAGE; CHRONIC IRIDOCYCLITIS; ANTINUCLEAR ANTIBODIES; CATARACT-EXTRACTION; ANTERIOR UVEITIS; CHILDREN; METHOTREXATE; CHLORAMBUCIL; THERAPY C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. NR 72 TC 6 Z9 6 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 91 EP 107 DI 10.1097/00004397-199603610-00011 PG 17 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100010 PM 8778072 ER PT J AU Smith, JA Foster, CS AF Smith, JA Foster, CS TI Sarcoidosis and its ocular manifestations SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID ANGIOTENSIN-CONVERTING-ENZYME; INFLAMMATORY GLAUCOMA; METHOTREXATE; INVOLVEMENT; DIAGNOSIS; DISEASE; TRABECULODIALYSIS; RADIOTHERAPY; RECOGNITION; GRANULOMAS RP Smith, JA (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL OPHTHALM EDUC,243 CHARLES ST,BOSTON,MA 02114, USA. NR 77 TC 34 Z9 34 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 109 EP 125 DI 10.1097/00004397-199603610-00012 PG 17 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100011 PM 8778057 ER PT J AU Bhisitkul, RB Foster, CS AF Bhisitkul, RB Foster, CS TI Diagnosis and ophthalmological features of Behcet's disease SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article AB Behcet's disease (ED) is a chronic systemic vasculitic disease of unknown etiology that is characterized by uveitis and retinal vasculitis, oral and genital aphthous ulcers, central nervous system (CNS) vasculitis, and dermatological findings [1]. Significant morbidity can develop during the relapsing and remitting course of ED, and loss of eyesight is a frequent outcome. Complications of ED or its treatment can be lethal. Described by the Turkish dermatologist Hulusi Behlet in 1937 as a triad of oral ulcers, genital ulcers, and hypopyon uveitis, the definition has since been expanded and modified to include multisystemic clinical features. In this chapter, we review these highly diverse clinical manifestations and the diagnostic criteria of ED, with an emphasis on its ophthalmological characteristics. C1 HARVARD UNIV, SCH MED, MASSACHUSETTS EYE & EAR INFIRM, DEPT OPHTHALMOL, BOSTON, MA USA. NR 19 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 127 EP 134 DI 10.1097/00004397-199603610-00013 PG 8 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100012 PM 8778058 ER PT J AU Ciulla, TA Gragoudas, ES AF Ciulla, TA Gragoudas, ES TI Serpiginous choroiditis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID PLACOID PIGMENT EPITHELIOPATHY; CHOROIDOPATHY; NEOVASCULARIZATION; PATIENT AB Serpiginous choroiditis is a rare inflammatory condition also known as geographic helicoid peripapillary choroidopathy [1], geographic choroiditis [2, 3], geographic choroidopathy [4], and geographic helicoid choroidopathy [5]. The clinical manifestations of this disease were first well described in the early 1970s: The disease affects the inner choroid and retinal pigment epithelium (RPE), causing chronically recurrent, asymmetrically bilateral, peripapillary or macular yellow-white geographical lesions [1-3, 6-8]. This disease affects healthy young or middle-aged adults, and it may affect men slightly more commonly than women [9]. There appears to be no racial predilection as it has been reported in whites, blacks, Asians, and Hispanics [10-12]. Likewise, there is no familial predisposition and no obvious association with systemic disease. In this chapter, a case is presented, and the clinical characteristics, differential diagnosis, pathogenesis, and treatment strategies are summarized. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA. NR 38 TC 13 Z9 13 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 135 EP 143 DI 10.1097/00004397-199603610-00014 PG 9 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100013 PM 8778059 ER PT J AU Kaiser, PK Gragoudas, ES AF Kaiser, PK Gragoudas, ES TI The subretinal fibrosis and uveitis syndrome SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID MULTIFOCAL CHOROIDITIS; BIRDSHOT RETINOCHOROIDOPATHY; HLA-A29 ANTIGEN AB The subretinal fibrosis and uveitis syndrome is a rare clinical entity that presents with a distinctive posterior uveitis and progresses to subretinal fibrosis. It belongs to a group of inflammatory conditions that cause multifocal lesions of the retinal pigment epithelium (RPE) and choroid and includes such entities as punctate inner choroidopathy and recurrent multifocal choroiditis. Although in some cases steroids have proved beneficial, the syndrome leads to progressive fibrotic retinal lesions with severe and permanent visual loss. The first published report of the subretinal fibrosis and uveitis syndrome was by Palestine and associates in 1984 [1]. They identified three otherwise healthy, young women with what they termed ''progressive subretinal fibrosis with uveitis syndrome'' [1]. Similar ophthalmoscopic findings were reported by Doran and Hamilton [2], who called the entity ''disciform macular degeneration in young adults.'' Later, Cantrill and Folk [3] described a group of patients with multifocal choroiditis, uveitis, and similar progressive retinal fibrosis and called the entity ''multifocal choroiditis associated with progressive subretinal fibrosis.'' Given that the retinal response to various insults is limited, it is not surprising that several names have been suggested to describe this disorder. The early clinical findings in these reports could easily be confused with several inflammatory conditions of the RPE or choriocapillaris; however, the late formation of subretinal fibrosis is unique to this entity and serves to differentiate the subretinal fibrosis and uveitis syndrome from other diseases. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA. NR 20 TC 11 Z9 11 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 145 EP 152 DI 10.1097/00004397-199603610-00015 PG 8 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100014 PM 8778060 ER PT J AU Foster, BS Mukai, S AF Foster, BS Mukai, S TI Intraocular retinoblastoma presenting as ocular and orbital inflammation SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article AB Retinoblastoma is the most common primary intraocular malignancy of childhood, usually presenting by age 3 years and only rarely after age 5 [1]. Common presenting signs include leukocoria and strabismus [2] and, with a complete, dilated, funduscopic examination, this malignancy often is accurately and expediently diagnosed. Less frequent presenting signs include hyphema, glaucoma, and inflammation. Ocular and orbital inflammation have been reported as initial signs of intraocular retinoblastoma [3-17], and both have been frequently associated with delayed or incorrect diagnosis. A delay in diagnosis can adversely affect prognosis in this potentially lethal disease. A rare subtype of retinoblastoma, diffuse infiltrating retinoblastoma, characterized by flat infiltration of the retina by tumor cells, is more likely to present with signs of intraocular inflammation and is discussed in detail in this chapter. Its demographics and diagnostic challenges, along with treatment options and prognosis, are reviewed. In addition, intraocular retinoblastoma sometimes can cause orbital inflammation. The characteristics of such cases are highlighted. The need to include retinoblastoma in the differential diagnosis of childhood ocular and orbital inflammatory conditions is stressed. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA. NR 23 TC 14 Z9 15 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 153 EP 160 DI 10.1097/00004397-199603610-00016 PG 8 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100015 PM 8778062 ER PT J AU Berger, JW Rubin, PAD Jakobiec, FA AF Berger, JW Rubin, PAD Jakobiec, FA TI Pediatric orbital pseudotumor: Case report and review of the literature SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Review ID INFLAMMATORY PSEUDOTUMOR; DIFFERENTIAL-DIAGNOSIS; CHILDHOOD; INVOLVEMENT; UVEITIS AB Inflammatory orbital pseudotumor represents an important diagnostic consideration in the approach to the patient with orbital disease. The diagnosis is applied to idiopathic orbital inflammation following exclusion of true neoplasm, primary infection, and other defined, often systemic inflammatory diseases [1]. Since the initial report by Birch-Hirschfield (as cited in Grossniklaus and coworkers [2]), there has been a rich literature describing the clinical manifestations, diagnosis, and treatment of this disorder. Pseudotumor must be distinguished from lymphoid neoplasms. In the past, these two disparate categories of orbital disease were lumped together, which obscured the natural histories of each and confounded the interpretation of therapeutic results, particularly with respect to radiotherapy (efficacious for lymphoid tumors) and corticosteroids (for pseudotumor). Inflammatory pseudotumor tends to be a more acute process, with distinctive topographical sites of involvement (Tenon's space, perioptic nerve connective tissues, lacrimal gland, extraocular muscles), and a hypocellular mixed inflammatory infiltrate with initial edema followed by progressive fibrosis. Lymphoid tumors, on the other hand, present more insidiously and usually are painless, tend to form unifocal masses in the orbit that mold to surrounding structures, and are hypercellular proliferations with a sparsity of collagen. Whereas pseudotumor can affect the orbital fat and form irregularly shaped and apparently infiltrative mass lesions as revealed by imaging studies (particularly subacute and chronic cases), because of pronounced fibrosis pseudotumors tend to be more symptomatic and cause more morbidity (motility restriction and optic nerve compression, for example) than comparably sized lymphoid tumors. Finally, although lymphoid tumors are probably the most common orbital neoplasms in adults, they are exceedingly rare in children. The bulk of the literature addresses orbital pseudotumor in adults. However, although inflammatory orbital pseudotumor is not common in the pediatric population, it is not rare. In the report of Blodi and Gass [3], 23 of 140 patients were younger than 20 years. The last major series of patients with pediatric orbital pseudotumor was presented by Jakobiec and coworkers [4, 5], but there are no recent, comprehensive reviews of the literature. To our knowledge, Grossniklaus and colleagues [2] describe the only reported case of inflammatory orbital pseudotumor in an infant. In this chapter, we present a case of a 7-month-old child with inflammatory orbital pseudotumor and review the literature regarding clinical characteristics, diagnosis, management, and prognosis. We then outline our approach to the child with orbital inflammation. RP Berger, JW (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 31 TC 15 Z9 18 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 161 EP 177 DI 10.1097/00004397-199603610-00017 PG 17 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100016 PM 8778063 ER PT J AU Lucarelli, MJ Shore, JW AF Lucarelli, MJ Shore, JW TI Management of thyroid optic neuropathy SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID TRANSFRONTAL ORBITAL DECOMPRESSION; SEVERE GRAVES OPHTHALMOPATHY; COMPUTED-TOMOGRAPHY; RADIATION-THERAPY; EYE DISEASE; RADIOTHERAPY; PREDNISONE; EXOPHTHALMOS; ORBITOPATHY; IRRADIATION AB Thyroid ophthalmopathy is the most common orbital disorder of adults. Synonymous terms include Graves' orbitopathy, thyroid-related immune orbitopathy, and dysthyroid ophthalmopathy. Thyroid orbitopathy most commonly occurs in patients with active or treated Graves' disease, typically within 1 year of development of hyperthyroidism. Patients with thyroid orbitopathy, however, may be euthyroid or hypothyroid. The disorder usually affects women in the fourth and fifth decades, the female-to-male ratio being approximately 4:1. Thyroid orbitopathy is clinically apparent to some extent in nearly half of all patients with Graves' disease. The incidence of Graves' disease in the United States is approximately 0.4%. The clinical manifestations of thyroid ophthalmopathy include eyelid retraction, proptosis, restrictive myopathy (most commonly involving the medial or inferior rectus muscles), conjunctival congestion, exposure keratopathy, elevated intraocular pressure, and optic neuropathy. Thyroid orbitopathy is considered to be of autoimmune etiology, but the specific pathophysiology is poorly understood. Both humoral and cell-mediated mechanisms have been invoked, although their exact roles are not yet defined. The stimulation of orbital fibroblasts to produce excess glycosaminoglycans and direct autoimmune damage to orbital tissues have been postulated as general mechanisms for the orbitopathy. The myriad immunological findings and experimental results attempting to pinpoint the pathophysiology of thyroid orbitopathy are beyond the scope of this discussion. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02115. NR 58 TC 8 Z9 9 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 179 EP 193 DI 10.1097/00004397-199603610-00018 PG 15 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100017 PM 8778064 ER PT J AU Samiy, N Foster, CS AF Samiy, N Foster, CS TI The role of nonsteroidal antiinflammatory drugs in ocular inflammation SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID CYSTOID MACULAR EDEMA; 0.5-PERCENT KETOROLAC TROMETHAMINE; HUMOR BARRIER BREAKDOWN; BLOOD-AQUEOUS BARRIER; POSTOPERATIVE INFLAMMATION; TOPICAL INDOMETHACIN; OPHTHALMIC SOLUTION; LENS IMPLANTATION; SODIUM; CONJUNCTIVITIS AB In the treatment of ocular inflammation, the appeal of nonsteroidal antiinflammatory drugs (NSAIDs) hinges on the complications associated with the more established therapy for ocular inflammation: corticosteroids. Although an overlap between the mechanisms of action of both NSAIDs and corticosteroids exists, the use of topical NSAIDs may be safer than the use of corticosteroids, as the latter may produce adverse effects such as glaucoma, opportunistic infections, and posterior subcapsular cataracts. In sharp contrast, topical NSAIDs are known to cause only minor adverse effects such as burning, stinging, and hyperemia of the conjunctiva [1]. Therefore, in the treatment of ocular inflammation, the goal of treating with oral and topical NSAIDs is to reduce or even eliminate steroid use. In this chapter, we review the uses of NSAIDs in the treatment of noninfectious ocular inflammation. The evidence supporting the therapeutic efficacy of both topical and oral NSAIDs in conditions such as allergic conjunctivitis, keratopathy, uveitis, postoperative inflammation, and cystoid macular edema are addressed. The use of NSAIDs in preventing intraoperative miosis, and the pharmacokinetics and pharmacodynamics of these agents are not discussed. RP Samiy, N (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 37 TC 26 Z9 26 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP 195 EP 206 DI 10.1097/00004397-199603610-00019 PG 12 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100018 PM 8778065 ER PT J AU Jakobiec, FA Adamis, AP Pineda, RA AF Jakobiec, FA Adamis, AP Pineda, RA TI Noninfectious inflammatory disorders of the eye and adnexa - Preface SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Editorial Material RP Jakobiec, FA (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1996 VL 36 IS 1 BP R15 EP R17 PG 3 WC Ophthalmology SC Ophthalmology GA UF001 UT WOS:A1996UF00100001 ER PT J AU Sales, A Moscovice, I Lurie, N AF Sales, A Moscovice, I Lurie, N TI Measuring seriousness of hospital quality of care issues SO JOINT COMMISSION JOURNAL ON QUALITY IMPROVEMENT LA English DT Article AB Background: A 1995 article showed that the discipline of the person who determines what constitutes a serious quality of care issue is significantly associated with the type of issues identified as serious. Moreover, what is a serious issue for one organization or provider may be a minor issue for another. Methods: Six hundred hospital administrators, physicians, nurses, and quality managers in 72 hospitals rated the seriousness of issues they had identified in their own hospitals. A panel of 90 external hospital administrators, physicians, and quality managers rated a condensed set of the same issues. Results: Across all the hospitals, internal scores were significantly lower (less serious) than external scores. Internal 'respondents consistently rated issues identified in their hospital lower than did external raters. The mean internal rating was .60 times the score for the anchor issue (''late lab or x-ray results,'' assigned a score of 300), while the mean external rating was 1.73 times the anchor score. Discussion: Convergence of internal and external perceptions of the seriousness of quality of care issues in hospitals cannot be assumed. This raises questions about the effects of applying external judgments on seriousness of quality of care issues, such as those used in report cards or other external reports on hospital quality of care. Conclusion: There is greater conformity of viewpoint when respondents are asked to adopt an industrywide perspective rather than an internal one. External raters are more likely to consider problems serious than are internal raters, possibly because they do not have local knowledge of mitigating circumstances. C1 UNIV MINNESOTA,SCH PUBL HLTH,INST HLTH SERV RES,MINNEAPOLIS,MN. HENNEPIN CTY MED CTR,MINNEAPOLIS,MN. RP Sales, A (reprint author), DEPT VET AFFAIRS MED CTR,VA PUGET SOUND HLTH CARE SYST,NW CTR OUTCOMES RES OLDER ADULT,SEATTLE,WA 98108, USA. RI Sales, Anne/D-9678-2012; OI Sales, Anne/0000-0001-9360-3334 NR 13 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 1070-3241 J9 JOINT COMM J QUAL IM JI Jt. Comm. J. Qual. Improv. PD DEC PY 1996 VL 22 IS 12 BP 811 EP 816 PG 6 WC Health Policy & Services SC Health Care Sciences & Services GA XT182 UT WOS:A1996XT18200004 PM 8986563 ER PT J AU Bragdon, CR Burke, D Lowenstein, JD OConnor, DO Ramamurti, B Jasty, M Harris, WH AF Bragdon, CR Burke, D Lowenstein, JD OConnor, DO Ramamurti, B Jasty, M Harris, WH TI Differences in stiffness of the interface between a cementless porous implant and cancellous bone in vivo in dogs due to varying amounts of implant motion SO JOURNAL OF ARTHROPLASTY LA English DT Article DE interface; tissue ingrowth; torque; displacement ID HIP-REPLACEMENT; INGROWTH; TITANIUM AB To determine the mechanical properties of the interface between the tissue ingrowth into porous coatings and the implant, porous-coated cylindrical implants were inserted into the distal femur in 20 mature dogs and oscillated in vivo 8 hours per day for 6 weeks at fixed amounts of micromotion (0, 20, 40, and 150 mu m) Applied torques and resulting displacements were recorded. The torsional resistance per unit angular displacement (TRIAD), reflecting the stiffness of the bone-porous coating interface, was 0.88 +/- 0.25 N-M/deg immediately after implantation in the 20-mu m displacement group. It increased with time after surgery, reaching a maximum of 1.25 +/- 0.60 N-M/deg at 6 weeks. The TRIAD was lower initially (0.77 +/- 0.43 N-M/deg) in the 40-mu m group and gradually decreased with time after surgery, reaching a maximum of 0.54 +/- 0.13 N-M/deg at 6 weeks. The TRIAD was even lower (0.24 +/- 0.10 N-M/deg) in the 150-mu m group initially and remained the same (0.16 +/- 0.09 N-M/deg) with time after surgery. Histologic evaluation showed bone ingrowth in continuity with the surrounding bone in the 20-mu m group consistent with the high stiffness values at sacrifice. In contrast, a mixture of fibrocallus and bone were found at the bone-porous coating interface in the 40-mu m group, consistent with the intermediate stiffness values. In contrast, despite the fact that bone was found in the depth of the porous coating in the dogs in the 150-mu m group, the low stiffness values were a reflection of fibrous tissue formation at the interface in that group, because of the large motion disrupting bony in growth at the bone-porous coating interface. By monitoring the torsional resistance per unit of angular displacement dynamically in viva, it was possible to evaluate the mechanical properties of the bone-porous coating interface as tissue ingrowth proceeded. Twenty microns of oscillating displacement was compatible with stable bone ingrowth with high interface stiffness, whereas 40 and 150 mu m of motion was not. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. NR 22 TC 52 Z9 53 U1 1 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD DEC PY 1996 VL 11 IS 8 BP 945 EP 951 DI 10.1016/S0883-5403(96)80136-7 PG 7 WC Orthopedics SC Orthopedics GA VZ623 UT WOS:A1996VZ62300012 PM 8986573 ER PT J AU Jupiter, JB Fernandez, DL Toh, CL Fellman, T Ring, D AF Jupiter, JB Fernandez, DL Toh, CL Fellman, T Ring, D TI Operative treatment of volar intra-articular fractures of the distal end of the radius SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID CLASSIFICATION AB We retrospectively reviewed the results of operative treatment of forty-nine volar marginal intra-articular fractures of the distal end of the radius. According to the Comprehensive Classification of Fractures, there were two B3.1 fractures (characterized by a small volar fragment, with the sigmoid notch intact), three B3.2 fractures (characterized by a large volar fragment that included the sigmoid notch), and forty-four B3.3 fractures (characterized by comminution of the volar fragment). Although all fractures healed and only nine patients had evidence of osteoarthrosis on follow-up radiographs, there were six early and fourteen late complications, some of which adversely influenced the over-all outcome, After an average of fifty-one months (range, twenty-four to 117 months), there were thirty-one excellent, ten good, and eight fair results according to the system described by Gartland and Werley, and thirty-two excellent, nine good, five fair, and three poor results according to the modified system of Green and O'Brien. Two factors were found to have a significant association with a fair or poor outcome: evidence of osteoarthrosis on the most recent follow-up radiographs and reversal of the normal volar tilt of the distal end of the radius. The age of the patient, the interval from the injury to the operation, a concomitant injury of the ipsilateral upper extremity, an associated fracture of the ulnar styloid process, the radio-ulnar index, ulnar angulation, the classification of the fracture, comminution of the volar fragment, and articular incongruity were not significantly associated with the outcome. C1 KANTONSSPITAL,AARAU,SWITZERLAND. RP Jupiter, JB (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPAED HAND SERV,WAC-527,BOSTON,MA 02114, USA. NR 32 TC 70 Z9 74 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD DEC PY 1996 VL 78A IS 12 BP 1817 EP 1828 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA VZ333 UT WOS:A1996VZ33300004 PM 8986658 ER PT J AU Katznelson, L Finkelstein, JS Schoenfeld, DA Rosenthal, DI Anderson, EJ Klibanski, A AF Katznelson, L Finkelstein, JS Schoenfeld, DA Rosenthal, DI Anderson, EJ Klibanski, A TI Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; ADIPOSE PRECURSOR CELLS; ESTROGEN DEFICIENCY; ANDROGEN RECEPTOR; HIP-FRACTURES; ELDERLY MEN; OSTEOPOROSIS; 1,25-DIHYDROXYVITAMIN-D; METABOLISM; INSULIN AB Acquired hypogonadism is being increasingly recognized in adult men. However, the effects of long term testosterone replacement on bone density and body composition are largely unknown. We investigated 36 adult men with acquired hypogonadism (age, 22-69 yr; median, 58 yr), including 29 men with central hypogonadism and 7 men with primary hypogonadism, and 44 age-matched eugonadal controls. Baseline evaluation included body composition analysis by bioimpedance, determination of site-specific adipose area by dual energy quantitative computed tomography scan (QCT) of the lumbar spine, and measurements of spinal hone mineral density (BMD) using dual energy x-ray absortiometry, spinal trabecular BMD with QCT, and radial BMD with single photon absorptiometry. Percent body fat was significantly greater in the hypogonadal men compared to eugonadal men (mean +/- SEM, 26.4 +/- 1.1% vs. 19.2 +/- 0.8%; P < 0.01). The mean trabecular BMD determined by QCT for the hypogonadal men was 115 +/- 6 mg K2HPO4/cc. Spinal BMD was significantly lower than that in eugonadal controls (1.006 +/- 0.024 vs. 1.109 +/- 0.028 g/cm(2); P = 0.02, respectively). Radial BMD was similar in both groups. Testosterone enanthate therapy was initiated in 29 hypogonadal men at a dose of 100 mg/week, and the subjects were evaluated at 6-month intervals for 18 months. During testosterone therapy the percent body fat decreased 14 +/- 4%(P < 0.001). There was a 13 +/- 14% decrease in subcutaneous fat (P < 0.01) and a 7 +/- 2% increase in lean muscle mass (P = 0.01) during testosterone therapy. Spinal BRID and trabecular BMD increased by 5 +/- 1% (P < 0.001) and 14 +/- 3%(P < 0.001), respectively. Radial BMD did not change. Serum bone-specific alkaline phosphatase and urinary deoxypyridinoline Excretion, markers of bone formation and resorption, respectively, decreased significantly over the 18 months (P = 0.003 and P = 0.04, respectively). We conclude that testosterone therapy given to adult men with acquired hypogonadism decreases sc fat and increases lean muscle mass. In addition, testosterone therapy reduces bone remodeling and increases trabecular bone density. The beneficial effects of androgen administration on body composition and bone density may provide additional indications for testosterone therapy in hypogonadal men. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE UNIT, DEPT MED,GEN CLIN RES CTR, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT RADIOL, BOSTON, MA 02114 USA. RP Katznelson, L (reprint author), MASSACHUSETTS GEN HOSP, NEUROENDOCRINE UNIT, BULFINCH 457, 32 FRUIT ST, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-01066]; NIDDK NIH HHS [DK-08738] NR 42 TC 489 Z9 496 U1 2 U2 9 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 DEC PY 1996 VL 81 IS 12 BP 4358 EP 4365 DI 10.1210/jc.81.12.4358 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VW462 UT WOS:A1996VW46200030 PM 8954042 ER PT J AU Waldstreicher, J Seminara, SB Jameson, JL Geyer, A Nachtigall, LB Boepple, PA Holmes, LB Crowley, WF AF Waldstreicher, J Seminara, SB Jameson, JL Geyer, A Nachtigall, LB Boepple, PA Holmes, LB Crowley, WF TI The genetic and clinical heterogeneity of gonadotropin-releasing hormone deficiency in the human SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; SECONDARY SEX CHARACTERISTICS; HEALTH-EXAMINATION-SURVEY; UNILATERAL RENAL APLASIA; KALLMANNS-SYNDROME; MEN; PUBERTY; INHERITANCE; DISORDERS; MOLECULES AB Despite recent advances in the understanding of the pathophysiology of Kallmann's syndrome (KS), the patterns of inheritance in the majority of cases of GnRH deficiency in human subjects remain unclear. To define further the genetic and phenotypic variability of this syndrome, detailed family histories were reviewed in 106 cases of GnRH deficiency with or without anosmia [i.e. KS or idiopathic hypogonadotropic hypogonadism (IHH)]. The great majority of cases appeared to be sporadic, with only 19 probands (18%) having at least 1 family member with GnRH deficiency. However, of the families in which the proband was the sole member affected by KS or IHH, 9 had individuals with isolated anosmia, and 8 had a strong history of delayed puberty. If these phenotypes were considered as alternative manifestations of the same genetic defect that presented as KS or IHH in the proband, 34% of the cases in the present series could be considered familial. In these families, the most likely modes of transmission were assessed in several ways, including analysis of probands with KS as a distinct subset, and separate determinations based upon whether the phenotypes of isolated anosmia and/or delayed puberty were considered relevant to the inheritance of KS or IHH. The proportion of familial cases that could be attributable to an X-linked mode of inheritance was no greater than 36% in any of these analyses. We conclude that I) most cases of GnRH deficiency in humans are sporadic and, thus, could represent new mutations; 2) the X-linked form is the least common among familial cases of KS or IHH; 3) defects in at least two autosomal genes can result in GnRH deficiency; and 4) associated clinical defects may well represent clues to the nature and/or location of these autosomal genes. C1 MASSACHUSETTS GEN HOSP, REPROD ENDOCRINE UNIT, DEPT MED, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, SERV PEDIAT, GENET & TERATOL UNIT, BOSTON, MA 02114 USA. NORTHWESTERN UNIV, DIV ENDOCRINOL METAB & MOL MED, CHICAGO, IL 60611 USA. OI Jameson, James/0000-0001-9538-4059 FU NCRR NIH HHS [RR-01066]; NICHD NIH HHS [R01 HD015788, R01-HD-15788, U54-HD-29164] NR 34 TC 110 Z9 113 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1996 VL 81 IS 12 BP 4388 EP 4395 DI 10.1210/jc.81.12.4388 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VW462 UT WOS:A1996VW46200035 PM 8954047 ER PT J AU Escalante, A Lichtenstein, MJ Rios, N Hazuda, HP AF Escalante, A Lichtenstein, MJ Rios, N Hazuda, HP TI Measuring chronic rheumatic pain in Mexican Americans: Cross-cultural adaptation of the McGill Pain Questionnaire SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE pain; questionnaires; cross-cultural comparison; Mexican Americans; language; rheumatic diseases ID CANCER PAIN; RELIABILITY; LANGUAGE; VALIDITY; VERSION; KAPPA AB We performed a cross-cultural adaptation of the McGill Pain Questionnaire (MPQ) from Englsh to Spanish for studying Mexican Americans in South Texas. Each of the 78 single-word pain descriptors in the original MPQ was translated into Spanish by a panel of nine bilingual health researchers, preserving the original structure of the questionnaire. The pain intensity content (PIC) of the words in each language was then rated on a 100 mm visual analog scale by 8 bilingual hearth care providers and 10 bilingual healthcare consumers. The correlation between Spanish and English average PIC ratings was strong (r = 0.85 for providers, r = 0.80 for consumers). The translated Spanish version was compared to the original English in a group of 50 bilingual Mexican-American patients with musculoskeletal pain, who completed the MPQ in both languages. There was no difference in Average Pain Rating Index between the Spanish and English versions (29.8 +/- 14.7 vs 29.1 +/- 15.8, p = 0.55), and agreement between the two language versions was almost perfect (r(i) = 0.85). Test-retest reliability was measured in two groups of hospitalized patients (25 per group), one composed of monolingual Spanish speakers and the other of monolingual English speakers. Each subject completed the MPQ, the McGill Pain Map, two 10-cm visual analog scales measuring pain now and within the past week, the bodily pain items of the MOS-SF36 survey, and the Modified Health Assessment Questionnaire, on two occasions one day apart. Test-retest reliability of the Spanish and English components of the MPQ was not significantly different and was comparable to that of the other pain and health status instruments. We conclude that the Spanish MPQ is cross-culturally equivalent to the original English and has similar concurrent validity and reliability. This questionnaire is suitable for cross cultural studies of pain comparing Spanish-speaking Mexican Americans with English-speaking members of the same and other ethnic groups. Copyright (C) 1996 Elsevier Science Inc. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,RHEUMATOL SECT,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GERIATR & GERONTOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CLIN EPIDEMIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. FU NCRR NIH HHS [M01-RR-01346]; NIA NIH HHS [1-RO1-AG-10444]; PHS HHS [1-U01-H507397] NR 34 TC 13 Z9 15 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 1996 VL 49 IS 12 BP 1389 EP 1399 DI 10.1016/S0895-4356(96)00276-4 PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA VY924 UT WOS:A1996VY92400010 PM 8970489 ER PT J AU Tseng, CC Kieffer, TJ Jarboe, LA Usdin, TB Wolfe, MM AF Tseng, CC Kieffer, TJ Jarboe, LA Usdin, TB Wolfe, MM TI Postprandial stimulation of insulin release by glucose-dependent insulinotropic polypeptide (GIP) - Effect of a specific glucose-dependent insulinotropic polypeptide receptor antagonist in the rat SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE glucagonlike peptide-1 (7-36) (GLP-1); incretin; insulin; GIP receptor ID GASTRIC-INHIBITORY POLYPEPTIDE; GLUCAGON-LIKE PEPTIDE-1; PHYSIOLOGICAL INCRETIN; FUNCTIONAL EXPRESSION; GLP-1 7-36AMIDE; PANCREAS; SECRETION; BLOOD; AMIDE; GENE AB Glucose-dependent insulinotropic polypeptide (GIP) is a 42-amino acid peptide produced by K cells of the mammalian proximal small intestine and is a potent stimulant of insulin release in the presence of hyperglycemia, However, its relative physiological importance as a postprandial insulinotropic agent is unknown. Using LGIPR2 cells stably transfected with rat GIP receptor cDNA, GIP (1-42) stimulation of cyclic adenosine monophosphate (cAMP) production was inhibited in a concentration-dependent manner by GIP (7-30)-NH2. Competition binding assays using stably transfected L293 cells demonstrated an IC50 for GIP receptor binding of 7 nmol/liter for GIP (1-42) and 200 nmol/liter for GIP (7-30)-NH2, whereas glucagonlike peptide-1 (GLP-1) binding to its receptor on beta TC3 cells was minimally displaced by GIP (7-30)-NH2. In fasted anesthetized rats, GTP (1-42) stimulated insulin release in a concentration-dependent manner, an effect abolished by the concomitant intraperitoneal administration of GIP (7-30)-NH2 (100 nmol/ kg). In contrast, glucose-, GLP-1-, and arginine-stimulated insulin release were not affected by GIP (7-30)-NH2. In separate experiments, GIP (7-30)-NH2 (100 nmol/kg) reduced postprandial insulin release in conscious rats by 72%. It is concluded that GIP (7-30)-NH2 is a GIP-specific receptor antagonist and that GIP plays a dominant role in mediating postprandial insulin release. C1 BRIGHAM & WOMENS HOSP,DIV GASTROENTEROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MOL ENDOCRINOL LAB,BOSTON,MA 02114. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [KO8DK-08753, R01DK-48042] NR 32 TC 105 Z9 110 U1 0 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 DEC 1 PY 1996 VL 98 IS 11 BP 2440 EP 2445 DI 10.1172/JCI119060 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VX291 UT WOS:A1996VX29100004 PM 8958204 ER PT J AU Chen, L Pulsipher, M Chen, DS Sieff, C Elias, A Fine, HA Kufe, DW AF Chen, L Pulsipher, M Chen, DS Sieff, C Elias, A Fine, HA Kufe, DW TI Selective transgene expression for detection and elimination of contaminating carcinoma cells in hematopoietic stem cell sources SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE adenovirus; bone marrow; breast cancer; thymidine kinase; gene therapy ID BREAST-CANCER CELLS; MONOCLONAL-ANTIBODY DF3; HIGH-DOSE CHEMOTHERAPY; HUMAN-BONE-MARROW; POLYMERASE CHAIN-REACTION; MEDIATED GENE DELIVERY; THYMIDINE KINASE GENE; TUMOR-CELLS; LIMITING DILUTION; PERIPHERAL-BLOOD AB Tumor contamination of bone marrow (BM) and peripheral blood (PB) may affect the outcome of patients receiving high dose chemotherapy with autologous transplantation of hematopoietic stem cell products. In this report, we demonstrate that replication defective adenoviral vectors containing the cytomegalovirus (CMV) or DF3/MUC1 carcinoma-selective promoter can be used to selectively transduce contaminating carcinoma cells, Adenoviral-mediated reporter gene expression in breast cancer cells was five orders of magnitude higher than that found in BM, PB, and CD34(+) cells. Our results demonstrate that CD34(+) cells have low to undetectable levels of integrins responsible for adenoviral internalization. We show that adenoviral-mediated transduction of a reporter gene can detect one breast cancer cell in 5 x 10(5) BM or PB cells with a vector containing the DF3/MUC1 promoter. We also show that transduction of the HSV-tk gene for selective killing by ganciclovir can be exploited for purging cancer cells from hematopoietic stem cell populations. The selective expression of TK followed by ganciclovir treatment resulted in the elimination of 6-logs of contaminating cancer cells. By contrast, there was little effect on CFU-GM and BFU-E formulation or on long term culture initiating cells. These results indicate that adenoviral vectors with a tumor-selective promoter provide a highly efficient and effective approach for the detection and purging of carcinoma cells in hematopoietic stem cell preparations. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL & ONCOL,BOSTON,MA 02115. NR 46 TC 53 Z9 55 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 DEC 1 PY 1996 VL 98 IS 11 BP 2539 EP 2548 DI 10.1172/JCI119072 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VX291 UT WOS:A1996VX29100016 PM 8958216 ER PT J AU Eaton, KA Dewhirst, FE Paster, BJ Tzellas, N Coleman, BE Paola, J Sherding, R AF Eaton, KA Dewhirst, FE Paster, BJ Tzellas, N Coleman, BE Paola, J Sherding, R TI Prevalence and varieties of Helicobacter species in dogs from random sources and pet dogs: Animal and public health implications SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GASTRIC BIOPSIES; GASTROSPIRILLUM-HOMINIS; SPIRAL BACTERIUM; DOMESTIC CAT; PYLORI; INFECTION; CAMPYLOBACTER; ORGANISMS; COLONIZATION; PHYLOGENY AB Gastric bacteria of a variety of ultrastructural morphologies have been identified in or isolated from domestic carnivores, but their prevalence in different populations of animals and their clinical significance are still unknown. The purposes of this study were (i) to evaluate the prevalence and morphologic types of gastric bacteria in three different populations of dogs; (ii) to determine which of the organisms were culturable, and if the cultured organisms mere morphologically similar to the organisms seen in situ; (iii) to identify the isolated organisms;and (iv) to determine if gastric bacteria were associated with gastritis. Three groups of dogs were examined: healthy laboratory dogs, healthy dogs from an animal shelter, and pet dogs with various nongastric illnesses. Of these, 100% of laboratory and shelter dogs and 67% of pet dogs were colonized by large, tightly coiled gastric spiral bacteria morphologically similar to Gastrospirillum hominis or Helicobacter felis (referred to as gastrospirilla). Regardless of the presence or density of gastric bacteria, all of the dogs in the study except one had mild to moderate gastritis. Helicobacter spp. were isolated from only 6 of 39 stomachs cultured, and only three of the organisms isolated were morphologically similar to the bacteria seen in situ. Five helicobacters were identified by 16S rDNA (genes coding for rRNA) sequence analysis. Three were strains of H. felis, one was H. bilis, and one was a novel helicobacter morphologically similar to ''Flexispira rappini.'' Gastrospirilla are almost universal in the stomachs of domestic dogs, and in most infected dogs, they do not appear to be associated,vith clinical signs or histologic lesions compared with uninfected dogs. Nongastrospirillum helicobacters are rare in dogs and are not histologically detectable. Helicobacter pylori was not isolated from domestic dogs. C1 FORSYTH DENT CTR,DEPT MOL GENET,BOSTON,MA 02115. RP Eaton, KA (reprint author), OHIO STATE UNIV,DEPT VET BIOSCI,1925 COFFEY RD,COLUMBUS,OH 43210, USA. FU NIDCR NIH HHS [DE-07009, DE-10374] NR 34 TC 147 Z9 154 U1 0 U2 6 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 DEC PY 1996 VL 34 IS 12 BP 3165 EP 3170 PG 6 WC Microbiology SC Microbiology GA VV005 UT WOS:A1996VV00500052 PM 8940465 ER PT J AU Lynch, T AF Lynch, T TI Topotecan today SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material RP Lynch, T (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 12 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1996 VL 14 IS 12 BP 3053 EP 3055 PG 3 WC Oncology SC Oncology GA VW229 UT WOS:A1996VW22900001 PM 8955649 ER PT J AU Ames, D Wirshing, WC Baker, RW Umbricht, DSG Sun, AB Carter, J Schooler, NR Kane, JM Marder, SR AF Ames, D Wirshing, WC Baker, RW Umbricht, DSG Sun, AB Carter, J Schooler, NR Kane, JM Marder, SR TI Predictive value of eosinophilia for neutropenia during clozapine treatment SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DENMARK; RISK AB Background: Myelotoxicity continues to hinder the widespread use of clozapine in the United States. It has been theorized that eosinophilia predicts later agranulocytosis and that agranulocytosis occurs due to an immunologic mechanism. Our study compares the rates of these dyscrasias in clozapine-treated patients and a control group. Method: Forty-one patients taking clozapine and 29 patients taking haloperidol were monitored for a period of 6 months. Rates of eosinophilia and neutropenia were compared between the two treatment groups. Results: Treatment-emergent eosinophilia occurred frequently in both haloperidol- and clozapine-treated patients. No significant difference was seen between groups in the incidence of eosinophilia and neutropenia. Conclusion: We find no statistical difference between the rates of eosinophilia or neutropenia in haloperidol- and clozapine-treated patients. This study does not support the use of eosinophilia as a reliable predictor of neutropenia. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. UNIV PITTSBURGH,MED CTR,SPECIAL STUDIES CTR,MAYVIEW STATE HOSP,PITTSBURGH,PA. HILLSIDE HOSP,GLEN OAKS,NY 11004. ALBERT EINSTEIN COLL MED,BRONX,NY 10467. RP Ames, D (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. FU NIMH NIH HHS [MH46484-03] NR 13 TC 15 Z9 16 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 1996 VL 57 IS 12 BP 579 EP 581 DI 10.4088/JCP.v57n1205 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA WD707 UT WOS:A1996WD70700005 PM 9010121 ER PT J AU Chen, HM Torchilin, V Langer, R AF Chen, HM Torchilin, V Langer, R TI Polymerized liposomes as potential oral vaccine carriers: Stability and bioavailability SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE oral vaccine carriers; polymerized liposomes; stability; bioavailability; Peyer's patches ID DELIVERY SYSTEM; IN-VITRO; MICROSPHERES; CELL AB The potential of polymerized liposomes as oral vaccine carriers is evaluated. The stability of polymerized liposomes is demonstrated in mouse gastrointestinal tracts using dual-labeled liposomes. Similar transit kinetics displayed by the two labels of different hydrophobicity indicate the intactness of the polymerized liposomes inside the gastrointestinal tract. Uptake of liposomes from mouse gastrointestinal tract by Peyer's patches is quantified by measuring the amount of radiolabeled liposomes retained in the tissues following liposome oral administration. Bioavailability of liposomal contents is examined in macrophage cultures with calcein-containing liposomes. Liberation of calcein in cells suggests the breakdown of liposomal membranes and the intracellular release of their encapsulated materials. C1 MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,CHARLESTOWN,MA 02129. NR 23 TC 57 Z9 58 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD DEC PY 1996 VL 42 IS 3 BP 263 EP 272 DI 10.1016/0168-3659(96)01459-9 PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA VQ845 UT WOS:A1996VQ84500007 ER PT J AU Gilligan, HM Bredy, B Brady, HR Hebert, MJ Slayter, HS Xu, YH Rauch, J Shia, MA Koh, JS Levine, JS AF Gilligan, HM Bredy, B Brady, HR Hebert, MJ Slayter, HS Xu, YH Rauch, J Shia, MA Koh, JS Levine, JS TI Antineutrophil cytoplasmic autoantibodies interact with primary granule constituents on the surface of apoptotic neutrophils in the absence of neutrophil priming SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; FC-GAMMA-RIII; WEGENERS GRANULOMATOSIS; CELL-DEATH; ANTIMYELOPEROXIDASE ANTIBODIES; RESPIRATORY BURST; ENDOTHELIAL-CELLS; ANTIGEN; GLOMERULONEPHRITIS; VASCULITIS AB The pathogenic role of antineutrophil cytoplasmic autoantibodies (ANCA) remains controversial because of the difficulty in explaining how extracellular ANCA can interact with intracellular primary granule constituents. It has been postulated that cytokine priming of neutrophils (PMN), as may occur during a prodromal infection, is an important trigger for mobilization of granules to the cell surface, where they may interact with ANCA. We show by electron microscopy that apoptosis of unprimed PMN is also associated with the translocation of cytoplasmic granules to the cell surface and alignment just beneath an intact cell membrane. Immunofluorescent microscopy and FACS(R) analysis demonstrate reactivity of ANCA-positive sera and antimyeloperoxidase antibodies with apoptotic PMN, but not with viable PMN. Moreover, we show that apoptotic PMN may be divided into two subsets, based on the presence or absence of granular translocation, and that surface immunogold labeling of myeloperoxidase occurs only in the subset of PMN showing translocation. These results provide a novel mechanism that is independent of priming, by which ANCA may gain access to PMN granule components during ANCA-associated vasculitis. C1 BOSTON UNIV,MED CTR HOSP,EVANS MEM DEPT CLIN RES,RENAL SECT,BOSTON,MA 02118. BOSTON UNIV,MED CTR HOSP,DEPT MED,BOSTON,MA 02118. BOSTON UNIV,MED CTR HOSP,DEPT BIOCHEM,BOSTON,MA 02118. NATL UNIV IRELAND UNIV COLL DUBLIN,MATER MISERICORDIAE HOSP,DEPT MED & THERAPEUT,DUBLIN 7,IRELAND. BRIGHAM & WOMENS HOSP,DEPT MED,DIV RENAL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BROCKTON W ROXBURY DEPT VET AFFAIRS MED CTR,MED SERV,RENAL SECT,BOSTON,MA 02132. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,ELECT MICROSCOPY & STRUCT MOL BIOL,BOSTON,MA 02132. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOL PHYSIOL,BOSTON,MA 02132. MCGILL UNIV,MONTREAL GEN HOSP,RES INST,DIV RHEUMATOL,MONTREAL,PQ H3G 1A4,CANADA. FU NIAMS NIH HHS [AR/AI42732]; NIDDK NIH HHS [DK 45047, DK 44380] NR 39 TC 123 Z9 127 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1996 VL 184 IS 6 BP 2231 EP 2241 DI 10.1084/jem.184.6.2231 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VZ413 UT WOS:A1996VZ41300016 PM 8976178 ER PT J AU Ghayur, T Hugunin, M Talanian, RV Ratnofsky, S Quinlan, C Emoto, Y Pandey, P Datta, R Huang, YY Kharbanda, S Allen, H Kamen, R Wong, W Kufe, D AF Ghayur, T Hugunin, M Talanian, RV Ratnofsky, S Quinlan, C Emoto, Y Pandey, P Datta, R Huang, YY Kharbanda, S Allen, H Kamen, R Wong, W Kufe, D TI Proteolytic activation of protein kinase C delta by an ICE/CED 3-like protease induces characteristics of apoptosis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DEATH GENE CED-3; POLY(ADP-RIBOSE) POLYMERASE; MAMMALIAN HOMOLOG; ENZYME; INHIBITION AB Recent studies have shown that protein kinase C (PKC) delta is proteolytically activated at the onset of apoptosis induced by DNA-damaging agents, tumor necrosis factor, and anti-Fas antibody. However, the relationship of PKC delta cleavage to induction of apoptosis is unknown. The present studies demonstrate that full-length PKC delta is cleaved at DMQD(330)N to a catalytically active fragment by the cysteine protease CPP32. The results also demonstrate that overexpression of the catalytic kinase fragment in cells is associated with chromatin condensation, nuclear fragmentation, induction of sub-G1 phase DNA and lethality. By contrast, overexpression of full-length PKC delta or a kinase inactive PKC delta fragment had no detectable effect. The findings suggest that proteolytic activation of PKC delta by a CPP32-like protease contributes to phenotypic changes associated with apoptosis. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV CANC PHARMACOL, BOSTON, MA 02115 USA. BASF BIORES CORP, WORCESTER, MA 01605 USA. FU NCI NIH HHS [CA29431, CA66996, P01 CA066996, R01 CA029431, CA55241] NR 25 TC 410 Z9 415 U1 0 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1996 VL 184 IS 6 BP 2399 EP 2404 DI 10.1084/jem.184.6.2399 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VZ413 UT WOS:A1996VZ41300032 PM 8976194 ER PT J AU Warde, C Allen, W Gelberg, L AF Warde, C Allen, W Gelberg, L TI Physician role conflict and resulting career changes - Gender and generational differences SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-04, 1996 CL WASHINGTON, DC SP Soc Gen Internal Med DE career choice; stress, family characteristics; marital status; physician practice patterns ID OCCUPATIONAL STRESS; JOB-SATISFACTION; PART-TIME; FAMILY; WOMEN; MEDICINE; HEALTH AB OBJECTIVE: To evaluate gender and generational differences both in the prevalence of role conflict and in resulting career changes among married physicians with children. STUDY DESIGN: Cross-sectional survey. PARTICIPANTS: We sent a survey to equal numbers of licensed male and female physicians (1,412 total) in a Southern California county; of the 964 delivered questionnaires, 656 (68%) were returned completed. Our sample includes 415 currently married physicians with children, 64% male and 36% female. MEASUREMENTS AND MAIN RESULTS: The prevalence of perceived role conflict, of career changes for marriage, and of career changes for children were evaluated. Types of career changes were also evaluated. More female than male physicians (87% vs 62%, p < .001) and more younger than older female physicians (93% vs 80%, p < .01) and male physicians (79% vs 54%, p < .001) experienced at least moderate levels of role conflict. Younger female and male physicians did not differ in their rates of career change for marriage (57% vs 49%), but female physicians from both age cohorts were more likely than their male peers to have made career changes for their children (85% vs 35%, p < .001). Younger male physicians were twice as likely as their older peers to have made a career change for marriage (49% vs 28%, p < .001) or children (51% vs 25%, p < .001). The most common type of career change made for marriage or children was a decrease in work hours. CONCLUSIONS: Most physicians experience role conflict, and many adjust their careers in response. Flexible career options may enable physicians to combine professional and family roles more effectively. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NR 31 TC 51 Z9 53 U1 0 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 1996 VL 11 IS 12 BP 729 EP 735 DI 10.1007/BF02598986 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA VZ358 UT WOS:A1996VZ35800003 PM 9016419 ER PT J AU Nikolic, B Sykes, M AF Nikolic, B Sykes, M TI Clonal deletion as a mechanism of transplantation tolerance SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID BONE-MARROW CHIMERAS; NEONATALLY-INDUCED TOLERANCE; MIXED ALLOGENEIC CHIMERAS; T-CELL TOLERANCE; POSITIVE SELECTION; NEGATIVE SELECTION; SELF-RECOGNITION; TRANSGENIC MICE; THYMUS; ANTIGEN C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BONE MARROW TRANSPLANTA,BOSTON,MA 02129. FU NHLBI NIH HHS [R01HL49915]; NIAID NIH HHS [P01AI37755] NR 72 TC 27 Z9 38 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD DEC PY 1996 VL 15 IS 12 BP 1171 EP 1178 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA WA946 UT WOS:A1996WA94600001 PM 8981201 ER PT J AU Ljubimov, AV Burgeson, RE Butkowski, RJ Couchman, JR Zardi, L Ninomiya, Y Sado, Y Huang, ZS Nesburn, AB Kenney, MC AF Ljubimov, AV Burgeson, RE Butkowski, RJ Couchman, JR Zardi, L Ninomiya, Y Sado, Y Huang, ZS Nesburn, AB Kenney, MC TI Basement membrane abnormalities in human eyes with diabetic retinopathy SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 21-26, 1996 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol DE diabetic; retinopathy; basement membrane, extracellular matrix; neovascularization; preretinal membranes; tenascin; collagens; fibronectin; laminins; immunofluorescence ID ENDOTHELIAL GROWTH-FACTOR; FIBRILLARY ACIDIC PROTEIN; HUMAN CILIARY BODY; EXTRACELLULAR-MATRIX; IV COLLAGEN; MESSENGER-RNA; IMMUNOCYTOCHEMICAL LOCALIZATION; RETINAL NEOVASCULARIZATION; MONOCLONAL-ANTIBODIES; EPIRETINAL MEMBRANES AB Vascular and parenchymal basement membranes (BMs) are thickened in diabetes, but alterations in individual BM components in diabetic eyes, especially in diabetic retinopathy (DR), are obscure. To identify abnormalities in the distribution of specific constituents, we analyzed cryostat sections of human eyes obtained at autopsy (seven normal, five diabetic without DR, and 13 diabetic with DR) by immunofluorescence with antibodies to 30 BM and extracellular matrix components. In non-DR eyes, no qualitative changes of ocular BM components were seen. In some DR corneas, epithelial BM: was stained discontinuously for laminin-l, entactin/nidogen, and alpha 3-alpha 4 Type IV collagen, in contrast to non-DR corneas. Major BM alterations were found in DR retinas compared to normals and non-DR diabetics. The inner limiting membrane (retinal BM) of DR eyes had accumulations of fibronectin (including cellular) and Types I, III, IV (alpha 1-alpha 2), and V collagen. The BM zone of new retinal blood vessels in neovascularized areas accumulated tenascin and Type XII ; collagen, whereas normal, diabetic, and adjacent DR retinas showed only weak and irregular staining. In preretinal membranes, perlecan, bamacan, and Types VI, VIII, XII, and XIV collagen were newly identified. Diabetic BM thickening appears to involve qualitative alterations of specific BM markers at an advanced disease stage, with the appearance of DR. C1 MASSACHUSETTS GEN HOSP EAST,HARVARD CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA. INCSTAR,STILLWATER,MN. UNIV ALABAMA,DEPT CELL BIOL,BIRMINGHAM,AL 35294. IST NAZL RIC CANC,I-16132 GENOA,ITALY. OKAYAMA UNIV,SCH MED,OKAYAMA 700,JAPAN. SHIGEI MED RES INST,OKAYAMA,JAPAN. RP Ljubimov, AV (reprint author), UNIV CALIF LOS ANGELES,CEDARS SINAI MED CTR,SCH MED,OPHTHALMOL RES LABS,8700 BEVERLY BLVD,LOS ANGELES,CA 90048, USA. RI Ljubimov, Alexander/E-5883-2013 FU NIAMS NIH HHS [AR 36457]; NICHD NIH HHS [N01-HD-2-3144] NR 75 TC 94 Z9 96 U1 2 U2 4 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD DEC PY 1996 VL 44 IS 12 BP 1469 EP 1479 PG 11 WC Cell Biology SC Cell Biology GA VZ426 UT WOS:A1996VZ42600013 PM 8985139 ER PT J AU Finger, EB Bruehl, RE Bainton, DF Springer, TA AF Finger, EB Bruehl, RE Bainton, DF Springer, TA TI A differential role for cell shape in neutrophil tethering and rolling on endothelial selectins under flow SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NODE HOMING RECEPTOR; LEUKOCYTE ADHESION MOLECULE-1; P-SELECTIN; PHYSIOLOGICAL FLOW; SPATIAL-DISTRIBUTION; CHEMOTACTIC FACTORS; CYTOPLASMIC DOMAIN; GMP-140 BINDS; LIGAND; PROTEINS AB We investigated the role of neutrophil microvilli in interactions with E-selectin and P-selectin in hydrodynamic shear flow by disruption with cytochalasin B, hypotonic swelling, and chilling. Cytochalasin B only marginally reduced microvilli numbers (from 30 +/- 6 to 16 +/- 6 per cell perimeter, p < 0.005) as shown by electron microscopy, completely disrupted tethering in shear flow to E-sesectin and P-selectin, increased the strength of rolling adhesions on E-selectin and P-selectin, and increased cell deformability in shear flow with a likely increase in the area of cell:substrate contact. Hypoosmotic swelling markedly reduced microvilli number (to 6 +/- 5 per perimeter, p < 0.005), almost completely inhibited tethering on E- and P-selectin, and increased the strength of rolling adhesions on P-selectin but not on E-selectin. Chilling almost completely abolished microvilli (to 3 +/- 3 per perimeter, p < 0.005), but pseudopod-like structures were present, and had little effect on tethering in flow. Immunogold labeling of L-selectin, which is normally clustered on tips of microvilli, showed that in the absence of microvilli it remained in small clusters. Our studies show that alterations in cell morphology and viscoelasticity can have opposing effects on tethering and rolling, showing that they are independently regulatable. Furthermore, our results suggest that the association of molecules that mediate rolling with microvilli tips may be important not just to enhance presentation, but for other functions such as to promote resistance to extraction from the membrane or cooperative interactions among clustered receptors. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,DEPT PATHOL,SAN FRANCISCO,CA 94143. FU NCI NIH HHS [CA31799]; NHLBI NIH HHS [HLB31610] NR 57 TC 73 Z9 73 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1996 VL 157 IS 11 BP 5085 EP 5096 PG 12 WC Immunology SC Immunology GA VU501 UT WOS:A1996VU50100045 PM 8943418 ER PT J AU Koyama, Y Tanaka, Y Saito, K Abe, M Nakatsuka, K Morimoto, I Auron, PE Eto, E AF Koyama, Y Tanaka, Y Saito, K Abe, M Nakatsuka, K Morimoto, I Auron, PE Eto, E TI Cross-linking of intercellular adhesion molecule 1 (CD54) induces AP-1 activation and IL-1 beta transcription SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN SYNOVIAL-CELLS; RHEUMATOID-ARTHRITIS; T-CELLS; GENE-EXPRESSION; TRANSENDOTHELIAL MIGRATION; COUNTER-RECEPTOR; LYMPHOCYTES-T; BINDING-SITE; I TAX; ICAM-1 AB Leukocytes adhere to target cells through their integrins and play a crucial role in self-defense, inflammation, and differentiation, Intercellular adhesion molecule-1 (ICAM-1;CD54) is a representative ligand for integrins and is expressed on many cell types, some of which are targets for leukocyte adhesion. Recent studies suggest that adhesion molecules function not only as a cellular glue, but also as a signal transducer. However, it remains to be clearly defined whether engagement of ICAM-1 is able to induce activation signals in target cells. In rheumatoid synovium, synovial cells are known to express abundant ICAM-1 and produce multiple inflammatory cytokines, such as IL-1 beta. In this study, we provide the first evidence that ICAM-1 engagement induces activation of the transcription factor AP-1 and transcription of the IL-1 beta gene using a specific Ab to cross-link ICAM-1 on a rheumatoid synovial cell line (Ell cells). This evidence includes ICAM-1 cross-linking-dependent induction of 1) in situ IL-1 beta transcription and protein synthesis, 2) transiently transfected chloramphenicol acety(transferase (CAT) reporter plasmids containing both the IL-1 beta LPS-responsive enhancer (between -3134 and -2729) as well as multiple copies of an AP-1 site from this enhancer (between -3117 and -3111), and 3) the binding of a Jun/Fos family complex to this AP-1 site. Thus, ICAM-1 not only functions as a glue for integrin binding, but also as a transducer for AP-1 activation signals important for IL-1 beta gene transcription. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV OCCUPAT & ENVIRONM HLTH,SCH MED,DEPT INTERNAL MED 1,KITAKYUSHU,FUKUOKA 807,JAPAN. RP Koyama, Y (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,WARREN ALPERT BLDG,ROOM 140,200 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 59 TC 74 Z9 75 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1996 VL 157 IS 11 BP 5097 EP 5103 PG 7 WC Immunology SC Immunology GA VU501 UT WOS:A1996VU50100046 PM 8943419 ER PT J AU Qureshi, AA Hosoi, J Xu, S Takashima, A Granstein, RD Lerner, EA AF Qureshi, AA Hosoi, J Xu, S Takashima, A Granstein, RD Lerner, EA TI Langerhans cells express inducible nitric oxide synthase and produce nitric oxide SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE mouse; dendritic cells; L-NAME ID GENE-RELATED PEPTIDE; ANTIGEN PRESENTATION; MURINE EPIDERMIS; DENDRITIC CELLS; SKIN; INDUCTION; GROWTH; LINES; KERATINOCYTES; MACROPHAGES AB The importance of nitric oxide (NO) in mediating macrophage functions has been demonstrated, but production of this potent gas has not been examined in Langerhans cells (LC). Using murine LC purified from epidermal cell suspensions and the recently established LC-like cell line derived from newborn BALB/c epidermis (XS-52), it was shown with reverse transcriptase (RT)-PCR that inducible nitric oxide synthase (iNOS) message is present in these cells. Murine keratinocytes did not contain iNOS message. iNOS mRNA was increased in a concentration-dependent manner by lipopolysaccharide (LPS) in purified murine LC and XS-52 cells, and immunofluorescence using an antibody to iNOS revealed bright cytoplasmic staining in LPS-treated XS-52 cells, Anti-iNOS antibody brightly stained LC on human neonatal foreskin cryosections, An increase in NO production by LPS-treated XS-52 cells over 16 h, as measured by the determination of nitrite levels in culture supernatants using the Griess Reaction, was observed. Interferon-gamma (IFN gamma) did not affect NO production on its own, In the presence of LPS and IFN gamma, NO production was 3 times more than observed with LPS alone. NO production was inhibited by the NOS inhibitor L-NAME. Western blots with anti-iNOS antibody demonstrated an increase in iNOS expression in LPS-treated XS-52 cells that was suppressed by IL-10. NO produced in EC may affect LC functions such as microbicidal activity, antigen presentation, and cytotoxicity and may affect adjacent keratinocytes and melanocytes. C1 HARVARD UNIV, CUTANEOUS BIOL RES CTR,MED SCH,DEPT DERMATOL, MASSACHUSETTS GEN HOSP, CHARLESTOWN, MA 02129 USA. UNIV TEXAS, SW MED CTR, DEPT DERMATOL, DALLAS, TX USA. FU NIAMS NIH HHS [R0-1 AR 42429, R0-1 AR42005] NR 50 TC 59 Z9 64 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1996 VL 107 IS 6 BP 815 EP 821 DI 10.1111/1523-1747.ep12330572 PG 7 WC Dermatology SC Dermatology GA VV220 UT WOS:A1996VV22000005 PM 8941667 ER PT J AU Compton, CC Kupper, TS Nadire, KB AF Compton, CC Kupper, TS Nadire, KB TI HIV-infected Langerhans cells constitute a significant proportion of the epidermal Langerhans cell population throughout the course of HIV disease SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE cultured epithelial autografts; aquired immunodeficiency syndrome; transfusion; burn injury ID AIDS PATIENTS; VIRUS; SKIN; TARGET; BLOOD; TRANSMISSION; REPLICATION; MONOCYTES; PROTEINS; TYPE-1 AB Human immunodeficiency virus (HIV) is known to infect Langerhans cells, but controversy still exists about the occurrence of HIV-infected Langerhans cells in the skin of HIV-infected individuals and about the density of epidermal Langerhans cells during the course of HIV disease. In this study, epidermal Langerhans cell population densities were analyzed quantitatively in serial biopsies from two burn patients acquired over an 11-y period following infection with HIV from transfusions received during their acute treatment, At each biopsy time point, the density of epidermal Langerhans cells and the proportion that were infected with HIV were analyzed by immunostaining. In both patients, skin grafts were slow to repopulate with Langerhans cells and did not attain normal Langerhans cell densities until about 2 y after grafting, Thereafter, Langerhans cell densities remained within normal limits with the exception of six biopsies at random times that showed a supernormal number of epidermal Langerhans cells. HIV-infected Langerhans cells were first detected at about 2 y post-infection and comprised about one-third of the Langerhans cell population, At subsequent times, HIV p24-stained Langerhans cells were identified in most biopsies and typically constituted about one third to one half of the total Langerhans cell population, The findings show that HIV-bearing Langerhans cells constitute a significant proportion of the epidermal Langerhans cell population over long periods of asymptomatic disease but are unevenly distributed throughout the skin. Normal population densities of epidermal Langerhans cells are maintained for years, although transient increases may occur randomly. C1 SHRINERS HOSP CRIPPLED CHILDREN,DEPT PATHOL,BOSTON BURN UNIT,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT DERMATOL,BOSTON,MA 02115. RP Compton, CC (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON BURN UNIT,WARREN 2,35 FRUIT ST,BOSTON,MA 02114, USA. FU PHS HHS [R01-35242] NR 40 TC 15 Z9 15 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 DEC PY 1996 VL 107 IS 6 BP 822 EP 826 DI 10.1111/1523-1747.ep12330574 PG 5 WC Dermatology SC Dermatology GA VV220 UT WOS:A1996VV22000006 PM 8941668 ER PT J AU Mendez, AJ Uint, L AF Mendez, AJ Uint, L TI Apolipoprotein-mediated cellular cholesterol and phospholipid efflux depend on a functional Golgi apparatus SO JOURNAL OF LIPID RESEARCH LA English DT Article DE apolipoprotein A-I; high density lipoproteins; efflux; cholesterol; phosphatidylcholine; sphingomyelin; brefeldin A; monesin ID HIGH-DENSITY-LIPOPROTEINS; SMOOTH-MUSCLE CELLS; HUMAN-SKIN FIBROBLASTS; BREFELDIN-A; LIPID EFFLUX; GUANINE-NUCLEOTIDE; MACROPHAGES; TRANSPORT; EXCHANGE; REDUCTION AB Several studies have demonstrated that lipid-free apolipoproteins can promote cholesterol and phospholipid efflux from cells; however, the mechanisms and the role of cell-mediated pathways involved remain incompletely elucidated. We have recently demonstrated that brefeldin A or monensin, agents that disrupt Golgi apparatus structure and function, inhibit intracellular cholesterol efflux from cells to high density lipoproteins. In the present study we examined the effects of those agents on cell cholesterol and phospholipid efflux to purified apolipoprotein A-I (apoA-I) and apolipoprotein-depleted accepters from cholesterol-loaded fibroblasts. Brefeldin A or monensin treatment of cells during incubation with apoA-I inhibited efflux of cellular cholesterol by greater than 80% compared with control cells, measured by changes in cellular cholesterol radioactivity, mass, and the substrate pool of cholesterol available for esterification by acyl coenzyme A:cholesterol acyltransferase. Inhibition of cholesterol efflux by these agents could not be overcome by increasing the apoA-I concentration and persisted during incubations up to 24 h. Similarly, brefeldin A and monensin inhibited up to 80% of apoA-I-mediated efflux of labeled phospholipids from cholesterol-loaded cells relative to controls. In contrast, lipid efflux mediated by apolipoprotein-depleated accepters (trypsin-modified HDL and sonicated phospholipid vesicles) was not sensitive to these drugs. On the basis the known effects of brefeldin A and monensin on Golgi apparatus structure and function, these results are consistent with the notion that efflux of cell lipids by apolipoprotein-dependent mechanisms, but not by apolipoprotein-independent mechanisms, require active cellular processes involving an intact and functional Golgi apparatus. RP Mendez, AJ (reprint author), MASSACHUSETTS GEN HOSP, CARDIAC UNIT GRJ1422, BOSTON, MA 02114 USA. FU NHLBI NIH HHS [HL53451] NR 38 TC 54 Z9 55 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD DEC PY 1996 VL 37 IS 12 BP 2510 EP 2524 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD855 UT WOS:A1996WD85500004 PM 9017504 ER PT J AU Glass, J Shustik, C Hochberg, FH Cher, L Gruber, ML AF Glass, J Shustik, C Hochberg, FH Cher, L Gruber, ML TI Therapy of primary central nervous system lymphoma with pre-irradiation methotrexate, cyclophosphamide, doxorubicin, vincristine, and dexamethasone (MCHOD) SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE antineoplastic agents; combined; brain neoplasms; cranial irradiation; lymphoma ID NON-HODGKINS-LYMPHOMA; HIGH-DOSE METHOTREXATE; PRIMARY CNS LYMPHOMA; PRIMARY MALIGNANT-LYMPHOMA; PRIMARY CEREBRAL LYMPHOMA; RADIATION-THERAPY; CHEMOTHERAPY; BRAIN; SURVIVAL; RADIOTHERAPY AB Prior studies have suggested that pre-irradiation methotrexate (MTX)-based chemotherapy improves duration of response and survival in primary central nervous system lymphoma (PCNSL). To circumvent the potential emergence of drug resistance, we combined high-dose MTX with agents highly active against systemic lymphoma. Patients received three week cycles of CHOD (cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), and vincristine 1.4 mg/m(2) [2 mg maximum] on day 1; dexamethasone 10 mg/m(2) days 1-5), and MTX (3.5 gm/m(2)) with leucovorin rescue on day 8 (or on recovery from the CHOD nadir). Whole brain irradiation (WBRT) was planned after at least three cycles. Eighteen patients were treated. Complete responses were seen in eleven patients, and partial responses in three. Four progressed during therapy, three succumbing to progressive disease and one subsequently responding to WBRT. Response duration was 37.5 months in those responding to therapy. The time to progression for all eighteen patients was 19.5 months. Medial survival was 25.5 months. Disease-free survival was 50% at 38 months in MCHOD responders. Grade 3 or 4 myelotoxicity was seen in 19 of 50 cycles. There were three instances of neutropenic fever, three of azotemia, two of deep vein thrombosis, and one each of community-acquired pneumonia, intracranial hemorrhage, superior vena cava syndrome, and hepatotoxicity. Late radiation-related toxicities were seen in two patients. Pre-irradiation MCHOD has activity against PCNSL, but appears to be no better than MTX monotherapy and has greater toxicity. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. ROYAL VICTORIA HOSP,MONTREAL,PQ H3A 1A1,CANADA. NR 31 TC 51 Z9 52 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD DEC PY 1996 VL 30 IS 3 BP 257 EP 265 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA VT415 UT WOS:A1996VT41500010 PM 8943101 ER PT J AU Singh, I Kremser, K Ghosh, B Singh, AK Pai, S AF Singh, I Kremser, K Ghosh, B Singh, AK Pai, S TI Abnormality in translational regulation of catalase expression in disorders of peroxisomal biogenesis SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE catalase; peroxisomes; Zellweger syndrome; X-adrenoleukodystrophy ID HEPATO-RENAL SYNDROME; NEURONAL MIGRATION; ZELLWEGER SYNDROME; FIBROBLASTS; DISEASE; LIVER; H2O2 AB Peroxisomal disorders are a newly described group of inherited neurological diseases. In disorders of peroxisomal biogenesis, e.g., Zellweger syndrome, owing to the lack of peroxisomes, catalase, a peroxisomal enzyme, is found to be present in the cytoplasm instead. We observed higher catalase activity (7.59 +/- 0.41 mU/mg of protein) in cultured skin fibroblasts from Zellweger patients than in control fibroblasts (4.45 +/- 0.29 mU/mg of protein). Moreover, we also found that the majority of the catalase in Zellweger cells was present in the inactive form. The specific activities following reactivation in Zellweger and control cells were 12.1 and 4.9 mU/mg of protein, respectively. To understand the molecular basis of higher levels of catalase in Zellweger than control cells, we examined the rate of synthesis and turnover of catalase and levels of catalase mRNA and protein levels in Zellweger cells as compared with control cells. The initial rates of synthesis of catalase in Zellweger (1.68 +/- 0.15 mU/mg of protein) and control (1.51 +/- 0.14 mU/mg of protein) cells were similar. The rates of turnover of catalase in Zellweger (t(1/2) = 47 +/- 8 h) and control (t(1/2) = 49 +/- 7 h) were also similar. Consistent with the enzyme activity, the levels of catalase protein were higher in Zellweger cells as compared with control cells. On the other hand, there was no difference in the level of catalase mRNA between control and Zellweger cells. Although the rate of synthesis in Zellweger and control cells was initially similar, it was down-regulated to a lower level at similar to 72 h of culture in control fibroblasts as compared with Zellweger cells, which continued to synthesize catalase at the same rate up to 5 days in culture. The presence of similar levels of mRNA in control and Zellweger cells and continued synthesis of catalase in Zellweger cells at a higher level as compared with control cells suggest a loss of regulation at the translational level. C1 RALPH H JOHNSON VA MED CTR,DEPT PATHOL & LAB MED,CHARLESTON,SC. RP Singh, I (reprint author), MED UNIV S CAROLINA,DEPT PEDIAT,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. FU NINDS NIH HHS [NS-34741, NS-22576] NR 30 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1996 VL 67 IS 6 BP 2373 EP 2378 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VU244 UT WOS:A1996VU24400017 PM 8931469 ER PT J AU Murray, DR Polizzi, SM Harris, TJ Maisel, AS AF Murray, DR Polizzi, SM Harris, TJ Maisel, AS TI Myocardial ischemia alters immunoregulatory cell traffic and function in the rat independent of exogenous catecholamine administration SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE catecholamines; myocardial ischemia; immune cells; beta-adrenergic ID BETA-ADRENERGIC RECEPTORS; LYMPHOCYTE SUBSETS; PERIPHERAL-BLOOD; SUPPRESSION; EXERCISE; HUMANS; SYSTEM AB Recent investigation has suggested there is an adrenergically-driven efflux of beta(2)-receptor rich lymphocyte subsets into the circulation with altered function following either exercise or infusion of exogenous catecholamines. Myocardial ischemia, like exercise, is associated with generalized sympathoadrenal activation. To determine whether ischemia influences immunoregulatory cell traffic and function in a manner comparable to beta(2)-adrenergic stimulation via isoproterenol, rats underwent thoracotomy with or without coronary ligation. Another group of rats received either isoproterenol (1 mg/kg) or vehicle (10 mM HCl) intraperitoneally. Thoracotomy, regardless of whether or not myocardial ischemia was induced, led to lymphocytosis, reflected primarily by an increase in T-helper (T-h) cells and, to a lesser degree, in T-suppressor/cytotoxic (T-s/c) and natural killer (NK) cells; with a tendency toward an increased T-h/T-s/c ratio. To the contrary, isoproterenol injection resulted in a relative lymphopenia characterized by diminished B and T-h cell numbers, preserved T-s/c and increased NK cell numbers leading to a significant decrease in the T-h/T-s/c ratio. With respect to splenic composition, 60 but not 15 min of myocardial ischemia led to diminished T-h and B cell numbers compared to sham operated controls, whereas isoproterenol appeared to stimulate an efflux of only NK cells. Both ischemia and isoproterenol enhanced basal splenocyte function; however, only ischemia significantly boosted splenocyte responsiveness to the mitogen Concanavalin A. Surgically induced myocardial ischemia leads to alterations in immunoregulatory cell migration and function which are distinct from those found with beta(2)-adrenergic stimulation via isoproterenol. C1 UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92161. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. HAHNAMAN MED SCH,PHILADELPHIA,PA 19106. RP Murray, DR (reprint author), VET AFFAIRS MED CTR,DEPT MED,SAN DIEGO,CA 92161, USA. NR 23 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC PY 1996 VL 71 IS 1-2 BP 107 EP 113 DI 10.1016/S0165-5728(96)00138-5 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA VZ443 UT WOS:A1996VZ44300015 PM 8982109 ER PT J AU Lyoo, IK Seol, HY Byun, HS Renshaw, PF AF Lyoo, IK Seol, HY Byun, HS Renshaw, PF TI Unsuspected multiple sclerosis in patients with psychiatric disorders: A magnetic resonance imaging study SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID CEREBROVASCULAR RISK-FACTORS; SIGNAL ABNORMALITIES; BRAIN; LESIONS; ILLNESS; TOMOGRAPHY; DEPRESSION; DEMENTIA; CT AB Over a 6-year period, 2,783 subjects, consecutively referred from the inpatient unit of a private psychiatric hospital, were evaluated with brain MRI. Twenty-three patients (0.83 %) had brain white matter hyperintensities (WMH) that were highly suggestive of multiple sclerosis (MS). The subjects with WMH consistent with MS were most commonly diagnosed with affective illness. They had a significantly longer length of hospital stay during the index admission, a greater number of past psychiatric admissions, a greater prevalence of brain atrophy, and a history of more frequent neurological symptoms and signs than those without these findings. C1 HARVARD UNIV, SCH MED, CONSOLIDATED DEPT PSYCHIAT, BOSTON, MA USA. MASSACHUSETTS GEN HOSP, DEPT RADIOL, BOSTON, MA 02114 USA. RP Lyoo, IK (reprint author), MCLEAN BRAIN IMAGING CTR, 115 MILL ST, BELMONT, MA 02178 USA. NR 49 TC 39 Z9 39 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1996 VL 8 IS 1 BP 54 EP 59 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TR911 UT WOS:A1996TR91100008 PM 8845702 ER PT J AU Savage, CR Keuthen, NJ Jenike, MA Brown, HD Baer, L Kendrick, AD Miguel, EC Rauch, SL Albert, MS AF Savage, CR Keuthen, NJ Jenike, MA Brown, HD Baer, L Kendrick, AD Miguel, EC Rauch, SL Albert, MS TI Recall and recognition memory in obsessive-compulsive disorder SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID HUNTINGTONS-DISEASE AB This study examined recall and recognition memory in 20 nonmedicated patients with obsessive-compulsive disorder (OCD) ann 20 matched control subjects. As hypothesized, OCD subjects showed abnormalities affecting delayed recall of nonverbal information but showed normal recognition. These results are interpreted as providing preliminary evidence of a nonverbal memory retrieval deficit consistent with proposed corticostriatal system dysfunction in OCD. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02129. HARVARD UNIV,DEPT PSYCHOL,BOSTON,MA. HARVARD UNIV,DEPT PSYCHOL,CAMBRIDGE,MA 02138. RP Savage, CR (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BLDG 149,13TH ST,BOSTON,MA 02129, USA. RI Miguel, Euripedes/B-2871-2008 NR 17 TC 73 Z9 73 U1 6 U2 9 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1996 VL 8 IS 1 BP 99 EP 103 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TR911 UT WOS:A1996TR91100017 PM 8845711 ER PT J AU Cummings, JL AF Cummings, JL TI Neuropsychiatry and society SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID PARKINSONS-DISEASE; NURSING-HOME; DISORDER C1 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. RP Cummings, JL (reprint author), UNIV CALIF LOS ANGELES,SCH MED,REED NEUROL RES CTR,DEPT NEUROL,710 WESTWOOD PLAZA,LOS ANGELES,CA 90024, USA. FU NIA NIH HHS [AG10123] NR 40 TC 4 Z9 5 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1996 VL 8 IS 1 BP 104 EP 109 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TR911 UT WOS:A1996TR91100018 PM 8845693 ER PT J AU Boppart, SA Bouma, BE Brezinski, ME Tearney, GJ Fujimoto, JG AF Boppart, SA Bouma, BE Brezinski, ME Tearney, GJ Fujimoto, JG TI Imaging developing neural morphology using optical coherence tomography SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE imaging; development; embryology; microscopy; optics; Xenopus laevis ID MICROSCOPY; TISSUE AB Imaging technologies offer numerous possibilities to investigate the processes involved in neural development. The optical coherence tomography (OCT) technology is analogous to ultrasound backscatter microscopy except reflections of light are detected rather than sound. The OCT technology combines high-resolution in vivo imaging in a diode-based benchtop instrument capable of micron-scale resolution in transparent and non-transparent biological specimens, In this paper, we examine the potential of using OCT for the investigation of developing neural morphology. To demonstrate the capabilities of this technique in assessing neural development, we have chosen to image early normal and abnormal neural morphology in a common developmental biology model, Xenopus laevis. In vivo images clearly identify gross and subtle differences in neural structure and may offer an alternative to the costly and time-consuming process of repeated histological preparation for neural developmental studies. Because imaging can be performed rapidly and repeatedly, the morphological changes of single specimens can be followed throughout development. To illustrate the future potential of this technique, a state-of-the-art Cr4+:forsterite modelocked laser is used as a broad bandwidth light source to image individual cells in a developing specimen. C1 HARVARD UNIV,SCH MED,CARDIAC UNIT,MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Boppart, SA (reprint author), MIT,HARVARD MIT DIV HLTH SCI & TECHNOL,DEPT ELECT ENGN & COMP SCI,ELECT RES LAB,CAMBRIDGE,MA 02139, USA. RI Boppart, Stephen/C-7338-2009 FU NEI NIH HHS [9-RO1-EY 11289-10] NR 19 TC 44 Z9 44 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD DEC PY 1996 VL 70 IS 1 BP 65 EP 72 DI 10.1016/S0165-0270(96)00104-5 PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VZ357 UT WOS:A1996VZ35700010 PM 8982983 ER PT J AU Kalkanis, SN Carroll, RS Zhang, JP Zamani, AA Black, PM AF Kalkanis, SN Carroll, RS Zhang, JP Zamani, AA Black, PM TI Correlation of vascular endothelial growth factor messenger RNA expression with peritumoral vasogenic cerebral edema in meningiomas SO JOURNAL OF NEUROSURGERY LA English DT Article DE vascular endothelial growth factor; meningioma; peritumoral vasogenic cerebral edema; microvascular extravasation; microvascular permeability; messenger RNA expression ID FOLLICULAR CELLS SECRETE; HUMAN BRAIN-TUMORS; PERMEABILITY FACTOR; RECEPTOR EXPRESSION; ANGIOGENESIS; FRAGMENTS; BINDING; FLUID AB Intracranial meningiomas are often complicated by peritumoral vasogenic cerebral edema, which appears to result from increased microvascular permeability and extravasation of proteinaceous and plasma fluid into the adjacent peritumoral space. The source of such edema has long been mysterious. The contents of this paper support the concept that vascular endothelial growth factor (VEGF) production plays a significant role in edema formation. Vascular endothelial growth factor messenger RNA expression has been found in a wide range of intracranial neoplasms, including malignant gliomas, metastatic melanomas, meningiomas, and other benign tumors. Several studies have confirmed the importance of VEGF in tumorigenesis, neovascularization, and edema production. This study tests the hypothesis that the presence of peritumoral edema in meningiomas is positively correlated with increased expression of VEGF mRNA. To investigate this hypothesis, 31 meningioma specimens were subjected to Northern blot analysis, hybridization with a complementary DNA VEGF probe, and laser densitometry to determine the relative levels of VEGF mRNA expression. Magnetic resonance imaging was then used in a double-blind fashion to correlate the neuropathological tissue samples with the presence of preoperative peritumoral edema. Of 31 patients studied, 14 exhibited no edema and 17 exhibited some level of peritumoral fluid accumulation. There was a marked increase in VEGF expression in patients with edema (p = 0.0004, Wilcoxon-Mann-Whitney rank-sum test). Meningiomas with peritumoral edema exhibited 3.4 times the level of VEGF mRNA as those without edema. These data demonstrate a strong link between VEGF mRNA expression and peritumoral edema and indicate that VEGF expression is an important factor in the etiology of edema around meningiomas. C1 BRIGHAM & WOMENS HOSP,SERV NEURORADIOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BRAIN TUMOR CTR,CHILDRENS HOSP,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. RP Kalkanis, SN (reprint author), BRIGHAM & WOMENS HOSP,NEUROSURG SERV,221 LONGWOOD AVE,ROOM 121,BOSTON,MA 02115, USA. NR 38 TC 99 Z9 106 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 DEC PY 1996 VL 85 IS 6 BP 1095 EP 1101 DI 10.3171/jns.1996.85.6.1095 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA VU233 UT WOS:A1996VU23300016 PM 8929501 ER PT J AU Houtman, JJ Fleming, JO AF Houtman, JJ Fleming, JO TI Pathogenesis of mouse hepatitis virus-induced demyelination SO JOURNAL OF NEUROVIROLOGY LA English DT Review DE multiple sclerosis; immunopathology; coronavirus ID CENTRAL-NERVOUS-SYSTEM; MURINE CORONAVIRUS JHM; T-CELL CLONES; TEMPERATURE-SENSITIVE MUTANTS; TUMOR-NECROSIS-FACTOR; MYELIN BASIC-PROTEIN; CARCINOEMBRYONIC ANTIGEN FAMILY; S-PEPLOMER PROTEIN; STRAIN JHM; SPIKE PROTEIN AB Infection of rodents with neurotropic mouse hepatitis virus (MHV) may result in lethal encephalitis or paralytic demyelinating disease resembling the human disease multiple sclerosis. The outcome of MHV infection is dependent on a number of variables, including the passage history of the viral isolate, dose and route of inoculation, and the age and immune status of the host. Alterations in surface glycoproteins, especially the spike protein, can profoundly influence pathogenesis. Innate resistance to MHV infection may be related to the expression of cellular receptors or to immunological factors. The immune system plays a major role in MHV pathogenesis, affecting encephalitis, viral clearance, and demyelination. Antiviral antibodies, CD4(+) T lymphocytes, or CD8(+) T lymphocytes may protect infected animals from lethal encephalitis, but both CD4(+) and CD8(+) T lymphocytes are required for effective viral clearance. Demyelination in MHV-infected animals has been attributed to the cytolytic effects of viral infection on myelin-producing oligodendrocytes, but more recent evidence supports an immunopathological mechanism for demyelination. Immunopathological models far demyelination include autoimmunity, direct immune cytotoxicity, and indirect 'bystander' damage. Although evidence exists supporting all of these models, the authors favor the bystander demyelination mo del. Much remains to be revealed about the processes leading to demyelination in MHV-infected mice, and information gained from these investigations may aid in the study of demyelinating disease in humans. C1 UNIV WISCONSIN, DEPT MED MICROBIOL & IMMUNOL, MADISON, WI 53706 USA. UNIV WISCONSIN, DEPT NEUROL, MADISON, WI 53706 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, MADISON, WI 53705 USA. NR 185 TC 98 Z9 100 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 1996 VL 2 IS 6 BP 361 EP 376 DI 10.3109/13550289609146902 PG 16 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA WA335 UT WOS:A1996WA33500001 PM 8972418 ER PT J AU Parker, JA Yester, MV DaubeWitherspoon, ME ToddPokropek, AE Royal, HJ AF Parker, JA Yester, MV DaubeWitherspoon, ME ToddPokropek, AE Royal, HJ TI Procedure guideline for general imaging: 1.0 SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE practice guidelines; nuclear medicine imaging C1 BETH ISRAEL HOSP, BOSTON, MA 02215 USA. UNIV ALABAMA, BIRMINGHAM, AL USA. UNIV CALIF LOS ANGELES, SCH MED, W LOS ANGELES VET ADM MED CTR, LOS ANGELES, CA 90024 USA. NIH, BETHESDA, MD 20892 USA. UCL, LONDON, ENGLAND. WASHINGTON UNIV, MED CTR, MALLINCKRODT INST RADIOL, ST LOUIS, MO 63110 USA. NR 4 TC 6 Z9 6 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 1996 VL 37 IS 12 BP 2087 EP 2092 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VY988 UT WOS:A1996VY98800045 PM 8970540 ER PT J AU Callahan, RJ Chilton, HM Goodwin, DA Hnatowich, DJ Ponto, JA Swanson, DP Royal, HJ AF Callahan, RJ Chilton, HM Goodwin, DA Hnatowich, DJ Ponto, JA Swanson, DP Royal, HJ TI Procedure guideline for imaging with radiopharmaceuticals: 1.0 SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE radiopharmaceuticals; practice guidelines; graphic studies C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BOWMAN GRAY SCH MED,WINSTON SALEM,NC. VET ADM MED CTR,PALO ALTO,CA 94304. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. UNIV IOWA HOSP & CLIN,IOWA CITY,IA 52242. UNIV PITTSBURGH,PITTSBURGH,PA. WASHINGTON UNIV,MED CTR,MALLINCKRODT INST RADIOL,ST LOUIS,MO 63110. NR 8 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 1996 VL 37 IS 12 BP 2092 EP 2094 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VY988 UT WOS:A1996VY98800046 PM 8970541 ER PT J AU Perrott, DH AF Perrott, DH TI Clinical and computed tomographic findings in costochondral grafts replacing the mandibular condyle - Discussion SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material ID TEMPOROMANDIBULAR-JOINT ANKYLOSIS; GROWTH; RECONSTRUCTION; RAMUS RP Perrott, DH (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD DEC PY 1996 VL 54 IS 12 BP 1400 EP 1401 DI 10.1016/S0278-2391(96)90252-9 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VX272 UT WOS:A1996VX27200005 ER PT J AU August, M Wang, J Plante, D Wang, CC AF August, M Wang, J Plante, D Wang, CC TI Complications associated with therapeutic neck radiation SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID HEAD; IRRADIATION; CARCINOMA; SHOULDER AB Purpose: This retrospective study of patients who underwent neck radiation as part of their treatment for squamous cell carcinoma of the oral cavity sought to identify and quantify the morbidity associated with this treatment. Patients and Methods: Thirty-five patients who received neck radiation between 1985 and 1992 were randomly recalled for examination. All patients had been treated in a standardized fashion by the Department of Radiation Oncology, The long-term effects of neck radiation on skin changes, thyroid function, and neck range of motion, of atherosclerotic carotid artery disease, xerostomia, and glottic structures were measured. Results: Fifty-seven percent of patients demonstrated grade 1 skin changes, No severe changes were noted, and no development of secondary neoplasia was observed., There was no linear trend observed between radiation dose and skin changes. Hypothyroidism developed in 14.3% of patients within 3.5 years posttreatment. Logistic regression demonstrated a significant association between hypothyroidism and radiation dose. Limitation of neck mobility was the most significant complication with deficits demonstrated in all ranges of motion. Carotid bruits were documented in 14.3% of patients, with a significant association between the higher neck dosage in N+ cases. Xerostomia was found in 68% of patients. There was persistent glottic erythema in 11.4% of patients. Conclusions: The results of this study indicate that there are persistent complications after neck radiation, which include limitation of neck movement, diminished thyroid function, accelerated carotid artery narrowing, and skin and salivary changes. RP August, M (reprint author), HARVARD UNIV,SCH DENT MED,DEPT ORAL & MAXILLOFACIAL SURG,MASSACHUSETTS GEN HOSP,32 FRUIT ST,BOSTON,MA 02114, USA. NR 19 TC 31 Z9 32 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD DEC PY 1996 VL 54 IS 12 BP 1409 EP 1415 DI 10.1016/S0278-2391(96)90254-2 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VX272 UT WOS:A1996VX27200007 PM 8957119 ER PT J AU Billings, JA Block, SD AF Billings, JA Block, SD TI Slow euthanasia SO JOURNAL OF PALLIATIVE CARE LA English DT Article ID VOLUNTARY ACTIVE EUTHANASIA; PHYSICIAN-ASSISTED SUICIDE; LIFE-SUSTAINING TREATMENTS; HOPELESSLY ILL PATIENTS; TERMINALLY ILL; DEATH; CARE; DEPRESSION; REQUESTS; CONSENT C1 MASSACHUSETTS GEN HOSP,PALLIAT CARE SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT AMBULATORY CARE & PREVENT,BOSTON,MA. BRIGHAM & WOMENS HOSP,DIV PSYCHIAT,BOSTON,MA 02115. HARVARD PILGRIM HLTH CARE,BOSTON,MA. RP Billings, JA (reprint author), MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114, USA. NR 81 TC 143 Z9 144 U1 1 U2 3 PU CENTER BIOETHICS CLIN RES INST MONTREAL PI MONTREAL PA 110 PINE AVE W, MONTREAL PQ H2W 1R7, CANADA SN 0825-8597 J9 J PALLIATIVE CARE JI J. Palliative Care PD WIN PY 1996 VL 12 IS 4 BP 21 EP 30 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA WD012 UT WOS:A1996WD01200004 PM 9019033 ER PT J AU Mizokami, A Eguchi, K Kawakami, A Ida, H Kawabe, Y Tsukada, T Aoyagi, T Maeda, K Morimoto, C Nagataki, S AF Mizokami, A Eguchi, K Kawakami, A Ida, H Kawabe, Y Tsukada, T Aoyagi, T Maeda, K Morimoto, C Nagataki, S TI Increased population of high fluorescence 1F7 (CD26) antigen on T cells in synovial fluid of patients with rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; synovial fluid; CD26; activated T cells; T cell migration ID TRANSENDOTHELIAL MIGRATORY CAPACITY; DIPEPTIDYL PEPTIDASE-IV; PERIPHERAL-BLOOD; PHENOTYPIC CHARACTERIZATION; MONOCLONAL-ANTIBODIES; GRAVES-DISEASE; LYMPHOCYTES-T; ACTIVATION; EXPRESSION; ASSOCIATION AB Objective. To investigate the activation of T cells in peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis (RA), Methods. The expression of CD26 (Tal and 1F7) antigen on T cells was analyzed in 7 women with RA and 7 healthy control subjects by immunofluorescence. Results, The percentage of CD3+ CD26+ cells was significantly higher in PB of patients with RA compared with healthy subjects. The 1F7+ cell population was divided into high (1F7+(high) cells) and low fluorescence populations (1F7+(low) cells), based on 1F7 antigen density. The percentage of 1F7+(high) cells in SF of RA was markedly increased compared with PB of patients and healthy subjects. However, RA SF contained lower percentages of whole 1F7+ cells compared with PB. Conclusion. Our results indicate that SF of patients with RA contains activated T cells, and suggest that T cells with high levels of CD26 antigen may preferentially migrate into the rheumatoid synovium to induce inflammation and tissue destruction. C1 NAGASAKI UNIV,SCH MED,DEPT INTERNAL MED 1,NAGASAKI 852,JAPAN. NATL URESHINO HOSP,DEPT ORTHOPED SURG,SAGA,JAPAN. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. OI nagataki, shigenobu/0000-0002-9974-3554 NR 45 TC 40 Z9 40 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 DEC PY 1996 VL 23 IS 12 BP 2022 EP 2026 PG 5 WC Rheumatology SC Rheumatology GA VX843 UT WOS:A1996VX84300005 PM 8970035 ER PT J AU Geller, DA Biederman, J Griffin, S Jones, J Lefkowitz, TR AF Geller, DA Biederman, J Griffin, S Jones, J Lefkowitz, TR TI Comorbidity of juvenile obsessive-compulsive disorder with disruptive behavior disorders SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE obsessive-compulsive disorder; comorbidity; pediatric samples; disruptive behavior ID ATTENTION-DEFICIT DISORDER; BIPOLAR DISORDER; CLINICAL-FEATURES; ADOLESCENTS; CHILDREN; EPIDEMIOLOGY; FAMILY; SCALE; PSYCHOTHERAPY; PHENOMENOLOGY AB Objective: To examine the full spectrum of psychiatric comorbidity in juvenile obsessive-compulsive disorder (OCD) in a naturalistic manner when no exclusionary criteria are used for sample selection. Method: Consecutive referrals to a specialized pediatric OCD clinic were evaluated by means of structured diagnostic interviews and rating scales. No exclusionary criteria were used for sample selection. Findings were compared with those of previously published reports of juvenile OCD. Results: Compared with previous studies, our sample of juveniles with OCD had high rates of comorbidity not only with tie, mood, and anxiety disorders but also with disruptive behavior disorders. Conclusions: Our findings indicate that in the naturalistic setting, juvenile OCD is heavily comorbid with both internalizing and externalizing disorders. The presence of such a complex comorbid state has important clinical and research implications and stresses the relevance of limiting exclusionary criteria in studies of juvenile OCD. C1 MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. RP Geller, DA (reprint author), MCLEAN HOSP,JOINT PROGRAM PEDIAT PSYCHOPHARMACOL,PEDIAT PSYCHOPHARMACOL UNIT,115 MILL ST,BELMONT,MA 02178, USA. NR 47 TC 139 Z9 139 U1 3 U2 12 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 DEC PY 1996 VL 35 IS 12 BP 1637 EP 1646 DI 10.1097/00004583-199612000-00016 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA VU998 UT WOS:A1996VU99800016 PM 8973071 ER PT J AU Bostic, JQ AF Bostic, JQ TI Use of neuroleptics in children - Richardson,MA, Haughland,G SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review RP Bostic, JQ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PEDIAT PSYCHOPHARMACOL CLIN,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 1996 VL 35 IS 12 BP 1694 EP 1695 DI 10.1097/00004583-199612000-00024 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA VU998 UT WOS:A1996VU99800024 ER PT J AU Gonzalez, E Gonzalez, S AF Gonzalez, E Gonzalez, S TI Drug photosensitivity, idiopathic photodermatoses, and sunscreens SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review ID POLYMORPHOUS LIGHT ERUPTION; CHRONIC ACTINIC DERMATITIS; PHOTOALLERGIC CONTACT-DERMATITIS; QUINOLONE ANTIBACTERIAL AGENTS; ULTRAVIOLET-RADIATION; NALIDIXIC-ACID; PHOTOCONTACT DERMATITIS; RETICULOID SYNDROME; SOLAR URTICARIA; HUMAN-SKIN AB Photosensitization may be defined as a process in which a reaction to normally innocuous radiation is induced by the introduction of a specific radiation-absorbing substance (the photosensitizer) that causes another component (the substrate) to be changed by the radiation. This review focuses on photosensitization produced by exogenous chemicals. Idiopathic photodermatoses, including polymorphous light eruption and its variants, solar urticaria and chronic actinic dermatitis, are also discussed. Clinical recognition patterns of the photodermatoses are stressed as well as several diagnostic procedures available for confirmation of the condition. Finally, descriptions, therapeutic uses, and adverse reactions of sunscreens are provided. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Gonzalez, E (reprint author), MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114, USA. NR 139 TC 59 Z9 62 U1 2 U2 8 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 1996 VL 35 IS 6 BP 871 EP 885 DI 10.1016/S0190-9622(96)90108-5 PG 15 WC Dermatology SC Dermatology GA VY377 UT WOS:A1996VY37700001 PM 8959945 ER PT J AU Grossman, MC Dierickx, C Farinelli, W Flotte, T Anderson, RR AF Grossman, MC Dierickx, C Farinelli, W Flotte, T Anderson, RR TI Damage to hair follicles by normal-mode ruby laser pulses SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID SKIN; HIRSUTISM; OPTICS AB Background: Although many temporary treatments exist for hirsutism and hypertrichosis, a practical and permanent hair removal treatment is needed. Objective: Our purpose was to study the use of normal-mode ruby laser pulses (694 nm, 270 mu sec, 6 mm beam diameter) for hair follicle destruction by selective photothermolysis. Methods: Histologically assessed damage in ex vivo black-haired dog skin after the use of different laser fluences was used to design a human study; 13 volunteers with brown or black hair were exposed to normal-mode ruby laser pulses at fluences of 30 to 60 J/cm(2), delivered to both shaved and wax-epilated skin sites. An optical delivery device designed to maximize light delivery to the reticular dermis was used. Hair regrowth was assessed at 1, 3, and 6 months after exposure by counting terminal hairs. Results: Fluence-dependent selective thermal injury to follicles was observed histologically. There was a significant delay in hair growth in all subjects at all laser-treated sites compared with the unexposed shaven and epilated control sites. At 6 months, there was significant hair loss only in the areas shaved before treatment at the highest fluence. At 6 months, four subjects had less than 50%, regrowth, two of whom showed no change between 3 and 6 months. Transient pigmentary changes were observed; there was no securing. Conclusion: Selective photothermolysis of hair follicles with the normal-mode ruby laser produces a growth delay consistent with induction of prolonged telogen with apparently permanent hair removal in some cases. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA. NR 20 TC 235 Z9 239 U1 0 U2 16 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 1996 VL 35 IS 6 BP 889 EP 894 DI 10.1016/S0190-9622(96)90111-5 PG 6 WC Dermatology SC Dermatology GA VY377 UT WOS:A1996VY37700002 PM 8959946 ER PT J AU Hyman, BT AF Hyman, BT TI Apolipoprotein E genotype: Utility in clinical practice in Alzheimer's disease SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID E ALLELE EPSILON-4; COGNITIVE DECLINE; TYPE-4 ALLELE; FREQUENCY; ASSOCIATION RP Hyman, BT (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,FRUIT ST,BOSTON,MA 02114, USA. NR 22 TC 9 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 1996 VL 44 IS 12 BP 1469 EP 1471 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VW457 UT WOS:A1996VW45700009 PM 8951318 ER PT J AU Gertler, JP Cambria, RP Brewster, DC Davison, JK Purcell, P Zannetti, S Johnson, S LItalien, G Koustas, G LaMuraglia, GM Laposata, M Abbott, WM AF Gertler, JP Cambria, RP Brewster, DC Davison, JK Purcell, P Zannetti, S Johnson, S LItalien, G Koustas, G LaMuraglia, GM Laposata, M Abbott, WM TI Coagulation changes during thoracoabdominal aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 10th Annual Meeting of the Eastern-Vascular-Society CY MAY 03-05, 1996 CL WASHINGTON, DC SP E Vasc Soc ID DISSEMINATED INTRAVASCULAR COAGULATION; AORTIC-ANEURYSMS; EXPERIENCE; COAGULOPATHY AB Purpose: The cause of coagulopathic hemorrhage during thoracoabdominal aneurysm (TAA) repair has not been well defined in human studies. We investigated changes in the coagulation system associated with supraceliac versus infrarenal cross-clamping to address this critical issue. Methods: Blood levels of fibrinogen, the prothrombin fragment F1.2, D-dimer, and factors II, V, VII, VIII, IX, X, XI, and XII were analyzed in 19 patients with TAAs and four patients with abdominal aortic aneurysms (AAAs) at: (A) induction; (B) 30 minutes into supraceliac (TAA) or infrarenal (AAA) clamping; (C) 30 minutes after release of supraceliac or infrarenal damps; and (D) immediately after surgery. Preoperative and intraoperative variables, including but not limited to aneurysm type, pathologic findings, comorbid conditions, damp times, volume and timing of blood products, and clinical outcome, mere prospectively recorded. Significance was determined by analysis of variance, Student's t test, and univariate linear regression. Results: Levels of fibrinogen and factors II, V, VIII, VIII, IX, X, XI, and XII decreased (p <0.05) at time A versus time A and returned to near baseline by time D. D-dimer and F1.2 increased starting at time B and reached significance (p <0.05) by time D. Data points were compared for the TAA and AAA groups. Although AAA groups demonstrated a trend to factor activity reduction and increased fibrinolysis, the effect was much less pronounced than in TAA and did not approach significance. No correlation of coagulation change with damping time was present; however, visceral clamping times were all less than 65 minutes (mean, 44 minutes). Blood and factor replacement was initiated after time B. Univariate regression analysis of factor level versus total blood replacement demonstrated a significant (p <0.04) correlation between the reduction in the levels of factors II, V, VIII, VIII, X, and XII, and the increase in the level of D-dimer at time B and subsequent total blood replacement. Conclusions: Thoracoabdominal aneurysm repair is associated with a reduction in clotting factor activity and an increase in fibrinolytic function, which occurs after placement of the supraceliac damp. Explanations include visceral ischemia or a greater and longer ischemic tissue burden as the likely cause of coagulation alterations. Total blood replacement during TAA procedures was correlated to the degree of factor reduction and fibrinolysis at the time of visceral cross-clamping. An aggressive approach to early blood component replacement and to coagulation monitoring could lessen blood loss during TAA repair and avoid potentially disastrous bleeding complications. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT LAB MED,BOSTON,MA 02114. RP Gertler, JP (reprint author), MASSACHUSETTS GEN HOSP,DIV VASC SURG,DEPT SURG,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 16 TC 43 Z9 44 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 1996 VL 24 IS 6 BP 936 EP 943 DI 10.1016/S0741-5214(96)70039-3 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA WA203 UT WOS:A1996WA20300007 PM 8976347 ER PT J AU Muluk, SC Kaufman, JA Torchiana, DF Gertler, JP Cambria, RP AF Muluk, SC Kaufman, JA Torchiana, DF Gertler, JP Cambria, RP TI Diagnosis and treatment of thoracic aortic intramural hematoma SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 10th Annual Meeting of the Eastern-Vascular-Society CY MAY 03-05, 1996 CL WASHINGTON, DC SP E Vasc Soc ID INTIMAL RUPTURE; DISSECTION AB Purpose: This report reviews our recent experience with nine patients who had intramural hematoma of the thoracic aorta. Methods: This was a retrospective study of all patients who had intramural hematoma at our institution from 1989 to 1994. Patients who had identifiable intimal flap, tear, or penetrating aortic ulcer mere excluded from the study. Results: Among these nine elderly patients (mean age, 76 years), the most common presentation was chest or back pain. Intramural hematoma was diagnosed by a variety of high-resolution imaging techniques. The descending thoracic aorta alone was involved in seven patients, whereas the ascending aorta was affected in the other two patients. One patient had evidence of an aneurysm (5.0 cm diameter) in the region of the hematoma. All patients were initially managed nonsurgically with blood pressure control. Both patients who had ascending aortic involvement had progression of aortic hematoma, which resulted in death in one case and in successful surgery in the ether. Sis of the seven patients who had descending aortic involvement alone were successfully managed without aortic surgery. The patient who had intramural hematoma and associated aortic aneurysm, however, had severe, recurrent pain and underwent successful aortic replacement. Another patient had recurrent pain associated with hypertension, but was successfully managed nonsurgically with antihypertensive therapy. All eight survivors are doing well at a median follow-up of 19 months. Conclusions: Intramural hematoma appears to be a distinct entity, although overlap with aortic dissection or penetrating aortic ulcer exists. Aggressive control of blood pressure with intensive care unit monitoring has been our initial management. Patients who have involvement of the descending thoracic aorta alone can frequently be managed without surgery in the absence of coexisting aneurysmal dilatation or disease progression Our experience suggests that a more aggressive approach with early surgery is warranted in patients who ha ie ascending aortic involvement or those who have coexisting aneurysm and intramural hematoma. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV VASC SURG,BOSTON,MA. NR 12 TC 46 Z9 47 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 1996 VL 24 IS 6 BP 1022 EP 1029 DI 10.1016/S0741-5214(96)70048-4 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA WA203 UT WOS:A1996WA20300022 PM 8976356 ER PT J AU Taddeo, B Carlini, F Verani, P Engelman, A AF Taddeo, B Carlini, F Verani, P Engelman, A TI Reversion of a human immunodeficiency virus type 1 integrase mutant at a second site restores enzyme function and virus infectivity SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; VIRAL-DNA ENDS; HIV-1 INTEGRASE; RETROVIRAL INTEGRATION; PRODUCTIVE INFECTION; ESCHERICHIA-COLI; GENETIC-ANALYSIS; CONSERVED RESIDUES; CATALYTIC DOMAIN; PROTEIN INVITRO AB The integration of a DNA copy of the retroviral RNA genome into the host cell genome is essential for viral replication. The virion-associated integrase protein, encoded by the 3' end of the viral pol gene, is required for integration, Stable virus-producing T-cell lines were established for replication-defective human immunodeficiency virus type 1 carrying single amino acid substitutions at conserved residues in the catalytic domain of integrase, Phenotypically reverted virus was detected 12 weeks after transfection with the integrase mutant carrying the P-109-->S mutation (P109S). Unlike the defective P109S virus, the revertant virus (designated P109S(R)) grew in CD4(+) SupT1 cells, In addition to the Ser substitution at Pro-109, P109S(R) had a second substitution of Ala for Thr at position 125 in integrase. Site-directed mutagenesis was used to show that the P109S T125A genotype was responsible for the P109S(R) replication phenotype. The T125A substitution also rescued the in vitro enzyme activities of recombinant P109S integrase protein. P109S integrase did not display detectable 3' processing or DNA strand transfer activity, although 5 to 10% of wild-type disintegration activity was detected, P109S T125A integrase displayed nearly wild-type levels of 3' processing, DNA strand transfer, and disintegration activities, confirming that T125A is a second-site intragenic suppressor of P109S. P109S integrase ran as a large aggregate on a size exclusion column, whereas wild-type integrase ran as a monomer and P109S T125A integrase ran as a mixed population, Pro-109 and Thr-125 are not immediately adjacent in the crystal structure of the integrase catalytic domain, We suggest that the T125A substitution restores integrase function by stabilizing a structural alteration(s) induced by the P109S mutation. C1 HARVARD UNIV,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Taddeo, B (reprint author), IST SUPER SANITA,VIROL LAB,VIALE REGINA ELENA 299,I-00161 ROME,ITALY. RI CARLINI, FRANCESCA/D-7945-2016 NR 71 TC 23 Z9 23 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 DEC PY 1996 VL 70 IS 12 BP 8277 EP 8284 PG 8 WC Virology SC Virology GA VT704 UT WOS:A1996VT70400004 PM 8970947 ER PT J AU Goncalves, J Korin, Y Zack, J Gabuzda, D AF Goncalves, J Korin, Y Zack, J Gabuzda, D TI Role of Vif in human immunodeficiency virus type 1 reverse transcription SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; DNA-SYNTHESIS; VIRAL-DNA; SOR GENE; NUCLEOCAPSID PROTEIN; PRIMARY LYMPHOCYTES; INVITRO SYNTHESIS; T-LYMPHOCYTES; IN-VITRO; HIV-1 AB The Vif protein of human immunodeficiency virus type 1 (HIV-1) is important for virion infectivity. Previous studies have shown that vif mutant HIV-1 virions are defective in their ability to synthesize proviral DNA in vivo. Here, we examine the role of Vif in viral DNA synthesis in the endogenous reverse transcriptase (RT) reaction, an in vitro assay in which virions synthesize viral DNA by using endogenous viral RNA as a template. vif mutant virions showed a significant reduction in endogenous RT activity despite similar levels of exogenous RT activity. Analysis of the viral DNA products on agarose gels demonstrated that this reflects reduced synthesis of short minus- and plus-strand DNA products in addition to those of full genomic length. Quantitative PCR analysis of endogenous reverse transcription provided further evidence for reduced formation of both initial and completed reverse transcripts. Vif had no effect on genomic RNA dimerization or the stability of the RNA dimer linkage. These results suggest that Vif is important for an early event after virus entry but preceding or during the early stages of viral DNA synthesis. This may be due to an intrinsic effect on reverse transcription or a preceding postentry event(s), such as virion uncoating or disassembly of the virion core. Drugs targeted to Vif function may provide a new therapeutic approach to inhibiting HIV-1 reverse transcription. C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. UNIV CALIF LOS ANGELES,SCH MED,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DIV HEMATOL ONCOL,DEPT MED,LOS ANGELES,CA 90024. RI iMed.ULisboa, iMed.ULisboa/C-6292-2014; Goncalves, Joao/B-2013-2008; iMed.ULisboa, M2B /B-5277-2014 OI Goncalves, Joao/0000-0002-1245-3715; FU NIAID NIH HHS [AI 33837, AI33259, AI36186] NR 44 TC 114 Z9 118 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 DEC PY 1996 VL 70 IS 12 BP 8701 EP 8709 PG 9 WC Virology SC Virology GA VT704 UT WOS:A1996VT70400054 PM 8970997 ER PT J AU Krolewski, M Eggers, PW Warram, JH AF Krolewski, M Eggers, PW Warram, JH TI Magnitude of end-stage renal disease in IDDM: A 35 year follow-up study SO KIDNEY INTERNATIONAL LA English DT Article ID DEPENDENT DIABETES-MELLITUS; CONVERTING ENZYME-INHIBITION; CORONARY-ARTERY DISEASE; NEPHROPATHY; MICROALBUMINURIA; PROGRESSION; PROTEINURIA; CAPTOPRIL; MORTALITY AB Significant improvements were made during the last two decades in the treatment of IDDM patients. To assess the risk of ESRD in a population that was exposed to these improvements, we determined the cumulative incidence of ESRD in a cohort of 142 white patients who were aged less than 21 years when they came to the Joslin Diabetes Center in 1959 with recently diagnosed IDDM. The first case of ESRD occurred after 13 years of IDDM, and a total of 25 cases have developed by 35 years' duration (cumulative incidence 21.3%). Median survival after the diagnosis Of ESRD for the 16 patients who began dialysis was only 3.5 years. A strong predictor of the development of ESRD was the level of glycemic control during the first two decades of IDDM. ESRD developed in 36.3% of patients in the worst tertile for glycemic control but only in 14.4% and 9.2% of those in the middle and best tertiles. In comparison with two population based studies, the onset of ESRD in the Joslin Cohort was postponed by about five years. This advantage is more plausibly attributable to differences arising after the diagnosis of diabetes than to referral of less severe cases of IDDM to the Joslin Diabetes Center. What differences in diabetes care accounted for the postponement of ESRD cannot be discerned from comparisons among published studies, but likely candidates include Joslin's long-term advocacy of good glycemic control and the prompt implementation of new clinical interventions, such as antihypertensive treatment. C1 JOSLIN DIABET CTR,EPIDEMIOL & GENET SECT,BOSTON,MA 02215. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. US HLTH CARE FINANCING ADM,RES OFF,BALTIMORE,MD 21207. FU NIDDK NIH HHS [DK 41526] NR 24 TC 92 Z9 99 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1996 VL 50 IS 6 BP 2041 EP 2046 DI 10.1038/ki.1996.527 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA VU763 UT WOS:A1996VU76300026 PM 8943488 ER PT J AU Brazy, PC Chobanian, MC AF Brazy, PC Chobanian, MC TI Interactions between D-glucose and phosphate in renal proximal tubule cells SO KIDNEY INTERNATIONAL LA English DT Article ID INORGANIC-PHOSPHATE; CELLULAR MECHANISMS; MEMBRANE-VESICLES; TRANSPORT; KIDNEY; METABOLISM; CRABTREE; SODIUM; RAT AB The addition of D-glucose to renal proximal tubule cells reduces phosphate transport and in conditions of limited phosphate availability reduces mitochondrial respiration, oxidative phosphorylation and ATP content, a phenomenon called the Crabtree effect. The present study examined the effects of D-glucose on cellular content of inorganic phosphate, phosphomonoesters, and ATP. These studies were performed in suspensions of canine proximal tubules using P-31 NMR spectroscopy. When the extracellular medium contained 0.4 mM phosphate, addition of 8.3 mM D-glucose to the perfusion fluid significantly lowered cell content of inorganic phosphate (by 31%), phosphomonoesters (by 23%) and ATP (by 25%). Addition of a similar concentration of manifold had no significant effect on these measured parameters. Removal of inorganic phosphate from the extracellular medium in the absence of glucose reduced the cellular content of inorganic phosphate by only 9%. These data indicate that a reduction in cellular phosphate occurs during the Crabtree effect. The glucose effect on cellular phosphates appears to be an inhibition of phosphate uptake and an enhancement of phosphate efflux. The data do not support the hypothesis that glucose induces an increase in sugar monophosphates. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. RP Brazy, PC (reprint author), UNIV WISCONSIN,H4-514 CSC,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 28 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1996 VL 50 SU 57 BP S30 EP S34 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA VW139 UT WOS:A1996VW13900007 ER PT J AU Sanchez, J AguileraTejero, E Estepa, JC Almaden, Y Rodriguez, M Felsenfeld, AJ AF Sanchez, J AguileraTejero, E Estepa, JC Almaden, Y Rodriguez, M Felsenfeld, AJ TI A reduced PTH response to hypocalcemia after a short period of hypercalcemia: A study in dogs SO KIDNEY INTERNATIONAL LA English DT Article ID INDIVIDUAL PARATHYROID CELLS; PLASMA CALCIUM CONCENTRATION; SECRETORY PROTEIN-I; CHROMOGRANIN-A; NORMAL HUMANS; HORMONE SECRETION; PANCREASTATIN; ASSAY; ADAPTATION; ENDOTHELIN AB The relationship between PTH and calcium is best represented as a sigmoidal curve. In the normal animal and human, basal PTH is positioned at approximately 25% of maximum PTH and responds rapidly to small changes in calcium in either directions. Since PTH secretion is designed to response to either hypo- or hypercalcemia, the study was performed to evaluate whether the parathyroid gland would respond differently to hypocalcemia when the reduction in serum calcium was initiated from sustained hypercalcemia with maximal PTH suppression. Nine dogs were studied and the experimental protocol consisted of two separate parts in which the same dogs were used and the order of study was randomly assigned. For the hypercalcemic part, calcium chloride was infused intravenously to increase serum calcium to between 1.60 and 1.70 mN at 30 minutes and then continued for another 90 minutes to clamp the serum calcium at a constant rate to less than 0.85 mM. For the normocalcemic part, 5% dextrose in water was infused for two hours to control for fluid volume and time, and then EDTA was infused to lower the serum calcium at a constant rate to less than 0.85 mM. The results show that for the same serum calcium concentration at every 0.05 mM decrement in serum calcium below normal, PTH was less in the hypercalcemic than the normocalcemic dogs (P < 0.02). During the induction of hypocalcemia in the normocalcemic dogs, a characteristic sigmoidal curve was observed in which a small decrease in the serum calcium induced a brisk increase in PTH and a maximal PTH level was rapidly attained; however, during the induction of hypocalcemia in the hypercalcemic dogs, a maximal PTH level was attained. In conclusion, a sustained period of hypercalcemia resulted in a decreased PTH response to hypocalcemia and reduced the efficiency of the sigmoidal PTH-calcium relationship. Whether the mechanism for this difference in PTH secretion is due to secretory products, modification of the calcium receptor, or changes in intercellular communication among parathyroid cells deserves further study. C1 W LOS ANGELES VET AFFAIRS MED CTR,NEPHROL SECT 111L,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV CORDOBA,DEPT PATOL CLIN VET,CORDOBA,SPAIN. HOSP UNIV REINA SOFIA,DEPT CIRUGIA,CORDOBA,SPAIN. HOSP UNIV REINA SOFIA,DEPT NEFROL,CORDOBA,SPAIN. HOSP UNIV REINA SOFIA,UNIDAD INVEST,CORDOBA,SPAIN. RI Rodriguez, teresa/H-5452-2011 NR 28 TC 16 Z9 16 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1996 VL 50 SU 57 BP S18 EP S22 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA VW139 UT WOS:A1996VW13900005 ER PT J AU Paulus, W Baur, I Beutler, AS Reeves, SA AF Paulus, W Baur, I Beutler, AS Reeves, SA TI Diffuse brain invasion of glioma cells requires beta 1 integrins SO LABORATORY INVESTIGATION LA English DT Article ID EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; GENE-EXPRESSION; ASTROCYTOMA-CELLS; RAT-BRAIN; MIGRATION; ADHESION; RECEPTORS; SUBUNIT AB Diffuse invasion of brain tissue by single tumor cells is a characteristic feature of gliomas and a major reason why these tumors cannot be completely resected. The molecular basis of brain invasion is poorly understood. We regulated the expression of beta 1 integrins, the major group of extracellular matrix receptors, in astrocytic tumor cells by using a tetracycline-dependent transcription control system. Rat C6 glioma cells were stably transfected with (a) the tetracycline-controlled transactivator (tTA) gene, (b) an antisense beta 1 cDNA under the control of a tTA/tetracycline-responsive promoter, and (c) the beta-galactosidase (lacZ) gene for histochemical identification. In one clone, C6TL beta, beta 1 protein levels were unaffected in the presence of tetracycline, but they were reduced by 60% in the absence of tetracycline because of production of antisense mRNA. C6TL beta cells were transplanted into the striatum of nude mice. After 14 days in the presence of tetracycline in the drinking water, tumors showed diffuse brain invasion, mainly along vascular basement membranes. In the absence of tetracycline, however, tumor cells were compact and generally well delineated from the surrounding brain tissue. These data, ie, blocking of brain invasion by antisense beta 1 mRNA, either because of disturbed interaction of beta 1 with brain extracellular matrix components or interference with beta 1-dependent signaling pathways, strongly suggest that beta 1 integrins are required for diffuse brain invasion of gliomas. C1 UNIV ZURICH HOSP,INST NEUROPATHOL,CH-8091 ZURICH,SWITZERLAND. MASSACHUSETTS GEN HOSP,MOL NEUROONCOL LAB,BOSTON,MA. RP Paulus, W (reprint author), UNIV ERLANGEN NURNBERG,SCH MED,INST PATHOL,DIV NEUROPATHOL,KRANKENHAUSSTR 8-10,D-91054 ERLANGEN,GERMANY. NR 37 TC 81 Z9 85 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD DEC PY 1996 VL 75 IS 6 BP 819 EP 826 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA VY754 UT WOS:A1996VY75400007 PM 8973477 ER PT J AU DeKay, ML AF DeKay, ML TI The difference between Blackstone like error ratios and probabilistic standards of proof SO LAW AND SOCIAL INQUIRY-JOURNAL OF THE AMERICAN BAR FOUNDATION LA English DT Article ID DECISION-MAKING; JURY VERDICTS; CIVIL TRIALS; BURDENS; LEGAL; ACCURACY; MODELS AB Statements regarding the ratio of erroneous acquittals to erroneous convictions are often thought to have clear implications for standards of proof. For example, Blackstone's comment that ''it is better that ten guilty persons escape, than that one innocent suffer'' is believed by many to imply a precise numerical value for proof beyond a reasonable doubt. Specifically, jurors should vote to convict only if they are at least 91% certain of the defendant's guilt. Unfortunately, the belief that this decision threshold will lead to the desired ratio of judicial errors is simply incorrect. Depending on (a) the accuracy with which juries discriminate between truly innocent and truly guilty defendants and (b) the proportion of defendants who are truly guilty, this probabilistic standard of proof mar lead to any ratio of judicial errors, including those favoring conviction of the innocent over acquittal of the guilty. Although standards of proof cannot be equated with error ratios in a simple manner, the problem lies not with probabilistic decision thresholds but with the desire to achieve a certain error ratio. C1 UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. UNIV PENN,WHARTON SCH,DEPT OPERAT & INFORMAT MANAGEMENT,PHILADELPHIA,PA 19104. RP DeKay, ML (reprint author), VET AFFAIRS MED CTR,PHILADELPHIA,PA, USA. NR 97 TC 32 Z9 32 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0897-6546 J9 LAW SOCIAL INQUIRY JI Law Soc. Inq.-J. Am. Bar Found. PD WIN PY 1996 VL 21 IS 1 BP 95 EP 132 DI 10.1111/j.1747-4469.1996.tb00013.x PG 38 WC Law SC Government & Law GA UR956 UT WOS:A1996UR95600007 ER PT J AU Tsai, T Davalath, S Rankin, C Radich, JP Head, D Appelbaum, FR Boldt, DH AF Tsai, T Davalath, S Rankin, C Radich, JP Head, D Appelbaum, FR Boldt, DH TI Tumor suppressor gene alteration in adult acute lymphoblastic leukemia (ALL). Analysis of retinoblastoma (Rb) and p53 gene expression in lymphoblasts of patients with de novo, relapsed, or refractory ALL treated in Southwest Oncology Group studies SO LEUKEMIA LA English DT Article DE ALL; tumor suppressor genes; retinoblastoma (Rb) gene; p53 ID LYMPHOID LEUKEMIA; GROUP EXPERIENCE; CELL LINES; MUTATIONS; PROTEIN; CANCER; CHILDHOOD; DELETION; ALLELE; RNA AB To examine the impact of inactivation of tumor suppressor genes on outcome in adult ALL, we compared two groups of patients registered to SWOG treatment protocols for loss of the Rb gene product end p53 overexpression: (1) 89 patients with de novo ALL, and (2) 26 patients with relapsed/refractory ALL. The groups were comparable with respect to age, sex, and race. Cell lysates (greater than or equal to 80% blasts) were analyzed by immunoblotting which enabled detection of Rb or p53 proteins in as little as 1 mu g of lysate. Loss of Rb expression (pRbneg) was found in 54/85 (64%) de novo and 11/19 (58%) relapsed patients (P = 0.79). Overexpression of p53 (p53abn), indicative of p53 point mutations, was found in 16/75 (21%) de novo and 8/19 (42%) relapsed patients (P = 0.08). Using a nonisotopic RNase cleavage assay, p53 point mutations in exons 5-9 were confirmed in 14/23 (61%) p53abn specimens. For the de novo ALL group, patients with normal Rb protein had higher WBC and higher peripheral blast and lymphocyte counts. Otherwise neither abnormal Rb or p53 expression correlated with any of a large panel of clinical and laboratory variables including FAB class, blast lineage, expression of myeloid antigens or CD34, and presence of the Ph1 chromosome or BCR-ABL. Analyses of treatment outcomes demonstrated no significant impact of Rb or p53 status alone on CR rates, relapse-free or overall survival. An identical percentage (11%) of both de novo and relapsed/refractory patients had concurrent abnormalities of both Rb and p53 expression (pRbneg/p53abn). The survival curve of these patients suggests an increased rate of early death, but the number of patients in this group was small. Summarizing, (1) loss of Rb expression is common in adult ALL; (2) overexpression of p53 may be more frequent in relapsed/refractory than de novo adult ALL; and (3) although Rb or p53 alterations alone are not strong independent predictors of outcome, their concurrent expression may predict a poor response to therapy. C1 UNIV TEXAS, HLTH SCI CTR, DEPT MED, DIV HEMATOL, SAN ANTONIO, TX 78284 USA. AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. FRED HUTCHINSON CANC RES CTR, SW ONCOL GRP, CTR STAT, SEATTLE, WA 98104 USA. FRED HUTCHINSON CANC RES CTR, DIV CLIN RES, SEATTLE, WA 98104 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. UNIV WASHINGTON, DEPT MED, SEATTLE, WA USA. SW ONCOL GRP, LEUKEMIA BIOL PROGRAM, SAN ANTONIO, TX USA. FU NCI NIH HHS [CA60432, CA54174, CA32102] NR 45 TC 31 Z9 31 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 1996 VL 10 IS 12 BP 1901 EP 1910 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA VZ830 UT WOS:A1996VZ83000009 PM 8946929 ER PT J AU Kelly, K AF Kelly, K TI Waist-high in the world: A life among the nondisabled - Mairs,N SO LIBRARY JOURNAL LA English DT Book Review RP Kelly, K (reprint author), MASSACHUSETTS GEN HOSP LIB,BOSTON,MA, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 1996 VL 121 IS 20 BP 132 EP 132 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA VY041 UT WOS:A1996VY04100230 ER PT J AU Donahue, KM Weisskoff, RM Chesler, DA Kwong, KK Bogdanov, AA Mandeville, JB Rosen, BR AF Donahue, KM Weisskoff, RM Chesler, DA Kwong, KK Bogdanov, AA Mandeville, JB Rosen, BR TI Improving MR quantification of regional blood volume with intravascular T-1 contrast agents: Accuracy, precision, and water exchange SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE blood volume; vascular proton exchange; angiogenesis; intravascular contrast agents ID RELAXATION-TIMES; RAT; TISSUE; ENHANCEMENT; PROTONS; MUSCLE; MEDIA; EPI AB The goal of this work was to develop a comprehensive understanding of the relationship between vascular proton exchange rates and the accuracy and precision of tissue blood volume estimates using intravascular T-1 contrast agents. Using computer simulations, the effects of vascular proton exchange and experimental pulse sequence parameters on measurement accuracy were quantified. T-1 and signal measurements made in a rat model implanted with R3230 mammary adenocarcinoma tumors demonstrated that the theoretical findings are biologically relevant; data demonstrated that over-simplified exchange models may result in measures of tumor, muscle, and liver blood volume fractions that depend on experimental parameters such as the vascular contrast concentration. As a solution to the measurement of blood volume in tissues with exchange that is unknown, methods that minimize exchange rate dependence were examined. Simulations that estimated both the accuracy and precision of such methods indicated that both the inversion recovery and the transverse-spoiled gradient echo methods using a ''noexchange'' model provide the best trade-off between accuracy and precision. C1 MASSACHUSETTS GEN HOSP,NMR CTR,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA66072]; NHLBI NIH HHS [HL39810] NR 23 TC 109 Z9 109 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD DEC PY 1996 VL 36 IS 6 BP 858 EP 867 DI 10.1002/mrm.1910360608 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VU890 UT WOS:A1996VU89000007 PM 8946351 ER PT J AU Wang, X Egan, KM Gragoudas, ES Kelsey, KT AF Wang, X Egan, KM Gragoudas, ES Kelsey, KT TI Constitutional alterations in p16 in patients with uveal melanoma SO MELANOMA RESEARCH LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 14-19, 1995 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol DE family history; genetics; p16; uveal melanoma ID K MOLE SYNDROME; CHOROIDAL MELANOMA; MALIGNANT-MELANOMA; FAMILIAL MELANOMA; MUTATIONS; P53; GENE; IRRADIATION; CANCER; SKIN AB Chromosome 9p21 contains a susceptibility gene for cutaneous melanoma. Recent studies suggest that the gene responsible may be CDK41, since it encodes a putative cell cycle inhibitor, p16, and is frequently lost or rearranged in melanoma cell lines. In this study we examined whether germline alterations in CDK41 could be identified in patients with melanoma of the uveal tract. From an archive of bloods collected from patients with uveal melanoma, we identified 13 samples drawn from patients with a history in a family member of uveal (n = 6) or cutaneous (n = 7) melanoma. An additional 24 'control' bloods (without melanoma or any other primary malignancy in a family member), similar to the 'cases' in age end number of first-degree relatives, were also selected for study. For each sample, DNA was extracted from the red blood cell fraction. Using the polymerase chain reaction-single strand conformation polymorphism method, we screened for alterations in p16. Specific changes were characterized by DNA sequencing. Six nucleotide changes were detected In five (13.5%) of the 37 samples examined. An altered gene was found in one (7.7%) of the 13 patients with a family history (of intra-ocular melanoma) and four (16.7%) of the 24 patients with no family history (P = 0.64) of melanoma. In this series the group with a positive family history was predominantly female and most pedigrees involved matrilineal descent. In these data prevalence of germline alteration in p16 was similar in familial and sporadic cases. The results provide evidence against a significant role for p16 in familial clustering of intra-ocular and cutaneous melanomas. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,OCCUPAT HLTH PROGRAM,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RI Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [ES 00002] NR 32 TC 23 Z9 24 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD DEC PY 1996 VL 6 IS 6 BP 405 EP 410 DI 10.1097/00008390-199612000-00001 PG 6 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA WB088 UT WOS:A1996WB08800001 PM 9013477 ER PT J AU Adams, PD Sellers, WR Sharma, SK Wu, AD Nalin, CM Kaelin, WG AF Adams, PD Sellers, WR Sharma, SK Wu, AD Nalin, CM Kaelin, WG TI Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; CELL-CYCLE; GROWTH SUPPRESSION; TRANSCRIPTION FACTOR; PROTEIN-KINASE; S-PHASE; MAMMALIAN FIBROBLASTS; DNA-REPLICATION; BINDING DOMAINS; BREAST-CANCER AB Understanding how cyclin-cdk complexes recognize their substrates is a central problem in cell cycle biology. We identified an E2F1-derived eight-residue peptide which blocked the binding of cyclin A and E-cdk2 complexes to E2F1 and p21. Short peptides spanning similar sequences in p107, p130, and p21-like cdk inhibitors likewise bound to cyclin A-cdk2 and cyclin E-cdk2. In addition, these peptides promoted formation of stable cyclin A-cdk2 complexes in vitro but inhibited the phosphorylation of the retinoblastoma protein by cyclin A- but not cyclin B-associated kinases. Mutation of the cyclin-cdk2 binding motifs in p107 and E2F1 likewise prevented their phosphorylation by cyclin A-associated kinases in vitro. The cdk inhibitor p21 was found to contain two functional copies of this recognition motif, as determined by in vitro kinase binding/inhibition assays and in vivo growth suppression assays. Thus, these studies have identified a cyclin A- and E-cdk2 substrate recognition motif. Furthermore, these data suggest that p21-like cdk inhibitors function, at least in part, by blocking the interaction of substrates with cyclin-cdk2 complexes. C1 DANA FARBER CANC INST,BOSTON,MA 02118. HARVARD UNIV,SCH MED,BOSTON,MA. SANDOZ INST MED RES,ONCOL RES PROGRAM,E HANOVER,NJ. NR 94 TC 284 Z9 284 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1996 VL 16 IS 12 BP 6623 EP 6633 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VU688 UT WOS:A1996VU68800002 PM 8943316 ER PT J AU Johnstone, RW See, RH Sells, SF Wang, J Muthukkumar, S Englert, C Haber, DA Licht, JD Sugrue, SP Roberts, T Rangnekar, VM Shi, Y AF Johnstone, RW See, RH Sells, SF Wang, J Muthukkumar, S Englert, C Haber, DA Licht, JD Sugrue, SP Roberts, T Rangnekar, VM Shi, Y TI A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ZINC FINGER PROTEIN; FACTOR-A-CHAIN; GENE-PRODUCT; NUCLEAR-LOCALIZATION; UROGENITAL SYSTEM; ADENOVIRUS E1A; POLYMERASE-II; DNA-BINDING; CELL-LINE; EXPRESSION AB The tumor suppressor WT1 represses and activates transcription, The loss and/or imbalance of the dual transcriptional activity of WT1 may contribute to Wilms' tumor, In this study, we identified par-4 (for prostate apoptosis response) as a WT1-interacting protein that itself functions as a transcriptional repressor, par-4 contains a putative leucine zipper domain and is specifically upregulated during apoptosis of prostate cells (S. F. Sells, D. P. Wood, Jr., S. S. Joshi-Barve, S. Muthukkumar, R. J. Jacob, S. A. Crist, S. Humphreys, and V. M. Rangnekar, Cell Growth Differ. 5:457-466, 1994). The leucine repeat domain of par-4 was shown to interact with the zinc finger DNA binding domain of WT1, Immunoprecipitation-Western blot (immunoblot) analyses demonstrated in vivo WT1-par-4 interactions, par-4 was ubiquitously expressed, and the protein was found in both the nucleus and the cytoplasm, Functionally, par-4 inhibited transcription activated by WT1, but not by the related protein EGR1, Inhibition of WT1-mediated transcription was dependent on the domain of par-4 that mediates its physical association with WT1. In addition, par-4 augmented WT1-mediated repression, possibly by contributing an additional repression domain, Consistent,vith these results, par-4 functioned as a transcriptional repressor when brought to a promoter via a heterologous DNA binding domain, Significantly, par-4, but not a mutant unable to interact with WT1, rescued growth suppression caused by WT1. Thus, we identified a novel repressor that modulates transcription as well as growth suppression functions of WT1. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. UNIV KENTUCKY,DEPT SURG,DIV UROL,LEXINGTON,KY 40536. MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. MT SINAI SCH MED,BROOKDALE CTR MOL BIOL,NEW YORK,NY 10029. UNIV FLORIDA,DEPT ANAT & CELL BIOL,GAINESVILLE,FL 32610. FU NCI NIH HHS [CA60872, CA68258] NR 72 TC 176 Z9 180 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1996 VL 16 IS 12 BP 6945 EP 6956 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VU688 UT WOS:A1996VU68800036 PM 8943350 ER PT J AU Skapek, SX Rhee, J Kim, PS Novitch, BG Lassar, AB AF Skapek, SX Rhee, J Kim, PS Novitch, BG Lassar, AB TI Cyclin-mediated inhibition of muscle gene expression via a mechanism that is independent of pRB hyperphosphorylation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LOOP-HELIX PROTEINS; DEPENDENT KINASE-ACTIVITY; FIBROBLAST GROWTH-FACTOR; CELL-CYCLE; MYOGENIC DIFFERENTIATION; RETINOBLASTOMA PROTEIN; DNA-BINDING; TERMINAL DIFFERENTIATION; TRANSCRIPTIONAL REPRESSION; MYOBLAST DIFFERENTIATION AB It was recently demonstrated that ectopic expression of cyclin D1 inhibits skeletal muscle differentiation and, conversely, that expression of cyclin-dependent kinase (cdk) inhibitors facilitates activation of this differentiation program (S. S. Rao, C. Chu, and D. S. Kohtz, Mol. Cell. Biol. 14:5259-5267, 1994; S. S. Rao and D. S. Kohtz, J. Biol. Chem. 270:4093-4100, 1995; S. X. Skapek, J. Rhee, D. B. Spicer, and A. B. Lassar, Science 267:1022-1024, 1995). Here we demonstrate that cyclin D1 inhibits muscle gene expression without affecting MyoD DNA binding activity, Ectopic expression of cyclin D1 inhibits muscle gene activation by both MyoD and myogenin, including a mutated form of myogenin in which two potential inhibitory cdk phosphorylation sites are absent. Because the retinoblastoma gene product, pRB, is a known target for cyclin D1-cdk phosphorylation, we determined whether cyclin D1-mediated inhibition of myogenesis was due to hyperphosphorylation of pRB In pRB-deficient fibroblasts, the ability of MyoD to activate the expression of muscle-specific genes requires coexpression of ectopic pRB (B. G. Novitch, G. J. Mulligan, T. Jacks, and A. B. Lassar, J. Cell Biol., 135:441-456, 1996). In these cells, the expression of cyclins A and E can lead to pRB hyperphosphorylation and can inhibit muscle gene expression. The negative effects of cyclins A or E on muscle gene expression are, however, reversed by the presence of a mutated form of pRB which cannot be hyperphosphorylated. In contrast, cyclin D1 can inhibit muscle gene expression in the presence of the nonhyperphosphorylatable form of pRB. On the basis of these results we propose that G(1) cyclin-cdk activity blocks the initiation of skeletal muscle differentiation by two distinct mechanisms: one that is dependent on pRB hyperphosphorylation and one that is independent of pRB hyperphosphorylation. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. OI Novitch, Bennett/0000-0002-2696-3708 FU NICHD NIH HHS [K08HD01105-01] NR 78 TC 99 Z9 100 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1996 VL 16 IS 12 BP 7043 EP 7053 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VU688 UT WOS:A1996VU68800045 PM 8943359 ER PT J AU Tanzi, RE Kovacs, DM Kim, TW Moir, RD Guenette, SY Wasco, W AF Tanzi, RE Kovacs, DM Kim, TW Moir, RD Guenette, SY Wasco, W TI Molecular analysis of the early onset familial Alzheimer's disease genes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,GENET & AGING UNIT,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 33 EP 33 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800032 ER PT J AU Jaenisch, R Tucker, K Beard, C Li, E AF Jaenisch, R Tucker, K Beard, C Li, E TI DNA methylation and genomic imprinting SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA. MASSACHUSETTS GEN HOSP EAST,CHARLESTOWN,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 43 EP 43 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800045 ER PT J AU Molnar, A Theodoras, AM Woodgett, JR Zon, LI Kyriakis, JM AF Molnar, A Theodoras, AM Woodgett, JR Zon, LI Kyriakis, JM TI Inhibition of cell cycle progression at G1/S by the Cdc42Hs-p38/RK signaling pathway. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DIABET RES LAB,BOSTON,MA 02114. MITOTIX INC,CAMBRIDGE,MA. ONTARIO CANC INST,TORONTO,ON M4X 1K9,CANADA. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 156 EP 156 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800158 ER PT J AU Lopes, UG Cooper, GM AF Lopes, UG Cooper, GM TI Induction of apoptosis by the disruption of the ubiquitin-proteasome pathway. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. FED UNIV RIO DE JANEIRO,INST BIOFIS CARLOS CHAGAS FILHO,RIO JANEIRO,BRAZIL. RI Lopes, Ulisses/N-4416-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 175 EP 175 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800176 ER PT J AU Kedersha, NL Fernandez, A Dember, L Xu, Y Medley, Q Streuli, M Anderson, P AF Kedersha, NL Fernandez, A Dember, L Xu, Y Medley, Q Streuli, M Anderson, P TI RNA-binding protein TIA-1 induces the formation of endoplasmic-reticulum-derived vacuoles during stress-induced apoptosis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 IMMUNOGEN INC,CAMBRIDGE,MA 02139. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 185 EP 185 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800187 ER PT J AU Hasson, T Gillespie, PG Garcia, J MacDonald, RB Mooseker, MS Corey, DP AF Hasson, T Gillespie, PG Garcia, J MacDonald, RB Mooseker, MS Corey, DP TI Differential distribution of unconventional myosins in the sensory epithelia of the inner ear. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 YALE UNIV,DEPT BIOL,NEW HAVEN,CT 06520. YALE UNIV,DEPT PATHOL,NEW HAVEN,CT 06520. YALE UNIV,DEPT CELL BIOL,NEW HAVEN,CT 06520. JOHNS HOPKINS UNIV,DEPT PHYSIOL,BALTIMORE,MD 21205. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 221 EP 221 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800220 ER PT J AU Oliver, TN Corey, DP Derfler, BH Pennisi, CM Cheney, RE AF Oliver, TN Corey, DP Derfler, BH Pennisi, CM Cheney, RE TI Myosin-X: An unconventional myosin with PH domains. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV N CAROLINA,DEPT PHYSIOL,CHAPEL HILL,NC 27599. MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 227 EP 227 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800226 ER PT J AU Neville, C Gonzales, D Rosenthal, N AF Neville, C Gonzales, D Rosenthal, N TI Fiber-specific regulation of muscle gene expression. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. RI Rosenthal, Nadia/O-7009-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 241 EP 241 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800241 ER PT J AU Amano, S Takahara, K Gerecke, D Nishiyama, T Lee, S Greenspan, DS Burgeson, RE AF Amano, S Takahara, K Gerecke, D Nishiyama, T Lee, S Greenspan, DS Burgeson, RE TI Bone morphogenetic protein-1 is the processing enzyme for laminin 5 in human keratinocytes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIO RES CTR,BOSTON,MA. SHISELDO RES CTR,YOKOHAMA,KANAGAWA,JAPAN. UNIV WISCONSIN,DEPT PATHOL & LAB MED,MADISON,WI. RI Nishiyama, Toshio/C-5434-2013 NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 338 EP 338 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800336 ER PT J AU Panzer, P Zuk, A Vignoud, L Matlin, KS AF Panzer, P Zuk, A Vignoud, L Matlin, KS TI Basolateral sorting signals in alpha 2/beta 1-integrins. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02129. UNIV GRENOBLE 1,LAB ETUD SYST ADHESIFS CELLULAIRE,F-38041 GRENOBLE,FRANCE. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 436 EP 436 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800434 ER PT J AU Boll, W Ohno, H Songyang, Z Rapoport, I Cantley, L Bonifacino, J Kirchhausen, T AF Boll, W Ohno, H Songyang, Z Rapoport, I Cantley, L Bonifacino, J Kirchhausen, T TI Recognition of tyrosine-based signals by clathrin AP-2 complexes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NIH,BETHESDA,MD 20892. BETH ISRAEL HOSP,BOSTON,MA 02115. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 459 EP 459 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800460 ER PT J AU Hudson, DL Amano, S Keene, D Burgeson, RE AF Hudson, DL Amano, S Keene, D Burgeson, RE TI Studies into the expression and function of the hemidesmosomal protein HD1 in human epidermal keratinocytes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 496 EP 496 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800496 ER PT J AU Li, SL Valente, AJ Zhao, SJ Clark, RA AF Li, SL Valente, AJ Zhao, SJ Clark, RA TI PU.1 is essential for p47phox promoter activity in myeloid cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. S TEXAS VET HLTH CARE SYST,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 840 EP 840 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800840 ER PT J AU Hofmann, F Martelli, F Livingston, DM Wang, ZY AF Hofmann, F Martelli, F Livingston, DM Wang, ZY TI Cell cycle regulated E2F1 degradation by the ubiquitin-proteasome pathway. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1012 EP 1012 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801011 ER PT J AU Loeser, RF Varnum, BC Carlson, CS Goldring, MB Liu, ET Sadiev, S Kute, TE Wallin, R AF Loeser, RF Varnum, BC Carlson, CS Goldring, MB Liu, ET Sadiev, S Kute, TE Wallin, R TI Chondrocyte expression of growth arrest specific gene 6 (Gas6) and the tyrosine kinase receptor axl: Role in autocrine signalling to promote cell survival SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT INTERNAL MED,WINSTON SALEM,NC 27106. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT COMPARAT MED,WINSTON SALEM,NC 27106. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PATHOL,WINSTON SALEM,NC 27106. AMGEN CORP,THOUSAND OAKS,CA 91320. MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. UNIV N CAROLINA,CHAPEL HILL,NC 27599. RI Liu, Edison/C-4141-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1125 EP 1125 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801123 ER PT J AU Tilly, K Perez, GI Tilly, JL AF Tilly, K Perez, GI Tilly, JL TI Ceramide-induced apoptosis in ovarian follicles: Kinetic analysis and modulation by potassium chloride efflux. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1128 EP 1128 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801127 ER PT J AU Maravei, DV Trbovich, AM Perez, GI Tilly, KI Wong, W Tilly, JL AF Maravei, DV Trbovich, AM Perez, GI Tilly, KI Wong, W Tilly, JL TI Recombinant CPP32 catalyzes proteolytic degradation of the cytoskeletal elements, alpha-fodrin and alpha-actin. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET GYNECOL,BOSTON,MA 02114. BASF BIORES CORP,DEPT BIOCHEM,WORCESTER,MA 01605. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1129 EP 1129 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801133 ER PT J AU Kahana, JA Schlenstedt, G Evanchuk, D Silver, PA AF Kahana, JA Schlenstedt, G Evanchuk, D Silver, PA TI YDG1 encodes a novel member of the yeast dynactin complex. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MOL & CELLULAR BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1208 EP 1208 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801208 ER PT J AU Vechio, JD Bruijn, LI Xu, Z Brown, RH Cleveland, DW AF Vechio, JD Bruijn, LI Xu, Z Brown, RH Cleveland, DW TI Sequence variants in human neurofilaments: Absence of linkage to familial ALS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 WORCESTER FDN EXPT BIOL INC,SHREWSBURY,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT NEUROSCI,LA JOLLA,CA 92093. LUDWIG INST CANC RES,LA JOLLA,CA 92093. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1273 EP 1273 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801273 ER PT J AU Wilson, PD Kaelin, W Burrow, CR AF Wilson, PD Kaelin, W Burrow, CR TI Co-expression of the PKD-1 protein with matrix receptor and adhesion plaque proteins in human fetal and ADPKD epithelia in vitro. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 MT SINAI SCH MED,DEPT MED,NEW YORK,NY. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1423 EP 1423 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801421 ER PT J AU Bosch, I DunussiJoannopoulos, K Wu, RL Furlong, ST Croop, J AF Bosch, I DunussiJoannopoulos, K Wu, RL Furlong, ST Croop, J TI Phosphatidylcholine and phosphatidylethanolamine behave as substrates or the human MDR1 P-glycoprotein. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1502 EP 1502 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801501 ER PT J AU Taura, T Schlenstedt, G Silver, PA AF Taura, T Schlenstedt, G Silver, PA TI Studies on the function of YRB2, a nuclear protein with a Ran-binding domain. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1688 EP 1688 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801687 ER PT J AU Koepp, DM Wong, DH Corbett, AH Silver, PA AF Koepp, DM Wong, DH Corbett, AH Silver, PA TI The nuclear import receptor interacts with the Ran GTPase activating protein, Rna1p SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1689 EP 1689 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801688 ER PT J AU Wong, DH Corbett, AH Silver, PA AF Wong, DH Corbett, AH Silver, PA TI Conditional alleles of yeast Ran define unique interactions with nuclear transport components. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MOL PHARMACOL & BIOCHEM,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1690 EP 1690 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801691 ER PT J AU Chen, W Li, YP AF Chen, W Li, YP TI Generation of osteoclast-inductive and osteoclastogenic cell lines immortalized with SV-40 large 7 antigen SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 FORSYTH DENT CTR,DEPT CYTOKINE BIOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1767 EP 1767 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801766 ER PT J AU Lee, GY Croop, JM Anderson, E AF Lee, GY Croop, JM Anderson, E TI The localization of multidrug-resistant gene (MDR1) product, P-glycoprotein, in normal and dehydroepiandrosterone induced cystogenic rat ovaries SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1785 EP 1785 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801781 ER PT J AU Couet, J Okamoto, T Ikezu, T Lisanti, MP AF Couet, J Okamoto, T Ikezu, T Lisanti, MP TI Interaction of caveolin with G(alpha) subunits is mediated by the recognition of a caveolin binding motif SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,SHRINERS HOSP CRIPPLED CHILDREN,DEPT ANESTHESIA,BOSTON,MA 02114. RI Lisanti, Michael/C-6866-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1962 EP 1962 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801958 ER PT J AU Wagner, DD AF Wagner, DD TI Selectin-deficient mice: Animal models for various human diseases. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,DEPT PATHOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1964 EP 1964 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801962 ER PT J AU Berditchevski, F Tolias, KF Wong, K Carpenter, CL Hemler, ME AF Berditchevski, F Tolias, KF Wong, K Carpenter, CL Hemler, ME TI Novel link between integrins, TM4SF proteins (CD63, CD81) and phosphatidylinositol 4-kinase. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 BETH ISRAEL HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1969 EP 1969 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801967 ER PT J AU Hansen, H Cheatham, B Feener, EP AF Hansen, H Cheatham, B Feener, EP TI Protein kinase C serine phosphorylates Shc and inhibits angiotensin II-mediated Shc tyrosine phosphorylation in rat aortic smooth muscle cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2004 EP 2004 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802000 ER PT J AU Prowse, DM Dotto, GP AF Prowse, DM Dotto, GP TI SP3 regulates expression of the p21 gene during keratinocyte differentiation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2073 EP 2073 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802070 ER PT J AU Kraeft, SK Chen, DS Li, HS Chen, LB Lai, MMC AF Kraeft, SK Chen, DS Li, HS Chen, LB Lai, MMC TI Mouse hepatitis virus infection induces an early, transient calcium influx in mouse astrocytoma cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. UNIV SO CALIF,SCH MED,HOWARD HUGHES MED INST,LOS ANGELES,CA 90033. UNIV SO CALIF,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90033. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2140 EP 2140 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802137 ER PT J AU Galneder, R Ludwig, M Goldmann, WH Wang, N Gaub, HE Ezzell, RM AF Galneder, R Ludwig, M Goldmann, WH Wang, N Gaub, HE Ezzell, RM TI Differences in viscoelasticity of vinculin-deficient F9 cells measured by magnetometry and atomic force microscopy. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,SURG RES UNIT,CHARLESTOWN,MA 02129. UNIV MUNICH,D-8000 MUNICH,GERMANY. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RI Goldmann, Wolfgang/H-5572-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2239 EP 2239 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802236 ER PT J AU GonzalezAgosti, C Xu, L Pinney, D Beauchamp, R Hobbs, W Gusella, JF Ramesh, V AF GonzalezAgosti, C Xu, L Pinney, D Beauchamp, R Hobbs, W Gusella, JF Ramesh, V TI The NF2 tumor suppressor protein, merlin, localizes preferentially in membrane ruffles. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2245 EP 2245 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802242 ER PT J AU Chen, Q Goetinck, PF AF Chen, Q Goetinck, PF TI Assembly of cartilage matrix protein networks requires a heptad repeat coiled coil. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 PENN STATE UNIV,COLL MED,DEPT ORTHOPAED & REHABIL,MUSCULOSKELETAL RES LAB,HERSHEY,PA. HARVARD UNIV,SCH MED,CBRC,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA. RI Chen, Qian/C-4354-2011 OI Chen, Qian/0000-0003-4406-5618 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2393 EP 2393 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802387 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 The extracellular matrix potently affects baculoviral gene transfer in primary cultures of adult rat hepatocytes SO MOLECULAR BIOLOGY OF THE CELL 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 SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2752 EP 2752 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802746 ER PT J AU Dalby, B Pesavento, PA Goldstein, LSB AF Dalby, B Pesavento, PA Goldstein, LSB TI A novel kinesin like motor involved in wingless (WNT) signaling in Drosophila. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV CALIF SAN DIEGO,DIV CELLULAR & MOL MED,DEPT PHARMACOL,LA JOLLA,CA 92093. DANA FARBER CANC INST,DEPT INFECT DIS,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2834 EP 2834 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802827 ER PT J AU Fleming, JC Cramer, EM Guichard, J Wagner, DD AF Fleming, JC Cramer, EM Guichard, J Wagner, DD TI The transmembrane domain contributes greatly to the granular targeting of P-selectin. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. TUFTS UNIV,PROGRAM CELL MOL & DEV BIOL,BOSTON,MA 02111. HOP HENRI MONDOR,INSERM U91,F-94010 CRETEIL,FRANCE. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2928 EP 2928 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802919 ER PT J AU Simon, AM Goodenough, DA Li, E Paul, DL AF Simon, AM Goodenough, DA Li, E Paul, DL TI Female infertility in mice lacking connexin37. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2960 EP 2960 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802955 ER PT J AU Valente, AJ Abramova, MA Pearson, DW Clark, RA AF Valente, AJ Abramova, MA Pearson, DW Clark, RA TI Identification of a retinoblastoma control element in the promoter of human calreticulin. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. S TEXAS VET HLTH CARE SYST,DEPT MED,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3071 EP 3071 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803061 ER PT J AU Guttenberg, Z Tempel, M Goldmann, WH Isenberg, G Sackmann, E Ezzell, RM AF Guttenberg, Z Tempel, M Goldmann, WH Isenberg, G Sackmann, E Ezzell, RM TI Examination of temperature-induced 'gel-sol' transformation of alpha-actinin cross-linked actin networks by rheology and light scattering. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129. TECH UNIV MUNICH,D-85747 GARCHING,GERMANY. RI Goldmann, Wolfgang/H-5572-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3150 EP 3150 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803140 ER PT J AU Sheng, M Kim, E Naisbitt, S Niethammer, M Rothschild, A AF Sheng, M Kim, E Naisbitt, S Niethammer, M Rothschild, A TI Structure and function of the PSD-95/SAP90 family of MAGUK proteins in synaptic junctions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HOWARD HUGHES MED INST,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3205 EP 3205 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803196 ER PT J AU Hsueh, YP Sheng, M AF Hsueh, YP Sheng, M TI The molecular mechanism of ion channel clustering by the synaptic MAGUK PSD-95 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. HOWARD HUGHES MED INST,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3206 EP 3206 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803195 ER PT J AU Severin, FF Schuyler, S Kaplan, KB Sorger, PK Hyman, AA AF Severin, FF Schuyler, S Kaplan, KB Sorger, PK Hyman, AA TI Interaction of yeast kinetochores with microtubules SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 EUROPEAN MOL BIOL LAB,PROT DESIGN GRP,D-69117 HEIDELBERG,GERMANY. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. RI Hyman, Anthony/B-3917-2017 OI Hyman, Anthony/0000-0003-3664-154X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3289 EP 3289 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803277 ER PT J AU Sorkin, BC Yelick, PC AF Sorkin, BC Yelick, PC TI Isolation and characterization of a cDNA encoding an novel zebrafish cadherin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 FORSYTH RES CTR,DEPT CYTOKINE BIOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3505 EP 3505 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803494 ER PT J AU Lerner, T Cheng, I Lee, R AF Lerner, T Cheng, I Lee, R TI Expression and localization of the Batten disease protein CLN3. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,MOL NEUROGENET LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3795 EP 3795 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803783 ER PT J AU Tsuruda, LM Lamperti, ED Lewis, SE Tolentino, PJ Dikkes, P VillaKomaroff, L Ebert, KM Fink, JS AF Tsuruda, LM Lamperti, ED Lewis, SE Tolentino, PJ Dikkes, P VillaKomaroff, L Ebert, KM Fink, JS TI Region-specific central nervous system expression and axotomy-induced regulation in sympathetic neurons of a VIP-beta-galactosidase fusion gene in transgenic mice SO MOLECULAR BRAIN RESEARCH LA English DT Article DE axotomy; brain; cell culture; histochemistry; beta-galactosidase; mouse; neuropeptide; superior cervical ganglion; transgene; vasoactive intestinal peptide ID VASOACTIVE INTESTINAL POLYPEPTIDE; LEUKEMIA INHIBITORY FACTOR; STAT PROTEINS; PEPTIDE GENE; PHENOTYPIC PLASTICITY; MESSENGER-RNA; PHORBOL ESTER; GLOBIN GENE; CYCLIC-AMP; RAT-BRAIN AB To assess the activity of cis-acting elements that direct human vasoactive intestinal peptide (VIP) expression in vivo, two independent transgenic mouse lines were created using a transgene comprised of 1.9 kb of 5'-flanking sequence of the human VIP gene joined to the Escherichia coli beta-galactosidase reporter gene. Transgene expression in brain was assessed using beta-galactosidase histochemistry and compared to the distribution of endogenous VIP expression. Transgene expression was observed in most central and peripheral nervous system sites in which endogenous VIP is expressed. We investigated whether the VIP-beta-galactosidase transgene was regulated in sympathetic neurons in experimental paradigms in which VIP regulation is dependent on the release of leukemia inhibitory factor (LIF). After dissociation in vitro and postganglionic axotomy in vivo there were parallel increases in endogenous VIP and transgene expression in superior cervical ganglia. These results indicate that the 1.9 kb region of 5'-flanking sequence of the human VIP gene includes genomic elements important for cell-specific expression and LIF-dependent regulation in neurons. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MOL NEUROBIOL LAB,BOSTON,MA 02114. TUFTS UNIV,SCH MED,DEPT ANAT CELL & REPROD BIOL,NORTH GRAFTON,MA 01536. TUFTS UNIV,SCH VET MED,DEPT ANAT CELL & REPROD BIOL,NORTH GRAFTON,MA 01536. TUFTS UNIV,SCH DENT MED,DEPT ANAT CELL & REPROD BIOL,NORTH GRAFTON,MA 01536. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02114. CHILDRENS HOSP,DEPT NEUROL,BOSTON,MA 02115. NR 44 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD DEC PY 1996 VL 42 IS 2 BP 181 EP 192 DI 10.1016/S0169-328X(96)00075-7 PG 12 WC Neurosciences SC Neurosciences & Neurology GA WD508 UT WOS:A1996WD50800001 ER PT J AU Grosson, CLS Cannon, SC Corey, DP Gusella, JF AF Grosson, CLS Cannon, SC Corey, DP Gusella, JF TI Sequence of the voltage-gated sodium channel beta(1)-subunit in wild-type and in quivering mice SO MOLECULAR BRAIN RESEARCH LA English DT Article DE voltage-gated sodium channel; beta(1)-subunit; mouse; quivering; neuromuscular disease; chromosome ID RAT SKELETAL-MUSCLE; FUNCTIONAL EXPRESSION; PERIODIC PARALYSIS; ALPHA-SUBUNIT; HUMAN BRAIN; HEART; BETA-1-SUBUNIT; INACTIVATION; CLONING; GENE AB SCN1B, the human gene encoding the beta(1)-subunit of the voltage-gated sodium channel has previously been cloned and mapped to Chr 19q13.1. The sequence of the homologous mouse gene, Scn1b, has now been determined from cDNA. The mouse gene is highly conserved, encoding a predicted protein with 99%, 98% and 96% amino acid identity to the rat, rabbit, and human homologs, respectively DNA sequence conservation is also striking in the 3' untranslated region which shows 67% and 98% to human and rat, respectively. Unlike the human and rat homologs, high expression of mRNA from the mouse gene is confined to adult skeletal muscle and brain, and is not observed in heart. As Scn1b maps to Chr 7, in close genetic proximity to the quivering gene (qv), the coding region of Scn1b was also cloned from a qv(J)/qv(J) homozygous mouse and assessed as a candidate for the site of this genetic defect. Comparison of qv and wild-type cDNAs showed no changes in the predicted amino acid sequence that could cause the go phenotype. However, three silent polymorphisms in the DNA coding region indicate that Scn1b is dose to qv, and is within a region of genetic identity with DBA/2J, the inbred background on which the qv(J) allele arose. C1 MASSACHUSETTS GEN HOSP EAST,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. HARVARD UNIV,DEPT GENET,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HOWARD HUGHES MED INST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114. OI Corey, David/0000-0003-4497-6016 NR 19 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD DEC PY 1996 VL 42 IS 2 BP 222 EP 226 DI 10.1016/S0169-328X(96)00123-4 PG 5 WC Neurosciences SC Neurosciences & Neurology GA WD508 UT WOS:A1996WD50800005 ER PT J AU Seol, W Mahon, MJ Lee, YK Moore, DD AF Seol, W Mahon, MJ Lee, YK Moore, DD TI Two receptor interacting domains in the nuclear hormone receptor corepressor RIP13/N-CoR SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID THYROID-HORMONE; CO-REPRESSOR; SUPERFAMILY; PROTEIN; GENE; PATHWAYS AB The thyroid hormone receptor (TR) and the retinoic acid receptor (RAR) act as transcriptional repressors when they are not occupied by their cognate ligands. This repressor function is mediated by proteins called corepressors. One of the nuclear hormone receptor corepressors, N-CoR, was originally isolated as a retinoid X receptor-interacting protein called RIP13. We have isolated a new potential variant of RIP13/N-CoR that is missing previously described transcriptional repressor domains but is similar in structure to the related corepressor termed SMRT or TRAC-2. Detailed analysis of the interaction with TR and RAR demonstrates that RIP13/N-CoR contains a new receptor interaction domain, termed ID-ii, in addition to the previously described domain, referred to here as ID-I. Both ID-I and ID-II are capable of interacting independently with either TR or RAR, as assessed by the yeast two-hybrid system, by a mammalian two-hybrid system, or by direct in vitro binding. Results with all three approaches confirm that RIP13/N-CoR also interacts with retinoid X receptor, but this interaction is weaker than that with TR or RAR. Together, these results demonstrate that RIP13/N-CoR can interact with several different nuclear hormone receptors via two separate receptor interaction domains. Differences between the interactions observed in the different systems suggest that compressor function may be modified by additional factors present in various cell types. C1 MASSACHUSETTS GEN HOSP, DEPT MOL BIOL, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-09438, R01 DK-43382] NR 36 TC 141 Z9 142 U1 0 U2 1 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 DEC PY 1996 VL 10 IS 12 BP 1646 EP 1655 DI 10.1210/me.10.12.1646 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VW494 UT WOS:A1996VW49400015 PM 8961273 ER PT J AU Hamberg, LM Hunter, GJ Fischman, AJ AF Hamberg, LM Hunter, GJ Fischman, AJ TI Use of positron emission tomography to study tumors in vivo SO MOLECULAR MEDICINE TODAY LA English DT Review ID F-18 FLUORODEOXYGLUCOSE; GLUCOSE-UTILIZATION; LUNG-CANCER; PET; 2--FLUORO-2-DEOXY-D-GLUCOSE; REGISTRATION; RECURRENCE; DIAGNOSIS; CARCINOMA; ONCOLOGY AB Positron emission tomography (PET) is a non-invasive imaging technique. The ability of PET to visualize biochemistry and physiology in vivo distinguishes this technique from other imaging modalities and renders it of particular interest for oncological studies. PET studies can often differentiate between normal and neoplastic tissue, as well as identify early signs of malignant degeneration through biochemical or physiological changes. Over the past several years, PET studies have been useful in the early diagnosis and the selection of treatment, as well as in following the progression or regression of malignant disease processes. Of particular significance, PET findings can be quantified by using mathematical modeling and computerized data analysis, which makes it possible to produce quantitative images of human pathophysiology in vivo. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,PET IMAGING CTR,CHARLESTOWN,MA 02129. RP Hamberg, LM (reprint author), MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,13TH ST,BLDG 149,CHARLESTOWN,MA 02129, USA. NR 32 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD DEC PY 1996 VL 2 IS 12 BP 528 EP 534 DI 10.1016/S1357-4310(97)81457-8 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WE077 UT WOS:A1996WE07700011 PM 9015794 ER PT J AU Peters, R Sikorski, RS AF Peters, R Sikorski, RS TI Nucleic acid databases on the web SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 NCI,BETHESDA,MD 20892. RP Peters, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114, USA. 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 DEC PY 1996 VL 14 IS 13 BP 1728 EP 1728 DI 10.1038/nbt1296-1728 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA VX107 UT WOS:A1996VX10700038 ER PT J AU Gimmi, CD Morrison, BW Mainprice, BA Gribben, JG Boussiotis, VA Freeman, GJ Park, SYL Watanabe, M Gong, JL Hayes, DF Kufe, DW Nadler, LM AF Gimmi, CD Morrison, BW Mainprice, BA Gribben, JG Boussiotis, VA Freeman, GJ Park, SYL Watanabe, M Gong, JL Hayes, DF Kufe, DW Nadler, LM TI Breast cancer-associated antigen, DF3/MUC1, induces apoptosis of activated human T cells SO NATURE MEDICINE LA English DT Article ID LYMPHOCYTES-T; MUCIN; IMMUNITY; PROTEIN; EPITOPE; DF3; CARCINOMAS; EPISIALIN; ADHESION; CORE AB Given the plethora of well-documented breast carcinoma-associated antigens in humans including MAGE-1, -2 and -3, mutated p53, p21ras, HER-2/neu and DF3/MUC-1, coupled with evidence that humoral and cytotoxic T-cell responses against these antigens exist(1-6), the central dilemma facing tumor immunologists is why the host immune response is so inefficient. One possibility is that tumor cells themselves are either inefficient or ineffective antigen-presenting cells (APCs). The failure of tumor cells to function as APCs may be due to their inability to process and present the antigen, the absence or insufficient numbers of adhesion and costimulatory molecules or, potentially, the secretion of inhibitory cytokines. Therefore, we sought to determine whether human breast cancer cell lines could function as APCs and, if not, to identify mechanism(s) responsible for this defect. Here, we show that human breast cancer cell lines fail to present alloantigen. This defect does not reside in their inherent capacity to present antigen but rather is due to apoptosis of activated T cells induced by exposure to the breast carcinoma-associated mucin antigen, DF3/MUC1. These results support the hypothesis that DF3/MUC1 may contribute to the paucity of clinically significant anticarcinoma-specific immune responses. C1 DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP Gimmi, CD (reprint author), DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [UO1-CA 64057, CA 38493] NR 20 TC 146 Z9 150 U1 0 U2 1 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 DEC PY 1996 VL 2 IS 12 BP 1367 EP 1370 DI 10.1038/nm1296-1367 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VW515 UT WOS:A1996VW51500044 PM 8946837 ER PT J AU Franken, M Estabrooks, A Cavacini, L Sherburne, B Wang, F Scadden, DT AF Franken, M Estabrooks, A Cavacini, L Sherburne, B Wang, F Scadden, DT TI Epstein-Barr virus-driven gene therapy for EBV-related lymphomas SO NATURE MEDICINE LA English DT Article ID SIGNAL-BINDING-PROTEIN; CELLS; EXPRESSION; CANCER; INFECTION; ELEMENTS; INVITRO AB Genetic alterations in malignant tissues are potential targets for gene-based cancer therapies. Alternatively, aberrant expression of certain specific genes associated with malignant transformation may be envisioned to enhance the expression of chemosensitizing drugs. Epstein-Barr virus (EBV)-related B-cell lymphomas are fatal complications of immunosuppression due to AIDS, organ transplantation or congenital immune abnormalities. The malignant cells latently infected with EBV typically express the transcription factor EBNA2 as one of nine latent viral genes. We tested whether an EBNA2-responsive EBV promoter may selectively target EBV-related lymphoma cells by virus-regulated expression of a suicide gene. Using the BamC promoter driving a hygromycin-thymidine kinase fusion gene or controls, we demonstrated that sensitivity to ganciclovir was selectively enhanced in cells expressing EBNA2. Further, there was complete macroscopic regression of established B-cell lymphomas in mice with severe combined immunodeficiency disease (SCID mice) treated with a single course of ganciclovir. These data provide in vitro and in vivo support for a model of exploiting the molecular basis of tumor development to enhance the specificity of gene therapy. C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,MGH CANC CTR,AIDS RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. FU NCI NIH HHS [R01-CA 55520] NR 24 TC 35 Z9 36 U1 1 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 DEC PY 1996 VL 2 IS 12 BP 1379 EP 1382 DI 10.1038/nm1296-1379 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VW515 UT WOS:A1996VW51500047 PM 8946840 ER PT J AU Singaram, C Sweet, MA Gaumnitz, EA Bass, P Snipes, RL AF Singaram, C Sweet, MA Gaumnitz, EA Bass, P Snipes, RL TI Evaluation of early events in the creation of amyenteric opossum model of achalasia SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE achalasia; animal model; benzalkonium chloride; enteric nervous system; myenteric neurons; nitric oxide ID NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE; DENERVATED RAT; NADPH DIAPHORASE; GUINEA-PIG; INTESTINE; NEURONS; ESOPHAGUS; JEJUNUM; DILATATION AB Benzyldimethyltetradecylammonium chloride (BAG) has previously been used to create amyenteric rat jejunal models. Fifteen opossums (D. virginiana) were injected with 10-15 mi, 4 mM BAG or saline in the distal oesophagus and along with controls underwent oesophagoscopy, manometry and barium oesophagrams. Atropine and sodium nitroprusside were studied in six of the BAG-treated and five controls using oesophageal manometry. Histologically several neuronal markers, B-NADPH-diaphorase and acetylcholine esterase histochemical staining were used. NADPH-diaphorase activity was assayed at the lower oesophageal sphincter (LOS) and 3 and 5 cm above LOS in both groups. Oesophagoscopy of the treated animals showed no mucosal inflammation, or strictures. Manometrically, LOS pressures were significantly higher in the BAG-treated group (25.7 +/- 8.6 mmHg) when compared to controls (8.7 +/- 1.8 mmHg). The oesophageal contraction amplitudes were similar in both groups. While sodium nitroprusside (SNP) significantly reduced the LOS pressure, atropine did not alter the resting LOS pressure in the BAG-treated animals. Histologically at the LOS the treated group showed: (i) absence of myenteric neurons, in contrast to prominent NADPH-diaphorase and other neuron and peptide markers in the control and (ii) increase in the number of nerve bundles that were not positive for AchE. No differences were seen in the oesophageal body between the groups. The NADPH-diaphorase assay showed a significant decrease of activity in the BAG-treated LOS, but no differences in the oesophageal body compared to controls. Several of these radiologic, manometric and histological observations resemble features of achalasia and the mechanism of the tonic pressure increase at this early time point appears to be due to a non-cholinergic mechanism. C1 UNIV WISCONSIN,SCH PHARM,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. MADISON VA GRECC,MADISON,WI. RP Singaram, C (reprint author), UNIV WISCONSIN HOSP,DIV GASTROENTEROL,SCH MED,H6-510,600 HIGHLAND AVE,MADISON,WI 53792, USA. FU NIDDK NIH HHS [DK 02470] NR 39 TC 8 Z9 10 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD DEC PY 1996 VL 8 IS 4 BP 351 EP 361 DI 10.1111/j.1365-2982.1996.tb00273.x PG 11 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA VX723 UT WOS:A1996VX72300008 PM 8959739 ER PT J AU Breiter, HC Rauch, SL AF Breiter, HC Rauch, SL TI Functional MRI and the study of OCD: From symptom provocation to cognitive-behavioral probes of cortico-striatal systems and the amygdala SO NEUROIMAGE LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; HUMAN BRAIN; SCHIZOPHRENIC-PATIENTS; HUNTINGTONS-DISEASE; SENSORY STIMULATION; ACTIVATION; CORTEX; TASK; PERFORMANCE; EMOTION AB Functional magnetic resonance imaging (fMRI) first appeared in 1991. Since that time there has been a burgeoning use of the technology by psychiatric researchers and neuroscientists. Our group first used fMRI to study obsessive compulsive disorder (OCD) with a symptom provocation paradigm and then moved to the use of circuitry-specific cognitive-behavioral probes. The techniques we utilized for the symptom provocation study remain valid today, but have been supplemented by a wide array of new tools. Functional MRI continues to be a rapidly developing technology which could become the gold standard for neuroimaging research in psychiatry. With this in mind, this paper focuses on the past, present, and future applications of fMRI to one model illness, namely OCD. We examine the strengths and limitations of our initial OCD symptom provocation study and then evaluate the use of fMRI with cognitive-behavioral probes of cortico-striatal circuitry and limbic (amygdala) circuitry. We conclude with a brief summary of foreseeable developments which will influence the implementation of fMRI for psychiatric neuroscience in general. (C) 1996 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02138. RP Breiter, HC (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,NUCL MAGNET RESONANCE CTR,CHARLESTOWN,MA 02129, USA. FU PHS HHS [00265, 01215] NR 81 TC 70 Z9 70 U1 2 U2 14 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 1996 VL 4 IS 3 BP S127 EP S138 DI 10.1006/nimg.1996.0063 PN 3 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA WC430 UT WOS:A1996WC43000008 PM 9345537 ER PT J AU Fisher, CM AF Fisher, CM TI Hypomanic symptoms caused by herpes simplex encephalitis SO NEUROLOGY LA English DT Editorial Material ID BRAIN INJURY; SECONDARY MANIA; MOOD DISORDERS; HEAD TRAUMA; PSYCHOSIS; LESIONS AB This is a case report of a brief episode of rather typical hypomanic symptoms in the acute phase of presumed herpes simplex encephalitis in a young woman. I infer that the hypomanic episode was triggered from the anterior inferomedial temporal lobe or limbic system, the presumed cerebral substrate of the emotions in general, and review the literature relating to the occurrence of hypomania associated with structural disease of the nervous system. RP Fisher, CM (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,FRUIT ST,BOSTON,MA 02114, USA. NR 24 TC 10 Z9 10 U1 0 U2 3 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1996 VL 47 IS 6 BP 1374 EP 1378 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA VX507 UT WOS:A1996VX50700005 PM 8960713 ER PT J AU Mega, MS Masterman, DL Benson, DF Vinters, HV Tomiyasu, U Craig, AH Foti, DJ Kaufer, D Scharre, DW Fairbanks, L Cummings, JL AF Mega, MS Masterman, DL Benson, DF Vinters, HV Tomiyasu, U Craig, AH Foti, DJ Kaufer, D Scharre, DW Fairbanks, L Cummings, JL TI Dementia with Lewy bodies: Reliability and validity of clinical and pathologic criteria SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE CERAD; SUPRANUCLEAR GAZE PALSY; BODY DISEASE; SENILE DEMENTIA; PARKINSONS-DISEASE; FEATURES; VARIANT; PROGRESSION; CONSORTIUM; IMPAIRMENT AB Clinical criteria for dementia with Lewy bodies (DLB) have been proposed, but their formulation, reliability, and validity require further study. Pathologic criteria for DLB are also undergoing evolution. Two studies were conducted with the goal of identifying the components of these evolving criteria that may benefit from further refinement; one study evaluated the components of the clinical criteria and another study operationalized the pathologic criteria for DLB. Twenty-four patients with a premorbid diagnosis of probable or possible Alzheimer's disease (AD) (n = 18), Parkinson's disease (PD) (n = 5), or progressive supranuclear palsy (PSP) (n = 1) were studied, Inter-rater reliability and validity of the clinical criteria were determined by a retrospective chart review, done by five neurologists, and a blinded pathologic evaluation. The Consortium on dementia with Lewy bodies (CDLB) pathologic criteria were operationalized to compare past criteria and test the validity of the evolving clinical criteria on the dementia patients. Three or more cortical fields (at 250x magnification) with many (four or more) Lewy bodies (LBs) on ubiquitin immunoreactive sections were required to meet the CDLB neocortical score of >6. Fifteen of the AD patients had at least one LB in a cortical section, four had many LBs, while three had no LBs; all patients with movement disorder had at least one LB in a cortical section. The sensitivity/specificity ratio of the CDLB probable DLB clinical criteria based upon many LBs being present was 75%/79%. Reformulated clinical criteria that require the presence of extrapyramidal signs significantly predicted those patients with many LBs versus those with few or no LBs (chi(2) = 5.48, p = 0.02) and increased clinical specificity to 100%. This preliminary study identifies components of the evolving clinical and pathologic criteria for DLB that require further refinement. C1 W LOS ANGELES VET AFFAIRS MED CTR,SECT NEUROPATHOL,DEPT LAB SERV,LOS ANGELES,CA 90073. UNIV PITTSBURGH,DEPT NEUROL,PITTSBURGH,PA 15260. OHIO STATE UNIV,DEPT NEUROL,COLUMBUS,OH 43210. RP Mega, MS (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,710 WESTWOOD PLAZA,LOS ANGELES,CA 90025, USA. RI Scharre, Douglas/E-4030-2011 FU NIA NIH HHS [P30, AG10123] NR 63 TC 144 Z9 146 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1996 VL 47 IS 6 BP 1403 EP 1409 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA VX507 UT WOS:A1996VX50700010 PM 8960718 ER PT J AU Gilden, DH KleinschmidtDeMasters, BK Wellish, M HedleyWhyte, ET Rentier, B Mahalingam, R AF Gilden, DH KleinschmidtDeMasters, BK Wellish, M HedleyWhyte, ET Rentier, B Mahalingam, R TI Varicella zoster virus, a cause of waxing and waxing vasculitis: The New England Journal of Medicine case 5-1995 revisited SO NEUROLOGY LA English DT Article AB A 73-year-old man developed an ill-defined fatal vasculitis involving the central nervous system. The case report was published as a clinicopathologic exercise in February 1995 in The New England Journal of Medicine.(1) We restudied the pathologic material and found both varicella tester virus (VZV) DNA and VZV-specific antigen, but not herpes simplex virus (HSV) or cytomegalovirus (CMV) DNA or HSV- or CMV-specific antigen, in three of the five cerebral arteries examined. The inflammatory response, disruption of the internal elastic lamina, and detection of viral antigen were patchy from one artery to another, as well as within a given artery. A search for VZV should be conducted in cases of vasculitis when both the central and peripheral nervous systems are involved, when focal narrowing is present in large arteries, when brain imaging reveals infarction in gray and white matter, both deep and superficial, and when white matter is disproportionally involved. Zosteriform rash is not required for diagnosis. C1 UNIV COLORADO,HLTH SCI CTR,DEPT MICROBIOL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT PATHOL,DENVER,CO 80262. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. UNIV LIEGE,DEPT PATHOL,LIEGE,BELGIUM. RP Gilden, DH (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT NEUROL,BOX B-182,4200 E 9TH AVE,DENVER,CO 80262, USA. FU NIA NIH HHS [AG 06127]; NINDS NIH HHS [NS 32623] NR 9 TC 101 Z9 102 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1996 VL 47 IS 6 BP 1441 EP 1446 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA VX507 UT WOS:A1996VX50700016 PM 8960724 ER PT J AU Przedborski, S Dhawan, V Donaldson, DM Murphy, PL McKennaYasek, D Mandel, FS Brown, RH Eidelberg, D AF Przedborski, S Dhawan, V Donaldson, DM Murphy, PL McKennaYasek, D Mandel, FS Brown, RH Eidelberg, D TI Nigrostriatal dopaminergic function in familial amyotrophic lateral sclerosis patients with and without copper/zinc superoxide dismutase mutations SO NEUROLOGY LA English DT Article ID MOTOR-NEURON DISEASE; MULTISYSTEM DEGENERATION; PARKINSONS-DISEASE; APOPTOTIC DEATH; TRANSGENIC MICE; GENE; NEUROTOXICITY; QUANTITATION; CELLS AB Some cases of familial amyotrophic lateral sclerosis (FALS) are associated with copper/zinc superoxide dismutase (Cu/Zn-SOD) mutations, which are implicated in the death of motor neurons. Because Cu/ZnSOD is present in high amounts in nigrostriatal dopaminergic neurons, we considered the possibility that FALS may be associated with subclinical nigrostriatal dopaminergic dysfunction. We used [F-18]fluorodopa (FDOPA) and PET to study 14 FALS patients (50+/-11 years [mean+/-SD]): seven with (FALS-1) and seven without (FALS-0) Cu/Zn-SOD mutations. Fourteen age-matched normal volunteers (48+/-18 years) served as controls. Striato-occipital ratios (SORs) for the caudate and the putamen were calculated. Five of the 14 FALS patients had reduced striatal FDOPA uptake in the caudate nucleus, putamen, or both. Mean caudate SOR did not differ among FALS-1, FALS-0, and control subjects. Mean putamen SOR was significantly abnormal in FALS-0 but not in FALS-1 patients. These findings indicate that subclinical nigrostriatal dopaminergic dysfunction is present in some FALS patients and that FDOPA/PET abnormalities are more likely to be associated with FALS-0 status. This suggests that SOD mutations are less cytotoxic to dopaminergic than to motor neurons. C1 N SHORE UNIV HOSP,DEPT NEUROL,MANHASSET,NY. N SHORE UNIV HOSP,DEPT RES,MANHASSET,NY. CORNELL UNIV MED COLL,MANHASSET,NY 11030. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CECIL B DAY LAB NEUROMUSCULAR RES,BOSTON,MA 02115. RP Przedborski, S (reprint author), COLUMBIA UNIV COLL PHYS & SURG,DEPT NEUROL,BB-307,650 W 168TH ST,NEW YORK,NY 10032, USA. RI Eidelberg, David/F-5214-2011 FU NIA NIH HHS [AG12922-01]; NINDS NIH HHS [1PO1NS31248-01, 1-K08-NS01724-02] NR 41 TC 25 Z9 27 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1996 VL 47 IS 6 BP 1546 EP 1551 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA VX507 UT WOS:A1996VX50700035 PM 8960743 ER PT J AU Isacson, O Deacon, TW AF Isacson, O Deacon, TW TI Specific axon guidance factors persist in the adult brain as demonstrated by pig neuroblasts transplanted to the rat SO NEUROSCIENCE LA English DT Article DE neural transplantation; fetal cells; Parkinson's disease; regeneration ID CENTRAL-NERVOUS-SYSTEM; NEURONAL GROWTH CONES; EFFERENT PROJECTIONS; GANGLIONIC EMINENCE; TARGET SELECTION; GLIAL PATHWAYS; NEURITE GROWTH; BASAL GANGLIA; SPINAL-CORD; GRAFTS AB The presence and specificity of axon guidance cues in the mature brain were examined by transplanting several types of xenogeneic neural cells from fetal pig brains into adult rat brains with selective neuronal loss. Committed neuronal phenotypes from cortical, mesencephalic and striatal fetal regions were implanted in homotopic or ectopic central nervous system locations. Using specific neurofilament and neural markers, axonal target selection by transplanted fetal neurons was determined throughout the central nervous system. Different types of donor neurons grew axons specifically to appropriate adjacent and distant host brain regions from ectopic or homotopic brain implantation sites and independent of the pattern of prior selective neuronal loss. Since the fetal donor neurons could orient axonal growth towards their normal synaptic. termination zones, it shows that the adult brain also elaborates highly specific signals for axon guidance. These results obtained by xenotransplantation also demonstrate that the adult brain exhibits a latent potential for long-distance axon guidance that is evolutionarily conserved. These and related studies indicate that the necessary processes for connection of specific neurocircuitry also exist in the adult central nervous system, if axonal growth inhibition is overcome. Copyright (C) 1996 IBRO. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT NEUROL, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02114 USA. BOSTON UNIV, DEPT BIOL ANTHROPOL, BOSTON, MA 02215 USA. RP HARVARD UNIV, MCLEAN HOSP, SCH MED, NEUROREGERAT LAB, BELMONT, MA 02178 USA. FU NINDS NIH HHS [NS29178-05, NS30064-04] NR 76 TC 83 Z9 83 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD DEC PY 1996 VL 75 IS 3 BP 827 EP 837 DI 10.1016/0306-4522(96)00305-3 PG 11 WC Neurosciences SC Neurosciences & Neurology GA VU268 UT WOS:A1996VU26800015 PM 8951876 ER PT J AU Hara, H Waeber, C Huang, PL Fujii, M Fishman, MC Moskowitz, MA AF Hara, H Waeber, C Huang, PL Fujii, M Fishman, MC Moskowitz, MA TI Brain distribution of nitric oxide synthase in neuronal or endothelial nitric oxide synthase mutant mice using [H-3]L-N-G-nitro-arginine autoradiography SO NEUROSCIENCE LA English DT Article DE autoradiography; brain; L-N-G-nitro-arginine; mouse; mutant; nitric oxide synthase ID RAT-BRAIN; 7-NITRO INDAZOLE; NADPH-DIAPHORASE; RODENT BRAIN; L-ARGININE; INHIBITION; MESSENGER; LACKING; BINDING; GENE AB The regional distribution of nitric oxide synthase in the central nervous system was assessed by quantitative autoradiography using [H-3]L-N-G-nitro-arginine binding in wild-type mice (SV-129 and C57black/6) and in mice lacking expression of the neuronal (type 1) and endothelial (type 3) nitric oxide synthase gene. The distribution of nitric oxide synthase binding sites in wild-type mice was similar to that described for rat brain by nicotinamide adenine dinucleotide phosphate-diaphorase staining and immunohistochemistry, and as determined by quantitative autoradiography. In the wild-type mice; the densest labelling was observed in the granular layer of the olfactory bulb, tenia tecta, rhinal fissure, amygdaloid complex and molecular layer of cerebellum. The islands of Calleja, the hippocampal CA1 and CA3 subfields, dentate gyrus, cortical layers I-II, the superficial gray layer of superior colliculus and the granule layer of cerebellum displayed intermediate binding. Cortical layers III-VI, the striatum and the thalamus were only weakly labelled. Binding was saturable and of high affinity, and was displaced by 7-nitroindazole (100 mu M), a potent and selective inhibitor of type 1 nitric oxide synthase, and by unlabelled L-N-G-nitro-arginine (10 mu M). The density of [H-3]L-N-G-nitro-arginine binding was dramatically reduced in all brain regions in type 1 mutant mice, whereas there were no detectable binding differences between wild-type and type 3 nitric oxide synthase mutant mice. Hence, type 1 nitric oxide synthase is the major source of [H-3]L-N-G-nitro-arginine binding in the mouse brain. [H-3]L-N-G-Nitro-arginine autoradiography may be a useful tool to quantify nitric oxide synthase in different brain areas after pharmacological or physiological manipulations. Copyright (C) 1996 IBRO. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG & NEUROL,STROKE & NEUROVASC REGULA,CHARLESTOWN,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NINDS NIH HHS [NS33335, NS10828, NS2683] NR 35 TC 44 Z9 46 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC PY 1996 VL 75 IS 3 BP 881 EP 890 DI 10.1016/0306-4522(96)00313-2 PG 10 WC Neurosciences SC Neurosciences & Neurology GA VU268 UT WOS:A1996VU26800020 PM 8951881 ER PT J AU Lieberman, E Lang, JM Cohen, A DAgostino, R Datta, S Frigoletto, FD AF Lieberman, E Lang, JM Cohen, A DAgostino, R Datta, S Frigoletto, FD TI Association of epidural analgesia with cesarean delivery in nulliparas SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID MATERNAL HEIGHT; BIRTH-WEIGHT; RISK-FACTORS; LABOR; MANAGEMENT; SECTION; TRIAL; PREGNANCY; DYSTOCIA; PROGRESS AB Objective: To evaluate whether epidural analgesia during the first stage of labor is associated with an increased risk of cesarean delivery. Methods: The association of epidural analgesia and cesarean delivery was examined in a retrospective study of 1733 low-risk, term nulliparas with singleton infants in vertex presentations, in which labor began spontaneously. To evaluate the effect of epidural analgesia on cesarean deliveries, independent of other factors influencing the use of epidural analgesia, we used propensity scores to create five subgroups (quintiles) of women who, based on characteristics discernible at admission, appeared equally likely to receive epidural analgesia. Multivariate logistic regression analysis was used to control for confounding. Results: Overall, the cesarean rate among women receiving epidural analgesia was 17% (168 of 991), compared with 4% (30 of 742) among those who did not receive epidural analgesia. An increased cesarean rate among women receiving epidural analgesia was present in all propensity quintiles. In an adjusted logistic regression analysis, women receiving epidural analgesia were 3.7 times more likely to undergo a cesarean (95% confidence interval 2.4, 5.7). The greatest increase in cesarean risk was noted when epidural analgesia was administered earlier in labor, but there was a more than twofold increase regardless of the dilation and station at administration of epidural analgesia. Conclusions: Epidural analgesia may increase substantially the risk of cesarean delivery. Although the causal nature of this association remains open to debate, prenatal care providers should routinely discuss the risks and benefits of epidural analgesia with women during their pregnancies so that they can make informed decisions about the use of pain relief during labor. (Copyright (C) 1996 by The American College of Obstetricians and Gynecologists.) C1 HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. BOSTON UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL & BIOSTAT,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. HARVARD UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,BOSTON,MA 02115. RP Lieberman, E (reprint author), HARVARD UNIV,SCH MED,DEPT OBSTET & GYNECOL,BRIGHAM & WOMENS HOSP,75 FRANCIS ST,BOSTON,MA 02115, USA. RI Dagostino Jr, Ralph/C-4060-2017 OI Dagostino Jr, Ralph/0000-0002-3550-8395 FU NICHD NIH HHS [R01-HD26813] NR 26 TC 93 Z9 100 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 1996 VL 88 IS 6 BP 993 EP 1000 DI 10.1016/S0029-7844(96)00359-6 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VU946 UT WOS:A1996VU94600016 PM 8942841 ER PT J AU Nicaeus, TE Tolentino, MJ Adamis, AP Rubin, PAD AF Nicaeus, TE Tolentino, MJ Adamis, AP Rubin, PAD TI Sucralfate and basic fibroblast growth factor promote endothelial cell proliferation around porous alloplastic implants in vitro SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article DE hydroxyapatite; porous polyethylene; hydron; sucralfate; basic fibroblast growth factor; proliferation ID ANGIOGENESIS; PROTEINASES; MEMBRANE AB Enhanced ingrowth of fibrovascular tissue into alloplastic orbital implants is clinically desirable. Basic fibroblast growth factor (bFGF) is an angiogenic factor that promotes proliferation of endothelial cells, Sucralfate is known to bind bFGF and render it stable by protecting it from degradation. To test the ability of bFGF to stimulate endothelial cell proliferation, porous orbital implants coated with a sustained-release and bioactively-stabilized preparation of the angiogenic peptide bFGF were studied. Hydroxyapatite (HA) and porous polyethylene (PP) implant discs (15 x 3 mm) were coated with sustained-release polymer polyhydroxyethylmethacrylate (hydron), sucralfate (a bFGF stabilizer), hydron plus or hydron/sucralfate plus bFGF. Discs were placed in tissue culture wells plated with 50,000 endothelial cells/well. After 5 days, cells were trypsinized and counted electronically using a Coulter counter. Statistical analysis was performed using unpaired Student's t-test. Implant discs coated with hydron/sucralfate/bFGF had significantly increased endothelial cell proliferation compared to discs coated with hydron alone or hydron/sucralfate (p < 0.05). There was no significant difference in the degree of enhanced proliferation between the HA and PP implants treated with hydron/sucralfate/bFGF (p > 0.05). Minimal proliferation occurred around discs treated with hydron alone or hydron/sucralfate. Coating both HA and PP orbital implants with the sustained-release form of sucralfate/bFGF promoted endothelial cell proliferation in vitro. The enhanced proliferation with hydron/sucralfate/bFGF warrants further exploration in an in vivo model. C1 MASSACHUSETTS EYE & EAR INFIRM,EYE PLAST & ORBIT SERV,BOSTON,MA 02114. NR 17 TC 12 Z9 17 U1 2 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0740-9303 J9 OPHTHALMIC PLAST REC JI Ophthalmic Plast. Reconstr. Surg. PD DEC PY 1996 VL 12 IS 4 BP 235 EP 239 DI 10.1097/00002341-199612000-00004 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA VU488 UT WOS:A1996VU48800004 PM 8944383 ER PT J AU Kim, RY Hu, LK Foster, BS Gragoudas, ES Young, LHY AF Kim, RY Hu, LK Foster, BS Gragoudas, ES Young, LHY TI Photodynamic therapy of pigmented choroidal melanomas of greater than 3-mm thickness SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT ARVO Annual Meeting CY MAY, 1995 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol ID CHLOROALUMINUM SULFONATED PHTHALOCYANINE; HEMATOPORPHYRIN PHOTORADIATION THERAPY; LIPOPROTEIN-DELIVERED BENZOPORPHYRIN; PROTON-BEAM IRRADIATION; TUMOR DESTRUCTION; MALIGNANT-TUMORS; UVEAL MELANOMAS; RABBIT MODEL; CANCER; PHOTOSENSITIZER AB Purpose: The purpose of the study is to determine the effect of photodynamic therapy in the destruction of experimental pigmented choroidal melanomas greater than or equal to 3 mm in thickness using a liposomal preparation of benzoporphyrin derivative, verteporfin. Methods: Pigmented choroidal turners were established in 32 New Zealand albino rabbit eyes, Animals were treated with daily injections of cyclosporine, and tumor growth was followed by serial fundus examinations and ultrasonography. When a tumor exceeded 3 mm in thickness (tumor height ranged from 3.1-4.6 mm), the authors administered benzoporphyrin derivative intravenously (1 mg/kg) and irradiated the tumor at 692-nm through an argon-pumped dye laser at different total light doses ranging from 60 to 120 J/cm(2), Control animals were treated with light or benzoporphyrin derivative only. Each animal then was followed-up for 4 to 6 weeks by fundus photography, fluorescein angiography, and ultrasonography. Results: All animals treated with benzoporphyrin derivative and light at fluences of greater than or equal to 80 J/cm(2) showed complete tumor arrest, In contrast,both control groups showed continuous tumor growth in all animals with tumors filling most of the vitreous cavity by 3 weeks. Histologic examination results of tumors treated with dye plus light immediately after treatment showed prominent vascular closure, No vascular changes were noted in the control eye treated with light or dye alone. Examination results of the eyes that showed tumor regression after a 4-week follow-up period showed tumor necrosis and extensive infiltration of mononuclear cells and pigment-laden macrophages at the tumor site, Conclusion: These data suggest that photodynamic therapy may have a role in the management of pigmented choroidal melanomas. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. FU NEI NIH HHS [EY10975-01] NR 44 TC 23 Z9 31 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 1996 VL 103 IS 12 BP 2029 EP 2036 PG 8 WC Ophthalmology SC Ophthalmology GA WB759 UT WOS:A1996WB75900011 PM 9003336 ER PT J AU MintzHittner, HA Ferrell, RE Sims, KB Fernandez, KM Gemmell, BS Satriano, DR Caster, J Kretzer, FL AF MintzHittner, HA Ferrell, RE Sims, KB Fernandez, KM Gemmell, BS Satriano, DR Caster, J Kretzer, FL TI Peripheral retinopathy in offspring of carriers of Norrie disease gene mutations - Possible transplacental effect of abnormal Norrin SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 30-NOV 03, 1994 CL SAN FRANCISCO, CA SP Amer Acad Ophthalmol ID FAMILIAL EXUDATIVE VITREORETINOPATHY; MISSENSE MUTATIONS; CANDIDATE GENE; NDP GENE; PREMATURITY; TRANSLOCATION; DYSPLASIA; LINKAGE; FEMALE; LOCUS AB Background: The Norrie disease (ND) gene (Xp11.3) (McKusick 310600) consists of one untranslated exon and two exons partially translated as the Norrie disease protein (Norrin). Norrin has sequence homology and computer-predicted tertiary structure of a growth factor containing a cystine knot motif, which affects endothelial cell migration and proliferation. Norrie disease (congenital retinal detachment), X-linked primary retinal dysplasia (congenital retinal fold), and X-linked exudative vitreoretinopathy (congenital macular ectopia) are allelic disorders. Methods: Blood was drawn for genetic studies from members of two families to test for ND gene mutations, Sixteen unaffected family members were examined ophthamlologically, If any retinal abnormality were identified, fundus photography and fluorescein angiography was performed. Results: Family A had ND (R109stp), and family B had X-linked exudative vitreoretinopathy (R121L), The retinas of II offspring of carrier females were examined: three of seven carrier females, three of three otherwise healthy females, and one of one otherwise healthy male had peripheral inner retinal vascular abnormalities; The retinas of five offspring of affected males were examined: none of three carrier females and none oi two otherwise healthy males had this peripheral retinal finding, Conclusions: Peripheral inner retinal vascular abnormalities similar to regressed retinopathy of prematurity were identified in seven offspring of carriers of ND gene mutations in two families. These ophthalmologic findings, especially in four genetically healthy offspring, strongly support the hypothesis that abnormal Norrin may have an adverse transplacental (environmental) effect on normal inner retinal vasculogenesis. C1 UNIV TEXAS,SCH MED,DEPT OPHTHALMOL & VISUAL SCI,HOUSTON,TX. BAYLOR COLL MED,DEPT OPHTHALMOL,HOUSTON,TX 77030. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT HUMAN GENET,PITTSBURGH,PA 15261. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOL NEUROGENET UNIT,BOSTON,MA. FU NEI NIH HHS [EY02520] NR 33 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 1996 VL 103 IS 12 BP 2128 EP 2134 PG 7 WC Ophthalmology SC Ophthalmology GA WB759 UT WOS:A1996WB75900025 PM 9003348 ER PT J AU Eavey, RD AF Eavey, RD TI Ear malformations - What a pediatrician can do to assist with auricular reconstruction SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID MICROTIA AB Microtia is a severe and conspicuous congenital ear malformation that involves both function and appearance. Happily, auricular reconstruction now can provide the patient with a very realistic auricle. Because of exciting research efforts, the future looks even brighter. As the initial medical contact, the pediatrician offers valuable reassurance and guidance to relieve the parents and direct the child for surgical reconstruction. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP Eavey, RD (reprint author), MASSACHUSETTS EYE & EAR INFIRM,ENT PEDIAT SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 13 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 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD DEC PY 1996 VL 43 IS 6 BP 1233 EP & DI 10.1016/S0031-3955(05)70516-2 PG 13 WC Pediatrics SC Pediatrics GA VY943 UT WOS:A1996VY94300006 PM 8973510 ER PT J AU Tague, BW Gallant, P Goodman, HM AF Tague, BW Gallant, P Goodman, HM TI Expression analysis of an Arabidopsis C2H2 zinc finger protein gene SO PLANT MOLECULAR BIOLOGY LA English DT Article DE Arabidopsis thaliana; beta-glucuronidase; C2H2 zinc finger protein; histochemical analysis; tissue-specific expression ID DNA-BINDING PROTEIN; TRANSCRIPTIONAL REPRESSOR; MESSENGER-RNAS; XENOPUS-LAEVIS; PHOSPHORYLATION; DROSOPHILA; DOMAIN; FAMILY; RECOGNITION; SUPERMAN AB C2H2 zinc finger protein genes encode nucleic acid-binding proteins involved in the regulation of gene activity. AtZFP1 (Arabidopsis thaliana zinc finger protein 1) is one member of a small family of C2H2 zinc finger-encoding sequences previously characterized from Arabidopsis. The genomic sequence corresponding to the AtZFP1 cDNA has been determined. Molecular analysis demonstrates that AtZFP1 is a unique, intronless gene which encodes a 1100 nucleotides mRNA highly expressed in roots and stems. A construct in which 2.5 kb of AtZFP1 upstream sequences is linked to the beta-glucuronidase gene was introduced into Arabidopsis by Agrobacterium-mediated transformation of roots. Histochemical analysis of transgenic Arabidopsis carrying the AtZFP1 promotor:beta-glucuronidase fusion shows good correlation with RNA blot hybridization analysis. This transgenic line will be a useful tool for analyzing the regulation of AtZFP 1 to further our understanding of its function. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. NR 53 TC 8 Z9 10 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-4412 J9 PLANT MOL BIOL JI Plant Mol.Biol. PD DEC PY 1996 VL 32 IS 5 BP 785 EP 796 DI 10.1007/BF00020477 PG 12 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA VY820 UT WOS:A1996VY82000002 PM 8980531 ER PT J AU DupontVersteegden, EE Kitten, AM Katz, MS McCarter, RJ AF DupontVersteegden, EE Kitten, AM Katz, MS McCarter, RJ TI Elevated levels of albumin in soleus and diaphragm muscles of mdx mice SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; SKELETAL-MUSCLE; HINDLIMB MUSCLES; MOUSE DIAPHRAGM; X-CHROMOSOME; MUTANT MICE; MEMBRANE; PERMEABILITY; REGENERATION; DISRUPTIONS AB Muscle damage is often associated with an influx of extracellular fluid containing albumin into the muscle, Muscles affected by muscular dystrophy undergo severe muscle damage; therefore, the hypothesis was tested that muscles of dystrophic (mdx) mice contain elevated levels of albumin, Albumin levels in diaphragm (DIA) and soleus (SOL) muscles of control and mdx mice were measured at 3 months and 1 year of age, Albumin in mdx DIA at 1 year of age was twice that of control, In mdx SOL at 1 year of age albumin was increased 25% compared with control, The increase in albumin correlates well with the decline in function in mdx DIA and SOL muscles, Electron microscopy of muscles suggests that albumin is co-localized with transverse tubules of muscle fibers and thus may be mainly located in extracellular fluid. We conclude that albumin is elevated in muscles affected by muscular dystrophy and suggest that this may be of clinical importance in view of substances bound to albumin under physiological conditions. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. NR 44 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD DEC PY 1996 VL 213 IS 3 BP 281 EP 286 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WA581 UT WOS:A1996WA58100009 PM 8985313 ER PT J AU Averboukh, L Liang, P Kantoff, PW Pardee, AB AF Averboukh, L Liang, P Kantoff, PW Pardee, AB TI Regulation of S100P expression by androgen SO PROSTATE LA English DT Article DE differential display; prostate carcinoma; androgen; S100P; PSA ID HUMAN PROSTATIC-CARCINOMA; DIFFERENTIAL DISPLAY; HUMAN PLACENTA; CELLS; CANCER; LNCAP; GENE; PROTEIN; ANTIGEN; MEMBER AB BACKGROUND. The growth and function the normal prostate is dependent on the presence of androgen. As prostate tumors progress there is a loss of androgen-dependent cell growth. The identification of the genes that are regulated by androgens may be of pathological and clinical significance. METHODS. In this study the differential display method was used to identify genes regulated by androgen in an androgen-responsive prostate cancer cell line, LNCaP-FGC. RESULTS. A gene whose expression is down-regulated in LNCaP-FGC cells after 30 hr of androgen deprivation has been identified. This gene is a previously identified member of the S100 gene family of calcium-binding proteins, namely S100P. Here we show that S100P expression is regulated by the synthetic androgen R1881, but not by serum growth factors. It is dysregulated in the androgen-independent prostate cancer cell lines LNCaP-R, DU145, and PC3. CONCLUSIONS. The data indicate that S100P may play a role in the etiology of prostate cancer. (C) 1996 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115. VANDERBILT CANC CTR,NASHVILLE,TN. DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. NR 21 TC 67 Z9 70 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 0270-4137 J9 PROSTATE JI Prostate PD DEC PY 1996 VL 29 IS 6 BP 350 EP 355 PG 6 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA WA097 UT WOS:A1996WA09700002 PM 8977631 ER PT J AU Herzog, DB Nussbaum, KM Marmor, AK AF Herzog, DB Nussbaum, KM Marmor, AK TI Comorbidity and outcome in eating disorders SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID MAJOR AFFECTIVE-DISORDER; R PERSONALITY-DISORDERS; 10-YEAR FOLLOW-UP; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; LONG-TERM; PSYCHIATRIC-DISORDERS; CLINICAL COURSE; SEXUAL ABUSE; RELAPSE AB This article reviews the data on comorbidity, course, and outcome in anorexia nervosa and bulimia nervosa. Recovery, relapse, the process of recovery, and predictors of outcome are reviewed. Although significant differences exist among outcome studies, the data suggest that patients with anorexia and bulimia tend to improve symptomatically over time. Anorexia nervosa and bu limia nervosa are associated with substantial rates of comorbidity. The relationship between eating disorders and depression, anxiety disorders, substance abuse, and personality disorders is discussed. C1 HARVARD UNIV, SCH MED, BOSTON, MA USA. MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT, EATING DISORDERS UNIT, BOSTON, MA 02114 USA. NR 89 TC 105 Z9 116 U1 4 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1996 VL 19 IS 4 BP 843 EP + DI 10.1016/S0193-953X(05)70385-3 PG 0 WC Psychiatry SC Psychiatry GA VT182 UT WOS:A1996VT18200014 PM 9045226 ER PT J AU Felker, B Yazel, JJ Short, D AF Felker, B Yazel, JJ Short, D TI Mortality and medical comorbidity among psychiatric patients: A review SO PSYCHIATRIC SERVICES LA English DT Article ID CORONARY HEART-DISEASE; IOWA RECORD-LINKAGE; PHYSICAL ILLNESS; FOLLOW-UP; AFFECTIVE-DISORDERS; ACCIDENTAL DEATHS; EXCESS MORTALITY; MENTAL-ILLNESS; PHOBIC ANXIETY; OUTPATIENTS AB Objectives: To fuel advocacy for improved health care for mentally ill persons, the authors reviewed the literature that describes excess mortality and underrecognition and undertreatment of comorbid medical conditions in this population. Barriers to optimal primary medical care for psychiatric patients are discussed. Methods: A MEDLINE search focusing on mortality rind medical problems in psychiatric patients yielded 66 papers in English published between 1934 and 1996. These studies and a German paper from 1912 are included in the review. Results and Conclusions: Standardized mortality ratios for psychiatric patients, derived from comparisons with the general population and matched control groups, have repeatedly demonstrated excess mortality from both natural and unnatural causes among psychiatric patients. Several large studies that have attempted to clarify the issues underlying increased death rates are discussed. Although no single diagnostic group emerges as being at particularly high risk, substance abuse disorders alone or in combination with other psychiatric disorders have been repeatedly found to lend to increased mortality rates. Other studies have also repeatedly demonstrated that psychiatric patients suffer a high rate of comorbid medical illnesses, which are largely undiagnosed and untreated and which may cause or exacerbate psychiatric symptoms. Atypical presentations are common, and changes in vision are the symptoms most predictive of medical illness. Elderly patients and those with diagnoses of organic brain syndromes are at highest risk for comorbid medical illness. Parity in the medical and mental health treatment of psychiatric patients requires both political advocacy and development of primary care programs capable of efficiently meeting their needs. C1 VET AFFAIRS PUGET SOUND HLTH CARE SYST,MENTAL HLTH SERV,SEATTLE,WA 98108. VET AFFAIRS MED CTR,PSYCHIAT RESIDENCY PROGRAM,SALEM,VA. VET AFFAIRS MED CTR,PSYCHIAT SERV,SALEM,VA. UNIV VIRGINIA,MED CTR,CHARLOTTESVILLE,VA. RP Felker, B (reprint author), UNIV WASHINGTON,SCH MED,SEATTLE,WA 98195, USA. NR 67 TC 225 Z9 228 U1 2 U2 14 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD DEC PY 1996 VL 47 IS 12 BP 1356 EP 1363 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA VV250 UT WOS:A1996VV25000010 PM 9117475 ER PT J AU Pollack, MH AF Pollack, MH TI Handbook of depression and anxiety: A biological approach - denBoer,JA, Sitsen,JMA SO PSYCHIATRIC SERVICES LA English DT Book Review C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Pollack, MH (reprint author), MASSACHUSETTS GEN HOSP,ANXIETY DISORDERS PROGRAM,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 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD DEC PY 1996 VL 47 IS 12 BP 1403 EP 1403 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA VV250 UT WOS:A1996VV25000038 ER PT J AU Slanetz, PJ Boland, GW Mueller, PR AF Slanetz, PJ Boland, GW Mueller, PR TI Imaging and interventional radiology in laparoscopic injuries to the gallbladder and biliary system SO RADIOLOGY LA English DT Article DE cholecystectomy; gallbladder, interventional procedure; interventional procedures, utilization; state-of-art reviews ID BILE-DUCT INJURIES; CHOLECYSTECTOMY; COMPLICATIONS; MANAGEMENT; MECHANISMS; DILATATION; STRICTURES; DIAGNOSIS; SPECTRUM; ANATOMY AB Laparoscopic cholecystectomy has been prevalent in the United States since the late 1980s. Because of its increased use and potential for complications that can often be treated with interventional means, radiologists have become involved in treating patients with postlaparoscopic injury. This review details the imaging and interventional procedures involved in the care of patients with gallbladder and biliary problems due to laparoscopic cholecystectomy. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. OI Slanetz, Priscilla/0000-0003-1248-5116 NR 40 TC 24 Z9 24 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1996 VL 201 IS 3 BP 595 EP 603 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VU500 UT WOS:A1996VU50000003 PM 8939202 ER PT J AU Benacerraf, BR AF Benacerraf, BR TI Use of sonographic markers to determine the risk of down syndrome in second-trimester fetuses SO RADIOLOGY LA English DT Editorial Material DE Down syndrome; editorials; fetus, abnormalities; fetus, skeletal system; fetus, US ID SERUM ALPHA-FETOPROTEIN; DOWN-SYNDROME; 2ND TRIMESTER; CHROMOSOMAL-ABNORMALITIES; 2ND-TRIMESTER FETUSES; PRENATAL DETECTION; SCORING INDEX; TRISOMY-21; IDENTIFICATION; ASSOCIATION C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 25 TC 12 Z9 13 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1996 VL 201 IS 3 BP 619 EP 620 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VU500 UT WOS:A1996VU50000007 PM 8939206 ER PT J AU Kaufman, JA Salamipour, H Geller, SC Rivitz, SM Waltman, AC AF Kaufman, JA Salamipour, H Geller, SC Rivitz, SM Waltman, AC TI Long-term outcomes of radiologically placed arm ports SO RADIOLOGY LA English DT Article DE catheters and catheterization, central venous access; Catheters and catheterization, complications; Catheters and catheterization, technology; veins, thrombosis ID CENTRAL VENOUS CATHETERS; VASCULAR EROSIONS; ACCESS DEVICE; THROMBOSIS; DIAGNOSIS AB PURPOSE: To evaluate long-term outcomes of an initial experience with radiologic placement of arm ports. MATERIALS AND METHODS: The follow-up of 46 consecutive arm port placements (44 patients) was reviewed by means of chart review (hospital, office, and clinic) in 41 patients, telephone interview in 20, physical examination in 15, and venous ultrasound in 14. Data on port complications and function were recorded. Statistical methods were the Fisher Exact Test and Cochran-Mantel-Haenszel Test. RESULTS: Technical success for placement was 100%. Follow-up was obtained in 41 (93%) of the 44 patients (43 ports); mean days of catheter use was 344 days (total, 14,797 days; range, 10-1,104 days; median, 278 days). Rate (per 100 catheter days) of symptomatic central venous thrombosis was 0.054; arm phlebitis, 0.007; confirmed infection, 0.034; and catheter dysfunction, 0.095. Prophylactic anticoagulants did not affect symptomatic central venous thrombosis (P > .05, Fisher Exact Test). Catheter tip high in the right atrium was marginally associated with better catheter function (P = .041, Fischer Exact Test). CONCLUSION: Good long-term results can be anticipated with radiologic placement of arm ports. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. RP Kaufman, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 20 TC 31 Z9 31 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1996 VL 201 IS 3 BP 725 EP 730 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VU500 UT WOS:A1996VU50000023 PM 8939222 ER PT J AU Pfleiderer, B Campbell, T Hulka, CA Kopans, DB Lean, CL Ackerman, JL Brady, TJ Garrido, L AF Pfleiderer, B Campbell, T Hulka, CA Kopans, DB Lean, CL Ackerman, JL Brady, TJ Garrido, L TI Silicone gel-filled breast implants in women: Findings at H-1 MR spectroscopy SO RADIOLOGY LA English DT Article DE breast; breast, prostheses; silicone ID LOCALIZED PROTON SPECTROSCOPY; CONNECTIVE-TISSUE DISEASES; AUGMENTATION MAMMAPLASTY; SYSTEMIC-SCLEROSIS; MAMMOPLASTY; MIGRATION; RUPTURE; INVIVO; PROSTHESES; SYMPTOMS AB PURPOSE: To evaluate, at hydrogen-1 magnetic resonance (MR) spectroscopy, the effect of implantation time, implant status, and implant removal on the amount of silicone in the liver in women with silicone gel-filled breast prostheses. MATERIALS AND METHODS: The study population included 55 women (39 patients with silicone gel-filled prostheses and seven from whom implants had been removed, and nine control subjects [eight with no implant and one with saline-filled implants]). Stimulated-echo acquisition mode, or STEAM, H-1 MR spectroscopy was performed to determine the concentration of silicone in the liver. Implant status at the time of spectroscopy was diagnosed at MR imaging. RESULTS: Twenty of 39 (51%) women with implants had ruptured prostheses. Resonances associated with the presence of silicone and partially hydrolyzed silicone (0.3 to -0.8 ppm with respect to water at 4.7 ppm) and other resonances that are not yet assigned (-2 to -5 ppm) were detected in 27 (69%) of the 39 women (17 with ruptured implants). Relative signal intensities of the silicone species detected in the liver in these women were found to vary substantially and were not correlated with the status of the implants (P > .70). Silicone resonances were not detected in the livers in the nine control subjects. After implant removal, no resonances between 0.3 and -0.8 ppm were observed in six of seven women, but silicone-related peaks were still detectable in the region of -2 to -5 ppm. CONCLUSION: Proton MR spectra obtained in the liver of women with silicone gel-filled breast implants helped measure silicone exposure. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT RADIOL,NUCL MAGNET RESONANCE CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,BREAST IMAGING CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. RI Garrido, Leoncio/K-3092-2014; Ackerman, Jerome/E-2646-2015 OI Garrido, Leoncio/0000-0002-7587-1260; Ackerman, Jerome/0000-0001-5176-7496 FU NCI NIH HHS [R01 CA 59651] NR 42 TC 10 Z9 10 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1996 VL 201 IS 3 BP 777 EP 783 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VU500 UT WOS:A1996VU50000032 PM 8939231 ER PT J AU Moriarty, HJ Carroll, R Cotroneo, M AF Moriarty, HJ Carroll, R Cotroneo, M TI Differences in bereavement reactions within couples following death of a child SO RESEARCH IN NURSING & HEALTH LA English DT Article ID NEONATAL DEATH; SOCIAL SUPPORT; INFANT DEATH; PARENTS; GRIEF; DEPRESSION; INTERVENTION; VALIDATION; SCL-90 AB Differences in distress within couples who have experienced the sudden death of a child were examined. Results from two independent samples (N = 50 couples and N = 60 couples) were compared. The SCL-90-R and the BSI were used to measure global psychological distress and distress in nine symptom dimensions. Paired t tests revealed similar findings in the two samples: Within couples, women had significantly greater global distress than men and significantly greater distress than men in most symptom dimensions. Hostility scores within couples were similar and indicated a high level of hostility. The findings may explain relational problems observed within bereaved couples. Interventions designed to help couples cope with their differences and their hostility may decrease relational problems. (C) 1996 John Wiley & Sons, Inc. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. SALISBURY STATE UNIV,SALISBURY,CT. UNIV PENN,SCH NURSING,PHILADELPHIA,PA 19104. RP Moriarty, HJ (reprint author), VILLANOVA UNIV,COLL NURSING,VILLANOVA,PA 19085, USA. FU NINR NIH HHS [NR06272, NR07036, NR97036] NR 41 TC 32 Z9 32 U1 5 U2 11 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD DEC PY 1996 VL 19 IS 6 BP 461 EP 469 DI 10.1002/(SICI)1098-240X(199612)19:6<461::AID-NUR2>3.0.CO;2-M PG 9 WC Nursing SC Nursing GA VV921 UT WOS:A1996VV92100003 PM 8948400 ER PT J AU Robbins, J AF Robbins, J TI Normal swallowing and aging SO SEMINARS IN NEUROLOGY LA English DT Article ID MOTOR FUNCTION; AGE; SPHINCTER; PERFORMANCE; PHARYNGEAL; ABNORMALITIES; SENSITIVITY; INDIVIDUALS; MUSCLES; REFLEX C1 UNIV WISCONSIN,DEPT MED,MADISON,WI. RP Robbins, J (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,GRECC 11G,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. FU NINDS NIH HHS [R01 NS24427] NR 69 TC 25 Z9 25 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD DEC PY 1996 VL 16 IS 4 BP 309 EP 317 DI 10.1055/s-2008-1040989 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA WU475 UT WOS:A1996WU47500003 PM 9112310 ER PT J AU Small, EJ Dawson, NA Kantoff, PW Vogelzang, NJ AF Small, EJ Dawson, NA Kantoff, PW Vogelzang, NJ TI Cancer and leukemia group B trials for advanced prostate cancer SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT Roundtable Workshop on Hormone-Refractory Prostate Cancer - An Emerging Epidemic CY MAY 22, 1996 CL PHILADELPHIA, PA ID FLUTAMIDE WITHDRAWAL SYNDROME; ANTIANDROGEN WITHDRAWAL; ANTIGEN DECLINE C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. RP Small, EJ (reprint author), UNIV CALIF SAN FRANCISCO,MT ZION CANC CTR,UROL ONCOL SECT,SCH MED,2356 SUTTER ST,5TH FLOOR,SAN FRANCISCO,CA 94115, USA. NR 13 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 1996 VL 23 IS 6 SU 14 BP 28 EP 31 PG 4 WC Oncology SC Oncology GA WC452 UT WOS:A1996WC45200007 PM 8996582 ER PT J AU Morgan, BJ AF Morgan, BJ TI Acute and chronic cardiovascular responses to sleep disordered breathing SO SLEEP LA English DT Article; Proceedings Paper CT Proceedings of the 4th International Symposium on Sleep and Respiration CY MAR 31-APR 03, 1996 CL CHARLOTTESVILLE, VA DE obstructive sleep apnea; arterial pressure; sympathetic nervous system; hypertension ID BLOOD-PRESSURE; EPISODIC HYPOXIA; SYMPATHETIC ACTIVITY; APNEA; HYPOXEMIA; ELEVATION AB Episodes of sleep disordered breathing are surprisingly common in asymptomatic, middle-aged individuals. The majority of these events are hypopneas, rather than apneas. Even though these events cause rather modest decreases in arterial oxygen saturation, they evoke substantial increases in arterial pressure. In this population, mild to moderate sleep disordered breathing is associated with elevated daytime blood pressure. The mechanisms responsible for the acute and chronic cardiovascular effects of sleep disordered breathing are incompletely understood. Chemoreflex mechanisms appear to be more important than intrathoracic pressure changes in causing the acute elevation in arterial pressure that occurs after obstructive sleep apnea. Arousal from sleep may contribute to this presser response, either in an additive or synergistic manner. Relatively brief exposure to combined hypoxia and hypercapnia during wakefulness can produce an increase in sympathetic outflow to skeletal muscle that persists after return to room air breathing. This lingering post-asphyxic effect on sympathetic outflow may be the basis of chronically elevated sympathetic nervous system activity which accompanies sleep apnea syndrome and may contribute to sustained hypertension in these individuals. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. RP Morgan, BJ (reprint author), UNIV WISCONSIN,DEPT KINESIOL,MED SCI CTR 5175,1300 UNIV AVE,MADISON,WI 53706, USA. NR 17 TC 14 Z9 14 U1 0 U2 0 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 1610 14TH STREET NW SUITE 300, ROCHESTER, MN 55806 SN 0161-8105 J9 SLEEP JI Sleep PD DEC PY 1996 VL 19 IS 10 SU S BP S206 EP S209 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WP543 UT WOS:A1996WP54300019 PM 9085512 ER PT J AU Ashton, CM Wray, NP AF Ashton, CM Wray, NP TI A conceptual framework for the study of early readmission as an indicator of quality of care SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE readmission; quality of care; process-outcome studies; evaluation ID HOSPITAL-CARE; PROSPECTIVE PAYMENT; CONTROLLED TRIAL; INPATIENT CARE; DISCHARGE; RATES; LENGTH; STAY; ASSOCIATION; VETERANS AB Despite the perennial popularity of readmission as an indicator of the quality of hospital care, the empiric evidence linking it to process-of-care problems during the prior hospitalization is inconsistent. We devised a conceptual model for the use of unscheduled readmission within 31 days as an indicator of the quality of medical-surgical inpatient care for adults, and then conducted a systematic review of the readmission literature to determine the extent to which the evidence supports the proposed relationships. A fairly complex web of relationships influences the association between the process of inpatient care and early readmission. From the evidence to date, it is impossible to say with confidence that early readmission is or is not a valid and useful quality indicator. In most negative studies, the absence of an association appears to be explainable on the basis of improper study design, omission of important variables, or mis-specification of variables. Variables intervening between or confounding the relationship of the process of inpatient care to early readmission have received inadequate attention in past work. Investigators can use the proposed model and literature review to ensure their work advances the field and puts the hypothesis that early readmission is a valid quality indicator to a rigorous test. This matter has a certain urgency in view of the vast amount of resources that providers and payers devote to monitoring readmission rates and reviewing readmissions. C1 BAYLOR COLL MED,HOUSTON,TX 77030. RP Ashton, CM (reprint author), VET AFFAIRS MED CTR 152,2002 HOLCOMBE,HOUSTON,TX 77030, USA. NR 39 TC 94 Z9 94 U1 3 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 1996 VL 43 IS 11 BP 1533 EP 1541 DI 10.1016/S0277-9536(96)00049-4 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA VV899 UT WOS:A1996VV89900002 PM 8961397 ER PT J AU Young, B Moore, WS Robertson, JT Toole, JF Ernst, CB Cohen, SN Broderick, JP Dempsey, RJ Hosking, JD AF Young, B Moore, WS Robertson, JT Toole, JF Ernst, CB Cohen, SN Broderick, JP Dempsey, RJ Hosking, JD TI An analysis of perioperative surgical mortality and morbidity in the asymptomatic carotid atherosclerosis study SO STROKE LA English DT Article DE carotid endarterectomy; carotid stenosis; clinical trials; complications ID MAGNETIC-RESONANCE ANGIOGRAPHY; POSTOPERATIVE HYPERTENSION; CONVENTIONAL ANGIOGRAPHY; ELDERLY PATIENTS; ARTERY STENOSIS; MR-ANGIOGRAPHY; ENDARTERECTOMY; COMPLICATIONS; EFFICACY AB Background and Purpose Our aim was to determine the perioperative morbidity and mortality rates of patients in the surgical arm of the multi-institutional, prospective, randomized Asymptomatic Carotid Atherosclerosis Study (ACAS). Methods Of 828 patients with carotid stenosis of 60% or more randomized to the surgical arm of ACAS, 721 underwent carotid endarterectomy (CEA). To qualify for participation, surgeons were required to have performed at least 12 CEAs per year with a combined neurological morbidity and mortality rate no greater than 3% for asymptomatic patients and 5% for symptomatic patients. Clinical centers had to demonstrate arteriographic morbidity less than 1% and mortality less than 0.1% per year. Primary events were stroke and death in the period between randomization and 30 days after surgery; secondary events were transient ischemic attack and myocardial infarction occurring in the same period. Results Of the 721 patients who underwent CEA, 1 died and 10 others had strokes within 30 days (1.5%). Of the 415 who underwent arteriography after randomization but before CEA, 5 (1.2%) suffered transient ischemic attack or stroke caused by arteriography. Thus, a nearly equal risk of stroke was associated with both CEA and carotid arteriography. In addition, 6 transient ischemic attacks and 3 myocardial infarctions could be directly linked to CEA, for a total CEA event rate of 2.6%. Conclusions Patients with asymptomatic internal carotid artery stenosis exceeding 60% reduction in diameter who are acceptable candidates for elective operation may be considered for CEA if the combined arteriographic and surgical complication rates are 3% or less. C1 UNIV KENTUCKY,ALBERT B CHANDLER MED CTR,LEXINGTON,KY 40536. UNIV TENNESSEE,DEPT NEUROSURG,MEMPHIS,TN. UNIV CALIF LOS ANGELES,DEPT SURG,LOS ANGELES,CA 90024. HENRY FORD HOSP,DEPT VASC SURG,DETROIT,MI 48202. UNIV N CAROLINA,CHAPEL HILL,NC. UNIV CINCINNATI,COLL MED,CINCINNATI,OH 45221. W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV,LOS ANGELES,CA. RP Young, B (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,MED CTR,ACAS,EDITORIAL OFF,STROKE CTR,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. FU NINDS NIH HHS [NS22611] NR 28 TC 122 Z9 126 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 DEC PY 1996 VL 27 IS 12 BP 2216 EP 2224 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VY009 UT WOS:A1996VY00900012 PM 8969784 ER PT J AU Ogilvy, CS Ojemann, RG AF Ogilvy, CS Ojemann, RG TI Indications for carotid endarterectomy SO SURGICAL NEUROLOGY LA English DT Editorial Material RP Ogilvy, CS (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD DEC PY 1996 VL 46 IS 6 BP 543 EP 544 DI 10.1016/S0090-3019(97)85980-0 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA VX478 UT WOS:A1996VX47800020 ER PT J AU Murai, H Murakami, S Ishida, K Sugawara, M AF Murai, H Murakami, S Ishida, K Sugawara, M TI Elevated serum interleukin-6 and decreased thyroid hormone levels in postoperative patients and effects of IL-6 on thyroid cell function in vitro SO THYROID LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA-CACHECTIN; SURGICAL STRESS; NONTHYROIDAL ILLNESSES; GENE-EXPRESSION; THYROXINE; METABOLISM; PEROXIDASE; 3,5,3'-TRIIODOTHYRONINE; OPERATION AB We studied a wide variety of surgical patients to determine whether serum levels of interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) correlate with the changes in serum thyroid hormone levels of the postoperative period. Surgical procedures were divided into minor surgery (cholecystectomy, n = 12), moderate surgery (colorectal cancer and stomach cancer, n = 54), and extensive surgery (esophageal cancer or pancreatic cancer, n = 6). One day after surgery, serum free T-3 levels decreased in all 3 groups when compared to the preoperative values; serum free T-4 levels did not change regardless of surgical procedure. Serum TSH levels decreased significantly 1 day after surgery in the groups of moderate and extensive surgery. Serum levels of IL-6 increased 12 h after surgery and began to decrease gradually thereafter. There was no change in serum levels of TNF-alpha before and after surgery. The increment of serum IL-6 was dependent on the surgical procedures: the more extensive the surgery, the greater the increase in serum IL-6. Serum free T-3 and free T-4 levels were inversely correlated with the serum levels of IL-6. To further examine whether IL-6 is responsible for alteration of thyroid hormone production, cultured porcine thyroid follicles were exposed to 0 to 20 ng/ml of recombinant human IL-6 for 24 to 48 h. Then, type 1 5'-deiodinase activity (T-4 to T-3 converting enzyme), iodide uptake, and thyroid peroxidase (TPO) activity were measured. Our in vitro experiments showed no effect of IL-6 on these parameters. In summary, surgical procedure can cause elevation of serum IL-6 and decrease in serum free T-3 levels. However, IL-6 alone does not appear to be a strong candidate for alteration of thyroid hormone production including T-3 generation from T-4. C1 W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90073. RP Murai, H (reprint author), SAITAMA MED SCH,DEPT SURG 2,38 MOROHONGO,MOROYAMA,SAITAMA 35004,JAPAN. NR 35 TC 19 Z9 20 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD DEC PY 1996 VL 6 IS 6 BP 601 EP 606 DI 10.1089/thy.1996.6.601 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WC354 UT WOS:A1996WC35400008 PM 9001195 ER PT J AU Dratman, MB Gordon, JT AF Dratman, MB Gordon, JT TI Thyroid hormones as neurotransmitters SO THYROID LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; FILM AUTORADIOGRAPHY; BINDING-SITES; TRIIODOTHYRONINE; LOCALIZATION; TRANSPORT; THYROXINE; RECEPTOR; 5'-DEIODINASE AB During brain development, before the apparatus of neurotransmission has been set into place, many neurotransmitters act as growth regulators. In adult brain, their role in neurotransmission comes to the fore but neuronal plasticity and other growth-related processes are their continuing responsibility. This has been clearly demonstrated for catecholamines. Previous as well as recent evidence now indicates that thyroid hormones may participate in the developing and adult brain through similar mechanisms. Immunohistochemical mapping of brain triiodothyronine (antibody specificity established by numerous appropriate tests) demonstrated that the hormone was concentrated in both noradrenergic centers and noradrenergic projection sites. In the centers (locus coeruleus and lateral tegmental system) triiodothyronine staining, like that of tyrosine hydroxylase, was heavily concentrated in cytosol and cell processes. By contrast, in noradrenergic targets, label was most prominent in cell nuclei. Combined biochemical and morphologic data allows a construct of thyroid hormone circuitry to unfold: The locus coeruleus is conveniently located just beneath the ependyma of the 4th ventricle. Thyroxine, entering the brain via the choroid plexus, is preferentially delivered to subependymal brain structures. High concentrations of locus coeruleus norepinephrine promote active conversion of thyroxine to triiodothyronine, leading to the preeminence of the locus coeruleus as a site of triiodothyronine concentration. Results of treatment with the locus coeruleus neurotoxin DSP-4 established that axonal transport accounts for delivery of both triiodothyronine and norepinephrine from locus coeruleus to noradrenergic terminal fields. The apparatus for transduction of thyronergic and noradrenergic signals at both membrane and nuclear sites resides in the postsynaptic target cells. Upon internalization of hormone in post-synaptic target cells, genomic effects of triiodothyronine, norepinephrine, and/or their second messengers are possible and expected. The evidence establishes a direct morphologic connection between central thyronergic and noradrenergic systems, supporting earlier proposals that triiodothyronine or its proximate metabolites may serve as cotransmitters with norepinephrine in the adrenergic nervous system. C1 ALLEGHENY UNIV HLTH SCI,MCP HAHNNEMAN SCH MED,DEPT MED,PHILADELPHIA,PA 19104. RP Dratman, MB (reprint author), VET AFFAIRS MED CTR,MED RES SERV,38TH & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. FU PHS HHS [45252] NR 35 TC 75 Z9 76 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD DEC PY 1996 VL 6 IS 6 BP 639 EP 647 DI 10.1089/thy.1996.6.639 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WC354 UT WOS:A1996WC35400014 PM 9001201 ER PT J AU Delgado, JC Yunis, DE Bozon, MV Salazar, M Deulofeut, R Turbay, D Mehra, NK Pasricha, JS Raval, RS Patel, H Shah, BK Bhol, K Alper, CA Ahmed, AR Yunis, EJ AF Delgado, JC Yunis, DE Bozon, MV Salazar, M Deulofeut, R Turbay, D Mehra, NK Pasricha, JS Raval, RS Patel, H Shah, BK Bhol, K Alper, CA Ahmed, AR Yunis, EJ TI MHC class II alleles and haplotypes in patients with pemphigus vulgaris from India SO TISSUE ANTIGENS LA English DT Article DE HLA alleles; pemphigus vulgaris; PCR-SSOP ID MAJOR HISTOCOMPATIBILITY COMPLEX; JEWISH PATIENTS; SUSCEPTIBILITY; AUTOIMMUNITY; IGG AB Pemphigus vulgaris (PV) is a blistering disease of the skin and mucous membranes characterized by an autoantibody response against a keratinocyte adhesion molecule, desmoglein 3, causing acantholysis and blister formation. We compared high resolution MHC class II alleles and haplotype frequencies (HLA-DRB, DQA1 and DQB1) in 37 patients with PV to 89 haplotypes of normal relatives from New Delhi and Ahmedabad. We found that PV patients had significantly increased frequencies of DRB1*1404 (P<0.001), DQA1*0101 (P=0.001), and DQB1*0503 (P<0.0001). These associations were due to the increased frequencies of the haplotype HLA-DRB1*1404, DRB3*0202, DQA1*0101, DQB1*0503 in patients compared to control haplotypes (p<0.0001). Also, patients from Ahmedabad had a significant increase in HLA-DQB1*0302 (p=0.03). An identical amino acid sequence (Leu-Leu-Glu-Arg-Arg-Arg-Ala-Glu), in positions 67-74 of the beta domain of DRB alleles is restricted to some DR14 alleles. Therefore, there are three possible explanations for class II allele involvement in autoantibody in PV patients with class II haplotypes marked by HLA-DR14. First, the class II alleles could be markers for an unidentified susceptibility gene in linkage disequilibrium with them. Second, the primary association could be with DQB1*0503 and the association with HLA-DR14 alleles would be the result of linkage disequilibrium. Third, the HLA-DRB1 locus susceptibility could involve a specific amino acid sequence in the third hypervariable region shared by several HLA-DR14 alleles. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. AMER RED CROSS,DEDHAM,MA. ALL INDIA INST MED SCI,NEW DELHI,INDIA. CIVIL HOSP,BJ MED COLL,AHMEDABAD,GUJARAT,INDIA. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH DENT MED,BOSTON,MA 02115. RP Delgado, JC (reprint author), DANA FARBER CANC INST,DIV IMMUNOGENET,BOSTON,MA 02115, USA. FU NEI NIH HHS [EY08379]; NHLBI NIH HHS [HL29583]; NIDCR NIH HHS [DE09978] NR 24 TC 36 Z9 37 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 DEC PY 1996 VL 48 IS 6 BP 668 EP 672 DI 10.1111/j.1399-0039.1996.tb02690.x PG 5 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA WA753 UT WOS:A1996WA75300007 PM 9008309 ER PT J AU Lewis, CB AF Lewis, CB TI Managing dementia - From the editor SO TOPICS IN GERIATRIC REHABILITATION LA English DT Editorial Material C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,WASHINGTON,DC 20052. MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. RP Lewis, CB (reprint author), PHYS THERAPY SERV WASHINGTON DC INC,WASHINGTON,DC, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21701 SN 0882-7524 J9 TOP GERIATR REHABIL JI Top. Geriatr. Rehabil. PD DEC PY 1996 VL 12 IS 2 BP R5 EP R6 PG 2 WC Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA VV436 UT WOS:A1996VV43600001 ER PT J AU Ocain, TD Bastos, CM Gordon, KA Granstein, RD Jenson, JC Jones, B McAuliffe, DJ Newcomb, JR AF Ocain, TD Bastos, CM Gordon, KA Granstein, RD Jenson, JC Jones, B McAuliffe, DJ Newcomb, JR TI A novel series of low molecular weight immunosuppressive agents SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd International Conference on New Trends in Clinical and Experimental Immunosuppression CY FEB 15-18, 1996 CL GENEVA, SWITZERLAND ID PROTEIN C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Ocain, TD (reprint author), PROCEPT INC,840 MEM DRV,CAMBRIDGE,MA 02139, USA. NR 4 TC 6 Z9 6 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1996 VL 28 IS 6 BP 3032 EP 3034 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA VW999 UT WOS:A1996VW99900008 PM 8962176 ER PT J AU Jacobs, IJ Skates, S Davies, AP Woolas, RP Jeyerajah, A Weidemann, P Sibley, K Oram, DH AF Jacobs, IJ Skates, S Davies, AP Woolas, RP Jeyerajah, A Weidemann, P Sibley, K Oram, DH TI Risk of diagnosis of ovarian cancer after raised serum CA 125 concentration: A prospective cohort study SO BRITISH MEDICAL JOURNAL LA English DT Article ID CA-125 LEVELS; MARKERS AB Objective-To determine the risk of invasive epithelial ovarian cancer and fallopian tube cancer associated with a raised concentration of the tumour marker CA 125 in asymptomatic postmenopausal women. Design-Serum CA 125 concentration was measured annually in study participants for one to four years. Participants with a concentration greater than or equal to 30 U/ml were recalled for abdominal ultrasonography. Follow up was by annual postal questionnaire. Setting-General practice, occupational health departments, ovarian cancer screening unit in a teaching hospital. Subjects-22 000 volunteers, all postmenopausal women greater than or equal to 45 years of age; recruited between 1 June 1986 and 1 May 1990. Intervention-Surgical investigation if the ultrasound examination was abnormal. Main outcome measures-Cumulative and relative (invasive fallopian tube) after a specified CA 125 result. Results-49 index cancers developed in the study population during a mean follow up of 6.76 years. The overall cumulative risk of developing an index cancer was 0.0022 for the entire study population and was lower for women with a serum CA 125 concentration <30 U/ml (cumulative risk 0.0012) but was appreciably increased for women with a concentration greater than or equal to 30 U/ml (0.030) and >100 U/ml (0.149). Compared with the entire study population the relative risk of developing an index cancer within one year and five years was increased 35.9-fold (95% confidence interval 18.3 to 70.4) and 14.3-fold (8.5 to 24.3) respectively after a serum CA 125 concentration greater than or equal to 30 U/ml and 204.8-fold (79.0 to 530.7) and 74.5-fold (31.1 to 178.3) respectively after a concentration greater than or equal to 100 U/ml. Conclusion-CA 125 is a powerful index of risk of ovarian and fallopian tube cancer in asymptomatic postmenopausal women. C1 ROYAL LONDON HOSP,LONDON EC1A 7BE,ENGLAND. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Jacobs, IJ (reprint author), ST BARTHOLOMEWS HOSP,DEPT GYNAECOL ONCOL,OVARIAN CANC SCREENING UNIT,LONDON EC1A 7BE,ENGLAND. RI Jacobs, Ian/F-1743-2013 OI Jacobs, Ian/0000-0002-8112-4624 NR 16 TC 122 Z9 126 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD NOV 30 PY 1996 VL 313 IS 7069 BP 1355 EP 1358 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA VW685 UT WOS:A1996VW68500021 PM 8956699 ER PT J AU Chu, BY Soncin, F Price, BD Stevenson, MA Calderwood, SK AF Chu, BY Soncin, F Price, BD Stevenson, MA Calderwood, SK TI Sequential phosphorylation by mitogen-activated protein kinase and glycogen synthase kinase 3 represses transcriptional activation by heat shock factor-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING; MAP KINASE; CELLS; STRESS; EXPRESSION; YEAST; GENE; MECHANISMS; TRANSITION; PATHWAYS AB Mammalian heat shock genes are regulated at the transcriptional level by heat shock factor-1 (HSF-1), a sequence-specific transcription factor. We have examined the role of serine phosphorylation of HSF-1 in the regulation of heat shock gene transcription, Our experiments show that mitogen-activated protein kinases (MAPKs) of the ERK-1 family phosphorylate HSF-1 on serine residues and repress the transcriptional activation of the heat shock protein 70B (HSP70B) promoter by HSP-1 in vivo, These effects of MAPK are transmitted through a specific serine residue (Ser-303) located in a proline-rich sequence within the transcriptional regulatory domain of human HSF-1, However, despite the importance of Ser-303 in transmitting the signal from the MAPK cascade to HSP70 transcription, there was no evidence that Ser-303 could be phosphorylated by MAPK in vitro, although an adjacent residue (Ser-307) was avidly phosphorylated by MAPK. Further studies revealed that Ser-303 is phosphorylated by glycogen synthase kinase 3 (GSK3) through a mechanism dependent on primary phosphorylation of Ser-307 by MAPK, Secondary phosphorylation of Ser-303 by GSK3 may thus repress the activity of HSF-1, and its requirement for priming by MAPK phosphorylation of Ser-307 provides a potential link between the MAPK cascade and HSF-1, Our experiments thus indicate that MAPK is a potent inhibitor of HSF-1 function and may be involved in repressing the heat shock response during normal growth and development and deactivating the heat shock response during recovery from stress. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, JOINT CTR RADIAT THERAPY, BOSTON, MA 02115 USA. RI SONCIN, Fabrice/A-1475-2009; OI Soncin, Fabrice/0000-0001-6312-0673 FU NCI NIH HHS [CA31303, CA47407, CA50642] NR 40 TC 267 Z9 277 U1 2 U2 9 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 29 PY 1996 VL 271 IS 48 BP 30847 EP 30857 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VV158 UT WOS:A1996VV15800085 PM 8940068 ER PT J AU Liu, CC Young, LHY Young, JDE AF Liu, CC Young, LHY Young, JDE TI Lymphocyte-mediated cytolysis and disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; TUMOR-INFILTRATING LYMPHOCYTES; CYTOTOXIC T-LYMPHOCYTES; ACTIVATED KILLER-CELLS; TARGET-CELLS; GRANZYME-A; CD8+ LYMPHOCYTES; PERFORIN GENE; HIV-INFECTION; MICE LACKING C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. RP Liu, CC (reprint author), ROCKEFELLER UNIV,LAB MOL IMMUNOL & CELL BIOL,1230 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA47307] NR 102 TC 78 Z9 85 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 NOV 28 PY 1996 VL 335 IS 22 BP 1651 EP 1659 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA VV936 UT WOS:A1996VV93600006 PM 8929363 ER PT J AU Hennekens, CH Albert, CM Godfried, SL Gaziano, JM Buring, JE AF Hennekens, CH Albert, CM Godfried, SL Gaziano, JM Buring, JE TI Adjunctive drug therapy of acute myocardial infarction evidence from clinical trials SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID LEFT-VENTRICULAR DYSFUNCTION; PROPHYLACTIC LIDOCAINE; MAGNESIUM-SULFATE; RANDOMIZED TRIALS; HEART-DISEASE; DOUBLE-BLIND; FOLLOW-UP; MORTALITY; PREVENTION; FIBRILLATION C1 BRIGHAM & WOMENS HOSP, DEPT MED, DIV CARDIOVASC, BOSTON, MA 02215 USA. MASSACHUSETTS GEN HOSP, DEPT MED, DIV CARDIOVASC, BOSTON, MA 02114 USA. BROCKTON W ROXBURY VET AFFAIRS MED CTR, DEPT MED, BOSTON, MA USA. HARVARD UNIV, SCH MED, DEPT AMBULATORY CARE & PREVENT, BOSTON, MA USA. RP Hennekens, CH (reprint author), BRIGHAM & WOMENS HOSP, DEPT MED, DIV PREVENT MED, 900 COMMONWEALTH AVE E, BOSTON, MA 02215 USA. NR 72 TC 188 Z9 192 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 28 PY 1996 VL 335 IS 22 BP 1660 EP 1667 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VV936 UT WOS:A1996VV93600007 PM 8929364 ER PT J AU Molpus, KL Koelliker, D Atkins, L Kato, DT BuczekThomas, J Fuller, AF Hasan, T AF Molpus, KL Koelliker, D Atkins, L Kato, DT BuczekThomas, J Fuller, AF Hasan, T TI Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID NUDE-MICE; CANCER; INTEGRINS; THERAPY; TUMORS AB A new xenograft model for human epithelial ovarian carcinoma, with extensive intraperitoneal (i.p.) carcinomatosis as the predominant disease manifestation, is described. Cells from the established NIH:OVCAR-5 cell line were injected i.p. into 6-to 8-week-old Swiss nude mice. Comparative analyses between cells cultured in vitro and tumor cells derived ex vivo were performed to assess histologic features, immunohistochemical cell markers, hormonal receptor expression, adhesion to extracellular matrix molecules and chromosomal constitution. Macroscopically, the extent of tumor development appeared to be site-dependent and tumor cell survival was dose-dependent. Advanced disease was characterized by extensive solid tumor burden and ascites with parenchymal invasion, lymphatic metastases and vascular dissemination. Individual tumor nodules exhibited developing neovasculature characterized by the absence of mature basement membrane. Despite some histologic loss of cellular differentiation in advanced disease, antigenic expression was preserved, distinguishing these cells as epithelial in origin. Karyotyping of tumor cells demonstrated multiple numeric and structural chromosomal abnormalities. Serum and ascites CA 125 levels were consistently elevated only in tumor-bearing mice. This new murine model closely resembles the aggressive disease process of human epithelial ovarian carcinoma, in which the efficacy of i.p. and systemic therapeutic modalities can be investigated. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT GYNECOL ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT CYTOGENET,BOSTON,MA 02114. FU NIAMS NIH HHS [R01AR40352] NR 22 TC 32 Z9 32 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 27 PY 1996 VL 68 IS 5 BP 588 EP 595 PG 8 WC Oncology SC Oncology GA VW532 UT WOS:A1996VW53200006 PM 8938139 ER PT J AU Albert, MS AF Albert, MS TI Cognitive and neurobiologic markers of early Alzheimer disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Memory - Recording Experience in Cells and Circuits CY FEB 17-20, 1996 CL NATL ACAD SCI IRVINE, IRVINE, CA HO NATL ACAD SCI IRVINE ID TEMPORAL-LOBE; NEURONAL LOSS; SYNAPSE LOSS; NEUROFIBRILLARY TANGLES; MEMORY IMPAIRMENT; BASAL FOREBRAIN; NUCLEUS BASALIS; WORKING MEMORY; RHESUS-MONKEY; DEMENTIA AB Recent studies indicate that impairments in two cognitive domains characterize the cognitive abnormalities that appear earliest in the course of Alzheimer disease (AD), These cognitive domains pertain to memory and executive function ability; in particular, memory test scores reflecting the difference between immediate and delayed recall and tasks that assess cognitive flexibility (e.g., set-shifting), Preliminary data indicate that tasks of this nature, along with specific genetic information (i.e., APOE-4 status), are important in identifying which individuals with recent cognitive changes (considered to have ''questionable'' disease) will progress to the point where they meet criteria for AD over time. When this cognitive and genetic information is combined with neuroimaging measures targeted at the brain regions demonstrating pathology early in AD, it may serve as specific and accurate prognostic markers of AD. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. RP Albert, MS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02114, USA. NR 62 TC 144 Z9 145 U1 3 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 26 PY 1996 VL 93 IS 24 BP 13547 EP 13551 DI 10.1073/pnas.93.24.13547 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700018 PM 8942970 ER PT J AU Acharya, S Wilson, T Gradia, S Kane, MF Guerrette, S Marsischky, GT Kolodner, R Fishel, R AF Acharya, S Wilson, T Gradia, S Kane, MF Guerrette, S Marsischky, GT Kolodner, R Fishel, R TI hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; HUMAN MSH2 PROTEIN; SACCHAROMYCES-CEREVISIAE; MISMATCH REPAIR; MUTS HOMOLOG; MICROSATELLITE INSTABILITY; MUTATIONS; GENE; DNA; CLONING AB The genetic and biochemical properties of three human MutS homologues, hMSH2, hMSH3, and hMSH6, have been examined, The full-length hMSH6 cDNA and genomic locus were isolated and characterized, and it was demonstrated that the hMSH6 gene consisted of 10 exons and mapped to chromosome 2p15-16, The hMSH3 cDNA was in some cases found to contain a 27-bp deletion resulting in a loss of nine amino acids, depending on the individual from which the cDNA was isolated, hMSH2, hMSH3, and hMSH6 all showed similar tissue-specific expression patterns, hMSH2 protein formed a complex with both hMSH3 and hMSH6 proteins, similar to protein complexes demonstrated by studies of the Saccharomyces cerevisiae MSH2, MSH3, and MSH6. hMSH2 was also found to form a homomultimer complex, but neither hMSH3 nor hMSH6 appear to interact with themselves or each other, Analysis of the mismatched nucleotide-binding specificity of the hMSH2-hMSH3 and hMSH2-hMSN6 protein complexes showed that they have overlapping but not identical binding specificity, These results help to explain the distribution of mutations in different mismatch-repair genes seen in hereditary nonpolyposis colon cancer. C1 THOMAS JEFFERSON UNIV,KIMMEL CANC CTR,DNA REPAIR & MOL CARCINOGENSIS PROGRAM,PHILADELPHIA,PA 19107. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CHARLES A DANA DIV HUMAN CANC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 06516, CA 44704, P30 CA006516, R01 CA056542, R01 CA067007]; NIGMS NIH HHS [GM50006, R01 GM050006] NR 32 TC 401 Z9 409 U1 1 U2 23 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 26 PY 1996 VL 93 IS 24 BP 13629 EP 13634 DI 10.1073/pnas.93.24.13629 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700033 PM 8942985 ER PT J AU Page, K Hollister, R Tanzi, RE Hyman, BT AF Page, K Hollister, R Tanzi, RE Hyman, BT TI In situ hybridization analysis of presenilin 1 mRNA in Alzheimer disease and in lesioned rat brain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hippocampal formation; excitotoxic lesion ID MISSENSE MUTATION; APOLIPOPROTEIN-E; MESSENGER-RNA; S182 GENE; PROTEIN; FAMILIES; PLAQUES AB Presenilin-1 (PS-1) gene mutations are responsible for the majority of the early onset familial forms of Alzheimer disease (AD), Neither PS-1's anatomic distribution in brain nor expression in AD have been reported, Using in situ hybridization in the rat forebrain, we show that PS-1 mRNA expression is primarily in cortical and hippocampal neurons, with less expression in subcortical structures, In a regional pattern similar to APP695, Excitotoxic lesions lead to loss of PS-1 signal, A neuronal pattern of expression of PS-1 mRNA was also observed in the human hippocampal formation, AD and control levels did not differ, PS-1 is expressed in brain areas vulnerable to AD changes more so than in areas spared in AD; however, PS-1 expression is not sufficient to mark vulnerable regions, Collectively, these data suggest that the neuropathogenic process consequent to PS-1 mutations begins in neuronal cell populations. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GENET & AGING LAB,BOSTON,MA 02114. FU NIA NIH HHS [P50 AG005134, AG05134, AG11337] NR 28 TC 42 Z9 42 U1 2 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 26 PY 1996 VL 93 IS 24 BP 14020 EP 14024 DI 10.1073/pnas.93.24.14020 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700101 PM 8943053 ER PT J AU Strobel, T Swanson, L Korsmeyer, S Cannistra, SA AF Strobel, T Swanson, L Korsmeyer, S Cannistra, SA TI BAX enhances paclitaxel-induced apoptosis through a p53-independent pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE drug resistance; chemotherapy; ovarian; cancer ID PROGRAMMED CELL-DEATH; TUMOR-SUPPRESSOR P53; BCL-2 HOMOLOG BAK; DNA FRAGMENTATION; IN-VIVO; MONOCLONAL-ANTIBODY; CANCER-THERAPY; OVARIAN-CANCER; GENE; EXPRESSION AB To investigate the role of BAX in chemotherapy-induced apoptosis, we transfected the SW626 human ovarian cancer cell line, which lacks functional p53, with a cDNA encoding for murine BAX. Immunoblotting revealed that BAX transfectants expressed a mean of 10-fold increased levels of BAX compared with neo-transfected control clones, with similar levels of BCL-2 and BCL-X(L). The cytotoxicity of paclitaxel, vincristine, and doxorubicin was significantly enhanced in BAX transfectants compared with control clones, whereas the cytotoxicity profile of carboplatin, etoposide, and hydroxyurea was unchanged, Increased paclitaxel-induced cytotoxicity of BAX clones was associated with enhanced apoptosis, as assessed by morphologic and flow cytometric criteria, These data suggest that sufficient levels of BAX may bypass the need for upstream molecules such as p53 in the process of chemotherapy-induced apoptosis. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV NEOPLAST DIS,BOSTON,MA 02115. WASHINGTON UNIV,SCH MED,DIV MOL ONCOL,ST LOUIS,MO 63110. FU NCI NIH HHS [CA 60670] NR 34 TC 191 Z9 197 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 26 PY 1996 VL 93 IS 24 BP 14094 EP 14099 DI 10.1073/pnas.93.24.14094 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700114 PM 8943066 ER PT J AU Li, TS Snyder, WK Olsson, JE Dryja, TP AF Li, TS Snyder, WK Olsson, JE Dryja, TP TI Transgenic mice carrying the dominant rhodopsin mutation P347S: Evidence for defective vectorial transport of rhodopsin to the outer segments SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EQUIVALENT LIGHT HYPOTHESIS; RETINITIS-PIGMENTOSA; RETINAL DEGENERATION; MUTANT MOUSE; GENE; OPSIN; LOCALIZATION; PHOTORECEPTORS; ANTIBODIES; MEMBRANES AB To explore the pathogenic mechanism of dominant mutations affecting the carboxyl terminus of rhodopsin that cause retinitis pigmentosa, me generated five lines of transgenic mice carrying the proline-347 to serine (P347S) mutation, The severity of photoreceptor degeneration correlated with the levels of transgene expression in these lines, Visual function as measured by the electroretinogram was approximately normal at an early age when there was little histologic evidence of photoreceptor degeneration, but it deteriorated as photoreceptors degenerated, Immunocytochemical staining showed the mutant rhodopsin predominantly in the outer segments prior to histologically evident degeneration, a finding supported by quantitation of signal intensities in different regions of the photoreceptor cells by confocal microscopy, A distinct histopathologic abnormality was the accumulation of submicrometer-sized vesicles extracellularly near the junction between inner and outer segments, The extracellular vesicles were bound by a single membrane that apparently contained rhodopsin as revealed by ultrastructural immunocytochemical staining with anti-rhodopsin antibodies, The outer segments, although shortened, contained well-packed discs, Proliferation of the endoplasmic reticulum as reported in Drosophila expressing dominant rhodopsin mutations was not observed, The accumulation of rhodopsin-laden vesicles likely represents aberrant transport of rhodopsin from the inner segments to the nascent disc membranes of the outer segments, It is possible that photoreceptor degeneration occurs because of a failure to renew outer segments at a normal rate, thereby leading to a progressive shortening of outer segments, or because of the loss of cellular contents to the extracellular space, or because of both. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,OCULAR MOL GENET INST,BOSTON,MA 02114. RP Li, TS (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY10309, R01 EY010309] NR 31 TC 166 Z9 174 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 NOV 26 PY 1996 VL 93 IS 24 BP 14176 EP 14181 DI 10.1073/pnas.93.24.14176 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700128 PM 8943080 ER PT J AU Meyer, TJ Prochazka, AV Hannaford, M Fryer, GE AF Meyer, TJ Prochazka, AV Hannaford, M Fryer, GE TI Randomized controlled trial of residents as gatekeepers SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MEDICAL-CARE; SATISFACTION; POPULATION AB Background: Managed care advocates suggest that primary care gatekeepers may improve patient care and reduce costs. Training internal medicine residents in these gatekeeping functions has not been emphasized in most internal medicine programs. Objective: To determine if residents could perform gatekeeper functions and if patient costs and satisfaction would be favorable. Methods: Patients (n=254) followed up by residents (n=26) in continuity clinics at the Denver Veterans Affairs Medical Center in Denver, Cole, were divided into 2 groups. A control group of 128 was followed up by residents with no restrictions on appointments made for them. An intervention group of 126 patients were followed up by residents who had to approve all referrals made for their patients. A research nurse assisted with the approvals when the residents were rotating through other institutions. Utilization of resources, satisfaction with care, and health status were monitored over a 1-year period. Results: A minor reduction of resource utilization was found in the intervention group, particularly in medication use. Significantly more visits were made to primary care providers in the intervention group (3.01 vs 2.59; P=.03). Patient satisfaction and health status were similar in both groups with a trend toward better satisfaction in the intervention group in some areas. Conclusions: Our study showed that residents can function as gatekeepers of highly complex patients and that satisfaction with care and utilization of resources does not suffer. Drug utilization and costs may be less when a gatekeeper exists. C1 UNIV COLORADO, HLTH SCI CTR, DEPT FAMILY MED, DENVER, CO USA. RP Meyer, TJ (reprint author), DENVER VET AFFAIRS MED CTR, 1055 CLERMONT, DENVER, CO 80220 USA. NR 14 TC 1 Z9 1 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 25 PY 1996 VL 156 IS 21 BP 2483 EP 2487 DI 10.1001/archinte.156.21.2483 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA VU816 UT WOS:A1996VU81600010 PM 8944741 ER PT J AU Perkins, LA Johnson, MR Melnick, MB Perrimon, N AF Perkins, LA Johnson, MR Melnick, MB Perrimon, N TI The nonreceptor protein tyrosine phosphatase corkscrew functions in multiple receptor tyrosine kinase pathways in Drosophila SO DEVELOPMENTAL BIOLOGY LA English DT Article ID SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; CENTRAL-NERVOUS-SYSTEM; FAINT-LITTLE-BALL; EMBRYONIC-DEVELOPMENT; PATTERN-FORMATION; TERMINAL SYSTEM; CELL-MIGRATION; X-CHROMOSOME; GENE TORSO; HOMOLOG AB Corkscrew (csw) encodes a nonreceptor protein tyrosine phosphatase (PTPase) that has been implicated in signaling from the Torso receptor tyrosine kinase (RTK). csw mutations, unlike for mutations, are associated with zygotic lethality, indicating that Csw plays additional roles during development. We have conducted a detailed phenotypic analysis of csw mutations to identify these additional functions of Csw. Our results indicate that Csw operates positively downstream of other Drosophila RTKs such as the Drosophila epidermal growth factor receptor (DER), the fibroblast growth factor receptor (Breathless), and likely other RTKs. This model is substantiated by specific dosage interactions between csw and DER. It is proposed that Csw is part of the evolutionarily conserved ''signaling cassette'' that operates downstream of all RTKs. In support of this hypothesis, we demonstrate that SHP-2, a vertebrate PTPase similar to Csw and previously implicated in RTK signaling, encodes the functional vertebrate homologue of Csw. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT GENET,BOSTON,MA 02115. RP Perkins, LA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PEDIAT SURG RES LABS,WARREN 1133,32 FRUIT ST,BOSTON,MA 02114, USA. NR 73 TC 90 Z9 92 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 25 PY 1996 VL 180 IS 1 BP 63 EP 81 DI 10.1006/dbio.1996.0285 PG 19 WC Developmental Biology SC Developmental Biology GA VW700 UT WOS:A1996VW70000006 PM 8948575 ER PT J AU Manfro, GG Otto, MW McArdle, ET Worthington, JJ Rosenbaum, JF Pollack, MH AF Manfro, GG Otto, MW McArdle, ET Worthington, JJ Rosenbaum, JF Pollack, MH TI Relationship of antecedent stressful life events to childhood and family history of anxiety and the course of panic disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE life event; panic disorder; childhood anxiety; comorbidity; course ID LONGITUDINAL COURSE; MAJOR DEPRESSION; ILLNESS; ONSET; LIABILITY AB The authors examined the incidence of significant life events during the year prior to the onset of panic disorder and its relationship to childhood and family history of anxiety difficulties, comorbidity, and the course of illness in 223 panic patients followed in a naturalistic study of panic disorder. Similar to previous reports, antecedent negative life events occurred in the majority (80%) of patients. Patients with a childhood history of anxiety and comorbid adulthood major depression were more likely to report an antecedent, stressful life event. Antecedent events were not linked with comorbid, adulthood anxiety disorders or a family history of anxiety difficulties. Despite its associations with childhood anxiety pathology and adulthood major depression, the presence of an identifiable antecedent at the onset of panic disorder was nor associated with the subsequent severity or course of the disorder. C1 MASSACHUSETTS GEN HOSP,ANXIETY DISORDERS RES PROGRAM,BOSTON,MA 02114. RI Manfro, Gisele/B-7020-2009 NR 19 TC 39 Z9 42 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD NOV 25 PY 1996 VL 41 IS 2 BP 135 EP 139 DI 10.1016/S0165-0327(96)00081-X PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VV834 UT WOS:A1996VV83400008 PM 8961041 ER PT J AU Morara, S Brecha, NC Marcotti, W Provini, L Rosina, A AF Morara, S Brecha, NC Marcotti, W Provini, L Rosina, A TI Neuronal and glial localization of the GABA transporter GAT-1 in the cerebellar cortex SO NEUROREPORT LA English DT Article DE cerebellum; Purkinje cell; basket cell; stellate cell; astrocyte; Bergmann glia; immunohistochemistry; rat; GABA uptake ID RAT-BRAIN; MESSENGER-RNA; CLONING; IMMUNOFLUORESCENCE; IDENTIFICATION; EXPRESSION AB THE distribution and neuronal or glial localization of GAT-1, a high affinity GABA transporter, in the cerebellar cortex was analysed by means of double-label immunofluorescence experiments with GAT-1 combined with calbindin D, synaptophysin, or GFAP antibodies. In the Purkinje cell (Pc) layer, prominent synaptic GAT-1-immunoreactivity (IR) was found in the axon terminals of basket cells surrounding the Pc axon hillock. GAT-1-IR was also found in neuronal and glial processes ensheathing Pc somata and dendrites. Numerous immunoreactive fibres and puncta originating from basket and stellate cells, or from Golgi cells, were also detected in the molecular or granular layer, respectively. These observations suggest that GAT-1 is involved in the termination of the action of GABA at the inhibitory synapses of all cerebellar interneurones, primarily of basket cell terminals at the Pc axon hillock. GAT-1 in the astroglial processes presumably plays the additional role of regulating the extracellular concentrations of GABA. C1 CNR,IST NEUROSCI & BIOIMMAGINI,I-20131 MILAN,ITALY. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV MILAN,IST FISIOL GEN CHIM BIOL,I-20134 MILAN,ITALY. UNIV CALIF LOS ANGELES,SCH MED,CURE DIGEST DIS RES CTR,DEPT NEUROBIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,CURE DIGEST DIS RES CTR,DEPT MED,LOS ANGELES,CA 90024. RI Morara, Stefano/F-7640-2015 OI Morara, Stefano/0000-0002-1742-1712 FU PHS HHS [NEI 04067] NR 20 TC 41 Z9 43 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 25 PY 1996 VL 7 IS 18 BP 2993 EP 2996 DI 10.1097/00001756-199611250-00039 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WB359 UT WOS:A1996WB35900039 PM 9116226 ER PT J AU Aiello, LP AF Aiello, LP TI Hot papers - Vascular endothelial growth factor - Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders by L.P. Aiello, R.L. Avery, P.G. Arrigg, B.A. Keyt, H.D. Jampel, S.T. Shah, L.R. Pasquale, H. Thieme, M.A. Iwamoto, J.E. Park, H.V. Nguyen, L.M. Aiello, N. Ferrara, G.L. King - Comments SO SCIENTIST LA English DT Editorial Material RP Aiello, LP (reprint author), JOSLIN DIABET CTR,BOSTON,MA 02215, USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD NOV 25 PY 1996 VL 10 IS 23 BP 15 EP 15 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA VU828 UT WOS:A1996VU82800012 ER PT J AU Ezekowitz, A AF Ezekowitz, A TI Mannose-binding protein and susceptibility to chronic hepatitis B infection SO LANCET LA English DT Editorial Material ID VIRUS-INFECTION RP Ezekowitz, A (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SERV PEDIAT,BOSTON,MA 02114, USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD NOV 23 PY 1996 VL 348 IS 9039 BP 1396 EP 1397 DI 10.1016/S0140-6736(05)67498-3 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VU986 UT WOS:A1996VU98600006 PM 8937276 ER PT J AU Slapak, CA Martell, RL Terashima, M Levy, SB AF Slapak, CA Martell, RL Terashima, M Levy, SB TI Increased efflux of vincristine, but not of daunorubicin, associated with the murine multidrug resistance protein (MRP) SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE MRP; vincristine resistance; drug efflux ID P-GLYCOPROTEIN; CELL-LINES; ERYTHROLEUKEMIA-CELLS; INTRACELLULAR PH; LEUKEMIA-CELLS; CANCER-CELLS; TUMOR-CELLS; DRUG-EFFLUX; GENE; OVEREXPRESSION AB The multidrug resistance protein (MRP) is a membrane protein that mediates altered transport of cytotoxic drugs. Although MRP overexpression has been described in doxorubicin-selected human tumor cell lines, the murine PC-V10 and PC-V40 cell lines are members of the only reported series of vincristine-selected cell lines that overexpress mrp. Western blotting, using an antiserum developed against human MRP, demonstrated high-level expression of murine MRP primarily in the plasma membranes in each of the vincristine-selected cell lines. Only PC-V160, selected for high level resistance, demonstrated concomitant overexpression of the P-glycoprotein. As compared with parental cells, each of the drug selected cell lines demonstrated an energy-dependent, decreased net accumulation of vincristine without any changes in the initial rates of vincristine influx. However, there was an enhanced rate of vincristine loss, 2.3-fold from the PC-V40 cell line and 3.9-fold from the PC-V160 cell line. Selective plasma membrane permeabilization with digitonin equalized vincristine accumulation among the parental, the PC-V40, and the PC-V160 cell lines. No intracellular pH differences were detected among the cell lines. Despite high-level MRP expression, daunorubicin accumulation and the rate of daunorubicin loss in the PC-V40 cells were the same as that observed in parental PC4 cells. Fluorescence microscopy demonstrated no difference in the pattern of subcellular daunorubicin accumulation between parental and PC-V40 cells. These studies demonstrate that murine MRP, overexpressed and found predominantly in the plasma membrane of vincristine-selected PC-V40 cells, is associated with an energy-dependent increased efflux of vincristine, but not with efflux or altered distribution of daunorubicin. Copyright (C) 1996 Elsevier Science Inc. C1 TUFTS UNIV,SCH MED,CTR ADAPT GENET & DRUG RESISTANCE,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT MOL BIOL & MICROBIOL,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT MED,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV CANC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 593451, CA-01613]; PHS HHS [T32-C A09429] NR 33 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 22 PY 1996 VL 52 IS 10 BP 1569 EP 1576 DI 10.1016/S0006-2952(96)00561-8 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VQ073 UT WOS:A1996VQ07300012 PM 8937472 ER PT J AU Harada, S Smith, RM Smith, JA White, MF Jarett, L AF Harada, S Smith, RM Smith, JA White, MF Jarett, L TI Insulin-induced egr-1 and c-fos expression in 32D cells requires insulin receptor, Shc, and mitogen-activated protein kinase, but not insulin receptor substrate-1 and phosphatidylinositol 3-kinase activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR-I; GENE-EXPRESSION; DNA-SYNTHESIS; MAP KINASE; S6 KINASE; STIMULATION; TRANSLOCATION; PATHWAY; IDENTIFICATION; ADIPOCYTES AB Many studies suggest that insulin utilizes multiple signal transduction pathways. Insulin's effects are initiated by insulin binding to the insulin receptor, resulting in tyrosine phosphorylation of insulin receptor and in tracellular substrates, such as insulin receptor substrate-1 (IRS-1), IRS-2, or She. We recently demonstrated that immediate-early gene egr-1 transcription was fully induced without phosphorylation of IRS-1 in Chinese hamster ovary cells (Harada, S., Smith, R. M., Smith, J. A., Shah, N., Hu, D.-Q. & Jarett, L. (1995) J. Biol. Chem. 270, 26632-26638). In the present study, we examined the effects of insulin on immediate-early gene egr-1 and c-fos expression in 32D cells overexpressing the insulin receptor (32D/IR), IRS-1 (32D/IRS), or both (32D/IR+IRS) and compared these effects with insulin induced tyrosine phosphorylation. Insulin (17 nM) increased egr-1 and c-fos expression in 32D-IR and 32D/IR+IRS cells, but not in parental cells or 32D/IRS cells, as determined by Northern blot analysis. Insulin treatment (5 min at 37 degrees C) markedly increased tyrosine phosphorylation of several proteins, including the insulin receptor, IRS-1, and She, in 32D/IR+IRS cells as determined by immunoprecipitation and Western blot analysis with anti-phosphotyrosine antibody. In contrast, only two tyrosine-phosphorylated proteins, i.e. insulin receptor and She, were detected in 32D/IR cells. These data suggest that insulin receptor and She phosphorylation is necessary for insulin-induced egr-1 and c-fos expression, but IRS-I phosphorylation is not necessary or sufficient for the expression of these genes. Furthermore, the effect of specific inhibitors on insulin-induced egr-1 expression was examined. Wortmannin (25 nM), a phosphatidylinositol 3-kinase inhibitor, had no effect on insulin-induced egr-1 expression. In contrast, PD 98059 (30 mu M), a mitogen-activated protein kinase kinase inhibitor, totally blocked egr-1 expression induced by insulin. These data indicate that mitogen-activated protein kinase activation, but not phosphatidylinositol 3-kinase activation, is involved in insulin-induced egr-1 expression. Taken together, insulin receptor tyrosine phosphorylation, She tyrosine phosphorylation, and mitogen-activated protein kinase activation appear to be the signal transduction pathway responsible for insulin induced egr-1 expression in 32D cells. These data demonstrate that insulin has multiple signal transduction pathways that vary from cell to cell. C1 UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. JOSLIN DIABET CTR,BOSTON,MA 02215. FU NIDDK NIH HHS [DK28143, DK28144, DK 43808] NR 24 TC 44 Z9 44 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 22 PY 1996 VL 271 IS 47 BP 30222 EP 30226 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VU525 UT WOS:A1996VU52500102 PM 8939974 ER PT J AU Seid, CA George, JM Sater, AK Kozlowski, MT Lee, H Govindarajan, V Ramachandran, RK Tomlinson, CR AF Seid, CA George, JM Sater, AK Kozlowski, MT Lee, H Govindarajan, V Ramachandran, RK Tomlinson, CR TI USF in the Lytechinus sea urchin embryo may act as a transcriptional repressor in non-aboral ectoderm cells for the cell lineage-specific expression of the LpS1 genes SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE USF; transcriptional repression; green fluorescent protein; lineage-specific; Lytechinus ID HELIX-LOOP-HELIX; MAJOR LATE PROMOTER; DNA-BINDING; LEUCINE-ZIPPER; PROTEINS; ELEMENT; UPSTREAM; NUCLEI; RNA; BOX AB Expression of the aboral ectoderm-specific LpS1 gene in Lytechinus was used to study lineage-specific transcriptional regulation during sea urchin development. Band shift assays using anti-USF antibody showed that a USF-like protein bound the USF core sequence 5'-CACGTG-3' in the promoter of the LpS1 gene. DNA constructs consisting of a wild-type LpS1 promoter and the same LpS1 promoter with a mutated USF binding site fused to the bacterial chloramphenicol acetyltransferase reporter gene were tested. The mutation in the USF binding site caused an increase in chloramphenicol acetyltransferse activity. We selected a clone that encodes USF, LvUSF, from a gastrula-stage cDNA library representing Lytechinus variegatus. Transactivation experiments, in which LvUSF RNA or a DNA construct consisting of the LvUSF cDNA clone fused to the Lytechinus pictus metallothionein promoter coinjected with the wild type or mutated LpS1 promoter-chloramphenicol acetyltransferase gene construct, showed that chloramphenicol acetyltransferase activity from the wild-type construct was repressed, while the construct mutated at the USF binding site was active. The same wild-type and mutated LpS1 promoter DNA fragments ligated to the green fluorescent protein reporter gene were used to examine spatial expression. The reporter gene constructs containing the mutated USF binding site were expressed inappropriately in all cell types including the gut and oral ectoderm in gastrula and larva stage embryos, while the wild-type constructs were expressed primarily in the aboral ectoderm. USF was expressed in all cells of the early embryo and in all tissues except the aboral ectoderm in later embryos. The data are consistent with a model depicting Lytechinus USF, as a temporal and spatial regulator by repressing LpS1 gene transcription in non-aboral ectoderm cells. (C) 1996 Academic Press Limited C1 UNIV HOUSTON,DEPT BIOL,HOUSTON,TX 77204. UNIV HOUSTON,INST MOL BIOL,HOUSTON,TX 77204. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,DIABET UNIT,CHARLESTOWN,MA 02120. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,MED SERV,CHARLESTOWN,MA 02120. RI Tomlinson, Craig/F-1319-2017 NR 32 TC 4 Z9 4 U1 0 U2 1 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 NOV 22 PY 1996 VL 264 IS 1 BP 7 EP 19 DI 10.1006/jmbi.1996.0619 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VU380 UT WOS:A1996VU38000002 PM 8950263 ER PT J AU Hotamisligil, GS Johnson, RS Distel, RJ Ellis, R Papaioannou, VE Spiegelman, BM AF Hotamisligil, GS Johnson, RS Distel, RJ Ellis, R Papaioannou, VE Spiegelman, BM TI Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein SO SCIENCE LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; TYROSINE PHOSPHORYLATION; ADIPOSE-TISSUE; EXPRESSION; RECEPTOR; MICE; GENE AB Fatty acid binding proteins (FABPs) are small cytoplasmic proteins that are expressed in a highly tissue-specific manner and bind to fatty acids such as oleic and retinoic acid. Mice with a null mutation in aP2, the gene encoding the adipocyte FABP, were developmentally and metabolically normal. The aP2-deficient mice developed dietary obesity but, unlike control mice, they did not develop insulin resistance or diabetes. Also unlike their obese wild-type counterparts, obese aP2(-/-) animals failed to express in adipose tissue tumor necrosis factor-alpha (TNF-alpha), a molecule implicated in obesity-related insulin resistance. These results indicate that aP2 is central to the pathway that links obesity to insulin resistance, possibly by linking fatty acid metabolism to expression of TNF-alpha. C1 UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. COLUMBIA UNIV,DEPT GENET & DEV,NEW YORK,NY 10032. RP Hotamisligil, GS (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. OI Johnson, Randall/0000-0002-4084-6639 FU NICHD NIH HHS [HD27295]; NIDDK NIH HHS [DK31405] NR 30 TC 475 Z9 511 U1 4 U2 18 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 22 PY 1996 VL 274 IS 5291 BP 1377 EP 1379 DI 10.1126/science.274.5291.1377 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VU954 UT WOS:A1996VU95400054 PM 8910278 ER PT J AU Lyle, RE Habener, JF McGehee, RE AF Lyle, RE Habener, JF McGehee, RE TI Antisense oligonucleotides to differentiation-specific element binding protein (DSEB) mRNA inhibit adipocyte differentiation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID REPLICATION FACTOR-C; ANGIOTENSINOGEN GENE; DNA-REPLICATION; EXPRESSION; CLONING; FIBROBLASTS; SUBUNIT; OLIGODEOXYNUCLEOTIDES; HOMOLOGY; PROMOTER AB The Differentiation-Specific Element Binding Protein (DSEB) was identified by binding to a specific cis-acting DNA element (DSE) responsible for the irreversible continued expression of the angiotensinogen gene after differentiation of 3T3-L1 adipoblasts to adipocytes. It was also identified as the large subunit of the Replication Factor C complex. During 3T3-L1 adipoblast differentiation, DSEB is induced early and interacts with the DSE that is essential for the sustained transcriptional activation of the angiotensinogen gene. Here we describe loss of function studies in 3T3-L1 cells performed with antisense phosphorothioate oligonucleotides that hybridize to DSEB mRNA. Treatment with 15, 25, and 50 mu M antisense DSEB resulted in a dose-dependent inhibition of differentiation-specific lipid accumulation after 3 days of hormonal stimulation. Similar treatment also markedly reduced differentiation-dependent expression of mRNAs encoding angiotensinogen and the fat-specific fatty acid binding protein, aP2. Further, 50 mu M antisense DSEB treatment resulted in a significant similar to 50% inhibition of the cell proliferation that occurs early in 3T3-L1 adipogenesis. Control experiments using the DSEB sense oligonucleotide had no effect on hormonal-stimulated adipocyte differentiation. Combined, these results suggest that DSEB serves an important role during the proliferative phase of 3T3-L1 adipoblast differentiation. (C) 1996 Academic Press, Inc. C1 UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT,LITTLE ROCK,AR 72205. ARKANSAS CHILDRENS HOSP,RES INST,LITTLE ROCK,AR 72205. MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,MOL ENDOCRINOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 25 TC 17 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 21 PY 1996 VL 228 IS 3 BP 709 EP 715 DI 10.1006/bbrc.1996.1721 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VV002 UT WOS:A1996VV00200009 PM 8941343 ER PT J AU Luo, C Copeland, NG Jenkins, NA Edelhoff, S Disteche, C Hogan, PG Rao, A AF Luo, C Copeland, NG Jenkins, NA Edelhoff, S Disteche, C Hogan, PG Rao, A TI Normal function of the transcription factor NFAT1 in wasted mice. Chromosome localization of NFAT1 gene SO GENE LA English DT Article DE DNA-binding protein; genetic diseases; RNA splicing; cytokine gene expression; T cell activation; transcription regulation ID IMMUNOSUPPRESSIVE DRUGS; ATAXIA-TELANGIECTASIA; NUCLEAR FACTOR; NF-ATP; FAMILY; MOUSE; CELLS; PROTEINS; BINDING; DEPHOSPHORYLATION AB NFAT1 (NFATp), a cytosolic component of the nuclear factor of activated T cells (NFAT), is encoded by a single gene which was mapped to mouse chromosome 2 in the vicinity of the wasted (wst) locus. Although wasted mice display a severe immune disorder, they express normal levels of NFAT1 protein. The NFAT1 protein in wasted mice is properly regulated and possesses comparable DNA binding activity as that in their littermate controls. Therefore, the wasted phenotype is not due to a defect in the expression or early regulation of the NFAT1 protein. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21701. UNIV WASHINGTON,SCH MED,DEPT PATHOL,SEATTLE,WA 98195. FU NCI NIH HHS [CA 42471]; NIGMS NIH HHS [GM 46227, GM 46883] NR 31 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 21 PY 1996 VL 180 IS 1-2 BP 29 EP 36 DI 10.1016/S0378-1119(96)00396-4 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA VY054 UT WOS:A1996VY05400005 PM 8973343 ER PT J AU Lipton, SA Schaefer, PW Adams, RD Ma, MJ AF Lipton, SA Schaefer, PW Adams, RD Ma, MJ TI A 37-year-old man with AIDS, neurologic deterioration, and multiple hemorrhagic cerebral lesions - Varicella-zoster leukoencephalitis with hemorrhage and large-vessel vasculopathy - Acquired immunodeficiency syndrome. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CENTRAL-NERVOUS-SYSTEM; HERPES-ZOSTER; CYTOMEGALOVIRUS-INFECTION; CEREBROSPINAL-FLUID; VIRUS ENCEPHALITIS; HIV-INFECTION; VASCULITIS; DISEASE; ANGIITIS; OPHTHALMICUS C1 BETH ISRAEL HOSP,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Lipton, SA (reprint author), CHILDRENS HOSP,MOL & CELLULAR NEUROSCI LAB,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 51 TC 10 Z9 10 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 NOV 21 PY 1996 VL 335 IS 21 BP 1587 EP 1595 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA VT341 UT WOS:A1996VT34100009 ER PT J AU Eng, C Clayton, D Schuffenecker, I Lenoir, G Cote, G Gagel, RF vanAmstel, HKP Lips, CJM Nishisho, I Takai, SI Marsh, DJ Robinson, BG FrankRaue, K Raue, F Xue, FY Noll, WW Romei, C Pacini, F Fink, M Niederle, B Zedenius, J Nordenskjold, M Komminoth, P Hendy, GN Gharib, H Thibodeau, SN Lacroix, A Frilling, A Ponder, BAJ Mulligan, LM AF Eng, C Clayton, D Schuffenecker, I Lenoir, G Cote, G Gagel, RF vanAmstel, HKP Lips, CJM Nishisho, I Takai, SI Marsh, DJ Robinson, BG FrankRaue, K Raue, F Xue, FY Noll, WW Romei, C Pacini, F Fink, M Niederle, B Zedenius, J Nordenskjold, M Komminoth, P Hendy, GN Gharib, H Thibodeau, SN Lacroix, A Frilling, A Ponder, BAJ Mulligan, LM TI The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2 - International RET mutation consortium analysis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MEDULLARY-THYROID CARCINOMA; TYROSINE KINASE DOMAIN; MEN 2A; PROTOONCOGENE MUTATIONS; HIRSCHSPRUNG DISEASE; POINT MUTATION; FMTC; FAMILIES AB Objective.-Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder. The 3 recognized subtypes include MEN 2A, characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (pheo), and hyperparathyroidism (HPT); MEN 2B, by MTC, pheo, and characteristic stigmata; and familial MTC (FMTC), by the presence of MTC only. The purpose of this study was to establish the relationship between specific mutations and the presence of certain disease features in MEN 2 which could help in clinical decision making. Design.-Correlative survey study of 477 MEN 2 families. Setting.-Eighteen tertiary referral centers worldwide. Patients.-A total of 477 independent MEN 2 families. Main Outcome Measures.-Association between the position and type of germline mutation in the RET proto-oncogene and the presence or absence of MTC, pheo, HPT, and/or other features in a family. Results.-There is a statistically significant association between the presence of any mutation at a specific position (codon 634) and the presence of pheo and HPT. The presence of a specific mutation, CGC at codon 634, has yet to be associated with FMTC, Conversely, mutations at codons 768 and 804 are thus far seen only with FMTC, while codon 918 mutation is MEN 2B-specific. Rare families with both MEN 2 and Hirschsprung disease were found to have MEN 2-specific codon mutations. Patients with Hirschsprung disease presenting with such mutations should be monitored for the possible development of MEN 2 tumors. Conclusions.-This consortium analysis suggests that genotype-phenotype correlations do exist and, if made reliably absolute, could prove useful in the future in clinical management with respect to screening, surveillance, and prophylaxis, as well as provide insight into the genetic effects of particular mutations. C1 QUEENS UNIV,DEPT PAEDIAT,KINGSTON,ON K7L 3N6,CANADA. UNIV CAMBRIDGE,CANC RES CAMPAIGN,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 1TN,ENGLAND. UNIV CAMBRIDGE,INST PUBL HLTH,MRC,BIOSTAT UNIT,CAMBRIDGE CB2 1TN,ENGLAND. INT AGCY RES CANC,F-69372 LYON,FRANCE. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. UNIV UTRECHT,DEPT INTERNAL MED,UTRECHT,NETHERLANDS. UNIV UTRECHT,CLIN GENET CTR,UTRECHT,NETHERLANDS. OSAKA UNIV,SCH MED,DEPT MED GENET,OSAKA,JAPAN. UNIV SYDNEY,ROYAL N SHORE HOSP,KOLLING INST MED RES,MOL GENET UNIT,ST LEONARDS,NSW 2065,AUSTRALIA. UNIV HEIDELBERG,DEPT INTERNAL MED 1,HEIDELBERG,GERMANY. DARTMOUTH HITCHCOCK MED CTR,DEPT PATHOL,LEBANON,NH 03766. UNIV PISA,INST ENDOCRINOL,PISA,ITALY. UNIV VIENNA,DEPT SURG,A-1010 VIENNA,AUSTRIA. KAROLINSKA HOSP,DEPT MOL MED,S-10401 STOCKHOLM,SWEDEN. KAROLINSKA HOSP,DEPT SURG,S-10401 STOCKHOLM,SWEDEN. KAROLINSKA HOSP,DEPT CLIN GENET,S-10401 STOCKHOLM,SWEDEN. UNIV ZURICH,DEPT PATHOL,CH-8006 ZURICH,SWITZERLAND. ROYAL VICTORIA HOSP,CALCIUM RES LAB,MONTREAL,PQ H3A 1A1,CANADA. MAYO CLIN,DIV ENDOCRINOL,ROCHESTER,MN. HOP HOTEL DIEU,CTR RECH,MONTREAL,PQ,CANADA. UNIV HAMBURG,DEPT SURG,HAMBURG,GERMANY. QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. QUEENS UNIV,DEPT PAEDIAT,KINGSTON,ON,CANADA. RP Eng, C (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV CANC EPIDEMIOL & CONTROL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 NR 35 TC 703 Z9 726 U1 0 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 20 PY 1996 VL 276 IS 19 BP 1575 EP 1579 DI 10.1001/jama.276.19.1575 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA VT025 UT WOS:A1996VT02500030 PM 8918855 ER PT J AU Peters, R Sikorski, R AF Peters, R Sikorski, R TI The Web, unplugged - Hardware, software, and connections SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID INTERNET C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. NATL CANC INST,BETHESDA,MD. RP Peters, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,WANG BLDG,ACC-1,FRUIT ST,BOSTON,MA 02114, USA. NR 11 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 20 PY 1996 VL 276 IS 19 BP 1607 EP 1608 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VT025 UT WOS:A1996VT02500036 ER PT J AU Isenberg, G Niggli, V Pieper, U Kaufmann, S Goldmann, WH AF Isenberg, G Niggli, V Pieper, U Kaufmann, S Goldmann, WH TI Probing phosphatidylinositolphosphates and adenosinenucleotides on talin nucleated actin polymerization SO FEBS LETTERS LA English DT Article DE actin; talin; phosphoinositide; ADP-actin polymerization ID BINDING PROTEIN; FILAMENTS; PROFILIN; VINCULIN; VESICLES; EXCHANGE; ENDS; PIP2; ADP AB We have investigated the binding of PI, PIP and PIP2 to talin and the effect of phosphoinositides and adenosinenucleotides on talin-induced actin polymerization. At physiological salt concentrations, talin coprecipitates with liposomes when containing phosphoinositides but not when containing PI. The nucleating effect of talin as reflected by a twofold increase of fluorescence during the polymerization of actin labelled with NBD is not inhibited by phosphoinositides, The polymerization of ADP-actin versus ATP-actin was investigated in the presence and absence of talin by NBD fluorescence, ADP-actin nucleation induced by talin is comparably efficient as with ATP-actin. These experimental findings in summary have implications when evaluating the role of talin during cell activation. C1 UNIV BERN,DEPT PATHOL,CH-3010 BERN,SWITZERLAND. RUHR UNIV BOCHUM,INST PHYSIOL CHEM,D-44780 BOCHUM,GERMANY. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,SURG RES LAB,CHARLESTOWN,MA 02129. RP Isenberg, G (reprint author), TECH UNIV MUNICH,JAMES FRANCK STR,D-85747 GARCHING,GERMANY. RI Goldmann, Wolfgang/H-5572-2013 NR 32 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 18 PY 1996 VL 397 IS 2-3 BP 316 EP 320 DI 10.1016/S0014-5793(96)01203-3 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VV171 UT WOS:A1996VV17100040 PM 8955371 ER PT J AU Lyoo, IK Noam, GG Lee, CK Lee, HK Kennedy, BP Renshaw, PF AF Lyoo, IK Noam, GG Lee, CK Lee, HK Kennedy, BP Renshaw, PF TI The corpus callosum and lateral ventricles in children with attention-deficit hyperactivity disorder: A brain magnetic resonance imaging study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE corpus callosum; lateral ventricle; brain magnetic resonance imaging; attention-deficit hyperactivity disorder; children; adolescent ID MORPHOMETRIC ANALYSIS; MORPHOLOGY C1 MCLEAN HOSP,BRAIN IMAGING CTR,BOSTON,MA. MCLEAN HOSP,LAB DEV PSYCHOL & DEV PSYCHOPATHOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,INJURY CONTROL CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 17 TC 77 Z9 78 U1 2 U2 3 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 NOV 15 PY 1996 VL 40 IS 10 BP 1060 EP 1063 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VQ713 UT WOS:A1996VQ71300015 PM 8915567 ER PT J AU Paglia, DE Walford, RL AF Paglia, DE Walford, RL TI Hematologic response to prolonged normobaric hypoxia and caloric restriction in biosphere-2 crew: Increased Hgb-O-2 affinity without erythrocytosis. SO BLOOD LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,HEMATOL RES LAB,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,SCH MED,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90024. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 20 EP 20 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300020 ER PT J AU Cheng, T Shen, H Giokas, D Scadden, DT AF Cheng, T Shen, H Giokas, D Scadden, DT TI Negative regulation of cell cycle progression in primary hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,AIDS RES CTR,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 173 EP 173 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300173 ER PT J AU Barber, DL Beattie, BK DAndrea, AD Frank, DA AF Barber, DL Beattie, BK DAndrea, AD Frank, DA TI An activation-specific STAT5 antibody selectively recognizes the tyrosine phosphorylated forms of the erythropoietin receptor and STAT5. SO BLOOD LA English DT Meeting Abstract C1 ONTARIO CANC INST,TORONTO,ON M4X 1K9,CANADA. DANA FARBER CANC INST,BOSTON,MA 02115. BETH ISRAEL HOSP,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 202 EP 202 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300202 ER PT J AU Chauhan, D Kharbanda, S Pandey, P Ogata, A Urashima, M Teoh, G Kufe, D Anderson, K AF Chauhan, D Kharbanda, S Pandey, P Ogata, A Urashima, M Teoh, G Kufe, D Anderson, K TI Irradiation-induced apoptosis in multiple myeloma (MM) cells is associated with activation of SAP/JNK kinase SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 392 EP 392 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300392 ER PT J AU Teoh, G Urashima, M Ogata, A Chauhan, D Treon, S Schlossman, R Anderson, K AF Teoh, G Urashima, M Ogata, A Chauhan, D Treon, S Schlossman, R Anderson, K TI Overexpression of murine double minute (MDM2) protein in multiple myeloma (MM) cells promotes tumor cell proliferation and survival SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 393 EP 393 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300393 ER PT J AU Urashima, M Teoh, G Ogata, A Chauhan, D Hoshi, Y Treon, S Schlossman, R Anderson, K AF Urashima, M Teoh, G Ogata, A Chauhan, D Hoshi, Y Treon, S Schlossman, R Anderson, K TI Interleukin-6 (IL-6) overcomes P21(WAF1) (P21) upregulation and G1 growth arrest induced by dexamethasone and interferon-gamma (IFN-gamma) in multiple myeloma (MM) cells SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 407 EP 407 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300407 ER PT J AU Ogata, A Chauhan, D Urashima, M Teoh, G Treon, S Anderson, K AF Ogata, A Chauhan, D Urashima, M Teoh, G Treon, S Anderson, K TI Blockade of interleukin-6 (IL-6) triggered MAPK signaling cascade in IL-6 independent multiple myeloma (MM) cells SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 408 EP 408 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300408 ER PT J AU Feliers, D Woodruff, KA Abboud, SL AF Feliers, D Woodruff, KA Abboud, SL TI Interferon-gamma regulates insulin-like growth factor binding protein (IGFBP)-4 expression in multiple myeloma (MM) cells. SO BLOOD LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 410 EP 410 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300410 ER PT J AU Webb, IJ Beach, M Daley, JF Anderson, KC AF Webb, IJ Beach, M Daley, JF Anderson, KC TI Sequential CD34+ and CD4+ cell selection from leukapheresis components. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 426 EP 426 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300426 ER PT J AU ArunKilic, B Spitzer, TR Rajagopal, C McAfee, S Lippman, ME Mazumder, A Meehan, KR AF ArunKilic, B Spitzer, TR Rajagopal, C McAfee, S Lippman, ME Mazumder, A Meehan, KR TI Survival for stage IIIB breast cancer following autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT). SO BLOOD LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,BONE MARROW TRANSPLANT PROGRAM,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. MASSACHUSETTS GEN HOSP,BONE MARROW TRANSPLANT PROGRAM,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 498 EP 498 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300498 ER PT J AU Tsang, AP Visvader, JE Turner, CA Fujiwara, Y Crossley, M Orkin, SH AF Tsang, AP Visvader, JE Turner, CA Fujiwara, Y Crossley, M Orkin, SH TI Fog-1 (friend of GATA-1): A candidate cofactor for the transcription factor GATA-1 in erythroid and megakaryocytic lineages. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 553 EP 553 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300553 ER PT J AU Anumanthan, A Bensussan, A Boumsell, L Voss, S Robertson, ML Nadler, LM Freeman, GJ AF Anumanthan, A Bensussan, A Boumsell, L Voss, S Robertson, ML Nadler, LM Freeman, GJ TI Cloning and characterization of BY55, an NK and cytolytic T lymphocyte specific cell surface protein SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. HOP ST LOUIS,INSERM,U93,F-75010 PARIS,FRANCE. RI Bensussan, Armand/E-5434-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 630 EP 630 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300630 ER PT J AU Schultze, JL Michalak, S Seamon, MJ Delgado, JC Gribben, JG Nadler, LM AF Schultze, JL Michalak, S Seamon, MJ Delgado, JC Gribben, JG Nadler, LM TI Advantages of human CD40 activated dendritic cells for presentation of human tumor antigens SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 636 EP 636 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300636 ER PT J AU Paw, BH Thompson, MA Ransom, DG Kieran, MW Donovan, A Brownlie, AJ Liao, EC Pratt, S Guo, W Postlethwait, JH Zon, LI AF Paw, BH Thompson, MA Ransom, DG Kieran, MW Donovan, A Brownlie, AJ Liao, EC Pratt, S Guo, W Postlethwait, JH Zon, LI TI Cloning of regulatory genes and analysis of mutations in the zebrafish define critical molecular events during hematopoietic cell differentiation. SO BLOOD LA English DT Meeting Abstract C1 BOSTON CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 754 EP 754 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300754 ER PT J AU Zhu, Y Jaster, R DAndrea, AD AF Zhu, Y Jaster, R DAndrea, AD TI The role of ETS, AP-1, and CBF sites in the activation of the beta C-inducible DUB-1 enhancer. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DIV PEDIAT ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,DIV CELLULAR & MOL BIOL,DANA FARBER CANC INST,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 766 EP 766 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300766 ER PT J AU Kieran, MW Mayer, B Zon, LI AF Kieran, MW Mayer, B Zon, LI TI Interactions between stress-activated MAP kinase cascades regulates the activity of their down stream targets (JNK/SAPK and P38) during erythroid differentiation. SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 772 EP 772 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300772 ER PT J AU Baumann, H Kuropatwinski, KK Wang, Y Kim, H Kordula, T Ripperger, J Fey, GH VanEtten, RA Wetzler, M AF Baumann, H Kuropatwinski, KK Wang, Y Kim, H Kordula, T Ripperger, J Fey, GH VanEtten, RA Wetzler, M TI BCR/ABL kinases MIMIC hematopoietin receptors by activating common sets of signal transducer and activator of transcription (STAT) proteins and inducing gene expression through cytokine-responsive elements. SO BLOOD LA English DT Meeting Abstract C1 ROSWELL PK CANC INST,DIV MED,BUFFALO,NY. ROSWELL PK CANC INST,DEPT MOL & CELLULAR BIOL,BUFFALO,NY 14263. JAGIELLONIAN UNIV,KRAKOW,POLAND. UNIV ERLANGEN NURNBERG,D-8520 ERLANGEN,GERMANY. INST GENET,ERLANGEN,GERMANY. HARVARD UNIV,SCH MED,CTR BLOOD RES,DEPT GENET,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 804 EP 804 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300804 ER PT J AU DunussiJoannopoulos, K Dranoff, G Weinstein, HJ Burakoff, SJ Ferrara, JLM Bierer, B Croop, JM AF DunussiJoannopoulos, K Dranoff, G Weinstein, HJ Burakoff, SJ Ferrara, JLM Bierer, B Croop, JM TI GM-CSF tumor cell vaccines are more effective than B7-1 vaccines in murine acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 829 EP 829 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300829 ER PT J AU DunussiJoannopoulos, K Krenger, W Weinstein, HJ Burakoff, SI Ferrara, JLM Croop, JM AF DunussiJoannopoulos, K Krenger, W Weinstein, HJ Burakoff, SI Ferrara, JLM Croop, JM TI CD8+ T-cells activated during the course of murine AML elicit therapeutic response to late B7 vaccines after cytoreductive treatment. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 830 EP 830 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300830 ER PT J AU Cardoso, AA Seamon, MJ Afonso, HM Sallan, SE Boussiotis, VA Freeman, G Gribben, JG Nadler, LM AF Cardoso, AA Seamon, MJ Afonso, HM Sallan, SE Boussiotis, VA Freeman, G Gribben, JG Nadler, LM TI Potential for adoptive therapy for pre-B cell leukemia: Ex vivo generation of anti-leukemia specific autologous CD8+ cytolytic T cells. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 835 EP 835 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300835 ER PT J AU Pan, L Falzarano, G Krenger, W Delmonte, J Bressler, S Ferrara, JLM AF Pan, L Falzarano, G Krenger, W Delmonte, J Bressler, S Ferrara, JLM TI Reduction of acute GVHD by Ig: Inhibition or TNF-alpha and nitric oxide production at two stages of monocyte effector cell activation. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 974 EP 974 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300974 ER PT J AU Beland, JL Adler, H Fanslow, W Rimm, IJ AF Beland, JL Adler, H Fanslow, W Rimm, IJ TI Recombinant CD40L protects allogeneic murine bone marrow recipients from HSV-1 induced mortality SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. IMMUNEX CORP,SEATTLE,WA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 983 EP 983 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300983 ER PT J AU Orsini, E Claret, EJ Alyea, EP Schlossman, R Canning, C Soiffer, RJ Anderson, KC Ritz, J AF Orsini, E Claret, EJ Alyea, EP Schlossman, R Canning, C Soiffer, RJ Anderson, KC Ritz, J TI Distinct changes in T cell repertoire associated with GVL and gvhd in patients receiving donor lymphocyte infusion after allogeneic bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1020 EP 1020 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301020 ER PT J AU Alyea, EP Schlossman, RL Canning, C Collins, H Pickett, C Wang, Y Soiffer, RJ Anderson, KC Ritz, J AF Alyea, EP Schlossman, RL Canning, C Collins, H Pickett, C Wang, Y Soiffer, RJ Anderson, KC Ritz, J TI CD8-depleted donor lymphocyte infusions mediate graft versus multiple myeloma (MM) effect. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1021 EP 1021 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301021 ER PT J AU Vance, EU Fleming, M Ritz, J Soiffer, RJ AF Vance, EU Fleming, M Ritz, J Soiffer, RJ TI Outcome of lymphoproliferative disease following CD6 T-cell depleted allogeneic bone marrow transplantation (BMT). SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1033 EP 1033 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301033 ER PT J AU Bauer, TR Winkler, A Andrews, RG Hickstein, DD AF Bauer, TR Winkler, A Andrews, RG Hickstein, DD TI The baboon as an animal model for gene transfer in leukocyte adherence deficiency. SO BLOOD LA English DT Meeting Abstract C1 UNIV WASHINGTON,SCH MED,VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1091 EP 1091 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301091 ER PT J AU Gollob, JA Mahajan, S Rudders, SA Ritz, J Frank, DA AF Gollob, JA Mahajan, S Rudders, SA Ritz, J Frank, DA TI IFN-gamma and IL-4 promote TH1 and TH2 development by differentially modulating high affinity IL-12 receptor expression and IL-12-induced activation of Stat1 and Stat5. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1100 EP 1100 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301100 ER PT J AU Mollick, JA Gimmi, CG Morrison, B Freeman, G Nadler, LM AF Mollick, JA Gimmi, CG Morrison, B Freeman, G Nadler, LM TI Tumor cell associated glycoprotein MUC-1 induces apoptosis of activated T lymphocytes. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1102 EP 1102 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301102 ER PT J AU vandenBrink, MRM Kapeller, R Burakoff, SE AF vandenBrink, MRM Kapeller, R Burakoff, SE TI Activation induced cell death of T cell hybridoma cell lines requires activation of the mitogen-activated protein kinase pathway. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,BETH ISRAEL HOSP,DEPT HEMATOL ONCOL,BOSTON,MA 02215. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1103 EP 1103 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301103 ER PT J AU Yakushijin, Y Grogan, TM Shipp, MA AF Yakushijin, Y Grogan, TM Shipp, MA TI Subcellular localization of nucleophosmin/B23 is associated with proliferation rate and clinical outcome in large B-cell lymphoma. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV ARIZONA,TUCSON,AZ 85721. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1161 EP 1161 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301161 ER PT J AU Urashima, M Teoh, G Ogata, A Chauhan, D Sugimoto, Y Kaihara, C Matsuzaki, M Hoshi, Y DeCaprio, J Anderson, K AF Urashima, M Teoh, G Ogata, A Chauhan, D Sugimoto, Y Kaihara, C Matsuzaki, M Hoshi, Y DeCaprio, J Anderson, K TI Upregulation of P16(INK4A) (p16) protein is associated with delayed growth arrest of interleukin-6(IL-6)-stimulated multiple myeloma (MM) cells SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1167 EP 1167 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301167 ER PT J AU Mahajan, S Rudders, SA Ritz, J Frank, DA AF Mahajan, S Rudders, SA Ritz, J Frank, DA TI Lymphocytes from patients with chronic lymphocytic leukemia contain STAT1 and STAT3 constitutively phosphorylated on serine. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1171 EP 1171 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301171 ER PT J AU Boussiotis, VA Lee, BJ Freeman, GJ Gribben, JG Nadler, LM AF Boussiotis, VA Lee, BJ Freeman, GJ Gribben, JG Nadler, LM TI Induction of human T cell clonal energy results in resistance whereas CD28 costimulation primes for susceptibility to Fas-mediated programmed cell death. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1177 EP 1177 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301177 ER PT J AU Yonemura, Y Ku, H Kawakita, M Lyman, SD Ogawa, M AF Yonemura, Y Ku, H Kawakita, M Lyman, SD Ogawa, M TI In vitro expansion of hematopoietic progenitors and maintenance of stem cells: Comparison between FLT3/FLK-2 ligand and kit ligand. SO BLOOD LA English DT Meeting Abstract C1 KUMAMOTO UNIV,SCH MED,DEPT INTERNAL MED 2,KUMAMOTO 860,JAPAN. IMMUNEX CO,SEATTLE,WA. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1183 EP 1183 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301183 ER PT J AU Soiffer, RJ Collins, H Ritz, J AF Soiffer, RJ Collins, H Ritz, J TI Defective GD3 ganglioside (CDw60) mediated T cell response following T cell depleted allogeneic bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1192 EP 1192 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301192 ER PT J AU Trimble, LA Lieberman, J AF Trimble, LA Lieberman, J TI A survival factor in serum is required for clonal expansion of antigen-specific CD8+ cytotoxic T lymphocytes SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. RI Lieberman, Judy/A-2717-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1250 EP 1250 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301250 ER PT J AU Shcherbina, A Reczek, D Bretscher, A Kenney, DM Rosen, FS RemoldODonnell, E AF Shcherbina, A Reczek, D Bretscher, A Kenney, DM Rosen, FS RemoldODonnell, E TI Ezrin and moesin in human blood cells: Possible role in Wiskott-Aldrich syndrome. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. CORNELL UNIV,ITHACA,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1272 EP 1272 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301272 ER PT J AU Webb, IJ Schott, DM Cook, J Andersen, JW Barrett, BB Anderson, KC AF Webb, IJ Schott, DM Cook, J Andersen, JW Barrett, BB Anderson, KC TI COBE Spectra(TM) LRS for preparation of leukoreduced single donor apheresis platelets without laboratory filtration. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1327 EP 1327 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301327 ER PT J AU Teicher, BA Kakeji, Y Rice, G Singer, J AF Teicher, BA Kakeji, Y Rice, G Singer, J TI Lisofylline (LSF) accelerates hematopoietic recovery and enhances tumor response after high dose chemotherapy. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. CELL THERAPEUT INC,SEATTLE,WA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1372 EP 1372 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301372 ER PT J AU Schmalz, C Harrigan, PM Fisher, DE AF Schmalz, C Harrigan, PM Fisher, DE TI Toxic vs beneficial effects of tumor cell hypoxia: Uncoupling of two distinct mechanisms relevant to apoptosis, p53 and treatment response SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1403 EP 1403 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301403 ER PT J AU Bloch, DB delaMonte, SM Guigaouri, P Filippov, A Orth, D Bloch, KD AF Bloch, DB delaMonte, SM Guigaouri, P Filippov, A Orth, D Bloch, KD TI Identification and characterization of a leukocyte-specific component of the nuclear body. SO BLOOD LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1468 EP 1468 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301468 ER PT J AU Yakushijin, Y Steckel, J Jiang, WM Rozenvald, I Shipp, M AF Yakushijin, Y Steckel, J Jiang, WM Rozenvald, I Shipp, M TI CD44 isoform-specific aggressive NHL transfectants exhibit distinct characteristics in vitro and in vivo. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1494 EP 1494 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301494 ER PT J AU Yakushijin, Y Grogan, T Shipp, M AF Yakushijin, Y Grogan, T Shipp, M TI Antigen processing pathways in aggressive non-Hodgkin's lymphomas: Enhanced expression of LMP-2, LMP-7 and TAP-1 in high risk patients. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV ARIZONA,TUCSON,AZ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1495 EP 1495 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301495 ER PT J AU Yakushijin, Y Shipp, M AF Yakushijin, Y Shipp, M TI A novel member of the protein tyrosine phosphatase (PTP)-U2 gene family is down-regulated in diffuse large B-cell lymphoma. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1496 EP 1496 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301496 ER PT J AU Urashima, M Dedera, D Chen, S Pinkus, G Bronson, R Hoshi, Y Teoh, G Ogata, A Chauhan, D Anderson, K AF Urashima, M Dedera, D Chen, S Pinkus, G Bronson, R Hoshi, Y Teoh, G Ogata, A Chauhan, D Anderson, K TI Development of a human multiple myeloma (MM) model in SCID-hu mice SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. SYSTEMIX,PALO ALTO,CA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1534 EP 1534 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301534 ER PT J AU Spitzer, TR Scavone, M Brown, C McAfee, SL Olszak, I Preffer, F AF Spitzer, TR Scavone, M Brown, C McAfee, SL Olszak, I Preffer, F TI Alterations of plasma cytokine levels and T-cell subset regeneration following intravenous immunoglobulin (IVIG) administration and allogeneic bone marrow transplantation (BMT). SO BLOOD LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1656 EP 1656 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301656 ER PT J AU Kupfer, GM Yamashita, T Suliman, A DAndrea, AD AF Kupfer, GM Yamashita, T Suliman, A DAndrea, AD TI The Fanconi anemia polypeptide-FAC binds to the cyclin-dependent kinase, cdc2. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1732 EP 1732 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301732 ER PT J AU LoCicero, R Shen, Q Harris, K AF LoCicero, R Shen, Q Harris, K TI The tyrosine phosphatase SHP-1 is deficient in polycythemia vera peripheral blood mononuclear cells. SO BLOOD LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,S TEXAS VET HLTH CARE SYST,SAN ANTONIO,TX. WILFORD HALL USAF MED CTR,SAN ANTONIO,TX 78236. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1735 EP 1735 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301735 ER PT J AU Beresford, PJ Lieberman, J AF Beresford, PJ Lieberman, J TI Recombinant human cytotoxic T lymphocyte granzyme a binds to two cytoplasmic proteins SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHILDRENS HOSP,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1739 EP 1739 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301739 ER PT J AU Ku, H Hirayama, F Kato, T Miyazaki, H Aritomi, V Ota, Y DAndrea, AD Lyman, SD Ogawa, M AF Ku, H Hirayama, F Kato, T Miyazaki, H Aritomi, V Ota, Y DAndrea, AD Lyman, SD Ogawa, M TI Soluble thrombopoietin receptor (Mpl) and G-CSF receptor directly stimulate proliferation of primitive hematopoietic progenitors of mice in synergy with steel factor or the ligand for Flt3/Flk2. SO BLOOD LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,DEPT MED,RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29425. KIRIN BREWERY CO LTD,PHARMACEUT RES LAB,MAEBASHI,GUMMA 371,JAPAN. PROT ENGN RES INST,SUITA,OSAKA,JAPAN. IMMUNEX CORP,SEATTLE,WA. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1769 EP 1769 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301769 ER PT J AU Barber, DL Fukazawa, T Reedquist, KA Druker, BI Band, H DAndrea, AD AF Barber, DL Fukazawa, T Reedquist, KA Druker, BI Band, H DAndrea, AD TI Erythropoietin and interleukin-3 activate tyrosine phosphorylation of Cbl and association with Crk adaptor proteins. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,LYMPHOCYTE BIOL SECT,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. ONTARIO CANC INST,TORONTO,ON M4X 1K9,CANADA. OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1772 EP 1772 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301772 ER PT J AU Carroll, M Tomasson, MH Barker, GF Golub, TR Gilliland, DG AF Carroll, M Tomasson, MH Barker, GF Golub, TR Gilliland, DG TI The TEL/PDGF beta R fission in CMML is a transforming protein which self-associates and activates PDGF beta R kinase-dependent signaling pathways. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1786 EP 1786 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301786 ER PT J AU Janicek, M Kaplan, W Neuberg, D Canellos, GP Shulman, L Shipp, M AF Janicek, M Kaplan, W Neuberg, D Canellos, GP Shulman, L Shipp, M TI Early resistance gallium scans predict outcome in poor prognosis patients with aggressive NHL treated with high dose induction therapy. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1797 EP 1797 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301797 ER PT J AU Aiuti, A Webb, IJ Bleul, C Springer, TA GutierrezRamos, JC AF Aiuti, A Webb, IJ Bleul, C Springer, TA GutierrezRamos, JC TI SDF-1 is a chemoattractant for human CD34(+) progenitor cells and provide a new mechanism to explain their mobilization to peripheral blood. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT GENET PATHOL & MED,BOSTON,MA. HARVARD UNIV,SCH MED,CTR BLOOD RES INC,BOSTON,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1808 EP 1808 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301808 ER PT J AU Richardson, P Krishnan, A Wheeler, C Hoppensteadt, D Tuchin, J Fyfe, H Bierer, B Guinan, E Antin, J Frei, E Fareed, J Elias, A AF Richardson, P Krishnan, A Wheeler, C Hoppensteadt, D Tuchin, J Fyfe, H Bierer, B Guinan, E Antin, J Frei, E Fareed, J Elias, A TI Elevation of plasminogen activator inhibitor-1 [PAI-1] levels in BMT-associated veno-occlusive disease [VOD] and changes seen with the use of defibrotide [DF] SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA. LOYOLA UNIV,MED CTR,HEMOSTASIS & THROMBOSIS RES LABS,CHICAGO,IL 60611. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1821 EP 1821 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301821 ER PT J AU Webb, IJ Soiffer, RJ Andersen, JW Cohen, CA Freeman, A Sugrue, M Ritz, J Anderson, KC AF Webb, IJ Soiffer, RJ Andersen, JW Cohen, CA Freeman, A Sugrue, M Ritz, J Anderson, KC TI FFP to adsorb isohemagglutinins prior to major ABO incompatible bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1823 EP 1823 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301823 ER PT J AU Karras, JG Wang, Z Huo, L Howard, RG Frank, DA Rothstein, TL AF Karras, JG Wang, Z Huo, L Howard, RG Frank, DA Rothstein, TL TI STAT3 activation following antigen receptor engagement in B lymphocytes: A new paradigm for STAT proteins. SO BLOOD LA English DT Meeting Abstract C1 BOSTON UNIV,MED CTR,BOSTON,MA 02215. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1844 EP 1844 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301844 ER PT J AU Boussiotis, VA Barber, DL Berezovskaya, A Freeman, GJ Gribben, JG Nadler, LM AF Boussiotis, VA Barber, DL Berezovskaya, A Freeman, GJ Gribben, JG Nadler, LM TI Increased fyn kinase activity initiates a cascade of signals that ultimately results in selective RAP1 activation blockade of Ras, and T cell anergy. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1847 EP 1847 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301847 ER PT J AU Shivdasani, RA McDevitt, M Fujiwara, Y deSauvage, FJ Orkin, SH AF Shivdasani, RA McDevitt, M Fujiwara, Y deSauvage, FJ Orkin, SH TI A lineage-restricted gene knockout reveals the critical role of erythroid transcription factor GATA-1 in regulating megakaryocyte growth and platelet formation in vivo. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. GENENTECH INC,SAN FRANCISCO,CA 94080. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1875 EP 1875 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301875 ER PT J AU Huang, LE Arany, Z Livingston, DM Bunn, HF AF Huang, LE Arany, Z Livingston, DM Bunn, HF TI Erythropoietin gene regulation: Activation of hypoxia-inducible factor 1 depends on stabilization of its alpha subunit. SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1879 EP 1879 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301879 ER PT J AU Gokemyer, J Deligiannidis, K Ligris, K Ernst, T AF Gokemyer, J Deligiannidis, K Ligris, K Ernst, T TI 3BP2 binds to phosphatidylinositols; Linking the hematopoietic tyrosine kinase c-fes to the cytoplasmic membrane in a phosphorylation dependent mechanism SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1882 EP 1882 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301882 ER PT J AU Sattler, M Shrikhande, G Verma, S Pisick, E Prasad, K Salgia, R Griffin, JD AF Sattler, M Shrikhande, G Verma, S Pisick, E Prasad, K Salgia, R Griffin, JD TI Identification of a new signal transduction complex associated with c-kit and activated by steel factor. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1884 EP 1884 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301884 ER PT J AU Luo, H Rose, P Barber, DI Hanratty, WP Lee, S Roberts, TM DAndrea, AD Dearolf, CR AF Luo, H Rose, P Barber, DI Hanratty, WP Lee, S Roberts, TM DAndrea, AD Dearolf, CR TI A mutation in the Jak kinase JH2 domain hyperactivates Drosophila and mammalian Jak-Stat SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEV GENET GRP,CANC BIOL SECT,JOINT CANC RADIAT THERAPY,BOSTON,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV PEDIAT ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1885 EP 1885 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301885 ER PT J AU Ritchie, K Aprikian, A BowenPope, D Conyers, S Sitnicka, E Bartelmez, S Hickstein, D AF Ritchie, K Aprikian, A BowenPope, D Conyers, S Sitnicka, E Bartelmez, S Hickstein, D TI The tel-PDGFR beta fusion gene associated with chronic myelomonocytic leukemia produces a chronic myeloproliferative syndrome in transgenic mice. SO BLOOD LA English DT Meeting Abstract C1 SEATTLE BIOMED RES INST,VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA 98109. UNIV WASHINGTON,SCH PUBL HLTH,DEPT PATHOL,SEATTLE,WA 98195. UNIV WASHINGTON,SCH PUBL HLTH,DEPT MED,SEATTLE,WA 98195. UNIV WASHINGTON,SCH PUBL HLTH,DEPT PATHOBIOL,SEATTLE,WA 98195. UNIV WASHINGTON,SCH MED,SEATTLE,WA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1907 EP 1907 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301907 ER PT J AU Andersen, NS Borus, J Poor, C Freedman, AS Pandite, L Nadler, LM Gribben, JG AF Andersen, NS Borus, J Poor, C Freedman, AS Pandite, L Nadler, LM Gribben, JG TI Resistance of mantle cell lymphoma but not B-cell CLL to immunologic purging. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1916 EP 1916 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301916 ER PT J AU Herbert, V AF Herbert, V TI Anti-hyperhomocysteinemic supplemental folic acid & vitamin B-12 are significantly destroyed in gastric juice if co-ingested with supplemental vitamin C and iron. SO BLOOD LA English DT Meeting Abstract C1 MT SINAI VET AFFAIRS MED CTR,NEW YORK,NY. BRONX VET AFFAIRS MED CTR,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1957 EP 1957 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301957 ER PT J AU Herbrecht, R Andres, E Letscher, V Graybill, JR Razmpour, A Gurwith, M Oberling, F AF Herbrecht, R Andres, E Letscher, V Graybill, JR Razmpour, A Gurwith, M Oberling, F TI Treatment with high cumulative doses of amphotericin B colloidal dispersion. Efficacy and tolerance in 96 patients. SO BLOOD LA English DT Meeting Abstract C1 HOP UNIV STRASBOURG,STRASBOURG,FRANCE. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. SEQUUS PHARMACEUT INC,MENLO PK,CA. RI Herbrecht, Raoul/D-3471-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1996 EP 1996 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301996 ER PT J AU Zhu, Y Lambert, K Corless, C DAndrea, AD AF Zhu, Y Lambert, K Corless, C DAndrea, AD TI DUB-2: A member of a novel family of cytokine-inducible deubiquitinating enzymes. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL LAB,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2004 EP 2004 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302004 ER PT J AU Astier, A Manie, S Law, S Canty, T Druker, B Salgia, R Golemis, E Freedman, A AF Astier, A Manie, S Law, S Canty, T Druker, B Salgia, R Golemis, E Freedman, A TI Involvement of CrkL, a cellular homologue of the v-crk proto-oncogene, in integrin and antigen receptor signalling in human B cells SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. RI Astier, Anne/A-1641-2008 OI Astier, Anne/0000-0002-0144-3431 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2007 EP 2007 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302007 ER PT J AU Astier, A Avraham, H Manie, S Groopman, J Druker, B Canty, T Avraham, S Freedman, A AF Astier, A Avraham, H Manie, S Groopman, J Druker, B Canty, T Avraham, S Freedman, A TI The related adhesion focal tyrosine kinase (RAFTK) is tyrosine phosphorylated after beta 1 integrin stimulation in B cells and binds to p130(CAS) SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. DEACONESS HOSP,BOSTON,MA. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. RI Astier, Anne/A-1641-2008 OI Astier, Anne/0000-0002-0144-3431 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2008 EP 2008 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302008 ER PT J AU Manie, S Beck, A Astier, A Law, S Canty, T Hirai, H Druker, B Avraham, H Sattler, M Salgia, R Griffin, J Golemis, E Freedman, A AF Manie, S Beck, A Astier, A Law, S Canty, T Hirai, H Druker, B Avraham, H Sattler, M Salgia, R Griffin, J Golemis, E Freedman, A TI Involvement of p130(CAS) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. DEACONESS HOSP,BOSTON,MA. UNIV TOKYO,TOKYO,JAPAN. OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. RI Astier, Anne/A-1641-2008 OI Astier, Anne/0000-0002-0144-3431 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2009 EP 2009 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302009 ER PT J AU Boussiotis, VA Barber, DL Freeman, GJ Lee, BJ Gribben, JG Nadler, LM AF Boussiotis, VA Barber, DL Freeman, GJ Lee, BJ Gribben, JG Nadler, LM TI Prevention of anergy is not dependent upon cellular proliferation but rather on activation of distinct signaling pathways. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2010 EP 2010 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302010 ER PT J AU Glowacki, J Greenberger, JS Rajavashisth, TB AF Glowacki, J Greenberger, JS Rajavashisth, TB TI Extramedullary hematopoiesis in calcified aortas of Apo E knockout mice. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SKELETAL BIOL RES CTR,BOSTON,MA. UNIV CALIF LOS ANGELES,HARBOR MED CTR,SCH MED,TORRANCE,CA 90509. UNIV PITTSBURGH,MED CTR,DEPT RADIAT ONCOL,PITTSBURGH,PA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2031 EP 2031 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302031 ER PT J AU Banu, N Wagner, DD Avraham, H AF Banu, N Wagner, DD Avraham, H TI P-selectin negatively regulates megakaryocytopoiesis. SO BLOOD LA English DT Meeting Abstract C1 BETH ISRAEL DEACONESS MED CTR,BOSTON,MA. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2119 EP 2119 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302119 ER PT J AU Li, J Xia, Y Kuter, DJ AF Li, J Xia, Y Kuter, DJ TI Analysis of the thrombopoietin receptor (MPL) on platelets from normal and essential thrombocythemic (ET) patients. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2168 EP 2168 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302168 ER PT J AU Shen, Q Nair, M Harris, K AF Shen, Q Nair, M Harris, K TI The soluble erythropoietin receptor expressed in yeast requires the WSXWS domain for secretion. SO BLOOD LA English DT Meeting Abstract C1 S TEXAS VET HLTH CARE SYST,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2185 EP 2185 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302185 ER PT J AU Ringold, S Libermann, T Golub, T AF Ringold, S Libermann, T Golub, T TI Functional characterization of the leukemogenic ETS protein TEL: Evidence for transcriptional repression. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. BETH ISRAEL HOSP,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2205 EP 2205 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302205 ER PT J AU Ernst, TJ Soiffer, R Stone, R Farber, D AF Ernst, TJ Soiffer, R Stone, R Farber, D TI Homoharringtonine with low dose cytarabine combination therapy induces both hematologic and cytogenetic remissions in patients with chronic myelogenous leukemia SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,DANA FARBER CANC INST,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2300 EP 2300 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302300 ER PT J AU Cooke, KR Murray, R Martin, TR Kobzik, L Brewer, J Bungard, D Nishinakamura, R Ferrara, JLM AF Cooke, KR Murray, R Martin, TR Kobzik, L Brewer, J Bungard, D Nishinakamura, R Ferrara, JLM TI Persistence of pulmonary pathology and abnormal lung function in IL-3/GM-CSF/IL-5 beta c receptor deficient mice despite correction of protein accumulation after BMT. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT PATHOL,BOSTON,MA. BRIGHAM & WOMENS HOSP,DIV RESP,BOSTON,MA 02115. DNAX RES INST MOL & CELLULAR BIOL INC,PALO ALTO,CA 94304. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2357 EP 2357 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302357 ER PT J AU Kieran, MW Perkins, AC Orkin, SH Zon, LI AF Kieran, MW Perkins, AC Orkin, SH Zon, LI TI Erythroid colony formation from mouse embryos lacking the erythropoietin receptor is rescued by thrombopoietin SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CHILDRENS HOSP,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. RI Perkins, Andrew/M-3216-2014 OI Perkins, Andrew/0000-0003-3644-7093 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2505 EP 2505 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302505 ER PT J AU Schultze, JL Michalak, S Seamon, MJ Gribben, JG Nadler, LM AF Schultze, JL Michalak, S Seamon, MJ Gribben, JG Nadler, LM TI CD40 activated follicular lymphoma cells are resistant to and can overcome generalized T cell unresponsiveness induced by IL-10 and TGF beta. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2534 EP 2534 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302534 ER PT J AU Liu, ZY Ganju, RK Ona, MA Hatch, WC Wang, JF Lee, J Wood, WI Zheng, T Gill, P Groopman, JE AF Liu, ZY Ganju, RK Ona, MA Hatch, WC Wang, JF Lee, J Wood, WI Zheng, T Gill, P Groopman, JE TI Cytokine signalling through the novel tyrosine kinase RAFTK in Kaposi's Sarcoma cells. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEACONESS MED CTR,DIV HEMATOL ONCOL,BOSTON,MA 02115. UNIV SO CALIF,LOS ANGELES,CA. GENENTECH INC,S SAN FRANCISCO,CA 94080. RI Ona, Mel/P-7761-2015 OI Ona, Mel/0000-0002-5522-2124 NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2609 EP 2609 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302609 ER PT J AU Jaster, R Zhu, Y Pless, M Merchav, S MatheyPrevot, B DAndrea, AD AF Jaster, R Zhu, Y Pless, M Merchav, S MatheyPrevot, B DAndrea, AD TI JAK2 is required for induction of the murine DUB-1 gene. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2621 EP 2621 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302621 ER PT J AU Qu, CK Shen, R Tsai, FY Hu, DP Feng, GS AF Qu, CK Shen, R Tsai, FY Hu, DP Feng, GS TI An essential role of SHP-2 in mammalian hematopoietic development. SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PEDIAT,DANA FARBER CANC INST,BOSTON,MA 02115. INDIANA UNIV,SCH MED,DEPT BIOCHEM MOL BIOL,INDIANAPOLIS,IN 46204. INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46204. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2627 EP 2627 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302627 ER PT J AU Cardoso, AA Seamon, M Afonso, HA McCullough, D Sallan, SE Gribben, JG Nadler, LM AF Cardoso, AA Seamon, M Afonso, HA McCullough, D Sallan, SE Gribben, JG Nadler, LM TI Pre-B all cells produce functional TGF-beta 1 that inhibits both early hematopoiesis acid T cell activation thereby facilitating leukemia cell growth. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2652 EP 2652 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302652 ER PT J AU Silverman, LB McLean, TW Donnelly, MJ Gilliland, DG Gelber, RD Sallan, SE AF Silverman, LB McLean, TW Donnelly, MJ Gilliland, DG Gelber, RD Sallan, SE TI Improved outcome for infants with acute lymphoblastic leukemia (ALL) with intensification of therapy. SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2660 EP 2660 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302660 ER PT J AU Kurtzberg, J Keating, M Moore, JO Gandhi, V Blaney, S Gold, S Ernst, T HensleeDowney, J Chang, A Kisor, D Plunkett, W Mitchell, B AF Kurtzberg, J Keating, M Moore, JO Gandhi, V Blaney, S Gold, S Ernst, T HensleeDowney, J Chang, A Kisor, D Plunkett, W Mitchell, B TI 2-amino-9-B-D-arabinosyl-6-methoxy-9H-guanine (GW 506U; compound 506U) is highly active in patients with T-cell malignancies: Results of a phase I trial in pediatric and adult patients with refractory hematological malignancies. SO BLOOD LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,DURHAM,NC. UNIV N CAROLINA,CHAPEL HILL,NC. DANA FARBER CANC INST,BOSTON,MA 02115. TEXAS CHILDRENS HOSP,HOUSTON,TX 77030. UNIV S CAROLINA,RICHLAND MEM HOSP,COLUMBIA,SC 29208. UNIV ROCHESTER,ROCHESTER,NY. GLAXO WELLCOME INC,RES TRIANGLE PK,NC 27709. NR 0 TC 6 Z9 6 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2666 EP 2666 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302666 ER PT J AU Ghia, P Boussiotis, VA Manie, S Cardoso, AA Gribben, JG Freedman, AS Nadler, LM AF Ghia, P Boussiotis, VA Manie, S Cardoso, AA Gribben, JG Freedman, AS Nadler, LM TI Activation of follicular lymphoma through CD40 upregulates BCL-X(L) thereby promoting survival. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2672 EP 2672 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302672 ER PT J AU Salgia, R Li, JL Curry, E Pisick, E Ewaniuk, D Burky, SA Ernst, T Sattler, M Chen, LB Griffin, JD AF Salgia, R Li, JL Curry, E Pisick, E Ewaniuk, D Burky, SA Ernst, T Sattler, M Chen, LB Griffin, JD TI Transformation of hematopoietic cells by BCR/ABL is associated with enhanced motility. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2684 EP 2684 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302684 ER PT J AU Okuda, K VanEtten, R DAndrea, A Griffin, JD AF Okuda, K VanEtten, R DAndrea, A Griffin, JD TI Construction of a ligand-regulated ABL tyrosine kinase which mimics the biological effects of BCR/ABL in hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2686 EP 2686 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302686 ER PT J AU Krenger, W Cooke, KR Crawford, JM Sonis, ST Simmons, R Pan, L Delmonte, J Karandikar, M Ferrara, JLM AF Krenger, W Cooke, KR Crawford, JM Sonis, ST Simmons, R Pan, L Delmonte, J Karandikar, M Ferrara, JLM TI Transplantation of polarized type 2 donor T cells reduces mortality from graft-versus-host disease to minor histocompatibility antigens. SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV ORAL MED,BOSTON,MA 02115. DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2692 EP 2692 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302692 ER PT J AU Yang, YG Dey, B Sergio, JJ Sykes, M AF Yang, YG Dey, B Sergio, JJ Sykes, M TI IL-12 induces complete protection from hyperacute GVHD in a full MHC haplotype-mismatched murine BMT model. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG SERV,TRANSPLANTAT BIOL RES CTR,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2693 EP 2693 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302693 ER PT J AU Dey, B Swenson, K Pearson, DA Sykes, M AF Dey, B Swenson, K Pearson, DA Sykes, M TI The fate of donor TCR transgenic T cells with known host antigen specificity in a GVHD model. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2694 EP 2694 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302694 ER PT J AU Gribben, JG Anderson, NS Freedman, AS Nadler, LM AF Gribben, JG Anderson, NS Freedman, AS Nadler, LM TI Molecular characterization of secondary non-Hodgkin's lymphomas occurring after ABMT for lymphoma. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2709 EP 2709 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302709 ER PT J AU MachPascual, S Lu, D Gribben, JG Gilliland, DG Legare, RD AF MachPascual, S Lu, D Gribben, JG Gilliland, DG Legare, RD TI Prevalence of clonal hematopoiesis in 60 patients with non-Hodgkin's lymphoma (NHL) at the time of autologous bone-marrow transplantation (ABMT). SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2710 EP 2710 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302710 ER PT J AU Alyea, EP Canning, C Collins, H Pickett, C Wang, Y Soiffer, RJ Ritz, J AF Alyea, EP Canning, C Collins, H Pickett, C Wang, Y Soiffer, RJ Ritz, J TI Efficacy and toxicity of CD4+ donor T lymphocyte infusion for treatment of relapsed chronic myelogenous leukemia (CML) after allogeneic BMT. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2715 EP 2715 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302715 ER PT J AU BartlettPandite, L Gribben, JG Soiffer, R Andersen, NS Anderson, K Fisher, DC Freedman, AS Ritz, J Neuberg, D Nadler, LM AF BartlettPandite, L Gribben, JG Soiffer, R Andersen, NS Anderson, K Fisher, DC Freedman, AS Ritz, J Neuberg, D Nadler, LM TI Potential for cure of B-cell CLL and SLL: Prolonged disease free survival and molecular remissions following autologous and allogeneic bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2718 EP 2718 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302718 ER PT J AU Soiffer, RJ Neuberg, D Freedman, AS Alyea, EP Fisher, DC BartlettPandite, L Gribben, J Schlossman, RL Freeman, A Anderson, KC Nadler, LM Ritz, J AF Soiffer, RJ Neuberg, D Freedman, AS Alyea, EP Fisher, DC BartlettPandite, L Gribben, J Schlossman, RL Freeman, A Anderson, KC Nadler, LM Ritz, J TI CD6 depleted allogeneic and syngeneic bone marrow transplantation (BMT) for non-Hodgkin's lymphoma. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2719 EP 2719 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302719 ER PT J AU Sullivan, R Romero, E AF Sullivan, R Romero, E TI Evidence that at least two types of K+ channels comprise the voltage-dependent outward current of the rat megakaryocyte. SO BLOOD LA English DT Meeting Abstract C1 BAYLOR COLL MED,HOUSTON VA MED CTR,DEPT MED,HOUSTON,TX 77030. BAYLOR COLL MED,HOUSTON VA MED CTR,DEPT MOL PHYSIOL & BIOPHYS,HOUSTON,TX 77030. BAYLOR COLL MED,HOUSTON VA MED CTR,RES SERV,HOUSTON,TX 77030. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2924 EP 2924 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98600185 ER PT J AU Dong, JF Krause, S Lopez, JA AF Dong, JF Krause, S Lopez, JA TI Differential effects of blocking antibodies on shear- and modulator-induced platelet aggregation SO BLOOD LA English DT Meeting Abstract C1 BAYLOR COLL MED,DEPT MED,HEMATOL ONCOL SECT,VA MED CTR,HOUSTON,TX 77030. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2932 EP 2932 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98600193 ER PT J AU Vonderheide, RH Thadhani, R Kuter, DJ AF Vonderheide, RH Thadhani, R Kuter, DJ TI Association of thrombocytopenia and use of intra-aortic balloon pump. SO BLOOD LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2979 EP 2979 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98600240 ER PT J AU Bennett, CL Webb, JJ Golub, RM Barrett, BB Anderson, KC AF Bennett, CL Webb, JJ Golub, RM Barrett, BB Anderson, KC TI Evaluating new technologies in blood banking: Comparison of COBE Spectra(TM) LRS system vs COBE Spectra 4.0 & 4.6 for preparation of leukoreduced single donor apheresis products (LR-SDAP) for transfusion to patients with AML. SO BLOOD LA English DT Meeting Abstract C1 NORTHWESTERN UNIV,CHICAGO,IL 60611. LAKESIDE VET ADM MED CTR,CHICAGO,IL 60611. HARVARD UNIV,SCH MED,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA 02115. RI Bennett, Charles/C-2050-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 3082 EP 3082 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98600343 ER PT J AU Lumelsky, NL Schwartz, BS AF Lumelsky, NL Schwartz, BS TI Signalling through protein kinase C may determine lineage selection during erythroid and megakaryocytic differentiation. SO BLOOD LA English DT Meeting Abstract C1 UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET HOSP,MADISON,WI. UNIV WISCONSIN,DEPT MED,SECT HEMATOL,MADISON,WI. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 3199 EP 3199 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98600460 ER PT J AU Uphoff, CC Denkmann, SA Golub, TR Borkhardt, A Janssen, JWG Drexler, HG AF Uphoff, CC Denkmann, SA Golub, TR Borkhardt, A Janssen, JWG Drexler, HG TI Occurrence of TEL-AML1 fusion resulting from t(12;21) in human pre-B leukemia cell lines. SO BLOOD LA English DT Meeting Abstract C1 DSMZ,GERMAN COLLECT MICROORGANISMS & CELL CULTURES,BRAUNSCHWEIG,GERMANY. DANA FABER CANC INST,BOSTON,MA. UNIV HOSP GIESSEN,GIESSEN,GERMANY. INST HUMAN GENET,HEIDELBERG,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 3302 EP 3302 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98600563 ER PT J AU Krajewski, S Krajewska, M Andersen, J Glick, J Smalley, R Gordon, L Venkatraj, U Reed, JC AF Krajewski, S Krajewska, M Andersen, J Glick, J Smalley, R Gordon, L Venkatraj, U Reed, JC TI BCL-2 expression appears to be associated with histology in low to intermediate grade non-Hodgkin's lymphoma (NHL): An ecog study. SO BLOOD LA English DT Meeting Abstract C1 BURNHAM INST,LA JOLLA,CA 92037. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV PENN,PHILADELPHIA,PA 19104. SYNETRON,MADISON,WI. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. ALBERT EINSTEIN COLL MED,BRONX,NY 10467. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 3469 EP 3469 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98600730 ER PT J AU Adler, H Beland, JL Kozlow, W Kobzik, L Brewer, J Martin, TR Rimm, IJ AF Adler, H Beland, JL Kozlow, W Kobzik, L Brewer, J Martin, TR Rimm, IJ TI Murine allogeneic bone marrow transplant recipients have increased pneumonitis and mortality but decreased influx of cells and antibody to the lungs after intranasal, herpes simplex virus-type I (HSV-1) infection. SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 3640 EP 3640 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98600901 ER PT J AU Spitzer, TR Mcafee, SL Powell, S AF Spitzer, TR Mcafee, SL Powell, S TI Dose escalated total body irradiation (TBI) and autologous peripheral blood stem cell transplantation (PBSCT) for refractory hematologic malignancy (HM). SO BLOOD LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 3880 EP 3880 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98601141 ER PT J AU Winter, JN Andersen, J Variakojis, D Gordon, LI Fisher, RI Oken, MM Neiman, RS Jiang, SW Bauer, KD AF Winter, JN Andersen, J Variakojis, D Gordon, LI Fisher, RI Oken, MM Neiman, RS Jiang, SW Bauer, KD TI Prognostic implications of ploidy and proliferative activity in the diffuse, aggressive non-Hodgkin's lymphomas SO BLOOD LA English DT Article ID STANDARD REGIMEN CHOP; LARGE CELL LYMPHOMAS; FLOW-CYTOMETRY; DNA CONTENT; S-PHASE; SURVIVAL; ANTIGEN; KI-67 AB The International Index is a powerful predictor of outcome in the aggressive non-Hodgkin's lymphomas that is based solely on clinical features. Proliferative activity (% S-phase) measured by flow cytometry has been reported to have prognostic significance in many series and may represent a biologic correlate of clinical behavior that further defines prognosis. Flow cytometric analysis of cellular DNA content and proliferative activity (% S-phase) was performed on fixed paraffin-embedded biopsy specimens from 242 previously untreated patients with diffuse, aggressive non-Hodgkin's lymphomas entered on phase III intergroup clinical trials. The International Index was calculated for each patient based on stage, lactate dehydrogenase, performance status, number of extranodal sites, and age, as previously reported. The International Index consistently predicted response to therapy (P =.027) and survival (P =.007) in this series. DNA aneuploidy was shown in 57% of cases, but was not predictive of clinical outcome. The median % S-phase was 9.9 (median coefficient of variation, 3.6%), which was highly correlated with mitotic index (P =.0001). Although a trend associating low proliferative activity with good early survival and very high S-phase with a shortened survival was shown, International Index risk was the only significant predictor of survival in the multivariate analysis. Although proliferative activity quantitated by flow cytometric analysis of nuclei extracted from paraffin-embedded specimens is probably predictive of survival, it is a less powerful prognostic indicator than clinical parameters represented by the International Index and provides no additional prognostic information. (C) 1996 by The American Society of Hematology. C1 NORTHWESTERN UNIV,ROBERT LURIE CANC CTR,CHICAGO,IL 60611. DANA FARBER CANC INST,EASTERN COOPERAT ONCOL GRP STAT CTR,BOSTON,MA 02115. ABBOTT NW HOSP,VIRGINIA PIPER CANC INST,MINNEAPOLIS,MN. LOYOLA UNIV,STRITCH SCH MED,MAYWOOD,IL 60153. INDIANA UNIV,MED CTR,INDIANAPOLIS,IN. OI Gordon, Leo/0000-0003-1666-7064 FU NCI NIH HHS [CA 17145, CA 23318, CA 49883] NR 29 TC 19 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 BP 3919 EP 3925 PG 7 WC Hematology SC Hematology GA VU984 UT WOS:A1996VU98400028 PM 8916958 ER PT J AU Hamblin, MR Miller, JL Hasan, T AF Hamblin, MR Miller, JL Hasan, T TI Effect of charge on the interaction of site-specific photoimmunoconjugates with human ovarian cancer cells SO CANCER RESEARCH LA English DT Article ID HORSERADISH-PEROXIDASE; PHOTODYNAMIC THERAPY; PHOTOSENSITIZERS; LYSOSOMES; ANTIBODY; PROTEINS; PHOTOIMMUNOTHERAPY; ENDOCYTOSIS; DESTRUCTION; DRUGS AB A marked effect of charge modification on the uptake and phototoxicity of a photoimmunoconjugate (PIC) was demonstrated. A site-specific conjugation strategy was developed to attach the photosensitizer chlorin(e6) (c(e6)) to the F(ab')(2) fragment of the murine antiovarian cancer monoclonal antibody OC125. Poly-L-lysine linkers carrying c(e6) with a cationic charge or by polysuccinylation with an anionic charge were used and covalently attached to partially reduced antibody via a heterobifunctional reagent. PICs were purified by column chromatography and were also radiolabeled with I-125. PIC binding and uptake were studied with a human ovarian cancer cell line, NIH-OVCAR-5, and a nonantigen-expressing colon cancer cell line, SW1116, and the data were compared with the binding and uptake of nonspecific rabbit IgG PICs. PICs with both cationic and anionic charges preserved antigen binding as shown by competition studies with native antibody, but the cationic PIC had up to 17 times higher cellular uptake of c(e6), probably due to enhanced internalization. The ratio of c(e6) to I-125 retained by the cells varied with the likelihood of internalization and lysosomal degradation. The phototoxicity of the PICs generally varied with their uptake, but a correlation was found between lysosomal hydrolysis as measured by an increased cellular ratio of c(e6):I-125 and increased relative phototoxicity. These data suggest cationic PICs may have advantages for photoimmunotherapy of disseminated intracavity cancer following local administration. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. OI Hamblin, Michael/0000-0001-6431-4605 FU NIAMS NIH HHS [R01 AR40352] NR 26 TC 55 Z9 56 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1996 VL 56 IS 22 BP 5205 EP 5210 PG 6 WC Oncology SC Oncology GA VT338 UT WOS:A1996VT33800018 PM 8912858 ER PT J AU Carabello, BA AF Carabello, BA TI Aortic regurgitation in women - Does the measuring stick need a change? SO CIRCULATION LA English DT Editorial Material DE editorials; regurgitation; aorta; surgery ID LEFT-VENTRICULAR FUNCTION; VALVE-REPLACEMENT; ASYMPTOMATIC PATIENTS; NATURAL-HISTORY; DYSFUNCTION; SURVIVAL; DETERMINANTS; PERFORMANCE; REVERSAL; TIME C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. MED UNIV S CAROLINA,GAZES CARDIAC RES INST,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS,CHARLESTON,SC. NR 16 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 NOV 15 PY 1996 VL 94 IS 10 BP 2355 EP 2357 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VT114 UT WOS:A1996VT11400002 PM 8921771 ER PT J AU Rao, AK Sun, L Chesebro, JH Fuster, V Harrington, RA Schwartz, D Gallo, P Matos, D Topol, EJ AF Rao, AK Sun, L Chesebro, JH Fuster, V Harrington, RA Schwartz, D Gallo, P Matos, D Topol, EJ TI Distinct effects of recombinant desulfatohirudin (Revasc) and heparin on plasma levels of fibrinopeptide a and prothrombin fragment F1.2 in unstable angina - A multicenter trial SO CIRCULATION LA English DT Article DE angina; coagulation; anticoagulants; hirudin; heparin ID ACUTE MYOCARDIAL-INFARCTION; FACTOR-XA; HIRUDIN CGP-39393; ANTITHROMBIN-III; THROMBIN INHIBITION; MECHANISM; THROMBOLYSIS; COAGULATION; GENERATION; COMPLEX AB Background Thrombin plays an important role in the pathogenesis of acute coronary thrombosis. We studied the effects of a direct thrombin inhibitor, recombinant desulfatohirudin, and heparin on plasma levels (at 0, 4, 12, and 24 hours) of fibrinopeptide A (FPA), which reflects thrombin action, and prothrombin fragment F1.2, which reflects thrombin generation, in patients with unstable angina. Methods and Results Patients were randomized to one of two doses of heparin (n=50) (target activated partial thromboplastin time, 65 to 90 seconds or 90 to 110 seconds) or one of four doses of r-hirudin (n=113) (0.05, 0.10, 0.20, or 0.30 mg . kg(-1)h(-1) by infusion). r-Hirudin induced a dose-dependent decline in plasma FPA. At 24 hours, FPA levels with 0.1- to 0.3-mg . kg(-1) h(-1) r-hirudin regimens were significantly lower than with 0.05 mg . kg(-1). h(-1) r-hirudin; levels with 0.1- to 0.2-mg . kg(-1). h(-1) r-hirudin regimens were lower than with both heparin regimens. Plasma F1.2 did not decline significantly during therapy with heparin or hirudin except at 0.3 mg . kg(-1). h(-1) hirudin. At 24 hours, they were higher with the 0.05-mg . kg(-1). h(-1) r-hirudin regimen than with other regimens. For comparable levels of thrombin generation (F1.2 levels), FPA levels were higher in heparin patients than in hirudin patients. For the same FPA values, the corresponding F1.2 values were higher in the hirudin group. Conclusions Our findings provide evidence for distinct in vivo effects of the two agents and suggest that r-hirudin is a relatively more potent inhibitor of thrombin action but a less effective inhibitor of thrombin generation than heparin. The lower FPA levels in hirudin patients may reflect its ability to inactivate clot-bound thrombin. The relative clinical efficacies of the two agents need to be defined by clinical trials in progress. C1 TEMPLE UNIV,SCH MED,DEPT MED,SOL SHERRY THROMBOSIS RES CTR,PHILADELPHIA,PA 19140. MAYO CLIN,ROCHESTER,MN. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. DUKE UNIV,MED CTR,DURHAM,NC. CIBA GEIGY CORP,SUMMIT,NJ 07901. CLEVELAND CLIN,CLEVELAND,OH 44106. RI Fuster, Valentin/H-4319-2015; OI Fuster, Valentin/0000-0002-9043-9986; Topol, Eric/0000-0002-1478-4729 NR 38 TC 32 Z9 33 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 NOV 15 PY 1996 VL 94 IS 10 BP 2389 EP 2395 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VT114 UT WOS:A1996VT11400009 PM 8921778 ER PT J AU Ting, AT PimentelMuinos, FX Seed, B AF Ting, AT PimentelMuinos, FX Seed, B TI RIP mediates tumor necrosis factor receptor 1 activation of NF-kappa B but not Fas/APO-1-initiated apoptosis SO EMBO JOURNAL LA English DT Article DE apoptosis; receptors; signal transduction; somatic cell mutant ID TNF RECEPTOR; DEATH DOMAIN; CELL-DEATH; CYTOPLASMIC DOMAIN; CD40; PROTEIN; INTERACTS; EXPRESSION; FAMILY; PHOSPHATIDYLSERINE AB The CD95 (Fas/APO-1) and tumor necrosis factor (TNF) receptor pathways share many similarities, including a common reliance on proteins containing 'death domains' for elements of the membrane-proximal signal relay. We have created mutant cell lines that are unable to activate NF-kappa B in response to TNF. One of the mutant lines lacks RIP, a 74 kDa Ser/Thr kinase originally identified by its ability to associate with Fas/APO-1 and induce cell death. Reconstitution of the line with RIP restores responsiveness to TNF. The RIP-deficient cell line is susceptible to apoptosis initiated by anti-CD95 antibodies. An analysis of cells reconstituted with mutant forms of RIP reveals similarities between the action of RIP and FADD/MORT-1, a Fas-associated death domain protein. RP Ting, AT (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114, USA. RI Pimentel-Muinos, Felipe/K-4557-2014 OI Pimentel-Muinos, Felipe/0000-0002-0258-2855 FU NIDDK NIH HHS [DK43031] NR 33 TC 404 Z9 412 U1 0 U2 5 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 15 PY 1996 VL 15 IS 22 BP 6189 EP 6196 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VW418 UT WOS:A1996VW41800019 PM 8947041 ER PT J AU Steingrimsson, E Nii, A Fisher, DE FerreDAmare, AR McCormick, RJ Russell, LB Burley, SK Ward, JM Jenkins, NA Copeland, NG AF Steingrimsson, E Nii, A Fisher, DE FerreDAmare, AR McCormick, RJ Russell, LB Burley, SK Ward, JM Jenkins, NA Copeland, NG TI The semidominant Mi(b) mutation identifies a role for the HLH domain in DNA binding in addition to its role in protein dimerization SO EMBO JOURNAL LA English DT Article DE bHLH-Zip transcription factors; DNA binding; melanocytes; microphthalmia; retinal degeneration ID RECESSIVE RETINITIS-PIGMENTOSA; INHERITED RETINAL DYSTROPHY; MICROPHTHALMIA GENE; TRANSCRIPTION FACTOR; B/HLH/Z DOMAIN; ALPHA-SUBUNIT; HUMAN HOMOLOG; BROWN LOCUS; MOUSE MODEL; ONE FORM AB The mouse microphthalmia (mi) locus encodes a basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor called MITF (microphthalmia transcription factor). Mutations at mi affect the development of several different cell types, including melanocytes, mast cells, osteoclasts and pigmented epithelial cells of the eye. Here we describe the phenotypic and molecular characterization of the semidominant Microphthalmia(brownish) (Mi(b)) mutation. We show that this mutation primarily affects melanocytes and produces retinal degeneration. The mutation is a G to A transition leading to a Gly244Glu substitution in helix 2 of the HLH dimerization domain. This location is surprising since other semidominant mi mutations characterized to date have been shown to affect DNA binding or transcriptional activation domains of MITF and act as dominant negatives, while mutations that affect MITF dimerization are inherited recessively. Gel retardation assays showed that while the mutant MITF(Mi-b) protein retains its dimerization potential, it is defective in its ability to bind DNA. Computer modeling suggested that the Gly244Glu mutation might disrupt DNA binding by interfering with productive docking of the protein dimer onto DNA. The Mi(b) mutation therefore appears to dissociate a DNA recognition function of the HLH domain from its role in protein dimerization. C1 NCI,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. ROCKEFELLER UNIV,HOWARD HUGHES MED INST,MOL BIOPHYS LAB,NEW YORK,NY 10021. OAK RIDGE NATL LAB,DIV BIOL,OAK RIDGE,TN 37831. NR 43 TC 38 Z9 38 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 NOV 15 PY 1996 VL 15 IS 22 BP 6280 EP 6289 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VW418 UT WOS:A1996VW41800029 PM 8947051 ER PT J AU Koike, G VanVooren, P Shiozawa, M Galli, J Li, LS Glaser, A Balasubramanyam, A Brown, LJ Luthman, H Szpirer, C MacDonald, MJ Jacob, HJ AF Koike, G VanVooren, P Shiozawa, M Galli, J Li, LS Glaser, A Balasubramanyam, A Brown, LJ Luthman, H Szpirer, C MacDonald, MJ Jacob, HJ TI Genetic mapping and chromosome localization of the rat mitochondrial glycerol-3-phosphate dehydrogenase gene, a candidate for non-insulin-dependent diabetes mellitus SO GENOMICS LA English DT Article ID LINKED GLYCEROPHOSPHATE DEHYDROGENASE; LINKAGE MAP; ISLETS; HYPERTENSION AB The mitochondrial FAD-dependent glycerol-3-phosphate dehydrogenase (mtGPD) plays an important role in the regulation of insulin secretion and has been postulated as a candidate responsible for the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) in humans as well as in rodent models of NIDDM. Recent molecular genetic studies of the Goto-Kakizaki (GK) rat model of NIDDM have identified loci linked to NIDDM. To elucidate whether rat mtGPD might play a role in the pathogenesis of NIDDM, the rat mtGPD gene (Gpd2) was cloned, and a genetic marker for Gpd2 was developed. The gene mapped to the region of rat chromosome 3 that contains a region linked to NIDDM in the GK rat. Fluorescence in situ hybridization was also carried out to verify the map position. (C) 1996 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. FREE UNIV BRUSSELS,DEPT BIOL MOL,B-1640 RHODE ST GENESE,BELGIUM. KAROLINSKA HOSP,DEPT MOL MED,ROLF LUFT CTR DIABET RES,S-17176 STOCKHOLM,SWEDEN. UNIV WISCONSIN,SCH MED,CHILDREN DIABET CTR,MADISON,WI 53706. FU NIDDK NIH HHS [DK238348, DK42176] NR 24 TC 13 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1996 VL 38 IS 1 BP 96 EP 99 DI 10.1006/geno.1996.0599 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VV024 UT WOS:A1996VV02400016 PM 8954787 ER PT J AU Dawood, MM Gutpa, DK Southern, J Walia, A Atkinson, JB Eagle, KA AF Dawood, MM Gutpa, DK Southern, J Walia, A Atkinson, JB Eagle, KA TI Pathology of fatal perioperative myocardial infarction: Implications regarding pathophysiology and prevention SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE myocardial infarction; postoperative; coronary plaque ID CORONARY ATHEROSCLEROTIC PLAQUES; THROMBOSIS; ISCHEMIA; RUPTURE AB The aim of this study was to determine the pathology of fatal postoperative myocardial infarction (MI) and compare it with that of non-operative myocardial infarction. Histopathological analyses of coronary arteries and myocardium were performed on autopsy heart specimens (n=67), and clinical attributes were studied. Findings of perioperative MI (n=42) were compared to those of non-perioperative MI (n=25). Significant atherosclerotic obstruction (>50% cross-sectional narrowing) was observed in the majority of patients (93%). Left main (>50% cross-sectional narrowing) and/or three-vessel coronary artery disease were especially common (44%) in this group. Evidence of unstable plaques with disruption was noted in 55% of perioperative MI patients (n=23); plaque hemorrhage was found in 45% (n=19). Predicting the site of infarction based on severity of underlying stenosis would have been unsuccessful in more than half the patients in both perioperative and nonoperative MI groups. Clinical profiles of the patients in the two groups were similar in terms of prior cardiac history, gender and age. Fatal perioperative MI occurs predominantly in patients with multivessel coronary disease, especially left main and three-vessel disease. The severity of preexisting underlying stenosis did not predict the resulting infarct territory. Evidence of acute plaque disruption in the infarct-related artery is common. Perioperative MIs have similar coronary artery pathology to non-operative MIs with regard to coronary plaque hemorrhage, rupture, and thrombus formation and probably occur by a similar mechanism. C1 UNIV MICHIGAN,CTR MED,DIV CARDIOL,ANN ARBOR,MI 48109. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. VANDERBILT UNIV,CTR MED,DIV CARDIOL,DEPT MED,NASHVILLE,TN 37232. VANDERBILT UNIV,CTR MED,DEPT PATHOL,NASHVILLE,TN 37232. NR 22 TC 204 Z9 212 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD NOV 15 PY 1996 VL 57 IS 1 BP 37 EP 44 DI 10.1016/S0167-5273(96)02769-6 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VV887 UT WOS:A1996VV88700005 PM 8960941 ER PT J AU Tebar, F Sorkina, T Sorkin, A Ericsson, M Kirchhausen, T AF Tebar, F Sorkina, T Sorkin, A Ericsson, M Kirchhausen, T TI Eps15 is a component of clathrin-coated pits and vesicles and is located at the rim of coated pits SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE SUBSTRATE; GROWTH-FACTOR RECEPTOR; PROTEIN; DYNAMIN; DOMAIN; AP-2; ENDOCYTOSIS AB Eps15, a phosphorylation substrate of the epidermal growth factor (EGF) receptor kinase, has been shown to bind to the alpha-subunit of the clathrin-associated protein complex AP-2. Here we report that in cells, virtually all Eps15 interacts with the cytosol and membrane-bound forms of AP-2. This association is not affected by the treatment of cells with EGF. Immunofluorescence microscopy reveals nearly absolute co-localization of Eps15 with AP-2 and clathrin, and analysis by immunoelectron microscopy shows that the localization of membrane-associated Eps15 is restricted to the profiles corresponding to endocytic coated pits and vesicles. Unexpectedly, Eps15 was found at the edge of forming coated pits and at the rim of budding coated vesicles. This asymmetric distribution is in sharp contrast to the localization of AP-2 that shows an even distribution along the same types of clathrin-coated structures. These findings suggest several possible regulatory roles of Eps15 during the formation of coated pits. C1 UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,DENVER,CO 80262. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02215. CTR BLOOD RES,BOSTON,MA 02115. RI Tebar, Francesc/H-1498-2015 OI Tebar, Francesc/0000-0002-9522-9726 FU NIDDK NIH HHS [DK46817]; NIGMS NIH HHS [GM36548] NR 26 TC 187 Z9 189 U1 3 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1996 VL 271 IS 46 BP 28727 EP 28730 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT052 UT WOS:A1996VT05200001 PM 8910509 ER PT J AU Bloch, DB delaMonte, SM Guigaouri, P Filippov, A Bloch, KD AF Bloch, DB delaMonte, SM Guigaouri, P Filippov, A Bloch, KD TI Identification and characterization of a leukocyte-specific component of the nuclear body SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; PRIMARY BILIARY-CIRRHOSIS; RECEPTOR-ALPHA GENE; ZINC-FINGER; CELL-LINE; TRANSCRIPTION FACTOR; VIRUS-INFECTION; PML PROTEIN; RAR-ALPHA; EXPRESSION AB The nuclear body (NB) is a cellular organelle that is involved in the pathogenesis of acute promyelocytic leukemia and viral infection. The NB is also a target of antibodies in the serum of patients with the autoimmune disease primary biliary cirrhosis. In this study, serum from a patient with primary biliary cirrhosis was used to identify a cDNA encoding a novel component of the NB, a 140-kDa protein designated Sp140. The predicted amino acid sequence of the amino-terminal portion of Sp140 was similar to Sp100, a previously identified NB protein. The carboxyl portion of Sp140 contained a zinc-finger domain and a bromodomain, motifs that are present in proteins regulating gene transcription. High levels of Sp140 mRNA were detected in human spleen and peripheral blood leukocytes, but not other human tissues. The level of SP140 mRNA in myeloid precursor cell lines HL60 and NB4 markedly increased in response to chemically induced cellular differentiation. Immunohistochemical techniques were used to demonstrate that SP140 localized to the NB in differentiated HL60 and NB4 cells. The location of Sp140 in the NB, and expression of this gene in cells involved in host defense, suggest that Sp140 may be involved in the pathogenesis of acute promyelocytic leukemia and viral infection. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,GEN MED SERV,ARTHRIT UNIT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,GEN MED SERV,CARDIOVASC RES CTR,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,GEN MED SERV,CTR CANC,DIV NEUROPATHOL,BOSTON,MA 02129. FU NHLBI NIH HHS [HL45895]; NIAMS NIH HHS [AR01866]; NIDDK NIH HHS [DK51179] NR 52 TC 70 Z9 71 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 15 PY 1996 VL 271 IS 46 BP 29198 EP 29204 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT052 UT WOS:A1996VT05200069 PM 8910577 ER PT J AU Argetsinger, LS Norstedt, G Billestrup, N White, MF CarterSu, C AF Argetsinger, LS Norstedt, G Billestrup, N White, MF CarterSu, C TI Growth hormone, interferon-gamma, and leukemia inhibitory factor utilize insulin receptor substrate-2 in intracellular signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; MEMBRANE-PROXIMAL REGION; C-FOS; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOTYROSINE PHOSPHATASE; 3T3-F442A PREADIPOCYTES; CYTOPLASMIC REGIONS; HEMATOPOIETIC-CELLS; 2-HYBRID SYSTEM; SYP PHOSPHATASE AB In this report, we demonstrate that insulin receptor substrate-2 (IRS-2) is tyrosyl-phosphorylated following stimulation of 3T3-F442A fibroblasts with growth hormone (GH), leukemia inhibitory factor and interferon-gamma. In response to GH and leukemia inhibitory factor, IRS-2 is immediately phosphorylated, with maximal phosphorylation detected at 15 min; the signal is substantially diminished by 60 min. In response to interferon-gamma, tyrosine phosphorylation of IRS-S was prolonged, with substantial signal still detected at 60 min. Characterization of the mechanism of signaling utilized by GH indicated that tyrosine residues in GH receptor are not necessary for tyrosyl phosphorylation of IRS-2; however, the regions of GH receptor necessary for IRS-2 tyrosyl phosphorylation are the same as those required for JAK2 association and tyrosyl phosphorylation. The role of IRS-2 as a signaling molecule for GH is further demonstrated by the finding that GH stimulates association of IRS-2 with the 85-kDa regulatory subunit of phosphatidylinositol 3'-kinase and with the protein-tyrosine phosphatase SHP2. These results are consistent with the possibility that IRS-2 is a downstream signaling partner of multiple members of the cytokine family of receptors that activate JAK kinases. C1 UNIV MICHIGAN,SCH MED,DEPT PHYSIOL,ANN ARBOR,MI 48109. JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. KAROLINSKA INST,CTR BIOTECHNOL,S-14157 STOCKHOLM,SWEDEN. HAGEDORN RES LAB,DK-2820 GENTOFTE,DENMARK. OI Billestrup, Nils/0000-0002-4968-8067 FU NIDDK NIH HHS [R01-DK36836, R01 DK034171, R01 DK043808, R01-DK 43808, R01-DK34171] NR 63 TC 100 Z9 101 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 15 PY 1996 VL 271 IS 46 BP 29415 EP 29421 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT052 UT WOS:A1996VT05200099 PM 8910607 ER PT J AU Hynes, RO Wagner, DD AF Hynes, RO Wagner, DD TI Genetic manipulation of vascular adhesion molecules in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article C1 MIT,DEPT BIOL,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Hynes, RO (reprint author), MIT,HOWARD HUGHES MED INST,CTR CANC RES,CAMBRIDGE,MA 02139, USA. NR 7 TC 50 Z9 50 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 15 PY 1996 VL 98 IS 10 BP 2193 EP 2195 DI 10.1172/JCI119027 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VU826 UT WOS:A1996VU82600003 PM 8941633 ER PT J AU Baumert, TF Rogers, SA Hasegawa, K Liang, TJ AF Baumert, TF Rogers, SA Hasegawa, K Liang, TJ TI Two core promotor mutations identified in a hepatitis B virus strain associated with fulminant hepatitis result in enhanced viral replication SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE core promotor; encapsidation; HBX gene ID X-PROTEIN; REVERSE TRANSCRIPTION; MESSENGER-RNA; DNA-SYNTHESIS; GENE; ENCAPSIDATION; TRANSLATION; BINDING; HEPADNAVIRUS; INITIATION AB Viral mutations have been implicated in alteration of the biological phenotype of hepatitis B virus (HBV). We recently cloned and sequenced the viral genome of an HBV strain associated with an outbreak of fulminant hepatitis (FH strain). The FH strain contained numerous mutations in all genomic regions and was functionally characterized by a more efficient encapsidation of pregenomic RNA leading to highly enhanced replication, To define the responsible mutation(s) for the enhanced replication, we introduced individual mutations of the FH strain into a wild-type construct by oligonucleotide-directed mutagenesis, Analysis of viral replication showed that two adjacent mutations in the HBV core promotor (C to T at nucleotide 1768 and T to A at nucleotide 1770) led to high level replication, Similar to the FH strain, this mutant displayed the phenotype of enhanced encapsidation of pregenomic RNA. Functional studies in an encapsidation assay demonstrated that the identified mutations resulted in a minor increase of pregenomic RNA transcription (two- to threefold) and a major transcription-independent enhancement (> 10-fold) of viral encapsidation, Our results demonstrate that the two adjacent mutations in the HBV core promotor region are responsible for the enhanced replication of the FH strain, These two mutations, outside the previously described encapsidation signal, core, and polymerase polypeptides, appeared to affect a novel genetic element involved in viral encapsidation. C1 NIDDK,LIVER DIS SECT,NIH,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NCI NIH HHS [CA-54524]; NIDDK NIH HHS [DK-01952, VF-DK-14361] NR 40 TC 142 Z9 152 U1 1 U2 7 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 15 PY 1996 VL 98 IS 10 BP 2268 EP 2276 DI 10.1172/JCI119037 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VU826 UT WOS:A1996VU82600013 PM 8941643 ER PT J AU Gonzalo, JA Lloyd, CM Kremer, L Finger, E Martinez, C Siegelman, MH Cybulsky, M GutierrezRamos, JC AF Gonzalo, JA Lloyd, CM Kremer, L Finger, E Martinez, C Siegelman, MH Cybulsky, M GutierrezRamos, JC TI Eosinophil recruitment to the lung in a murine model of allergic inflammation - The role of T cells, chemokines, and adhesion receptors SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE lung eosinophilia; leukocytes; chemotactic cytokines; integrins; selectins ID VASCULAR ENDOTHELIAL-CELLS; ANTIGEN-INDUCED EOSINOPHIL; HUMAN ALVEOLAR MACROPHAGES; LATE ACTIVATION ANTIGEN-4; COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; LYMPHOCYTES-T; TRANSENDOTHELIAL MIGRATION; BLOOD MONOCYTES; MICE LACKING AB Eosinophil accumulation is a distinctive feature of lung allergic inflammation, Here, we have used a mouse model of OVA (ovalbumin)-induced pulmonary eosinophilia to study the cellular and molecular mechanisms for this selective recruitment of eosinophils to the airways, In this model there was an early accumulation of infiltrating monocytes/macrophages in the lung during the OVA treatment, whereas the increase in infiltrating T-lymphocytes paralleled the accumulation of eosinophils. The kinetics of accumulation of these three leukocyte subtypes correlated with the levels of mRNA expression of the chemokines monocyte chemotactic peptide-1/JE, eotaxin, and RANTES (regulated upon activation in normal T cells expressed and secreted), suggesting their involvement in the recruitment of these leukocytes, Furthermore, blockade of eotaxin with specific antibodies in vivo reduced the accumulation of eosinophils in the lung in response to OVA by half, Mature CD4(+) T-lymphocytes were absolutely required for OVA-induced eosinophil accumulation since lung eosinophilia was prevented in CD4(+)-deficient mice, However, these cells were neither the main producers of the major eosinophilic chemokines eotaxin, RANTES, or MIP-1 alpha, nor did they regulate the expression of these chemokines, Rather, the presence of CD4(+) T cells was necessary for enhancement of VCAM-1 (vascular cell adhesion molecule-1) expression in the lung during allergic inflammation induced by the OVA treatment, In support of this, mice genetically deficient for VCAM-1 and intercellular adhesion molecule-1 failed to develop pulmonary eosinophilia, Selective eosinophilic recruitment during lung allergic inflammation results from a sequential accumulation of certain leukocyte types, particularly T cells, and relies on the presence of both eosinophilic chemoattractants and adhesion receptors. 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,E-28049 MADRID,SPAIN. UNIV TEXAS,SW MED CTR DALLAS,DEPT PATHOL,DALLAS,TX 75235. BRIGHAM & WOMENS HOSP,DIV PATHOL,BOSTON,MA 02115. RI Kremer, Leonor/L-5445-2015 OI Kremer, Leonor/0000-0002-2235-2010 FU NCPDCID CDC HHS [CICYT PB93-0317]; NHLBI NIH HHS [HL 148675-01, HL94-10-B]; Wellcome Trust [087618] NR 80 TC 352 Z9 363 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 NOV 15 PY 1996 VL 98 IS 10 BP 2332 EP 2345 DI 10.1172/JCI119045 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VU826 UT WOS:A1996VU82600021 PM 8941651 ER PT J AU Schulz, RJ Parkes, A Mizoguchi, E Bhan, AK Koyasu, S AF Schulz, RJ Parkes, A Mizoguchi, E Bhan, AK Koyasu, S TI Development of CD4(-)CD8(-) alpha beta TCR(+)NK1.1(+) T lymphocytes - Thymic selection by self antigen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; RECEPTOR TRANSGENIC MICE; CLASS-I MOLECULES; LARGE GRANULAR LYMPHOCYTES; MARROW GRAFT-REJECTION; ALPHA-BETA+ THYMOCYTES; FC-GAMMA-RII/III; MONOCLONAL-ANTIBODY; BONE-MARROW; EXTRATHYMIC DEVELOPMENT AB Development of CD4(-)CD8(-) double negative (DN) alpha beta TCR(+) cells were examined by cell transfer experiments using an Ly-5 congenic mouse system, Purified DN alpha beta TCR(+) thymocytes injected intrathymically emigrated from the thymus to the spleen, The same cells did not return to the thymus when injected i.v. Similarly, peripheral DN alpha beta TCR(+) cells from spleen and liver did not go to the thymus when injected i.v. but migrated to the spleen, These results indicate that DN alpha beta TCR(+) thymocytes develop within the thymus and emigrate to peripheral organs, It is thus likely that peripheral DN alpha beta TCR(+) cells are at least partly of thymic origin, DN alpha beta TCR(+) thymocytes are unique in that they express a natural killer cell marker, NK1.1, which is not found on conventional T cells, We further examined the thymic selection of DN alpha beta TCR(+)NK1.1(+) thymocytes by using an anti-HY TCR-transgenic (tg)/Rag-2(-/-) mouse system with H-2 backgrounds that were negative, positive, or nonselecting for conventional T cells, The number of DNtgTCR alpha beta(+)NK1.1(+) cells was most prominent in male H-2(b) animals in which conventional T cells are deleted by HY/H-2D(b) recognition. Fewer DNtgTCR alpha beta(+)NK1.1(+) cells were found in H-2(b) females (positive selecting background), and almost no DNtgTCR alpha beta(+)NK1.1(+) cells were detected in H-2(d) animals (nonselecting background), Unlike conventional T cells, DNtgTCR alpha beta(+)NK1.1(+) cells from anti-HY/Rag-2(-/-) H-2(b) mice express Fc epsilon Rl gamma and CD3 zeta as DN alpha beta TCR(+)NK1.1(+) cells from normal C57BL/6 mice, Our results indicate that DNtgTCR alpha beta(+)NK1.1(+) cells are positively selected by self Ag/MHC and emigrate to the peripheral organs. C1 DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. 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. RI Koyasu, Shigeo/J-5583-2015 OI Koyasu, Shigeo/0000-0001-9585-3038 FU NIAID NIH HHS [AI-19807, AI-33017]; NIDDK NIH HHS [DK-47677] NR 97 TC 48 Z9 48 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1996 VL 157 IS 10 BP 4379 EP 4389 PG 11 WC Immunology SC Immunology GA VR793 UT WOS:A1996VR79300016 PM 8906813 ER PT J AU Dean, LS Mickel, M Bonan, R Holmes, DR ONeill, WW Palacios, IF Rahimtoola, S Slater, JN Davis, K Kennedy, JW AF Dean, LS Mickel, M Bonan, R Holmes, DR ONeill, WW Palacios, IF Rahimtoola, S Slater, JN Davis, K Kennedy, JW TI Four-year follow-up of patients undergoing percutaneous balloon mitral commissurotomy - A report from the National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CLOSED COMMISSUROTOMY; SHORT-TERM; STENOSIS; CATHETER; VALVOTOMY; VALVE AB Objectives. This study reports the long-term outcome of patients undergoing percutaneous balloon mitral commissurotomy who were enrolled in the National Heart, Lung, and Blood Institute (NHLBI) Balloon Valvuloplasty Registry. Background. The NHLBI established the multicenter Balloon Valvuloplasty Registry in November 1987 to assess both short- and long-term safety and efficiency of percutaneous balloon mitral commissurotomy. Methods. Between November 1987 and October 1989, 736 patients greater than or equal to 18 years old underwent percutaneous balloon mitral commissurotomy at 23 registry sites in North America. The maximal follow-up period was 5.2 years. Results. The actuarial survival rate was 93 +/- 1% (mean +/- SD), 90 +/- 1.2%, 87 +/- 1.4% and 84 +/- 1.6% at 1, 2, 3 and 4 years, respectively. Eighty percent of the patients were alive and free of mitral surgery or repeat balloon mitral commissurotomy at 1 year. The event-free survival rate was 80 +/- 1.5% at 1 year, 71 +/- 1.7% at 2 years, 66 +/- 1.8% at 3 years and 60 +/- 2.0% at 4 gears, important univariable predictors of actuarial mortality at 4 years included age > 70 years (51% survival), New York Heart Association functional class IV (41% survival) and baseline echocardiographic scare > 12 (24% survival), Multivariable predictors of mortality included functional class IV, higher echocardiographic score and higher postprocedural pulmonary artery systolic and left ventricular end-diastolic pressures (p < 0.01), Conclusions. Percutaneous balloon mitral commissurotomy has a favorable effect on the hemodynamic variables of mitral stenosis, and long-term follow-up data suggest that it is a viable alternative dth respect to surgical commissurotomy in selected patients. C1 UNIV WASHINGTON, DEPT MED, SEATTLE, WA USA. UNIV MONTREAL, MONTREAL, PQ, CANADA. MAYO CLIN & MAYO FDN, ROCHESTER, MN 55905 USA. WILLIAM BEAUMONT HOSP, DIV CARDIOL, ROYAL OAK, MI 48072 USA. MASSACHUSETTS GEN HOSP, CARDIAC UNIT, BOSTON, MA 02114 USA. UNIV SO CALIF, DIV CARDIOL, LOS ANGELES, CA USA. ST LUKES ROOSEVELT HOSP, CARDIAC CATHETERIZAT LAB, NEW YORK, NY 10025 USA. RP Dean, LS (reprint author), UNIV ALABAMA, DIV CARDIOVASC DIS, UAB STN, DEPT MED, BIRMINGHAM, AL 35294 USA. FU NHLBI NIH HHS [1-HV-78100] NR 25 TC 84 Z9 93 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 15 PY 1996 VL 28 IS 6 BP 1452 EP 1457 DI 10.1016/S0735-1097(96)00350-6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VT310 UT WOS:A1996VT31000003 PM 8917257 ER PT J AU PerezBalino, NA Masoli, OH Meretta, AH Rodriguez, A Cragnolino, DE Perrone, S Boullon, F Mele, E Palacios, I Brown, KA AF PerezBalino, NA Masoli, OH Meretta, AH Rodriguez, A Cragnolino, DE Perrone, S Boullon, F Mele, E Palacios, I Brown, KA TI Amrinone stimulation test: Ability to predict improvement in left ventricular ejection fraction after coronary bypass surgery in patients with poor baseline left ventricular function SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; MYOCARDIAL OXYGEN-CONSUMPTION; CONGESTIVE HEART-FAILURE; DOBUTAMINE ECHOCARDIOGRAPHY; ARTERY DISEASE; COMPUTED-TOMOGRAPHY; VIABLE MYOCARDIUM; F-18 DEOXYGLUCOSE; N-13 AMMONIA; WALL-MOTION AB Objectives. This study sought to det-ermine whether the response! to amrinone in patients with severe baseline left ventricular dysfunction can predict improvement in left ventricular ejection fraction after coronary artery bypass graft surgery, Background, Previous studies have suggested that the inotropic response to dobutamine can identify viable myocardium in the setting of chronic coronary disease and left ventricular dysfunction, However, increased oxygen demand stimulated by dobutamine can lead to superimposition of ischemia on the hibernating stale, potentially confounding interpretation of results, Amrinone is an inotropic agent that does not critically augment myocardial oxygen demand and may be useful for identification of hibernating myocardium in thf chronically ischemic state, Methods. Forty-four consecutive patients with coronary artery disease and left ventricular ejection fraction < 40% referred far coronary artery bypass graft surgery underwent amrinone stimulation (1 mg/kg body weight). Left ventricular ejection fraction nas determined before amrinone stimulation, 20 min after infusion and 21 days after bypass surgery. Results. Baseline ejection fraction was 28 +/- 7% (mean +/- SD), Ejection fraction increased to 35 +/- 5% after amrinone stimulation (p < 0.0001) and, to 33 +/- 6% after bypass surgery (p < 0,0001), Postbypass ejection fraction was significantly correlated with postamrinone ejection fraction (r = 0.65, p < 0.0001), Furthermore, the change in ejection fraction from baseline to after bypass surgery aas highly correlated with the change in ejection fraction after amrinone stimulation (r = 0.75, p < 0.0001), Of 13 patients with an increase in ejection fraction greater than or equal to 10% after amrinone, all 13 had an increase of at least 8% and II (85%) of 13 had an increase greater than or equal to 10% after bypass surgery, In contrast, of 31 patients with an increase in ejection fraction < 10% after amrinone, only 2 (6%) had an increase greater than or equal to 10% (p < 0.0001) and 28 (90%) of 31 had an increase < 5% after bypass surgery, Conclusions. Augmentation of myocardial contraction by amrinone in patients with chronic coronary artery disease and severe baseline left ventricular dysfunction predicts improvement in left ventricular ejection fraction after coronary artery bypass graft surgery. C1 SANATORIO ANCHORENA,CARDIOL UNIT,BUENOS AIRES,DF,ARGENTINA. MASSACHUSETTS GEN HOSP,CARDIOL UNIT,BOSTON,MA 02114. UNIV VERMONT,COLL MED,CARDIOL UNIT,BURLINGTON,VT. NR 35 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 15 PY 1996 VL 28 IS 6 BP 1488 EP 1492 DI 10.1016/S0735-1097(96)00332-4 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VT310 UT WOS:A1996VT31000008 PM 8917262 ER PT J AU Schoenfeld, DA AF Schoenfeld, DA TI Long-term follow-up in AIDS clinical trials SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Statistical Issues in HIV/AIDS Research CY JUN 12-13, 1995 CL NIH, BETHESDA, MD HO NIH ID DESIGN AB There are several different strategies for the follow-up of patients on AIDS clinical trials. In some trials, data are only collected until patients stop protocol therapy for any reason. Alternatively, patients are followed until they have disease progression or the study ends. It has been suggested in some trials that patients have data collected after they have stopped protocol therapy either because they reached a study endpoint or all patients on the trial have been switched to the superior therapy. The effect of these strategies on the conclusions that can be drawn from a trial will be described using simulations. To calculate the operating characteristics of a strategy that involves a primary and a secondary endpoint, it is necessary to formalize the notion that the results of a secondary analysis support or contradict the primary analysis. RP Schoenfeld, DA (reprint author), MASSACHUSETTS GEN HOSP,FRUIT ST,BOSTON,MA 02114, USA. FU PHS HHS [N01-95030] NR 2 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 1996 VL 15 IS 21-22 BP 2359 EP 2366 PG 8 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA VQ193 UT WOS:A1996VQ19300009 PM 8931206 ER PT J AU Krenger, W Cooke, KR Crawford, JM Sonis, ST Simmons, R Pan, LY Delmonte, J Karandikar, M Ferrara, JLM AF Krenger, W Cooke, KR Crawford, JM Sonis, ST Simmons, R Pan, LY Delmonte, J Karandikar, M Ferrara, JLM TI Transplantation of polarized type 2 donor T cells reduces mortality caused by experimental graft-versus-host disease SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; MINOR HISTOCOMPATIBILITY ANTIGENS; NECROSIS-FACTOR-ALPHA; MONOCLONAL-ANTIBODY; MURINE MODEL; STIMULATORY FACTOR; LETHAL GRAFT; IFN-GAMMA; MICE; CYTOKINES AB Acute graft-versus-host disease (GVHD) is thought to be initiated by alloreactive type 1 T cells that secrete gamma-interferon (IFN-gamma). IFN-gamma induces the production of inflammatory cytokines, e.g., tumor necrosis factor-alpha and interleukin (IL)-1, which are the distal mediators of GVHD. We demonstrate that the transplantation of polarized type 2 murine T cells (i.e., cells secreting IL-4 but not IFN-gamma) together with T-cell-depleted bone marrow results in a significant increase in survival (P<0.001) after bone marrow transplantation across minor histocompatibility barriers (E10.BR-->CBA/J). Further analysis demonstrated that increased survival ill recipients of polarized type 2 T cells correlated with diminished production of both IFN-gamma and tumor necrosis factor-alpha but with increases in IL-4 2 weeks after transplantation. Despite improved survival, histologic changes of GVHD were evident in oral mucosal and hepatic tissues at 7 weeks after bone mac-row transplantation, These data provide further evidence that inflammatory cytokines in the immediate posttransplant period are pivotal to the development of mortality but that they do not correlate with individual target organ damage. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV ORAL MED ORAL & MAXILLOFACIAL SURG & DENT,BOSTON,MA 02115. RP Krenger, W (reprint author), DANA FARBER CANC INST,DEPT PEDIAT ONCOL,D1640,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA39542]; NIDDK NIH HHS [DK39512] NR 48 TC 51 Z9 52 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 1996 VL 62 IS 9 BP 1278 EP 1285 DI 10.1097/00007890-199611150-00018 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA VU117 UT WOS:A1996VU11700018 PM 8932272 ER PT J AU Li, SF Neethling, FA Taniguchi, S Yeh, JC Kobayashi, T Ye, Y Koren, E Cummings, RD Cooper, DKC AF Li, SF Neethling, FA Taniguchi, S Yeh, JC Kobayashi, T Ye, Y Koren, E Cummings, RD Cooper, DKC TI Glycans derived from porcine stomach mucin are effective inhibitors of natural anti-alpha-galactosyl antibodies in vitro and after intravenous infusion in baboons. SO TRANSPLANTATION LA English DT Article ID ORGAN XENOTRANSPLANTATION; CARBOHYDRATE ANTIGENS; PIG-TISSUES; MODEL; CELLS; REJECTION; OLIGOSACCHARIDES; PK15 AB The current shortage of donor organs has stimulated investigation of pig-to-human xenotransplantation as a practical alternative to allotransplantation. However, a major obstacle to this xenotransplantation is hyperacute rejection, which is believed to be initiated. by the interaction of natural anti-alpha-galactosyl (alpha Gal) antibodies with alpha Gal epitopes on pig vascular endothelium. Previously, we reported that neutral oligosaccharides derived from porcine stomach mucin (PSM) are effective inhibitors of human anti-alpha Gal IgG in vitro. We now report that O-glycans derived from PSM by beta-elimination (PSMO) reduce the cytotoxicity of both baboon and human sera to pig kidney (PK15) cells in vitro. Crude PSM had some inhibitory effect in vitro, but PSMO were more than 100 times more potent. Moreover, 1 mu g/ml of beta-eliminated PSMO that bound to an immunoaffinity column of anti-alpha Gal antibodies were four times mope efficient than total PSMO in protecting PK15 cells from the cytotoxic effect of baboon or human sera. flood recovered from baboons after intravenous infusion of PMSO also showed significant protection of PK15 cells. We conclude that PSMO eluted from an anti-alpha Gal immunoaffinity column demonstrate potent inhibitory effects against baboon and human serum cytotoxicity to PK15 cells in vitro and when administered intravenously. PSM may provide a cheap and readily available source of glycans that will be of therapeutic value in the prevention of hyperacute rejection. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. BAPTIST MED CTR,OKLAHOMA TRANSPLANTAT INST,OKLAHOMA CITY,OK 73112. UNIV OKLAHOMA,HLTH SCI CTR,DEPT BIOCHEM & MOL BIOL,OKLAHOMA CITY,OK 73190. OKLAHOMA MED RES FDN,OKLAHOMA CITY,OK 73104. FU PHS HHS [37626] NR 26 TC 16 Z9 17 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 NOV 15 PY 1996 VL 62 IS 9 BP 1324 EP 1331 DI 10.1097/00007890-199611150-00026 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA VU117 UT WOS:A1996VU11700026 PM 8932280 ER PT J AU Vance, EA Soiffer, RJ McDonald, GB Myerson, D Fingeroth, J Ritz, J AF Vance, EA Soiffer, RJ McDonald, GB Myerson, D Fingeroth, J Ritz, J TI Prevention of transmission of hepatitis G virus in bone marrow transplantation by treating the donor with alpha-interferon SO TRANSPLANTATION LA English DT Article ID C VIRUS; INFECTION; RECIPIENTS AB Transmission of hepatitis C virus (HCV) in the setting of allogeneic bone marrow transplantation can occur through an infected marrow donor. Prevention of transmission may reduce the risks of peritransplant complications. We describe a 43-year-old patient with chronic myelogenous leukemia whose HLA-identical donor was found to be HCV antibody positive and HCV RNA positive by polymerase chain reaction (PCR). The patient was HCV antibody negative and HCV RNA negative by PCR of the serum. For 6 months before bone marrow transplantation, the donor was treated with ol-interferon at a standard dose. After 3 months, HCV RNA was no longer detectable by PCR. Interferon was discontinued 1 week before harvest. Bone marrow cellularity was normal, Engraftment was prompt. The recipient's serum. remained negative for HCV RNA at 1, 3, 5, and 10 months after transplantation. Hepatitis C transmission hom a viremic donor to an HCV-seronegative recipient may be preventable by treating the donor with alpha-interferon. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02146. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV INFECT DIS,BOSTON,MA 02146. FRED HUTCHINSON CANC RES CTR,GASTROENTEROL HEPATOL SECT,SEATTLE,WA 98104. FRED HUTCHINSON CANC RES CTR,PATHOL SECT,SEATTLE,WA 98104. UNIV WASHINGTON,SEATTLE,WA 98104. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NIAID NIH HHS [AI29530] NR 10 TC 27 Z9 27 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 1996 VL 62 IS 9 BP 1358 EP 1360 DI 10.1097/00007890-199611150-00032 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA VU117 UT WOS:A1996VU11700032 PM 8932286 ER PT J AU Wu, LJ Gerard, NP Wyatt, R Choe, H Parolin, C Ruffing, N Borsetti, A Cardoso, AA Desjardin, E Newman, W Gerard, C Sodroski, J AF Wu, LJ Gerard, NP Wyatt, R Choe, H Parolin, C Ruffing, N Borsetti, A Cardoso, AA Desjardin, E Newman, W Gerard, C Sodroski, J TI CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5 SO NATURE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; ENVELOPE GLYCOPROTEINS; T-CELL; BINDING; CD4; INFECTION; IDENTIFICATION; EPITOPES; FUSION AB FOR efficient entry into target cells, primary macrophage-tropic and laboratory-adapted human immunodeficiency viruses type 1 (HIV-1) require particular chemokine receptors, CCR-5 and CXCR-4, respectively, as well as the primary receptor CD4 (refs 1-6). Here we show that a complex of gp120, the exterior envelope glycoprotein, of macrophage-tropic primary HIV-1 and soluble CD4 interacts specifically with CCR-5 and inhibits the binding of the natural CCR-5 ligands, macrophage inflammatory protein (MIP)-1 alpha and MLP-1 beta (refs 7, 8). The apparent affinity of the interaction between gp120 and CCR-5 was dramatically lower in the absence of soluble CD4. Additionally, in the absence of gp120, an interaction between a two-domain CD4 fragment and CCR-5 was observed. A gp120 fragment retaining the CD4-binding site and overlapping epitopes was able to interact with CCR-5 only if the V3 loop, which can specify HIV-1 tropism and chemokine receptor choice(2,9-11), was also present on the molecule. Neutralizing antibodies directed against either CD4-induced or V3 epitopes on gp120 blocked the interaction of gp120-CD4 complexes with CCR-5. These results suggest that HIV-1 attachment to CD4 creates a high-affinity binding site for CCR-5, leading to membrane fusion and virus entry. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIOROL,BOSTON,MA 02115. LEUKOSITE INC,CAMBRIDGE,MA 02142. CHILDRENS HOSP,INA SUE PERLMUTTER LAB,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT PEDIAT,BOSTON,MA 02115. UNIV PADUA,INST MICROBIOL,I-35121 PADUA,ITALY. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. RI borsetti, alessandra/K-4103-2016 NR 29 TC 982 Z9 1006 U1 4 U2 37 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD NOV 14 PY 1996 VL 384 IS 6605 BP 179 EP 183 DI 10.1038/384179a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VT336 UT WOS:A1996VT33600069 PM 8906795 ER PT J AU Watanabe, G Howe, A Lee, RJ Albanese, C Shu, IW Karnezis, AN Zon, L Kyriakis, J Rundell, K Pestell, RG AF Watanabe, G Howe, A Lee, RJ Albanese, C Shu, IW Karnezis, AN Zon, L Kyriakis, J Rundell, K Pestell, RG TI Induction of cyclin D1 by simian virus 40 small tumor antigen SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SMALL-T-ANTIGEN; ACTIVATED PROTEIN-KINASE; CREB TRANSCRIPTIONAL STIMULATION; A-PHOSPHORYLATED CREB; RNA-POLYMERASE-II; MAP KINASE; C-JUN; CELL-CYCLE; GROWTH-FACTOR; RETINOBLASTOMA PROTEIN AB Cell-cycle progression is mediated by a coordinated interaction between cyclin-dependent kinases and their target proteins including the pRB and E2F/DP-1 complexes. Immunoneutralization and antisense experiments have established that the abundance of cyclin D1, a regulatory subunit of the cyclin-dependent kinases, may be rate-limiting for G(1) phase progression of the cell cycle. Simian virus 40 (SV40) small tumor (t) antigen is capable of promoting G(1) phase progression and augments substantially the efficiency of SV40 transformation through several distinct domains, In these studies, small t antigen stimulated cyclin D1 promoter activity 7-fold, primarily through an AP-1 binding site at -954 with additional contributions from a CRE site at -57. The cyclin D1 AP-I and CRE sites were sufficient for activation by small t antigen when linked to an heterologous promoter, Point mutations of small t antigen between residues 97-103 that reduced PP2A binding were partially defective in the induction of the cyclin DI promoter, These mutations also reduced activation of MEK1 and two distinct members of the mitogen-activated protein kinase family, the ERKs (extracellular signal regulated kinases) and the SAPKs (stress activated protein kinases), in transfected cells, Dominant negative mutants of either MEK1, ERK or SEK1, reduced small t-dependent induction of the cyclin D1 promoter, SV40 small t induction of the cyclin D1 promoter involves both the ERK and SAPK pathways that together may contribute to the proliferative and transformation enhancing activity of small t antigen. C1 NORTHWESTERN UNIV,DEPT MED,CHICAGO,IL 60611. NORTHWESTERN UNIV,LURIE CANC CTR,DEPT MICROBIOL & IMMUNOL,CHICAGO,IL 60611. CHILDRENS HOSP,DIV HEMATOL & ONCOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MED SERV,DIABET RES LAB,CHARLESTOWN,MA 02129. FU NCI NIH HHS [T32 CA009560, CA 21327, R 29CA 70896-01, R29 CA070896, R01 CA021327]; NIGMS NIH HHS [5 T32 GM0852-10] NR 58 TC 183 Z9 186 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 12 PY 1996 VL 93 IS 23 BP 12861 EP 12866 DI 10.1073/pnas.93.23.12861 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VT054 UT WOS:A1996VT05400036 PM 8917510 ER EF