FN Thomson Reuters Web of Science™ VR 1.0 PT J AU DOU, QP MOLNAR, G PARDEE, AB AF DOU, QP MOLNAR, G PARDEE, AB TI CYCLIN D1 CDK2 KINASE IS PRESENT IN A G1 PHASE-SPECIFIC PROTEIN COMPLEX YI1 THAT BINDS TO THE MOUSE THYMIDINE KINASE GENE PROMOTER SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RETINOBLASTOMA PROTEIN; VIRAL ONCOPROTEINS; DNA-SEQUENCES; E2F; IDENTIFICATION; TRANSCRIPTION; EXPRESSION; STABILITY; GROWTH; CELLS AB Our studies provide evidence for the presence of cyclin D1 in an early G1 cycle-specific DNA binding complex Yi1. Previously we identified several complexes including Yi and E2F that at different times during G0 to S transition bind to three distinct DNA sequences (MT1, MT2, MT3) located in the mouse thymidine kinase upstream promoter. These various complexes contain DNA binding proteins (Sp1, E2F, p110, p60), cyclins A and E, cyclin-dependent kinase 2 (cdk2), and retinoblastoma-related proteins (pRB, p107). Here we report that Yi1 is different from the E2F complexes. Yi1 contains cyclin D1/cdk2 kinase as shown by using specific antibodies to cyclins, cdks and the Yi1 DNA-binding protein in gel retardation, western blotting, and immunoprecipitation assays. Yi1 binding is specific to a consensus sequence different from that of E2F. (C) 1994 Academic Press, Inc. C1 PITTSBURGH CANC INST,DIV BASIC RES,PITTSBURGH,PA 15261. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP DOU, QP (reprint author), UNIV PITTSBURGH,SCH MED,DEPT PHARMACOL,W902,BIOMED SCI TOWER,PITTSBURGH,PA 15261, USA. FU NIGMS NIH HHS [GM24571] NR 26 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 30 PY 1994 VL 205 IS 3 BP 1859 EP 1868 DI 10.1006/bbrc.1994.2887 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PZ997 UT WOS:A1994PZ99700052 PM 7811275 ER PT J AU KOCHEVAR, IE BOUVIER, J LYNCH, M LIN, CW AF KOCHEVAR, IE BOUVIER, J LYNCH, M LIN, CW TI INFLUENCE OF DYE AND PROTEIN LOCATION ON PHOTOSENSITIZATION OF THE PLASMA-MEMBRANE SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE PHOTOSENSITIZATION; SINGLET OXYGEN; PLASMA MEMBRANE; PHOTODYNAMIC THERAPY; MEMBRANE POTENTIAL; GLUCOSE TRANSPORT; PROLINE TRANSPORT; 5'-NUCLEOTIDASE ID ROSE-BENGAL; PHOTODYNAMIC-ACTION; CELL-MEMBRANES; TRANSPORT-SYSTEMS; MEROCYANINE-540; MECHANISM; 5'-NUCLEOTIDASE; INVOLVEMENT; THERAPY; OXYGEN AB Two membrane-photosensitizing dyes were used to investigate whether selected sites in the plasma membrane vary in their sensitivity to damage by singlet oxygen (O-1(2)*) and, if so, what factors are responsible for the variation. The relative ability of Rose bengal (RB) and merocyanine 540 (MC540), both of which localize in the plasma membrane and produce O-1(2)*, to photosensitize five plasma membrane functions in P388D(1) cells was evaluated. The five membrane functions assessed were: plasma membrane potential, proline transport, facilitated glucose diffusion, 5'-nucleotidase activity, and dye exclusion. Photosensitization efficiency by RB varied by a factor of 188 for these membrane functions, whereas for MC540 a range of only 24 was found. RB was a more efficient photosensitizer than MC540 but the relative efficiencies varied with the membrane function. The wide range of P-50 values for RB suggests that it binds selectively to membrane sites where it causes damage with high efficiency; possibly a non-O-1(2)* mechanism is involved. In contrast, MC540 photosensitized the three membrane functions involving integral membrane proteins about equally suggesting that differences are due to small variations in the distribution of MC540 in the plasma membrane and/or variations in the inherent reactivity of the membrane targets with O-1(2)*. The results indicate that the lability of membrane sites to photosensitization depends both on their inherent reactivity with O-1(2)* and the relative location of specific protein and dye molecules. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT UROL, BOSTON, MA USA. RP KOCHEVAR, IE (reprint author), MASSACHUSETTS GEN HOSP, DEPT DERMATOL, WELLMAN LABS PHOTOMED, WEL-224, BOSTON, MA 02114 USA. FU NIGMS NIH HHS [R01 GM30755] NR 28 TC 47 Z9 47 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 EI 0006-3002 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD DEC 30 PY 1994 VL 1196 IS 2 BP 172 EP 180 DI 10.1016/0005-2736(94)00236-3 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QB836 UT WOS:A1994QB83600009 PM 7841181 ER PT J AU DEACON, TW PAKZABAN, P ISACSON, O AF DEACON, TW PAKZABAN, P ISACSON, O TI THE LATERAL GANGLIONIC EMINENCE IS THE ORIGIN OF CELLS COMMITTED TO STRIATAL PHENOTYPES - NEURAL TRANSPLANTATION AND DEVELOPMENTAL EVIDENCE SO BRAIN RESEARCH LA English DT Article DE STRIATAL GRAFT; ALLOGRAFT; CELL FATE; HUNTINGTONS DISEASE; NEURONAL REGENERATION; DARPP-32; CALBINDIN; ACETYLCHOLINESTERASE; TYROSINE HYDROXYLASE ID ACID-LESIONED STRIATUM; RAT NEOSTRIATAL GRAFTS; ELECTRON-MICROSCOPIC ANALYSIS; HOST DOPAMINERGIC AFFERENTS; INTRASTRIATAL GRAFTS; EFFERENT PROJECTIONS; HUNTINGTONS-DISEASE; PRIMARY CULTURE; MESSENGER-RNA; TISSUE GRAFTS AB In order to determine whether the lateral ganglionic eminence (LGE) of the fetal telencephalon is the primary source of striatal precursors in striatal transplants and tissue cultures, cells derived exclusively from the LGE of fetal rat brains were transplanted into the quinolinic-acid-lesioned striatum of adult rats. After 2-3 months they produced grafts that were almost entirely AChE-positive as well as DARPP-32-, TH-, and calbindin-immunoreactive. The grafts were integrated into the host striatum so that host corticofugal fiber tracts interdigitated with graft tissues similar to the way they penetrate the gray matter of the normal striatum. Fast Blue dye injected into the ipsilateral globus pallidus of LGE grafted produced retrogradely labeled neurons within the grafts, but Fluorogold dye injected into the ipsilateral substantia nigra did not. In a separate experiment using DARPP-32-immunohistochemstry as a striatal marker, fetal (E16) and neonatal (P2) rat brains showed DARPP-32 immunoreactivity in the LGE but not in the adjacent medial ganglionic eminence (MGE). In summary, both fetal LGE cells and LGE grafts express specific striatal markers, and LGE grafts integrate into the host striatum and innervate the major striatal efferent target within the host brain. These data suggest that the LGE is the origin of cells committed to striatal phenotypes in the developing brain. C1 HARVARD UNIV, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROSURG, BOSTON, MA 02115 USA. BOSTON UNIV, BOSTON, MA 02115 USA. RP MCLEAN HOSP, MRC 119, NEUROREGENERAT LAB, 115 MILL ST, BELMONT, MA 02178 USA. FU NINDS NIH HHS [5T32 NS07340, NS29178, NS30064] NR 41 TC 150 Z9 154 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD DEC 30 PY 1994 VL 668 IS 1-2 BP 211 EP 219 DI 10.1016/0006-8993(94)90526-6 PG 9 WC Neurosciences SC Neurosciences & Neurology GA QB354 UT WOS:A1994QB35400023 PM 7704606 ER PT J AU TONTONOZ, P HU, ED SPIEGELMAN, BM AF TONTONOZ, P HU, ED SPIEGELMAN, BM TI STIMULATION OF ADIPOGENESIS IN FIBROBLASTS BY PPAR-GAMMA-2, A LIPID-ACTIVATED TRANSCRIPTION FACTOR SO CELL LA English DT Article ID ENHANCER-BINDING-PROTEIN; PHOSPHOENOLPYRUVATE CARBOXYKINASE GTP; HORMONE RECEPTOR SUPERFAMILY; PEROXISOME PROLIFERATOR; GENE-EXPRESSION; RETINOIC ACID; FATTY-ACIDS; ADIPOCYTE DIFFERENTIATION; 3T3-L1 PREADIPOCYTES; NUCLEAR RECEPTORS AB Peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2) is an adipocyte-specific nuclear hormone receptor that has recently been identified as a key regulator of two fat cell enhancers. Transcriptional activation by PPAR gamma 2 is potentiated by a variety of lipids and lipid-like compounds, including naturally occurring polyunsaturated fatty acids. We demonstrate here that retroviral expression of PPAR gamma 2 stimulates adipose differentiation of cultured fibroblasts. PPAR activators promote the differentiation of PPAR gamma 2-expressing cells in a dose-dependent manner. C/EBP alpha, a second transcription factor induced during adipocyte differentiation, can cooperate with PPAR gamma 2 to stimulate the adipocyte program dramatically. Our results suggest that the physiologic role of PPAR gamma 2 is to regulate development of the adipose lineage in response to endogenous activators and that this factor may serve to link the process of adipocyte differentiation to systemic lipid metabolism. C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. RP TONTONOZ, P (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK31405]; NIGMS NIH HHS [T32 GM007753, T32 GM07753] NR 49 TC 2520 Z9 2590 U1 21 U2 111 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD DEC 30 PY 1994 VL 79 IS 7 BP 1147 EP 1156 DI 10.1016/0092-8674(94)90006-X PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PZ860 UT WOS:A1994PZ86000006 PM 8001151 ER PT J AU OUWENS, DM VANDERZON, GCM PRONK, GJ BOS, JL MOLLER, W CHEATHAM, B KAHN, CR MAASSEN, JA AF OUWENS, DM VANDERZON, GCM PRONK, GJ BOS, JL MOLLER, W CHEATHAM, B KAHN, CR MAASSEN, JA TI A MUTANT INSULIN-RECEPTOR INDUCES FORMATION OF A SHC-GROWTH FACTOR-RECEPTOR BOUND PROTEIN-2 (GRB2) COMPLEX AND P21(RAS)-GTP WITHOUT DETECTABLE INTERACTION OF INSULIN-RECEPTOR SUBSTRATE-1 (IRS1) WITH GRB2 - EVIDENCE FOR IRS1-INDEPENDENT P21(RAS)-GTP FORMATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KINASE DOMAIN AUTOPHOSPHORYLATION; GUANINE-NUCLEOTIDE EXCHANGE; SIGNAL-TRANSDUCTION; TYROSINE KINASES; PHOSPHATIDYLINOSITOL 3'-KINASE; GENE-EXPRESSION; RAS; ACTIVATION; P21RAS; PHOSPHORYLATION AB The activation of p21(ras) by receptor tyrosine kinases involves the translocation of the growth factor receptor bound protein 2-mammalian son of sevenless protein (Grb2.SOS) complex to the plasma membrane where p21(ras) is localized, Insulin receptors induce p21(ras)-GTP formation by two possible mechanisms: tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) and its subsequent association with Grb2, or Shc phosphorylation and its subsequent association with Grb2. We investigated the contribution of the major tyrosine autophosphorylation sites Tyr(1158), Tyr(1162), and Tyr(1163) of the insulin receptor to IRS1.Grb2 and Shc.Grb2 association and the formation of p21(ras)-GTP. Chinese hamster ovary-derived cell lines were used overexpressing mutant insulin receptors in which the major tyrosine autophosphorylation sites were stepwise replaced by phenylalanines. In cell lines expressing wild type or mutant Y1158F,Y1162,Y1163 (FYY) receptors, insulin stimulated tyrosine phosphorylation of IRS1 and She and the formation of IRS1.Grb2 and Shc.Grb2 protein complexes, together with an increase in p21(ras)-GTP. Cell lines expressing mutant Y1158,Y1162F,Y1163F (YFF) receptors showed insulin-induced tyrosine phosphorylation of Shc, Shc.Grb2 complex formation, and p21(ras)-GTP formation, whereas tyrosine phosphorylation of IRS1 was strongly decreased and formation of IRS1.Grb2 complexes was undetectable. The activity of FYY and YFF receptors to mediate p21(ras)-GTP formation correlated with their activity to induce She phosphorylation and Shc.Grb2 association. The mutant insulin receptors Y1158F,Y1162F,Y1163 and Y1158F,Y1162F,Y1163F were inactive in inducing any of these responses, We conclude that phosphorylation of Tyr(1158) and Tyr(1162) of the insulin receptor is linked to distinct post-receptor processes and that YFF receptors generate p21(ras)-GTP via the Shc.Grb2 pathway rather than one involving IRS1.Grb2 interaction. C1 LEIDEN STATE UNIV,DEPT BIOCHEM MED,SYLVIUS LAB,PROT SYNTH & HORMONE REGULAT SECT,2333 AL LEIDEN,NETHERLANDS. UNIV UTRECHT,PHYSIOL CHEM LAB,3584 CG UTRECHT,NETHERLANDS. JOSLIN DIABET CTR,BOSTON,MA 02215. RI Ouwens, Margriet/H-2442-2013 OI Ouwens, Margriet/0000-0001-6709-2702 NR 57 TC 69 Z9 69 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 30 PY 1994 VL 269 IS 52 BP 33116 EP 33122 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QA638 UT WOS:A1994QA63800058 PM 7806540 ER PT J AU BURTON, MD MARK, EJ SHEPARD, JAO GAVARASANA, S WAIN, JC KAZEMI, H AF BURTON, MD MARK, EJ SHEPARD, JAO GAVARASANA, S WAIN, JC KAZEMI, H TI A 35-YEAR-OLD SMOKER WITH AN AIR-FLUID LEVEL IN AN UPPER-LOBE BULLA - ADENOCARCINOMA OF THE LUNG, ARISING IN A BULLA - BULLOUS EMPHYSEMA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID SPONTANEOUS PNEUMOTHORAX; PULMONARY; ASPERGILLOSIS; CARCINOMA; COLLAGEN; DISEASE; CANCER C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP BURTON, MD (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 46 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 29 PY 1994 VL 331 IS 26 BP 1761 EP 1767 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PZ266 UT WOS:A1994PZ26600008 ER PT J AU KELLY, CP KELSEY, PB GRAEMECOOK, F AF KELLY, CP KELSEY, PB GRAEMECOOK, F TI CASE-30-1994 - ANTIENDOMYSIAL ANTIBODIES AND CELIAC-DISEASE - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP KELLY, CP (reprint author), BOSTON UNIV,MED CTR,BOSTON,MA 02118, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 29 PY 1994 VL 331 IS 26 BP 1776 EP 1776 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PZ266 UT WOS:A1994PZ26600023 ER PT J AU MULROW, CD CORNELL, JA HERRERA, CR KADRI, A FARNETT, L AGUILAR, C AF MULROW, CD CORNELL, JA HERRERA, CR KADRI, A FARNETT, L AGUILAR, C TI HYPERTENSION IN THE ELDERLY - IMPLICATIONS AND GENERALIZABILITY OF RANDOMIZED TRIALS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID CORONARY HEART-DISEASE; BLOOD-PRESSURE; CARDIOVASCULAR HEALTH; SYSTOLIC HYPERTENSION; RISK-FACTORS; MANAGEMENT; MORTALITY; MORBIDITY; PREVALENCE; THERAPY AB Objective.-To estimate morbidity and mortality benefits of drug therapy for hypertensive elderly subjects, compare these benefits with effects in younger subjects, and provide a framework for generalizing results derived from trials to actual patients. Data Sources.-A literature search using MEDLINE from 1966 to 1993, references from reviews and trial articles, and experts. Study Selection.-Randomized trials lasting at least 1 year that evaluated effects of drug treatment on morbidity and mortality outcomes in hypertensive persons. Data Extraction.-Four independent reviewers appraised protocol characteristics and quality of selected trials. Data Synthesis.-There were 13 trials involving 16 564 elderly persons (age 60 years and older). The prevalence of cardiovascular risk factors, cardiovascular disease, and competing comorbid diseases was lower among trial participants than the general population of hypertensive elderly persons. When the six large high-quality trials were combined, trial results showed 43 subjects (95% confidence interval [CI], 31 to 69) and 61 subjects (95% CI, 39 to 141) needed to be treated for 5 years to prevent one cerebrovascular event and one coronary heart disease event, respectively. Including the other seven trials did not change the results significantly. Only 18 subjects (95% CI, 14 to 25) needed to be treated to prevent one cardiovascular event (cerebrovascular or cardiac). Twelve trials in primarily younger and middle-aged adults involved approximately 33 000 persons. For all outcomes except cardiac mortality, two to four times as many of the younger subjects as the older subjects needed to be treated for 5 years to prevent morbid and mortal events. No significant effect on cardiac mortality was seen among younger subjects, while 78 older subjects (95% CI, 50 to 180) needed to be treated to prevent a fatal cardiac event. Conclusions.-Randomized trials demonstrate that treating healthy older persons with hypertension is highly efficacious. Five-year morbidity and mortality benefits derived from trials are greater for older than younger subjects. Extrapolating benefits from trials to individual patients is difficult, but should take into account multiple issues including the patient's risk factors, preexisting cardiovascular disease, and competing comorbid illnesses. C1 UNIV TEXAS, HLTH SCI CTR, HOUSTON, TX USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX USA. RP MULROW, CD (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR, CTR GERIATR RES EDUC & CLIN, 7400 MERTON MINTER BLVD, SAN ANTONIO, TX 78284 USA. NR 51 TC 188 Z9 189 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 28 PY 1994 VL 272 IS 24 BP 1932 EP 1938 DI 10.1001/jama.272.24.1932 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PX927 UT WOS:A1994PX92700039 PM 7990246 ER PT J AU BILEZIKIAN, JP BAILEY, L ELMER, PJ FAVUS, MJ GO, VLW GOLDRING, SR HOLT, LH INSOGNA, KL KRIMGOLD, B MALLETTE, LE SHAPIRO, JR STJEOR, ST STERN, PH TILLEY, BC YAMAMOTO, ME AF BILEZIKIAN, JP BAILEY, L ELMER, PJ FAVUS, MJ GO, VLW GOLDRING, SR HOLT, LH INSOGNA, KL KRIMGOLD, B MALLETTE, LE SHAPIRO, JR STJEOR, ST STERN, PH TILLEY, BC YAMAMOTO, ME TI OPTIMAL CALCIUM INTAKE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 UNIV FLORIDA,DEPT FOOD SCI & HUMAN NUTR,GAINESVILLE,FL 32611. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. UNIV CHICAGO,PRITZKER SCH MED,DEPT MED,CHICAGO,IL 60637. UNIV CHICAGO,PRITZKER SCH MED,GEN CLIN RES CTR,CHICAGO,IL 60637. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,DIV CLIN NUTR,CLIN NUTR RES UNIT,LOS ANGELES,CA 90024. HARVARD UNIV,SCH MED,BOSTON,MA. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. EVANSTON HOSP CORP,DEPT OBSTET GYNECOL,WOMENS MED GRP,SKOKIE,IL. YALE UNIV,SCH MED,DEPT INTERNAL MED,DIV ENDOCRINOL,YALE BONE CTR,NEW HAVEN,CT 06510. WOMENS RES & EDUC INST,WOMENS HLTH PROJECT,WASHINGTON,DC. BAYLOR COLL MED,DEPT MED ENDOCRINOL & METAB,HOUSTON,TX 77030. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV GERIATR MED & GERONTOL,BALTIMORE,MD 21205. JOHNS HOPKINS BAYVIEW MED CTR,GEN CLIN RES CTR,BALTIMORE,MD. UNIV NEVADA,SCH MED,NUTR EDUC & RES PROGRAM,RENO,NV 89557. NORTHWESTERN UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,CHICAGO,IL. HENRY FORD HLTH SCI CTR,DIV BIOSTAT RES EPIDEMIOL & MED INFORMAT,DETROIT,MI. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,PITTSBURGH,PA. RP BILEZIKIAN, JP (reprint author), COLUMBIA UNIV,COLL PHYS & SURG,DEPT MED,DIV ENDOCRINOL,NEW YORK,NY 10032, USA. NR 0 TC 414 Z9 422 U1 0 U2 3 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 DEC 28 PY 1994 VL 272 IS 24 BP 1942 EP 1948 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PX927 UT WOS:A1994PX92700041 ER PT J AU WU, G RAINES, DE MILLER, KW AF WU, G RAINES, DE MILLER, KW TI A HYDROPHOBIC INHIBITOR OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR ACTS ON THE RESTING STATE SO BIOCHEMISTRY LA English DT Article ID RICH MEMBRANE-FRAGMENTS; NONCOMPETITIVE INHIBITOR; TORPEDO-MARMORATA; ION CHANNELS; QUINACRINE AZIDE; BINDING-SITES; AGONIST; ALCOHOLS; BLOCKER; CHLORPROMAZINE AB 3-(Trifluoromethyl)-3-(m-iodophenyl)diazirine (TID) has recently been found to be a noncompetitive inhibitor of the nicotinic acetylcholine receptor (nAcChoR) by both photolabeling and flux assays (White et al., 1991). However, these experiments were done when TID was in equilibrium with the nAcChoR, and thus only its interactions with the resting and the desensitized states of the nAcChoR were studied. In this work we characterized the interaction between TID and nAcChoR in the open and resting states using a flux assay. When TID and acetylcholine were simultaneously mixed with the nAcChoR in native Torpedo vesicles, TID did not inhibit agonist-induced Rb-86(+) flux. However, following prolonged preincubation (4 min) of TLD with nAcChoR, complete inhibition was observed with a half-inhibition constant of 0.4 mu M TID and a Hill coefficient of 0.9. This suggested that TLD might act either on the resting or the desensitized state in preference to the open state of the nAcChoR. Preincubation of nAcChoR with TID, followed by a 7 ms agonist-induced flux assay, showed that the flux response declined exponentially with preincubation time. Assuming a pseudo-first-order process, analysis revealed the rate constant for the onset of inhibition of nAcChoR in the resting state to be in the range of (1.2-3.4) x 10(6) M(-1) s(-1). To test if fast desensitization was enhanced by TID under these conditions, we used a fluorescent analog of acetylcholine. Stopped-flow fluorimetry showed that the fraction of nAcChoR in the predesensitized state did not increase during preincubation with TID. Thus, the inhibition of nAcChoR by TID occurs primarily by an interaction with the resting state of the nAcChoR. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02114. FU NIGMS NIH HHS [GM-15904] NR 34 TC 19 Z9 19 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 27 PY 1994 VL 33 IS 51 BP 15375 EP 15381 DI 10.1021/bi00255a018 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PZ269 UT WOS:A1994PZ26900018 PM 7803400 ER PT J AU SZEBENI, J WANG, MG PEARSON, DA SZOT, GL SYKES, M AF SZEBENI, J WANG, MG PEARSON, DA SZOT, GL SYKES, M TI IL-2 INHIBITS EARLY INCREASES IN SERUM GAMMA-INTERFERON LEVELS ASSOCIATED WITH GRAFT-VERSUS-HOST DISEASE SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; NATURAL SUPPRESSOR ACTIVITY; MAJOR HISTOCOMPATIBILITY BARRIERS; NITRIC-OXIDE PRODUCTION; HELPER T-CELLS; IFN-GAMMA; MONOCLONAL-ANTIBODY; ALLOGENEIC CHIMERAS; CYTOKINE PRODUCTION AB We have recently demonstrated that a short course of high-dose IL-2 administered to lethally irradiated mice leads to marked protection from early and late GVHD mortality, especially when T cell-depleted (TCD) host-type bone marrow cells (BMC) are also administered. IL-2 inhibits the GVHD-inducing activity of donor CD4(+) cells without inhibiting their graft-vs.-leukemia effects. Since CD4(+) T-lymphocytes produce a variety of cytokines, some of which have recently been implicated in the pathogenesis of GVHD, we have studied the possible effect of IL-2 administration on serum levels of various cytokines. Acute GVHD was induced in lethally irradiated B10 mice by bone marrow transplantation (BMT) with MHC-mismatched allogeneic (A/J) BMC and splenocytes. TCD B10 (host-type) BMC were coadministered to maximize the protective effect of IL-2. Serum cytokine levels were compared in recipients of these inocula with or without a protective course of IL-2 treatment. A marked increase in serum IFN-gamma levels was noted on days 3 through 5 post-BMT in GVHD mice compared with syngeneic EMT control recipients. This GVHD-induced rise in serum IFN-gamma was markedly inhibited in IL-2-protected mice. Murine IL-2 levels were only slightly increased in sera of GVHD mice, and were not influenced by treatment with human recombinant IL-2. Serum levels of the monokines TNF-alpha and IL-1 alpha showed variable early elevations in GVHD mice with or without IL-2 treatment, and were not different from levels observed in syngeneic controls. Serum levels of IFN-gamma, IL-1 alpha, and TNF-alpha all declined markedly by day 7 to 8 post-BMT, when GVHD mortality begins. Administration of neutralizing anti-IFN-gamma mAb did not attenuate and tended to accelerate GVHD mortality, and administration of exogenous IFN-gamma did not overcome the protective effect of IL-2 against GVHD. Together, our results indicate that GVHD is associated with high serum levels of several proinflammatory cytokines in the first week post-BMT, but that these levels decline by the time when GVHD mortality begins. IL-2 specifically inhibits the GVHD-associated production of IFN-gamma, but this inhibition in itself does not explain and may even mitigate the protective effect of IL-2 against early GVHD mortality. However, the demonstration that IL-2 markedly inhibits the production of a GVHD-associated cytokine raises the possibility that alterations in the production of as yet undefined cytokines may be responsible for IL-2-induced GVHD protection. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG SERV,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NIAID NIH HHS [R01AI31158] NR 62 TC 45 Z9 46 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 DEC 27 PY 1994 VL 58 IS 12 BP 1385 EP 1393 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA PZ923 UT WOS:A1994PZ92300017 PM 7809932 ER PT J AU TONTONOZ, P GRAVES, RA BUDAVARI, AI ERDJUMENTBROMAGE, H LUI, M HU, E TEMPST, P SPIEGELMAN, BM AF TONTONOZ, P GRAVES, RA BUDAVARI, AI ERDJUMENTBROMAGE, H LUI, M HU, E TEMPST, P SPIEGELMAN, BM TI ADIPOCYTE-SPECIFIC TRANSCRIPTION FACTOR-ARF6 IS A HETERODIMERIC COMPLEX OF 2 NUCLEAR HORMONE RECEPTORS, PPAR-GAMMA AND RXR-ALPHA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID 9-CIS RETINOIC ACID; GENE-EXPRESSION; PEROXISOME PROLIFERATOR; TRANSGENIC MICE; ACTIVATED RECEPTOR; FATTY-ACIDS; 3T3-L1 PREADIPOCYTES; RNA-POLYMERASE; DIFFERENTIATION; ENHANCER AB Previously, we identified a novel transcription factor, ARF6, as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer, In order to identify the proteins which comprise the adipocyte ARF6 complex, we have purified this DNA binding activity from a cultured adipocyte cell line. We have developed a system for growth and differentiation of HIB-1B brown adipocytes in suspension culture that facilitates the production of large quantities of adipocyte nuclear extract, ARF6 was purified from HIB-1B nuclear extract by a combination of conventional and sequence-specific DNA affinity chromotography. Chemical sequencing and mass spectral analysis of tryptic peptides derived from the purified polypeptides identifies the ARF6 complex as a heterodimer of the retinoid X receptor alpha (RXR alpha) and the murine peroxisome proliferator activated receptor gamma (PPAR gamma). Of the known PPAR gamma isoforms, PPAR gamma is the predominant form expressed in adipose tissue, These results suggest that PPAR gamma 2 serves a unique function among PPAR family members as an important regulator of adipocyte-specific gene expression. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. MEM SLOAN KETTERING CANC CTR,PROGRAM MOLEC BIOL,NEW YORK,NY 10021. FU NCI NIH HHS [5 P30 CA08748-9]; NIDDK NIH HHS [DK31405]; NIGMS NIH HHS [T32 GM007753, T32 GM07753-14] NR 43 TC 266 Z9 280 U1 0 U2 14 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 25 PY 1994 VL 22 IS 25 BP 5628 EP 5634 DI 10.1093/nar/22.25.5628 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QC753 UT WOS:A1994QC75300015 PM 7838715 ER PT J AU LIANG, P ZHU, WM ZHANG, XY GUO, Z OCONNELL, RP AVERBOUKH, L WANG, FL PARDEE, AB AF LIANG, P ZHU, WM ZHANG, XY GUO, Z OCONNELL, RP AVERBOUKH, L WANG, FL PARDEE, AB TI DIFFERENTIAL DISPLAY USING ONE-BASE ANCHORED OLIGO-DT PRIMERS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CLONING; RNA C1 GENHUNTER CORP,BROOKLINE,MA 02146. RP LIANG, P (reprint author), CHILDRENS HOSP,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115, USA. NR 11 TC 296 Z9 365 U1 1 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 25 PY 1994 VL 22 IS 25 BP 5763 EP 5764 DI 10.1093/nar/22.25.5763 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QC753 UT WOS:A1994QC75300034 PM 7838734 ER PT J AU SRIKANTH, S RADO, TA AF SRIKANTH, S RADO, TA TI A 30-BASE PAIR ELEMENT IS RESPONSIBLE FOR THE MYELOID-SPECIFIC ACTIVITY OF THE HUMAN NEUTROPHIL ELASTASE PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN MYELOPEROXIDASE GENE; CD11B PROMOTER; NF-M; EXPRESSION; PROTEIN; DIFFERENTIATION; CELLS; IDENTIFICATION; PROTOONCOGENE; REGION AB Human neutrophil elastase (HNE), a serine protease, is expressed only in the promyelocytic stages of granulocyte maturation. We examined several regions of the promoter for transcriptional activity and report that a 30-base pair (bp) element located between -76 and -106 in the 5'-flanking region of HNE is sufficient for myeloid-specific expression of HNE. Gel shift assays using nuclear extracts from myeloid and non-myeloid cells reveal several myeloid-specific complexes binding to the 30-bp element. Examination of DNA-protein interactions shows that at least two myeloid-specific proteins of 38 and 55 kDa bind to this element. DNase I protection analysis reveals two distinct footprints between -80 to -91 and -94 to -104 within this element. Transient expression studies using deletion constructs of the HNE 5'-flanking region show that the 30-bp element is active in myeloid cells It 562 and U 937 but not in HeLa cells. Internal deletion of this element results in a 60-85% loss of promoter activity in myeloid cells. Additional functional studies also show that a 19-bp region between -112 and -131 contributes to transcriptional activity of the elastase promoter as well. C1 UNIV ALABAMA,DEPT MED,DIV HEMATOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MICROBIOL,DIV HEMATOL,BIRMINGHAM,AL 35294. BIRMINGHAM VET AFFAIRS MED CTR,BIRMINGHAM,AL 35294. FU NIDA NIH HHS [R01 DA07237] NR 43 TC 17 Z9 17 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 23 PY 1994 VL 269 IS 51 BP 32626 EP 32633 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX304 UT WOS:A1994PX30400090 PM 7798268 ER PT J AU ROSOWSKY, A MOTA, CE WRIGHT, JE QUEENER, SF AF ROSOWSKY, A MOTA, CE WRIGHT, JE QUEENER, SF TI 2,4-DIAMINO-5-CHLOROQUINAZOLINE ANALOGS OF TRIMETREXATE AND PIRITREXIM - SYNTHESIS AND ANTIFOLATE ACTIVITY SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; GONDII DIHYDROFOLATE-REDUCTASE; LIPID-SOLUBLE ANTIFOLATE; TERMINAL L-ORNITHINE; TOXOPLASMA-GONDII; FOLIC-ACID; FOLYLPOLYGLUTAMATE SYNTHETASE; POTENTIAL ANTIPNEUMOCYSTIS; 5,8-DIDEAZA ANALOGS AB Ten heretofore undescribed 2,4-diamino-5-chloroquinazoline analogues of trimetrexate (TMQ) and piritrexim (PTX) were synthesized and tested as inhibitors of dihydrofolate reductase (DHFR) from rat liver, Pneumocystis carinii, and Toxoplasma gondii. The most active quinazolines against both the P. carinii and the T. gondii enzyme were those with an ArCH2-NH or ArNHCH2 side chain. Among ArNH(CH2)(n) compounds with n = 1-3 and either 2',5'-dimethoxyphenyl or 3',4',5'-trimethoxyphenyl as the Ar moiety, activity decreased in the order n = 1 > n = 2 > n = 3. The best inhibitor of P. carinii DHFR, 2,4-diamino-5-chloro-6-[(N-methyl-3',4',5'-trimethoxyanilino)methyl (10) had an IC50 of 0.012 mu M and was slightly more potent than TMQ and PTX Compound 10 was also the best inhibitor of T. gondii DHFR, with an IC50 of 0.0064 mu M corresponding again to a minor increase in activity over TMQ and PTX. However, as with these standard agents, 10 showed no appreciable selectivity for either the P. carinii or T. gondii enzyme relative to the rat liver enzyme. The highest selectivity achieved in this limited series was with 2,4-diamino-5-chloro-6-[N-(3',4',5'-trimethoxybenzyl)-N-methylamino]quinazoline (17) against T. gondii DHFR. While 17 (IC50 = 0.016 mu M) was somewhat less potent than 10, its selectivity, as defined by the ratio IC50(rat liver)/IC50(T. gondii) was ca. 30-fold higher than that of TMQ or PTX. Two compounds, 2,4-diamino-5-chloro-6-[(3',4',5'-trimethoxyanilino)methyl]quinazoline (9) and 2,4-diamino-5-chloro-6-[N-(3',4',5'-trimethoxybenzyl)amino]quinazoline (15), were also tested against human DHFR and were found to have an IC50/[E] of 0.5, indicating that their binding was near-stoichiometric. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. INDIANA UNIV,SCH MED,DEPT PHARMACOL & TOXICOL,INDIANAPOLIS,IN 46202. RP ROSOWSKY, A (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [N01-AI35171, R01-AI29904] NR 52 TC 36 Z9 36 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 23 PY 1994 VL 37 IS 26 BP 4522 EP 4528 DI 10.1021/jm00052a011 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PY518 UT WOS:A1994PY51800011 PM 7799402 ER PT J AU SANCHEZ, I HUGHES, RT MAYER, BJ YEE, K WOODGETT, JR AVRUCH, J KYRIAKIS, JM ZON, LI AF SANCHEZ, I HUGHES, RT MAYER, BJ YEE, K WOODGETT, JR AVRUCH, J KYRIAKIS, JM ZON, LI TI ROLE OF SAPK/ERK KINASE-1 IN THE STRESS-ACTIVATED PATHWAY REGULATING TRANSCRIPTION FACTOR C-JUN SO NATURE LA English DT Article ID MAP KINASE; PROTEIN-KINASE; PHOSPHORYLATION; EXPRESSION; TYROSINE; CLONING; FAMILY; MEK AB THE stress-activated protein kinases (SAPKs), which are distantly related to the MAP kinases, are the dominant c-Jun amino-terminal protein kinases activated in response to a variety of cellular stresses, including treatment with tumour-necrosis factor-a and interleukin-beta (refs 1, 2). SAPK phosphorylation of c-Jun probably activates the c-Jun transactivation function(3). SAPKs are part of a signal transduction cascade related to, but distinct from, the MAPK pathway(1). We have now identified a novel protein kinase, called SAPK/ERK kinase-1 (SEK1), which is structurally related to the MAP kinase kinases (MEKs)(4). SEK1 is a potent activator of the SAPKs in vitro and in vivo. An inactive SEK1 mutant blocks SAPK activation by extracellular stimuli without interfering with the MAPK pathway. Although alternative mechanisms of SAPK activation may exist, as an immediate upstream activator of the SAPKs, SEK1 further defines a signalling cascade that couples cellular stress agonists to the c-Jun transcription factor. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02129 USA. HARVARD UNIV, CHILDRENS HOSP, SCH MED, DIV HEMATOL ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, CHILDRENS HOSP, SCH MED, DEPT MICROBIOL & MOLEC GENET, BOSTON, MA 02115 USA. HARVARD UNIV, CHILDRENS HOSP, SCH MED, HOWARD HUGHES MED INST, BOSTON, MA 02115 USA. HARVARD UNIV, CHILDRENS HOSP, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. PRINCESS MARGARET HOSP, ONTARIO CANC INST, TORONTO M4X 1K9, ON, CANADA. RP SANCHEZ, I (reprint author), MASSACHUSETTS GEN HOSP E, MED SERV, DIABET RES LAB, 149 13TH ST, BOSTON, MA 02129 USA. RI Woodgett, Jim/F-1087-2010 OI Woodgett, Jim/0000-0003-3731-5797 NR 28 TC 938 Z9 946 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 22 PY 1994 VL 372 IS 6508 BP 794 EP 798 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY212 UT WOS:A1994PY21200057 PM 7997269 ER PT J AU YAN, MH DAI, TN DEAK, JC KYRIAKIS, JM ZON, LI WOODGETT, JR TEMPLETON, DJ AF YAN, MH DAI, TN DEAK, JC KYRIAKIS, JM ZON, LI WOODGETT, JR TEMPLETON, DJ TI ACTIVATION OF STRESS-ACTIVATED PROTEIN-KINASE BY MEKK1 PHOSPHORYLATION OF ITS ACTIVATOR SEK1 SO NATURE LA English DT Article ID RAF; TYROSINE AB A KINASE distinct from the MEK activator Raf(1-3), termed MEK kinase-1 (MEKK), was originally identified by virtue of its homology to kinases involved in yeast mating signal cascades(4). Like Raf, MEKK is capable of activating MEK in vitro(4,5). High-level expression of MEKK in COS-7 cells(4) or using vaccinia virus vectors(5) also activates MEK and MAPK, indicating that MEKK and Raf provide alternative means of activating the MAPK signalling pathmay. We have derived NIH3T3 cell sublines that can be induced to express active MEKK. Here we show that induction of MEKK does not result in the activation of MAPK, but instead stimulates the stress-activated protein kinases (SAPKs)(6-8) which are identical to a Jun amino-terminal kinase(9,10). We find that MEKK regulates a new signalling cascade by phosphorylating an SAPK activator, SEK1 which in turn phosphorylates and activates SAPK. C1 CASE WESTERN RESERVE UNIV HOSP, SCH MED, CELL BIOL PROGRAM, CLEVELAND, OH 44106 USA. PRINCESS MARGARET HOSP, ONTARIO CANC INST, TORONTO M4X 1K9, ON, CANADA. MASSACHUSETTS GEN HOSP E, MED SERV, DIABET RES LAB, BOSTON, MA 02129 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP EAST, DEPT MED, BOSTON, MA 02129 USA. HARVARD UNIV, CHILDRENS HOSP,SCH MED,HOWARD HUGHES MED INST, DIV HEMATOL, BOSTON, MA 02115 USA. RP YAN, MH (reprint author), CASE WESTERN RESERVE UNIV HOSP, SCH MED, INST PATHOL, 10900 E EUCLID AVE, CLEVELAND, OH 44106 USA. RI Templeton, Dennis/F-7695-2011; Woodgett, Jim/F-1087-2010 OI Woodgett, Jim/0000-0003-3731-5797 NR 20 TC 685 Z9 688 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 22 PY 1994 VL 372 IS 6508 BP 798 EP 800 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY212 UT WOS:A1994PY21200058 PM 7997270 ER PT J AU FUCHS, CS GIOVANNUCCI, EL COLDITZ, GA HUNTER, DJ SPEIZER, FE WILLETT, WC AF FUCHS, CS GIOVANNUCCI, EL COLDITZ, GA HUNTER, DJ SPEIZER, FE WILLETT, WC TI A PROSPECTIVE-STUDY OF FAMILY HISTORY AND THE RISK OF COLORECTAL-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SELF-ADMINISTERED QUESTIONNAIRE; CORONARY HEART-DISEASE; ALCOHOL-CONSUMPTION; COLON; REPRODUCIBILITY; FREQUENCY; RECTUM; POLYPS AB Background. A family history of colorectal cancer is recognized as a risk factor for the disease. However, as a result of the retrospective design of prior studies, the strength of this association is uncertain, particularly as it is influenced by characteristics of the person at risk and the affected family members. Methods. We conducted a prospective study of 32,085 men and 87,031 women who had not previously been examined by colonoscopy or sigmoidoscopy and who provided data on first-degree relatives with colorectal cancer, diet, and other risk factors for the disease. During the follow-up period, colorectal cancer was diagnosed in 148 men and 315 women. Results. The age-adjusted relative risk of colorectal cancer for men and women with affected first-degree relatives, as compared with those without a family history of the disease, was 1.72 (95 percent confidence interval, 1.34 to 2.19). The relative risk among study participants with two or more affected first-degree relatives was 2.75 (95 percent confidence interval, 1.34 to 5.63). For participants under the age of 45 years who had one or more affected first-degree relatives, the relative risk was 5.37 (95 percent confidence interval, 1.98 to 14.6), and the risk decreased with increasing age (P for trend, <0.001). Conclusions. A family history of colorectal cancer is associated with an increased risk of the disease, especially among younger people. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RP FUCHS, CS (reprint author), HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA 40935, CA 55075] NR 28 TC 482 Z9 486 U1 1 U2 8 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 22 PY 1994 VL 331 IS 25 BP 1669 EP 1674 DI 10.1056/NEJM199412223312501 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PX382 UT WOS:A1994PX38200001 PM 7969357 ER PT J AU RUSTGI, AK AF RUSTGI, AK TI MEDICAL PROGRESS - HEREDITARY GASTROINTESTINAL POLYPOSIS AND NONPOLYPOSIS SYNDROMES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID FAMILIAL ADENOMATOUS POLYPOSIS; PEUTZ-JEGHERS SYNDROME; COLI GARDNERS-SYNDROME; OCULAR FUNDUS LESIONS; MUIR-TORRE SYNDROME; (LYNCH SYNDROME-I; APC GENE-PRODUCT; COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; JUVENILE POLYPOSIS C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP RUSTGI, AK (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,JACKSON 7,50 BLOSSOM ST,BOSTON,MA 02114, USA. FU PHS HHS [R01 43351] NR 105 TC 167 Z9 173 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 22 PY 1994 VL 331 IS 25 BP 1694 EP 1702 DI 10.1056/NEJM199412223312507 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA PX382 UT WOS:A1994PX38200007 PM 7969362 ER PT J AU FINBERG, RW MATTIA, AR ZERBEY, AL MARK, EJ FISHMAN, JA SPITZER, TR AMBROSINO, D AF FINBERG, RW MATTIA, AR ZERBEY, AL MARK, EJ FISHMAN, JA SPITZER, TR AMBROSINO, D TI A 47-YEAR-OLD MAN WITH INGUINAL LYMPHADENOPATHY AND FEVER DURING PREPARATION FOR A BONE-MARROW TRANSPLANT - HERPES-SIMPLEX VIRUS TYPE-2 NECROTIZING LYMPHADENITIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID GRANULOMA INGUINALE; ORAL ACYCLOVIR; LYMPH-NODES; INFECTION; RECIPIENTS; MIMICKING; LEUKEMIA; PROPHYLAXIS; MANAGEMENT; NECROSIS C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP FINBERG, RW (reprint author), DANA FARBER CANC INST,INFECT DIS SERV,BOSTON,MA 02115, USA. NR 41 TC 2 Z9 2 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 DEC 22 PY 1994 VL 331 IS 25 BP 1703 EP 1709 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PX382 UT WOS:A1994PX38200008 ER PT J AU BLUMENTHAL, D AF BLUMENTHAL, D TI MAKING MEDICAL ERRORS INTO MEDICAL TREASURES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. RP BLUMENTHAL, D (reprint author), MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,50 STANIFORD ST,9TH FLOOR,BOSTON,MA 02114, USA. NR 8 TC 79 Z9 80 U1 0 U2 5 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 DEC 21 PY 1994 VL 272 IS 23 BP 1867 EP 1868 DI 10.1001/jama.272.23.1867 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PW980 UT WOS:A1994PW98000038 PM 7990223 ER PT J AU WALKER, WH SANBORN, BM HABENER, JF AF WALKER, WH SANBORN, BM HABENER, JF TI AN ISOFORM OF TRANSCRIPTION FACTOR CREM EXPRESSED DURING SPERMATOGENESIS LACKS THE PHOSPHORYLATION DOMAIN AND REPRESSES CAMP-INDUCED TRANSCRIPTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ALTERNATIVE EXON SPLICING; PROTEIN KINASE A; SPERMATIDS; SEMINIFEROUS TUBULE ID BINDING PROTEIN CREB; GENE-EXPRESSION; ADENOSINE-3',5'-MONOPHOSPHATE; ACTIVATION; VERSATILITY; REGULATORS; EXTRACTION; INDUCTION; ENHANCER; SUBUNIT AB cAMP response element-binding protein (CREB) and modulator protein (CREM) regulate the transcription of cAMP-responsive genes via phosphorylation by cAMP-dependent protein kinase A. Reverse transcription and polymerase chain amplification of RNA from male germ cells identify an alternatively spliced CREM isoform, CREM Delta C-G, lacking four exons including those encoding the protein kinase A-regulated phosphorylation domain and the flanking glutamine-rich transcriptional activation domains. CREM Delta C-G retains exons that encode the basic-leucine zipper (bZIP) DNA-binding domain, binds to cAMP response elements (CREs), and competitively inhibits binding of CREB and CREM to CREs. Expression of CREM Delta C-G inhibits transcription of a CRE containing chloramphenicol acetyltransferase reporter plasmid induced by endogenous CREB. Antiserum to CREM detects CREM Delta C-G in elongated spermatids from rat testis. These observations indicate that CREM Delta C-G is a unique form of a competitive negative regulator of CREB-mediated gene transcription expressed in a maturation-dependent manner in haploid germ cells. The developmental specificity of CREM Delta C-G suggests that it may play a role in transcriptional regulation during spermatogenesis. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,MOLEC ENDOCRINOL LAB,BOSTON,MA 02114. UNIV TEXAS,SCH MED,DEPT BIOCHEM & MOLEC BIOL,HOUSTON,TX 77030. FU NICHD NIH HHS [HD17795]; NIDDK NIH HHS [DK25532] NR 36 TC 68 Z9 69 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 20 PY 1994 VL 91 IS 26 BP 12423 EP 12427 DI 10.1073/pnas.91.26.12423 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY294 UT WOS:A1994PY29400015 PM 7809053 ER PT J AU COHEN, L MOHR, R CHEN, YY HUANG, M KATO, R DORIN, D TAMANOI, F GOGA, A AFAR, D ROSENBERG, N WITTE, O AF COHEN, L MOHR, R CHEN, YY HUANG, M KATO, R DORIN, D TAMANOI, F GOGA, A AFAR, D ROSENBERG, N WITTE, O TI TRANSCRIPTIONAL ACTIVATION OF A RAS-LIKE GENE (KIR) BY ONCOGENIC TYROSINE KINASES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DIFFERENTIAL GENE EXPRESSION ID CHRONIC MYELOGENOUS LEUKEMIA; POSITIVE HUMAN LEUKEMIAS; P210 BCR ABL; PHILADELPHIA-CHROMOSOME; MESSENGER-RNA; CATALYTIC DOMAIN; PROTEIN GAP; C-ABL; MICE; TRANSFORMATION AB We report the characterization of a member of the ras gene family that is overexpressed in cells transformed by abl tyrosine kinase oncogenes. The gene, named kir (for kinase-inducible ras-like), is induced at the transcriptional level, kit mRNA has a rapid turnover and encodes a protein of 33 kDa with guanine nucleotide-binding activity but undetectable intrinsic GTPase activity. kir was cloned by differential screening of genes present in fully malignant versus growth factor-independent cell lines expressing wild-type or mutant forms of BCR/ABL, BCR/ABL and v-Abl induce transcription of the kir gene via specific signaling pathway(s), but kir overexpression alone is not sufficient to mediate transformation. C1 UNIV CALIF LOS ANGELES,DEPT MICROBIOL & MOLEC GENET,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,INST MOLEC BIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,HOWARD HUGHES MED INST,LOS ANGELES,CA 90024. TUFTS UNIV,SCH MED,DEPT MOLEC BIOL & MICROBIOL,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT PEDIAT HEMATOL & ONCOL,BOSTON,MA 02115. FU NCI NIH HHS [CA24220, CA53867]; NINDS NIH HHS [NS30054] NR 37 TC 79 Z9 82 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 20 PY 1994 VL 91 IS 26 BP 12448 EP 12452 DI 10.1073/pnas.91.26.12448 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY294 UT WOS:A1994PY29400020 PM 7809057 ER PT J AU LIANG, P AVERBOUKH, L ZHU, WM PARDEE, AB AF LIANG, P AVERBOUKH, L ZHU, WM PARDEE, AB TI RAS ACTIVATION OF GENES - MOB-1 AS A MODEL SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CELL TRANSFORMATION; DIFFERENTIAL DISPLAY; PCR; SIGNAL TRANSDUCTION ID DIFFERENTIAL DISPLAY; MESSENGER-RNA; GROWTH-FACTOR; INTERFERON; ONCOGENE; TRANSFORMATION; FIBROBLASTS; EXPRESSION; PROTEIN; PROLIFERATION AB The ras oncogenes function by indirectly controlling expression of a subset of Set-undefined genes that are crucial for cell growth and differentiation. In a differential display strategy, numerous genes were identified on the basis of their differential expression in rat embryo fibroblasts transformed by the cooperation of mutant Ha-ras and p53 genes. We demonstrate here that one such gene, designated mob-1, is a downstream target of the Ras signaling pathway. The 417-bp mob-1 promoter, which contains dual NF-kappa B and AP-1 binding sites, confers the pas inducibility. Oncogenic pas as well as serum growth factors that activate endogenous Ras can induce mob-1 expression, but with a fundamental difference in that the oncogenic induction is constitutive whereas the serum induction is transient. mob-1 encodes a small secretory protein with a high degree of homology to LP-10, a member of a proinflammatory cytokine family. These findings link chronic inflammatory response to constitutive ras activation and tumorigenesis. Mob-1 may serve as a secreted marker for oncogenic Ha-ras mutations. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP LIANG, P (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIGMS NIH HHS [GM24571] NR 35 TC 61 Z9 65 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 20 PY 1994 VL 91 IS 26 BP 12515 EP 12519 DI 10.1073/pnas.91.26.12515 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY294 UT WOS:A1994PY29400034 PM 7809069 ER PT J AU ANDROLEWICZ, MJ ORTMANN, B VANENDERT, PM SPIES, T CRESSWELL, P AF ANDROLEWICZ, MJ ORTMANN, B VANENDERT, PM SPIES, T CRESSWELL, P TI CHARACTERISTICS OF PEPTIDE AND MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I BETA(2)-MICROGLOBULIN BINDING TO THE TRANSPORTERS ASSOCIATED WITH ANTIGEN-PROCESSING (TAP1 AND TAP2) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CLASS-I MOLECULES; P-GLYCOPROTEIN; GENE; MHC; SEQUENCE; TRANSLOCATION; SUPERFAMILY; HOMOLOGY; PROTEINS; PATHWAY AB The transporter proteins associated with antigen processing (TAP proteins) transport antigenic peptides across the endoplasmic reticulum membrane where they can assemble with newly synthesized major histocompatibility complex (MHC) class I/beta(2)-microglobulin (beta(2)m) dimers. We have shown previously that TAP possesses a peptide-recognition site with broad specificity and that MHC class I/beta(2)m dimers physically associate with TAP, Here, we further characterize the nature of the peptide-binding site on TAP, and the site of interaction of TAP with MHC class I/beta(2)m dimers. TAP photoaffinity labeling experiments revealed that both TAP1 and TAP2 are photolabeled by two distinct photopeptide analogues, suggesting that elements of both TAP1 and TAP2 compose the peptide-recognition site. TAP photolabeling analysis on transfectant cell lines that express TAP1 and TAP2 both individually and together revealed that efficient formation of the peptide-binding site occurs only when TAP1 and TAP2 are coexpressed, which correlates with the finding that peptide translocation via TAP occurs only in the presence of both TAP1 and TAP2. These data strongly support the notion that TAP functions as a heterodimer. MHC class I/beta(2)m dimers were shown to associate with individual TAP1 chains but were not detectable with individual TAP(2) chains. This result suggests that the site of interaction for MHC class I/beta(2)m dimers with TAP is on TAP1. C1 YALE UNIV,SCH MED,HOWARD HUGHES MED INST,IMMUNOBIOL SECT,NEW HAVEN,CT 06510. INSERM UNITE,F-75743 PARIS 15,FRANCE. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. NR 30 TC 137 Z9 137 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 20 PY 1994 VL 91 IS 26 BP 12716 EP 12720 DI 10.1073/pnas.91.26.12716 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY294 UT WOS:A1994PY29400075 PM 7809108 ER PT J AU BESRA, GS SIEVERT, T LEE, RE SLAYDEN, RA BRENNAN, PJ TAKAYAMA, K AF BESRA, GS SIEVERT, T LEE, RE SLAYDEN, RA BRENNAN, PJ TAKAYAMA, K TI IDENTIFICATION OF THE APPARENT CARRIER IN MYCOLIC ACID SYNTHESIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MYCOBACTERIA; 6-O-MYCOLYL-MANNOSYL-1-PHOSPHOPOLYPRENOL; ANTITUBERCULOSIS DRUGS ID CELL-FREE SYSTEM; MYCOBACTERIUM-TUBERCULOSIS; CORYNEBACTERIUM-DIPHTHERIAE; HOMOLOGOUS SERIES; SMEGMATIS; BIOSYNTHESIS; EXTRACT; ESTER; H37RA AB The mycolic acids are large (C-70-90) alpha-alkyl, beta-hydroxy fatty acids and are the major determinants of the mycobacterial cell wall's impermeable barrier. The biosynthesis of mycolic acids is barely understood (they are probably the products of specialized elongation and Claisen-type condensation), and yet their synthesis is the site of action of several mainline antituberculosis drugs. We describe the isolation from Mycobacterium smegmatis and the full characterization of a 6-O-mycolyl-beta-D-mannopyranosyl-1-monophosphoryl-3,7,11, 15,19,23,27-heptamethyl-(2Z,6E,10E)-octacosatrien-1-ol. The identification of a mycolyl-mannosylphosphopolyprenol supported by cell-free labeling experiments and earlier literature suggests unusual biochemical pathways in which mature mycolic acids are formed from beta-oxo precursors while attached to a mannosyl-P-polyprenol, in which form they are transported through the membrane prior to final deposition as arabinan-bound mycolates. C1 UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET HOSP,MYCOBACTERIOL RES LAB,MADISON,WI 53706. UNIV WISCONSIN,COLL AGR & LIFE SCI,DEPT BACTERIOL,MADISON,WI 53706. RP BESRA, GS (reprint author), COLORADO STATE UNIV,DEPT MICROBIOL,FT COLLINS,CO 80523, USA. RI Lee, Richard/J-4997-2013; Slayden, Richard/O-8626-2016; OI Lee, Richard/0000-0002-2397-0443; Slayden, Richard/0000-0001-6857-7277; Besra, Gurdyal/0000-0002-5605-0395 FU NIAID NIH HHS [AI 30189]; PHS HHS [AZ-18357] NR 36 TC 70 Z9 73 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 20 PY 1994 VL 91 IS 26 BP 12735 EP 12739 DI 10.1073/pnas.91.26.12735 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY294 UT WOS:A1994PY29400079 PM 7809112 ER PT J AU ZHANG, R TSAI, FY ORKIN, SH AF ZHANG, R TSAI, FY ORKIN, SH TI HEMATOPOIETIC DEVELOPMENT OF VAV(-/-) MOUSE EMBRYONIC STEM-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GENE TARGETING; ERYTHROID AND MYELOID CELLS; SIGNALING PATHWAYS ID VAV PROTOONCOGENE PRODUCT; TYROSINE PHOSPHORYLATION; HOMOLOGOUS RECOMBINATION; GENE-EXPRESSION; ES CELLS; TRANSCRIPTION; ONCOGENE; RECEPTOR; INVITRO; DIFFERENTIATION AB The vav protooncogene product is expressed nearly exclusively in hematopoietic lineages and contains several structural motifs (SH2/SH3 domains and a dbl-oncogene homology region) typical of proteins functioning in signaling pathways. To ascertain if vav expression is required for hematopoiesis we generated vav-negative mouse embryonic stem cells by gene targeting and examined the consequences of loss of vav function on erythroid and myeloid development in vitro and in vivo. In conflict with the conclusions drawn from expression of antisense vav RNA in embryonic stem cells [Wulf, G. M., Adra, C. N. and Lim, B. (1993) EMBO J. 12, 5065-5074], we observed erythroid and myeloid development in the absence of vav. These experiments demonstrate that vav expression is not absolutely required for hematopoietic development. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. RP ZHANG, R (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115, USA. NR 33 TC 42 Z9 42 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 20 PY 1994 VL 91 IS 26 BP 12755 EP 12759 DI 10.1073/pnas.91.26.12755 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY294 UT WOS:A1994PY29400083 PM 7809116 ER PT J AU SEGAL, RA GOUMNEROVA, LC KWON, YK STILES, CD POMEROY, SL AF SEGAL, RA GOUMNEROVA, LC KWON, YK STILES, CD POMEROY, SL TI EXPRESSION OF THE NEUROTROPHIN RECEPTOR TRKC IS LINKED TO A FAVORABLE OUTCOME IN MEDULLOBLASTOMA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BRAIN TUMOR; RECEPTOR TYROSINE KINASE; CEREBELLUM ID NERVE GROWTH-FACTOR; TYROSINE PROTEIN-KINASE; MOLECULAR-CLONING; CEREBELLAR MEDULLOBLASTOMA; HIGH-AFFINITY; NGF RECEPTOR; RAT TRKC; BRAIN; GENE; CELLS AB Medulloblastoma, the most common malignant brain tumor of childhood, has a variable prognosis. Although half of the children and young adults with the disease survive longer than 10 years after diagnosis, the others relapse and die despite identical therapy. We have examined the expression of neurotrophins and their receptors in medulloblastoma blastoma samples snap frozen in the operating room to preserve RNA integrity. All tumors (n = 12) were found to express mRNA encoding neurotrophin 3 and its receptor TrkC. The level of trkC expression was highly variable, with a more than 50-fold difference between the highest and lowest values. By Kaplan-Meier analysis, patients with tumors expressing high levels of trkC mRNA had significantly longer intervals without disease progression than those with low levels (log-rank, P = 0.03) and a more favorable overall survival (log-rank, P = 0.05). Thus, trkC expression is a prognostic indicator for patients with medulloblastoma. C1 CHILDRENS HOSP,DEPT NEUROL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT NEUROSURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MOLEC & CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. FU NIGMS NIH HHS [GM31489]; NINDS NIH HHS [NS27773] NR 41 TC 188 Z9 190 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 20 PY 1994 VL 91 IS 26 BP 12867 EP 12871 DI 10.1073/pnas.91.26.12867 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY294 UT WOS:A1994PY29400106 PM 7809137 ER PT J AU FINLEY, RL BRENT, R AF FINLEY, RL BRENT, R TI INTERACTION MATING REVEALS BINARY AND TERNARY CONNECTIONS BETWEEN DROSOPHILA CELL-CYCLE REGULATORS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE INTERACTION TRAP; 2-HYBRID; PROTEIN NETWORKS; INTERACTION MATRIX ID SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; SCHIZOSACCHAROMYCES-POMBE; DEPENDENT KINASES; DNA SPECIFICITY; YEAST; CDK2; SUBUNIT; HOMOLOG; TRANSFORMATION AB We characterized interactions between Drosophila melanogaster cell cycle regulatory proteins by a yeast interaction-mating technique. The results were displayed as two-dimensional matrices that revealed individual binary interactions between proteins, Each protein (Cdi, cyclin-dependent kinase interactor) interacted with a distinct spectrum of cyclin-dependent kinases (Cdk) from Drosophila and other organisms. Some Cdis interacted with other Cdis, indicating that these proteins may form trimeric complexes that include Cdks. Similar analysis of interaction matrices may be generally useful in detecting other multiprotein complexes and in establishing connectivity between individual complex members. Moreover, such analysis may also help assign function to newly identified proteins, identify domains involved in protein-protein interactions, and aid the dissection of genetic regulatory networks. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RP FINLEY, RL (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,50 BLOSSOM ST,BOSTON,MA 02114, USA. NR 36 TC 219 Z9 225 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 20 PY 1994 VL 91 IS 26 BP 12980 EP 12984 DI 10.1073/pnas.91.26.12980 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY294 UT WOS:A1994PY29400129 PM 7809159 ER PT J AU HALPERN, HJ YU, C PERIC, M BARTH, E GRDINA, DJ TEICHER, BA AF HALPERN, HJ YU, C PERIC, M BARTH, E GRDINA, DJ TEICHER, BA TI OXYMETRY DEEP IN TISSUES WITH LOW-FREQUENCY ELECTRON-PARAMAGNETIC-RESONANCE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HYPERFINE COUPLING-CONSTANTS; NMR CONTRAST AGENTS; OXYGEN DISTRIBUTION; SPIN-RESONANCE; TENSION MEASUREMENTS; RECONSTRUCTION; LABEL; SENSITIVITY; DEPENDENCE; OXIMETRY AB We have measured the oxygen concentration in the body water of murine FSa and NFSa fibrosarcomas using a new method for quantitative oxygen concentration determination deep in the tissues of a living animal. The measurement uses unusually low-frequency electron paramagnetic spectroscopy sensitive to substrate 7 cm deep in tissue, partially deuterated spin probes (spin labels of molecular mass 195, approximating that of glucose) whose distribution compartment can be targeted with facile adduct substitution, and novel analytic techniques. We show that the water-compartment oxygen concentration of the tumors decreases as the tumor size increases and also shows a trend to decrease as radiobiologic hypoxia increases. An oxymetric spectral image of the tumor is presented. The technique will improve with larger human tissue samples. It provides the potential to quantitatively assess tissue hypoxia in ischemic or preischemic states in stroke and myocardial infarction. It will allow direct assessment of tumor hypoxia to determine the usefulness of radiation and chemotherapy adjuvants directed to hypoxic cell compartments. C1 UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. ARGONNE NATL LAB,DIV BIOL & MED SCI,ARGONNE,IL 60439. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP HALPERN, HJ (reprint author), UNIV CHICAGO,CTR RADIAT THERAPY,CHICAGO,IL 60637, USA. FU NCI NIH HHS [CA50679] NR 33 TC 133 Z9 135 U1 0 U2 8 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 20 PY 1994 VL 91 IS 26 BP 13047 EP 13051 DI 10.1073/pnas.91.26.13047 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY294 UT WOS:A1994PY29400143 PM 7809170 ER PT J AU BIRD, TA KYRIAKIS, JM TYSHLER, L GAYLE, M MILNE, A VIRCA, GD AF BIRD, TA KYRIAKIS, JM TYSHLER, L GAYLE, M MILNE, A VIRCA, GD TI INTERLEUKIN-1 ACTIVATES P54 MITOGEN-ACTIVATED PROTEIN (MAP) KINASE KINASE STRESS-ACTIVATED PROTEIN-KINASE BY A PATHWAY THAT IS INDEPENDENT OF P21(RAS), RAF-1, AND MAP KINASE KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR RECEPTOR; MYELIN BASIC-PROTEIN; SMOOTH-MUSCLE CELLS; SUBSTRATE RECOGNITION; HUMAN-FIBROBLASTS; SIGNAL TRANSDUCTION; FACTOR-ALPHA; C-MYC; PHOSPHORYLATION AB In KB epidermoid cells, we previously showed that interleukin-1 alpha (IL-1) and various mitogens activate the mitogen-activated protein (MAP) kinases ERK1 and ERK2, which phosphorylate both myelin basic protein (MBP) and a peptide containing Thr(669) of the epidermal growth factor receptor. In cell-free extracts made from gingival fibroblasts treated with platelet-derived growth factor or HepG2 hepatoma cells stimulated with phorbol myristate acetate, MBP and Thr(669) kinase were both elevated 4-fold, and ERK1 and ERK2 were tyrosine-phosphorylated. In these cells IL-1 activated a kinase(s) that phosphorylated Thr(669) peptide but not MBP and failed to cause tyrosine phosphorylation of ERK1/ERK2. Ceramide has been proposed as an intracellular mediator of IL-1 action, but C-2-ceramide or sphingosine stimulated predominantly MBP-specific kinase activity in fibroblasts and had no effect in HepG2 cells, p54 MAP kinase (also called stress-activated protein kinase) is a c-Jun kinase first isolated from livers of cycloheximide-treated rats. After IL-1 stimulation, immunoprecipitates of lysates made from all three cell types with specific anti-p54 MAP kinase serum contained Thr(669) and c-Jun phosphorylating activity, whereas precipitates from unstimulated cells contained no detectable p54 kinase activity. The major peak of IL-1 stimulated HepG2 Thr(669) kinase activity co chromatographed on Mono Q and phenyl-Superose with immunodetectable p54 MAP kinase. IL-1 did not cause p21(ras) activation in any cell type. Induction of Thr(669) kinase activity was not abrogated by elevation of cAMP levels, which has been shown to interfere with the activation of Raf-1. We could not detect MAP kinase kinase phosphorylating activity in unfractionated lysates made from IL-1-stimulated fibroblasts or HepG2 cells. KB cells contained a small amount of this activity, but it was not precipitated with an anti-Raf-1 antibody. We conclude that most of the IL-1-activated Thr(669) kinase activity in fibroblasts and HepG2 cells, and a portion in KB cells, is due to p54 MAP kinase and that its activation is Ras-, Raf-, and MAP kinase kinase-independent. C1 IMMUNEX CORP,DEPT BIOCHEM,SEATTLE,WA 98101. IMMUNEX RES & DEV CORP,DEPT MOLEC BIOL,SEATTLE,WA 98101. IMMUNEX RES & DEV CORP,DEPT PROT CHEM,SEATTLE,WA 98101. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIABET UNIT,BOSTON,MA 02129. NR 64 TC 103 Z9 103 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 16 PY 1994 VL 269 IS 50 BP 31836 EP 31844 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX303 UT WOS:A1994PX30300078 PM 7527398 ER PT J AU IKEZU, T OKAMOTO, T MURAYAMA, Y OKAMOTO, T HOMMA, Y OGATA, E NISHIMOTO, I AF IKEZU, T OKAMOTO, T MURAYAMA, Y OKAMOTO, T HOMMA, Y OGATA, E NISHIMOTO, I TI BIDIRECTIONAL REGULATION OF C-FOS PROMOTER BY AN ONCOGENIC GIP2 MUTANT OF G-ALPHA(12) - A NOVEL IMPLICATION OF RETINOBLASTOMA GENE-PRODUCT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH FACTOR-II; CYCLIC-AMP ACCUMULATION; PROTEIN-KINASE-C; SUSCEPTIBILITY GENE; TRANSCRIPTIONAL ACTIVATION; RESPONSE ELEMENT; ALPHA-SUBUNITS; CELL-CYCLE; 3T3 CELLS; EXPRESSION AB G alpha(i2) is a tissue-specific proto-oncogene product, whose activated mutant gip2 induces transformation through less defined downstream pathways, We found that c-fos promoter is a target of gip2 in multiple kinds of cells, Serum response element was shown to be the positive enhancer element that mediates gip2-induced c-fos expression. We further demonstrated that gip2 stimulates the negative silencer activity of the retinoblastoma (Rb) control element (RCE) and inhibits the c-fos promoter activity through RCE located in the c-fos promoter region. The effect of gip2 on RCE was shown to be mediated by the Rb gene product (pRb). Furthermore, gip2 augmented underphosphorylated active form of pRb by promoting pRb expression and by affecting the phosphorylation state of pRb. gip2 therefore propagates both positive and negative signals to the c-fos promoter through two different elements, and pRb mediates the negative signal of gip2. We conclude that gip2 has bifunctional roles in transformation which pRb critically regulates. Given that Rat-1 cells, which gip2 can transform, lack the sensitivity to the gip2/pRb-mediated negative pathway, this study provides a novel insight into oncogenesis by gip2 and its tissue specificity. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIOVASC RES CTR,CVRC,DEPT MED,BOSTON,MA 02129. UNIV TOKYO,SCH MED,DEPT INTERNAL MED 4,BUNKYO KU,TOKYO 112,JAPAN. CANC RES INST,TOSHIMA KU,TOKYO 170,JAPAN. NR 39 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 16 PY 1994 VL 269 IS 50 BP 31955 EP 31961 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX303 UT WOS:A1994PX30300095 PM 7989371 ER PT J AU THOMPSON, NM GULLEY, ML ROGENESS, GA CLAYTON, RJ JOHNSON, C HAZELTON, B CHO, CG ZELLMER, VT AF THOMPSON, NM GULLEY, ML ROGENESS, GA CLAYTON, RJ JOHNSON, C HAZELTON, B CHO, CG ZELLMER, VT TI NEUROBEHAVIORAL CHARACTERISTICS OF CGG AMPLIFICATION STATUS IN FRAGILE-X FEMALES SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE TRINUCLEOTIDE REPEAT; NEUROPSYCHOLOGICAL; PSYCHIATRIC; INTELLIGENCE ID DISORDERS; CARRIERS; REGION; WOMEN; GENE; DNA AB Neurobehavioral correlates of CGG amplification were studied in 17 nonretarded adult female carriers of fragile X syndrome. The results revealed a significant relationship between IQ and the number of CGG repeats in the 5' untranslated region of the FMR1 gene. Women with a full mutation (>200 CGG repeats) scored below average in IQ, visual-spatial perception, visual-spatial organization, and executive function. There were no differences in hue motor dexterity or memory as a function of CGG amplification status. A history of major depressive disorder was identified in 71% of the sample, but incidence of depression was not associated with the degree of CGG amplification. Schizotypal features were noted in 18%. No intellectual or neuropsychological deficit was found in women with a premutation (<200 CGG repeats). Decrements in IQ, visual-spatial perception, and executive function appear to arise as a consequence of the CGG amplification. (C) 1994 Wiley-Liss, Inc, C1 UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PEDIAT,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. ST MARYS UNIV,DEPT PSYCHOL,SAN ANTONIO,TX. NR 28 TC 45 Z9 45 U1 3 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 15 PY 1994 VL 54 IS 4 BP 378 EP 383 DI 10.1002/ajmg.1320540418 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA QF860 UT WOS:A1994QF86000017 PM 7726212 ER PT J AU YANNUZZI, LA SORENSON, JA SOBEL, RS DALY, JR DEROSA, JT SEDDON, JM GRAGOUDAS, ES PULIAFITO, CA GELLES, E GONET, R BURTON, TC CULVER, J METZGER, K KALBFLEISCH, N ZARLING, D FARBER, MD BLAIR, N STELMACK, T AXELROD, A WAITR, SE CROSS, A ROLNICK, C FLOM, T HALLER, J PUSIN, S CASSEL, G APPLEGATE, CA SEIGEL, D SPERDUTO, RD HILLER, R MOWERY, R CHEW, E TAMBOLI, A DUNN, M SHAMBAN, K LENTO, D AF YANNUZZI, LA SORENSON, JA SOBEL, RS DALY, JR DEROSA, JT SEDDON, JM GRAGOUDAS, ES PULIAFITO, CA GELLES, E GONET, R BURTON, TC CULVER, J METZGER, K KALBFLEISCH, N ZARLING, D FARBER, MD BLAIR, N STELMACK, T AXELROD, A WAITR, SE CROSS, A ROLNICK, C FLOM, T HALLER, J PUSIN, S CASSEL, G APPLEGATE, CA SEIGEL, D SPERDUTO, RD HILLER, R MOWERY, R CHEW, E TAMBOLI, A DUNN, M SHAMBAN, K LENTO, D TI RISK-FACTORS FOR IDIOPATHIC MACULAR HOLES SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID FELLOW EYES; BREAKS AB PURPOSE: A case-control study was conducted to identify possible risk factors for idiopathic macular holes. METHODS: One hundred ninety-eight patients with idiopathic macular holes and 1,023 control subjects were identified at five clinical centers, Data were obtained through interviews, clinical examinations, and laboratory analyses of blood specimens. RESULTS: One hundred forty-three (72%) affected patients were women. Very few of a broad array of possible risk factors were statistically significant. In a logistic regression model that included both genders, higher plasma fibrinogen levels (P = .0007) and a history of glaucoma (P = .04) were associated with an increased risk of idiopathic macular holes. When the same model was used for women, with estrogen use and parity added as variables, a higher fibrinogen level (P = .002) was positively associated, and estrogen use (P = .04) was negatively associated with risk of macular holes. CONCLUSIONS: Of the two factors that stood out as possible risk factors for idiopathic macular holes, the increased risk for women has long been recognized. The association with fibrinogen level was unexpected, and it is unclear whether this is a chance finding or whether higher levels of fibrinogen can increase susceptibility to the forces of vitreous traction, perhaps by compromising the macular blood supply or by some yet unexplained mechanism. C1 NEI,BIOMETRY & EPIDEMIOL PROGRAM,BETHESDA,MD 20892. MANHATTAN EYE EAR & THROAT HOSP,NEW YORK,NY 10021. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. MED COLL WISCONSIN,MILWAUKEE,WI 53226. UNIV ILLINOIS,CHICAGO,IL. JOHNS HOPKINS UNIV HOSP,WILMER OPHTHALMOL INST,BALTIMORE,MD 21205. ORKAND CORP,COORDINATING CTR,SILVER SPRING,MD. PHOTOG READING CTR,BOSTON,MA. NR 20 TC 45 Z9 46 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC 15 PY 1994 VL 118 IS 6 BP 754 EP 761 PG 8 WC Ophthalmology SC Ophthalmology GA PW189 UT WOS:A1994PW18900009 ER PT J AU MARCUS, DM FREDERICK, AR AF MARCUS, DM FREDERICK, AR TI STREPTOKINASE-INDUCED TENONS HEMORRHAGE AFTER RETINAL-DETACHMENT SURGERY SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Note AB PURPOSE/METHODS: We studied a ease in which a streptokinase-induced Tenon's hemorrhage developed after retinal detachment surgery. The patient received intravenous streptokinase for myocardial infarction two hours after pars plana vitrectomy and encircling scleral buckling surgery. RESULTS/CONCLUSIONS: A Tenon's hemorrhage with an orbital compartment syndrome developed in the patient's left eye, and he underwent lateral canthotomy and inferior cantholysis. Symptoms of the compartment syndrome resolved and final visual acuity was 20/40. Although there are potential ocular-related side effects to thrombolytic therapy, there has been no permanent ocular morbidity reported after thrombolytic-related hemorrhage. We recommend not to defer such life-saving therapy after ocular surgery. C1 MASSACHUSETTS EYE & EAR INFIRM,OPHTHALM CONSULTANTS BOSTON,BOSTON,MA 02114. RP MARCUS, DM (reprint author), MED COLL GEORGIA,DEPT OPHTHALMOL,AUGUSTA,GA 30912, USA. NR 5 TC 6 Z9 6 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC 15 PY 1994 VL 118 IS 6 BP 815 EP 817 PG 3 WC Ophthalmology SC Ophthalmology GA PW189 UT WOS:A1994PW18900022 PM 7977615 ER PT J AU TO, KW MUKAI, S FRIEDMAN, AH AF TO, KW MUKAI, S FRIEDMAN, AH TI ASSOCIATION AND CHANCE OCCURRENCE OF ANIRIDIA AND RETINOBLASTOMA SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Note ID POLYMORPHISMS AB PURPOSE/METHODS: A 9-month-old infant had inherited aniridia and unilateral retinoblastoma. Family history disclosed three generations of aniridia; yet there were no instances of retinoblastoma. The coincidental occurrence of retinoblastoma and aniridia is rare. RESULTS/CONCLUSIONS: With. DNA probes from within the retinoblastoma gene, we were able to determine that a retinoblastoma-predisposing mutation was not inherited with aniridia in this family. The occurrence of these two diseases in the same individual therefore represents a chance event. C1 BROWN UNIV,RHODE ISL HOSP,SCH MED,DEPT PATHOL,PROVIDENCE,RI 02903. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. CUNY MT SINAI SCH MED,DEPT OPHTHALMOL,NEW YORK,NY 10029. RP TO, KW (reprint author), BROWN UNIV,RHODE ISL HOSP,SCH MED,DEPT OPHTHALMOL,593 EDDY ST,APC-744,PROVIDENCE,RI 02903, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC 15 PY 1994 VL 118 IS 6 BP 820 EP 822 PG 3 WC Ophthalmology SC Ophthalmology GA PW189 UT WOS:A1994PW18900025 PM 7977618 ER PT J AU CARRERA, AC BORLADO, LR ROBERTS, TM MARTINEZA, C AF CARRERA, AC BORLADO, LR ROBERTS, TM MARTINEZA, C TI TYROSINE KINASE SPECIFIC MOTIF AT SUBDOMAIN-VIII DOES NOT CONFER SPECIFICITY FOR TYROSINE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN-KINASE; THREONINE; SERINE; SEQUENCE; GENE AB The majority of protein kinases fall within one of the two broad classes, kinases that phosphorylate serine or threonine and kinases that phosphorylate tyrosine. The structural basis that confers residue specificity is not known. However, it has been hypothesized that a region in subdomain VIII of the catalytic domain may be involved in determining kinase specificity. This region contains a motif which is conserved among serine/threonine kinases and different from the one conserved among tyrosine kinases. We have prepared a chimera of the tyrosine kinase pp56(lck) in which the tyrosine kinase motif at subdomain VIII has been exchanged for the corresponding region of the serine/threonine kinase c-Raf. Our results indicate that this motif itself does not confer amino acid specificity since the chimeric kinase still displays specificity for tyrosine. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MOLEC & CELLULAR BIOL,BOSTON,MA 02115. RP CARRERA, AC (reprint author), UNIV AUTONOMA MADRID,CSIC,CTR NACL BIOTECNOL,CAMPUS CANTOBLANCO,E-28049 MADRID,SPAIN. OI Carrera, Ana/0000-0002-3999-5434 FU NCI NIH HHS [CA 43803] NR 12 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 15 PY 1994 VL 205 IS 2 BP 1114 EP 1120 DI 10.1006/bbrc.1994.2781 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PY706 UT WOS:A1994PY70600020 PM 7528498 ER PT J AU JUBINSKY, PT LAURIE, AS NATHAN, DG YETZALDEPE, J SIEFF, CA AF JUBINSKY, PT LAURIE, AS NATHAN, DG YETZALDEPE, J SIEFF, CA TI EXPRESSION AND FUNCTION OF THE HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-RECEPTOR ALPHA-SUBUNIT SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HUMAN GM-CSF; HEMATOPOIETIC GROWTH-FACTORS; ACUTE MYELOBLASTIC-LEUKEMIA; CELL-LINES; ANTIGEN EXPRESSION; MOLECULAR-CLONING; SURFACE-RECEPTOR; ERYTHROPOIETIN; PROLIFERATION AB To determine the expression and function of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha chain (GMR alpha) during hematopoiesis and on leukemic cells, monoclonal antibodies were raised by immunizing mice with cells expressing high levels of human GMR alpha. A pool of five antibodies isolated from three different mice was used to characterize GMR alpha. This antibody pool (anti-GMR alpha) immunoprecipitated a protein with the expected molecular weight of GMR alpha from COS cells transiently transfected with the GMR alpha gene. In factor-dependent cells, GMR alpha existed as a phosphoprotein, However, its phosphorylation was not stimulated by the presence of GM-CSF, Anti-GMR alpha inhibited the GM-CSF-dependent growth of cell lines and normal bone marrow cells and inhibited the binding of iodinated GM-CSF to its receptor, Cell surface expression of GMR alpha was examined using anti-GMR alpha and flow cytometry. GMR alpha was readily detectable on both blood monocytes and neutrophils. In adherence-depleted normal bone marrow, two separate populations expressed GMR alpha. The most positive cells were predominantly macrophages, whereas the cells that expressed less GMR alpha were largely myelocytes and metamyelocytes, A small population of lin(-)CD34(+) or CD34(+)CD38(-) cells also expressed GMR alpha, but they were not capable of significant growth in colony-forming assays. In contrast, the majority of lin(-)CD34(+) and CD34(+)CD38(-) cells were GMR alpha(-), yet they produced large numbers of myeloid and erythroid colonies in the same assay. Malignant cells from patients with leukemia were also tested for GMR alpha expression, All of the myeloid leukemias and only rare lymphoid leukemias surveyed tested positive for GMR alpha. These results show that anti-GMR alpha is useful for the functional characterization of the GMR alpha and for the detection of myeloid leukemia and that GMR alpha is expressed on certain lineages throughout hematopoietic development; however, progenitors that express the receptor may have a reduced capacity to proliferate in response to hematopoietic growth factors. (C) 1994 by The American Society of Hematology. C1 CHILDRENS HOSP,DIV PEDIAT HEMATOL & ONCOL,CAMBRIDGE,MA. GENET INST INC,CAMBRIDGE,MA 02140. RP JUBINSKY, PT (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DANA 1628,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIGMS NIH HHS [GM 13452] NR 39 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 15 PY 1994 VL 84 IS 12 BP 4174 EP 4185 PG 12 WC Hematology SC Hematology GA PX146 UT WOS:A1994PX14600021 PM 7994031 ER PT J AU HOCHBERG, FH FISCHMAN, AJ METZ, R AF HOCHBERG, FH FISCHMAN, AJ METZ, R TI IMAGING OF BRAIN-TUMORS SO CANCER LA English DT Editorial Material ID POSITRON EMISSION TOMOGRAPHY C1 MASSACHUSETTS GEN HOSP,SERV NEUROL,BOSTON,MA. MASSACHUSETTS GEN HOSP,SERV RADIOL NUCL MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,MORPHOMETRY LAB,BOSTON,MA. NR 10 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 1994 VL 74 IS 12 BP 3080 EP 3082 DI 10.1002/1097-0142(19941215)74:12<3080::AID-CNCR2820741203>3.0.CO;2-J PG 3 WC Oncology SC Oncology GA PW268 UT WOS:A1994PW26800002 PM 7982170 ER PT J AU BUBLEY, GJ OGATA, GK DUPUIS, NP TEICHER, BA AF BUBLEY, GJ OGATA, GK DUPUIS, NP TEICHER, BA TI DETECTION OF SEQUENCE-SPECIFIC ANTITUMOR ALKYLATING AGENT DNA-DAMAGE FROM CELLS TREATED IN CULTURE AND FROM A PATIENT SO CANCER RESEARCH LA English DT Note ID CISPLATIN CHEMOTHERAPY; CROSS-LINKING; ADDUCTS; CIS-DIAMMINEDICHLOROPLATINUM(II); CYCLOPHOSPHAMIDE; IDENTIFICATION; QUANTITATION AB Detection of sequence-specific DNA damage induced by antitumor alkylating agents might provide a mechanism for detecting and discriminating damage specific to one or more of these drugs. Using repetitive primer-extension and human alphoid DNA as a substrate, lesions specific for an activated form of cyclophosphamide, 4-hydroperoxycyclophosphamide, were detected at 32 of 33 guanines within a 200-base pair region in DNA from cells treated in culture. There was a marked variation in lesion site intensity among affected guanines. For instance, guanines flanked by cytosine were weak sites of 4-hydroperoxycyclophosphamide-induced damage. Damage at bases other than guanine induced by cisplatin, UV irradiation, and adozelesin were compared to drug-DNA lesions induced by 4-hydroperoxycyclophosphamide. Using this method it was possible to detect, and at some sites distinguish, between cyclophosphamide- and cisplatin-induced DNA damage within WBC DNA from a patient treated with both agents. There was a different damage pattern for DNA derived from cells treated in culture compared to DNA derived from the patient sample. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02215. RP BUBLEY, GJ (reprint author), HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV HEMATOL ONCOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NCI NIH HHS [R-29 CA51438]; PHS HHS [P0-1-38493] NR 20 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1994 VL 54 IS 24 BP 6325 EP 6329 PG 5 WC Oncology SC Oncology GA PX306 UT WOS:A1994PX30600009 PM 7987822 ER PT J AU KOBATA, T AGEMATSU, K KAMEOKA, J SCHLOSSMAN, SF MORIMOTO, C AF KOBATA, T AGEMATSU, K KAMEOKA, J SCHLOSSMAN, SF MORIMOTO, C TI CD27 IS A SIGNAL-TRANSDUCING MOLECULE INVOLVED IN CD45RA(+) NAIVE T-CELL COSTIMULATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; TUMOR-NECROSIS-FACTOR; PROTEIN-TYROSINE KINASE; HUMAN LYMPHOCYTES-B; SURFACE-ANTIGEN; BIOLOGICAL CHARACTERIZATION; ACTIVATION ANTIGEN; ADHESION MOLECULES; GENE FAMILY; EXPRESSION AB CD27 is a 120-kDa transmembrane homodimeric molecule expressed on the majority of T cells, B cells, and NK cells that belongs to the TNFR/nerve growth factor receptor family. The interaction between CD27 and its ligand, CD70, is thought to play an important role in T cell activation. In this paper, we have examined the signal-transducing potential of CD27 in T cell costimulation. Anti-CD27 mAb, anti-1A4, induced substantial proliferation of peripheral blood T cells in the presence of a suboptimal dose of PMA, phytohemagglutinin, anti-CD2, or anti-CD3 together with a second Ab to cross-link the CD27 molecule. This T cell proliferation was also observed by using CD70 transfectant cells. CD27 cross-linking maximally induced proliferation of CD45 RA(+)CD4 T cells but only slightly induced proliferation of CD45RO(+)CD4 T cells. CD27-mediated T cell proliferation did not seem to be dependent on the IL-2/IL-2R system because no detectable level of IL-2 was secreted, and only a partial inhibition was observed with anti-IL-2 and anti-IL-2R Abs. Furthermore, an increase in intracellular Ca2+ was observed in PMA-treated T cells when the CD27 molecule was cross-linked. More importantly, CD27 ligation induced protein tyrosine phosphorylation, especially 70 kDa of cellular substrate, including ZAP-70, in T cells. Herbimycin A, a protein tyrosine kinase inhibitor, and staurosporine, a protein kinase C inhibitor, blocked T cell proliferation induced by CD27 ligation, suggesting the possibility that the activation of protein tyrosine ki nase and protein kinase C is required for CD27-mediated T cell costimulation. These results clearly demonstrate that the CD27/CD70 interaction induces costimulatory signals in T cells, especially CD45RA(+) naive T cells, indicating that CD27 serves as a T cell signal-transducing molecule. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV TUMOR IMMUNOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI 12609, AI 29530]; NIAMS NIH HHS [AR 33713] NR 62 TC 115 Z9 116 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 1994 VL 153 IS 12 BP 5422 EP 5432 PG 11 WC Immunology SC Immunology GA PW703 UT WOS:A1994PW70300008 PM 7989747 ER PT J AU SIDERAS, P MULLER, S SHIELS, H JIN, H KHAN, WN NILSSON, L PARKINSON, E THOMAS, JD BRANDEN, L LARSSON, I PAUL, WE ROSEN, FS ALT, FW VETRIE, D SMITH, CIE XANTHOPOULOS, KG AF SIDERAS, P MULLER, S SHIELS, H JIN, H KHAN, WN NILSSON, L PARKINSON, E THOMAS, JD BRANDEN, L LARSSON, I PAUL, WE ROSEN, FS ALT, FW VETRIE, D SMITH, CIE XANTHOPOULOS, KG TI GENOMIC ORGANIZATION OF MOUSE AND HUMAN BRUTONS AGAMMAGLOBULINEMIA TYROSINE KINASE (BTK) LOCI SO JOURNAL OF IMMUNOLOGY LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; SIGNALING PROTEINS; HEMATOPOIETIC-CELLS; CLOSE LINKAGE; SRC FAMILY; PH DOMAIN; B-CELLS; GENE; IMMUNODEFICIENCY; TRANSCRIPTION AB Btk is a cytoplasmic protein tyrosine kinase (PTK) that has been directly implicated in the pathogenesis of X-linked agammaglobulinaemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. We have isolated phage and cosmid clones that allowed us to deduce the genomic structure of mouse and human Btk loci. The mouse and human genes are contained within genomic regions that span approximately 43.5 kb and 37.5 kb, respectively. Both loci contain 18 coding exons ranging between 55 and 560 bp in size with introns ranging in size from 164 bp to approximately 9 kb. The 5'-untranslated regions are encoded by single exons located approximately 9 kb upstream of the first coding exon. Exon 18 encodes for the last 23 carboxyl-terminal amino acids and the entire 3'-untranslated region. The location of intron/exon boundaries in the catalytic domains of the mouse and human Btk loci differs from that found in other described sub-families of intracellular PTKs, namely that of Src, Fes/Fer, Csk, and Abl/Arg. This observation is consistent with the classification of Btk together with the recently characterized kinases, Tec and Itk, into a separate sub-family of cytoplasmic PTKs. Putative transcription initiation sites in the mouse and human Btk loci have been determined by using the rapid amplification of cDNA ends assay. Similar to many other PTK specific genes, the putative Btk promoters lack obvious TATAA and CAAAT motifs. Putative initiator elements and potential binding sites for Ets (PEA-3), zeste, and PuF transcription factors are located within the 300 bp which are located upstream of the major transcription start site in both species. These sequences can mediate promoter activity when placed upstream of a promotorless chloramphenicol acetyl transferase reporter gene in an orientation-dependent manner. The present analysis will significantly facilitate the mutational analyses of patients with XLA and the further characterization of the function and regulation of the Btk molecule. C1 KAROLINSKA INST,NOVUM,CTR BIOTECHNOL,HUDDINGE,SWEDEN. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. UNITED MED & DENT SCH,DIV MED & MOLEC GENET,LONDON SE1 9RT,ENGLAND. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP SIDERAS, P (reprint author), UMEA UNIV,APPL CELL & MOLEC BIOL UNIT,S-90187 UMEA,SWEDEN. NR 53 TC 72 Z9 75 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 1994 VL 153 IS 12 BP 5607 EP 5617 PG 11 WC Immunology SC Immunology GA PW703 UT WOS:A1994PW70300026 PM 7989760 ER PT J AU FINKELSTEIN, JS KLIBANSKI, A SCHAEFER, EH HORNSTEIN, MD SCHIFF, I NEER, RM AF FINKELSTEIN, JS KLIBANSKI, A SCHAEFER, EH HORNSTEIN, MD SCHIFF, I NEER, RM TI PARATHYROID-HORMONE FOR THE PREVENTION OF BONE LOSS INDUCED BY ESTROGEN DEFICIENCY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID X-RAY ABSORPTIOMETRY; MINERAL DENSITY; OVARIECTOMIZED RATS; RANDOMIZED TRIAL; TRABECULAR BONE; SPINAL BONE; WOMEN; MASS; OSTEOPOROSIS; THERAPY AB Background. Analogues of gonadotropin-releasing hormone (GnRH) are often given to induce hypogonadism in women who have estrogen-dependent disorders such as endometriosis and uterine leiomyomas. Because estrogen deficiency causes bone loss, concern about premature osteoporosis has prevented long-term therapy with GnRH analogues. We conducted a study to determine whether parathyroid hormone could prevent bone loss in women receiving therapy with GnRH analogues. Methods. We administered human parathyroid hormone (40 mu g subcutaneously daily) to 20 of 40 women with endometriosis who were being treated with nafarelin (200 mu g intranasally twice daily) for six months; the remaining 20 women received only nafarelin. Cortical and trabecular bone density and biochemical markers of bone turnover were measured every three months during the six-month study period. Results. Serum estradiol concentrations fell to postmenopausal values in 36 of the 40 women. In the women who received nafarelin alone, the mean (+/-SE) bone density in the lumbar spine decreased by 2.8+/-0.5 percent (P<0.001) when measured in the anteroposterior projection and by 3.5+/-0.8 percent (P<0.001) when measured in the lateral projection. In contrast, bone density in the lumbar spine did not change when measured in the anteroposterior projection and increased by 3.4+/-1.2 percent when measured in the lateral projection (P = 0.01) in the women who also received parathyroid hormone. Bone density at the femoral neck decreased slightly and similarly in both groups. Radial bone density did not change in either group. Serum alkaline phosphatase and osteocalcin concentrations and urinary hydroxyproline and pyridinoline excretion increased (P<0.001) in the women who received nafarelin plus parathyroid hormone. Conclusions. Parathyroid hormone can prevent bone loss in the lumbar spine in young women with estrogen deficiency caused by treatment with GnRH analogues. C1 MASSACHUSETTS GEN HOSP,DEPT MED,NEUROENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT GYNECOL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. RP FINKELSTEIN, JS (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BULFINCH 327,BOSTON,MA 02114, USA. FU NCRR NIH HHS [RR-1066]; NICHD NIH HHS [HD-21204]; NIDDK NIH HHS [1 R29 DK/43341-01A2] NR 38 TC 189 Z9 190 U1 1 U2 5 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 15 PY 1994 VL 331 IS 24 BP 1618 EP 1623 DI 10.1056/NEJM199412153312404 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PW446 UT WOS:A1994PW44600004 PM 7969342 ER PT J AU MOREL, D TAUPIN, JL COMBE, C POTAUX, L GUALDE, N MOREAU, JF AF MOREL, D TAUPIN, JL COMBE, C POTAUX, L GUALDE, N MOREAU, JF TI ONE-YEAR ENZYME-LINKED-IMMUNOSORBENT-ASSAY FOLLOW-UP OF HUMAN INTERLEUKIN FOR DA CELLS LEUKEMIA INHIBITORY FACTOR IN BLOOD AND URINE OF 22 KIDNEY-TRANSPLANT RECIPIENTS SO TRANSPLANTATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR LIF; STIMULATING FACTOR; HILDA LIF; CELLS; MICE AB The cytokine human interleukin for Da cells/leukemia inhibitory factor (HILDA/LIF) exerts multiple biological effects in vitro. In mice, high circulating levels of HILDA/LIF induce a wide range of pathophysiological events, some of them closely involved with immunological and inflammatory responses. Using a sandwich ELISA recognizing the natural human HILDA/LIF molecule with a threshold of 50 pg/ml in urine and 150 pg/ml in plasma, we monitored the urine and plasma HILDA/LIF levels of 22 patients in their first year after a kidney transplant. HILDA/LIF urine excretion is increased during acute rejection, and infections also trigger heavy HILDA/LIF plasma concentrations or urine excretion. In addition, this study raises the question of HILDA/LIF involvement in post-kidney-transplant phenomena such as hypercalcemia, osteoporosis, or the reversal of anemia. C1 UNIV BORDEAUX 2,CNRS,URA 1456,BORDEAUX,FRANCE. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT TUMOR IMMUNOL,BOSTON,MA 02115. RP MOREL, D (reprint author), HOP PELLEGRIN,SERV NEPHROL,F-33076 BORDEAUX,FRANCE. RI Combe, Christian/N-3726-2015 OI Combe, Christian/0000-0002-0360-573X NR 23 TC 5 Z9 5 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 DEC 15 PY 1994 VL 58 IS 11 BP 1190 EP 1195 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA PW732 UT WOS:A1994PW73200009 PM 7992361 ER PT J AU KRENGER, W SNYDER, K SMITH, S FERRARA, JLM AF KRENGER, W SNYDER, K SMITH, S FERRARA, JLM TI EFFECTS OF EXOGENOUS INTERLEUKIN-10 IN A MURINE MODEL OF GRAFT-VERSUS-HOST DISEASE TO MINOR HISTOCOMPATIBILITY ANTIGENS SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; T-CELL PROLIFERATION; GROWTH-FACTOR-BETA; IFN-GAMMA; MACROPHAGE; BARRIERS; INVIVO; IMMUNOSUPPRESSION; ANTIBODIES AB IL-10 is a regulatory cytokine of both T cells and monocytes. We have investigated the ability of IL-10 to regulate responses to alloantigens in vitro and in vivo. Addition of IL-10 to mixed lymphocyte cultures profoundly decreased the proliferation and IL-2 production by donor B10.BR cells stimulated with CBA cells expressing minor histocompatibility antigens. Administration of IL-10 for a period of 2 weeks after bone marrow transplantation decreased the expansion of CD4(+) and CD8(+) donor T cells. In addition, splenocytes from BMT mice treated with IL-10 secreted less IFN-gamma after stimulation with Con A in vitro. The suppression of the mitogen-driven proliferative response of lymphocytes from the IL-10-treated group could also be reversed with significantly less anti-IFN-gamma antibody than for saline-treated controls. However, treatment with IL-10 was not sufficient to alter significantly the clinical course of graft-versus-host disease in CBA recipient mice as assessed by survival, weight loss, and splenomegaly. The results suggest that exogenous IL-10 suppresses the afferent Th1 response in a graft-versus-host reaction but does not significantly diminish the effector stage of graft-versus-host disease. C1 DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. SCHERING PLOUGH CORP,RES INST,KENILWORTH,NJ 07033. FU NIAID NIH HHS [AI 30018] NR 38 TC 56 Z9 56 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 DEC 15 PY 1994 VL 58 IS 11 BP 1251 EP 1257 DI 10.1097/00007890-199412150-00020 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA PW732 UT WOS:A1994PW73200020 PM 7992370 ER PT J AU HANNA, M SZOSTAK, JW AF HANNA, M SZOSTAK, JW TI SUPPRESSION OF MUTATIONS IN THE CORE OF THE TETRAHYMENA RIBOZYME BY SPERMIDINE, ETHANOL AND BY SUBSTRATE STABILIZATION SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PHENYLALANINE TRANSFER-RNA; CRYSTALLOGRAPHIC REFINEMENT; THERMAL-STABILITY; YEAST; BINDING; MAGNESIUM; CRYSTAL; INTRON AB We have previously described a collection of mutations in conserved residues of the core of the Tetrahymena self-splicing intron. Most of these single base substitutions have less than 10% of the activity of their parental intron derivative [Couture,S., et al., (1990) J. Mol. Biol., 215, 345 - 358]. We examined the effect of two agents known to stabilize RNA structure, spermidine and ethanol, on the activity of many of these mutant RNAs. In the presence of either 5 mM spermidine or 20% ethanol most substitution mutations were partially or completely suppressed. These conditions also increased the temperature optima of both wild-type and mutant ribozymes. In addition, we find that mutations are also suppressed by a high concentration of GTP, a substrate in the reaction which is bound specifically by the intron. Thus we observe a general suppression of mutations in an RNA enzyme (ribozyme) by spermidine, ethanol and by substrate stabilization. These results are consistent with the idea that most mutations destabilize the folded structure of the ribozyme and can be suppressed by any of a variety of stabilizing influences. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 23 TC 12 Z9 12 U1 3 U2 5 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 11 PY 1994 VL 22 IS 24 BP 5326 EP 5331 DI 10.1093/nar/22.24.5326 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PZ487 UT WOS:A1994PZ48700026 PM 7816622 ER PT J AU HOLDEN, SA TEICHER, BA FREI, E AF HOLDEN, SA TEICHER, BA FREI, E TI LONG-TERM PERSISTENCE AND CYTOKINETICS OF HUMAN TUMOR-CELLS IN-VITRO FOLLOWING HIGH-DOSE ALKYLATING AGENT EXPOSURE IT SO CANCER LETTERS LA English DT Article DE PERSISTENCE; CYTOKINETICS; ALKYLATING AGENT THERAPY; HUMANS; MCF-7 BREAST CARCINOMA ID CYCLE PROGRESSION; RESISTANT; LINES; DERIVATIVES; TRANSPORT AB Relapse after high-dose alkylating agent therapy continues to be an important clinical issue. To begin to understand the characteristics of cells surviving alkylating agent exposure human MCF-7 breast carcinoma cells were exposed to a range of concentrations of melphalan or cis-diamminedichloroplatinum(II) and cell survival determined by colony formation over time course of 4 weeks. When antitumor alkylating agent exposure killed 3-4 logs of cells as determined by surviving fraction after 1 week of colony formation a progressive increase in surviving fraction was evident over the 4-week course of the experiment. Many attached single cells with abnormal morphology were evident in these dishes; however, the colonies which arose over the 4-week observation time were made up of cells morphologically indistinguishable from the control cells. Cell cycle patterns in the cultures exposed to high concentrations of the antitumor alkylating agents indicated a block in G(2)/M but by 4 weeks post-drug exposure most had returned to a normal exponential growth pattern. When MCF-7 cells or human SW2 small cell lung cancer cells were exposed to a concentration of melphalan or cis-diamminedichloroplatinum(II) that killed 1-2 logs of cells followed by exposure to a concentration range of the same drug for 24 h or 7 days later resistance to the second drug exposure was evident in both cell lines. Using [C-14]melphalan the uptake of the drug into MCF-7 cells pre-treated with melphalan or not pretreated was compared. Decreased drug uptake did not appear to be a factor in resistance to melphalan observed upon re-exposure to the drug. The potential clinical implications of these findings is discussed. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [P0I-CA38493, R0I-CA50174] NR 28 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 9 PY 1994 VL 87 IS 2 BP 211 EP 222 DI 10.1016/0304-3835(94)90225-9 PG 12 WC Oncology SC Oncology GA QA562 UT WOS:A1994QA56200014 PM 7812943 ER PT J AU SHENG, SJ PEMBERTON, PA SAGER, R AF SHENG, SJ PEMBERTON, PA SAGER, R TI PRODUCTION, PURIFICATION, AND CHARACTERIZATION OF RECOMBINANT MASPIN PROTEINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CONFORMATIONAL CHANGE; ESCHERICHIA-COLI; BINDING; ALPHA-1-ANTITRYPSIN; PAI-1 AB Maspin, a novel mammary serine protease inhibitor, was shown to have tumor suppressing activity (Zou, Z., Anisowicz, A., Hendrix, M. J. C., Thor, A., Neveu, M., Sheng, S., Rafidi, K., Seftor, E., and Sager, R. (1994) Science 263, 526-529). In this paper, we report the production of recombinant glutathione S-transferase-maspin fusion protein, expressed in the bacterium Escherichia coli, and recombinant maspin, expressed in the insect Spodoptera frugiperda cells. The fusion protein was purified by glutathione affinity chromatography. Maspin expressed in insect cells was purified by a combination of Bio-Rad AG1-2X anion exchange chromatography and heparin affinity chromatography. The recombinant maspin from insect cells was cleaved at the putative reactive center, as confirmed by protein sequencing. Both recombinant proteins demonstrated strong inhibitory effects on the invasion by two breast tumor cell lines across reconstituted basement membranes and such inhibitory effect was abolished in the presence of the polyclonal antibody made against the reactive center region of maspin. The trypsin-cleaved recombinant maspin did not inhibit invasion, indicating that the inhibitory activity requires the intact putative reactive center. This paper provides evidence that recombinant maspin protein itself inhibits invasion, and supports the role of maspin as a tumor suppressor. C1 LXR BIOTECHNOL INC,RICHMOND,CA 94804. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC GENET,BOSTON,MA 02115. NR 20 TC 138 Z9 143 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 9 PY 1994 VL 269 IS 49 BP 30988 EP 30993 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV510 UT WOS:A1994PV51000041 PM 7983035 ER PT J AU WU, YT GLIMCHER, MJ REY, C ACKERMAN, JL AF WU, YT GLIMCHER, MJ REY, C ACKERMAN, JL TI A UNIQUE PROTONATED PHOSPHATE CROUP IN BONE-MINERAL NOT PRESENT IN SYNTHETIC CALCIUM PHOSPHATES - IDENTIFICATION BY P-31 SOLID-STATE NMR-SPECTROSCOPY SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HYDROXYAPATITE; BRUSHITE; OCTACALCIUM PHOSPHATE; AMORPHOUS CALCIUM PHOSPHATE; DIFFERENTIAL CROSS POLARIZATION ID NUCLEAR-MAGNETIC-RESONANCE; TRANSFORM INFRARED-SPECTROSCOPY; MAGIC-ANGLE; P-31 NMR; CROSS-POLARIZATION; TRABECULAR BONE; EARLY DEPOSITS; PO4 DOMAIN; MAS-NMR; PHASES AB The detailed chemical composition and microstructure of freshly deposited bone mineral, and haw these properties change with maturation of the mineral, have been studied intensively and still remain controversial. For example, current analytical technology is inadequate for the unambiguous characterization of the monohydrogen phosphate ions in bone mineral. Using a differential cross polarization/magic angle spinning solid state nuclear magnetic resonance spectroscopy technique, we suppress the dominant orthophosphate (PO4-3) signal to reveal the spectra of the minor phosphate constituents. This method depends upon differences in the cross polarization time constants for phosphorus-31 nuclei in protonated and non-protonated phosphate ions. It is now possible for the first time to directly measure both the proportion of acid phosphate (HPO4-2) as well as the parameters which characterize its isotropic and anisotropic chemical shift. In bone from three species at several developmental stages, we have found a single type of acid phosphate species, identical in all of the specimens examined. The phosphorus-31 isotropic chemical shift of this acid phosphate group in bone mineral. corresponds precisely with that of acid phosphate in octacalcium phosphate, and not with that of brushite. In contrast, the bone acid phosphate anisotropic chemical shift parameters are close to those of brushite, and differ significantly from those of octacalcium phosphate. The orthophosphate resonances of bone mineral, synthetic hydroxyapatite and synthetic octacalcium phosphate share identical chemical isotropic shifts, and similar chemical shift anisotropies. The implication of these results is that the intimate structure of the acid phosphate group in bone mineral is unique, and that none of the common synthetic calcium phosphates accounts well for all of the observed solid state phosphorus-31 NMR properties of bone mineral. C1 MASSACHUSETTS GEN HOSP, DEPT RADIOL, CTR NUCL MAGNET RESONANCE, BIOMAT LAB, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02129 USA. CHILDRENS HOSP, DEPT ORTHOPAED SURG, STUDY SKELETAL DISORDERS & REHABIL LAB, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RI Ackerman, Jerome/E-2646-2015 OI Ackerman, Jerome/0000-0001-5176-7496 FU NCRR NIH HHS [RR06229]; NIAMS NIH HHS [AR07112, AR34078] NR 65 TC 109 Z9 109 U1 2 U2 25 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 DEC 9 PY 1994 VL 244 IS 4 BP 423 EP 435 DI 10.1006/jmbi.1994.1740 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PW983 UT WOS:A1994PW98300006 PM 7990131 ER PT J AU DEC, GW FUSTER, V AF DEC, GW FUSTER, V TI IDIOPATHIC DILATED CARDIOMYOPATHY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID CONGESTIVE-HEART-FAILURE; POLYMERASE CHAIN-REACTION; CONVERTING-ENZYME-INHIBITION; PLACEBO-CONTROLLED TRIAL; COXSACKIEVIRUS B3 RNA; LOW-DOSE AMIODARONE; TERM BETA-BLOCKADE; VENTRICULAR ARRHYTHMIAS; CARDIAC TRANSPLANTATION; CLINICAL COURSE RP DEC, GW (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BULFINCH 211,BOSTON,MA 02114, USA. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 155 TC 487 Z9 496 U1 1 U2 18 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 8 PY 1994 VL 331 IS 23 BP 1564 EP 1575 DI 10.1056/NEJM199412083312307 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA PV292 UT WOS:A1994PV29200007 PM 7969328 ER PT J AU AMREIN, PC EISENBERG, PJ HARRIS, NL BAKER, GP WEISSMAN, DJ DEMIRJIAN, ZN AF AMREIN, PC EISENBERG, PJ HARRIS, NL BAKER, GP WEISSMAN, DJ DEMIRJIAN, ZN TI A 52-YEAR-OLD WOMAN WITH WEAKNESS, DIARRHEA, AND DIFFUSE LYMPHADENOPATHY - MANTLE-CELL LYMPHOMA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID INTERMEDIATE LYMPHOCYTIC LYMPHOMA; NON-HODGKINS-LYMPHOMAS; CENTROCYTIC LYMPHOMA; MALIGNANT-LYMPHOMA; PROGNOSTIC FACTORS; DIFFERENTIATION; REARRANGEMENT; SUBTYPE; FEATURES; ENTITY C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP AMREIN, PC (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA, USA. NR 37 TC 2 Z9 2 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 DEC 8 PY 1994 VL 331 IS 23 BP 1576 EP 1582 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PV292 UT WOS:A1994PV29200008 ER PT J AU WEEKS, JC AF WEEKS, JC TI PREFERENCES OF OLDER CANCER-PATIENTS - CAN YOU JUDGE A BOOK BY ITS COVER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER; OUTCOMES RP WEEKS, JC (reprint author), DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 11 TC 11 Z9 11 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 7 PY 1994 VL 86 IS 23 BP 1743 EP 1744 DI 10.1093/jnci/86.23.1743 PG 2 WC Oncology SC Oncology GA PU633 UT WOS:A1994PU63300002 PM 7966406 ER PT J AU SHIODA, T OHTA, T ISSELBACHER, KJ RHOADS, DB AF SHIODA, T OHTA, T ISSELBACHER, KJ RHOADS, DB TI DIFFERENTIATION-DEPENDENT EXPRESSION OF THE NA+/GLUCOSE COTRANSPORTER (SGLT1) IN LLC-PK1 CELLS - ROLE OF PROTEIN-KINASE-C ACTIVATION AND ONGOING TRANSCRIPTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RENAL EPITHELIAL CELLS; MESSENGER-RNA DEGRADATION ID GLUTAMYL-TRANSFERASE TRANSPEPTIDASE; MESSENGER-RNA; EPITHELIAL MEMBRANE; GLUCOSE; TRANSPORT; SYSTEM; ORGANIZATION; SIMILARITY; CLONING; KIDNEY AB We examined changes in the mRNA level of SGLT1, a Na+/glucose cotransporter, by the differentiation status of LLC-PK1 renal epithelial cells, Proliferating (undifferentiated) cells revealed no detectable SGLT1 mRNA by Northern blot analysis, However, when tells became confluent and differentiated into polarized monolayers, there was an abrupt appearance of the SGLT1 mRNA. When confluent (differentiated) cells were dedifferentiated by reseeding at a subconfluent density, SGLT1 mRNA levels decreased quickly to nondetectable levels (t(1/2) = 1.5 h), white the mRNA levels of gamma-glutamyltranspeptidase, another differentiation marker, decreased only slowly (t(1/2) > 40 h), This decrease in SGLT1 mRNA was completely blocked by H-7, a protein kinase inhibitor. Since protein kinase C was highly activated in the undifferentiated cells and treatment of differentiated cells with a phorbol ester also induced quick and complete loss of SGLT1 mRNA (t(1/2) = 1.5 h) but not of gamma-glutamyltranspeptidase mRNA, protein kinase C activation appears to be involved in the dedifferentiation-induced decrease in SGLT1 mRNA, Although the phorbol ester-induced decrease in the SGLT1 mRNA level was blocked completely by inhibition of transcription, inhibitors of translation blocked the decrease in mRNA levels only partially. C1 MASSACHUSETTS GEN HOSP,CTR CANC 1497207,TUMOR BIOL LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. FU NIDDK NIH HHS [DK01392-34] NR 24 TC 35 Z9 35 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 6 PY 1994 VL 91 IS 25 BP 11919 EP 11923 DI 10.1073/pnas.91.25.11919 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PW708 UT WOS:A1994PW70800032 PM 7991557 ER PT J AU MCKEE, M SCAVONE, C NATHANSON, JA AF MCKEE, M SCAVONE, C NATHANSON, JA TI NITRIC-OXIDE, CGMP, AND HORMONE REGULATION OF ACTIVE SODIUM-TRANSPORT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NA,K-ATPASE; SODIUM PUMP; KIDNEY; GUANYLYL CYCLASE ID PROTEIN-KINASE-C; RENAL TUBULE CELLS; ATPASE ACTIVITY; CYCLIC-GMP; CAUSES INHIBITION; NADPH DIAPHORASE; RELAXING FACTOR; NA+ TRANSPORT; K+-ATPASE; SYNTHASE AB The inter- and intracellular regulator nitric oxide (NO) has been suggested to play a role in the modulation of cellular excitability, but the mechanism(s) by which this occurs remain unclear. Using the kidney as a model system, we report here evidence that NO, produced in response to various hormones and cytokines, can effect long-term alterations in the activity of the membrane sodium pump. This regulation of Na,K-ATPase, which occurs in a system of NO containing renal tubules, involves cGMP and cGMP-dependent protein kinase. Na,K-ATPase can also be regulated by alterations of cGMP initiated through NO-independent factors, such as atriopeptin, and in nonrenal tissues, such as cerebellum. Regulation of the membrane sodium pump by NO and cGMP, therefore, represents a mechanism for hormonal modulation of ion gradients, not only in kidney but also in other organs, including brain, where NO and cGMP play a prominent role in cellular function. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,NEUROPHARMACOL RES LAB,BOSTON,MA 02129. OI Scavone, Cristoforo/0000-0002-1206-0882 FU PHS HHS [05077] NR 38 TC 187 Z9 189 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 6 PY 1994 VL 91 IS 25 BP 12056 EP 12060 DI 10.1073/pnas.91.25.12056 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PW708 UT WOS:A1994PW70800060 PM 7527549 ER PT J AU CASTIGLI, E ALT, FW DAVIDSON, L BOTTARO, A MIZOGUCHI, E BHAN, AK GEHA, RS AF CASTIGLI, E ALT, FW DAVIDSON, L BOTTARO, A MIZOGUCHI, E BHAN, AK GEHA, RS TI CD40-DEFICIENT MICE GENERATED BY RECOMBINATION-ACTIVATING GENE-2-DEFICIENT BLASTOCYST COMPLEMENTATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CD40 KNOCKOUT; ISOTYPE SWITCHING; B LYMPHOCYTE ID X-LINKED IMMUNODEFICIENCY; HYPER-IGM SYNDROME; HUMAN B-CELLS; CD40 LIGAND; DEFECTIVE EXPRESSION; DENDRITIC CELLS; CYTOKINES; RECEPTOR; ANTIBODY; SIGNAL AB To study the role of the B-cell antigen CD40 in immune responses, mouse embryonic stem (ES) cells in which both copies of the gene encoding CD40 had been disrupted by homologous recombination were injected in RAG-2 (recombination-activating gene-2)-deficient blastocysts to generate chimeras in which all mature lymphocytes are derived from the CD40-deficient ES cells. T- and B-cell number and phenotype were normal in the CD40(-/-) chimeras. However, B cells failed to proliferate and undergo isotype switching in vitro in response to soluble CD40 ligand (sCD40L) with interleukin 4 (IL-4) but responded normally to lipopolysaccharide (LPS) with IL-4. CD40(-/-) chimeras completely failed to mount an antigen-specific antibody response or to develop germinal centers following immunization with the T cell-dependent (TD) antigen keyhole limpet hemocyanin. In contrast, CD40(-/-) mutant mice responded normally to the T cell-independent (TI) antigens 2,4,6-trinitrophenyl (TNP)-LPS and TNP-Ficoll. The most noticeable alteration in the serum immunoglobulin levels of young (6-8 weeks old) CD40(-/-) animals was absence of IgE and severe decrease of IgG1 and IgG2a. These results confirm the essential role of CD40-CD40L interactions in the antibody response to TD antigens and in isotype switching. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,IMMUNOPATHOL UNIT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RP CASTIGLI, E (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV IMMUNOL,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI-31541, AI-28046]; NIDDK NIH HHS [DK-43351] NR 24 TC 220 Z9 222 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 6 PY 1994 VL 91 IS 25 BP 12135 EP 12139 DI 10.1073/pnas.91.25.12135 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PW708 UT WOS:A1994PW70800076 PM 7527552 ER PT J AU PAROUSH, Z FINLEY, RL KIDD, T WAINWRIGHT, SM INGHAM, PW BRENT, R ISHHOROWICZ, D AF PAROUSH, Z FINLEY, RL KIDD, T WAINWRIGHT, SM INGHAM, PW BRENT, R ISHHOROWICZ, D TI GROUCHO IS REQUIRED FOR DROSOPHILA NEUROGENESIS, SEGMENTATION, AND SEX DETERMINATION AND INTERACTS DIRECTLY WITH HAIRY-RELATED BHLH PROTEINS SO CELL LA English DT Article ID HELIX-LOOP-HELIX; RULE GENE-EXPRESSION; OF-SPLIT COMPLEX; PAN-NEURAL GENE; FUSHI-TARAZU; DETERMINATION SIGNAL; ACHAETE-SCUTE; DNA-BINDING; ZYGOTIC CONTROL; SHOWS HOMOLOGY AB We have used the interaction trap, a yeast two-hybrid system, to identify proteins interacting with hairy, a basic-helix-loop-helix (bHLH) protein that represses transcription during Drosophila embryonic segmentation. We find that the groucho (gro) protein binds specifically to hairy and also to hairy-related bHLH proteins encoded by deadpan and the Enhancer of split complex. The C-terminal WRPW motif present in all these bHLH proteins is essential for this interaction. We demonstrate that these associations reflect in vivo maternal requirements for gro during neurogenesis, segmentation, and sex determination, three processes regulated by the above bHLH proteins, and we propose that gro is a transcriptional corepressor recruited to specific target promoters by hairy-related bHLH proteins. C1 UNIV OXFORD,DEPT ZOOL,IMPERIAL CANC RES FUND,DEV BIOL UNIT,DEV GENET LAB,OXFORD OX1 3PS,ENGLAND. UNIV OXFORD,DEPT ZOOL,IMPERIAL CANC RES FUND,DEV BIOL UNIT,MOLEC EMBRYOL LAB,OXFORD OX1 3PS,ENGLAND. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. RI Ingham, Philip/E-6710-2010; Ingham, Philip/G-9903-2011; OI Ingham, Philip/0000-0001-8224-9958; Kidd, Thomas/0000-0001-7190-4208 NR 72 TC 466 Z9 479 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 2 PY 1994 VL 79 IS 5 BP 805 EP 815 DI 10.1016/0092-8674(94)90070-1 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PW054 UT WOS:A1994PW05400008 PM 8001118 ER PT J AU EDER, M ERNST, TJ GANSER, A JUBINSKY, PT INHORN, R HOELZER, D GRIFFIN, JD AF EDER, M ERNST, TJ GANSER, A JUBINSKY, PT INHORN, R HOELZER, D GRIFFIN, JD TI A LOW-AFFINITY CHIMERIC HUMAN ALPHA/BETA-GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-RECEPTOR INDUCES LIGAND-DEPENDENT PROLIFERATION IN A MURINE CELL-LINE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GM-CSF RECEPTOR; HUMAN GROWTH-HORMONE; COMMON BETA-SUBUNIT; HUMAN MYELOID CELLS; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; EXTRACELLULAR DOMAIN; HEMATOPOIETIC-CELLS; CYTOPLASMIC DOMAINS; MOLECULAR CONTROL AB The high affinity receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) is composed of at least two subunits, an 85-kDa low affinity GM-CSF-binding protein (alpha-GMR) and a 120-kDa beta-subunit (beta-GMR) necessary for high affinity binding and signal transduction. Previous studies have shown that deletion of the intracellular do main of alpha-GMR inactivates the receptor's ability to support proliferation, but has no effect on GM-CSF binding. Using anti-alpha-GMR and anti-beta-GMR-specific antibodies, we show that alpha-GMR and beta-GMR coprecipitate only after GM-CSF binding, suggesting that binding of GM-CSF induces stabilization or assembly of an activated receptor complex involving recruitment of beta-GMR chains. To understand the contribution of each subunit of this receptor to the generation of an activated receptor complex, we attempted to construct minimal receptors with some or all of the functions of the wild-type heterodimer. We found that a hybrid human alpha/beta-GMR molecule in which the extracellular and transmembrane segments are composed of alpha-GMR sequences and the intracellular segment is composed of beta-GMR bound GM-CSF with low affinity, but activated tyrosine kinase activity, induced receptor internalization, and supported short- and long-term proliferation of transfected Ba/F3 cells. At least 1 ng/ml human GM-CSF was required for growth stimulation, and maximal proliferation occurred at a concentration of 10 ng/ml. This was 10-100-fold more than needed to stimulate growth of Ba/F3 cells expressing both full-length human alpha-GMR and beta-GMR and 1000-fold less than needed to stimulate growth of Ba/F3 cells expressing only human alpha-GMR. These results indicate that the cytoplasmic domain of alpha-GMR is not required to initiate a unique signaling event for proliferation in Ba/F3 cells, but can be functionally replaced by the cytoplasmic domain of beta-GMR. C1 UNIV FRANKFURT,DEPT HEMATOL,D-60590 FRANKFURT,GERMANY. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCY,BOSTON,MA 02115. DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NCI NIH HHS [CA34183, CA 36167] NR 36 TC 41 Z9 41 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 2 PY 1994 VL 269 IS 48 BP 30173 EP 30180 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU525 UT WOS:A1994PU52500023 PM 7982923 ER PT J AU FESCHENKO, MS SWEADNER, KJ AF FESCHENKO, MS SWEADNER, KJ TI CONFORMATION-DEPENDENT PHOSPHORYLATION OF NA,K-ATPASE BY PROTEIN-KINASE-A AND PROTEIN-KINASE-C SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KINETIC-ANALYSIS; XENOPUS OOCYTES; OUABAIN BINDING; NA+/K+-ATPASE; PUMP; STIMULATION; SODIUM; NA+,K+-ATPASE; DIGITONIN; CELLS AB Phosphorylation of sodium and potassium ion-activated adenosine triphosphatase (Na,K-ATPase) by protein kinase A (PKA) and protein kinase C (PKC) was investigated in vitro, where substrate conformation, kinase activity, and consequent effects on Na,K-ATPase activity could be controlled. With Na, K-ATPase from rat kidney, optimal stoichiometries were close to 1 mol P-32/mol Na,K-ATPase for both kinases. Addition of Na+, K+, P-i, or ouabain is known to stabilize the Na,K-ATPase in different states and was found to affect phosphorylation by the two kinases in a reciprocal way. This indicates that exposure of the phosphorylation sites varies with conformation and suggests a structural basis for the variable responses to kinase activation in intact cells. Further evidence for the importance of Na,K-ATPase conformation in its interaction with kinase came from the autophosphorylation of PKC, which varied in proportion to both the concentration and conformation of rat Na,K-ATPase. With pig and dog Na,K-ATPase, little phosphorylation by PKC was detected, and yet the PKC phosphorylated itself when the Na,K-ATPase was in the optimal conformation. The location of the PKA phosphorylation site was con firmed to be Ser-938 by sequence analysis of a tryptic peptide. Effects of PRA on Na,K-ATPase activity could not be measured because of inhibition by the Triton X-100 needed to obtain phosphorylation. Phosphorylation by PKC, even in optimal conditions, failed to result in inhibition of Na,K-ATPase activity. This suggests that any physiological role of phosphorylation either entails a subtle modulation of enzyme properties, or requires additional regulatory proteins. C1 MASSACHUSETTS GEN HOSP,CTR NEUROSCI,MEMBRANE BIOL LAB,BOSTON,MA 02129. FU NINDS NIH HHS [NS 27653] NR 35 TC 105 Z9 105 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 2 PY 1994 VL 269 IS 48 BP 30436 EP 30444 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU525 UT WOS:A1994PU52500062 PM 7982958 ER PT J AU MCCAFFREY, PG GOLDFELD, AE RAO, A AF MCCAFFREY, PG GOLDFELD, AE RAO, A TI THE ROLE OF NFATP IN CYCLOSPORINE A-SENSITIVE TUMOR-NECROSIS-FACTOR-ALPHA GENE-TRANSCRIPTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED T-CELLS; NUCLEAR FACTOR; INTERLEUKIN-4 GENE; PROMOTER; CALCINEURIN; MACROPHAGE; IDENTIFICATION; EXPRESSION; CONTAINS; SIGNALS AB The tumor necrosis factor-alpha (TNF alpha) gene is an immediate early gene in activated T cells, in that it is rapidly induced without a requirement for protein synthesis. Maximal induction of TNP alpha mRNA can be induced by treatment of T cells with calcium ionophores alone, via a calcineurin dependent process that is blocked by cyclosporin A. We have previously identified a promoter element, kappa 3, that is required for calcium-stimulated, cyclosporin A-sensitive induction of the TNF alpha gene in activated T cells. Here, we demonstrate that the kappa 3 binding factor contains NFATp, a cyclosporin-sensitive DNA-binding protein required for interleukin-a gene transcription. NFATp binds to two sites within the kappa 3 element, and occupancy of both sites is required for TNF alpha gene induction. Thus, although the kappa 3 element has little sequence similarity to other NFATp-binding sites, it appears to function as a cyclosporin-sensitive promoter element in T cells by virtue of its ability to bind NFATp. The involvement of NFATp in transcriptional activation of both the interleukin-2 and TNF alpha genes suggests that this factor plays an important role in the coordinate induction of multiple cytokine genes, starting at the earliest stages of T cell activation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA-42471, CA-58735]; NIGMS NIH HHS [GM-46227] NR 38 TC 118 Z9 119 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 2 PY 1994 VL 269 IS 48 BP 30445 EP 30450 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU525 UT WOS:A1994PU52500063 PM 7982959 ER PT J AU GARCIA, P SHOELSON, SE DREW, JS MILLER, WT AF GARCIA, P SHOELSON, SE DREW, JS MILLER, WT TI PHOSPHOPEPTIDE OCCUPANCY AND PHOTOAFFINITY CROSS-LINKING OF THE V-SRC SH2 DOMAIN ATTENUATES TYROSINE KINASE-ACTIVITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; PHOSPHORYLATED PEPTIDES; BINDING-SITE; PI 3-KINASE; PP60C-SRC; ACTIVATION; VIRUS; PHOSPHOTYROSINE; GENE; ASSOCIATION AB Phosphorylation of c-Src at carboxyl-terminal Tyr-527 suppresses tyrosine kinase activity and transforming potential, presumably by facilitating the intramolecular interaction of the C terminus of Src with its SH2 domain. In addition, it has been shown previously that occupancy of the c-Src SH2 domain with a phosphopeptide stimulates c-Src kinase catalytic activity. We have performed analogous studies with v-Src, the transforming protein from Rous sarcoma virus, which has extensive homology with c-Src. v-Src lacks an autoregulatory phosphorylation site, and its kinase domain is constitutively active. Phosphopeptides corresponding to the sequences surrounding c-Src Tyr-527 and a Tyr-Glu-Glu-Ile motif from the hamster polyoma virus middle T antigen inhibit tyrosine kinase activity of baculovirus-expressed v-Src 2- and 4-fold, respectively. To determine the mechanism of this regulation, the Tyr-527 phosphopeptide was substituted with the photoactive amino acid p-benzoylphenylalanine at the adjacent positions (N- and C-terminal) to phosphotyrosine. These peptides photoinactivate the v-Src tyrosine kinase 5-fold in a time and concentration-dependent manner. Furthermore, the peptides cross-link an isolated Src SH2 domain with similar rates and specificity. These data indicate that occupancy of the v-Src SH2 domain induces a conformational change that is transmitted to the kinase domain and attenuates tyrosine kinase activity. C1 SUNY STONY BROOK, SCH MED, DEPT PHYSIOL & BIOPHYS, STONY BROOK, NY 11794 USA. BRIGHAM & WOMENS HOSP, DEPT MED, JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02215 USA. FU NCI NIH HHS [CA5853001]; NIDDK NIH HHS [T32DK07521] NR 51 TC 10 Z9 10 U1 0 U2 0 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 DEC 2 PY 1994 VL 269 IS 48 BP 30574 EP 30579 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU525 UT WOS:A1994PU52500082 PM 7527032 ER PT J AU HAQQ, CM KING, CY UKIYAMA, E FALSAFI, S HAQQ, TN DONAHOE, PK WEISS, MA AF HAQQ, CM KING, CY UKIYAMA, E FALSAFI, S HAQQ, TN DONAHOE, PK WEISS, MA TI MOLECULAR-BASIS OF MAMMALIAN SEXUAL DETERMINATION - ACTIVATION OF MULLERIAN-INHIBITING SUBSTANCE GENE-EXPRESSION BY SRY SO SCIENCE LA English DT Article ID HUMAN ANDROGEN RECEPTOR; DETERMINING REGION; HMG BOX; CRYSTAL-STRUCTURE; MINOR-GROOVE; DNA-SEQUENCES; DUCT SYNDROME; Y-CHROMOSOME; TATA ELEMENT; XY FEMALES AB The pathway of male sexual development in mammals is initiated by SRY, a gene on the short arm of the Y chromosome. Its expression in the differentiating gonadal ridge directs testicular morphogenesis, characterized by elaboration of Mullerian inhibiting substance (MIS) and testosterone. SRY and MIS each belong to conserved gene families that function in the control of growth and differentiation. Structural and biochemical studies of the DNA binding domain of SRY (the HMG box) revealed a protein-DNA interaction consisting of partial side chain intercalation into a widened minor groove. Functional studies of SRY in a cell line from embryonic gonadal ridge demonstrated activation of a gene-regulatory pathway leading to expression of MIS. SRY molecules containing mutations associated with human sex reversal have altered structural interactions with DNA and failed to induce transcription of MIS. C1 MASSACHUSETTS GEN HOSP, PEDIAT SURG RES LABS, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT SURG, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, DEPT MED, BOSTON, MA 02114 USA. FU NICHD NIH HHS [HD30812, P30HD28138]; NIGMS NIH HHS [GM51558] NR 83 TC 202 Z9 210 U1 0 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD DEC 2 PY 1994 VL 266 IS 5190 BP 1494 EP 1500 DI 10.1126/science.7985018 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PV015 UT WOS:A1994PV01500029 PM 7985018 ER PT J AU SINGER, EJ STONER, GL SINGER, P TOMIYASU, U LICHT, E FAHYCHANDON, B TOURTELLOTTE, WW AF SINGER, EJ STONER, GL SINGER, P TOMIYASU, U LICHT, E FAHYCHANDON, B TOURTELLOTTE, WW TI AIDS PRESENTING AS PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY WITH CLINICAL-RESPONSE TO ZIDOVUDINE SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Note DE PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; JC VIRUS; AIDS; HIV-1; ZIDOVUDINE; CYTARABINE; VIRUS-SPECIFIC PCR ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; JC-VIRUS; NERVOUS-SYSTEM; INFECTION; DNA; BRAIN; PATHOGENESIS; CYTARABINE; AUTOPSY AB Progressive multifocal leukoencephalopathy (PML) due to JC virus can be the initial manifestation of AIDS. A 40-year-old man seropositive for HIV-1 presented with aphasia, hemiparesis, and hemianopsia, and with magnetic resonance imaging of the brain typical of PML. He quickly became bed bound, incontinent, and mute. The diagnosis of PML was established by histopathology in a brain biopsy with positive immunocytochemistry for polyomavirus capsid proteins, and detection of JCV DNA by polymerase chain reaction using JCV-specific primers. High dose zidovudine therapy was initiated (1200 mg/day). Within two weeks the patient began to respond, and after three months he was able to walk and care for himself and was discharged. He lived for two years from the onset of PML. While cytarabine has been the drug most widely used for PML treatment, this is the second confirmed case with apparent response to zidovudine. High dose zidovudine may benefit some previously untreated AIDS patients with onset as PML. C1 W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT PATHOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA 90024. NINCDS,EXPTL NEUROPATHOL LAB,BETHESDA,MD 20892. RP SINGER, EJ (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV W127,WILSHIRE & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. FU NIMH NIH HHS [MH47281 RO1] NR 27 TC 19 Z9 19 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6314 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD DEC PY 1994 VL 90 IS 6 BP 443 EP 447 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA PW675 UT WOS:A1994PW67500012 PM 7892765 ER PT J AU GILL, PS MILES, SA MITSUYASU, RT MONTGOMERY, T MCCARTHY, S ESPINA, BM FELDSTEIN, M LEVINE, AM AF GILL, PS MILES, SA MITSUYASU, RT MONTGOMERY, T MCCARTHY, S ESPINA, BM FELDSTEIN, M LEVINE, AM TI PHASE-I AIDS CLINICAL-TRIALS GROUP(075) STUDY OF ADRIAMYCIN, BLEOMYCIN AND VINCRISTINE CHEMOTHERAPY WITH ZIDOVUDINE IN THE TREATMENT OF AIDS-RELATED KAPOSIS-SARCOMA SO AIDS LA English DT Article DE KAPOSIS SARCOMA; CHEMOTHERAPY; HIV; ANTIRETROVIRAL; ZIDOVUDINE; AIDS ID ACQUIRED IMMUNODEFICIENCY SYNDROME; IMMUNE-DEFICIENCY SYNDROME; VINBLASTINE; COMBINATION AB Objective: To determine the toxicity and maximum tolerated dose of doxorubicin (adriamycin) in combination with fixed doses of bleomycin, vincristine (ABV) and zidovudine in patients with advanced AIDS-related Kaposi's sarcoma. Patients and methods: Twenty-six HIV-seropositive men with Kaposi's sarcoma were treated daily with 100mg zidovudine orally every 4h, along with combination chemotherapy using bleomycin 10 U/m(2) and vincristine 1.4mg/m(2) (maximum, 2mg) given intravenously in 2-week cycles. In addition, three successive cohorts of eight patients received escalating doses of doxorubicin each beginning with no doxorubicin (level I), doses of 10mg/m(2) (level II), and 15mg/m(2) (level III). Results: The major dose-limiting toxicity experienced with the combination therapy was severe neutropenia in eight patients, four of whom received level III doxorubicin (15mg/m(2)). Therefore, 10mg/m(2) of doxorubicin in combination with zidovudine and BV chemotherapy was defined as the maximum tolerated dose. Other dose-limiting toxicities included neuropathy (n = 2), cutaneous toxicity associated with bleomycin (n = 1), and diarrhea (n = 1). Seventeen patients (71%; 95% confidence interval, 46-85) experienced either partial (n = 13) or clinical complete remission (n = 4) to therapy after a median of five cycles (range, 2-9). Conclusion: The maximum tolerated dose of doxorubicin is 10mg/m(2) when given in combination with zidovudine and BV chemotherapy. Response rats observed with the combined antiretroviral and chemotherapy regimen are similar to those previously reported with ABV chemotherapy alone. C1 UNIV SO CALIF,SCH MED,DEPT INTERNAL MED,DIV HEMATOL,LOS ANGELES,CA 90033. UNIV CALIF LOS ANGELES,CARES CTR,LOS ANGELES,CA. FRONTIER SCI & TECHNOL RES FDN INC,BOSTON,MA. DANA FARBER CANC INST,DIV BIOSTAT & EPIDEMIOL,BOSTON,MA. FU PHS HHS [A127550, A127660] NR 13 TC 34 Z9 34 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD DEC PY 1994 VL 8 IS 12 BP 1695 EP 1699 DI 10.1097/00002030-199412000-00009 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PU185 UT WOS:A1994PU18500009 PM 7534090 ER PT J AU JASSOY, C HEINKELEIN, M KLINKER, H WALKER, BD AF JASSOY, C HEINKELEIN, M KLINKER, H WALKER, BD TI HIV TYPE 1-SPECIFIC CYTOTOXIC T-LYMPHOCYTES STIMULATE HLA CLASS-I AND INTERCELLULAR-ADHESION MOLECULE TYPE-1 EXPRESSION AND INCREASE BETA(2)-MICROGLOBULIN LEVELS IN-VITRO SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTO-TOXIC LYMPHOCYTES; TUMOR-NECROSIS-FACTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; LIMITING DILUTION ANALYSIS; AIDS DEMENTIA COMPLEX; CEREBROSPINAL-FLUID; INTERFERON-GAMMA; FACTOR-ALPHA; NEUROLOGIC DISEASE AB Besides acting in a direct manner, cytolytic HIV-1-specific CTLs release a variety of cytokines. To assess the potential role of cytokines released by these CTLs we tested the ability of soluble products secreted by HTV-1-specific CTLs to induce HLA class I and ICAM-1 expression and to raise beta(2)-microglobulin (beta(2)M) concentrations in cell culture. To this end, supernatants were derived from HIV-1-specific CTLs incubated with autologous B lymphoblasts presenting either the cognate HIV-1 epitope or a control peptide. Cell lines and peripheral blood mononuclear cells (PBMCs) were incubated with these supernatants for 24-48 hr. Similarly, cells were cocultured with CTLs and their targets. This study demonstrates that in parallel with lysis of their cognate target, HIV-1-specific CTLs secreted products that stimulated HLA class I and ICAM-1 expression on cell lines and PBMCs. As few as 1000 CTLs significantly induced the expression of these molecules. In addition, secreted products of HIV-specific CTLs enhanced beta(2)M release by PBMCs and Jurkat cells. These effects were mediated primarily by IFN-gamma and suggest that HIV-specific CTLs may contribute to increased HLA class I expression in infected tissue and elevated ICAM-1 and beta(2)M concentrations in serum and cerebrospinal fluid of infected individuals. C1 UNIV WURZBURG,DEPT MED,D-97078 WURZBURG,GERMANY. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP JASSOY, C (reprint author), UNIV WURZBURG,INST VIROL & IMMUNBIOL,VERSBACHER STR 7,D-97078 WURZBURG,GERMANY. FU NIAID NIH HHS [AI30914, AI28568] NR 62 TC 5 Z9 5 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC PY 1994 VL 10 IS 12 BP 1685 EP 1693 DI 10.1089/aid.1994.10.1685 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PZ088 UT WOS:A1994PZ08800014 PM 7888228 ER PT J AU LAVIE, CJ MILANI, RV AF LAVIE, CJ MILANI, RV TI PATIENTS WITH HIGH BASE-LINE EXERCISE CAPACITY BENEFIT FROM CARDIAC REHABILITATION AND EXERCISE TRAINING-PROGRAMS SO AMERICAN HEART JOURNAL LA English DT Article ID MYOCARDIAL-INFARCTION; RETURN; HEART; WORK AB Despite the well-proven benefits of cardiac rehabilitation and exercise training, no data are available on the benefits of this therapy in patients with preserved baseline exercise capacity. Therefore we assessed data before and after phase II cardiac rehabilitation and exercise programs at two large teaching institutions to determine the benefits in 163 patients with high baseline exercise capacity (greater than or equal to 6 estimated [mean 8.8 +/- 2.4] metabolic equivalents [METs]) compared with 125 patients with low baseline functional capacity (<6 estimated [mean 4.6 +/- 0.8] METs). After cardiac rehabilitation and exercise training, patients with high baseline exercise capacity had significant improvements in triglyceride (-10%; p < 0.05), high-density lipoprotein cholesterol (+7%; p < 0.001), and low-density lipoprotein cholesterol (-4%; p = 0.09) levels; low-density lipoprotein/high-density lipoprotein ratio (-10%; p < 0.01); body mass index (-1.5%; (p < 0.001); percent body fat (-6%; p < 0.0001); and exercise capacity (+22%; p < 0.0001). Patients with high baseline exercise capacity had less relative improvement in exercise capacity (p < 0.0001) after cardiac rehabilitation but had greater relative improvement in low-density lipoprotein cholesterol level (p < 0.05) and low-density lipoprotein/high-density lipoprotein ratio (p < 0.05) than did patients with low baseline exercise capacity. These data demonstrate the benefits of cardiac rehabilitation and exercise training in patients with preserved exercise capacity and support routine referral of these patients to these programs after major cardiac events. C1 ALTON OCHSNER MED FDN & OCHSNER CLIN,DEPT INTERNAL MED,CARDIOL SECT,NEW ORLEANS,LA 70121. ALTON OCHSNER MED FDN & OCHSNER CLIN,CARDIOVASC HLTH CTR,NEW ORLEANS,LA 70121. MASSACHUSETTS GEN HOSP,CARDIOVASC HLTH CTR,DEPT PREVENT MED,BOSTON,MA 02114. RI Lavie, Carl/A-6014-2011; Milani, Richard/A-6045-2011 NR 21 TC 34 Z9 35 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 1994 VL 128 IS 6 BP 1105 EP 1109 DI 10.1016/0002-8703(94)90740-4 PN 1 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PV557 UT WOS:A1994PV55700006 PM 7985590 ER PT J AU VUILLE, C NIDORF, M WEYMAN, AE PICARD, MH AF VUILLE, C NIDORF, M WEYMAN, AE PICARD, MH TI NATURAL-HISTORY OF VEGETATIONS DURING SUCCESSFUL MEDICAL-TREATMENT OF ENDOCARDITIS SO AMERICAN HEART JOURNAL LA English DT Article ID INFECTIVE ENDOCARDITIS; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; MITRAL REGURGITATION; DOCUMENTATION; LESIONS AB Although initial morphologic features of vegetations have been related to the risk of early complications, there is little information about the natural history of the vegetations during medical treatment or the relation of morphologic changes in vegetation to late complications. To assess the evolution of valvular vegetations by echocardiography during treatment of infective endocarditis and to relate the morphologic changes in vegetation to late prognosis, serial echocardiograms of patients with successful medical treatment for native valve infective endocarditis were reviewed to assess the presence and morphologic features of valvular vegetations at the onset and at the end of therapy. The evolution of vegetation size, mobility, consistency, the extent of the disease, and the severity of valvular regurgitation were related to late complications such as embolism, valve replacement, or death occurring after the end of therapy. Forty-one vegetations were identified in 32 patients on initial echocardiograms. At the end of treatment, 29 vegetations were still present; 59% had no significant change in size and 52% appeared to be denser in consistency. Morphologic changes did not relate to late complications, but the presence of severe valvular regurgitations was associated with late valve replacement. The echocardiographic persistence of vegetations is common after successful medical treatment of infective endocarditis. In the absence of severe valvular dysfunction, however, persistent vegetations are not independently associated with late complications. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. OI Picard, Michael/0000-0002-9264-3243 NR 19 TC 39 Z9 40 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 1994 VL 128 IS 6 BP 1200 EP 1209 DI 10.1016/0002-8703(94)90752-8 PN 1 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PV557 UT WOS:A1994PV55700018 PM 7985602 ER PT J AU BRUGGE, WR ROSENBERG, DJ ALAVI, A AF BRUGGE, WR ROSENBERG, DJ ALAVI, A TI DIAGNOSIS OF POSTOPERATIVE BILE LEAKS SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID LAPAROSCOPIC CHOLECYSTECTOMY; CHOLESCINTIGRAPHY; COMPLICATIONS AB Bile leaks are the most common biliary complication of laparoscopic cholecystectomy. Cholescintigraphy has been utilized in the past to diagnose postoperative bile leaks after open cholecystectomy. However, the sensitivity and specificity of this imaging technique has not been defined or compared to other clinical tests. We have retrospectively studied 30 patients over a 2-yr period who underwent cholescintigraphy for a possible postoperative bile leak. This study reviewed the cholescintigraphy images, clinical presentations, and abdominal ultrasonography/CT scanning. Using a gold standard that consisted of the findings of cholangiography and clinical outcome, we determined the diagnostic accuracy of these tests. Symptoms, laboratory testing, and physical examination were found to be poor predictors for the presence of postoperative bile leaks. Ultrasound and CT imaging were less sensitive and nonspecific. In contrast, cholescintigraphy was found to be quite accurate (83-87%) for predicting the presence of bile leaks after laparoscopic cholecystectomy, as well as other biliary surgeries. C1 HOSP UNIV PENN,DEPT MED,PHILADELPHIA,PA 19104. HOSP UNIV PENN,DEPT NUCL MED,PHILADELPHIA,PA 19104. RP BRUGGE, WR (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BULFINCH 127,BOSTON,MA 02114, USA. NR 17 TC 27 Z9 27 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD DEC PY 1994 VL 89 IS 12 BP 2178 EP 2183 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PW195 UT WOS:A1994PW19500016 PM 7977237 ER PT J AU SMALL, GW AF SMALL, GW TI HANNAHS HEIRS - THE QUEST FOR THE GENETIC ORIGINS OF ALZHEIMERS-DISEASE - POLLEN,DA SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Book Review C1 UNIV CALIF LOS ANGELES, INST NEUROPSYCHIAT, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES HOSP, LOS ANGELES, CA USA. W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA USA. RP SMALL, GW (reprint author), UNIV CALIF LOS ANGELES, SCH MED, GERIATR CONSULTAT PSYCHIAT SERV, LOS ANGELES, CA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD WIN PY 1994 VL 2 IS 1 BP 86 EP 87 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA MY119 UT WOS:A1994MY11900011 ER PT J AU WHALEY, JM NAGLICH, J GELBERT, L HSIA, YE LAMIELL, JM GREEN, JS COLLINS, D NEUMANN, HPH LAIDLAW, J LI, FP KLEINSZANTO, AJP SEIZINGER, BR KLEY, N AF WHALEY, JM NAGLICH, J GELBERT, L HSIA, YE LAMIELL, JM GREEN, JS COLLINS, D NEUMANN, HPH LAIDLAW, J LI, FP KLEINSZANTO, AJP SEIZINGER, BR KLEY, N TI GERM-LINE MUTATIONS IN THE VON HIPPEL-LINDAU TUMOR-SUPPRESSOR GENE ARE SIMILAR TO SOMATIC VON HIPPEL-LINDAU ABERRATIONS IN SPORADIC RENAL-CELL CARCINOMA SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DISEASE GENE; CEREBELLAR HEMANGIOBLASTOMA; MOLECULAR CHARACTERIZATION; GEL-ELECTROPHORESIS; SHORT ARM; PCR-SSCP; VONHIPPEL; CHROMOSOME-3; DNA; DELETION AB von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome predisposing to multifocal bilateral renal. cell carcinomas (RCCs), pheochromocytomas, and pancreatic tumors, as well as angiomas and hemangioblastomas of the CNS. A candidate gene for VHL was recently identified, which led to the isolation of a partial cDNA clone with extended open reading frame, without significant homology to known genes or obvious functional motifs, except for an acidic pentamer repeat domain. To further characterize the functional domains of the VHL gene and assess its involvement in hereditary and nonhereditary tumors, we performed mutation analyses and studied its expression in normal and tumor tissue. We identified germline mutations in 39% of VHL disease families. Moreover, 33% of sporadic RCCs and ah (6/6) sporadic RCC cell lines analyzed showed mutations within the VHL gene. Both germ-line and somatic mutations included deletions, insertions, splice-site mutations, and missense and nonsense mutations, all of which clustered at the 3' end of the corresponding partial VHL cDNA open reading frame, including an alternatively spliced exon 123 nt in length, suggesting functionally important domains encoded by the VHL gene in this region. Over 180 sporadic tumors of other types have shown no detectable base changes within the presumed coding sequence of the VHL gene to date. We conclude that the gene causing VHL has an important and specific role in the etiology of sporadic RCCs, acts as a recessive tumor-suppressor gene, and appears to encode important functional domains within the 3' end of the known open reading frame. C1 UNIV HAWAII,JOHN A BURNS SCH MED,HONOLULU,HI. BROOKE ARMY MED CTR,DEPT CLIN INVEST,FT SAM HOUSTON,TX. MEM UNIV NEWFOUNDLAND,HLTH SCI CTR,ST JOHNS,NF,CANADA. UNIV KANSAS,MED CTR,DIV ENDOCRINOL METAB & GENET,KANSAS CITY,KS. UNIV FREIBURG,DEPT MED,FREIBURG,GERMANY. DANA FARBER CANC INST,BOSTON,MA. FOX CHASE CANC CTR,PHILADELPHIA,PA. RP WHALEY, JM (reprint author), BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOLEC GENET & CELL BIOL,POB 4000,PRINCETON,NJ 08543, USA. NR 45 TC 179 Z9 181 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 1994 VL 55 IS 6 BP 1092 EP 1102 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA QB684 UT WOS:A1994QB68400004 PM 7977367 ER PT J AU ROGGLI, VL HAMMAR, SP PRATT, PC MADDOX, JC LEGIER, J MARK, EJ BRODY, AR AF ROGGLI, VL HAMMAR, SP PRATT, PC MADDOX, JC LEGIER, J MARK, EJ BRODY, AR TI DOES ASBESTOS OR ASBESTOSIS CAUSE CARCINOMA OF THE LUNG SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Editorial Material DE ASBESTOS; ASBESTOSIS; LUNG CANCER; CARCINOMA ID CANCER; MORTALITY; EXPOSURE; FIBROSIS C1 VET ADM MED CTR, DEPT PATHOL, DURHAM, NC USA. DIAGNOST SPECIALTIES LAB, BREMERTON, WA USA. RIVERSIDE REG MED CTR, DEPT PATHOL, NEWPORT NEWS, VA USA. MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. TULANE UNIV, SCH MED, DEPT PATHOL, NEW ORLEANS, LA 70112 USA. RP ROGGLI, VL (reprint author), DUKE UNIV, MED CTR, DEPT PATHOL, BOX 3712, DURHAM, NC 27710 USA. NR 19 TC 24 Z9 25 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0271-3586 EI 1097-0274 J9 AM J IND MED JI Am. J. Ind. Med. PD DEC PY 1994 VL 26 IS 6 BP 835 EP 838 DI 10.1002/ajim.4700260613 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QF922 UT WOS:A1994QF92200012 PM 7892835 ER PT J AU WESTGATE, MN HOLMES, LB AF WESTGATE, MN HOLMES, LB TI DOUBLE FINGERNAILS ON 5TH FINGERS SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter C1 MASSACHUSETTS GEN HOSP,GENET & TERATOL UNIT,BOSTON,MA 02114. NR 3 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 1 PY 1994 VL 53 IS 4 BP 395 EP 395 DI 10.1002/ajmg.1320530424 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA QF817 UT WOS:A1994QF81700023 PM 7864057 ER PT J AU MOORREES, CFA AF MOORREES, CFA TI SEEDS ARE SPROUTING SO AMERICAN JOURNAL OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS LA English DT Letter C1 FORSYTH DENT CTR,BOSTON,MA 02115. RP MOORREES, CFA (reprint author), HARVARD UNIV,SCH DENT MED,CAMBRIDGE,MA 02138, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0889-5406 J9 AM J ORTHOD DENTOFAC JI Am. J. Orthod. Dentofac. Orthop. PD DEC PY 1994 VL 106 IS 6 BP A11 EP A11 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PW727 UT WOS:A1994PW72700004 PM 7977200 ER PT J AU PIERCE, GF TARPLEY, JE ALLMAN, RM GOODE, PS SERDAR, CM MORRIS, B MUSTOE, TA BERG, JV AF PIERCE, GF TARPLEY, JE ALLMAN, RM GOODE, PS SERDAR, CM MORRIS, B MUSTOE, TA BERG, JV TI TISSUE-REPAIR PROCESSES IN HEALING CHRONIC PRESSURE ULCERS TREATED WITH RECOMBINANT PLATELET-DERIVED GROWTH-FACTOR BB SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX; HUMAN-FIBROBLASTS; MESSENGER-RNA; WOUND REPAIR; FACTOR-BETA; COLLAGEN; FIBRONECTIN; STIMULATION; PDGF; DEPOSITION AB Cellular and molecular mechanisms responsible for the observed vulnerary effects of recombinant human platelet-derived growth factor BB (rPDGF-BB) in man have not been elucidated In a double-blinded trial, patients having chronic pressure ulcers were treated topically with either rPDGF-BB or placebo for 28 days. To explore how rPDGF-BB may induce chronic wounds to heal, biopsies were taken from the ulcers of a cohort of 20 patients from the trial and evaluated in a blinded fashion by light microscopy for 1), fibroblast content, 2), neovessel formation, and 3), collagen deposition. Electron microscopy also was used to assess fibroblast activation and collagen deposition. Before initiation of therapy most wounds had few fibroblasts and most of those present were not activated. When mean scores for the total active treatment phase (days 8, 15, and 29) for rPDGF-BB-treated ulcers were compared with the scores for placebo-treated ulcers, fibroblast content was significantly higher for the rPDGF-BB-treated ulcers (P = 0.03, Kruskal-Wallis test). More significant differences in fibroblast and neovessel content were observed when six nonhealing wounds were eliminated from the analysis (three placebo, three treatment). Thus, in all healing wounds, rPDGF-BB therapy significantly increased fibroblast (P = 0.0007) and neovessel (P = 0.02) content. These results were correlated with increased collagen fibrillogenesis by fibroblasts from healing rPDGF-BB-treated wounds, as assessed by intracellular procollagen type I immunostaining, and by electron microscopy, and were concordant with clinical measurements (eg, area of ulcer opening and ulcer volume) which showed greater healing in rPDGF-BB-treated wounds. These results suggest induction of fibroblast proliferation and differentiation is one mechanism by which rPDGF-BB can accelerate wound healing and that rPDGF-BB can augment healing responses within a majority of, but not all, nonhealing chronic pressure ulcers in man. C1 AMGEN INC,DEPT EXPTL PATHOL,THOUSAND OAKS,CA 91320. UNIV ALABAMA,CTR AGING,DEPT MED,BIRMINGHAM,AL. BIRMINGHAM VET AFFAIRS MED CTR,BIRMINGHAM,AL. AMGEN INC,DEPT CLIN AFFAIRS,THOUSAND OAKS,CA 91320. NORTHWESTERN UNIV,DIV PLAST & RECONSTRUCT SURG,CHICAGO,IL 60611. UNIV CALIF SAN DIEGO,VET AFFAIRS MED CTR,CORE ELECTRON MICROSCOPY LAB,SAN DIEGO,CA 92161. RI Allman, Richard/D-5964-2011 NR 45 TC 60 Z9 60 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 1994 VL 145 IS 6 BP 1399 EP 1410 PG 12 WC Pathology SC Pathology GA PW173 UT WOS:A1994PW17300019 PM 7992843 ER PT J AU RAMIREZ, JA GOODMAN, WG BELIN, TR GALES, B SEGRE, GV SALUSKY, IB AF RAMIREZ, JA GOODMAN, WG BELIN, TR GALES, B SEGRE, GV SALUSKY, IB TI CALCITRIOL THERAPY AND CALCIUM-REGULATED PTH SECRETION IN PATIENTS WITH SECONDARY HYPERPARATHYROIDISM SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE PARATHYROID HORMONE; 1,25-DIHYDROXYVITAMIN D ID PARATHYROID-HORMONE RELEASE; INTRAVENOUS CALCITRIOL; HEMODIALYSIS-PATIENTS; ORAL CALCITRIOL; UREMIC PATIENTS; CELLS; DIALYSIS; ASSAY; 1,25-DIHYDROXYVITAMIN-D; HYPERCALCEMIA AB Calcitriol lowers serum parathyroid hormone (PTH) levels in patients with secondary hyperparathyroidism, but its effect on calcium-regulated PTH release remains controversial. Thus 11 patients with secondary hyperparathyroidism underwent dynamic tests of parathyroid function before and after 4 mo of intermittent calcitriol therapy. Serum calcitriol levels rose from 8 +/- 1 to 55 +/- 9 (SE) pg/ml, P < 0.01, serum total and ionized calcium levels increased, and serum PTH levels decreased from 584 +/- 154 to 154 +/- 31 pg/ml, P < 0.05. The maximum increase in serum PTH during hypocalcemia did not differ before (248 +/- 78 pg/ml) or after (280 +/- 100 pg/ml) treatment, but the increase in PTH, expressed as a percentage of preinfusion values, was greater after treatment (329 +/- 73 vs. 132 +/- 10%, P < 0.05). The decreases in serum PTH during calcium infusions did not differ before (70 +/- 5%) or after (73 +/- 5%) therapy, and the set point for PTH release did not change (1.20 +/- 0.03 vs. 1.23 +/- 0.01 mmol/l, not significant). Calcitriol modifies PTH secretion during hypocalcemia in secondary hyperparathyroidism without affecting the set point for PTH release; although calcitriol lowers serum PTH levels, it may also restore the secretory reserve of hyperplastic parathyroid tissues during hypocalcemia. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT PEDIAT, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT RADIOL, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT BIOMATH, LOS ANGELES, CA 90024 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED, ENDOCRINE UNIT, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-00865]; NIAMS NIH HHS [AR-41853]; NIDDK NIH HHS [DK-35423] NR 30 TC 39 Z9 39 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD DEC PY 1994 VL 267 IS 6 BP E961 EP E967 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PX940 UT WOS:A1994PX94000024 PM 7810641 ER PT J AU KIRALY, A SUTO, G LIVINGSTON, EH GUTH, PH STPIERRE, S TACHE, Y AF KIRALY, A SUTO, G LIVINGSTON, EH GUTH, PH STPIERRE, S TACHE, Y TI CENTRAL VAGAL ACTIVATION BY TRH INDUCES GASTRIC HYPEREMIA - ROLE OF CGRP IN CAPSAICIN-SENSITIVE AFFERENTS IN RATS SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE CALCITONIN GENE RELATED PEPTIDE ANTAGONIST; VAGAL EFFERENT; CAPSAICIN-SENSITIVE SPLANCHNIC AFFERENT FIBERS; NITRIC OXIDE; GASTRIC MUCOSAL BLOOD FLOW; THYROTROPIN-RELEASING HORMONE ANALOG; RX-77368; BETHANECHOL; SUBSTANCE P ANTAGONIST ID GENE-RELATED PEPTIDE; MUCOSAL BLOOD-FLOW; THYROTROPIN-RELEASING-HORMONE; HYDROGEN GAS CLEARANCE; NITRIC-OXIDE; SENSORY NEURONS; SUBSTANCE-P; CALCITONIN; ANALOG; ACID AB The role of calcitonin gene-related peptide (CGRP) in the vagal cholinergic-mediated increase in gastric mucosal blood flow (GMBF) induced by the stable thyrotropin-releasing hormone (TRH) analogue RX-77368 injected intracisternally (ic, 30 ng) was investigated in urethan-anesthetized rats using the hydrogen gas clearance technique. alpha-CGRP (14 mu g.kg(-1).h(-1)) or bethanechol (150 mu g.kg(-1).h(-1)) infused close intra-arterially to the stomach or RX-77368 injected intracisternally increased GMBF by 76, 102, and 131%, respectively, 30 min after administration. The CGRP antagonist, human CGRP-(8-37) [hCGRP-(8-37)], injected intravenously (15 mu g/kg bolus and 3 mu g.kg(-1).h(-1)) inhibited by 100, 97, and 73% the gastric hyperemic response to alpha-CGRP, TRH analogue, and bethanechol, respectively, whereas the substance P antagonist CP-96,345 (3 mg/kg iv) had no effect. In capsaicin-pretreated rats, hCGRP-(8-37) no longer blocked the increase in GMBF induced by intracisternal RX-77368. These results suggest that the gastric hyperemic response to central vagal activation induced by intracisternal TRH analogue at 30 ng is mediated by local effector function of capsaicin-sensitive afferent fibers releasing CGRP. C1 UNIV CALIF LOS ANGELES, W LOS ANGELES VET AFFAIRS MED CTR, CTR ULCER RES & EDUC, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, DEPT MED & SURG, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, INST BRAIN RES, LOS ANGELES, CA 90073 USA. UNIV QUEBEC, INST NATL RECH SCI SANTE, POINTE CLAIRE, PQ H9R 1G6, CANADA. NR 39 TC 30 Z9 30 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD DEC PY 1994 VL 267 IS 6 BP G1041 EP G1049 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA PY111 UT WOS:A1994PY11100013 ER PT J AU ZITTEL, TT ROTHENHOFER, I MEYER, JH RAYBOULD, HE AF ZITTEL, TT ROTHENHOFER, I MEYER, JH RAYBOULD, HE TI SMALL-INTESTINAL CAPSAICIN-SENSITIVE AFFERENTS MEDIATE FEEDBACK INHIBITION OF GASTRIC-EMPTYING IN RATS SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Note DE SENSORY; DUODENUM; SMALL INTESTINE; LIPID; HYDROCHLORIC ACID; GLUCOSE; NUTRIENTS ID SENSORY NEURONS; NERVE-FIBERS; GLUCOSE AB Functional studies have implied the existence of small intestinal receptive mechanisms for components of chyme to mediate feedback inhibition of gastric function. However, it is not known if the sensors are in the wall of the small intestine or located at another site. The present studies evaluated the localization of receptive mechanisms mediating intestinal feedback inhibition of gastric emptying by functional ablation of intestinal capsaicin-sensitive afferents. Perfusion of the small intestine of conscious rats with hydrochloric acid (0.1 N; total amount 50 meg), glucose (1 M; total amount 90 mg), or a lipid emulsion (Intralipid 10%; total amount 50 mg) inhibited gastric emptying. One to 7 days after perfusion of the intestine with capsaicin (3.6 mu mol), feedback inhibition of gastric emptying produced by acid, glucose, or lipid was inhibited 100, 59, and 42%, respectively. We conclude that acid-induced inhibition of gastric emptying is mediated entirely by small intestinal capsaicin-sensitive afferent neurons and that a major portion of the glucose-induced inhibition of gastric emptying is mediated by small intestinal afferents. However, only a minor part of the response to lipid is mediated by this pathway. C1 UNIV CALIF LOS ANGELES, W LOS ANGELES VET AFFAIRS MED CTR, CTR ULCER RES & EDUC, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, BRAIN RES INST, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, BRAIN RES INST, DEPT PHYSIOL, LOS ANGELES, CA 90073 USA. NR 22 TC 42 Z9 42 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD DEC PY 1994 VL 267 IS 6 BP G1142 EP G1145 PG 4 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA PY111 UT WOS:A1994PY11100025 ER PT J AU ABBATE, M BONVENTRE, JV BROWN, D AF ABBATE, M BONVENTRE, JV BROWN, D TI THE MICROTUBULE NETWORK OF RENAL EPITHELIAL-CELLS IS DISRUPTED BY ISCHEMIA AND REPERFUSION SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE ACUTE RENAL FAILURE; KIDNEY; MICROTUBULES; COLCHICINE ID COLCHICINE-INDUCED REDISTRIBUTION; PROTEINS; TUBULIN; CALCIUM; KIDNEY; DELIVERY; ATPASE; POLYMERIZATION; CYTOSKELETON; FAILURE AB Ischemia results in alterations in the integrity of the plasma membrane of renal epithelial cells, changes in cell polarity, and initiation of cell division. Because microtubules are implicated in these processes, we examined the effects of ischemia and reperfusion on the microtubular cytoskeleton in rat kidney. Major alterations in the microtubule network of S3 proximal tubules were detected after 40 min of ischemia followed by 1 h of reperfusion. There was fragmentation of microtubules and considerably less intense staining with antitubulin antibodies than with normal kidneys. Some thick ascending limbs of Henle close to medullary vascular bundles showed a variable loss of tubulin staining. After 24 and 48 h of reperfusion, tubulin labeling was again present in most proximal tubule cells in contact with the basement membrane but was not detectable in exfoliated cells. Numerous mitotic figures were present in kidneys 48 h after reperfusion. Kidneys subjected to 40 min of ischemia without reperfusion and contralateral kidneys studied after 1 h of reperfusion showed only mild microtubular disruption. Because of the established role of microtubules in the generation and maintenance of epithelial cell polarity, their loss may contribute to structural changes that occur after ischemia and reperfusion. C1 MASSACHUSETTS GEN HOSP, RENAL UNIT, BOSTON, MA 02129 USA. MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02129 USA. FU NIDDK NIH HHS [DK-42956, DK-38452, DK-39773] NR 33 TC 40 Z9 40 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrol. Physiol. PD DEC PY 1994 VL 267 IS 6 BP F971 EP F978 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA PX951 UT WOS:A1994PX95100010 PM 7810705 ER PT J AU HAMMOND, TG MAJEWSKI, RR MUSE, KE OBERLEY, TD MORRISSEY, LW AMENDTRADUEGE, AM AF HAMMOND, TG MAJEWSKI, RR MUSE, KE OBERLEY, TD MORRISSEY, LW AMENDTRADUEGE, AM TI ENERGY-TRANSFER ASSAYS OF RAT RENAL CORTICAL ENDOSOMAL FUSION - EVIDENCE FOR SUPERFUSION SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the American-Society-of-Nephrology CY NOV 15-18, 1992 CL BALTIMORE, MD SP AMER SOC NEPHROL DE KIDNEY; FLOW CYTOMETRY; ENERGY TRANSFER; ENDOCYTOSIS; CYTOSOL ID CELL-FREE SYSTEM; MEMBRANE-VESICLES; PROTEINS; ENDOCYTOSIS; SECRETION; RECEPTORS; WATER AB The complex of components necessary to allow endosomal fusion includes both membrane-bound receptors and several soluble proteins. Although these factors have been isolated from cultured cell lines, and endosomal fusion has been reconstituted in vitro for vesicular systems from yeast to synaptosomes, there is a paucity of data from mammalian systems. To investigate fusion in rat renal cortical endosomes, we began by developing a fusion assay. As the immunoglobulin and avidin-based probes almost universally employed in fusion assays are excluded by the glomerular ultrafiltration barrier, it was necessary to begin by finding ultrafilterable probes which could serve as a fusion assay. We labeled the apical endosomal pathway of the renal proximal tubule by intravenous infusion of ultrafilterable fluorescent dextrans. Energy transfer from entrapped fluorescein-dextran to rhodamine-dextran had a narrow concentration dependence but allowed fluorometric assay of endosomal fusion. The ''spectroscopic ruler'' property of energy transfer, whereby it will only occur at < 60 Angstrom, makes fusion measurements unequivocal. The energy transfer efficiency of fluorometric (48 +/- 1%) and flow cytometry (57 +/- 1%) assays were close to the theoretical optimum (57%). Energy transfer is detected as a decrease in fluorescence of the fluorescein donor and an increase in fluorescence of the rhodamine acceptor. Our endosomal fusion assay was utilized to determine the optimal conditions for fusion of rat renal cortical light endosomes and heavy endosomes. Independent measurements of fluorescein-dextran and rhodamine-dextran on an endosome-by-endosome basis using dual-beam two-color flow cytometry demonstrated that each fusion event involves multiple endosomes rather than a single pair of endosomes. Electron microscopy analysis demonstrated that the average vesicle diameter was five times larger in the fused heavy endosomal fractions compared with control fractions without fusion. Hence, fusion of mammalian renal cortical endosomes reconstituted in vitro is consistent with multiple fusion events dubbed superfusion. C1 UNIV WISCONSIN, HOSP & CLIN, DEPT MED, MADISON, WI 53706 USA. UNIV WISCONSIN, HOSP & CLIN, DEPT PATHOL, MADISON, WI 53706 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, MADISON, WI 53706 USA. UNIV WISCONSIN, CTR COMPREHENS CANC, FLOW CYTOMETRY LAB, MADISON, WI 53792 USA. NR 32 TC 10 Z9 10 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrol. Physiol. PD DEC PY 1994 VL 267 IS 6 BP F1021 EP F1033 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA PX951 UT WOS:A1994PX95100016 ER PT J AU BERESIN, EV AF BERESIN, EV TI DEVELOPMENTAL FORMULATION AND PSYCHOTHERAPY OF BORDERLINE ADOLESCENTS SO AMERICAN JOURNAL OF PSYCHOTHERAPY LA English DT Article ID PERSONALITY-DISORDER AB The author describes the process of arriving at a developmental formulation and psychotherapeutic technique for the borderline adolescent A variety of theoretical models of etiology and treatment are discussed, many of which conflict. The author points out that therapists must choose among conflicting models and, at times, mix or change therapeutic models during the course of treatment. The potential risks and benefits of altering therapeutic models is described in detail. A case example in which the developmental formulation and therapeutic model changed during the course of therapy is presented. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MCLEAN HOSP,DEPT PSYCHIAT,BELMONT,MA 02178. RP BERESIN, EV (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BULFINCH 449,BOSTON,MA 02114, USA. NR 35 TC 2 Z9 3 U1 1 U2 3 PU ASSN ADVAN PSYCHOTHERAPY PI BRONX PA BELFER EDUC CENTER, ROOM 402 ALBERT EINSTEIN COLL MED 1300 MORRIS PARK AVE, BRONX, NY 10461-1602 SN 0002-9564 J9 AM J PSYCHOTHER JI Am. J. Psychother. PD WIN PY 1994 VL 48 IS 1 BP 5 EP 29 PG 25 WC Psychology, Clinical; Psychiatry; Psychology; Psychology, Psychoanalysis SC Psychology; Psychiatry GA MW622 UT WOS:A1994MW62200002 PM 8179027 ER PT J AU GANS, JS AF GANS, JS TI INDIRECT COMMUNICATION AS A THERAPEUTIC TECHNIQUE - A NOVEL USE OF COUNTERTRANSFERENCE SO AMERICAN JOURNAL OF PSYCHOTHERAPY LA English DT Article AB Recognizing those moments in psychotherapy when it is not useful or even counterproductive to speak directly to the patient, this paper discusses indirect communication as a therapeutic technique. Using this method, the therapist thinks aloud in the room without looking at the patient. The therapist formulates the soliloquy in response to bis or her countertransference. Winnicottian concepts provide a theoretical rationale The background and description of the technique, along with concerns about and contraindications to its use are discussed. Three clinical applications are presented. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,BOSTON,MA 02115. NR 23 TC 3 Z9 3 U1 0 U2 1 PU ASSN ADVAN PSYCHOTHERAPY PI BRONX PA BELFER EDUC CENTER, ROOM 402 ALBERT EINSTEIN COLL MED 1300 MORRIS PARK AVE, BRONX, NY 10461-1602 SN 0002-9564 J9 AM J PSYCHOTHER JI Am. J. Psychother. PD WIN PY 1994 VL 48 IS 1 BP 120 EP 140 PG 21 WC Psychology, Clinical; Psychiatry; Psychology; Psychology, Psychoanalysis SC Psychology; Psychiatry GA MW622 UT WOS:A1994MW62200011 PM 8179024 ER PT J AU BENNETT, CL WEINSTEIN, RA SHAPIRO, MF KESSLER, HA DICKINSON, GM PETERSON, B COHN, SE GEORGE, WL GILMAN, SC AF BENNETT, CL WEINSTEIN, RA SHAPIRO, MF KESSLER, HA DICKINSON, GM PETERSON, B COHN, SE GEORGE, WL GILMAN, SC TI A RAPID PREADMISSION METHOD FOR PREDICTING INPATIENT COURSE OF DISEASE FOR PATIENTS WITH HIV-RELATED PNEUMOCYSTIS-CARINII PNEUMONIA SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IN-HOSPITAL MORTALITY; SERUM LACTATE-DEHYDROGENASE; SYSTEM; EXPERIENCE; ERROR AB Pneumocystis carinii pneumonia (FCP) has been the most common reason for hospitalization and the most common cause of death for persons with HIV infection. Hospital mortality rates for PCP range from 10 to 60%. Studies that evaluate differences in hospital mortality rates must control for differences in patient severity of illness. We developed a simple staging system for categorizing severity of illness in patients with PCP. We analyzed the relation between clinical factors and in-hospital mortality for 576 hospitalized patients with HIV-related PCP treated at 56 hospitals for the years 1987 to 1990. Four stages of PCP could be identified based on three routinely measured clinical variables: alveolar-arterial oxygen difference, total lymphocyte count, and body mass index. The mortality rate increased by stage: 1% for Stage 1, 8% for Stage 2, 23% for Stage 3, and 48% for Stage 4. The four-stage severity system compared well with previous models developed for AIDS and for PCP, and is easier to use in clinical practice. Our staging system identifies patients with a high and low risk of in-hospital death upon admission. Physicians may benefit from consideration of PCP stage in deciding on management strategies. In addition, researchers involved in clinical trials of new agents for FCP might consider stratification by PCP stage in order to define homogenous groups. C1 DURHAM VET ADM HOSP,DIV HLTH SERV RES,DURHAM,NC. DUKE UNIV,DIV HEMATOL ONCOL,DURHAM,NC. DUKE UNIV,CTR HLTH POLICY RES & EDUC,DURHAM,NC. DUKE UNIV,DIV BIOSTAT,DURHAM,NC. DUKE UNIV,DEPT MED,DURHAM,NC. RUSH PRESBYTERIAN ST LUKES MED SCH,CHICAGO,IL. UNIV ILLINOIS,URBANA,IL 61801. UNIV ROCHESTER,ROCHESTER,NY. UNIV MIAMI,MIAMI,FL 33152. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. RAND CORP,SANTA MONICA,CA. VET ADM MED CTR,WESTERN REG SPECIAL STUDIES GRP,LONG BEACH,CA 90822. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP BENNETT, CL (reprint author), LAKESIDE VET ADM MED CTR,111,333 E HURON ST,CHICAGO,IL 60611, USA. RI Bennett, Charles/C-2050-2008 FU AHRQ HHS [1-RO1-HS-06494-01]; PHS HHS [1 R03 H 507846-1] NR 18 TC 38 Z9 39 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC PY 1994 VL 150 IS 6 BP 1503 EP 1507 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PV967 UT WOS:A1994PV96700004 PM 7952607 ER PT J AU HERLIHY, JP VENEGAS, JG SYSTROM, DM GREENE, RE MCKUSICK, KA WAIN, JC GINNS, LC AF HERLIHY, JP VENEGAS, JG SYSTROM, DM GREENE, RE MCKUSICK, KA WAIN, JC GINNS, LC TI EXPIRATORY FLOW PATTERN FOLLOWING SINGLE-LUNG TRANSPLANTATION IN EMPHYSEMA SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID LIMITATION; DIAGNOSIS; OBSTRUCTION AB In single lung transplantation (SLT) recipients, a ''plateau'' of the maximal expiratory Row volume curve (MEFV) and a ''biphasic'' MEFV have been reported to reflect anastomosis pathology. A plateau is defined as constant airflow over a large expired volume early in the MEFV. A biphasic MEFV has an initial period of high flow followed by a terminal low flow phase. Models of expiratory flow limitation by wave speed, however, predict that the MEFV of SLT recipients with emphysema should both be biphasic and demonstrate a plateau even without anastomosis pathology. Review of the spirometries and clinical courses of our first ten patients receiving SLT for emphysema demonstrated a biphasic MEFV, and a plateau of the MEFV in all patients. No patient showed evidence of anastomosis pathology. Independent lung spirometries, generated by a novel technique, revealed that the initial high flow phase of the MEFV came from the transplanted lung and the terminal low flow from the native emphysematous lung. The location of the flow limitation was demonstrated to be immediately downstream from the anastomosis. Therefore, the MEFV of SLT recipients with emphysema routinely demonstrates both a biphasic pattern and a plateau, neither of which necessarily reflect anastomosis pathology. C1 MASSACHUSETTS GEN HOSP,LUNG TRANSPLANTAT PROGRAM,PULM & CRIT CARE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,LUNG TRANSPLANTAT PROGRAM,THORAC SURG UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,LUNG TRANSPLANTAT PROGRAM,RADIOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,LUNG TRANSPLANTAT PROGRAM,BIOMED ENGN UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NHLBI NIH HHS [K08HL42593-03, R01-HL38267, T32 HL07354] NR 16 TC 10 Z9 10 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC PY 1994 VL 150 IS 6 BP 1684 EP 1689 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PV967 UT WOS:A1994PV96700033 PM 7952633 ER PT J AU GALLI, SJ WERSHIL, BK COSTA, JJ TSAI, M AF GALLI, SJ WERSHIL, BK COSTA, JJ TSAI, M TI FOR BETTER OR FOR WORSE - DOES STEM-CELL FACTOR IMPORTANTLY REGULATE MAST-CELL FUNCTION IN PULMONARY PHYSIOLOGY AND PATHOLOGY SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Editorial Material ID C-KIT LIGAND; MEDIATOR RELEASE; IGE C1 BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. CHILDRENS HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA. RP GALLI, SJ (reprint author), BETH ISRAEL HOSP,DEPT PATHOL,DIV EXPTL PATHOL,RES N 227,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 12 TC 8 Z9 8 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 1994 VL 11 IS 6 BP 644 EP 645 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA PW261 UT WOS:A1994PW26100002 PM 7524569 ER PT J AU GREENE, R THOMPSON, S JANTSCH, HS TEPLICK, R CULLEN, DJ GREENE, EM WHITMAN, GJ HULKA, CA LLEWELLYN, HJ AF GREENE, R THOMPSON, S JANTSCH, HS TEPLICK, R CULLEN, DJ GREENE, EM WHITMAN, GJ HULKA, CA LLEWELLYN, HJ TI DETECTION OF POOLED SECRETIONS ABOVE ENDOTRACHEAL-TUBE CUFFS - VALUE OF PLAIN RADIOGRAPHS IN SHEEP CADAVERS AND PATIENTS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID MECHANICALLY VENTILATED PATIENTS; NOSOCOMIAL PNEUMONIA; RISK; ASPIRATION; INFECTIONS; PROGNOSIS AB OBJECTIVE. Mechanical ventilation is thought to increase the risk of nosocomial pneumonia by permitting leakage of bacteria-laden gastro-oropharyngeal secretions into the upper airways. The goal of this study was (a) to validate radiographic signs of pooled secretions above endotracheal-tube cuffs (supracuff liquid) in an animal model and (b) to determine whether suctionable pooled supracuff liquid can be identified on bedside radiographs of intubated patients. MATERIALS AND METHODS. Diagnostic criteria for supracuff liquid were initially validated by three radiologists interpreting 162 randomized radiographs made in an intubated sheep cadaver. The primary criteria included (a) replacement of the normal supracuff lucency with liquid opacity and (b) the formation of a sharp interface between the lucency of the upper edge of the cuff below and the liquid above. Graded infusions of 0, 3, 8, 13, and 23 mi of saline were made in triplicate into the space above the cuff, and radiographs were evaluated for the presence or absence of saline. The validated diagnostic criteria were used by two radiologists to estimate the frequency with which pooled liquid was seen on portable chest radiographs of 47 patients undergoing elective short-term postanesthetic mechanical ventilation. RESULTS. In the sheep-cadaver model, the diagnostic criteria for supracuff liquid allowed successful differentiation between no liquid, a small amount of liquid (3-8 mi), and a large amount of liquid (13-23 mi; c2, p < .0001). In a clinical study, radiographic signs of supracuff liquid were identified in 57% of 47 patients. In a small subset of patients (n = 18), the estimated liquid volume (mean +/- SEM) was calculated to be 7.8 +/- 1.1 mt (range = 2.1-18.4 mi). CONCLUSIONS. Radiography is a sensitive means of identifying small volumes of supracuff liquid above the inflated cuffs of endotracheal tubes. Potentially contaminating liquid pooled above the cuff of an endotracheal tube can be identified in about half of patients undergoing short-term mechanical ventilation. Our results suggest the suction of the supracuff space may be a reasonable prophylactic maneuver against nosocomial pneumonia. A much larger study is suggested to investigate the actual relation between pooled supracuff liquid and the development of nosocomial pneumonia. C1 WESLEY COLL HOSP,DEPT RADIOL,BRISBANE,QLD 4066,AUSTRALIA. GOLDEN KREUTZ,DEPT RADIOL,A-1090 VIENNA,AUSTRIA. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. RP GREENE, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL 23591] NR 18 TC 33 Z9 36 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 1994 VL 163 IS 6 BP 1333 EP 1337 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PX337 UT WOS:A1994PX33700010 PM 7992723 ER PT J AU GETACHEW, MM WHITMAN, GJ CHEW, FS AF GETACHEW, MM WHITMAN, GJ CHEW, FS TI RETROPERITONEAL SCHWANNOMA SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note ID CT C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 4 TC 5 Z9 6 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 1994 VL 163 IS 6 BP 1356 EP 1356 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PX337 UT WOS:A1994PX33700014 PM 7992727 ER PT J AU SAINI, S REIMER, P HAHN, PF COHEN, MS AF SAINI, S REIMER, P HAHN, PF COHEN, MS TI ECHOPLANAR MR-IMAGING OF THE LIVER IN PATIENTS WITH FOCAL HEPATIC-LESIONS - QUANTITATIVE-ANALYSIS OF IMAGES MADE WITH VARIOUS PULSE SEQUENCES SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID MAGNETIC-RESONANCE; ANGIOGRAPHY; METASTASES AB OBJECTIVE. We undertook this study to evaluate pulse-sequence performance in terms of liver signal-to-noise ratio (SNR) and lesion-liver contrast-to-noise ratio (CNR) on T1- and Ta-weighted echoplanar MR imaging. SUBJECTS AND METHODS. Forty-nine patients referred for MR imaging of the liver were examined at 1.5 T with echoplanar MR imaging using spin-echo, inversion recovery, and gradient-echo pulse sequences. TP-weighted spin-echo (TE = 25, 50, 100, and 150 msec), T1-weighted inversion-recovery (T1 = 100, 380, 600, and 800 msec), and T2*-weighted gradient echo (TE = 20 msec) images were acquired after one excitation (TR = infinite), using a 128 x 128 data matrix. T2-weighted spin-echo (TE = 20, 50, 100, and 150 msec) images were also obtained with two excitations (TR = 6 sec), resulting in a 128 x 256 data matrix. Signal intensity measurements were made to calculate liver SNR and lesion-liver CNR. RESULTS. Single-excitation, TS-weighted, spin-echo images at a minimum TE of 25 msec provided the highest liver SNR (p < .05). Single-excitation, TP-weighted, spin-echo images at TEs of 50 and 100 msec, and T1-weighted inversion-recovery images at Tls of 100 and 380 msec provided the highest lesion-liver CNR (p < .05). However, the latter two pulse sequences had considerably inferior liver SNR (p < .05). CONCLUSION. Single-excitation, T2-weighted, spin-echo images provide both superior liver SNR and superior lesion-liver CNR. These results can be used to guide technique selection when echoplanar MR imaging is used to examine the liver. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP SAINI, S (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 NR 14 TC 31 Z9 31 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 1994 VL 163 IS 6 BP 1389 EP 1393 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PX337 UT WOS:A1994PX33700022 PM 7992735 ER PT J AU BENACERRAF, BR AF BENACERRAF, BR TI SONOGRAPHIC DETECTION OF FETAL ANOMALIES OF THE AORTIC AND PULMONARY-ARTERIES - VALUE OF 4-CHAMBER VIEW VS DIRECT IMAGES SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CONGENITAL HEART-DISEASE; 4-CHAMBER VIEW; LOW-RISK; DIAGNOSIS; DEFECTS AB Some investigators support the notion that the four-chamber view of the fetal heart is sufficient for the sonographic identification of most serious heart defects [1, 2]. We have found that the evaluation of the great vessels (aorta and pulmonary artery) is crucial for the detection of some of the most common heart defects, such as tetralogy of Fallot and transposition of the great arteries [3-5]. Although many abnormalities of the great vessels can be recognized indirectly by an abnormal four-chamber view, the detection of the ductus dependent lesions often requires evaluation of the aorta and pulmonary artery outflow tracts [3-5]. This pictorial essay illustrates abnormalities of the great vessels and shows those likely to be identified with a four-chamber view as opposed to those that require direct images of the great vessels for detection. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02117. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNECOL,BOSTON,MA 02117. NR 8 TC 31 Z9 33 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 1994 VL 163 IS 6 BP 1483 EP 1489 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PX337 UT WOS:A1994PX33700040 PM 7992752 ER PT J AU GOLDBERG, MA SHARIF, HS ROSENTHAL, DI BLACKSCHAFFER, S FLOTTE, TJ COLVIN, RB THRALL, JH AF GOLDBERG, MA SHARIF, HS ROSENTHAL, DI BLACKSCHAFFER, S FLOTTE, TJ COLVIN, RB THRALL, JH TI MAKING GLOBAL TELEMEDICINE PRACTICAL AND AFFORDABLE - DEMONSTRATIONS FROM THE MIDDLE-EAST SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID DIAGNOSTIC-ACCURACY; TELERADIOLOGY SYSTEM; COMPRESSION AB (OBJECTIVE. The purpose of this study was to demonstrate the first use of voice-grade telephone lines for the international transmission of both high-resolution digital images (radiology and pathology) and video in near real-time. MATERIALS AND METHODS. Eight live demonstrations were performed from the United Arab Emirates and the Kingdom of Saudi Arabia at the invitation of the respective ministries of health. Thirty radiologic studies (CT, MR, and radiographs) were digitized, compressed, and transmitted to Cambridge, MA, where they were interpreted on diagnostic workstations (1792 x 2252 display matrix) by a team of subspecialist radiologists. Near real-time image transmission was achieved by combining wavelet-based image compression (average compression ratio of 23:1) and multiplexing technology that used four phone lines simultaneously During each demonstration, one pathology image was transmitted from Cambridge to the demonstration site, where it was interpreted by a visiting pathologist. Videoconferencing was implemented with a drl-kilobits-per-sec leased line from the United Arab Emirates and with four multiplexed telephone lines from Saudi Arabia. RESULTS. For teleradiology and telepathology, transmission times ranged from 2-5 min per image. Image fidelity was judged to be of diagnostic quality in all transmitted cases. The video link to the United Arab Emirates was highly reliable. Bandwidth for videoconferencing from Saudi Arabia was marginal on four voice-grade telephone lines, resulting in some downtime (10-20%). Live consultations provided by subspecialists in Cambridge assisted in the management of patients at both venues. The system was well received by both the referring physicians in the Middle East and the participants in the United States. CONCLUSION. Image compression and multiplexing technologies enabled high-resolution teleradiology and telepathology as well as real-time video consultations over international telephone lines. While telecommunications systems are advancing rapidly in many parts of the world, those areas most in need of telemedicine services are likely to be the last to upgrade their telecommunications infrastructures. This ''proof of concept'' article outlines a practical and affordable approach that makes telemedicine more accessible to underserved areas worldwide. C1 RIYADH ARMED FORCES HOSP,DEPT RADIOL & IMAGING,RIYADH 11159,SAUDI ARABIA. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP GOLDBERG, MA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 22 TC 28 Z9 28 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 1994 VL 163 IS 6 BP 1495 EP 1500 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PX337 UT WOS:A1994PX33700042 PM 7992754 ER PT J AU KOPANS, DB AF KOPANS, DB TI BREAST-CANCER SCREENING FOR WOMEN 40-50 YEARS OLD SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 8 TC 3 Z9 3 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 1994 VL 163 IS 6 BP 1524 EP 1525 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PX337 UT WOS:A1994PX33700049 PM 7992760 ER PT J AU LEE, MJ BREATNACH, E AF LEE, MJ BREATNACH, E TI PLEURAL THICKENING CAUSED BY LEUKEMIC INFILTRATION - PLEURAL FINDINGS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter ID CT C1 MATER MISERICORDIAE HOSP,DUBLIN 7,IRELAND. RP LEE, MJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 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 1994 VL 163 IS 6 BP 1527 EP 1528 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PX337 UT WOS:A1994PX33700057 PM 7992765 ER PT J AU ROSENBERG, AE OCONNELL, JX AF ROSENBERG, AE OCONNELL, JX TI EPITHELIOID HEMANGIOMA OF BONE - REPLY SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter C1 VANCOUVER HOSP & HLTH SCI CTR,DEPT PATHOL,VANCOUVER,BC,CANADA. RP ROSENBERG, AE (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,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 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 1994 VL 18 IS 12 BP 1271 EP 1271 DI 10.1097/00000478-199412000-00013 PG 1 WC Pathology; Surgery SC Pathology; Surgery GA PT843 UT WOS:A1994PT84300013 ER PT J AU BARKLEY, B LICHTENSTEIN, MJ GARZA, C HAZUDA, HP AF BARKLEY, B LICHTENSTEIN, MJ GARZA, C HAZUDA, HP TI CLINICAL VALIDATION OF THE WELCH-ALLYN PNEUMOCHECK(TM) HAND-HELD SPIROMETER SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE AGED; PULMONARY FUNCTION TESTING; VALIDATION STUDY ID MORTALITY; OBSTRUCTION; POPULATION; DISEASE; ADULTS; SAMPLE AB Pulmonary function is predictive of morbidity and mortality. Therefore, in epidemiologic studies, researchers seek to measure pulmonary function with portable spirometers feasible for use in clinics or participants' homes. The purpose of this study was to validate a hand held spirometer, the Welch-Allyn Pneumocheck(TM), against standard pulmonary function tests. The authors used a convenience sample of 66 subjects. All subjects were asked to perform three vital capacity maneuvers with the Welch-Allyn Pneumocheck(TM) and then either a water seal spirometer or heated pneumotach in a hospital pulmonary function laboratory. The mean forced vital capacity (FVC) obtained with the Pneumocheck(TM) was 3.50 liters (standard deviation (SD) = 1.28) compared with 3.31 liters (SD = 1.24) for the pulmonary function laboratory. The correlation between the two measures was 0.98; the mean difference was 0.19 L (95% confidence interval = 0.12 to 0.26). The mean forced expiratory volume at one second (FEV(1)) was 2.31 L (SD = 1.07) for the Pneumocheck(TM) compared with 2.32 L (SD = 1.06) for the pulmonary function laboratory values. The correlation between the two measures was 0.99; the mean difference was 0.01 L (95% confidence interval = -0.03 to 0.04). Of the 46 subjects originally classified by the Pneumocheck(TM) as having FEV(1)/FVC ratios of less than 0.75, 10 (22%) had ratios greater than or equal to 0.75 after correcting for the FVC difference between methods. Therefore, there was an excellent correlation between the Welch-Allyn Pneumocheck(TM) and pulmonary function laboratory values for FVC and FEV(1). Small systematic differences in FVC measures can lead to substantial misclassification rates when evaluating FEV(1)/FVC ratios. C1 AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN 181,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,PULM FUNCT LAB,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DIV CLIN EPIDEMIOL,SAN ANTONIO,TX. FU NCRR NIH HHS [M01-RR-01346]; NIA NIH HHS [1-R01-AG10939-01, T-35-AG00230-01] NR 7 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD DEC PY 1994 VL 308 IS 6 BP 357 EP 359 DI 10.1097/00000441-199412000-00009 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA PV995 UT WOS:A1994PV99500009 PM 7985725 ER PT J AU MONTOYA, ID HESS, JM COVI, L FUDALA, PJ JOHNSON, RE AF MONTOYA, ID HESS, JM COVI, L FUDALA, PJ JOHNSON, RE TI A COMPARATIVE-STUDY OF PSYCHOPATHOLOGY AND COGNITIVE FUNCTIONS BETWEEN COCAINE-DEPENDENT AND OPIATE-DEPENDENT PATIENTS SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article; Proceedings Paper CT International Narcotics Research Conference CY JUN 23-27, 1992 CL KEYSTONE, CO ID OPIOID ADDICTS; ABUSERS; DISORDERS; IMPAIRMENT; DIAGNOSIS; ALCOHOL; MMPI AB The authors examined cognitive and psychological differences between cocaine- and opiate-dependent individuals, using the Symptom Check List-90-Revised (SCL-90-R) and the Shipley Institute of Living Scale (SILS). They studied a sample of 135 cocaine-dependent and 162 opiate-dependent patients entering drug abuse treatment studies at the National Institute on Drug Abuse-Addiction Research Center (NIDA-ARC) outpatient clinic. Cocaine-dependent patients had significantly higher estimated Wechsler Adult Intelligence Scale (WAIS-R) IQ, vocabulary, abstraction, and total T scores, as measured by the SILS. On the SCL-90-R, cocaine-dependent patients had significantly higher scores for interpersonal sensitivity, anxiety, phobic anxiety, paranoid ideation, and psychoticism; opiate-dependent patients had higher scores for somatization, The results suggest that cocaine-dependent patients have better cognitive function and more psychopathology than opiate-dependent patients entering drug abuse outpatient treatment studies. C1 DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA. UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. RP MONTOYA, ID (reprint author), NIDA,ARC,TREATMENT BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 31 TC 3 Z9 3 U1 1 U2 6 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD WIN PY 1994 VL 3 IS 1 BP 36 EP 42 PG 7 WC Substance Abuse SC Substance Abuse GA MY146 UT WOS:A1994MY14600004 ER PT J AU RAINES, DE MILLER, KW AF RAINES, DE MILLER, KW TI ON THE IMPORTANCE OF VOLATILE AGENTS DEVOID OF ANESTHETIC ACTION SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. NR 11 TC 19 Z9 20 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 1994 VL 79 IS 6 BP 1031 EP 1033 PG 3 WC Anesthesiology SC Anesthesiology GA PU602 UT WOS:A1994PU60200001 PM 7677814 ER PT J AU KEARSE, LA MANBERG, P CHAMOUN, N DEBROS, F ZASLAVSKY, A AF KEARSE, LA MANBERG, P CHAMOUN, N DEBROS, F ZASLAVSKY, A TI BISPECTRAL ANALYSIS OF THE ELECTROENCEPHALOGRAM CORRELATES WITH PATIENT MOVEMENT TO SKIN INCISION DURING PROPOFOL NITROUS-OXIDE ANESTHESIA SO ANESTHESIOLOGY LA English DT Article DE ANESTHETICS, INTRAVENOUS, PROPOFOL; MONITORING, ELECTROENCEPHALOGRAPHY, BISPECTRAL INDEX ID PHARMACODYNAMICS; QUANTITATION; FENTANYL; DEPTH; EEG AB Background: Bispectral analysis is a signal-processing technique that determines the harmonic and phase relations among the various frequencies in the electroencephalogram. Our purpose was to compare the accuracy of a bispectral descriptor, the bispectral index, with that of three power spectral variables (95% spectral edge, median frequency, and relative delta power) in predicting patient movement in response to skin incision during propofol-nitrous oxide anesthesia. Methods: Forty-four adult patients scheduled for elective noncranial surgery were studied. Gold cup electroencephalographic electrodes were placed on each patient in a frontoparietal montage (F-p1, F-p2, P-3, and P-4) referred to C-2, and the electroencephalogram was recorded continuously and processed off-line. Conventional frequency bands were used to describe power spectrum variables. Anesthesia was induced with propofol (1.5-3.0 mg(-1).kg(-1)) and maintained with 60% nitrous oxide in oxygen and with propofol at one of three randomized infusion rates (100, 200, or 300 mu g.kg(-1).min(-1)). Inadequate anesthetic depth was defined as patient movement in response to a 2-cm skin incision at the planned site of surgery. Plasma propofol concentrations were measured within 2 min after skin incision. Results: Complete data were available for 38 patients, of whom 17 moved in response to skin incision. Analysis of the area under the receiver operating characteristic curves showed that only for bispectral index and drug dose group was there a significant predictive relation (area > 0.5). Furthermore, the bispectrum was significantly predictive even after stratification by dose group. Conclusions: The bispectral index of the electroencephalogram is a more accurate predictor of patient movement in response to skin incision during propofol-nitrous oxide anesthesia than are standard power spectrum parameters or plasma propofol concentrations. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. ASPECT MED SYST,FRAMINGHAM,MA. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,DEPT STAT,BOSTON,MA 02115. RP KEARSE, LA (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. NR 19 TC 122 Z9 128 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 1994 VL 81 IS 6 BP 1365 EP 1370 DI 10.1097/00000542-199412000-00010 PG 6 WC Anesthesiology SC Anesthesiology GA PV982 UT WOS:A1994PV98200010 PM 7992904 ER PT J AU ABRUTYN, E KAYE, D AF ABRUTYN, E KAYE, D TI ASYMPTOMATIC BACTERIURIA AND SURVIVAL - REPLY SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 MED COLL PENN,PHILADELPHIA,PA 19129. HAHNEMANN UNIV,PHILADELPHIA,PA 19129. RP ABRUTYN, E (reprint author), VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 1 PY 1994 VL 121 IS 11 BP 896 EP 896 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PT628 UT WOS:A1994PT62800017 ER PT J AU BEAL, MF HENSHAW, DR JENKINS, BG ROSEN, BR SCHULZ, JB AF BEAL, MF HENSHAW, DR JENKINS, BG ROSEN, BR SCHULZ, JB TI COENZYME Q(10) AND NICOTINAMIDE BLOCK STRIATAL LESIONS PRODUCED BY THE MITOCHONDRIAL TOXIN MALONATE SO ANNALS OF NEUROLOGY LA English DT Article ID D-ASPARTATE RECEPTOR; EXCITOTOXIC LESIONS; 3-NITROPROPIONIC ACID; RAT STRIATUM; THERAPY; IMPAIRMENT; MELAS; ENCEPHALOMYOPATHY; SPECTROSCOPY; METABOLISM AB A potential mechanism of neuronal injury in neurodegenerative diseases is a defect in energy metabolism that may lead to slow excitotoxic neuronal death. Consistent with this possibility, we showed that specific inhibitors of the electron transport chain produce excitotoxic lesions in vivo. In the present study we examined whether agents that improve energy metabolism can block lesions produced by the mitochondrial toxin malonate. Striatal lesions produced by the complex II inhibitor malonate were blocked in a dose-dependent manner by oral pretreatment with coenzyme Q(10). Administration of nicotinamide by Alzet pump for 1 week attenuated malonate-induced lesions, but riboflavin had no effect. Administration of nicotinamide intraperitoneally just prior to and following induction of the lesions produced dose-dependent neuroprotection. A combination of coenzyme Q(10) with nicotinamide was more effective than either compound alone, as shown by both lesion size and magnetic resonance imaging in vivo. Both coenzyme Q(10) and nicotinamide blocked adenosine triphosphate depletions and lactate increases. These results confirm that mitochondrial toxins produce striatal excitotoxic lesions by a mechanism involving energy depletion in vivo. Furthermore, they suggest novel neuroprotective strategies that may be useful in the treatment of both mitochondrial encephalopathies and neurodegenerative diseases. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR NUCL MAGNET RESONANCE,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP BEAL, MF (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,WARREN 408,FRUIT ST,BOSTON,MA 02114, USA. RI Schulz, Jorg/D-9786-2012 OI Schulz, Jorg/0000-0002-8903-0593 FU NINDS NIH HHS [NS10828, NS31579]; PHS HHS [16367] NR 39 TC 143 Z9 143 U1 3 U2 6 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 1994 VL 36 IS 6 BP 882 EP 888 DI 10.1002/ana.410360613 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PW487 UT WOS:A1994PW48700012 PM 7998775 ER PT J AU KAYE, EM DOLL, RF NATOWICZ, MR SMITH, FI AF KAYE, EM DOLL, RF NATOWICZ, MR SMITH, FI TI PELIZAEUS-MERZBACHER DISEASE PRESENTING AS SPINAL MUSCULAR-ATROPHY - CLINICAL AND MOLECULAR STUDIES SO ANNALS OF NEUROLOGY LA English DT Article ID PROTEOLIPID PROTEIN GENE; POINT MUTATION; X-CHROMOSOME; PLP GENE; MYELIN; FAMILY; EXPRESSION; DISORDER; DELETION; LINKAGE AB Two brothers with profound neonatal hypotonia and hyporeflexia and electrodiagnostic testing consistent with lower motor neuron pathology were found to have a leukodystrophy. Using single-strand conformational polymorphism analysis and direct sequencing, a mutation within exon 3 of the gene encoding proteolipid protein (Gly(73)Arg substitution) was previously detected in both brothers and their mother, establishing the diagnosis of Pelizaeus-Merzbacher disease. Despite reported sparing of the peripheral nervous system in Pelizaeus-Merzbacher disease, we suggest that proteolipid protein gene products may influence the development of anterior horn cells or peripheral nervous system myelin and that some individuals affected with this disease may present with clinical and electromyographic features suggestive of neonatal spinal muscular atrophy. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV BIOMED SCI,WALTHAM,MA 02154. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV MED GENET,WALTHAM,MA 02154. RP KAYE, EM (reprint author), TUFTS UNIV,FLOATING HOSP CHILDREN,SCH MED,DIV PEDIAT NEUROL,BOSTON,MA 02111, USA. FU NIDDK NIH HHS [DK 38381]; NINDS NIH HHS [KO8NS01390] NR 30 TC 16 Z9 16 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 1994 VL 36 IS 6 BP 916 EP 919 DI 10.1002/ana.410360618 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PW487 UT WOS:A1994PW48700017 PM 7998780 ER PT J AU HIBBERD, PL AF HIBBERD, PL TI USE AND MISUSE OF STATISTICS FOR EPIDEMIOLOGIC STUDIES OF MULTIPLE-SCLEROSIS SO ANNALS OF NEUROLOGY LA English DT Article; Proceedings Paper CT Workshop on Multiple Sclerosis - Epidemiology and Genetics CY JUN 01-05, 1993 CL ALGHERO PORTO CONTE, ITALY SP ITALIAN NEUROL SOC RAVENNA ID FAROE ISLANDS; SELECTION; DISEASE; CANCER; BIAS; MS AB Despite a vast literature on the epidemiology of multiple sclerosis, the cause of this disease remains elusive. The majority of the studies have focused on prevalence, so that a worldwide distribution of multiple sclerosis can now be mapped. Tantalizing apparent differences in prevalence have resulted in an abundance of hypotheses about risk factors for multiple sclerosis, none of which have been firmly established. This article reviews the difficulties inherent in the use of any type of descriptive study to investigate etiology of disease and provides an update of appropriate statistical methodology to analyze study results. The major focus is on the use of analytical study design, specifically the case-control study, to investigate a specific hypothesis about association between a risk factor and multiple sclerosis. An update on new epidemiological and statistical methodology to enhance the design of future case-control studies is presented. Future opportunities to study multiple sclerosis in new ways, such as in cohort studies or nested case-control studies, using large medical insurance and other types of health-related data bases, are discussed. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP HIBBERD, PL (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,GRAY 5,FRUIT ST,BOSTON,MA 02114, USA. NR 51 TC 18 Z9 18 U1 1 U2 3 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 1994 VL 36 SU 2 BP S218 EP S230 DI 10.1002/ana.410360809 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PX129 UT WOS:A1994PX12900008 PM 7998791 ER PT J AU WRIGHT, CD MATHISEN, DJ WAIN, JC GRILLO, HC HILGENBERG, AD MONCURE, AC CAREY, RW CHOI, NC DALY, M LOGAN, DL AF WRIGHT, CD MATHISEN, DJ WAIN, JC GRILLO, HC HILGENBERG, AD MONCURE, AC CAREY, RW CHOI, NC DALY, M LOGAN, DL TI EVOLUTION OF TREATMENT STRATEGIES FOR ADENOCARCINOMA OF THE ESOPHAGUS AND GASTROESOPHAGEAL JUNCTION SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 31-FEB 02, 1994 CL NEW ORLEANS, LA SP SOC THORAC SURGEONS ID NEOADJUVANT CHEMOTHERAPY; SURGICAL RESECTION; CARCINOMA; RADIOTHERAPY; THERAPY; 5-FLUOROURACIL; CISPLATIN AB Between 1980 and 1988, 91 patients with adenocarcinoma of the esophagus were treated by surgical resection and selective postoperative therapy. Operative mortality was 2%. Pathologic stage was I in 4, II in 26, and III in 61. Actuarial 2- and 5-year survival was 24% and 8%. From 1987 to 1989, 16 patients with adenocarcinoma of the esophagus were treated with two cycles of 5-fluorouracil and cisplatin followed by surgical resection. There was 1 complete response (6%), 5 partial responses (31%), and 10 with no response (63%). Twelve patients had resection. Pathologic stage was I in 1, II in 4, and III in 8. There was one chemotherapy-related death and one surgical death. Actuarial 4-year survival is 42%. From 1990 to 1993, 22 patients with adenocarcinoma of the esophagus were treated with two cycles of etoposide, doxorubicin, and cisplatin followed by surgical resection. There was 1 complete response (5%), 11 partial responses (50%), and 10 with no response (45%). Eighteen patients had resection. Pathologic stage was 0 in 1, II in 8, and III in 9. There were no treatment-related deaths. The actuarial 2-year survival is 58%. Conclusions are necessarily limited because the patients were not treated in a randomized fashion. These preliminary results with preoperative chemotherapy appear improved (p = 0.04 and p = 0.004, respectively) as compared with results from 1980 to 1988 without preoperative chemotherapy. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. RP WRIGHT, CD (reprint author), MASSACHUSETTS GEN HOSP,DIV MED ONCOL,GEN THORAC SURG UNIT,WARREN 1212,BOSTON,MA 02114, USA. NR 16 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 1994 VL 58 IS 6 BP 1574 EP 1579 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PU986 UT WOS:A1994PU98600004 PM 7979718 ER PT J AU DALEY, J GROVER, FL HAMMERMEISTER, KE AF DALEY, J GROVER, FL HAMMERMEISTER, KE TI USING OUTCOMES DATA TO IMPROVE CLINICAL-PRACTICE - BUILDING ON MODELS FROM CARDIAC-SURGERY - JUNE 6-7, 1994 KEYSTONE, COLORADO SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,BOSTON,MA. DENVER VA MED CTR,DENVER,CO. UNIV COLORADO,HLTH SCI CTR,BOULDER,CO 80309. RP DALEY, J (reprint author), BROCKTON W ROXBURY VET AFFAIRS MED CTR,BROCKTON,MA, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 1994 VL 58 IS 6 BP 1807 EP 1808 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PU986 UT WOS:A1994PU98600078 ER PT J AU HAMMERMEISTER, KE DALEY, J GROVER, FL AF HAMMERMEISTER, KE DALEY, J GROVER, FL TI USING OUTCOMES DATA TO IMPROVE CLINICAL-PRACTICE - WHAT WE HAVE LEARNED SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT National Symposium on Using Outcomes Data to Improve Clinical Practice - Building on Models from Cardiac Surgery CY JUN 06-07, 1994 CL KEYSTONE, CO C1 DENVER VA MED CTR,SURG SERV,DENVER,CO 80220. UNIV COLORADO,HLTH SCI CTR,DEPT MED,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DIV CARDIOTHORAC SURG,DENVER,CO 80262. BROCKTON W ROXBURY VET AFFAIRS MED CTR,HLTH SERV RES & DEV,BOSTON,MA. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,BOSTON,MA. RP HAMMERMEISTER, KE (reprint author), DENVER VA MED CTR,SERV CARDIOL,1055 CLERMONT,DENVER,CO 80220, USA. NR 18 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 1994 VL 58 IS 6 BP 1809 EP 1811 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PU986 UT WOS:A1994PU98600079 PM 7979773 ER PT J AU SINGH, AK DHAUNSI, GS GUPTA, MP ORAK, JK ASAYAMA, K SINGH, I AF SINGH, AK DHAUNSI, GS GUPTA, MP ORAK, JK ASAYAMA, K SINGH, I TI DEMONSTRATION OF GLUTATHIONE-PEROXIDASE IN RAT-LIVER PEROXISOMES AND ITS INTRAORGANELLAR DISTRIBUTION SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID SUPEROXIDE-DISMUTASE; HUMAN-PLASMA; HUMAN-DISEASES; FREE-RADICALS; PROTEINS; PURIFICATION; ENZYME; IDENTIFICATION; METABOLISM; SEQUENCE AB Earlier, we reported that rat liver peroxisomes contain Cu-Zn superoxide dismutase (J. Biol. Chem. 267, 6870), thereby suggesting a new antioxidant role for this organelle in free radical metabolism. In this study, we report for the first time that mammalian peroxisomes also contain glutathione peroxidase. Using highly purified rat Liver peroxisomes isolated by Nycodenz gradient, we found that peroxisomes contain glutathione peroxidase which shows enzymatic activity with different substrates such as hydrogen peroxide, cumene hydroperoxide, and t-butyl hydroperoxide. This activity could be inhibited in vitro by mercaptosuccinate. Western blot analysis revealed that peroxisomes from control and ciprofibrate-treated Livers show immunoreactive bands with antibodies raised against glutathione peroxidase. The intraperoxisomal distribution of glutathione peroxidase was investigated by using peroxisomal membrane and matrix proteins. The results revealed that glutathione peroxidase is a matrix enzyme. The presence of glutathione peroxidase in peroxisomes provides an alternate enzyme system responsible for the degradation of organic peroxides and the degradation of H2O2 under conditions in which catalase is inactivated (e.g., ischemia-reperfusion and endotoxemia). These findings suggest that glutathione peroxidase in peroxisomes may play a novel role in the cellular antioxidant responses to various oxidative stress conditions. (C) 1994 Academic Press, Inc. C1 MED UNIV S CAROLINA,DEPT PEDIAT,CHARLESTON,SC 29425. YAMANASHI MED COLL,DEPT PEDIAT,YAMANASHI 40938,JAPAN. RP SINGH, AK (reprint author), RALPH H JOHNSON VET ADM MED CTR,DEPT PATHOL & LAB MED,109 BEE ST,CHARLESTON,SC 29401, USA. FU NINDS NIH HHS [NS-22576] NR 52 TC 36 Z9 38 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD DEC PY 1994 VL 315 IS 2 BP 331 EP 338 DI 10.1006/abbi.1994.1508 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PV829 UT WOS:A1994PV82900017 PM 7986075 ER PT J AU GREEN, MF NUECHTERLEIN, KH MINTZ, J AF GREEN, MF NUECHTERLEIN, KH MINTZ, J TI BACKWARD-MASKING IN SCHIZOPHRENIA AND MANIA .1. SPECIFYING A MECHANISM SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID COLLEGE-STUDENTS; PATTERN MASKING; DISORDERS; DEFICIT AB Background: Backward masking is a neuropsychological procedure that involves the earliest phases of visual processing. Compared with normal controls, the performance of schizophrenic patients is more disrupted by a visual mask. Masking procedures used previously with schizophrenic patients have combined two separate masking mechanisms (interruption and integration), which prevent interpretation pf the nature of the abnormality. The current study systematically limited the masking mechanism to interruption to specify the underlying mechanisms. Manic patients were included to examine diagnostic specificity. Methods: Sixty-three schizophrenic inpatients, 31 manic inpatients, and 48 normal controls received three versions of the backward masking procedure. One version used a high-energy mask that combines both integration and interruption mechanisms. Another procedure used a low-energy mask that works mainly through interruption. A final condition altered the features of the mask so that masking was almost entirely through interruption. Results: Schizophrenic patients showed performance deficits across masking conditions, even in procedures that were largely limited to masking by interruption. The masking performance of the patients did not appear to fit a simple generalized deficit. Manic patients performed significantly worse than normal controls and comparably with the schizophrenic patients. Conclusions: Schizophrenic patients have abnormalities at least with interruptive mechanisms. The results suggest that deficits on masking procedures are not entirely specific to schizophrenia because comparable masking deficits were found in manic inpatients with chronic disease. The current study addresses the neuropsychological mechanisms of the masking deficit. The next step will be to investigate the contributions of two distinct neuroanatomical visual pathways to the masking abnormality in schizophrenia. C1 W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA 90073 USA. RP UNIV CALIF LOS ANGELES, CLIN RES CTR, DEPT PSYCHIAT & BIOBEHAV SCI, BOX 6022, CAMARILLO, CA 93011 USA. RI Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 FU NIMH NIH HHS [MH-43292] NR 27 TC 149 Z9 149 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-990X EI 1538-3636 J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 1994 VL 51 IS 12 BP 939 EP 944 PG 6 WC Psychiatry SC Psychiatry GA PW005 UT WOS:A1994PW00500001 PM 7979881 ER PT J AU GREEN, MF NUECHTERLEIN, KH MINTZ, J AF GREEN, MF NUECHTERLEIN, KH MINTZ, J TI BACKWARD-MASKING IN SCHIZOPHRENIA AND MANIA .2. SPECIFYING THE VISUAL CHANNELS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CEREBRAL LATERALITY; LOCALIZATION; INTEGRATION; DEPRESSION AB Background: The backward masking procedures that have been used in psychopathology research have confounded two types of masking mechanisms (integration and interruption) and two types of visual channels (transient and sustained). In an earlier study, we attempted to limit the masking mechanism to interruption The current study limited the role of sustained (parvocellular) visual channels to masking performance. Methods: Masking procedures were altered in the following two ways to reduce reliance on sustained visual channels: (1) the spatial frequency was lowered by blurring the target and (2) a location task was used instead of an identification task. Manic patients were included to examine the specificity of deficits on these tasks to schizophrenia and to test the hypothesis that mania is associated with abnormalities on visuospatial tasks. Results: Schizophrenic patients differed significantly from normal controls on both masking conditions. Manic patients also showed deficits relative to normal controls. Manic patients showed a significantly different masking function from that of schizophrenic patients on the location condition. Conclusions: Schizophrenic deficits within masking paradigms may involve abnormalities in transient, as opposed to sustained, visual channels. Masking performance deficits were also found in manic patients, but the underlying processes are probably different. A reformulation is offered concerning the nature of early visual processing deficits in schizophrenia. C1 W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA 90073 USA. RP UNIV CALIF LOS ANGELES, CLIN RES CTR, DEPT PSYCHIAT & BIOBEHAV SCI, BOX 6022, CAMARILLO, CA 93011 USA. FU NIMH NIH HHS [MH-43292] NR 24 TC 145 Z9 147 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-990X EI 1538-3636 J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 1994 VL 51 IS 12 BP 945 EP 951 PG 7 WC Psychiatry SC Psychiatry GA PW005 UT WOS:A1994PW00500002 PM 7979882 ER PT J AU JELLINEK, MS LITTLE, M MURPHY, JM AF JELLINEK, MS LITTLE, M MURPHY, JM TI PERFORMANCE OF SCREENING TOOLS FOR MENTAL-HEALTH PROBLEMS IN CHRONICALLY ILL CHILDREN SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Letter RP JELLINEK, MS (reprint author), MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,15 PKMAN ST,BOSTON,MA 02114, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD DEC PY 1994 VL 148 IS 12 BP 1354 EP 1355 PG 2 WC Pediatrics SC Pediatrics GA PW006 UT WOS:A1994PW00600026 PM 7951826 ER PT J AU CENDAN, JC MOLDAWER, LL SOUBA, WW COPELAND, EM LIND, DS AF CENDAN, JC MOLDAWER, LL SOUBA, WW COPELAND, EM LIND, DS TI ENDOTOXIN-INDUCED NITRIC-OXIDE PRODUCTION IN PULMONARY-ARTERY ENDOTHELIAL-CELLS IS REGULATED BY CYTOKINES SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the Surgical-Infection-Society CY APR 27-30, 1994 CL TORONTO, CANADA SP SURG INFECT SOC ID HUMAN-MONOCYTES; L-ARGININE AB Background: L-Arginine is the sole precursor of nitric oxide (NO). Bacterial lipopolysaccharide (endotoxin) (LPS) stimulates carrier-mediated L-arginine transport in porcine pulmonary artery endothelial cells (PAECs) through an autocrine pathway that involves interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor a (TNF-alpha). Objectives: To determine if Escherichia coli LPS stimulates NO synthesis in PAECs and, if so, if LPS stimulation of NO production is also mediated by autocrine secretion of IL-1 alpha and TNF-alpha. Design: Monolayers of PAECs were incubated with various concentrations of LPS, recombinant human TNF-alpha, or IL-1 alpha, and total nitrate-nitrite accumulation was measured at different time points with the Greiss reagent following cadmium reduction. Release of TNF-alpha and IL-1 alpha release by LPS-stimulated PAECs were measured using the WEHI (for TNF-alpha) and A375.S2 (for IL-1 alpha) bioassays. The PAECs were then incubated with saline solution or LPS in the presence or absence of either a polyclonal antibody to human TNF or IL-1 receptor antagonist, and nitrate-nitrite accumulation was measured at 48 hours. Results: Production of NO by PAECs was increased 230% by LPS (1 mu g/mL), 350% by TNF-alpha. (1000 U/mL), and 240% by IL-1 alpha (1000 U/mL) (P<.05 vs control). The LPS-stimulated NO production was inhibited by IL-1 receptor antagonist (100 mu g/mL) or antibody to TNF (10 mu g/mL) to control levels (P<.05 vs LPS; difference vs saline solution was not significant). The LPS-stimulated TNF-alpha secretion by PAECs and TNF-alpha activity were maximal at 6 hours (400+/-42 pg/mL). The IL-1 alpha activity was not detectable in LPS-stimulated PAECs by the A375.S2 bioassay. Conclusions: Endotoxin, TNF-alpha, and lL-1 alpha stimulated NO synthesis in PAECs. Endotoxin-stimulated NO synthesis through an autocrine pathway involving the cytokines TNF-alpha and IL-1 alpha. C1 UNIV FLORIDA,DEPT SURG,GAINESVILLE,FL 32610. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,DIV SURG ONCOL,BOSTON,MA. RI Cendan, Juan/F-2303-2011 OI Cendan, Juan/0000-0002-2744-4838 FU NCI NIH HHS [CA-52108, T-32-CA09605]; NIGMS NIH HHS [GM-40586] NR 14 TC 28 Z9 29 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD DEC PY 1994 VL 129 IS 12 BP 1296 EP 1300 PG 5 WC Surgery SC Surgery GA PW186 UT WOS:A1994PW18600011 PM 7986159 ER PT J AU TOUSSAINT, JF SOUTHERN, JF FUSTER, V KANTOR, HL AF TOUSSAINT, JF SOUTHERN, JF FUSTER, V KANTOR, HL TI C-13-NMR SPECTROSCOPY OF HUMAN ATHEROSCLEROTIC LESIONS - RELATION BETWEEN FATTY-ACID SATURATION, CHOLESTERYL ESTER CONTENT, AND LUMINAL OBSTRUCTION SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE C-13-NMR SPECTROSCOPY; ATHEROSCLEROSIS; UNSATURATED FATTY ACIDS; OXIDATION; LIPOPROTEIN; HUMANS; MOBILE LIPIDS ID LOW-DENSITY-LIPOPROTEIN; NUCLEAR-MAGNETIC-RESONANCE; OXIDATIVE MODIFICATION; LIPID-PEROXIDATION; PHASE-BEHAVIOR; ADIPOSE-TISSUE; OLEATE-RICH; INVITRO; PLAQUES; ESTERIFICATION AB Previous investigations have used C-13-nuclear magnetic resonance (NMR) spectroscopy to demonstrate the similarities between lipoproteins and the mobile lipids of atheroma. In this study, we tested the hypothesis that C-13-NMR changes are related to indices of histological severity. We classified 20 human arteries according to their obstruction ratio (OR), defined as the ratio of the plaque area to the area delimited by the external elastic lamina. In group A, OR was <40%, and in group B, OR was <40%. We analyzed at 9.4 T the resonances of unsaturated (UFA) and polyunsaturated (PUFA) carbons, the resonances of the carbons 19 and 21 (C19,C21) of cholesteryl esters (CE), the methine carbon peak of fatty acids (CH2)(n), the choline peak from phospholipids (PL), and the glycerol peak from triglyceride (TG). The UFA/PUFA, UFA/(CH2)(n) and PUFA/(CH2)(n) ratios are markers of fatty acid saturation. (C19,C21)/(CH2)(n), choline/ (CH2)(n), and glycerol/(CH2)(n) are indices of CE, PL, and TG content, respectively. UFA/PUFA in group A is 1.15+/-0.34 versus 1.63+/-0.32 in group B (P=.005). PUFA/(CH2)(n) is 0.26+/-0.10 in group A versus 0.16+/-0.04 in group B (P=.049). C19,C21/(CH2)(n) in group A is 0.32+/-0.15 Versus 0.63+/-0.23 for group B (P=.003). No significant difference was found in UFA/(CH2)(n) or in the TG or PL ratios. C-13 spectral examination of human atherosclerosis demonstrates decreased resonances for polyunsaturated fatty acyl chains and cholesteryl esters with increasing obstruction. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR NMR,CARDIAC UNIT,BOSTON,MA. RP TOUSSAINT, JF (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,JACKSON 1410,32 FRUIT ST,BOSTON,MA 02114, USA. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 FU NHLBI NIH HHS [R01-HL-39371] NR 54 TC 44 Z9 44 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD DEC PY 1994 VL 14 IS 12 BP 1951 EP 1957 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PX015 UT WOS:A1994PX01500011 PM 7981185 ER PT J AU AUGUSTIN, HG KOZIAN, DH JOHNSON, RC AF AUGUSTIN, HG KOZIAN, DH JOHNSON, RC TI DIFFERENTIATION OF ENDOTHELIAL-CELLS - ANALYSIS OF THE CONSTITUTIVE AND ACTIVATED ENDOTHELIAL-CELL PHENOTYPES SO BIOESSAYS LA English DT Review ID RECEPTOR TYROSINE KINASES; BLOOD-BRAIN-BARRIER; MONOCLONAL-ANTIBODY; VASCULAR ENDOTHELIUM; MICROVASCULAR ENDOTHELIUM; SURFACE GLYCOPROTEIN; GROWTH-FACTOR; LUNG INJURY; EXPRESSION; SELECTIN AB Endothelial cells line the inside of all blood vessels, forming a structurally and functionally heterogenous population of cells. Their complexity and diversity has long been recognized, yet very little is known about the molecules and regulatory mechanisms that mediate the heterogeneity of different endothelial cell populations, The constitutive organ- and microenvironment-specific phenotype of endothelial cells controls internal body compartmentation, regulating the trafficking of circulating cells to distinct vascular beds, In contrast, surface molecules associated with the activated cytokine-inducible endothelial phenotype play a critical role in pathological conditions including inflammation, tumor angiogenesis, and wound healing. Differentiation of the endothelial cell phenotypes appears to follow similar mechanisms to the differentiation of hematopoietic cells, with the exception that endothelial cells maintain transdifferentiating competence, The present review offers a scheme of endothelial cell differentiation and discusses the possible applications of differentially expressed endothelial cell molecules as targets for directed therapeutic intervention. C1 HARVARD UNIV, SCH MED, CTR BLOOD RES, BOSTON, MA 02115 USA. RP AUGUSTIN, HG (reprint author), UNIV GOTTINGEN, SCH MED, DEPT OBSTET & GYNECOL, CELL BIOL LAB, D-37075 GOTTINGEN, GERMANY. NR 60 TC 155 Z9 162 U1 2 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD DEC PY 1994 VL 16 IS 12 BP 901 EP 906 DI 10.1002/bies.950161208 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA PX317 UT WOS:A1994PX31700007 PM 7840769 ER PT J AU HENDERSON, DC GOFF, DC AF HENDERSON, DC GOFF, DC TI CLOZAPINE FOR POLYDIPSIA AND HYPONATREMIA IN CHRONIC-SCHIZOPHRENICS SO BIOLOGICAL PSYCHIATRY LA English DT Note DE SCHIZOPHRENIA; POLYDIPSIA; HYPONATREMIA; CLOZAPINE; ANTIPSYCHOTICS; WATER INTOXICATION ID INDUCED WATER-INTOXICATION; PSYCHOGENIC POLYDIPSIA; PSYCHIATRIC-PATIENTS; DEMECLOCYCLINE C1 MASSACHUSETTS GEN HOSP,ERICH LINDEMANN MENTAL HLTH CTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BOSTON,MA 02114. NR 18 TC 30 Z9 30 U1 4 U2 6 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 DEC 1 PY 1994 VL 36 IS 11 BP 768 EP 770 DI 10.1016/0006-3223(94)90089-2 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA PV117 UT WOS:A1994PV11700008 PM 7858074 ER PT J AU CORBLEY, MJ CHERINGTON, V FEIG, LA COOPER, GM ROBERTS, TM AF CORBLEY, MJ CHERINGTON, V FEIG, LA COOPER, GM ROBERTS, TM TI RAPID REGENERATION OF VIRUS FROM CELLS INFECTED WITH A RETROVIRAL VECTOR SO BIOTECHNIQUES LA English DT Article ID BLADDER-CARCINOMA ONCOGENE; RAS GENE; PACKAGING CELL; TRANSFORMING GENES; MAMMALIAN-CELLS; SARCOMA-VIRUS; CONSTRUCTION; HARVEY; P21; ACTIVATION AB Recombinant retroviral vectors usually encode the genes of interest in place of the viral structural genes, which must be provided in trans. These viruses are therefore defective for replication: infected cells cannot produce progeny virus. However in some cases it may be desirable to generate virus from an infected cell clone displaying a phenotype of interest. We describe a rapid method for producing virus, which involves fusing the infected cells to fresh packaging cells. Stable producer lines are generated after fusion by co-selecting for the Ecogpt(+) marker in the packaging cells and the G418 resistance (neo(r)) marker in the infected cells. We have used this method to develop cell lines that produce retroviruses encoding a Leu 61-activated c-Ha-ras oncogene as well as a neo(r) gene. The viruses confer oncogenic transformation on 95%-100% of infected target cells as assayed by altered morphology, focus formation and soft agar growth. C1 TUFTS UNIV,SCH MED,BOSTON,MA. RP CORBLEY, MJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 41 TC 7 Z9 7 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 1994 VL 17 IS 6 BP 1102 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PW017 UT WOS:A1994PW01700016 PM 7873180 ER PT J AU PAI, SY FRUMAN, DA LEONG, T NEUBERG, D ROSANO, TG MCGARIGLE, C ANTIN, JH BIERER, BE AF PAI, SY FRUMAN, DA LEONG, T NEUBERG, D ROSANO, TG MCGARIGLE, C ANTIN, JH BIERER, BE TI INHIBITION OF CALCINEURIN PHOSPHATASE-ACTIVITY IN ADULT BONE-MARROW TRANSPLANT PATIENTS TREATED WITH CYCLOSPORINE-A SO BLOOD LA English DT Article ID VERSUS-HOST-DISEASE; T-CELL ACTIVATION; LYMPHOCYTES-T; CHRONIC GRAFT; INTERLEUKIN-2 PRODUCTION; SIGNAL-TRANSDUCTION; IMMUNOPHILIN LIGAND; CYCLOPHILIN; FK-506; CD28 AB In vitro studies have demonstrated that cyclosporine A (CsA) acts by inhibiting the phosphatase activity of calcineurin, an important mediator of T-cell activation. The relationship of CsA administration in vivo, calcineurin activity, and graft-versus-host disease (GVHD) has yet to be studied. The calcineurin activities of mononuclear cells isolated from 62 bone marrow transplant recipients and 12 normal volunteers were determined and analyzed with respect to administration of CsA, presence or absence of CsA in plasma, and presence or absence of GVHD. Of 62 patients, 33 were taking CsA and 29 were not. Early posttransplant (<100 days), the calcineurin activity of patients on CsA was significantly lower than that of patients not on CsA (P = .0004) and than that of normal volunteers (P < .0001). Similarly, late posttransplant (>100 days), the calcineurin activity of patients taking CsA was inhibited compared with normal volunteers (P < .05). The calcineurin activity of patients with acute GVHD who were taking CsA was lower than that of patients on CsA without acute GVHD matched for time posttransplant (P = .02). Calcineurin activity in patients on CsA with chronic GVHD was similar to those without chronic GVHD on drug. In conclusion, calcineurin activity is significantly suppressed by in vivo administration of CsA. The lower calcineurin activity of patients on CsA with acute GVHD suggests that CsA-resistant GVHD is not the result of inadequate suppression of calcineurin activity. These data suggest that if inhibition of calcineurin is the only physiologic target of CsA administration, simply increasing doses of CsA or treatment with other inhibitors of calcineurin, such as FK506, would not be expected to ameliorate GVHD. (C) 1994 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA. ALBANY MED CTR,DEPT PATHOL & LAB MED,ALBANY,NY. BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA. NR 44 TC 50 Z9 50 U1 2 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 DEC 1 PY 1994 VL 84 IS 11 BP 3974 EP 3979 PG 6 WC Hematology SC Hematology GA PV776 UT WOS:A1994PV77600046 PM 7949153 ER PT J AU JIA, GQ GUTIERREZRAMOS, JC AF JIA, GQ GUTIERREZRAMOS, JC TI MESSENGER-RNA QUANTITATION OF CYTOKINE RECEPTOR SUBUNIT SO BLOOD LA English DT Letter ID POLYMERASE CHAIN-REACTION; GAMMA-CHAIN; CELLS C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. RP JIA, GQ (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA, USA. NR 8 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 DEC 1 PY 1994 VL 84 IS 11 BP 3981 EP 3982 PG 2 WC Hematology SC Hematology GA PV776 UT WOS:A1994PV77600048 PM 7949155 ER PT J AU PERETZ, I KOLINSKY, R TRAMO, M LABRECQUE, R HUBLET, C DEMEURISSE, G BELLEVILLE, S AF PERETZ, I KOLINSKY, R TRAMO, M LABRECQUE, R HUBLET, C DEMEURISSE, G BELLEVILLE, S TI FUNCTIONAL DISSOCIATIONS FOLLOWING BILATERAL LESIONS OF AUDITORY-CORTEX SO BRAIN LA English DT Article DE AUDITORY AGNOSIA; AMUSIA; AUDITORY CORTEX; VOICE; PROSODY ID PURE WORD DEAFNESS; SEQUENCE DISCRIMINATION; SPEECH-PERCEPTION; MUSICAL ALEXIA; NORMATIVE DATA; TERM-MEMORY; AGNOSIA; APHASIA; COMPREHENSION; RECOGNITION AB We present true patients with bilateral lesions of the superior temporal cortex who manifested a number of functional dissociations in the auditory domain. The perception of speech and environmental sounds were preserved; yet, the perception of times, prosody and voice was impaired. As the processing of melodic but not rhythmic variations in musical sequences was selectively disturbed, the deficit cannot be attributed to a general impairment in auditory memory or sequential processing. These findings suggest that melody processing is not mediated by a general-purpose auditory architecture bur by specialized cortical subsystems residing within the lesioned areas. Current taxonomies of auditory agnosia and models of normal music cognition are evaluated in light of the functional dissociations manifested by these patients. C1 UNIV MONTREAL,CTR RECH HOSP,MONTREAL,PQ,CANADA. FREE UNIV BRUSSELS,EXPTL PSYCHOL LAB,BRUSSELS,BELGIUM. HOP UNIV BRUGMANN,SERV REVALIDAT NEUROL,BRUSSELS,BELGIUM. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. RP PERETZ, I (reprint author), UNIV MONTREAL,DEPT PSYCHOL,CP 6128,SUCC CTR VILLE,MONTREAL,PQ H3C 3J7,CANADA. NR 81 TC 199 Z9 204 U1 2 U2 16 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD DEC PY 1994 VL 117 BP 1283 EP 1301 DI 10.1093/brain/117.6.1283 PN 6 PG 19 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA QD046 UT WOS:A1994QD04600005 PM 7820566 ER PT J AU BARNHILL, RL AGUIAR, M COHEN, C KANG, SW KENNEDY, J SCHMIDT, B SOBER, AJ SOLOMON, AR AF BARNHILL, RL AGUIAR, M COHEN, C KANG, SW KENNEDY, J SCHMIDT, B SOBER, AJ SOLOMON, AR TI CONGENITAL MELANOCYTIC NEVI AND DNA CONTENT - AN ANALYSIS BY FLOW AND IMAGE CYTOMETRY SO CANCER LA English DT Article DE DNA CONTENT; IMAGE CYTOMETRY; FLOW CYTOMETRY; CONGENITAL MELANOCYTIC NEVI; MELANOMA ID PARAFFIN-EMBEDDED TISSUE; NEVOMELANOCYTIC NEVI; MELANOMA AB Background. Potential risk factors for the development of melanoma in congenital melanocytic nevi (CMN) are not well established. DNA aneuploidy may constitute such a risk factor but has not been sufficiently studied in CMN. Methods. In the present study, DNA analysis of eight giant CMN, nine medium CMN (1.5-20 cm), and eight small CMN (< 1.5 cm) was assessed by flow cytometry and selected lesions (six nevi)by DNA image cytometry. DNA content was correlated with patient age, nevus size, and degree of cytologic atypia. Results. DNA aneuploidy was detected by flow cytometry in two giant CMN from adult patients and in a small CMN from a child. DNA aneuploidy was not observed in any of the six CMN studied by image cytometry, although an increased S-phase was noted in a markedly atypical giant CMN. No DNA aneuploidy was detected in medium-sized CMN or in the CMN of nine patients 1 year of age or younger. Conclusion. In contrast to previous studies, it was observed that abnormal DNA content does tend to correlate with cytologic atypia, particularly in giant CMN with atypia or melanoma, in adults. Conversely, frank DNA aneuploidy in any CMN in children younger than 1 year of age, irrespective of histologic findings, was not detected. Finally, based on these limited studies, greater sensitivity of image over flow cytometry for detection of DNA aneuploidy cannot be verified. C1 CHILDRENS HOSP,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. EMORY UNIV,SCH MED,DEPT PATHOL,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT DERMATOL,ATLANTA,GA 30322. RP BARNHILL, RL (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV DERMATOPATHOL,75 FRANCIS ST,BOSTON,MA 02114, USA. NR 17 TC 11 Z9 11 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 1994 VL 74 IS 11 BP 2935 EP 2943 DI 10.1002/1097-0142(19941201)74:11<2935::AID-CNCR2820741108>3.0.CO;2-G PG 9 WC Oncology SC Oncology GA PT806 UT WOS:A1994PT80600007 PM 7954257 ER PT J AU WATTERSON, J TOOGOOD, I NIEDER, M MORSE, M FRIERDICH, S LEE, YS MOERTEL, CL PRIEST, JR AF WATTERSON, J TOOGOOD, I NIEDER, M MORSE, M FRIERDICH, S LEE, YS MOERTEL, CL PRIEST, JR TI EXCESSIVE SPINAL-CORD TOXICITY FROM INTENSIVE CENTRAL-NERVOUS-SYSTEM DIRECTED THERAPIES SO CANCER LA English DT Article DE SPINAL CORD TOXICITY; BURKITTS LYMPHOMA; INTRATHECAL CHEMOTHERAPY; SPINAL RADIATION; CYTOSINE ARABINOSIDE; PARAPARESIS; PARAPLEGIA ID ACUTE LYMPHOBLASTIC-LEUKEMIA; INTRATHECAL CYTOSINE-ARABINOSIDE; MYELIN BASIC-PROTEIN; PEDIATRIC-ONCOLOGY-SOCIETY; CEREBROSPINAL-FLUID; ACTIVE DEMYELINATION; SURVIVAL RATE; STAGE-III; CHEMOTHERAPY; PARAPLEGIA AB Background. Intrathecal chemotherapy, radiation therapy, and systemic chemotherapy are used for both prophylaxis and treatment of central nervous system (CNS) disease in hematologic malignancies. Twenty-three cases of myelopathy that occurred in patients who received intensive CNS-directed therapy were evaluated to identify the determinants of this severe CNS toxicity. Methods. Nine cases treated by the authors and 14 collected from the literature are discussed. Twelve had Burkitt's leukemia/lymphoma. Patient ages ranged from 3 to 30 years (median, 15 years). The dose intensity of CNS-directed therapies, including intrathecal cytosine arabinoside (ara-C), intrathecal methotrexate (MTX), systemic high dose (HD) MTX, systemic HD ara-C, systemic thiotepa, and CNS radiation, was evaluated by the determination of single drug doses and cumulative total drug or irradiation doses over elapsed treatment durations. Results. Central nervous system treatment was prophylactic in 10 cases; active CNS disease was being treated in 13 cases. One patient received only intrathecal ara-C before toxicity occurred; others received intrathecal ara-C and varying combinations of intrathecal MTX, HD ara-C, HD MTX, CNS radiation, and systemic thiotepa. Eight patients died of toxicity, of whom 6 had autopsy-proven cord necrosis; 3 were ventilator-dependent; 10 had persistent paraplegia or paraparesis; and 2 recovered completely. Conclusion. Both highly intensive, short CNS treatment sequences and lower intensity, long term cumulative treatments may result in this rare but severe myelopathy. The cause is multifactorial, with systemic chemotherapy, intrathecal chemotherapy, and radiation therapy contributing to toxicity. Multiple intrathecal ara-C and/or MTX doses given at frequent (daily) intervals should be avoided. Concurrent intrathecal ara-C and systemic HD ara-C also appear to be especially toxic. Intrathecal hydrocortisone given with intrathecal ara-C does not protect against myelopathy. Multiple, frequently spaced courses of CNS-directed therapies must be avoided, especially in patients who have received prior CNS radiation. C1 CHILDRENS HOSP,ST PAUL,MN 55105. ADELAIDE CHILDRENS HOSP INC,ADELAIDE,SA,AUSTRALIA. RAINBOW BABIES & CHILDRENS HOSP,CLEVELAND,OH. CHILDRENS HOSP,DENVER,CO. UNIV WISCONSIN HOSP,MADISON,WI. DANA FARBER CANC INST,BOSTON,MA. NR 34 TC 57 Z9 58 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 1994 VL 74 IS 11 BP 3034 EP 3041 DI 10.1002/1097-0142(19941201)74:11<3034::AID-CNCR2820741122>3.0.CO;2-O PG 8 WC Oncology SC Oncology GA PT806 UT WOS:A1994PT80600021 PM 7954266 ER PT J AU SHIELDS, JA CHAR, DH GRAGOUDAS, ES AF SHIELDS, JA CHAR, DH GRAGOUDAS, ES TI MANAGEMENT OF UVEAL MELANOMA - A CONTINUING DILEMMA - REPLY SO CANCER LA English DT Letter ID COBALT PLAQUE RADIOTHERAPY; SURVIVAL RATES; CILIARY BODY; IRRADIATION; ENUCLEATION C1 THOMAS JEFFERSON UNIV,PHILADELPHIA,PA 19107. UNIV CALIF SAN FRANCISCO,MED CTR,DEPT OCULAR ONCOL,SAN FRANCISCO,CA 94143. MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP SHIELDS, JA (reprint author), WILLS EYE HOSP & RES INST,OCULAR ONCOL SERV,PHILADELPHIA,PA 19107, USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 1994 VL 74 IS 11 BP 3074 EP 3075 PG 2 WC Oncology SC Oncology GA PT806 UT WOS:A1994PT80600031 ER PT J AU LI, FP FRAUMENI, JF AF LI, FP FRAUMENI, JF TI COLLABORATIVE INTERDISCIPLINARY STUDIES OF P53 AND OTHER PREDISPOSING GENES IN LI-FRAUMENI SYNDROME SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID CANCER FAMILY; MUTATIONS C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20893. RP LI, FP (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 10 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 1994 VL 3 IS 8 BP 715 EP 717 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA PW570 UT WOS:A1994PW57000012 PM 7881346 ER PT J AU JHANWAR, SC CHEN, QG LI, FP BRENNAN, MF WOODRUFF, JM AF JHANWAR, SC CHEN, QG LI, FP BRENNAN, MF WOODRUFF, JM TI CYTOGENETIC ANALYSIS OF SOFT-TISSUE SARCOMAS - RECURRENT CHROMOSOME-ABNORMALITIES IN MALIGNANT PERIPHERAL-NERVE SHEATH TUMORS (MPNST) SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID ROUND CELL TUMORS; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; MOLECULAR CHARACTERIZATION; DELETIONS; GENE; TRANSLOCATION; ABERRATIONS; MUTATIONS; REGION; NEUROFIBROSARCOMAS AB Malignant peripheral nerve sheath tumors (MPNST) are known to develop in patients with neurofibromatosis 1 (NF1), thus providing an excellent model for the study of multistep carcinogenesis in genetically predisposed individuals. To determine the sites of gene(s) involved in such a process, we have performed cytogenetic analysis on 10 tumors. The patients were five males and five females ranging in age from 15 to 77 years. Nine patients had NF1. Karyotypic analysis of these tumors exhibited complex clonal abnormalities of several chromosomes. Recurrent abnormalities (numerical as well as structural) of chromosomes 1, 11, 12, 14, 17, and 22 occurred in a substantial proportion of tumors studied. Although abnormalities of these chromosomes have been seen in a variety of other tumors, the aberrations of chromosomes 17 and 22 are of particular interest; chromosomes 17 and 22 carry the genes for NF1 and NF2, respectively. In addition to other clonal aberrations, six tumors had abnormalities of both chromosomes 17 and 22, while three tumors only had an abnormality of chromosome 17. In eight tumors a structural abnormality of chromosome 17 included deletion or a relative deficiency of 17p; in four of the tumors there was also either deletion or rearrangement of the NF1 locus at the cytogenetic level. One tumor had monosomy of chromosome 17. The abnormality of chromosome 22 was deletion of 22q11.2-->qter. This study suggests that the germline mutation in one of the copies accompanied by loss or inactivation of the second copy of the NF1 gene and tumor suppressor gene(s) on 17p and 22q may be associated with the neoplastic transformation; abnormalities of other chromosomes may be related to progression of MPNST. Although the role of the p53 gene in carcinogenesis is well documented in several tumor types, the role of the NF2 gene or other unidentified tumor suppressor gene(s) on chromosomes 22q, Ip, 11, 12, 14 remains to be seen. C1 MEM SLOAN KETTERING CANC CTR,DEPT SURG,NEW YORK,NY 10021. DANA FARBER CANC INST,DEPT EPIDEMIOL,BOSTON,MA. RP JHANWAR, SC (reprint author), MEM SLOAN KETTERING CANC CTR,DEPT PATHOL,SOLID TUMOR GENET LAB,BOX 147,1275 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA-47179, N01-CP-71126] NR 41 TC 69 Z9 69 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD DEC PY 1994 VL 78 IS 2 BP 138 EP 144 DI 10.1016/0165-4608(94)90081-7 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA QB635 UT WOS:A1994QB63500003 PM 7828144 ER PT J AU HAMBERG, LM KRISTJANSEN, PEG HUNTER, GJ WOLF, GL JAIN, RK AF HAMBERG, LM KRISTJANSEN, PEG HUNTER, GJ WOLF, GL JAIN, RK TI SPATIAL HETEROGENEITY IN TUMOR PERFUSION MEASURED WITH FUNCTIONAL COMPUTED-TOMOGRAPHY AT 0.05-MU-L RESOLUTION SO CANCER RESEARCH LA English DT Note ID RESONANCE SPECTROSCOPY; BLOOD-FLOW; LUNG; CARCINOMA; INVIVO AB High speed (200 ms temporal resolution) functional computed tomography was used to demonstrate tumor vascular heterogeneity with 0.05 mu l spatial resolution. Vascular topologies were investigated in 2 human snail cen lung cancer lines implanted either s.c. or as a tissue isolated preparation in immunocompromised mice. Peripheral versus central vascular topology was identified in the s.c. and tissue-isolated preparations, respectively. Pharmacokinetic analysis demonstrated that tumor physiology was influenced by cell line (P = 0.016) and not by location (P > 0.6). This sew technique has the potential to characterize individual tumors in patients with minimal invasiveness, permitting more detailed prognosis and management. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,STEELE LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP HAMBERG, LM (reprint author), MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,DEPT RADIOL,BOSTON,MA 02129, USA. FU NCI NIH HHS [R35-CA-56591] NR 21 TC 47 Z9 47 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1994 VL 54 IS 23 BP 6032 EP 6036 PG 5 WC Oncology SC Oncology GA PU942 UT WOS:A1994PU94200004 PM 7954440 ER PT J AU PALACIOS, IF AF PALACIOS, IF TI WHAT IS THE GOLD STANDARD TO MEASURE MITRAL-VALVE AREA POSTMITRAL BALLOON VALVULOPLASTY SO CATHETERIZATION AND CARDIOVASCULAR DIAGNOSIS LA English DT Editorial Material ID FOLLOW-UP; ATRIAL; VALVOTOMY RP PALACIOS, IF (reprint author), MASSACHUSETTS GEN HOSP,DIV INTERVENT CARDIOL,BOSTON,MA 02114, USA. NR 7 TC 29 Z9 29 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0098-6569 J9 CATHETER CARDIO DIAG JI Catheter. Cardiovasc. Diagn. PD DEC PY 1994 VL 33 IS 4 BP 315 EP 316 DI 10.1002/ccd.1810330405 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QF929 UT WOS:A1994QF92900003 PM 7889548 ER PT J AU WANG, L GOILLOT, E TEPPER, RI AF WANG, L GOILLOT, E TEPPER, RI TI IL-10 INHIBITS ALLOREACTIVE CYTOTOXIC T-LYMPHOCYTE GENERATION IN-VIVO SO CELLULAR IMMUNOLOGY LA English DT Article ID INTERLEUKIN-10 IL-10; CELL PROLIFERATION; IFN-GAMMA; B-CELLS; ACTIVATED MACROPHAGES; CYTOKINE PRODUCTION; MICE; INFECTION; SECRETE; GENE AB In this report, we present evidence that the CTL response directed against MHC Class I allodeterminants can be inhibited as a result of IL-10 expression in vivo. The presence of localized IL-10 secretion at the site of allogeneic tumor cell challenge resulted in marked inhibition of the CTL response and allowed growth of the tumor in the allogeneic host. Using purified CD4(+) T cells from mice immunized in the presence or absence of IL-10, we have shown that the loss of alloreactivity as a consequence of IL-10 expression results from the inhibition of CD4(+) T cell function. The expression of either IL-2 or IFN-gamma with IL-10 locally at the time of allogeneic cell challenge completely restored CTL alloreactivity, suggesting that the action of IL-10 could be bypassed by providing helper T lymphocyte-derived cytokines of the Th1 type at the site of immunization. Inhibition of alloreactivity by IL-10 was observed using either purified macrophages or dendritic cells as APC in an in vitro assay. Thus, the expression of IL-10 following antigenic challenge (such as that observed in Th2-like immune responses) may profoundly limit the ability for generating functional CTL in vivo. (C) 1994 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,MGH CANC CTR,BOSTON,MA 02129. NR 29 TC 51 Z9 51 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD DEC PY 1994 VL 159 IS 2 BP 152 EP 169 DI 10.1006/cimm.1994.1304 PG 18 WC Cell Biology; Immunology SC Cell Biology; Immunology GA PX262 UT WOS:A1994PX26200004 PM 7994751 ER PT J AU GOLDBERG, RT AF GOLDBERG, RT TI CHILDHOOD ABUSE, DEPRESSION, AND CHRONIC PAIN SO CLINICAL JOURNAL OF PAIN LA English DT Article DE CHRONIC PAIN; CHILDHOOD SEXUAL ABUSE; CHILDHOOD PHYSICAL ABUSE; DEPRESSION ID CHRONIC PELVIC PAIN; SEXUAL ABUSE; WOMEN AB Objective: To investigate the relationships among history of childhood abuse, type of pain, and depression. Design: Survey, consecutive sample, correlational. Setting: An interdisciplinary pain-management center in a rehabilitation hospital. Patients: The participants were 201 consecutive patients with chronic pain complaints, 68% women, mean age 38 years, of whom 28% complained of pain in more than three major sites, 26% had low back pain, 19% had craniofacial pain, and 25% had pain in other regions. Outcome Measures: Beck Depression Inventory, Childhood History recorded presence or absence of abuse, age of onset, age when abuse was acknowledged, duration and frequency of abuse, relationship of abuser to the participant. Pain type was classified by IASP. Results: Patients with history of both sexual and physical abuse in childhood had more depression. The differences among abuse groups was significant (p < 0.03). The impact of childhood abuse and type of pain on depression was tested by a two-factor analysis of variance. The influence of childhood abuse was significant (p < 0.04), whereas the influence of type of pain (p < 0.76) and the interaction between type of pain and childhood abuse (p < 0.40) were not significant. Conclusions: There is a positive, significant relationship between depression and history of childhood sexual and physical abuse. The influence of type of pain on depression was not significant. Prevailing research explained depression as an expected, natural consequence of chronic pain. Our research suggests that the relationship between chronic pain and depression may be attributable in part to childhood abuse history. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BOSTON,MA 02114. RP GOLDBERG, RT (reprint author), SPAULDING REHABIL HOSP,125 NASHUA ST,BOSTON,MA 02114, USA. NR 20 TC 35 Z9 38 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0749-8047 J9 CLIN J PAIN JI Clin. J. Pain PD DEC PY 1994 VL 10 IS 4 BP 277 EP 281 DI 10.1097/00002508-199412000-00006 PG 5 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA PV142 UT WOS:A1994PV14200006 PM 7858356 ER PT J AU NICHOLS, DH AF NICHOLS, DH TI THE EPIDEMIOLOGIC CHARACTERISTICS OF BREAST-CANCER SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article ID RISK; AGE; WOMEN; FAT; PREGNANCY; LACTATION; DISEASE; HISTORY RP NICHOLS, DH (reprint author), MASSACHUSETTS GEN HOSP,VINCENT MEM GYNECOL SERV,32 FRUIT ST,BOSTON,MA 02114, USA. NR 35 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD DEC PY 1994 VL 37 IS 4 BP 925 EP 932 DI 10.1097/00003081-199412000-00019 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PQ357 UT WOS:A1994PQ35700017 PM 7842560 ER PT J AU SPRINGFIELD, DS ROSENBERG, AE MANKIN, HJ MINDELL, ER AF SPRINGFIELD, DS ROSENBERG, AE MANKIN, HJ MINDELL, ER TI RELATIONSHIP BETWEEN OSTEOFIBROUS DYSPLASIA AND ADAMANTINOMA SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID LONG-BONE; FIBROUS DYSPLASIA; TIBIA AB The records and computer files of 32 patients treated at 1 institution for ossifying fibroma, fibrous dysplasia, osteofibrous dysplasia-like adamantinoma, or adamantinoma of the tibia were reviewed. Nineteen patients had their diagnosis changed, either because of a recurrence or through review of their histology. Six of the 9 patients who had a typical adamantinoma and 6 of the 10 patients who had an osteofibrous dysplasia-like adamantinoma had a diagnosis of 1 of the benign conditions before their adamantinoma was recognized. Only 6 patients actually had osteofibrous dysplasia. Three patients required a resection, but only 1 of the other 3 has been observed >5 years. This review suggests that many patients with a diagnosis of fibrous dysplasia or osteofibrous dysplasia of the tibia actually have an adamantinoma, and that osteofibrous dysplasia is often a locally aggressive lesion that progresses until it is widely resected. In addition, osteofibrous dysplasia and adamantinoma appear to be related, and osteofibrous dysplasia may be a precursor of adamantinoma. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP SPRINGFIELD, DS (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,GRAY 6,FRUIT ST,BOSTON,MA 02114, USA. NR 25 TC 37 Z9 40 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 1994 IS 309 BP 234 EP 244 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PX372 UT WOS:A1994PX37200030 PM 7994967 ER PT J AU LEE, MJ DAWSON, SL MUELLER, PR HAHN, PF SAINI, S LU, DSK GOLDBERG, MA GAZELLE, GS AF LEE, MJ DAWSON, SL MUELLER, PR HAHN, PF SAINI, S LU, DSK GOLDBERG, MA GAZELLE, GS TI FAILED METALLIC BILIARY STENTS - CAUSES AND MANAGEMENT OF DELAYED COMPLICATIONS SO CLINICAL RADIOLOGY LA English DT Article ID ENDOPROSTHESES; OBSTRUCTION; DRAINAGE AB Objective: To describe the incidence, management and long-term outcome of metal stent failure in patients with malignant biliary obstruction. Subjects and Methods: Sixty-nine patients received a total of 93 metallic biliary stents for relief of malignant biliary obstruction. Twenty-nine patients had hilar tumours; 40 had common bile duct tumours. Results: Ten of 69 patients (14%) presented with stent occlusion at a mean interval of 4 months after stent insertion. Five of 29 patients (17%) with hilar lesions and five of 40 patients (12%) with common bile duct lesions had stent occlusion. Occlusion was due to tumour overgrowth in eight patients and to occlusion by debris in two. The eight patients with tumour overgrowth were treated with internal/external catheters (5 patients), no therapy (2 patients), and further metal stents (1 patient). These eight patients with tumour overgrowth had a limited lifespan after tumour overgrowth occurred with a mean survival of 2.6 months. The two patients with occlusion due to debris were treated by sweeping the stent with a balloon catheter and these patients survived 26 and 27 months, respectively. Conclusion: Adequate peripheral purchase in the biliary tree and overstenting are necessary to prevent tumour overgrowth when stenting hilar lesions. The development of stent occlusion due to tumour overgrowth heralds a limited survival and internal/external catheters are preferred over further metal stents for palliation. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP LEE, MJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114, USA. NR 16 TC 26 Z9 26 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 1994 VL 49 IS 12 BP 857 EP 862 DI 10.1016/S0009-9260(05)82875-2 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PZ424 UT WOS:A1994PZ42400004 PM 7530177 ER PT J AU JOHNSON, DC KAZEMI, H AF JOHNSON, DC KAZEMI, H TI CENTRAL CONTROL OF VENTILATION IN NEUROMUSCULAR DISEASE SO CLINICS IN CHEST MEDICINE LA English DT Article ID RESPIRATORY MUSCLE WEAKNESS; MOUTH OCCLUSION PRESSURE; ACID MALTASE DEFICIENCY; MYOTONIC-DYSTROPHY; MUSCULAR-DYSTROPHY; CONGENITAL MYOPATHY; PULMONARY-FUNCTION; SLEEP; HYPOVENTILATION; DISORDERS AB Control of ventilation depends on both peripheral and central chemoreceptors. Neuromuscular diseases cause many changes that may affect ventilation and ventilatory control, often leading to an abnormal pattern of ventilation, hypoventilation during sleep, and reduced ventilatory response to CO2. A combination of factors can lead to abnormal patterns of breathing and hypoventilation in these disorders, and no single pathophysiologic mechanism can explain all the abnormalities. C1 MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 85 TC 13 Z9 13 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD DEC PY 1994 VL 15 IS 4 BP 607 EP 617 PG 11 WC Respiratory System SC Respiratory System GA PW200 UT WOS:A1994PW20000002 PM 7867278 ER PT J AU BASSI, DG FOITZIK, T RATTNER, DW LEWANDROWSKI, K WARSHAW, AL DELCASTILLO, CF AF BASSI, DG FOITZIK, T RATTNER, DW LEWANDROWSKI, K WARSHAW, AL DELCASTILLO, CF TI FAILURE OF PENTOXIFYLLINE TO AMELIORATE SEVERE ACUTE-PANCREATITIS IN THE RAT - RESULTS OF A PROSPECTIVE, RANDOMIZED, CONTROLLED-STUDY SO CRITICAL CARE MEDICINE LA English DT Article DE PANCREATITIS ACUTE; PENTOXIFYLLINE; MICROCIRCULATION; TRYPSINOGEN ACTIVATION; CRITICAL ILLNESS; HEMODYNAMICS; PANCREAS ID TRYPSINOGEN-ACTIVATION PEPTIDES; HEMORRHAGIC-SHOCK; BLOOD-FLOW; DECREASES; IMPROVES; MICROCIRCULATION; PERFUSION; ISCHEMIA; NECROSIS; THERAPY AB Objective: To investigate the benefit of pentoxifylline in severe experimental pancreatitis. Design: Prospective, randomized, controlled study. Setting: Experimental animal laboratory in a University hospital. Subjects: Forty-two adult male Sprague-Dawley rats. Interventions: Acute pancreatitis was induced by supramaximal stimulation with cerulein plus a pressure and volume controlled 10 min intraductal infusion of 10-mM glycodeoxycholic acid. Thirty minutes after pancreatitis was induced, animals were randomized to receive pentoxifylline (60 mg/kg over 2.5 hrs), or saline. All animals received fluid resuscitation with lactated Ringer's solution (8 mL/kg/hr), and surviving animals were killed at 24 hrs. Measurements and Main Results: There was a progressively significant decrease in mean arterial pressure after pancreatitis was induced, with no difference between pentoxifylline-treated rats and controls. Hematocrit increased significantly in both groups at 6 hrs, and returned to baseline values at 24 hrs. Ascites volume and levels of trypsinogen activation peptide in plasma and ascites were similar in both groups. Twenty-four hour mortality was 47% for the pentoxifylline group and 52% for the control group. Histologic scores for necrosis, edema, inflammation, and hemorrhage showed no significant differences between the two groups. Conclusion: Treatment with pentoxifylline failed to improve outcome in a model of severe acute pancreatitis in the rat. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 28 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 1994 VL 22 IS 12 BP 1960 EP 1963 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA PW272 UT WOS:A1994PW27200012 PM 7988133 ER PT J AU SPIEGELMAN, B WATT, FM AF SPIEGELMAN, B WATT, FM TI CELL-DIFFERENTIATION - EDITORIAL OVERVIEW SO CURRENT OPINION IN CELL BIOLOGY LA English DT Editorial Material C1 IMPERIAL CANC RES FUND,LONDON WC2A 3PX,ENGLAND. RP SPIEGELMAN, B (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 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 1994 VL 6 IS 6 BP 781 EP 782 DI 10.1016/0955-0674(94)90044-2 PG 2 WC Cell Biology SC Cell Biology GA PV275 UT WOS:A1994PV27500001 ER PT J AU DANDREA, AD AF DANDREA, AD TI HEMATOPOIETIC GROWTH-FACTORS AND THE REGULATION OF DIFFERENTIATIVE DECISIONS SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID STIMULATING FACTOR-RECEPTOR; FRIEND ERYTHROLEUKEMIA CELLS; ERYTHROPOIETIN RECEPTOR; ERYTHROID-DIFFERENTIATION; CYTOPLASMIC DOMAIN; GENE-EXPRESSION; PROLIFERATION; INDUCTION; REGIONS; LINE AB Hematopoietic growth factors control the growth and differentiation of hematopoietic progenitor cells and bind to specific receptors that are expressed on the surface of immature hematopoietic cells found in the bone marrow. Many studies have demonstrated that these growth factors stimulate cellular growth and division by receptor activation. More recently, it has become apparent that they also influence, either directly or indirectly, the process of cellular differentiation. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP DANDREA, AD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [R01 DK 43889-01] NR 33 TC 32 Z9 32 U1 0 U2 0 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 1994 VL 6 IS 6 BP 804 EP 808 DI 10.1016/0955-0674(94)90048-5 PG 5 WC Cell Biology SC Cell Biology GA PV275 UT WOS:A1994PV27500005 PM 7880526 ER PT J AU BEAL, MF AF BEAL, MF TI NEUROCHEMISTRY AND TOXIN MODELS IN HUNTINGTONS-DISEASE SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID 3-NITROPROPIONIC ACID; NEURONAL DEATH; GLUCOSE CONSUMPTION; ENERGY-METABOLISM; BRAIN-LESIONS; DEGENERATION; EXCITOTOXIN; IMPAIRMENT; STRIATUM; INHIBITION AB Huntington's disease (HD) is a prototypical neurodegenerative disease characterized by selective loss of neurons in the basal ganglia. Although the gene defect has recently been identified, the mechanism by which it leads to neuronal degeneration remains unknown. We have hypothesized that a defect in oxidative phosphorylation may lead to slow, excitotoxic neuronal degeneration in this illness. Evidence for such a defect is reviewed here, including our recent studies using magnetic resonance imaging spectroscopy that show elevated lactate levels in the basal ganglia and cerebral cortex of patients with HD. If a defect in energy metabolism is responsible for neuronal degeneration in HD, it should be possible to mimic the neurodegenerative process with mitochondrial toxins. Our recent studies with 3-nitropropionic acid, an irreversible inhibitor of succinate dehydrogenase, show that it can produce striking similarities to the neuropathologic and neurochemical features of HD in both rodents and primates. If such a mechanism is indeed relevant to the pathogenesis of HD, then agents that can improve oxidative phosphorylation might prove to be efficacious. We found that both coenzyme Q(10) and nicotinamide can ameliorate striatal lesions produced by mitochondrial toxins in vivo. Furthermore, they reduced elevated lactate concentrations when administered to patients with HD. This finding raises the possibility that such an approach might prove useful in trying to slow the neurodegenerative process. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP BEAL, MF (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,WARREN 408,BOSTON,MA 02114, USA. NR 40 TC 86 Z9 90 U1 0 U2 2 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 1994 VL 7 IS 6 BP 542 EP 547 DI 10.1097/00019052-199412000-00012 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PV143 UT WOS:A1994PV14300012 PM 7866587 ER PT J AU GARRISON, MW CAMPBELL, DM SCLAR, DA ANDERSON, DE AF GARRISON, MW CAMPBELL, DM SCLAR, DA ANDERSON, DE TI COMPARATIVE ACTIVITY OF TEMAFLOXACIN, OFLOXACIN, AND CIPROFLOXACIN AGAINST STREPTOCOCCUS-PNEUMONIAE USING AN IN-VITRO PHARMACODYNAMIC MODEL APPARATUS SO CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL LA English DT Article ID RESPIRATORY-TRACT PATHOGENS; INVITRO; SPARFLOXACIN; ANTIBIOTICS; VANCOMYCIN; RESISTANCE; BACTERIA AB The activity of quinolone antimicrobials against Streptococcus pneumoniae has been controversial. Although currently available quinolones are rarely advocated in the treatment of streptococcal infections, differences in antistreptococcal activity exist within the quinolone class. This study addresses the issue by using an in vitro pharmacodynamic modeling apparatus (PDM) to accurately characterize the bacterial kill rates of temafloxacin (TM; 400 mg and 600 mg), ofloxacin (OFX; 400 mg), and ciprofloxacin (CP; 500 mg and 750 mg) (minimum inhibitory concentrations for all three are 1.0 mu g/mL) against a clinical isolate of S pneumoniae. The bacterial kill rates and the time required to achieve a 99.9% reduction in the initial inoculum for each quinolone were statistically compared using an analysis of variance with a Duncan multiple range test to detect potential differences in antimicrobial activity among the quinolones. Five commonly used, single doses were simulated using the PDM (initial concentration): low-dose TM (2.4 mu g/mL); high-dose TM (3.9 mu g/mL); standard-dose OFX (4.0 mu g/mL); low-dose CP (2.4 mu g/mL); and high-dose CP (3.5 mu g/mL). An elimination half-life (t(1/2)) of 6 hours was used for TM and OFX, and a t(1/2) of 3 hours was used for CP. Two experiments were conducted for each dose and the mean bacterial kill rate was determined. Comparison of bacterial kill rates (mean +/- SD) revealed significantly steeper slopes for both TM regimens (-1.62 +/- 0.12, low TM; -1.78 +/- 0.15, high TM) relative to the OFX and CP regimens (-0.89 +/- 0.01, OFX; -0.81 +/- 0.04, low CP; -0.96 +/- 0.12, high CP). Similarly, the kill time (mean +/- SD) needed for 99.9% inoculum reduction was approximately 50% shorter for the TM trials (1.85 +/- 0.01 hours, low TM; 1.69 +/- 0.04 hours, high TM) compared with the other regimens (3.36 +/- 0.02 hours, OFX; 3.72 +/- 0.20 hours, low CP; 3.16 +/- 0.39 hours, high CP). When compared with OFX and CP, TM at both low and high doses is associated with significantly greater activity against this clinical isolate of S pneumoniae. C1 DEACONESS MED CTR,DEPT MICROBIOL,SPOKANE,WA. SACRED HEART MED CTR,DEPT MICROBIOL,SPOKANE,WA. RP GARRISON, MW (reprint author), WASHINGTON STATE UNIV,COLL PHARM,601 W 1ST AVE,SPOKANE,WA 99204, USA. NR 28 TC 3 Z9 3 U1 0 U2 0 PU EXCERPTA MEDICA INC PI BELLE MEAD PA 105 RAIDER BLVD, BELLE MEAD, NJ 08502 SN 0011-393X J9 CURR THER RES CLIN E JI Curr. Ther. Res.-Clin. Exp. PD DEC PY 1994 VL 55 IS 12 BP 1432 EP 1441 DI 10.1016/S0011-393X(05)80749-0 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA PY443 UT WOS:A1994PY44300002 ER PT J AU WEIR, GC NATHAN, DM SINGER, DE AF WEIR, GC NATHAN, DM SINGER, DE TI STANDARDS OF CARE FOR DIABETES SO DIABETES CARE LA English DT Review ID CONVERTING-ENZYME-INHIBITION; BLOOD-GLUCOSE CONTROL; KIDNEY-FUNCTION; PROTEIN RESTRICTION; INSULIN-TREATMENT; MICROVASCULAR COMPLICATIONS; ANTIHYPERTENSIVE TREATMENT; MYOCARDIAL-INFARCTION; CLINICAL NEPHROPATHY; DIETARY-PROTEIN C1 MASSACHUSETTS GEN HOSP,DEPT MED,DIABET UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,GEN INTERNAL MED UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP WEIR, GC (reprint author), JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 111 TC 32 Z9 32 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 1994 VL 17 IS 12 BP 1514 EP 1522 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PU321 UT WOS:A1994PU32100024 PM 7882829 ER PT J AU GEBAUER, F XU, WH COOPER, GM RICHTER, JD AF GEBAUER, F XU, WH COOPER, GM RICHTER, JD TI TRANSLATIONAL CONTROL BY CYTOPLASMIC POLYADENYLATION OF C-MOS MESSENGER-RNA IS NECESSARY FOR OOCYTE MATURATION IN THE MOUSE SO EMBO JOURNAL LA English DT Article DE C-MOS; CYTOPLASMIC POLYADENYLATION; MOUSE; OOCYTE MATURATION ID MATERNAL MESSENGER-RNA; PROTO-ONCOGENE PRODUCT; MEIOTIC MATURATION; XENOPUS-OOCYTES; MAP KINASE; PLASMINOGEN-ACTIVATOR; POLY(A) ELONGATION; SOMATIC-CELLS; MEIOSIS-II; EGGS AB The c-mos proto-oncogene product is a key element in the cascade of events leading to meiotic maturation of vertebrate oocytes, We have investigated the role of cytoplasmic polyadenylation in the translational control of mouse c-mos mRNA and its contribution to meiosis, Using an RNase protection assay we show that optimal cytoplasmic polyadenylation of c-mos mRNA requires three cis elements in the 3' UTR: the polyadenylation hexanucleotide AAUAAA and two U-rich cytoplasmic polyadenylation elements (CPEs) located 4 and 51 nucleotides upstream of the hexanucleotide. When fused to CAT coding sequences, the wild-type 3' UTR of c-mos mRNA, but not a 3' UTR containing mutations in both CPEs, confers translational recruitment during maturation, This recruitment coincides with maximum polyadenylation. To assess whether c-mos mRNA polyadenylation is necessary for maturation of mouse oocytes, we have ablated endogenous c-mos mRNA by injecting an antisense oligonucleotide, which results in a failure to progress to meiosis II after emission of the first polar body, Such antisense oligonucleotide-injected oocytes could be efficiently rescued by co-injection of a c-mos mRNA carrying a wild-type 3' UTR, However, co-injection of a c-mos mRNA lacking functional CPEs substantially lowered the rescue activity, These results demonstrate that translational control of c-mos mRNA by cytoplasmic polyadenylation is necessary for normal development. C1 WORCESTER FDN EXPTL BIOL INC,SHREWSBURY,MA 01545. HARVARD UNIV,DANA FARBER CANC INST,SCH MED,DEPT PATHOL,DIV MOLEC GENET,BOSTON,MA 02115. RI Gebauer, Fatima/E-7725-2015 OI Gebauer, Fatima/0000-0001-7563-0013 FU NCI NIH HHS [CA40189]; NICHD NIH HHS [HD26594]; NIGMS NIH HHS [GM46779] NR 56 TC 176 Z9 178 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 DEC 1 PY 1994 VL 13 IS 23 BP 5712 EP 5720 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PW345 UT WOS:A1994PW34500023 PM 7988567 ER PT J AU ABOUSAMRA, AB GOLDSMITH, PK XIE, LY JUPPNER, H SPIEGEL, AM SEGRE, GV AF ABOUSAMRA, AB GOLDSMITH, PK XIE, LY JUPPNER, H SPIEGEL, AM SEGRE, GV TI DOWN-REGULATION OF PARATHYROID (PTH) PTH-RELATED PEPTIDE RECEPTOR IMMUNOREACTIVITY AND PTH BINDING IN OPOSSUM KIDNEY-CELLS BY PTH AND DEXAMETHASONE SO ENDOCRINOLOGY LA English DT Article ID HORMONE-RELATED PEPTIDE; TUMOR-NECROSIS-FACTOR; OSTEOBLAST-LIKE CELLS; CULTURED BONE-CELLS; ADENYLATE-CYCLASE; OSTEOSARCOMA CELLS; DESENSITIZATION; MEMBRANES; RESPONSES; UMR-106 AB Recent data have shown that PTH down-regulation of its receptor on opossum kidney (OK) cells is not associated with any change in the steady state level of the PTH/PTH-related peptide (PTHrP) receptor messenger RNA. For analysis of down-regulation of the PTH/PTHrP receptor in OK cells, the present work uses a specific receptor antiserum, SR-2, that is useful for detection and quantification of PTH/PTHrP receptor immunoreactivity on intact cells bearing the opossum PTH/PTHrP receptor. SR-2 specifically binds to COS-7 cells transiently expressing the opossum PTH/PTHrP receptor complementary DNA (OK-O), to LLCPK1 cells stably expressing the recombinant opossum PTH/PTHrP receptor (AOK cells), and to OK cells expressing endogenous PTH/PTHrP receptors, but not to mock-transfected COS-7 cells or untransfected LLCPK1 cells. SR-2 binding was also linearly correlated with PTH binding in COS-7 cells transfected with different amounts of OK-O plasmid DNA. Treatment with PTH (100 nM) for 4 and 6 h did not significantly down-regulate the PTH/PTHrP receptor immunoreactivity, although PTH binding was decreased to 51% and 49% of control, respectively, and PTH-stimulated cAMP accumulation was decreased to 27% and 28% of control, respectively. Treatment with PTH (100 nM) for 24 and 48 h significantly decreased PTH binding to 51% and 60% of control and decreased PTH/PTHrP receptor immunoreactivity to 68% and 58% of control, respectively. Incubation of OK cells with 0.1 nM to 1 mu M PTH for 4 h did not downregulate the PTH/PTHrP receptor immunoreactivity, although PTH binding was decreased dramatically. Scatchard blot analysis revealed that the binding affinity was decreased by 7-fold in OK cells treated with PTH for 4 h without change in receptor number. Conversely, treatment of OK cells with PTH for 24 h resulted in a parallel decrease in both receptor number and receptor immunoreactivity without any change in receptor binding affinity. Treatment of OK cells with dexamethasone (0.1 nM to 1 mu M) had no effect on PTH binding or PTH/PTHrP receptor immunoreactivity. Incubation of OK cells with both dexamethasone (1 mu M) and PTH (0.1 nM to 1 mu M), however, caused a significantly greater down-regulation of both PTH binding and PTH/PTHrP receptor immunoreactivity than in cells treated with PTH alone. These data indicate that during the first 4 h of exposure of OK cells to PTH, PTH/PTHrP receptors remain on the cell surface but have lowered affinity to bind the ligand and that dexamethasone potentiates the effect of PTH on PTH/PTHrP receptor down-regulation in OK cells. C1 MASSACHUSETTS GEN HOSP, DEPT PEDIAT, BOSTON, MA 02114 USA. NIDDKD, METAB DIS BRANCH, BETHESDA, MD 20892 USA. RP ABOUSAMRA, AB (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, ENDOCRINE UNIT, BLDG 327, BOSTON, MA 02114 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [DK-11794-26] NR 27 TC 27 Z9 27 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 1994 VL 135 IS 6 BP 2588 EP 2594 DI 10.1210/en.135.6.2588 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PW235 UT WOS:A1994PW23500042 PM 7988447 ER PT J AU YAMIN, M GORN, AH FLANNERY, MR JENKINS, NA GILBERT, DJ COPELAND, NG TAPP, DR KRANE, SM GOLDRING, SR AF YAMIN, M GORN, AH FLANNERY, MR JENKINS, NA GILBERT, DJ COPELAND, NG TAPP, DR KRANE, SM GOLDRING, SR TI CLONING AND CHARACTERIZATION OF A MOUSE-BRAIN CALCITONIN RECEPTOR COMPLEMENTARY DEOXYRIBONUCLEIC-ACID AND MAPPING OF THE CALCITONIN RECEPTOR GENE SO ENDOCRINOLOGY LA English DT Article ID MOLECULAR-CLONING; BINDING-SITES; EXPRESSION CLONING; XENOPUS EMBRYOS; RAT-BRAIN; PEPTIDE; PITUITARY; HORMONE; CYCLASE; POLYPEPTIDE AB We have identified and characterized a mouse brain calcitonin receptor (CTR) complementary DNA (cDNA). This cDNA encodes a receptor protein that, after expression, has high affinity binding for salmon calcitonin (K-d similar to, 12.5 nM) and is coupled to adenylate cyclase. The binding affinity of this expressed receptor for salmon calcitonin is lower than that described for the previously cloned porcine renal and human ovarian CTRs, but is similar to that of the recently described rat brain CTR, designated the C1b form of the receptor. Analysis of the deduced structure of the mouse brain CTR reveals that it is highly related to the other CTR cDNAs that belong to a distinct family of G-protein-coupled receptors with seven transmembrane-spanning domains. The major structural feature that distinguishes the mouse cDNA clone from the other CTRs is the presence of a consecutive 111-basepair nucleotide sequence that encodes a 37-amino acid sequence which is predicted to localize to the first extracellular loop between the second and third transmembrane-spanning domains. We have mapped the CTR gene in the mouse to the proximal region of chromosome 6, which is homologous to the 7q region of human chromosome 7; only a single CTR gene was identified. Preliminary analysis of the mouse CTR gene reveals that it is complex, consisting of multiple exons separated by lengthy introns that would allow for splice variants consistent with the existence of multiple CTR isoforms predicted from the CTR cDNA clones. The differential cellular and tissue distribution of these functionally distinct CTR isoforms provides the molecular basis for the previously reported widespread distribution and functional heterogeneity of the CTR. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,MED SERV, ARTHRIT UNIT, BOSTON, MA 02114 USA. NEW ENGLAND DEACONESS HOSP, DEPT MED, BOSTON, MA 02115 USA. NCI, FREDERICK CANC RES & DEV CTR, MAMMALIAN GENET LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-74101]; NIAMS NIH HHS [AR-03564, K11-AR01895] NR 46 TC 58 Z9 59 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 1994 VL 135 IS 6 BP 2635 EP 2643 DI 10.1210/en.135.6.2635 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PW235 UT WOS:A1994PW23500048 PM 7988453 ER PT J AU HASS, R MEINHARDT, G HADAM, M BARTELS, H AF HASS, R MEINHARDT, G HADAM, M BARTELS, H TI CHARACTERIZATION OF HUMAN TUR LEUKEMIA-CELLS - CONTINUED CELL-CYCLE PROGRESSION IN THE PRESENCE OF PHORBOL ESTER IS ASSOCIATED WITH RESISTANCE TO APOPTOSIS SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE LEUKEMIA CELLS; PHORBOL ESTER; DIFFERENTIATION; CELL CYCLE APOPTOSIS ID KINASE-C ISOZYMES; MONOCYTIC DIFFERENTIATION; MYC ONCOPROTEIN; DNA-BINDING; EXPRESSION; PROTEIN; MAX; INDUCTION; RETRODIFFERENTIATION; FIBROBLASTS AB Human TUR leukemia cells were generated as a subclone of U937 monoblastoid leukemia cells. There was no obvious difference in the ultrastructure of both cell lines, Like in U937 cells, the expression of monocyte specific surface markers such as CD14 was negligible in TUR cells, U937 cells and other human myeloid leukemia cell lines (HL-60, THP-1) can be induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) to differentiate along the monocytic pathway In contrast, exposure to TPA had no effect on the induction of the differentiation program in TUR cells. Thus, the presence of leukocyte integrins including CD11 and CD18, which are significantly induced during TEA-induced differentiation of HL-60, U937 and THP-1 cells, remained nearly unchanged at low levels in both TUR and TPA treated TUR cells. Furthermore, while expression of major histocompatibility complex (MHC) class II antigens on U937 and TPA-treated U937 cells is barely detectable, there was a significantly constitutive expression of MHC class II, particularly human lymphocyte antigen (HLA-DR) on the surface of TUR and TPA-treated TUR cells. Exposure of human myeloid leukemia cells to TPA is also associated with growth arrest resulting either in a retrodifferentiation process or in programmed cell death. In contrast, TUR cells continued to proliferate in the presence of TPA although the proliferative capacity was continuously reduced by increasing concentrations of TPA. In this context, sychronized TUR cells were progressively retarded in the traverse of all phases throughout the cell cycle at concentrations up to 500 nM TPA. However, the expression of genes involved in the regulation of proliferation and cell cycle progression including c-myc and c-max were continuously increased up to 8-fold in TPA-treated TUR cells, although growth reduction by TPA in U937 cells is associated with a significant down-regulation of the c-myc gene, Furthermore, unlike in U937 cells, exposure of TUR cells to TPA did not induce detectable levels of internucleosomal DNA fragmentation or the generation of apoptotic bodies, Whereas differentiation and cell cycle progression are mutually exclusive phenomena and may thus determine the induction of the cell death program, the present data suggest significant differences in the regulation of these pathways in TPA-treated human U937 cells compared to TPA-treated TUR cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA. HANNOVER MED SCH,DEPT PEDIAT SURG,HANNOVER,GERMANY. HANNOVER MED SCH,DEPT ELECTRON MICROSCOPY,HANNOVER,GERMANY. RP HASS, R (reprint author), INST PEPTIDE RES,MED PK,FEODOR LYNEN STR 31,D-30625 HANNOVER,GERMANY. RI Hass, Ralf/F-3197-2012 OI Hass, Ralf/0000-0002-2481-7547 NR 34 TC 24 Z9 24 U1 0 U2 0 PU WISSENSCHAFTLICHE VERLAG GMBH PI STUTTGART 10 PA BIRKENWALDSTRASSE 44 POSTFACH 105339, W-7000 STUTTGART 10, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD DEC PY 1994 VL 65 IS 2 BP 408 EP 416 PG 9 WC Cell Biology SC Cell Biology GA PZ559 UT WOS:A1994PZ55900017 PM 7720732 ER PT J AU TAUPIN, JL ANDERSON, P AF TAUPIN, JL ANDERSON, P TI ACTIVATION-INDUCED PROTEOLYSIS OF THE CYTOPLASMIC DOMAIN OF ZETA IN T-CELL RECEPTORS AND FC-RECEPTORS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T CELL RECEPTOR; FC RECEPTOR; LYMPHOCYTE ACTIVATION ID NATURAL-KILLER-CELLS; ANTIGEN RECEPTOR; ZETA-CHAIN; SIGNAL TRANSDUCTION; TYROSINE KINASES; CD3-ZETA CHAIN; GAMMA-CHAIN; EXPRESSION; COMPLEX; INDUCTION AB The CD3-T cell receptor (TCR) complex on T cells and the Fc gamma receptor type III (Fc gamma RIII)-zeta-gamma complex on natural killer cells are functionally analogous activation receptors that associate with a family of disulfide-linked dimers composed of the related subunits zeta and gamma. Immunochemical analysis of receptor complexes separated on two-dimensional diagonal gels allowed the identification of a previously uncharacterized zeta-p14 heterodimer. zeta-p14 is a component of both CD3-TCR and Fc gamma RIII-zeta-gamma. Peptide mapping analysis shows that p14 is structurally related to zeta, suggesting that it is either: (i) derived from zeta proteolytically or (ii) the product of an alternatively spliced mRNA. The observation that COS cells transformed with a cDNA encoding zeta express zeta-p14 supports the former possibility. The expression of CD3-TCR complexes including zeta-p14 increases following activation with phorbol 12-myristate 13-acetate or concanavalin A, suggesting that proteolysis of zeta may contribute to receptor modulation or desensitization. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. FU NCI NIH HHS [CA53595] NR 28 TC 13 Z9 13 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 1994 VL 24 IS 12 BP 3000 EP 3004 DI 10.1002/eji.1830241212 PG 5 WC Immunology SC Immunology GA PZ242 UT WOS:A1994PZ24200012 PM 7805728 ER PT J AU HAGAN, M PATCHEN, M WEINBERG, S MACVITTIE, T AF HAGAN, M PATCHEN, M WEINBERG, S MACVITTIE, T TI ERYTHROID PROGENITOR (BFU-E, CFU-E) PROLIFERATION AS INFERRED FROM 5'BROMODEOXYURIDINE LABELING SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE BFU-E; PROLIFERATION; BROMODEOXYURIDINE; CFU-E; STEM CELLS ID MOUSE BONE-MARROW; HEMATOPOIETIC STEM; MICE; CELLS; ERYTHROPOIETIN; DIFFERENTIATION; PRECURSORS; INVITRO AB Survival patterns of burst-forming unit-erythroid (BFU-E) and cluster-forming unit-erythroid (CFU-E) were studied in B6D2F1 mice after 5'bromodeoxycytidine (BrdCyd) infusion and near-ultraviolet (near-UV) light treatment. Comparison of the kinetics of BrdCyd sensitization of these colony formers with the kinetics of granulocyte-monocyte colony-forming cells (GM-CFC) and colony-forming unit-spleen (CFU-S) demonstrated a similar, but distinguishable, pattern of labeling between BFU-E and CFU-S. BFU-E and CFU-S each contain a subpopulation of unlabeled cells that diminishes with a half-life of 35 to 40 hours. Subsequent comparisons of this close association of BFU-E and CFU-S in Sl/Sl(d) mice, again, showed similar patterns of BrdCyd labeling without evidence of an unlabeled or Go subpopulation. These results are dis- cussed with respect to the likelihood of a precursor relationship between these two cell types. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. ARMED FORCES RADIOBIOL RES INST,DEPT EXPTL HEMATOL,BETHESDA,MD 20814. USN,MED RES & DEV COMMAND,BETHESDA,MD. NR 33 TC 1 Z9 1 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD DEC PY 1994 VL 22 IS 13 BP 1221 EP 1226 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PT541 UT WOS:A1994PT54100001 PM 7957708 ER PT J AU DONOVAN, MJ YUNIS, EJ DEGIROLAMI, U FLETCHER, JA SCHOFIELD, DE AF DONOVAN, MJ YUNIS, EJ DEGIROLAMI, U FLETCHER, JA SCHOFIELD, DE TI CHROMOSOME-ABERRATIONS IN CHOROID-PLEXUS PAPILLOMAS SO GENES CHROMOSOMES & CANCER LA English DT Note ID NERVOUS-SYSTEM TUMORS; CELLULAR DNA CONTENT; CYTOGENETIC ANALYSIS; FLOW-CYTOMETRY; PLOIDY AB Karyotypic data on choroid plexus papillomas are scarce and, to date, have revealed no consistent aberrations. We karyotyped a choroid plexus papilloma which was characterized by a stemline of 52, XX, + 7, + 11, + 12, + 12, + 15, + 18. Additional copies of chromosomes 16, 17, and 20 were also observed in a significant proportion of the metaphase cells analyzed. Based upon this index case, we retrospectively analyzed eight additional choroid plexus papillomas by fluorescence in situ hybridization by using pericentromeric probes to chromosomes 7, 11, 12, 15, 16, 17, 18, and 20. Extra hybridization signals were observed in five of the eight cases examined. All five cases had extra signals with the chromosome 7 probe, four cases had extra signals with the chromosome 12 probe, and three cases had extra signals with the chromosome 15, 17, and 18 probes. The overall DNA content of these same cases (as determined by image analysis) suggests that gains of additional chromosomes other than those examined may be present. (C) 1994 Wiley-Liss, Inc. C1 CHILDRENS HOSP, DEPT PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. BRIGHAM & WOMENS HOSP, BOSTON, MA USA. CHILDRENS HOSP PITTSBURGH, PITTSBURGH, PA USA. DANA FARBER CANC INST, DIV PEDIAT ONCOL, BOSTON, MA USA. CHILDRENS HOSP, DIV PEDIAT ONCOL, BOSTON, MA USA. NR 11 TC 16 Z9 16 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-2257 EI 1098-2264 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD DEC PY 1994 VL 11 IS 4 BP 267 EP 270 DI 10.1002/gcc.2870110410 PG 4 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA QF961 UT WOS:A1994QF96100009 PM 7533531 ER PT J AU KOLODNER, RD HALL, NR LIPFORD, J KANE, MF RAO, MRS MORRISON, P WIRTH, L FINAN, PJ BURN, J CHAPMAN, P EARABINO, C MERCHANT, E BISHOP, DT AF KOLODNER, RD HALL, NR LIPFORD, J KANE, MF RAO, MRS MORRISON, P WIRTH, L FINAN, PJ BURN, J CHAPMAN, P EARABINO, C MERCHANT, E BISHOP, DT TI STRUCTURE OF THE HUMAN MSH2 LOCUS AND ANALYSIS OF 2 MUIR-TORRE KINDREDS FOR MSH2 MUTATIONS SO GENOMICS LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; LYNCH SYNDROME-II; FAMILY SYNDROME; MICROSATELLITE INSTABILITY; MISMATCH REPAIR; COLON-CANCER; GENETIC INSTABILITY; TUMOR VARIATION; SMALL BOWEL; CARCINOMA AB Hereditary nonpolyposis colorectal carcinoma (HNPCC) is a major cancer susceptibility syndrome known to be caused by inheritance of mutations in genes such as hMSH2 and hMLH1, which encode components of a DNA mismatch repair system. The MSH2 genomic locus has been cloned and shown to cover similar to 73 kb of genomic DNA and to contain 16 exons. The sequence of all of the intron-exon junctions has been determined and used to develop methods for analyzing each MSH2 exon for mutations. These methods have been used to analyze two large HNPCC kindreds exhibiting features of the Muir-Torre syndrome and demonstrate that cancer susceptibility is due to the inheritance of a frameshift mutation in the MSH2 gene in one family and a nonsense mutation in the MSH2 gene in the other family. (C) 1994 Academic Press, Inc. C1 DANA FARBER CANC INST,DIV CELL & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. ST JAMES UNIV HOSP,GENET EPIDEMIOL LAB,IMPERIAL CANC RES FUND,LEEDS LS9 7TF,W YORKSHIRE,ENGLAND. GEN INFIRM,DEPT SURG,LEEDS LS1 3EX,W YORKSHIRE,ENGLAND. GEN INFIRM,CTR DIGEST DIS,LEEDS LS1 3EX,W YORKSHIRE,ENGLAND. UNIV NEWCASTLE UPON TYNE,DEPT HUMAN GENET,NEWCASTLE TYNE NE2 4AA,TYNE & WEAR,ENGLAND. RP KOLODNER, RD (reprint author), DANA FARBER CANC INST,MOLEC BIOL CORE FACIL,44 BINNEY ST,BOSTON,MA 02115, USA. OI Bishop, Tim/0000-0002-8752-8785 FU NCI NIH HHS [CA06516]; NHGRI NIH HHS [HG00305]; NIGMS NIH HHS [GM50006] NR 58 TC 257 Z9 260 U1 0 U2 12 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1994 VL 24 IS 3 BP 516 EP 526 DI 10.1006/geno.1994.1661 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PZ985 UT WOS:A1994PZ98500015 PM 7713503 ER PT J AU HOGAN, K POWERS, PA GREGG, RG AF HOGAN, K POWERS, PA GREGG, RG TI CLONING OF THE HUMAN SKELETAL-MUSCLE ALPHA(1) SUBUNIT OF THE DIHYDROPYRIDINE-SENSITIVE L-TYPE CALCIUM-CHANNEL (CACNL1A3) SO GENOMICS LA English DT Note ID CHAIN C1 UNIV WISCONSIN,DEPT ANESTHESIOL,MADISON,WI 53705. UNIV WISCONSIN,DEPT PEDIAT,MADISON,WI 53705. UNIV WISCONSIN,WAISMAN CTR MENTAL RETARDAT & HUMAN DEV,MADISON,WI 53705. RP HOGAN, K (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT ANESTHESIOL,B6-319 CLIN SCI CTR,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 8 TC 19 Z9 20 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1994 VL 24 IS 3 BP 608 EP 609 DI 10.1006/geno.1994.1677 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PZ985 UT WOS:A1994PZ98500031 PM 7713519 ER PT J AU SINGARAM, C SENGUPTA, A SWEET, MA SUGARBAKER, DJ GOYAL, RK AF SINGARAM, C SENGUPTA, A SWEET, MA SUGARBAKER, DJ GOYAL, RK TI NITRINERGIC AND PEPTIDERGIC INNERVATION OF THE HUMAN ESOPHAGUS SO GUT LA English DT Article ID LOWER ESOPHAGEAL SPHINCTER; NITRIC-OXIDE SYNTHASE; GENE-RELATED PEPTIDE; NEURONAL NADPH DIAPHORASE; SMOOTH-MUSCLE; SUBSTANCE-P; OPOSSUM; CALCITONIN; MEDIATOR; PIG AB The distribution, colocalisation, and interconnections of nitrinergic and peptidergic neurons and nerves in the human oesophagus were examined. Cryosections of surgically resected tissues from eight subjects were studied with indirect immunofluorescence for the presence of 11 neuropeptides and neuron specific enolase. After immunohistochemistry, nitric oxide synthase was shown on the same sections with the beta nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemical reaction. The histochemical findings were verified immunohistochemically on other sections with an antiserum against nitric oxide synthase. Most myenteric neurons (55%) were nitrinergic. Most (96%) received terminations positive for vasoactive intestinal polypeptide (VIP), calcitonin gene related peptide (CGRP) (80%), and galanin (59%). The neuronal somata of 14% also contained VIP, while 10% had galanin. Of the NADPH-diaphorase containing fibres seen in the muscle layers, many had closely associated VIP and galanin, but only rarely CGRP and substance P. Thus, despite abundant representation of both peptidergic and nitrinergic systems in oesophageal smooth muscle, only VIP and galanin colocalised to any significant extent with the nitrinergic elements. These findings provide morphological support for the role of nitric oxide as the non-adrenergic non-cholinergic inhibitory mediator in the human oesophagus and for its possible interactive role with the peptidergic system. fluorescence were nitrinergic. Most (96%) terminations Dositive for C1 UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET HOSP,DIV GASTROENTEROL,MADISON,WI. BOSTON UNIV,SCH MED,DIV PEDIAT GASTROENTEROL & NUTR,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV GASTROENTEROL,BOSTON,MA 02215. FU NIDDK NIH HHS [DK 31092] NR 33 TC 55 Z9 59 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD DEC PY 1994 VL 35 IS 12 BP 1690 EP 1696 DI 10.1136/gut.35.12.1690 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PW402 UT WOS:A1994PW40200003 PM 7530228 ER PT J AU NIKLASON, LT MARX, MV CHAN, HP AF NIKLASON, LT MARX, MV CHAN, HP TI THE ESTIMATION OF OCCUPATIONAL EFFECTIVE DOSE IN DIAGNOSTIC-RADIOLOGY WITH 2 DOSIMETERS SO HEALTH PHYSICS LA English DT Article DE DOSIMETRY; EXPOSURE, OCCUPATIONAL; RADIATION, IONIZING; RADIATION PROTECTION AB Annual effective dose limits have been proposed by national and international radiation protection committees. Radiation protection agencies must decide upon a method of converting the radiation dose measured from dosimeters to an estimate of effective dose. A proposed method for the estimation of effective dose from the radiation dose to two dosimeters is presented. Correction factors are applied to an over-apron collar dose and an under-apron dose to estimate the effective dose. Correction factors are suggested for two cases, both with and without a thyroid shield. Effective dose may be estimated by the under-apron dose plus 6% of the over-collar dose if a thyroid shield is not worn or plus 2% of the over-collar dose if a thyroid shield is worn. This method provides a reasonable estimate of effective dose that is independent of lead apron thickness and accounts for the use of a thyroid shield. C1 HARVARD UNIV, SCH MED, DEPT RADIOL, BOSTON, MA 02114 USA. UNIV MICHIGAN HOSP, DEPT RADIOL, ANN ARBOR, MI 48109 USA. RP NIKLASON, LT (reprint author), MASSACHUSETTS GEN HOSP, FRUIT ST, BOSTON, MA 02114 USA. NR 17 TC 69 Z9 72 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD DEC PY 1994 VL 67 IS 6 BP 611 EP 615 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA PU922 UT WOS:A1994PU92200004 PM 7960781 ER PT J AU NADOL, JB BURGESS, BJ AF NADOL, JB BURGESS, BJ TI SUPRANUCLEAR EFFERENT SYNAPSES ON OUTER HAIR-CELLS AND DEITERS CELLS IN THE HUMAN ORGAN OF CORTI SO HEARING RESEARCH LA English DT Article DE EFFERENT; SYNAPSE; OUTER HAIR CELL; DEITERS CELL; SYNAPTOPHYSIN ID GUINEA-PIG ORGAN; IMMUNOELECTRON MICROSCOPY; COCHLEAR MECHANICS; LOCALIZATION; INNERVATION AB Synaptophysin immunoreactivity and transmission electron microscopy have demonstrated vesiculated nerve endings synapsing on the supranuclear zone of outer hair cells and also of Deiters' cells in the human organ of Corti. These fibers seem similar to supranuclear fibers, apparently derived from the olivocochlear efferent system, which have been described in the animal. However, these endings were found throughout the cochlea in the human whereas in the animal such fibers were limited to the apical cochlea. Although such fibers have been demonstrated among supporting cells by immunohistochemical techniques, this is the first demonstration by transmission electron microscopy of morphology consistent with a chemical synapse between such fibers and Deiters' cells. Although the role of such fibers is unknown, neurophysiologic evidence suggests that they may modify the micromechanics of the outer hair cell. The function of neural innervation of Deiters' cells is speculative. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02114. RP NADOL, JB (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC00152-14] NR 28 TC 22 Z9 22 U1 0 U2 1 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 PY 1994 VL 81 IS 1-2 BP 49 EP 56 DI 10.1016/0378-5955(94)90152-X PG 8 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA QD778 UT WOS:A1994QD77800006 PM 7737929 ER PT J AU FRIEDBERG, RC AF FRIEDBERG, RC TI TRANSFUSION THERAPY IN THE PATIENT UNDERGOING HEMATOPOIETIC STEM-CELL TRANSPLANTATION SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID BONE-MARROW TRANSPLANTATION; HUMAN FETAL BLOOD; PLATELET TRANSFUSIONS; PROGENITOR CELLS; HLA; ALLOIMMUNIZATION; RECONSTITUTION; RECIPIENTS; BANK AB Optimal transfusion therapy for the patient undergoing stem cell transplantation will vary, depending on a variety of independent factors. These factors include the source of hematopoietic progenitor cells, The relationship between donor and recipient, and the timing of the transfusion relative to the transplant. Stem cell transplantation also changes the traditional views of blood groups: a patient may have more than one of the traditional blood groups at different stages of transplantation. C1 BIRMINGHAM VET AFFAIRS MED CTR,PATHOL & LAB MED SERV,BIRMINGHAM,AL. RP FRIEDBERG, RC (reprint author), UNIV ALABAMA,DEPT PATHOL,DIV LAB MED,WP-230,619 S 19TH ST,BIRMINGHAM,AL 35233, USA. NR 34 TC 4 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 1994 VL 8 IS 6 BP 1105 EP 1116 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA PT766 UT WOS:A1994PT76600005 PM 7860439 ER PT J AU FRIEDBERG, RC AF FRIEDBERG, RC TI ISSUES IN TRANSFUSION THERAPY IN THE PATIENT WITH MALIGNANCY SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID VERSUS-HOST DISEASE; BONE-MARROW TRANSPLANTATION; CYTOMEGALO-VIRUS INFECTION; WHITE CELL-REDUCTION; PROPHYLACTIC PLATELET TRANSFUSION; RED-BLOOD-CELL; RECOMBINANT-HUMAN-ERYTHROPOIETIN; OPEN-HEART SURGERY; ACUTE LUNG INJURY; LEUKOCYTE-DEPLETION AB The role of transfusion therapy has become increasingly more critical as improved therapeutic regimens augment the survival of the patient with malignancy. Curiously, these improvements have led to the realization that transfusion therapy has significant but previously unexpected sequelae. Fortunately, many of these complications are controllable with modified or specifically selected components. C1 BIRMINGHAM VET AFFAIRS MED CTR,PATHOL & LAB MED SERV,BIRMINGHAM,AL. RP FRIEDBERG, RC (reprint author), UNIV ALABAMA,DEPT PATHOL,DIV LAB MED,WP-230,619 S 19TH ST,BIRMINGHAM,AL 35233, USA. NR 212 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 1994 VL 8 IS 6 BP 1223 EP 1253 PG 31 WC Oncology; Hematology SC Oncology; Hematology GA PT766 UT WOS:A1994PT76600012 PM 7860446 ER PT J AU REID, AE LIANG, TJ AF REID, AE LIANG, TJ TI TUMOR-MARKER FOR METASTASIS - SEARCHING FOR AN ABNORMAL NEEDLE IN A HAYSTACK SO HEPATOLOGY LA English DT Editorial Material ID SERUM ALPHA-FETOPROTEIN; HEPATOCELLULAR-CARCINOMA; LIVER-TRANSPLANTATION; COMPLICATING CIRRHOSIS; HEPATIC RESECTION; CLINICAL-FEATURES; PERIPHERAL-BLOOD; CANCER; RECURRENCE; ADENOCARCINOMA C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. NR 32 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 1994 VL 20 IS 6 BP 1631 EP 1634 DI 10.1002/hep.1840200637 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PV634 UT WOS:A1994PV63400036 PM 7527008 ER PT J AU CHAN, JKC BANKS, PM CLEARY, ML DELSOL, G DEWOLFPEETERS, C FALINI, B GATTER, KC GROGAN, TM HARRIS, NL ISAACSON, PG JAFFE, BS KNOWLES, DM MASON, DY MULLERHERMELINK, HK PILERI, SA PIRIS, MA RALFKIAER, E STEIN, H WARNKE, RA AF CHAN, JKC BANKS, PM CLEARY, ML DELSOL, G DEWOLFPEETERS, C FALINI, B GATTER, KC GROGAN, TM HARRIS, NL ISAACSON, PG JAFFE, BS KNOWLES, DM MASON, DY MULLERHERMELINK, HK PILERI, SA PIRIS, MA RALFKIAER, E STEIN, H WARNKE, RA TI A PROPOSAL FOR CLASSIFICATION OF LYMPHOID NEOPLASMS (BY THE INTERNATIONAL LYMPHOMA STUDY-GROUP) SO HISTOPATHOLOGY LA English DT Article DE LYMPHOMA; NON-HODGKINS LYMPHOMA; HODGKINS DISEASE; CLASSIFICATION AB A new classification of lymphoid neoplasms, mostly based on existing terminology, is proposed by the International Lymphoma Study Group. The proposed classification was reached through a consensus of the members, despite their diverse backgrounds, and consists of a listing of currently recognized clinicopathological entities. These tumours are divided into three major categories: B-cell neoplasms, T-cell and postulated natural killer cell neoplasms, and Hodgkin's disease. The characterization of each entity is based on a synthesis of all available information. This concept departs from a purely morphological approach to lymphoma classification, which is considered to be inadequate, because many biologically distinctive lymphoma types can exhibit a broad and overlapping morphological spectrum. Some entities are provisional, pending further data to confirm that their recognition is reproducible. The salient clinicopathological features of each entity are summarized in this review. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. STANFORD UNIV,SCH MED,STANFORD,CA. UNIV TOULOUSE 3,FAC MED PURPAN,TOULOUSE,FRANCE. CATHOLIC UNIV LEUVEN,LOUVAIN,BELGIUM. UNIV PERUGIA,INST HAEMATOL,PERUGIA,ITALY. UNIV OXFORD,JOHN RADCLIFFE HOSP,OXFORD OX3 9DU,ENGLAND. UNIV ARIZONA,SCH MED,TUCSON,AZ. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. UNIV COLL & MIDDLESEX HOSP,LONDON,ENGLAND. NCI,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,NEW YORK HOSP,NEW YORK,NY. UNIV WURZBURG,W-8700 WURZBURG,GERMANY. UNIV BOLOGNA,BOLOGNA,ITALY. HOSP VIRGEN SALUD,TOLEDO,SPAIN. UNIV COPENHAGEN,HERLEV,DENMARK. FREE UNIV BERLIN,KLINIKUM STEGLITZ,W-1000 BERLIN,GERMANY. RP CHAN, JKC (reprint author), QUEEN ELIZABETH HOSP,DEPT PATHOL,WYLIE RD,KOWLOON,HONG KONG. OI Piris, Miguel A/0000-0001-5839-3634 NR 6 TC 88 Z9 89 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD DEC PY 1994 VL 25 IS 6 BP 517 EP 536 DI 10.1111/j.1365-2559.1994.tb01371.x PG 20 WC Cell Biology; Pathology SC Cell Biology; Pathology GA PY476 UT WOS:A1994PY47600002 PM 7698729 ER PT J AU TSUANG, JW LOHR, JB AF TSUANG, JW LOHR, JB TI EFFECTS OF ALCOHOL ON SYMPTOMS IN ALCOHOLIC AND NONALCOHOLIC PATIENTS WITH SCHIZOPHRENIA SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Note ID ABUSE C1 VET AFFAIRS MED CTR,PSYCHIAT SERV,SAN DIEGO,CA 92161. UNIV CALIF SAN DIEGO,SCH MED,SAN DIEGO,CA 92103. RP TSUANG, JW (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. FU NIMH NIH HHS [R29-MH45142-01] NR 10 TC 4 Z9 4 U1 1 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD DEC PY 1994 VL 45 IS 12 BP 1229 EP 1230 PG 2 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA PV435 UT WOS:A1994PV43500013 PM 7868108 ER PT J AU HARMON, C RAMES, L AF HARMON, C RAMES, L TI FOLIE-A-DEUX IN IDENTICAL-TWINS SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Note C1 MED UNIV S CAROLINA,COLL MED,DEPT PSYCHIAT & BEHAV SCI,CHARLESTON,SC 29425. RP HARMON, C (reprint author), MASSACHUSETTS GEN HOSP,WARREN 605,32 FRUIT ST,BOSTON,MA 02114, USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD DEC PY 1994 VL 45 IS 12 BP 1238 EP 1239 PG 2 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA PV435 UT WOS:A1994PV43500017 PM 7868112 ER PT J AU GIBSON, WT WALTER, MA AHMED, AR ALPER, CA COX, DW AF GIBSON, WT WALTER, MA AHMED, AR ALPER, CA COX, DW TI THE IMMUNOGLOBULIN HEAVY-CHAIN AND DISEASE ASSOCIATION - APPLICATION TO PEMPHIGUS-VULGARIS SO HUMAN GENETICS LA English DT Article ID FRAGMENT LENGTH POLYMORPHISMS; VARIABLE REGION GENES; NON-JEWISH PATIENTS; IG VH LOCUS; PHYSICAL MAP; LINKAGE DISEQUILIBRIUM; MULTIPLE-SCLEROSIS; SUBCLASS LOCUS; GAMMA-GENES; RESTRICTION AB Genes involved in the immune response are generally encoded from a complex cluster of gene segments. Studies of the association of diseases with such genes require well-defined genetic markers throughout the selected region. A set of 15 polymorphic loci that span 1500 kb of the immunoglobulin heavy chain (IGH) complex, 8 in the variable (VH) region and 7 in the constant (CH) region, were selected for the study of disease association. We present a protocol for the use of multiple immunoglobulin heavy chain (IGH) polymorphisms for general application in disease association studies. No microsatellite repeat markers are available for this region. To demonstrate the applicability of this approach, we have examined these IGH polymorphisms in families with individuals affected with pemphigus vulgaris (PV), an autoimmune dermatologic disease. Allele frequencies in 12 patients with PV were compared with those found in their spouses, and with those in a white Canadian control population. A significant difference was found between PV patients and both control groups for the presence of the VH gene VH3f-R4, and possibly for the absence of VH3f-R3, suggesting the possibility of susceptibility factors in these regions. Examination of the frequencies of the IGH region Cy-haplotypes of PV patients indicated that, while the patients did not differ significantly from their spouses (chi(2)=1.79), both groups were found to differ significantly from the white Canadian control group (chi(2)=10.10), emphasizing the importance of matching the ethnic background of controls with that of the patient test group in disease association studies. Unexpectedly, two patients had large deletions of genes in the IGH constant region, which could play a role in the development of PV and require further investigation. C1 HOSP SICK CHILDREN,RES INST,TORONTO,ON,CANADA. UNIV TORONTO,DEPT PAEDIAT,TORONTO M5G 1X8,ON,CANADA. UNIV TORONTO,DEPT MOLEC & MED GENET,TORONTO M5G 1X8,ON,CANADA. CTR BLOOD RES,BOSTON,MA. BOSTON UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA. OI Gibson, William/0000-0002-6552-402X FU NEI NIH HHS [EY08379]; NIDCR NIH HHS [DE09978] NR 51 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD DEC PY 1994 VL 94 IS 6 BP 675 EP 683 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA PT732 UT WOS:A1994PT73200014 PM 7989043 ER PT J AU YUNIS, JJ OSSA, H SALAZAR, M DELGADO, MB DEULOFEUT, R DELAHOZ, A BING, DH RAMOS, O YUNIS, EJ YUNIS, EJ AF YUNIS, JJ OSSA, H SALAZAR, M DELGADO, MB DEULOFEUT, R DELAHOZ, A BING, DH RAMOS, O YUNIS, EJ YUNIS, EJ TI MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II ALLELES AND HAPLOTYPES AND BLOOD-GROUPS OF 4 AMERINDIAN TRIBES OF NORTHERN COLOMBIA SO HUMAN IMMUNOLOGY LA English DT Article ID AMERICAN-INDIAN TRIBE; HLA-B ALLELES; LOWER AMAZONIA; ANTIGENS; SYSTEM; DNA; AMPLIFICATION; POPULATIONS; FREQUENCIES; POLYMERASE AB MHC class II alleles and haplotypes were determined from unrelated individuals and families of the Arhuaco (n = 107), Kogi (n = 42), Arsario (n = 18), and Wayu (n = 88) tribes located in the northern part of Colombia. Class II DRB, DQA1, and DQB1 alleles were determined by PCR-SSO and PCR-RFLP based methods. Four haplotypes, [DRB1(*)0407, DRB4(*)0101, DQA1(*)03, DQB1(*)03021; DRB1(*)0403, DRB4(*)0101, DQA1(*)03, DQB1(*)0302]; [DRB1(*)1402/1406, DRB3(*)0101, DQA1(*)0501, DQB1(*)0301]; and [DRB1(*)0802, DQA1(*)0401, DQB1(*)0402], were observed among these four tribes. In addition to these haplotypes, the Wayu Indians showed a frequency of 21.3% for the [DRB1(*)1602, DRB5(*)02, DQA1(*)0501, DQB1(*)030] haplotype, 13.1% for the [DRB1(*)0411, DRB4(*)0101, DQA1(*)03, DQB1(*)0302] haplotype, and rio showed no genetic admixture while the Arhuaco tribe showed admixture with genes of African origin and the Wayu showed admixture with Caucasians as well as genes of African origin. These findings were confirmed by the MHC class II allele and haplotype data obtained, as alleles and haplotypes of Caucasian and African origin were detected in the Wayu and Arhuaco and not in the Kogi or Arsario. These studies will be important in disease association and transplantation studies for Amerindian and Colombian populations and for correlating genetic traits with the anthropologic and linguistic data available in order to better understand the Amerindian populations. C1 CBR LABS INC,CTR BLOOD RES,BOSTON,MA. UNIV NACL COLOMBIA,INST GENET,BOGOTA,COLOMBIA. AMER RED CROSS,BLOOD SERV,DEDHAM,MA. INST COLOMBIANO BIENESTAR FAMILIAR,BOGOTA,COLOMBIA. RP YUNIS, JJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV IMMUNOGENET,44 BINNEY ST,BOSTON,MA 02115, USA. NR 47 TC 69 Z9 70 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD DEC PY 1994 VL 41 IS 4 BP 248 EP 258 DI 10.1016/0198-8859(94)90043-4 PG 11 WC Immunology SC Immunology GA PY188 UT WOS:A1994PY18800002 PM 7883592 ER PT J AU MULLIGAN, LM ENG, C ATTIE, T LYONNET, S MARSH, DJ HYLAND, VJ ROBINSON, BG FRILLING, A VERELLENDUMOULIN, C SAFAR, A VENTER, DJ MUNNICH, A PONDER, BAJ AF MULLIGAN, LM ENG, C ATTIE, T LYONNET, S MARSH, DJ HYLAND, VJ ROBINSON, BG FRILLING, A VERELLENDUMOULIN, C SAFAR, A VENTER, DJ MUNNICH, A PONDER, BAJ TI DIVERSE PHENOTYPES ASSOCIATED WITH EXON-10 MUTATIONS OF THE RET PROTOONCOGENE SO HUMAN MOLECULAR GENETICS LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; TERM FOLLOW-UP; PROTOONCOGENE; TYPE-2A; LOCUS; LINE AB Mutations of the RET proto-oncogene are the underlying cause of some cases of Hirschsprung disease (HSCR) and the inherited cancer syndromes multiple endocrine neoplasia types 2A (MEN 2A) and 28 (MEN 28) and familial medullary thyroid carcinoma (FMTC). In HSCR these mutations are dispersed throughout the gene, while in MEN 2A and FMTC, they are tightly clustered in five cysteine codons of the RET extracellular domain. HSCR and MEN 2 are usually distinct but occasional families have been reported with both diseases. In each of five families with HSCR with or without MEN 2A or FMTC, we have identified a nucleotide substitution in one of the five cysteine codons previously associated with MEN 2A or FMTC, In one family, which had HSCR as its only phenotype, we detected a Cys --> Trp mutation at codon 609 which had not been previously observed, In three families, both HSCR and MEN 2A were associated with a single Cys --> Arg mutation at either codon 618 or 620 of RET. In the fifth family, FMTC and HSCR were present but we could not determine whether HSCR arose from mutation of the RET locus, We suggest that specific mutations in cysteine codons 618 and 620 result in MEN 2A or FMTC, but can also C1 UNIV CAMBRIDGE,DEPT PATHOL,CANC RES CAMPAIGN,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 1QP,ENGLAND. QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. HARVARD UNIV,SCH MED,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HOP NECKER ENFANTS MALAD,INSERM,U393,UNITE RECH HANDICAPS GENET ENFANT,F-75743 PARIS 15,FRANCE. HOP NECKER ENFANTS MALAD,CHIRURG INFANTILE CLIN,SERV GENET MED,F-75743 PARIS,FRANCE. ROYAL N SHORE HOSP,KOLLING INST MED RES,DEPT MOLEC GENET,ST LEONARDS,NSW 2065,AUSTRALIA. UNIV HAMBURG,KRANKENHAUS EPPENDORF,CHIRURG KLIN,W-2000 HAMBURG 20,GERMANY. UNIV CATHOLIQUE LOUVAIN,CTR MED GENET,B-1200 BRUSSELS,BELGIUM. HOP ST VINCENT DE PAUL,SERV CHIRURG PEDIAT,PARIS,FRANCE. ROYAL CHILDRENS HOSP,PARKVILLE,VIC 3052,AUSTRALIA. RP MULLIGAN, LM (reprint author), QUEENS UNIV,DEPT PEDIAT,20 BARRIE ST,KINGSTON,ON K7L 3N6,CANADA. RI Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 NR 26 TC 185 Z9 188 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC PY 1994 VL 3 IS 12 BP 2163 EP 2167 DI 10.1093/hmg/3.12.2163 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PY481 UT WOS:A1994PY48100010 PM 7881414 ER PT J AU BERNAD, A KOPF, M KULBACKI, R WEICH, N KOEHLER, G GUTIERREZRAMOS, JC AF BERNAD, A KOPF, M KULBACKI, R WEICH, N KOEHLER, G GUTIERREZRAMOS, JC TI INTERLEUKIN-6 IS REQUIRED IN-VIVO FOR THE REGULATION OF STEM-CELLS AND COMMITTED PROGENITORS OF THE HEMATOPOIETIC SYSTEM SO IMMUNITY LA English DT Article ID RECOMBINANT HUMAN INTERLEUKIN-6; LEUKEMIA INHIBITORY FACTOR; 5-FLUOROURACIL TREATMENT; MEGAKARYOCYTES INVITRO; CFU-S; MURINE; MARROW; MICE; INVIVO; SPLEEN AB The development of blood cells from hematopoietic stem cells is controlled by multiple cytokines. These growth factors influence survival, cell cycle status, differentiation into lineage-committed progenitors, final maturation into blood cells, and perhaps self-renewal of stem cells. The specific contribution of IL-6 to these processes in vivo was evaluated in mice with a targeted disruption of the IL-6 gene. Decreases in the absolute numbers of CFU-Sd12 and preCFU-S, as well as in the functionality of LTRSC in these mutant mice, suggests a role for IL-6 in the survival, self-renewal, or both of hematopoietic stem cells and early progenitors. In addition, as a result of the IL-6 deficiency, the control between proliferation and differentiation of the progenitor cells of the granulocytic-monocytic, megakaryocytic, and erythroid lineages into mature blood cells is altered, leading to abnormal levels of committed progenitors of these lineages and to a slow recovery from hematopoietic ablation. C1 MAX PLANCK INST IMMUNOBIOL,W-7800 FREIBURG,GERMANY. GENET INST INC,CAMBRIDGE,MA 02140. RP BERNAD, A (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES INC,DEPT GENET,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [1PO1HL 48675-02] NR 45 TC 129 Z9 129 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 1994 VL 1 IS 9 BP 725 EP 731 DI 10.1016/S1074-7613(94)80014-6 PG 7 WC Immunology SC Immunology GA PX648 UT WOS:A1994PX64800002 PM 7895162 ER PT J AU SMITH, DJ TAUBMAN, MA KING, WF EIDA, S POWELL, JR EASTCOTT, J AF SMITH, DJ TAUBMAN, MA KING, WF EIDA, S POWELL, JR EASTCOTT, J TI IMMUNOLOGICAL CHARACTERISTICS OF A SYNTHETIC PEPTIDE ASSOCIATED WITH A CATALYTIC DOMAIN OF MUTANS STREPTOCOCCAL GLUCOSYLTRANSFERASE SO INFECTION AND IMMUNITY LA English DT Article ID GLUCAN-BINDING DOMAIN; SOBRINUS GLUCOSYLTRANSFERASE; SUBSEQUENCE PEPTIDE; NUCLEOTIDE-SEQUENCE; GTFC GENE; IMMUNIZATION; INHIBITION; ENZYME AB The immunogenicity of a multiple antigenic peptide construct consisting of four copies of the synthetic 21-mer peptide DANFDSIRVDAVDNVDADLLQ was measured. The composition of this peptide was derived from a sequence in the N-terminal region of mutans streptococcal glucosyltransferases (GTFs) containing an aspartic acid implicated in catalysis. The peptide (CAT) construct was synthesized as a tetramer on a lysine backbone and subcutaneously injected into Sprague-Dawley rats for polyclonal antibody formation or intraperitoneally injected into BALB/c mice, and then spleen cell fused with Sp2/0Ag14 murine myeloma cells for monoclonal antibody formation. The resulting rat antisera and mouse monoclonal antibodies reacted with CAT and with native GTF isozymes from Streptococcus sobrinus and Streptococcus mutans (in enzyme-linked immunosorbent assay and Western blot [immunoblot] analyses). Functional inhibition of the water-insoluble glucan synthetic activity of S. sobrinus GTF-I was demonstrated with an immunoglobulin M anti-CAT monoclonal antibody (>80% inhibited) and with rat sera (approximately 17% inhibited). The monoclonal antibody preparation also modestly inhibited the water-soluble glucan synthetic activity of an S. mutans GTF mixture. These results suggest that the CAT peptide contains B-cell epitopes that are similar to those of intact mutans streptococcal GTFs and has the potential to elicit antibody that can inhibit GTF function. Thus,sequences within this peptide construct may have value for inclusion in a synthetic dental caries vaccine. C1 UNILEVER DENT RES,BEDFORD MK44 1LQ,ENGLAND. RP SMITH, DJ (reprint author), FORSYTH DENT CTR,DEPT IMMUNOL,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-04733, DE-06153] NR 30 TC 36 Z9 37 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1994 VL 62 IS 12 BP 5470 EP 5476 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PT329 UT WOS:A1994PT32900036 PM 7960128 ER PT J AU RIZZO, JA AF RIZZO, JA TI PHYSICIAN INCOME TARGETS - NEW EVIDENCE ON AN OLD CONTROVERSY SO INQUIRY-THE JOURNAL OF HEALTH CARE ORGANIZATION PROVISION AND FINANCING LA English DT Article ID SERVICES AB This study uses a unique set of data to identify the factors that affect physician income targets among a nationally representative sample of young (under age 40) physicians in 1987. The study reveals that income targets respond directly to actual income, but that this relationship is rather inelastic. Among self-employed physicians, for example, a 10% decline in actual income would reduce the target by only 3%. Thus, our study provides the first direct evidence to quantify how a decline in income will increase the divergence between actual and target income. Moreover, in quantifying this divergence, our results provide an upper bound on the dollar value of any demand inducement that may ensue. The results suggest that targets are set, at least in part, to compensate physicians for pecuniary and nonpecuniary costs associated with medical practice. Discrimination, dissatisfaction, financial risks, and training costs all appear to raise income targets. Physicians may desire higher incomes to compensate them for discrimination or other difficulties they have encountered in practicing medicine. C1 MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP RIZZO, JA (reprint author), YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,60 COLL ST,NEW HAVEN,CT 06510, USA. NR 19 TC 3 Z9 3 U1 0 U2 1 PU BLUE CROSS BLUE SHIELD ASSN PI CHICAGO PA 676 N ST CLAIR ST, CHICAGO, IL 60611 SN 0046-9580 J9 INQUIRY-J HEALTH CAR JI Inquiry-J. Health Care Organ. Provis. Financ. PD WIN PY 1994 VL 31 IS 4 BP 394 EP 404 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA QE337 UT WOS:A1994QE33700006 PM 7821993 ER PT J AU PERROTT, DH UMEDA, H KABAN, LB AF PERROTT, DH UMEDA, H KABAN, LB TI COSTOCHONDRAL GRAFT CONSTRUCTION RECONSTRUCTION OF THE RAMUS CONDYLE UNIT - LONG-TERM FOLLOW-UP SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article DE COSTOCHONDRAL GRAFT; TEMPOROMANDIBULAR JOINT RECONSTRUCTION; TEMPOROMANDIBULAR JOINT, CONDYLE REPLACEMENT ID TEMPOROMANDIBULAR-JOINT ANKYLOSIS; UNPREDICTABLE GROWTH-PATTERN; HEMIFACIAL MICROSOMIA AB This is a retrospective study of 26 patients (seven growing and 19 nongrowing) who received costochondral grafts (n=33) for construction or reconstruction of the ramus/condyle unit (RCU). Facial appearance, jaw motion, occlusion, contour, and linear growth changes were documented preoperatively, immediately postoperatively, and long-term (>1 year). Average follow-up was 48.6 months for growing and 46.4 months for nongrowing patients. Facial asymmetry and malocclusion were successfully corrected in all patients except for those with hemifacial microsomia, where partial correction was most common. For the growing patients, mean change in RCU length (n=8) during the observation period was +3.1 mm on the constructed/reconstructed side and +3.2 mm on the unoperated side. For nongrowing patients, mean change in the RCU length (n=25) was -5.7 mm for the reconstructed side. Three patients developed lateral contour overgrowth of the articulating surface; no patients developed clinically significant linear overgrowth with malocclusion. The results of this study indicate that a costochondral graft may be used successfully to construct/reconstruct the RCU and that linear overgrowth of the graft does not appear to be a clinical problem with the method described in this paper. C1 HARVARD UNIV,SCH DENT MED,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA. RP PERROTT, DH (reprint author), UNIV CALIF SAN FRANCISCO,DEPT ORAL & MAXILLOFACIAL SURG,521 PARNASSUS AVE,ROOM C-5222,BOX 0440,SAN FRANCISCO,CA 94143, USA. NR 27 TC 93 Z9 98 U1 1 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD DEC PY 1994 VL 23 IS 6 BP 321 EP 328 DI 10.1016/S0901-5027(05)80046-3 PN 1 PG 8 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA QC185 UT WOS:A1994QC18500001 PM 7699266 ER PT J AU LIPFORD, JR WORLAND, ST FARNET, CM AF LIPFORD, JR WORLAND, ST FARNET, CM TI NUCLEOTIDE-BINDING BY THE HIV-1 INTEGRASE PROTEIN IN-VITRO SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; DNA BINDING; INTEGRASE; ATP; NUCLEOTIDE ANALOGS ID VIRAL-DNA; RETROVIRAL DNA; INVITRO; RECOMBINATION; DOMAINS; TYPE-1; SEQUENCES; COMPLEX; VIRUSES; SITES AB Recombinant human immunodeficiency virus type 1 (HIV-1) integrase was shown to bind ATP and other nucleoside triphosphates and nucleotide analogs in vitro. Cross-linking of ATP and the photoaffinity analog 8-azido-ATP to integrase occurred in a UV dose-dependent manner. Covalent binding of ATP to integrase was also achieved without UV irradiation when the nucleotide was oxidized to the 2',3'-dialdehyde derivative (oxidized ATP) prior to incubation with the protein, indicating the presence of a reactive lysine residue in the nucleotide binding region of the protein. A number of experimental observations indicate that nucleotides and DNA substrates bind at the same or overlapping site(s) on the integrase protein. For example, the binding of nucleotides or nucleotide analogs to integrase was blocked by prior incubation with DNA substrates, and the covalent cross-linking of 8-azido-ATP to integrase inhibited the DNA binding and oligonucleotide cleavage activities of the protein. Oxidized ATP inhibited the oligonucleotide cleavage activity of integrase at concentrations that had no effect on DNA binding, suggesting that oxidized nucleotides may specifically target the catalytic center of the enzyme. These studies indicate that nucleotide analogs may serve as probes for the DNA binding and catalytic sites of the enzyme and may serve as models for the design of active site inhibitors of retroviral integrase. C1 HARVARD UNIV, SCH MED,DANA FARBER CANC INST,DEPT PATHOL, DIV HUMAN RETROVIROL, BOSTON, MA 02115 USA. AGOURON PHARMACEUT INC, SAN DIEGO, CA USA. OI Farnet, Chris/0000-0003-4927-198X FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [P30 AI28691, U01 AI24845] NR 22 TC 21 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD DEC PY 1994 VL 7 IS 12 BP 1215 EP 1223 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PV290 UT WOS:A1994PV29000001 PM 7965631 ER PT J AU PARK, IW MYRICK, K SODROSKI, J AF PARK, IW MYRICK, K SODROSKI, J TI EFFECTS OF VIF MUTATIONS ON CELL-FREE INFECTIVITY AND REPLICATION OF SIMIAN IMMUNODEFICIENCY VIRUS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE SIMIAN IMMUNODEFICIENCY VIRUS; VIF PROTEIN; MUTATIONS; CELL-FREE INFECTIVITY; REPLICATION ID SOR GENE-PRODUCT; NUCLEOTIDE-SEQUENCE; GENOME ORGANIZATION; HTLV-III/LAV; TYPE-1 VIF; DNA-SYNTHESIS; MUTANTS; PROTEIN; RETROVIRUSES; EXPRESSION AB To investigate the function of the Vif protein of the simian immunodeficiency virus (SIV), mutations were introduced into the SIV(mac)239 vif gene without affecting the reading frames of other overlapping genes. The phenotypes of these mutant viruses were examined with respect to viral replication and the expression and processing of viral proteins. Transfection of vif-mutant proviral DNA into established T cell lines resulted in a significant delay in the onset of virus replication compared to that seen with the wild-type provirus. The efficiency of replication of the vif-mutant virus was dependent on cell type. MT-4 cells were permissive for replication of the vif mutant, while replication in CEMx174 cells was severely restricted. Little or no virus replication was observed following cell-free infection of the CEMx174 cell line and macaque peripheral blood mononuclear cells (PBMC). These results indicate that the requirement for vif during the replication of SIV(mac)239 is dependent on eel type, as has been observed for HIV-1. Following cell-free infection, mutant viruses containing combined deletions in vif and the other regulatory genes (vpx, vpr, and nef) displayed replication kinetics similar to that of viruses containing the deletion of vif alone. Viral protein expression and processing in MT-4 cells of vif-deleted viruses were indistinguishable from those of the wildtype virus. The effects of two different point mutations in vif were examined. One point mutant in vif reverted to the genetic sequence of the wild-type virus within 2 weeks. A second point mutant that did not show genetic reversion displayed a similar kinetics of virus replication to that of the vif deletion mutant. These data show that impaired replication of vif mutant viruses results from mutation of the vif gene rather than the deletion of cis-acting elements, and also indicate that a strong selection exists against vif-defective viruses. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA. FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [P30 AI28691, R01 AI29333] NR 31 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD DEC PY 1994 VL 7 IS 12 BP 1228 EP 1236 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PV290 UT WOS:A1994PV29000003 PM 7965633 ER PT J AU GUDMUNDSSON, S VOGELMAN, B CRAIG, WA AF GUDMUNDSSON, S VOGELMAN, B CRAIG, WA TI DECREASED BACTERICIDAL ACTIVITY DURING THE PERIOD OF THE POSTANTIBIOTIC EFFECT SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID BENZYLPENICILLIN; THERAPY; INVITRO; INVIVO AB Standard and clinical strains of Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae were subjected to continuous exposure to beta-lactams and aminoglycosides during the postantibiotic effect phase induced by rifampicin or erythromycin (for S. aureus). A significant inhibition of bactericidal activity by these agents during the PAE period was observed. The degree of inhibition was dependent both on the class of antimicrobial agent (beta-lactams > aminoglycosides) and the microorganism (Gram-negative bacilli > S. aureus). C1 UNIV ICELAND, SCH MED, REYKJAVIK, ICELAND. WILLIAM S MIDDLETON MEM VET ADM MED CTR, MED SERV, MADISON, WI USA. UNIV WISCONSIN, DEPT MED, MADISON, WI USA. RP GUDMUNDSSON, S (reprint author), LANDSPITALINN, DEPT MED, REYKJAVIK, ICELAND. NR 19 TC 16 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD DEC PY 1994 VL 34 IS 6 BP 921 EP 930 DI 10.1093/jac/34.6.921 PG 10 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA QE597 UT WOS:A1994QE59700007 PM 7730235 ER PT J AU ODONNELL, RJ SPRINGFIELD, DS MOTWANI, HK READY, JE GEBHARDT, MC MANKIN, HJ AF ODONNELL, RJ SPRINGFIELD, DS MOTWANI, HK READY, JE GEBHARDT, MC MANKIN, HJ TI RECURRENCE OF GIANT-CELL TUMORS OF THE LONG BONES AFTER CURETTAGE AND PACKING WITH CEMENT SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID ACRYLIC CEMENTATION AB The nine-year experience with sixty patients who had had a giant-cell tumor of a long bone was reviewed to determine the rate of recurrence after treatment with curettage and packing with polymethylmethacrylate cement, The demographic characteristics, including the age and sex of the patient and the site of the tumor, were similar to those that have been reported for other large series. An average of four years (range, two to ten years) after the operation, the over-all rate of initial local recurrence was 25 per cent (fifteen of sixty patients). Patients who had had a tumor of the distal aspect of the radius had a higher rate of recurrence (five of ten) than those who had had a tumor of the proximal aspect of the tibia (seven [28 per cent] of twenty-five) or of the distal part of the femur (three [13 per cent] of twenty-three). Higher rates of recurrence were also noted for patients who had had a pathological fracture (three of six), those who had had a Stage-III tumor according to the classification of Campanacci et al, (six of sixteen), and those who had not had adjuvant treatment with either a high-speed burr or phenol (eight of nineteen). Patients who had had an initial recurrence after packing with cement had a low rate of secondary recurrence when the initial recurrence had been treated with a wide resection or a second intralesional procedure (zero of ten and one of five patients, respectively), after an average of three years (range, ten months to eight years). No patient had a multicentric tumor or metastasis. This study demonstrates that curettage and packing with cement compares favorably with traditional methods of intralesional treatment of giant-cell tumors of the long bones in terms of the rate of initial local recurrence. Furthermore, the effectiveness of treatment of a recurrence with either an intralesional or a wide excisional procedure does not appear to be diminished by initial curettage and cementing. RP ODONNELL, RJ (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPAED SERV,ORTHOPAED ONCOL UNIT,GRAY 6,FRUIT ST,BOSTON,MA 02114, USA. NR 43 TC 184 Z9 198 U1 1 U2 4 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 1994 VL 76A IS 12 BP 1827 EP 1833 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PY829 UT WOS:A1994PY82900009 PM 7989388 ER PT J AU FINKELSTEIN, JS BUTLER, JP CLEARY, RL NEER, RM AF FINKELSTEIN, JS BUTLER, JP CLEARY, RL NEER, RM TI COMPARISON OF 4 METHODS FOR CROSS-CALIBRATING DUAL-ENERGY X-RAY ABSORPTIOMETERS TO ELIMINATE SYSTEMATIC-ERRORS WHEN UPGRADING EQUIPMENT SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID LUMBAR SPINE; RADIOGRAPHIC ABSORPTIOMETRY; PHOTON-ABSORPTIOMETRY; BONE DENSITOMETER; PRECISION; OSTEOPOROSIS; ACCURACY; DENSITY AB Dual-energy x-ray absorptiometry (DXA) is a widely employed technique for making noninvasive measurements of bone mineral density (BMD). Advances in DXA technology have resulted in the development of new densitometers that offer increased scan speed, improved spatial resolution, and the ability to make measurements at additional skeletal sites. However, changing from a first to a second-generation DXA system generates two additional potential sources of error. First, if the densitometers produce results that are substantially different, diagnostic errors occur if the results from both instruments are compared to the same normative database. Second, even if the densitometers produce results that are nearly identical, small systematic errors may influence interpretation of serial bone density measurements in individual patients. To assess the impact of changing from a first- to a second-generation DXA scanner, we made measurements using the standard ''pencil beam'' mode on 133 consecutive patients using both a Hologic QDR-1000 and a QDR-2000 densitometer when the latter instrument was calibrated according to the manufacturer's routine procedure using a single anthropomorphic spine phantom, We then recalculated the results for the QDR-2000 densitometer using cross-calibration factors based on (1) a regression line generated by scanning three anthropomorphic spine phantoms whose BMD ranged from osteoporotic to high normal on each instrument, (2) an adult human lumbar spine embedded in tissue-equivalent plastic, or (3) a regression line derived from scans of the first 83 patients that was then applied to the last 50 patients. Next, we made measurements in 200 consecutive patients with the QDR-2000 densitometer using both the pencil beam mode and the ''fan beam'' mode when the instrument was calibrated according to the manufacturer's routine procedure. The results for the ''fan beam'' measurements of the last 100 patients were then recalculated using cross-calibration factors based on a regression line derived from scans of the first 100 patients. Measurements of bone area, bone mineral content (BMC), and BMD on the QDR-1000 and QDR-2000 densitometers were highly correlated (r greater than or equal to 0.997). Still, there were small, significant systematic differences in bone area and BMD, so that BMD values on the QDR-1000 were 0.007 g/cm(2) higher (p < 0.005). Recalculation of the QDR-2000 pencil beam values using cross-calibration factors generated by scanning the three anthropomorphic spine phantoms decreased, but did not eliminate, these systematic differences. Recalculation of the QDR-2000 pencil beam values using calibration factors based on the adult human lumbar spine phantom failed to eliminate the differences in bone area and BMD and introduced a new systematic difference in BMC. In contrast, recalculation of the QDR-2000 pencil beam values using cross-calibration factors generated by scanning a series of patients eliminated these systematic differences. Similar results were obtained when comparing the results of scans performed with the QDR-2000 densitometer in the pencil and fan beam modes. The residual variability around the regression line relating the QDR-2000 pencil and fan beam measurements was twice as great as that relating the QDR-1000 and QDR-2000 pencil beam measurements (p < 0.001). These results demonstrate that routine calibration methods based on phantoms are adequate for diagnosing osteopenia when changing from a first- to a second-generation DXA system. However, such calibration methods may introduce systematic errors that have important effects on the interpretation of serial BMD measurements. These errors can be eliminated by calibrating the densitometers based on measurements of a large number of heterogeneous patients from a routine referral population. RP FINKELSTEIN, JS (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BULFINCH 3,BOSTON,MA 02114, USA. NR 19 TC 21 Z9 21 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 1994 VL 9 IS 12 BP 1945 EP 1952 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PT814 UT WOS:A1994PT81400013 PM 7872060 ER PT J AU ALON, R ROSSITER, H WANG, XH SPRINGER, TA KUPPER, TS AF ALON, R ROSSITER, H WANG, XH SPRINGER, TA KUPPER, TS TI DISTINCT CELL-SURFACE LIGANDS MEDIATE T-LYMPHOCYTE ATTACHMENT AND ROLLING ON P-SELECTIN AND E-SELECTIN UNDER PHYSIOLOGICAL FLOW SO JOURNAL OF CELL BIOLOGY LA English DT Article ID LEUKOCYTE ADHESION MOLECULE-1; SIALYL-LEWIS-X; MYELOID CELLS; GLYCOPROTEIN LIGAND; PASTEURELLA-HAEMOLYTICA; O-SIALOGLYCOPROTEINS; ENDOTHELIAL LIGAND; HOMING RECEPTOR; EXPRESSION; BINDING AB Memory T lymphocytes extravasate at sites of inflammation, but the mechanisms employed by these cells to initiate contact and tethering with endothelium are incompletely understood. An important part of leukocyte extravasation is the initiation of rolling adhesions on endothelial selectins; such events have been studied in monocytes and neutrophils but not lymphocytes. In this study, the potential of T lymphocytes to adhere and roll on endothelial selectins in vitro was investigated. We demonstrate that T cells can form tethers and rolling adhesions on P selectin and E selectin under physiologic flow conditions. Tethering and rolling on P selectin was independent of cell-surface cutaneous lymphocyte antigen (CLA) expression, which correlated strictly with the capacity of T cells to form rolling adhesions under flow on E selectin. T cell tethering to P selectin was abolished by selective removal of cell surface sialomucins by a 19 haemolytica O-glycoprotease, while cutaneous lymphocyte antigen expression was unaffected. A sialomucin molecule identical or closely related to P selectin glycoprotein ligand-1 (PSGL-1), the major P selectin ligand on neutrophils and HL-60 cells, appears to be a major T cell ligand for P selectin. P selectin glycoprotein ligand-l does not appear to support T cell rolling on E selectin. In turn, E selectin ligands do not appear to be associated with sialomucins. These data demonstrate the presence of structurally distinct ligands for P or E selectins on T cells, provide evidence that both ligands can be coexpressed on a single T cell, and mediate tethering and rolling on the respective selectins in a mutually exclusive fashion. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,HARVARD SKIN DIS RES CTR,DIV DERMATOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,DEPT PATHOL,BOSTON,MA 02115. UNIV CALIF LOS ANGELES,DIV DERMATOL,LOS ANGELES,CA 90024. FU NIAID NIH HHS [AI25082]; NIAMS NIH HHS [AR42124, AR40124] NR 52 TC 133 Z9 136 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC PY 1994 VL 127 IS 5 BP 1485 EP 1495 DI 10.1083/jcb.127.5.1485 PG 11 WC Cell Biology SC Cell Biology GA PU781 UT WOS:A1994PU78100025 PM 7525609 ER PT J AU RIEU, P UEDA, T HARUTA, I SHARMA, CP ARNAOUT, MA AF RIEU, P UEDA, T HARUTA, I SHARMA, CP ARNAOUT, MA TI THE A-DOMAIN OF BETA-2 INTEGRIN CR3 (CD11B/CD18) IS A RECEPTOR FOR THE HOOKWORM-DERIVED NEUTROPHIL ADHESION INHIBITOR NIF SO JOURNAL OF CELL BIOLOGY LA English DT Article ID COMPLEMENT RECEPTOR; LEUKOCYTE ADHESION; MONOCLONAL-ANTIBODIES; CELL-SURFACE; SUBCELLULAR-LOCALIZATION; GLYCOPROTEIN; MAC-1; PROTEINS; SUBUNIT; LIGAND AB The A-domain is a similar to 200-amino acid peptide present within structurally diverse proadhesive proteins including seven integrins. A recombinant form of the A-domain of beta 2 integrins CR3 and LFA-1 has been recently shown to bind divalent cations and to contain binding sites for protein ligands that play essential roles in leukocyte trafficking to inflammatory sites, phagocytosis and target cell killing. In this report we demonstrate that the neutrophil adhesion inhibitor, NIF produced by the hookworm Ancylostoma caninum is a selective CD11b A-domain binding protein. NIF bound directly, specifically and with high affinity (K-d of similar to 1 nM) to recombinant CD11b A-domain (r11bA). The binding reaction was characterized by rapid association and very slow dissociation, and was blocked by an anti-r11bA monoclonal antibody. No binding was observed to rCD11aA. The NIF-r11bA interaction required divalent cations, and was absent when the mutant r11bA D140GS/AGA (that lacks divalent cation binding capacity) was used. The NIF binding site in r11bA was mapped to four short peptides, one of which being an iC3b binding site. The interaction of NIF with CR3 in intact cells followed similar binding kinetics to those with r11bA, and occurred with similar affinity in resting and activated human neutrophils, suggesting that the NIF epitope is activation independent. Binding of NIF to CR3 blocked its ability to bind to its ligands iC3b, fibrinogen, and CD54, and inhibited the ability of human neutrophils to ingest serum opsonized particles. NIF thus represents the first example of a disintegrin that targets the integrin A-domain, and is likely to be used by the hookworm to evade the hosts inflammatory response. The unique structure of NIF, which lacks a disintegrin motif, emphasizes basic structural differences in antagonists targeting A(+) and A(-) integrins, that should be valuable in drug design efforts aimed at generating novel therapeutics. Identification of the region in NIF mediating A-domain binding should also be useful in this regard, and may, as in the case of disintegrins, unravel a new structural motif with cellular counterparts mediating important physiologic functions. C1 MASSACHUSETTS GEN HOSP,DEPT MED,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIAID NIH HHS [AI-28465]; NIDDK NIH HHS [DK-48549] NR 61 TC 89 Z9 89 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC PY 1994 VL 127 IS 6 BP 2081 EP 2091 DI 10.1083/jcb.127.6.2081 PN 2 PG 11 WC Cell Biology SC Cell Biology GA PZ272 UT WOS:A1994PZ27200028 PM 7528750 ER PT J AU KUNZELMANN, K SLOTKI, IN KLEIN, P KOSLOWSKY, T AUSIELLO, DA GREGER, R CABANTCHIK, ZI AF KUNZELMANN, K SLOTKI, IN KLEIN, P KOSLOWSKY, T AUSIELLO, DA GREGER, R CABANTCHIK, ZI TI EFFECTS OF P-GLYCOPROTEIN EXPRESSION ON CYCLIC-AMP AND VOLUME-ACTIVATED ION FLUXES AND CONDUCTANCES IN HT-29 COLON ADENOCARCINOMA CELLS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID CYSTIC-FIBROSIS GENE; CFTR CHLORIDE CHANNEL; MULTIDRUG-RESISTANCE; SECRETORY EPITHELIUM; DOWN-REGULATION; HT(29) CELLS; PROTEIN; LOCALIZATION; VERAPAMIL; TRANSPORT AB The tissue distribution of P-glycoprotein (Pgp) and the structurally related cystic fibrosis transmembrane conductance regulator (CFTR) is apparently mutually exclusive, particularly in epithelia; where one protein is expressed the other is not. To study the possible function(s) of Pgp and its potential effects on CFTR expression in epithelia, HT-29 colon adenocarcinoma cells, which constitutively ex press CFTR, were pharmacologically adapted to express the classical multidrug resistance (MDR) phenotype (Pgp(+)). Concomitant-with the appearance of Pgp and MDR phenotype (drug resistance, reduced drug accumulation and increased drug efflux), CFTR levels and cAMP-stimulated Cl conductances were markedly decreased compared to wild-type HT-29 (Pgp(-)) cells (as shown using the whole cell patch clamp technique). Removal of drug pressure led to the gradual decrease in Pgp levels and MDR phenotype, as evidenced by increased rhodamine 123 accumulation (Pgp-Rev). Concomitantly, CFTR levels and cAMP-stimulated Cl- conductances increased. The cell responses of Pgp/Rev cells were heterogeneous with respect to both Pgp and CFTR functions. We also stud led the possible contribution of Pgp to hypotonically activated (HCS) ion conductances. K+ and Cl- effluxes from Pgp(-) cells were markedly increased by HCS. This increase was twice as high as that induced by the cation ionophore gramicidin; it was blocked by the Cl(-)channel blocker DIDS (4,4'-disothiocyano-2,2'-disulfonic stilbene) and required extracellular Ca2+. In Pgp(+) cells, the HCS-induced fluxes were not significantly different from those of Pgp(-) cells. Verapamil (10 mu M), wh ich caused 80% reversal of Pgp-associated drug extrusion, failed to inhibit the HCS-evoked Cl- efflux of Pgp(+) cells. Similarly, HCS increased Cl- conductance to the same extent in Pgp(-), Pgp(+) and Pgp-Rev cells. Verapamil (100 mu M), but not 1,9-dideoxyforskolin (50 and 100 mu M), partially inhibited the HCS-evoked whole cell current (WCC) in all three lines. Since the inhibition by verapamil was not detected in the presence of the K+ channel blocker Ba2+ (3 mM), it is suggested that verapamil affects K+ and not Cl- conductance. We conclude that hypotonically activated Cl- and K+ conductances are similar in HT-29 cells irrespective of Pgp expression. Expression of high levels of Pgp in HT-29 cells confers no physiologically significant capacity for cell volume regulation. (C) 1994 Wiley-Liss, Inc. C1 HEBREW UNIV JERUSALEM,INST LIFE SCI,DEPT BIOL CHEM,IL-91904 JERUSALEM,ISRAEL. UNIV FREIBURG,INST PHYSIOL,D-79104 FREIBURG,GERMANY. SHAARE ZEDEK MED CTR,RENAL UNIT,IL-91031 JERUSALEM,ISRAEL. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,RENAL SECT,BOSTON,MA 02113. OI Kunzelmann, Karl/0000-0002-4583-7037 NR 56 TC 45 Z9 46 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1994 VL 161 IS 3 BP 393 EP 406 DI 10.1002/jcp.1041610302 PG 14 WC Cell Biology; Physiology SC Cell Biology; Physiology GA QF855 UT WOS:A1994QF85500001 PM 7962123 ER PT J AU COX, DJ KOVATCHEV, BP JULIAN, DM GONDERFREDERICK, LA POLONSKY, WH SCHLUNDT, DG CLARKE, WL AF COX, DJ KOVATCHEV, BP JULIAN, DM GONDERFREDERICK, LA POLONSKY, WH SCHLUNDT, DG CLARKE, WL TI FREQUENCY OF SEVERE HYPOGLYCEMIA IN INSULIN-DEPENDENT DIABETES-MELLITUS CAN BE PREDICTED FROM SELF-MONITORING BLOOD-GLUCOSE DATA SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IMPAIRMENT; EPISODES AB Severe hypoglycemia is associated with insulin-dependent diabetes mellitus and may occur mole frequently as metabolic control approaches normal. The goal of this study was to determine whether the frequency of severe hypoglycemia could be predicted by the following predictor variables: 1) frequency and degree of low blood glucose (BG) readings, 2) degree of BG variability during routine self-monitoring blood glucose (SMBG) readings, and 3) level of glycemic control measured by glycosylated hemoglobin-A(1) (HbA(1)). Seventy-eight insulin-dependent diabetes mellitus subjects from 3 different sites had their glycosylated HbA(1) assayed and then performed 50 SMBG recordings during the next 2-3 weeks. Over the following 6 months, subjects recorded their severe hypoglycemic episodes (stupor or unconsciousness). There was no difference in the number of severe hypoglycemic episodes between subjects in good us. poor metabolic control. A higher frequency of severe hypoglycemia during the subsequent 6 months was predicted by frequent and extreme low SMBG readings and variability in day to day SMBG readings. Regression analysis indicated that 44% of the variance in severe hypoglycemic episodes could be accounted for by initial measures of BG variance and the extent of low BG readings. Patients who recorded variable and frequent very low BG readings during routine SMBG were at higher risk for subsequent severe hypoglycemia. Individuals who had lower glycosylated Hb levels were not at higher risk of severe hypoglycemic episodes. C1 JOSLIN DIABET CTR, BOSTON, MA 02215 USA. VANDERBILT UNIV, NASHVILLE, TN 37240 USA. RP COX, DJ (reprint author), UNIV VIRGINIA, HLTH SCI CTR, BOX 223, CHARLOTTESVILLE, VA 22908 USA. FU NCRR NIH HHS [M01-RR-00847]; NIDDK NIH HHS [R01-DK-28288] NR 17 TC 69 Z9 70 U1 1 U2 3 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 1994 VL 79 IS 6 BP 1659 EP 1662 DI 10.1210/jc.79.6.1659 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PX775 UT WOS:A1994PX77500024 PM 7989471 ER PT J AU GOLDRING, MB BIRKHEAD, JR SUEN, LF YAMIN, R MIZUNO, S GLOWACKI, J ARBISER, JL APPERLEY, JF AF GOLDRING, MB BIRKHEAD, JR SUEN, LF YAMIN, R MIZUNO, S GLOWACKI, J ARBISER, JL APPERLEY, JF TI INTERLEUKIN-1-BETA-MODULATED GENE-EXPRESSION IN IMMORTALIZED HUMAN CHONDROCYTES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE SIMIAN VIRUS 40 LARGE T ANTIGEN; COLLAGEN; PROTEOGLYCAN; CARTILAGE; CYTOKINE ID SERUM-FREE MEDIUM; MULTIPLICATION-STIMULATING ACTIVITY; RABBIT ARTICULAR CHONDROCYTES; PROCOLLAGEN MESSENGER-RNA; NECROSIS FACTOR-ALPHA; GROWTH FACTOR-I; CELL-LINE; MOLECULAR-CLONING; SIMIAN VIRUS-40; X COLLAGEN AB Immortalized human chondrocytes were established by transfection of primary cultures of juvenile costal chondrocytes with vectors encoding simian virus 40 large T antigen and selection in suspension culture over agarose. Stable cell lines were generated that exhibited chondrocyte morphology, continuous proliferative capacity (> 80 passages) in monolayer culture in serum-containing medium, and expression of mRNAs encoding chondrocyte-specific collagens II, IX, and XI and proteoglycans in an insulin-containing serum substitute. They did not express type X collagen or versican mRNA. These cells synthesized and secreted extracellular matrix molecules that were reactive with monoclonal antibodies against type II collagen, large proteoglycan (PG-H, aggrecan), and chondroitin-4- and chondroitin-6-sulfate. Interleukin-1 beta (IL-1 beta) decreased the levels of type LI collagen mRNA and increased the levels of mRNAs for collagenase, stromelysin, and immediate early genes (egr-1 c-fos, c-jun, and jun-B). These cell lines also expressed reporter gene constructs containing regulatory sequences (-577/+3,428 bp) of the type II collagen gene (COL2A1) in transient transfection experiments, and IL-1 beta suppressed this expression by 50-80%. These results show that immortalized human chondrocytes displaying cartilage-specific modulation by IL-1 beta can be used as a model for studying normal and pathological repair mechanisms. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. BRIGHAM & WOMENS HOSP,DEPT ORTHOPED SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HAMMERSMITH HOSP,LONDON W12 0NN,ENGLAND. RP GOLDRING, MB (reprint author), MASSACHUSETTS GEN HOSP,ARTHRITIS RES LAB,MED SERV,149 13TH ST,BOSTON,MA 02129, USA. FU NIAMS NIH HHS [AR-03564, AR-07258, AR-34390]; Wellcome Trust NR 68 TC 300 Z9 304 U1 0 U2 4 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 PY 1994 VL 94 IS 6 BP 2307 EP 2316 DI 10.1172/JCI117595 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PV810 UT WOS:A1994PV81000021 PM 7989586 ER PT J AU STONE, RM NEUBERG, D SOIFFER, R TAKVORIAN, T WHELAN, M RABINOWE, SN ASTER, JC LEAVITT, P MAUCH, P FREEDMAN, AS NADLER, LM AF STONE, RM NEUBERG, D SOIFFER, R TAKVORIAN, T WHELAN, M RABINOWE, SN ASTER, JC LEAVITT, P MAUCH, P FREEDMAN, AS NADLER, LM TI MYELODYSPLASTIC SYNDROME AS A LATE COMPLICATION FOLLOWING AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR NON-HODGKINS-LYMPHOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INTERMEDIATE-GRADE; 1ST REMISSION; LEUKEMIA; THERAPY; CHEMOTHERAPY; CARCINOMA; SECONDARY; DISEASE; RISK AB Purpose: To determine the incidence, natural history, and risk factors associated with myelodysplastic syndrome (MDS) occurring as a late complication following autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma. Methods: We retrospectively reviewed the charts of all 262 patients who underwent autologous bone marrow transplantation for non-Hodgkin's lymphoma at the Dana-Farber Cancer Institute from 1982 through 1991. Although patients received a variety of treatments before they were eligible for transplant, identical myeloablative therapy (cyclophosphamide 60 mg/kg/d for 2 days plus total-body irradiation twice daily for 3 days) was administered in each case. By collecting data on pretransplant and early posttransplant variables, we attempted to identify risk factors for the development of MDS. Results: The crude overall incidence of posttransplant MDS or acute myeloid leukemia (AML) was 7.6%. The actuarial risk at 6 years was 18% +/- 9%. The median time of onset was 31 months (range, 10 to 101) after transplant or 69 months (range, 27 to 141) after initial treatment for lymphoma. Pretreatment variables predictive for the development of MDS (univariate analysis) included prolonged interval between initial treatment and the transplant procedure (P =.003), increased duration of exposure to chemotherapy (P =.019) or to alkylating agents (P =.045), and use of radiation therapy (P =.032) or pelvic radiation (P =.003) before transplant. Conclusion: MDS is a potential complication of autologous bone marrow transplantation for non-Hodgkin's lymphoma; bone marrow stem-cell damage sustained before the transplant may be the most important risk factor. (C) 1994 by American Society of Clinical Oncology. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP STONE, RM (reprint author), DANA FARBER CANC INST,DIV CANC PHARMACOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 32 TC 210 Z9 212 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 1994 VL 12 IS 12 BP 2535 EP 2542 PG 8 WC Oncology SC Oncology GA PV811 UT WOS:A1994PV81100004 PM 7989927 ER PT J AU MARCUS, KC KALISH, LA COLEMAN, CN SHULMAN, LN ROSENTHAL, DS CANELLOS, GP MAUCH, PM AF MARCUS, KC KALISH, LA COLEMAN, CN SHULMAN, LN ROSENTHAL, DS CANELLOS, GP MAUCH, PM TI IMPROVED SURVIVAL IN PATIENTS WITH LIMITED STAGE IIIA HODGKINS-DISEASE TREATED WITH COMBINED RADIATION-THERAPY AND CHEMOTHERAPY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COMBINED MODALITY THERAPY; PROGNOSTIC FACTORS; COMBINATION CHEMOTHERAPY; ANATOMIC SUBSTAGES; 1ST RELAPSE; MOPP; RADIOTHERAPY; ABVD; IRRADIATION; STAGE-III1A AB Purpose: Patients with laparotomy-staged (PS) III1A Hodgkin's disease confined to the upper abdomen are believed to have a favorable prognosis and require less aggressive treatment than patients with more-extensive stage III disease. We evaluated prognostic factors and outcome in 93 patients with PS III1A Hodgkin's disease treated either with radiation therapy (RT) alone or combined RT and chemotherapy (combined modality treatment [CMT]) to determine the extent of treatment needed in this subgroup of stage IIIA patients. Materials and Methods: We retrospectively reviewed the freedom from relapse (FFR) rate, sites of recurrence, and survival rate of PS III1A patients selected to receive extended-field irradiation (MPA, n = 27), total-nodal irradiation (TNI, n = 34), and CMT (n = 32) between 1969 and 1987. CMT consisted of six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy and MPA. Patients treated with MPA were part of ct prospective trial designed to reduce treatment to patients with minimal stage III disease with very favorable characteristics. Results: Histologic subclass and treatment were the only prognostic factors for FFR and survival rates. Patients with nodular sclerosis or lymphocyte predominance histology had significantly higher FFR and survival rates compared to patients with mixed-cellularity (MC) histology. The 10-year actuarial FFR of PSIII1A patients treated with MPA was only 39%, versus 55% for TNI (P =.02) and 94% for CMT (v MPA, P <.0001; v TNI, P = .006). The patterns of recurrence in patients who received MPA and TNI were significantly different, with MPA patients relapsing more often in untreated pelvic or inguinal nodes, and TNI patients relapsing more often in extranodal sites with or without nodal sites. The 10-year actuarial overall survival rate for patients treated with CMT was 89% versus 78% for MPA (v CMT, P =.09) and 70% for TNI (v CMT, P =.05). Conclusion: Patients with PSIII1A Hodgkin's disease treated with PT have a significantly higher risk of relapse and potentially a poorer survival compared with patients treated with CMT. These findings suggest that CMT should play a greater role in the treatment of this favorable substage of patients. Management with modified chemotherapy and PT in an attempt to reduce long-term treatment-induced complications may be a preferred approach for future trials. (C) 1994 by American Society of Clinical Oncology. C1 BRIGHAM & WOMENS HOSP,JOINT CTR RADIAT THERAPY,BOSTON,MA. DANA FARBER CANC INST,DIV HEMATOL ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,SCH PUBL HLTH,DIV MED ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,SCH PUBL HLTH,DIV BIOSTAT,BOSTON,MA. NR 28 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1994 VL 12 IS 12 BP 2567 EP 2572 PG 6 WC Oncology SC Oncology GA PV811 UT WOS:A1994PV81100008 PM 7989930 ER PT J AU SEIDEN, MV KANTOFF, PW KRITHIVAS, K PROPERT, K BRYANT, M HALTOM, E GAYNES, L KAPLAN, I BUBLEY, G DEWOLF, W SKLAR, J AF SEIDEN, MV KANTOFF, PW KRITHIVAS, K PROPERT, K BRYANT, M HALTOM, E GAYNES, L KAPLAN, I BUBLEY, G DEWOLF, W SKLAR, J TI DETECTION OF CIRCULATING TUMOR-CELLS IN MEN WITH LOCALIZED PROSTATE-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PRIMARY BREAST-CANCER; PREDICT PATHOLOGICAL STAGE; POLYMERASE CHAIN-REACTION; CLINICAL STAGE; BONE-MARROW; REVERSE-TRANSCRIPTASE; ANTIGEN CONCENTRATION; RECTAL EXAMINATION; ULTRASONOGRAPHY; ADENOCARCINOMA AB Purpose: Using prostate-specific antigen (PSA) mRNA as a marker for prostatic epithelial cells, we have developed a sensitive technique that involves reverse transcription and polymerase chain reaction (RT-PCR) to detect circulating tumor cells in the peripheral blood of men with prostatic carcinoma (Cap). Patients and Methods: A sensitive RT-PCR assay was used to evaluate the peripheral blood of 135 men with a history of Cap. Fourteen men with benign prostate disease, many of whom had elevated serum PSA levels, were used as a control group. Results: All patients with benign prostate disease had a negative result in the RT-PCR assay. Of particular interest was a subgroup of 65 patients with clinically localized Cap evaluated before definitive local therapy. Five of these patients had detectable PSA mRNA by RT- PCR, suggesting circulating tumor cells. Within this group, systemic disease was detected by RT-PCR in some men with PSA levels less than 10 ng/mL and clinical stage B disease. Blood from men with hormone-refractory and progressive Cap demonstrated a higher frequency of PSA mRNA detectable by RT-PCR (10 of 20 patients). In contrast, none of seven patients with newly diagnosed metastatic prostate cancer and only one of seven patients with metastatic, hormone-responsive disease had blood that wets positive for PSA mRNA by RT-PCR. Conclusion: Circulating tumor cells can be detected in the blood aa subset of patients with clinically localized Cap and a larger subset of patients with progressive metastatic disease. (C) 1994 by American Society of Clinical Oncology. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT MED,BOSTON,MA. BETH ISRAEL HOSP,BOSTON,MA 02215. NEW ENGLAND DEACONESS HOSP,DEPT RADIOTHERAPY,BOSTON,MA. BETH ISRAEL HOSP,METRO W MED CTR,DEPT UROL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RP SEIDEN, MV (reprint author), MASSACHUSETTS GEN HOSP,DIV MED ONCOL,FRUIT ST,BOSTON,MA 02114, USA. NR 25 TC 140 Z9 141 U1 0 U2 3 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 1994 VL 12 IS 12 BP 2634 EP 2639 PG 6 WC Oncology SC Oncology GA PV811 UT WOS:A1994PV81100018 PM 7527455 ER PT J AU HAMM, J SCHILLER, JH CUFFIE, C OKEN, M FISHER, RI SHEPHERD, F KAISER, G AF HAMM, J SCHILLER, JH CUFFIE, C OKEN, M FISHER, RI SHEPHERD, F KAISER, G TI DOSE-RANGING STUDY OF RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN SMALL-CELL LUNG-CARCINOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID AUTOLOGOUS BONE-MARROW; GM-CSF; ADVANCED MALIGNANCY; CANCER; CHEMOTHERAPY; THERAPY; NEUTROPHILS; SURVIVAL; TOXICITY; TUMORS AB Purpose: This randomized, multicenter, dose-finding study was undertaken to determine the dose of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) that can safely reduce neutropenia after cyclophosphamide, doxorubicin, and etoposide (CAVP-16) chemotherapy in patients with small-cell lung cancer (SCLC). Secondary clinical end points included incidence of infection, intravenous (IV) antimicrobial use, and chemotherapy delivered. Patients and Methods: A total of 290 newly diagnosed SCLC patients were to receive six cycles of standard CAVP-16 chemotherapy on days 1 to 3 of every 21 days alone or with rhGM-CSF at 5, 10, or 20 mu g/kg, administered subcutaneously (SC) on days 4 to 13 of each cycle. Results: In cycle 1, median absolute neutrophil count (ANC) nadirs were twofold to threefold higher in patients who received rhGM-CSF, although all values were less than 500/mu L, and recovery from neutropenia was faster at all rhGM-CSF dosages versus observation (P less than or equal to .01). In cycle 2, 56% of all patients given rhGM-CSF received full chemotherapy dosages (87.5% to 112.% of projected dose) versus 36% of observation patients. During days 5 to 21 of cycle 1, fewer patients who received 10 mu g/kg of rhGM-CSF required antibiotics compared with observation patients (11% v 29%, P less than or equal to .01). Adverse events that occurred more frequently in rhGM-CSF-treated patients included injection-site reaction, edema, asthenia, paesthesia, diarrhea, myalgia, musculoskeletal pain, pruritus, and rash (P less than or equal to .10). Fewer occurred more frequently in the 10- and 20-mu g/kg rhGM-CSF groups than in the observation groups. The incidence in the 5-mu g/kg group was comparable to that in observation patients. Patients who received rhGM-CSF had a higher incidence of thrombocytopenia. Conclusion: rhGM-CSF at 5 to 10 mu g/kg reduces chemotherapy-associated neutropenia and should be the dose range used in future studies. C1 UNIV LOUISVILLE,JAMES GRAHAM BROWN CANC CTR,LOUISVILLE,KY 40292. UNIV WISCONSIN,CTR CLIN CANC,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. SCHERING PLOUGH CORP,RES INST,KENILWORTH,NJ 07033. ABBOTT NW HOSP,PIPER CANC INST,MINNEAPOLIS,MN. LOYOLA UNIV,MED CTR,MAYWOOD,IL 60153. TORONTO GEN HOSP,TORONTO,ON,CANADA. MUNICIPAL MED CTR,MED DEPT HEMATOL ONCOL 5,NURNBERG,GERMANY. NR 32 TC 39 Z9 39 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 1994 VL 12 IS 12 BP 2667 EP 2676 PG 10 WC Oncology SC Oncology GA PV811 UT WOS:A1994PV81100022 PM 7989942 ER PT J AU EISENBERG, E BERKEY, CS CARR, DB MOSTELLER, F CHALMERS, TC AF EISENBERG, E BERKEY, CS CARR, DB MOSTELLER, F CHALMERS, TC TI EFFICACY AND SAFETY OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS FOR CANCER PAIN - A METAANALYSIS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DOUBLE-BLIND; ANALGESIC EFFICACY; PLUS CODEINE; BONE PAIN; MANAGEMENT; PENTAZOCINE; THERAPY; RELIEF; SODIUM; ACETAMINOPHEN AB Purpose: To assess the efficacy and safety of nonsteroidal inflammatory drugs (NSAIDs) in the treatment of cancer pain by meta-analyses of the published randomized control trials (RCTs). Patients and Methods: Twenty-five studies met inclusion criteria for analysis. Of these, 13 tested a single-dose effect, nine multiple-dose effects, and three both single- and multiple-dose effects of 16 different NSAIDs in a total of 1,545 patients. Baseline pain intensity (when provided) of moderate or higher was indicated in 81% of patients. Results: Single-dose NSAID studies found greater analgesic efficacy than placebo, with rough equivalence to 5 to 10 mg of intramuscular morphine. Pain scores differed insignificantly for aspirin versus three other NSAIDs. Analgesic responses to low- and high-dose NSAIDs suggested a dose-response relationship, but this was not statistically significant. Recommended and supramaximal single doses of three NSAIDs produced comparable changes in pain scores, which indicates a ceiling analgesic effect. Common side effects included upper gastrointestinal symptoms, dizziness, and drowsiness. The incidence of side effects showed a trend to increase with dose, without a ceiling effect, and to increase with dose, without a ceiling effect, and to increase with multiple doses. Single or multiple doses of weak opioids (WO) alone or in combination (WO/C) with nonopioid analgesics did not produce greater analgesia than NSAIDs alone. Single doses of WO/C analgesics produced more side effects than NSAIDs alone, although both side effect incidence and patient dropout rates were equal when multiple doses were administered. Conclusion: These findings question whether the traditional World Health Organization (WHO) second analgesic step (addition of a weak opioid when pain is inadequately treated by a nonopioid when pain is inadequately treated by a nonopioid analgesic alone) is warranged. A lack of comparable studies precluded testing the hypothesis that NSAIDs are particularly effective for malignant bone pain. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT ANESTHESIA,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,DIV CLIN CARE RES,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,TECHNOL ASSESSMENT GRP,BOSTON,MA 02115. TUFTS UNIV,SCH MED,BOSTON,MA 02111. RAMBAM MED CTR,PAIN RELIEF CLIN,HAIFA,ISRAEL. NR 47 TC 128 Z9 133 U1 0 U2 4 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 1994 VL 12 IS 12 BP 2756 EP 2765 PG 10 WC Oncology SC Oncology GA PV811 UT WOS:A1994PV81100034 PM 7989953 ER PT J AU VANDERKOLK, BA DREYFUSS, D MICHAELS, M SHERA, D BERKOWITZ, R FISLER, R SAXE, G AF VANDERKOLK, BA DREYFUSS, D MICHAELS, M SHERA, D BERKOWITZ, R FISLER, R SAXE, G TI FLUOXETINE IN POSTTRAUMATIC-STRESS-DISORDER SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PHARMACOTHERAPY; TRIAL; PHENELZINE; IMIPRAMINE; PTSD AB Background: This study was designed to establish the efficacy of the serotonin reuptake blocker fluoxetine in the treatment of posttraumatic stress disorder (PTSD). Method: 64 subjects (22 women and 42 men; 31 veterans and 33 nonveterans) with PTSD entered a 5-week randomized double-blind trial comparing fluoxetine (N = 33) and placebo (N = 31). Results: By Week 5 fluoxetine, but not placebo, significantly reduced overall PTSD symptomatology, as assessed by the Clinician-Administered PTSD Scale (CAPS) score. Changes were most marked in the arousal and numbing symptom subcategories. Non-VA patients responded much better than VA patients. Fluoxetine was an effective antidepressant independent of its effects on PTSD. Conclusion: Fluoxetine is an effective pharmacotherapeutic agent for treating PTSD and its associated features, particularly in patients without chronic treatment histories. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. DEPT VET AFFAIRS,OUTPATIENT CLIN,BOSTON,MA. TUFTS UNIV,SCH MED,BOSTON,MA 02111. NR 27 TC 324 Z9 330 U1 2 U2 16 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 1994 VL 55 IS 12 BP 517 EP 522 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA QC302 UT WOS:A1994QC30200001 PM 7814344 ER PT J AU LEWIN, L GONZALES, LR AF LEWIN, L GONZALES, LR TI TREATMENT OF URETHRAL CATHETER DEPENDENCE - A CASE-STUDY OF INTERVENTION IN THE INTERDISCIPLINARY GERIATRIC SETTING SO JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS LA English DT Article DE URETHRAL CATHETER DEPENDENCE; PHOBIA; DECONDITIONING; INTERDISCIPLINARY AB This case report describes the assessment and treatment of a 69-year-old male medical patient with urethral catheter dependence. Assessment revealed an anxiety/phobic component to the dependence and hypothesized detrusor muscle deconditioning. Retraining of the bladder and desensitization to the anxiety-provoking situation were achieved by exposure to decatheterization in the context of a supportive adult day health care setting. Interdisciplinary collaboration between nursing and psychology were associated with successful functional social, and psychological outcomes. C1 OREGON HLTH SCI UNIV,DEPT MED PSYCHOL,PORTLAND,OR 97201. PORTLAND VA MED CTR,PORTLAND,OR. RP LEWIN, L (reprint author), CLARK COLL,FOSTER HALL,1800 E MCLOUGHLIN BLVD,VANCOUVER,WA 98663, USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 1068-9583 J9 J CLIN PSYCHOL MED S JI J. Clin. Psychol. Med. Settings PD DEC PY 1994 VL 1 IS 4 BP 363 EP 373 DI 10.1007/BF01991079 PG 11 WC Psychology, Clinical SC Psychology GA RK317 UT WOS:A1994RK31700008 PM 24225862 ER PT J AU NIERENBERG, AA FEIGHNER, JP RUDOLPH, R COLE, JO SULLIVAN, J AF NIERENBERG, AA FEIGHNER, JP RUDOLPH, R COLE, JO SULLIVAN, J TI VENLAFAXINE FOR TREATMENT-RESISTANT UNIPOLAR DEPRESSION SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Note ID FOLLOW-UP; MAJOR DEPRESSION AB The purpose of this study is to evaluate the novel antidepressant venlafaxine for the management of treatment-resistant unipolar depression. We gave unblinded venlafaxine to 84 consecutive outpatients and inpatients who met DSM-III-R criteria for major depression and who had failed to respond to at least three adequate trials of antidepressants from at least two different antidepressant classes or electroconvulsive therapy, plus at least one attempt at augmentation. Patients were evaluated after a drug free period at baseline and regular intervals with the 21-item Hamilton Rating Stale for Depression (HAM-D-21), Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions Scale Improvement item (CGI). Full response for each scale was defined as follows: HAM-D-21 score of 8 or lower, a MADRS score of 12 or lower, and CGI score of 1; partial responses was defined as a 50% decrease in the HAM-D and MADRS, with final scores greater than 8 and 12, respectively, and for the CGI, a score equal to 2. About a third of patients were considered to be either full or partial responders (32.9% by HAM-D-21, 30.0% by MADRS, and 40% by CGI) after 12 weeks of venlafaxine treatment. To date, about 46% of responders have sustained their response for at least 3 months after the acute response. Venlafaxine is effective for a significant, but small, minority of patients with rigorously defined triple-resistant depression; the improvement was maintained for about half of the responders for the first 3 months of maintenance therapy. C1 HARVARD UNIV,MCLEAN HOSP,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,MCLEAN HOSP,SCH MED,DEPT PSYCHIAT,AFFECT DISORDERS PROGRAM,BOSTON,MA 02115. FEIGHNER RES INST,SAN DIEGO,CA. WYETH AYERST RES,RADNOR,PA. RP NIERENBERG, AA (reprint author), MASSACHUSETTS GEN HOSP,DEPRESS RES PROGRAM,CLIN PSYCHOPHARMACOL UNIT,WACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 12 TC 157 Z9 157 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 1994 VL 14 IS 6 BP 419 EP 423 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA PV514 UT WOS:A1994PV51400008 PM 7884023 ER PT J AU MCLELLAN, AT ALTERMAN, AI METZGER, DS GRISSOM, GR WOODY, GE LUBORSKY, L OBRIEN, CP AF MCLELLAN, AT ALTERMAN, AI METZGER, DS GRISSOM, GR WOODY, GE LUBORSKY, L OBRIEN, CP TI SIMILARITY OF OUTCOME PREDICTORS ACROSS OPIATE, COCAINE, AND ALCOHOL TREATMENTS - ROLE OF TREATMENT SERVICES SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID ADDICTION SEVERITY INDEX; SUBSTANCE-ABUSE TREATMENT; PSYCHOPATHOLOGY AB This study examined the patient and treatment factors associated with 6-month outcome in 649 opiate-, alcohol-, and cocaine-dependent (male and female) adults, treated in inpatient and outpatient settings, in 22 publicly and privately funded programs. Outcomes were predicted by similar factors, regardless of the drug problem of the patient or the type of treatment setting or funding. Greater substance use at follow-up was predicted only by greater severity of alcohol and drug use at treatment admission, not by the number of services received during treatment. Better social adjustment at follow-up was negatively predicted by more severe psychiatric, employment, and family problems at admission and positively predicted C1 INTEGRA INC,RADNOR,PA. RP MCLELLAN, AT (reprint author), UNIV PENN,SCH MED,VET AFFAIRS MED CTR,CTR STUDIES ADDICT,DEPT PSYCHIAT,BLDG 7,UNIV AVE,PHILADELPHIA,PA 19104, USA. RI Metzger, David/D-9499-2012 NR 48 TC 262 Z9 266 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 1994 VL 62 IS 6 BP 1141 EP 1158 DI 10.1037//0022-006X.62.6.1141 PG 18 WC Psychology, Clinical SC Psychology GA PX232 UT WOS:A1994PX23200006 PM 7860812 ER PT J AU SEN, J SHINKAI, Y ALT, FW SEN, RJ BURAKOFF, SJ AF SEN, J SHINKAI, Y ALT, FW SEN, RJ BURAKOFF, SJ TI NUCLEAR FACTORS THAT MEDIATE INTRATHYMIC SIGNALS ARE DEVELOPMENTALLY-REGULATED SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IMMATURE CD4+CD8+ THYMOCYTES; RECEPTOR-BETA-CHAIN; NF-KAPPA-B; T-CELLS; MONOCLONAL-ANTIBODY; TRANSCRIPTION; EXPRESSION; ACTIVATION; COMPLEXES; EVENTS AB Thymocytes mature through several stages of development, defined by cell surface markers such as CD3, CD4, and CD8, in response to environmental cues. Signal transduction resulting from lymphocyte-stromal cell interactions is likely to activate inducible transcription factors which in turn govern stage-specific gene expression. In this report we show that inducible transcription factors such as AP-1 and NF-AT are constitutively nuclear, in response to intrathymic signals, in freshly isolated thymocytes at all stages of maturation. In CD4(+)CD8(+) double positive (DP), but not in the more immature CD4(-)CD8(-) double negative (DN) thymocytes, constant stimulus from the thymic environment is required to maintain nuclear AP-1. Thus, disruption of the thymus and incubation of thymocytes at 37 degrees C downregulates DNA binding by nuclear factors AP-1 and NF-AT. Similar treatment of thymocytes has previously been shown to downregulate CD3 zeta chain phosphorylation and increase T cell receptor CD3 expression on DP thymocytes, which is a feature of repertoire selection. Since mature T cells maintain inducible nuclear factors in an inactive form until an encounter with antigen, we propose that downregulation of nuclear DNA binding proteins may reflect another feature of this stage of T cell maturation. C1 CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. BRANDEIS UNIV,ROSENSTIEL BASIC MED SCI RES CTR,WALTHAM,MA 02254. RP SEN, J (reprint author), DANA FARBER CANC INST,DIV PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Shinkai, Yoichi/N-3909-2014 OI Shinkai, Yoichi/0000-0002-6051-2484 FU NIAID NIH HHS [R0 -AI-17258]; NIGMS NIH HHS [GM-00563, GM-43874] NR 28 TC 27 Z9 27 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1994 VL 180 IS 6 BP 2321 EP 2327 DI 10.1084/jem.180.6.2321 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PU361 UT WOS:A1994PU36100032 PM 7964504 ER PT J AU MERKEL, PA CAPUTO, GC AF MERKEL, PA CAPUTO, GC TI EVALUATION OF A SIMPLE OFFICE-BASED STRATEGY FOR INCREASING INFLUENZA VACCINE ADMINISTRATION AND THE EFFECT OF DIFFERING REIMBURSEMENT PLANS ON THE PATIENT ACCEPTANCE RATE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE INFLUENZA VACCINATION; IMMUNIZATION; COST; PREVENTIVE HEALTH SERVICES; PATIENT ACCEPTANCE; REIMBURSEMENT; OFFICE-BASED REMINDERS AB Objective: To study an office-based strategy for increasing influenza vaccine delivery to high-risk patients at a university hospital general medicine practice. Design: Historically controlled study of physician practices in an out-patient general medicine setting. Setting: A group practice with two separate offices: a fee-for-service (FFS) office, where the patients pay the cost of immunizations, and a health maintenance organization (HMO)-styled office, where the costs for immunizations are fully covered by the insurer. Patients: All outpatients seen at each practice setting from October to December, 1991. Intervention: For each patient visit, a simple reminder data sheet was completed by the clinician detailing the vaccination eligibility (Centers for Disease Control and Prevention criteria) and status of the patient, the reasons for failure to vaccinate eligible patients, and 1990 vaccination information. Results: During the study period, 511 patients were seen by the practice (353 in the FFS office, 158 in the HMO office), 297 patients (58%) were eligible for vaccination; 219 in the FFS office, 78 in the HMO office (p < 0.01). At the end of the study period, 73% of all the eligible patients were vaccinated: 67% of the FFS patients vs 90% of the HMO patients (p < 0.01), 22% of the eligible patients refused vaccination: 27% in the FFS office vs 9% in the HMO office (p < 0.01), 11% of the eligible FFS patients vs 0% of the eligible HMO patients refused vaccination due to vaccine cost (p < 0.05). Of the eligible patients seen at the two offices in both 1990 and 1991, 50% were vaccinated in 1990 (preintervention) vs 66% in 1991 (postintervention) (p < 0.01). Conclusions: As shown in this study, a simple, low-cost office-based reminder system can significantly increase the influenza vaccination rate for high-risk outpatients and can help meet national vaccination rate goals. Vaccine cost to patients may be a barrier to vaccine acceptance, in some cases. RP MERKEL, PA (reprint author), MASSACHUSETTS GEN HOSP,ARTHRITIS UNIT,BULFINCH 1,BOSTON,MA 02114, USA. NR 0 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 1994 VL 9 IS 12 BP 679 EP 683 DI 10.1007/BF02599008 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA PX747 UT WOS:A1994PX74700004 PM 7876950 ER PT J AU CANNON, SC AF CANNON, SC TI A PREDILECTION FOR MYOTONIA OR PARALYSIS BASED ON DIFFERENT DEFECTS IN NA CHANNEL INACTIVATION SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. NR 3 TC 3 Z9 3 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD DEC PY 1994 VL 104 IS 6 BP A20 EP A20 PG 1 WC Physiology SC Physiology GA PY569 UT WOS:A1994PY56900050 ER PT J AU CHEN, CF CANNON, S AF CHEN, CF CANNON, S TI PARADOXICAL ACCELERATION OF SODIUM CURRENT INACTIVATION BY ALPHA-SCORPION TOXIN FROM LEIURUS-QUINQUESTRIATUS SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD DEC PY 1994 VL 104 IS 6 BP A20 EP A21 PG 2 WC Physiology SC Physiology GA PY569 UT WOS:A1994PY56900051 ER PT J AU RIZZO, JA BLUMENTHAL, D AF RIZZO, JA BLUMENTHAL, D TI PHYSICIAN LABOR SUPPLY - DO INCOME EFFECTS MATTER SO JOURNAL OF HEALTH ECONOMICS LA English DT Article DE PHYSICIAN LABOR SUPPLY; PHYSICIAN EARNINGS; INCOME EFFECTS ID MEDICAL-PROFESSION AB This paper estimates a model of physician labor supply, focusing on the impacts of wage and non-wage income. We find evidence of significant income effects. For male physicians, the income effect of a wage change on labor supply is negative, with an elasticity of -0.26. The pure substitution effect of a wage change increases labor supply: a 1% increase in wages leads to a 0.49% increase in labor supply, controlling for income effects. The results also suggest that the labor supply decisions of females are more responsive to variations in their earnings than are those of males. C1 MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP RIZZO, JA (reprint author), YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,60 COLLEGE ST,NEW HAVEN,CT 06510, USA. NR 30 TC 49 Z9 49 U1 4 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-6296 J9 J HEALTH ECON JI J. Health Econ. PD DEC PY 1994 VL 13 IS 4 BP 433 EP 453 DI 10.1016/0167-6296(94)90012-4 PG 21 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA QF803 UT WOS:A1994QF80300003 PM 10140533 ER PT J AU DELAMONTE, SM WANDS, JR AF DELAMONTE, SM WANDS, JR TI DIAGNOSTIC UTILITY OF QUANTITATING NEUROFILAMENT-IMMUNOREACTIVE ALZHEIMERS-DISEASE LESIONS SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE NEUROFILAMENT IMMUNOREACTIVITY; ALZHEIMERS DISEASE; PARKINSONS DISEASE; DOWNS SYNDROME; NEUROFIBRILLARY TANGLE; PAIRED HELICAL FILAMENTS; DYSTROPHIC NEURITES AND DENDRITES ID PAIRED HELICAL FILAMENTS; PROTEIN-TAU TAU; MICROTUBULE-ASSOCIATED PROTEINS; PROGRESSIVE SUPRANUCLEAR PALSY; SHARE ANTIGENIC DETERMINANTS; NEUROFIBRILLARY TANGLES; LEWY BODIES; MONOCLONAL-ANTIBODY; NEUROPIL THREADS; NEURITIC PLAQUES AB The diagnosis of Alzheimer's disease (AD) neurodegeneration is based on histopathological detection of paired helical filament-associated lesions. Silver stains are routinely used but the results are fraught with intra- and interinstitutional variability. This study employed monoclonal antibodies to middle and high molecular weight neurofilament subunits in an immunohistochemical assay to assess the extent of paired helical filament-associated lesions in brains with AD, Down's syndrome plus AD lesions (AD+DN), Parkinson's disease dementia (PD), AD+PD, and normal aging changes. The densities of neurofilament-immunoreactive (NFI) cortical neurofibrillary tangles and plaques were significantly higher in AD and AD+DN than in PD and aged control brains (p<0.001), and NFI neurofibrillary tangles and plaques were more abundant in AD and AD+DN compared with AD+PD and PD, yet all patients with AD, AD+PD, or PD died with end-stage dementia. In contrast, the densities of NFI dystrophic neurites (primarily dendrites) in cortical Layer 2 were similar among the AD, AD+DN, AD+PD, and PD groups, and all were significantly higher than control (p<0.005). Stepwise multivariate regression analysis demonstrated significant correlations between AD diagnosis and high densities of NFl neurofibrillary tangles and plaques (p<0.001) and between end-stage AD-type dementia and high densities of NFI dystrophic neurites (<0.001). This study demonstrates that the histopathological lesions correlated with AD dementia can be readily detected and quantified by immunostaining with monoclonal antibodies to phosphorylated and non-phosphorylated neurofilaments. Moreover, the findings suggest that NFI neurite pathology may be an important feature contributing to the clinically manifested AD-type dementia in individuals with Parkinson's disease. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL & MED SERV,BOSTON,MA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666]; NICHD NIH HHS [HD-20469] NR 70 TC 15 Z9 15 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD DEC PY 1994 VL 42 IS 12 BP 1625 EP 1634 PG 10 WC Cell Biology SC Cell Biology GA PW589 UT WOS:A1994PW58900012 PM 7983363 ER PT J AU AVERY, AC MARKOWITZ, JS GRUSBY, MJ GLIMCHER, LH CANTOR, H AF AVERY, AC MARKOWITZ, JS GRUSBY, MJ GLIMCHER, LH CANTOR, H TI ACTIVATION OF T-CELLS BY SUPERANTIGEN IN CLASS II-NEGATIVE MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STAPHYLOCOCCAL ENTEROTOXIN-A; MONOCLONAL ANTIBODY; DEFICIENT MICE; TARGET-CELLS; MOLECULES; BINDING; ANERGY; STIMULATION; EXPRESSION; INDUCTION AB The ability of the staphylococcal enterotoxins to stimulate T cells has been thought to depend on their association with class II MHC products. Here, we demonstrate that a subgroup of staphylococcal enterotoxins, which includes staphylococcal enterotoxin C and staphylococcal enterotoxin E, stimulates strong MHC-independent responses, thereby resulting in T cell expansion and generation of CTL. The immunologic consequences of MHC-independent activation of T cells by superantigens differ from those of class II-dependent activation, inasmuch as this pathway does not result in detectable T cell deletion. These findings delineate a novel MHC-independent T cell activation pathway that leads to both clonal expansion and expression of CTL effector function in response to a subgroup of bacterial superantigens. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,IMMUNOPATHOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. FU NIAID NIH HHS [AI 13600, AI 31541, AI 12184] NR 29 TC 51 Z9 52 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 1 PY 1994 VL 153 IS 11 BP 4853 EP 4861 PG 9 WC Immunology SC Immunology GA PT301 UT WOS:A1994PT30100001 PM 7963549 ER PT J AU FLESCHER, E LEDBETTER, JA SCHIEVEN, GL VELAROCH, N FOSSUM, D DANG, H OGAWA, N TALAL, N AF FLESCHER, E LEDBETTER, JA SCHIEVEN, GL VELAROCH, N FOSSUM, D DANG, H OGAWA, N TALAL, N TI LONGITUDINAL EXPOSURE OF HUMAN T-LYMPHOCYTES TO WEAK OXIDATIVE STRESS SUPPRESSES TRANSMEMBRANE AND NUCLEAR SIGNAL-TRANSDUCTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE PHOSPHORYLATION; CELL ANTIGEN RECEPTOR; DNA-BINDING PROTEINS; TRANSCRIPTION FACTOR; HYDROGEN-PEROXIDE; N-ACETYLCYSTEINE; PHOSPHOLIPASE-C; HEAT-SHOCK; POLYAMINE OXIDATION; GENE-EXPRESSION AB Products of polyamine oxidase activity, at micromolar levels and during a period of 2 to 3 days, down-regulate IL-2 mRNA levels and activity in human lymphocytes. We studied whether this suppression was associated with signal transduction abnormalities. We found that polyamine oxidase activity suppresses both anti-CD3-induced IL-2 production and protein tyrosine phosphorylation. Polyamine oxidase activity also caused a reduction in intracellular calcium mobilization after mitogenic stimulation. The most distal step of CD3-mediated signal transduction is dependent upon transcription factors that regulate a set of genes, including IL-2. We found that polyamine oxidase-treated cells exhibited very low DNA binding activity of two such factors: NFAT and NF-kappa B. On the other hand, AP-1 DNA binding activity was enhanced in polyamine oxidase-treated cells, suggesting a possible role for AP-1 in the human lymphocyte stress response. In accordance with the oxidation dependence of this suppressive mechanism, N-acetylcysteine (NAC; an antioxidant) significantly reversed the polyamine oxidase effects on lymphokine production and signal transduction. These results suggest that NAC contributes, under oxidizing conditions, to the preservation of immune function. In summary, our data suggest that chronic low-level oxidative stress; via suppression of mitogen-induced transmembrane signaling (protein-tyrosine phosphorylation and calcium mobilization), causes a decrease in the DNA binding activity of transcription factors that regulate the IL-2 gene. This results in decreased IL-2 production. C1 UNIV TEXAS,AUDIE L MURPHY MEM VET HOSP,CLIN IMMUNOL SECT,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. FU NIDCR NIH HHS [DE10863, DE09311] NR 56 TC 88 Z9 89 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 1994 VL 153 IS 11 BP 4880 EP 4889 PG 10 WC Immunology SC Immunology GA PT301 UT WOS:A1994PT30100004 PM 7963551 ER PT J AU BORRIELLO, F FREEMAN, GJ EDELHOFF, S DISTECHE, CM NADLER, LM SHARPE, AH AF BORRIELLO, F FREEMAN, GJ EDELHOFF, S DISTECHE, CM NADLER, LM SHARPE, AH TI CHARACTERIZATION OF THE MURINE B7-1 GENOMIC LOCUS REVEALS AN ADDITIONAL EXON ENCODING AN ALTERNATIVE CYTOPLASMIC DOMAIN AND A CHROMOSOMAL LOCATION OF CHROMOSOME-16, BAND B5 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL ACTIVATION; PROTEIN-KINASE-C; CTLA-4 COUNTER-RECEPTOR; COSTIMULATORY SIGNAL; FUNCTIONAL EXPRESSION; MOUSE CHROMOSOME-16; ANTIGEN PROVIDES; APOLIPOPROTEIN-D; CLONAL ANERGY; LYMPHOCYTES-T AB The murine B7-1 (mB7-1) molecule expressed on APCs delivers a costimulatory signal for T cell activation through its T cell counter-receptor CD28, resulting in T cell proliferation and IL-2 production. Signaling through the TCR in the absence of CD28 signaling results in T cell anergy. We have analyzed the genomic structure of mB7-1 and here describe the identification of a previously unrecognized sixth exon at the far 3' end of the locus, which encodes an alternative cytoplasmic domain. Reverse transcriptase-PCR amplification of mB7-1 transcripts demonstrates that exon 6 is functionally spliced to the transmembrane-encoding exon 4. Furthermore, using 5' rapid amplification of cDNA ends, we determined that the 5'-untranslated region extends over 1505 bp beyond the previously reported transcriptional start site. In addition, we report the chromosomal location of mB7-1 to chromosome 16, band B5. C1 BRIGHAM & WOMENS HOSP,LONGWOOD MED RES CTR,DEPT PATHOL,DIV IMMUNOL RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [CA-40216]; NIGMS NIH HHS [GM46883] NR 52 TC 37 Z9 38 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 1 PY 1994 VL 153 IS 11 BP 5038 EP 5048 PG 11 WC Immunology SC Immunology GA PT301 UT WOS:A1994PT30100021 PM 7525722 ER PT J AU VILLANUEVA, POF REISER, H STADECKER, MJ AF VILLANUEVA, POF REISER, H STADECKER, MJ TI REGULATION OF T-HELPER CELL RESPONSES IN EXPERIMENTAL MURINE SCHISTOSOMIASIS BY IL-10 - EFFECT ON EXPRESSION OF B7 AND B7-2 COSTIMULATORY MOLECULES BY MACROPHAGES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN-PRESENTING CELL; CTLA-4 COUNTER-RECEPTOR; CD4+ LYMPHOCYTES-T; MESSENGER-RNA; GRANULOMATOUS HYPERSENSITIVITY; INTERLEUKIN-2 PRODUCTION; ACTIVATION ANTIGEN-B7; CYTOKINE PRODUCTION; MEDIATED RESPONSE; DOWN-REGULATION AB Granulomatous inflammation in schistosomiasis is a manifestation of cell-mediated hypersensitivity to parasite egg Ags that is predictably reduced in size over the course of the disease. This down-regulation may reflect a state of anergy in the T cells mediating granuloma formation after interaction with accessory cells incapable of providing full stimulation. The present studies were conducted to investigate this mechanism at the molecular level. We found that granuloma macrophages (CM) strongly inhibit the ability of splenic APC to stimulate egg Ag-specific Th1 responses. This property was shown to be dependent on their secretion of IL-10. Moreover, activated CM in culture were found to express little or no costimulatory Ags B7 or B7-2. However, when their autocrine secretion of IL-10 was neutralized with specific mAb, GM displayed an up-regulation of costimulatory molecules as well as of MHC class II Ags. Most importantly, GM cultured in the presence of anti-IL-10 mAb, acquired the ability to stimulate egg Ag-specific T cells. By independently blocking each of the induced costimulatory Ags, it appeared that B7-2 molecules provided stronger costimulation than B7. In separate experiments, culture supernatants from GM exerted a powerful inhibition of costimulatory Ag expression on Con-A-stimulated peritoneal exudate cells in vivo, which could similarly be attributed to IL-10. Our results demonstrate that IL-10 can play a critical role in the generation of accessory cells that, by virtue of down-regulation of costimulatory molecules, may be capable of inducing anergy in T cells mediating the vigorous granulomatous response of acute stage schistosomiasis. Our studies lend support to the contention that a state of unresponsiveness in pathogenic T cells may precipitate the down-regulation of granuloma formation and provide a molecular basis for the underlying mechanisms. C1 TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. NR 65 TC 72 Z9 73 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1994 VL 153 IS 11 BP 5190 EP 5199 PG 10 WC Immunology SC Immunology GA PT301 UT WOS:A1994PT30100037 ER PT J AU RUSCONI, S MERRILL, DP HIRSCH, MS AF RUSCONI, S MERRILL, DP HIRSCH, MS TI INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION IN CYTOKINE-STIMULATED MONOCYTES MACROPHAGES BY COMBINATION THERAPY SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MONOCYTES-MACROPHAGES; HIV REPLICATION; GM-CSF; CELLS; INFECTION; AZIDOTHYMIDINE; PROTEASE; AGENTS AB Combination regimens against human immunodeficiency virus type 1 (HIV-1) were studied in granulocyte-macrophage colony-stimulating factor (GM-CSF)-stimulated monocyte/macrophage cultures. Regimens included those that inhibited the same target (reverse transcriptase) or multiple targets. Treatment conditions assessed efficacy during prophylaxis and ongoing infection. Drugs included zidovudine, didanosine, nevirapine, foscarnet, pyridinone, the protease inhibitor RO31-8959 (also known as saquinavir), interferon-alpha A, the Tat inhibitor RO24-7429, and N-butyl-deoxynojirimycin. Two-, three-, and foul-drug combinations were tested. Drugs were tested at individually inhibitory concentrations of IC99, IC95, IC75, and IC50. All prophylactic regimens prevented HIV-1 replication at IC99. As drug concentrations were reduced, differences among the regimens became apparent. Regimens that acted at both single and multiple targets were effective in prophylactic settings and less so in acute infection. In ongoing infections, only modest reductions in viral replication were seen, even at IC99. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,INFECT DIS UNIT,BOSTON,MA 02114. RI Rusconi, Stefano/H-9263-2012 FU NCI NIH HHS [CA-12464, CA-35020] NR 24 TC 22 Z9 23 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1994 VL 170 IS 6 BP 1361 EP 1366 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PW152 UT WOS:A1994PW15200002 PM 7527825 ER PT J AU KLOCZEWIAK, M BLACK, KM LOISELLE, P CAVAILLON, JM WAINWRIGHT, N WARREN, HS AF KLOCZEWIAK, M BLACK, KM LOISELLE, P CAVAILLON, JM WAINWRIGHT, N WARREN, HS TI SYNTHETIC PEPTIDES THAT MIMIC THE BINDING-SITE OF HORSESHOE-CRAB ANTILIPOPOLYSACCHARIDE FACTOR SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ANTI-LPS FACTOR; ENDOTOXIN-NEUTRALIZING PROTEIN; MONOCLONAL-ANTIBODIES; TACHYPLEUS-TRIDENTATUS; LIPOPOLYSACCHARIDE; ACTIVATION; MECHANISMS; MONOCYTES; TOLERANCE; INVITRO AB Tachypleus antilipopolysaccharide (LPS) factor (TALF) is a protein of 102 amino acids in the lysate of amebocytes of Tachypleus tridentatus that binds bacterial LPS with high affinity and blocks its biologic activity in numerous assays. To elucidate the minimal sequences that bind LPS, overlapping synthetic peptides based on the sequence of TALF were assessed for the ability to bind and neutralize LPS. TALF41-53 was the minimal sequence that bound LPS, as assessed by a slot blot capture assay. TALF29-59 bound LPS with the highest potency. TALF29-59 decreased LPS-induced coagulation of limulus amebocyte lysate, induction of cytokines from human monocytes, and LPS-induced lethality in sensitized mice. Synthetic peptides based on TALF or other LPS-binding proteins may be useful for the design of drugs for treatment of endotoxemia. C1 MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,DEPT PEDIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MARINE BIOL LABS,WOODS HOLE,MA. INST PASTEUR,DEPT IMMUNOALLERGY,PARIS,FRANCE. FU NIAID NIH HHS [AI-28943] NR 33 TC 41 Z9 41 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1994 VL 170 IS 6 BP 1490 EP 1497 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PW152 UT WOS:A1994PW15200018 PM 7995989 ER PT J AU KOCHEVAR, IE MORAN, M GRANSTEIN, RD AF KOCHEVAR, IE MORAN, M GRANSTEIN, RD TI EXPERIMENTAL PHOTOAGING IN C3H/HEN, C3H/HEJ, AND BALB/C MICE - COMPARISON OF CHANGES IN EXTRACELLULAR-MATRIX COMPONENTS AND MAST-CELL NUMBERS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE UVB; SOLAR ELASTOSIS; ELASTIN; GLYCOSAMINOGLYCANS ID HAIRLESS MOUSE SKIN; NECROSIS-FACTOR-ALPHA; ADULT DERMAL FIBROBLASTS; ELASTIN GENE-EXPRESSION; ULTRAVIOLET-LIGHT-B; BIOCHEMICAL-CHANGES; VISIBLE CHANGES; AGED SKIN; RADIATION; DAMAGE AB Chronic exposure of human or murine skin to ultraviolet B (UVB) radiation alters dermal extracellular matrix composition and increases the number of mast cells and inflammatory cells. Experiments were designed to test the possible role of UVB-induced tumor necrosis factor-alpha in these photoaging changes based on reports that C3H/HeN, but not C3H/HeJ or Balb/c mice, produce excess TNF-alpha in response to UVB exposure. Pigmented C3H/HeN and C3H/HeJ strains were exposed to a total of 75 J/cm(2) of UVB radiation, and unpigmented Balb/c mice were exposed to 19 J/cm(2) The UVB-induced increases in collagen, glycosaminoglycans, and neutrophil number were similar or the same in all three strains. The elastin increase was greater in C3H/HeJ than in C3H/HeN mice. The most striking difference between the strains was a 7.7-fold UVB-induced increase in mast cells in C3H/HeN mice compared to no increase in irradiated C3H/HeJ mice and a 2.3-fold increase in Balb/c mice. These results suggest that excess TNF-alpha (or other mediator) produced in C3H/HeN skin (but not C3H/HeJ skin) in response to UVB exposure is involved in the mast cell increase and partial inhibition of elastin increase, but that neither these mediators nor mast cell products are important mediators for the chronic UVB-induced increases in neutrophils, glycosaminoglycans, and collagen. When a possible source of the excess TNF-alpha was investigated, it was found that isolated epidermal cells from all three strains produced increases in TNF-alpha in response to UVB radiation. These results, as well as the previous results showing differences between these strains in UVB-induced effects on cutaneous immune function, are consistent with a model in which UVB-induced mediators from the epidermis stimulate another cell type to produce excess TNF-alpha (and other mediators) in the C3H/HeN but not C3H/HeJ or Balb/c mice. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. RP KOCHEVAR, IE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,WEL-224,BOSTON,MA 02114, USA. FU NIAMS NIH HHS [AR40667] NR 35 TC 13 Z9 13 U1 0 U2 4 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1994 VL 103 IS 6 BP 797 EP 800 DI 10.1111/1523-1747.ep12413286 PG 4 WC Dermatology SC Dermatology GA QA803 UT WOS:A1994QA80300010 PM 7798617 ER PT J AU AZAR, GB AWWAD, JT KHAYATA, GM SUIDAN, FJ AF AZAR, GB AWWAD, JT KHAYATA, GM SUIDAN, FJ TI DELAYED INTERVAL DELIVERY IN A TRIPLET SO JOURNAL OF MATERNAL-FETAL INVESTIGATION LA English DT Article DE TRIPLETS; MULTIPLE GESTATION; PRETERM DELIVERY; MATERNAL MORBIDITY; SEPSIS; DELAYED DELIVERY AB Objective: To deliver a single member of a multiple gestation in a preterm delivery. Methods: We report the sixth case of triplets presenting with the above condition and managed by delaying delivery of the remaining 2 fetuses. Results: Neonatal death was the outcome of the first triplet, and the other 2 survived, following 12 days of expectant management, but the expense was severe maternal morbidity. Conclusion: The positive fetal value of expectant management is not denied. Concerns are raised, however, regarding potential maternal morbidity, a serious complication often masked by the wish for good fetal outcome. C1 MASSACHUSETTS GEN HOSP,VINCENT MEM GYNECOL SERV,BURNHAM BLDG,ROOM 127,BOSTON,MA 02114. AMER UNIV BEIRUT,MED CTR,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,BEIRUT,LEBANON. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0939-6322 J9 J MATERN-FETAL INVES JI J. Matern.-Fetal Invest. PD WIN PY 1994 VL 4 IS 1 BP 43 EP 45 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA ND028 UT WOS:A1994ND02800010 ER PT J AU ALBERT, MM ADAMS, K LUTHER, MJ SUN, SH GRAYBILL, JR AF ALBERT, MM ADAMS, K LUTHER, MJ SUN, SH GRAYBILL, JR TI EFFICACY OF AMBISOME IN MURINE COCCIDIOIDOMYCOSIS SO JOURNAL OF MEDICAL AND VETERINARY MYCOLOGY LA English DT Note ID AMPHOTERICIN-B AMBISOME; FORMULATION AMBISOME; MENINGITIS AB ICR mice were infected intranasally with arthroconidia of Coccicioides immitis. Mice were treated intravenously with amphotericin B deoxycholate (Fungizone) or an amphotericin B-lipid vehicle (AmBisome). Doses ranged from 0.05 to 1.0 mg kg(-1). Lung weight, which parallels disease severity and fungal burden in this infection, was used as the index of protection. Both Fungizone and AmBisome were significantly and equally protective at 0.3 and 1.0 mg kg(-1) body weight. C1 AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,DEPT RES,SAN ANTONIO,TX 78284. NR 23 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0268-1218 J9 J MED VET MYCOL JI J. Med. Vet. Mycol. PD DEC PY 1994 VL 32 IS 6 BP 467 EP 471 PG 5 WC Mycology SC Mycology GA QJ945 UT WOS:A1994QJ94500007 PM 7738729 ER PT J AU ROSENFELD, PJ MCKUSICK, VA AMBERGER, JS DRYJA, TP AF ROSENFELD, PJ MCKUSICK, VA AMBERGER, JS DRYJA, TP TI RECENT ADVANCES IN THE GENE MAP OF INHERITED EYE DISORDERS - PRIMARY HEREDITARY-DISEASES OF THE RETINA, CHOROID, AND VITREOUS SO JOURNAL OF MEDICAL GENETICS LA English DT Review ID ORNITHINE-DELTA-AMINOTRANSFERASE; STATIONARY NIGHT BLINDNESS; LINKED OCULAR ALBINISM; SYNDROME TYPE-II; STICKLER SYNDROME ARTHROOPHTHALMOPATHY; FAMILIAL EXUDATIVE VITREORETINOPATHY; COLOR-VISION DEFECTS; RAB GERANYLGERANYL TRANSFERASE; GRADIENT GEL-ELECTROPHORESIS; DUCHENNE MUSCULAR-DYSTROPHY C1 JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21287. RP ROSENFELD, PJ (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,HOWE LAB,243 CHARLES ST,BOSTON,MA 02114, USA. NR 227 TC 37 Z9 37 U1 1 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD DEC PY 1994 VL 31 IS 12 BP 903 EP 915 DI 10.1136/jmg.31.12.903 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA PX579 UT WOS:A1994PX57900001 PM 7891370 ER PT J AU MUTISYA, EM BOWLING, AC BEAL, MF AF MUTISYA, EM BOWLING, AC BEAL, MF TI CORTICAL CYTOCHROME-OXIDASE ACTIVITY IS REDUCED IN ALZHEIMERS-DISEASE SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE ALZHEIMERS DISEASE; MITOCHONDRIA; CYTOCHROME OXIDASE; EXCITOTOXICITY; NEURODEGENERATIVE DISEASE ID ELECTRON-TRANSPORT CHAIN; MITOCHONDRIAL-FUNCTION; ENTORHINAL CORTEX; MONKEY BRAIN; COMPLEX-I; RAT; ABNORMALITIES; METABOLISM; EXPRESSION; DEMENTIA AB A defect in energy metabolism may play a role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease. In the present study, we examined the activities of the enzymes that catalyze oxidative phosphorylation in frontal, temporal, parietal, and occipital cortex from Alzheimer's disease patients and age-matched controls. Complex I and complex II-III activities showed a small decrease in occipital cortex, but were unaffected in the other cortical areas. The most consistent change was a significant decrease of cytochrome oxidase (complex IV) activity of 25-30% in the four cortical regions examined. These results provide further evidence of a cytochrome oxidase defect in Alzheimer's disease postmortem brain tissue. A deficiency in this key energy-metabolizing enzyme could lead to a reduction in energy stores and thereby contribute to the neurodegenerative process. C1 MASSACHUSETTS GEN HOSP,NEUROCHEM LAB,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIA NIH HHS [AG05134, IP50AG05134, P01-AG11337] NR 47 TC 325 Z9 340 U1 1 U2 3 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 1994 VL 63 IS 6 BP 2179 EP 2184 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PT409 UT WOS:A1994PT40900023 PM 7964738 ER PT J AU VALLEJO, M AF VALLEJO, M TI TRANSCRIPTIONAL CONTROL OF GENE-EXPRESSION BY CAMP-RESPONSE ELEMENT-BINDING PROTEINS SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Review DE TRANSCRIPTION FACTORS; SIGNED TRANSDUCTION; BZIP PROTEINS; CREB; CREM; PROTEIN KINASE-A ID PANCREATIC-ISLET CELLS; DNA-BINDING; CYCLIC-AMP; FACTOR CREB; LEUCINE ZIPPER; KINASE-A; ADENYLYL CYCLASE; NUCLEAR-PROTEIN; MEMBRANE DEPOLARIZATION; SIGNAL-TRANSDUCTION RP VALLEJO, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,REPROD ENDOCRINE UNIT,BOSTON,MA 02114, USA. NR 105 TC 38 Z9 38 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD DEC PY 1994 VL 6 IS 6 BP 587 EP 596 DI 10.1111/j.1365-2826.1994.tb00623.x PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA PX573 UT WOS:A1994PX57300001 PM 7894460 ER PT J AU ROYALL, DR MAHURIN, R AF ROYALL, DR MAHURIN, R TI EXIT, QED, AND DSM-IV - REGIONAL SYNDROMES SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Letter C1 AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. RP ROYALL, DR (reprint author), UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX, USA. NR 8 TC 2 Z9 2 U1 1 U2 1 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 1994 VL 6 IS 1 BP 60 EP 62 PG 3 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA MV318 UT WOS:A1994MV31800014 PM 8148641 ER PT J AU ROYALL, DR MAHURIN, R AF ROYALL, DR MAHURIN, R TI EXIT, QED, AND DSM-IV - VERY EARLY ALZHEIMERS-DISEASE SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Letter C1 AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. RP ROYALL, DR (reprint author), UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX, USA. NR 12 TC 14 Z9 14 U1 1 U2 1 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 1994 VL 6 IS 1 BP 62 EP 64 PG 3 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA MV318 UT WOS:A1994MV31800015 PM 8148642 ER PT J AU BORSOOK, D FALKOWSKI, O ROSEN, H COMB, M HYMAN, SE AF BORSOOK, D FALKOWSKI, O ROSEN, H COMB, M HYMAN, SE TI OPIOIDS MODULATE STRESS-INDUCED PROENKEPHALIN GENE-EXPRESSION IN THE HYPOTHALAMUS OF TRANSGENIC MICE - A MODEL OF ENDOGENOUS OPIOID GENE-REGULATION BY EXOGENOUS OPIOIDS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE PROENKEPHALIN; ENKEPHALIN; OPIOID; STRESS; GENE EXPRESSION; TRANSGENIC MICE; HYPOTHALAMUS; PARAVENTRICULAR NUCLEUS; C-FOS ID PREPROENKEPHALIN MESSENGER-RNA; MORPHINE-DEPENDENT RATS; CENTRAL NERVOUS-SYSTEM; PARAVENTRICULAR NUCLEUS; CYCLIC-AMP; INSITU HYBRIDIZATION; SUPRAOPTIC NUCLEI; BETA-ENDORPHIN; SPINAL-CORD; BRAIN AB Stressful stimuli strongly induce proenkephalin gene expression within the paraventricular nucleus (PVN) of the hypothalamus. A human proenkephalin-beta-galactosidase fusion gene has previously been shown to give correct phenotypic expression and appropriate stress regulation within the hypothalamus of transgenic mice; this model provides high sensitivity, cellular resolution, and ready quantification of levels of proenkephalin gene expression. Here we describe use of this transgenic model to study modulation of stress-regulated gene expression in the PVN by opiates. Acute or subacute morphine administration prior to a hypertonic saline stress produced marked superinduction of transgene expression compared with hypertonic saline stress alone. In contrast, chronic morphine administration decreased basal expression of the transgene, and inhibited stress-induced expression of the transgene. The endogenous proenkephalin mRNA was induced in parallel with the transgene as demonstrated by in situ hybridization; the immediate-early gene c-fos was also regulated in parallel with the transgene. These data suggest that acute or subacute morphine administration sensitizes proenkephalin neurons within the PVN and other regions of the hypothalamus to stress and that chronic morphine administration desensitizes this response. Because the molecular mechanisms regulating the expression of the transgene are well understood, this model provides a useful tool for investigating cellular and molecular effects of opioids on the hypothalamus. C1 MASSACHUSETTS GEN HOSP,MOLEC & DEV NEUROSCI LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02114. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT MOLEC VIROL,IL-91010 JERUSALEM,ISRAEL. FU NIDA NIH HHS [DA07745, DA 07134]; NIMH NIH HHS [MH44160] NR 62 TC 18 Z9 18 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC PY 1994 VL 14 IS 12 BP 7261 EP 7271 PG 11 WC Neurosciences SC Neurosciences & Neurology GA PY006 UT WOS:A1994PY00600003 PM 7996174 ER PT J AU MATSUYAMA, SS BONDAREFF, W AF MATSUYAMA, SS BONDAREFF, W TI TAN-LIKE IMMUNOREACTIVITY IN ALZHEIMER AND CONTROL SKIN FIBROBLASTS SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE TAU; MICROTUBULES; INTERMEDIATE FILAMENTS ID PAIRED HELICAL FILAMENTS; PROTEIN-TAU; AMYLOID PRECURSOR; DISEASE; PHOSPHORYLATION; ANTIBODY; ISOFORMS; BRAIN; CORE AB The presence of the microtubule-associated protein tan in skin fibroblasts derived from Alzheimer patients and normal controls was investigated using a panel of well-characterized anti-tau antibodies against epitopes spanning the tau protein from the amino to the carboxyl end. The antibodies immunolabeled a fine, fibrillar cytoplasmic network in all skin fibroblasts. Disruption of the microtubule network with colchicine did not affect the immunolabeling of the fibrillar network nor did treatment with cytochalasin B known to disrupt the microfilament network. Immunoelectron microscopy with the antitau antibodies revealed colocalization of the label with the 10 nm intermediate filaments, Furthermore, immunoblots found no reactivity against purified vimentin, suggesting that the antibodies recognize an intermediate filament-associated protein. The findings indicate the presence of tau or a protein with considerable homology to tau in fibroblasts associated with intermediate filaments and not microtubules. (C) 1994 Wiley-Liss, Inc. C1 W LOS ANGELES VET AFFAIRS MED CTR,BRENTWOOD DIV,PSYCHOGERIATR UNIT & LAB,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. UNIV SO CALIF,DEPT PSYCHIAT,DIV GERIATR PSYCHIAT,LOS ANGELES,CA. FU NIA NIH HHS [P30 AG10123] NR 31 TC 8 Z9 8 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD DEC 1 PY 1994 VL 39 IS 5 BP 519 EP 524 DI 10.1002/jnr.490390503 PG 6 WC Neurosciences SC Neurosciences & Neurology GA QF969 UT WOS:A1994QF96900002 PM 7534356 ER PT J AU BARKER, FG OGILVY, CS CHIN, JK JOSEPH, MP PILESPELLMAN, J CROWELL, RM AF BARKER, FG OGILVY, CS CHIN, JK JOSEPH, MP PILESPELLMAN, J CROWELL, RM TI TRANSETHMOIDAL TRANSSPHENOIDAL APPROACH FOR EMBOLIZATION OF A CAROTID-CAVERNOUS FISTULA - CASE-REPORT SO JOURNAL OF NEUROSURGERY LA English DT Note DE CAROTID-CAVERNOUS FISTULA; TRANSETHMOIDAL APPROACH; TRANSSPHENOIDAL APPROACH; EMBOLIZATION ID OBLITERATION AB The authors describe a case of carotid-cavernous fistula that was not treatable by the standard interventional neuroradiological techniques of transarterial or transvenous occlusion of the fistula because access was blocked by prior trapping procedures. Access to the venous side of the fistula was gained by means of a transethmoidal transsphenoidal exposure, making it possible to embolize the lesion with coils. The details of this approach are described. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 11 TC 13 Z9 13 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 1994 VL 81 IS 6 BP 921 EP 923 DI 10.3171/jns.1994.81.6.0921 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA PU322 UT WOS:A1994PU32200015 PM 7965123 ER PT J AU YU, JS SHORT, MP SCHUMACHER, J CHAPMAN, PH HARSH, GR AF YU, JS SHORT, MP SCHUMACHER, J CHAPMAN, PH HARSH, GR TI INTRAMEDULLARY HEMORRHAGE IN SPINAL-CORD HEMANGIOBLASTOMA - REPORT OF 2 CASES SO JOURNAL OF NEUROSURGERY LA English DT Note DE HEMANGIOBLASTOMA; INTRAMEDULLARY HEMORRHAGE; SUBARACHNOID HEMORRHAGE; SPINAL CORD TUMOR; VON HIPPEL LINDAU DISEASE ID SUBARACHNOID HEMORRHAGE; TUMOR AB The authors describe two cases of intramedullary hemorrhage caused by thoracic hemangioblastoma. Both patients presented with acute paraplegia. The lesion in the first case was diagnosed by myelography and in the second by magnetic resonance imaging. Emergency surgical evacuation of the intramedullary hematoma and tumor was performed in these patients. Hemangioblastoma was confirmed by histopathological examination in both cases. Both patients remain paraplegic after 7 and 1 years, respectively. Intramedullary hemorrhage is a rare and devastating effect of spinal hemangioblastoma. C1 MASSACHUSETTS GEN HOSP,NEUROPATHOL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP YU, JS (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114, USA. NR 11 TC 31 Z9 32 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 1994 VL 81 IS 6 BP 937 EP 940 DI 10.3171/jns.1994.81.6.0937 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA PU322 UT WOS:A1994PU32200020 PM 7965128 ER PT J AU RITTENHOUSE, PA BAKKUM, EA LEVY, AD LI, Q CARNES, M VANDEKAR, LD AF RITTENHOUSE, PA BAKKUM, EA LEVY, AD LI, Q CARNES, M VANDEKAR, LD TI EVIDENCE THAT ACTH-SECRETION IS REGULATED BY SEROTONIN(2A/2C) (5-HT2A/2C) RECEPTORS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; SERUM CORTICOSTERONE CONCENTRATION; PITUITARY-ADRENOCORTICAL AXIS; RENIN SECRETION; 5-HT RECEPTORS; RAT-BRAIN; SYMPATHOADRENOMEDULLARY SYSTEM; PARA-CHLOROAMPHETAMINE; MESSENGER-RNA AB The present study characterized the serotonin (5-HT) receptor subtypes mediating adrenal corticotropic hormone (ACTH) and corticosterone responses to 5-HT agonists in conscious rats. The 5-HT2A/5-HT2C agonist (+/--1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HC1 (DOl) increased plasma ACTH and corticosterone in a dose-dependent manner. The 5-HT2A/5HT(2C) antagonist ritanserin (0.01 and 0.1 mg/kg sc) inhibited the DOl-induced increase in plasma ACTH, but not corticosterone. Low doses of spiperone (0.01 and 0.1 mg/kg sc) significantly reduced the ACTH response to DOl. Because spiperone has a higher affinity for 5-HT2A than 5-HT2C receptors, these data suggest that DOl stimulates ACTH secretion through 5-HT2A receptors. 5-methoxy-3-[1,2,3,4-tetrahydro-4-pyridinyl]-1 H-indole (RU 24969) is a potent 5-HT1A/1B and moderate S-HT2C agonist that also has been suggested to release 5-HT. However, p-chlorophenylalanine (PCPA) did not reduce the effect of RU 24969 on plasma ACTH, suggesting that RU 24969 only acts as a direct agonist. and 6-methyl-1-[1-methylethyl]ergoline-8-carboxylic acid (LY53857) injected into the lateral cerebral ventricles (i.c.v.) inhibited the ACTH, but not corticosterone response to peripheral injection of RU 24969, suggesting that central 5-HT2A/2C receptors mediate the ACTH response. LY53857 injection (i.c.v.) also inhibited the effect of p-chloroamphetamine (i.c.v.) on plasma ACTH. However, the corticosterone response was not inhibited by LY53857, suggesting a distinct location of 5-HT receptors regulating corticosterone secretion. Lesions using the cell-selective neurotoxin ibotenic acid in the hypothalamic paraventricular nucleus significantly lowered the ACTH response to both RU 24969 (43% decrease) and p-chloroamphetamine (26% decrease). In contrast, lesions in the dorsomedial or ventromedial nuclei did not alter the ACTH response to p-chloroamphetamine. The corticosterone response followed the ACTH response in each of these experiments. The results from these experiments suggest the following: (1) a greater role exists for 5-HT2A than 5-HT2C receptors in the hypothalamus in mediating DOl's effect on ACTH secretion; (2) a peripheral 5-HT receptor is important in stimulating corticosterone secretion, independent or separate from control by ACTH and (3) relatively modest increases in plasma ACTH produce maximal increases in plasma corticosterone. C1 LOYOLA UNIV,STRITCH SCH MED,DEPT PHARMACOL,MAYWOOD,IL 60153. BOSTON UNIV,MED CTR,DEPT PHARMACOL,BOSTON,MA 02118. WILLIAM S MIDDLETON MEM VET ADM MED CTR,GERIATR SECT,MADISON,WI 53705. FU NIMH NIH HHS [MH-45812] NR 55 TC 42 Z9 44 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1994 VL 271 IS 3 BP 1647 EP 1655 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PX343 UT WOS:A1994PX34300071 PM 7996480 ER PT J AU SZACHNOWSKI, P BRIDGES, AJ AF SZACHNOWSKI, P BRIDGES, AJ TI SUBCUTANEOUS CHOLESTEROL NODULES SO JOURNAL OF RHEUMATOLOGY LA English DT Letter ID DIAGNOSIS; DISEASE RP SZACHNOWSKI, P (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705, USA. NR 9 TC 3 Z9 3 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 1994 VL 21 IS 12 BP 2391 EP 2392 PG 2 WC Rheumatology SC Rheumatology GA PX446 UT WOS:A1994PX44600047 PM 7699652 ER PT J AU SOBER, AJ AF SOBER, AJ TI MALIGNANT-MELANOMA IN A CHILD SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter RP SOBER, AJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BARTLETT 410,BOSTON,MA 02114, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 1994 VL 31 IS 6 BP 1078 EP 1078 PG 1 WC Dermatology SC Dermatology GA PT856 UT WOS:A1994PT85600038 PM 7962771 ER PT J AU YOSHIKAWA, TT AF YOSHIKAWA, TT TI RISKS OF LONG-TERM URETHRAL CATHETERIZATION SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID URINARY RP YOSHIKAWA, TT (reprint author), US DEPT VET AFFAIRS,WASHINGTON,DC, USA. NR 9 TC 1 Z9 1 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 1994 VL 42 IS 12 BP 1304 EP 1304 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA PV279 UT WOS:A1994PV27900017 PM 7983299 ER PT J AU OBARA, K MEYER, JS MORTEL, KF MURAMATSU, K AF OBARA, K MEYER, JS MORTEL, KF MURAMATSU, K TI COGNITIVE DECLINES CORRELATE WITH DECREASED CORTICAL VOLUME AND PERFUSION IN DEMENTIA OF ALZHEIMER-TYPE SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE ALZHEIMERS DISEASE; CEREBRAL ATROPHY; CEREBRAL BLOOD FLOW; COMPUTED TOMOGRAPHY; CT DENSITY; LONGITUDINAL STUDIES ID CEREBRAL BLOOD-FLOW; COMPUTED-TOMOGRAPHY; SENILE DEMENTIA; PRESENILE-DEMENTIA; VENTRICULAR SIZE; LONGITUDINAL CT; DISEASE; PROGRESSION; PERFORMANCE; DIAGNOSIS AB Cerebral CT changes are correlated with cognitive declines among 18 patients with probable dementia of Alzheimer type (DAT) (7 men, 11 women, mean age 75.4 years) and are compared for control purposes with similar measures among 18 age-matched normal volunteers (8 men, 10 women, mean age 73.7 years). Mean follow-up intervals are 28.6 months for DAT and 27.0 months for controls. For DAT, annual rates for ventricular volume enlargement are + 9.2% and for cortical atrophy are -2.1%. Annual reductions in regional cerebral perfusions per 100 g brain/min, are: total cortex -1.1 ml, frontal -1.2 ml, temporal and parietal -0.9 ml, basal ganglia -1.6 ml, thalamus - 2.5 ml, total white matter - 0.6 ml, frontal white matter - 0.7 ml. At entry evaluation, compared to normals, DAT patients had reduced CT densities in white matter, but not in cortex. Nevertheless, cortical CT densities declined progressively at annual rates of -0.72 Hounsfield units (HU), but remained constant in white matter. Annual point score declines for Cognitive Capacity Screening Examinations were -2.0 and for Mini Mental State: -2.8. Controls showed no cognitive change. Multiple regression analyses correlate cognitive declines with: (1) reductions in perfusion within parietal cortex (p = 0.015), (2) decreases in cortical volume (p = 0.019), and (3) decreases in HU within subcortical gray matter (p = 0.007). C1 BAYLOR COLL MED,DEPT VET AFFAIRS MED CTR,CEREBROVASC RES LABS,HOUSTON,TX. BAYLOR COLL MED,DEPT NEUROL,HOUSTON,TX. NR 42 TC 35 Z9 35 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD DEC 1 PY 1994 VL 127 IS 1 BP 96 EP 102 DI 10.1016/0022-510X(94)90141-4 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PX672 UT WOS:A1994PX67200013 PM 7699398 ER PT J AU HORNBERGER, LK DALVI, B BENACERRAF, BR AF HORNBERGER, LK DALVI, B BENACERRAF, BR TI PRENATAL SONOGRAPHIC DETECTION OF CARDIAC ANEURYSMS AND DIVERTICULA SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE HEART DISEASE, FETUS; ARRHYTHMIA; ANEURYSM, CARDIAC; DIVERTICULUM, CARDIAC ID LEFT-VENTRICULAR DIVERTICULUM AB We describe three cases of isolated ventricular aneurysm or diverticulum detected antenatally, with subsequent prenatal serial study and postnatal follow-up. Two pregnancies with in utero left ventricular aneurysm, both involving the apex, were referred for fetal atrial arrhythmias at 28 and 25 weeks of gestation, respectively. The aneurysms had a saccular appearance and were thin-walled and hypokinetic. In a third pregnancy, referred for an abnormal four-chamber view, the fetus was found to have a right ventricular aneurysm or divertriculum protruding beneath the tricuspid valve annulus. All three continued to term and at no time demonstrated cardiovascular compromise. C1 HARVARD UNIV,CHILDRENS HOSP,DEPT CARDIOL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. KING EDWARD VII MEM HOSP,DEPT CARDIOL,BOMBAY,INDIA. NR 12 TC 37 Z9 39 U1 0 U2 2 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD DEC PY 1994 VL 13 IS 12 BP 967 EP 970 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA QE409 UT WOS:A1994QE40900008 PM 7877209 ER PT J AU SPARWASSER, C DRESCHER, P WILL, JA MADSEN, PO AF SPARWASSER, C DRESCHER, P WILL, JA MADSEN, PO TI SMOOTH-MUSCLE TONE REGULATION IN RABBIT CAVERNOSAL AND SPONGIOSAL TISSUE BY CYCLIC-AMP-DEPENDENT AND CYCLIC-GMP-DEPENDENT MECHANISMS SO JOURNAL OF UROLOGY LA English DT Article DE CYCLIC AMP; CYCLIC GMP; NITRIC OXIDE; PHOSPHODIESTERASE INHIBITORS; PENIS ID NITRIC-OXIDE; CORPUS CAVERNOSUM; PENILE ERECTION; NONCHOLINERGIC NEUROTRANSMISSION; RELAXATION; CGMP; ENDOTHELIUM; MEDIATOR; PEPTIDE; SIN-1 AB The relaxing effects of several specific and nonspecific inhibitors of phosphodiesterases (PDE) on rabbit isolated corpus cavernosum (CC) and spongiosum (CS) were investigated. Preparations were mounted in organ baths, and isometric tension was recorded. The results were compared with the effects of direct administration of analogs of the second messenger cyclic nucleotides and the effects of forskolin, a direct stimulator of adenylate cyclase, and the nitric oxide donor 3-morpholinosydnonimine (SIN 1). All drugs relaxed the phenylephrine-induced contractions in CC and CS in a dose-dependent fashion. In CC: and CS, type III (SK&F 95654) and type V (zaprinast and dipyramidole) PDE inhibitors, as well as the nonspecific inhibitors papaverine and trequinsin, showed no differences in IC50. The type IV inhibitor rolipram relaxed CC and CS at significantly lower concentrations (p<0.005) than any other PDE inhibitor, and in CC the type III and IV inhibitor zardaverine was more potent (p<0.05) than SK&F 95654. SIN 1 stimulates guanylate cyclase and effectively inhibits contractions in CC and CS. Activation of adenylate cyclase by forskolin also was highly effective (p<0.005). It is concluded that PDE inhibition constitutes an effective relaxing mechanism in rabbit CC and CS. The marked effects of the different types of PDE inhibitors support the importance of cyclic guanosine 3',5'-monophosphate and cyclic adenosine 3',5'-monophosphate in smooth muscle relaxation in erectile tissue. C1 UNIV WISCONSIN,SCH MED,DEPT SURG,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,UROL SECT,MADISON,WI 53705. UNIV WISCONSIN,SCH MED,DEPT ANESTHESIOL,MADISON,WI. UNIV WISCONSIN,SCH MED,DEPT ANIM HLTH & BIOMED SCI,MADISON,WI. NR 27 TC 34 Z9 34 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 1994 VL 152 IS 6 BP 2159 EP 2163 PN 1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA PR245 UT WOS:A1994PR24500081 PM 7966707 ER PT J AU MULUK, SC GERTLER, JP BREWSTER, DC CAMBRIA, RP LAMURAGLIA, GM MONCURE, AC DARLING, RC ABBOTT, WM CRONENWETT, JL BABU, SC HAIMOV, M GRAHAM, A AF MULUK, SC GERTLER, JP BREWSTER, DC CAMBRIA, RP LAMURAGLIA, GM MONCURE, AC DARLING, RC ABBOTT, WM CRONENWETT, JL BABU, SC HAIMOV, M GRAHAM, A TI PRESENTATION AND PATTERNS OF AORTIC-ANEURYSMS IN YOUNG-PATIENTS SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 8th Annual Meeting of the Eastern-Vascular-Society CY MAY 12-15, 1994 CL MONTREAL, CANADA SP E VASC SOC ID SUGGESTED STANDARDS; PATHOGENESIS; ARTERIAL; SMOKING AB Purpose: Although aortic aneurysm (AA) is primarily a disease of older age groups, younger (<51 years) patients infrequently are admitted requiring AA surgery. We sought to compare the characteristics of these patients with those of a randomly selected group of older patients with AA. Methods: We identified 26 patients with AA (group I) under age 51 (mean age 44.8) treated surgically between 1977 and 1993, after excluding patients with acute aortic dissection, traumatic pseudoaneurysms, and ascending or arch aneurysms, and compared them with 75 randomly selected patients with AA between the ages of 65 and 75 (mean age 70.3) who were surgically treated during the same time period (group II). Results: Prevalence of hypertension, diabetes, coexisting heart, kidney, or occlusive peripheral vascular disease was similar between the two groups, and familial aneurysm rates and sex distribution did not differ significantly. More patients in group I had symptoms at the time of presentation (46% vs 6.7%,p < 0.001), and they also had larger AAs (6.9 cm vs 6.0 cm, p = 0.01). Definable causes of aneurysmal disease, such as Takayasu's, Cogan's, and Marfan syndromes, were more common among the young patients (23% vs 0%, p = 0.01), but most (77%) young patients did not have an identifiable syndrome associated with their aneurysm disease. Group I had a marked shift toward proximal aneurysms, defined as involvement of juxtarenal suprarenal, or thoracoabdominal aorta (46% vs 18% in group II, p < 0.01). This difference persisted even when aneurysms associated with the above syndromes were excluded from consideration (p = 0.02). Cigarette smoking was much more common among the young patients (83% vs 51% in group II,p < 0.01). Smoking in group II was associated with more extensive aneurysm disease (p = 0.04). Conclusions: Aneurysmal disease presenting in the young adult is more likely to be symptomatic and associated with more proximal aortic involvement than aneurysmal disease in older patients. Smoking appears to play an important role in the pathogenesis of aneurysmal disease in the young patient and was associated in our study with more proximal aneurysms among older patients. A subgroup of patients at risk for early and aggressive aneurysm disease is suggested by these data. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,DIV VASC SURG,BOSTON,MA. NR 25 TC 24 Z9 26 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 1994 VL 20 IS 6 BP 880 EP 888 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA PX335 UT WOS:A1994PX33500005 PM 7990182 ER PT J AU YAO, F SCHAFFER, PA AF YAO, F SCHAFFER, PA TI PHYSICAL INTERACTION BETWEEN THE HERPES-SIMPLEX VIRUS TYPE-1 IMMEDIATE-EARLY REGULATORY PROTEINS ICPO AND ICP4 SO JOURNAL OF VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; EARLY POLYPEPTIDE VMW110; DNA-BINDING PROPERTIES; THYMIDINE KINASE GENE; MESSENGER-RNA; MACROMOLECULAR-SYNTHESIS; DELETION MUTANTS; FUNCTIONAL DOMAINS; VIRAL POLYPEPTIDES; EARLY PROMOTERS AB The herpes simplex virus type 1 immediate-early protein ICPO enhances expression of a spectrum of viral genes alone and synergistically with ICP4. To test whether ICPO and ICP4 interact physically, we performed far-Western blotting analysis of proteins from mock-, wild-type, and ICP4 mutant virus infected cells with in vitro-synthesized [S-35]Met-labeled ICPO and ICP4 as probes. The ICP I and ICPO polypeptides synthesized in vitro exhibited molecular weights similar to those of their counterparts in herpes simplex virus type 1-infected cells, and the in vitro-synthesized ICP 1 was able to bind to a probe containing the ICP4 consensus binding site. Far-Western blotting experiments demonstrated that ICPO interacts directly and specifically with ICP I and with itself. To further define the interaction between ICPO and ICP4 we generated a set of glutathione S transferase (GST)-ICPO fusion proteins that contain GST and either ICPO N-terminal amino acids 1 to 244 or 1 to 394 or C-terminal amino acids 395 to 616 or 395 to 775. Using GST-ICPO fusion protein affinity chromatography and in vitro-synthesized [S-35]Met-labeled ICPO and ICP4, ICP4 was shown to interact preferentially with the fusion protein containing ICPO C-terminal amino acids 395 to 775, whereas ICPO interacted efficiently with both the N-terminal GST-ICPO fusion proteins and the C-terminal GST-ICPO fusion proteins containing amino acids 395 to 775. Fusion protein affinity chromatography also demonstrated that the C-terminal 235 amino acid residues of ICP4 are important for efficient interaction with ICPO. Collectively, these results reveal a direct and specific physical interaction between ICPO and ICP4. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV MOLEC GENET, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT MICROBIOL & MOLEC GENET, BOSTON, MA 02115 USA. FU NCI NIH HHS [R37-CA20260] NR 69 TC 52 Z9 54 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1994 VL 68 IS 12 BP 8158 EP 8168 PG 11 WC Virology SC Virology GA PR432 UT WOS:A1994PR43200056 PM 7966607 ER PT J AU DORFMAN, T BUKOVSKY, A OHAGEN, A HOGLUND, S GOTTLINGER, HG AF DORFMAN, T BUKOVSKY, A OHAGEN, A HOGLUND, S GOTTLINGER, HG TI FUNCTIONAL DOMAINS OF THE CAPSID PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; GAG GENE; NUCLEOCAPSID PROTEIN; MATRIX PROTEIN; REVERSE-TRANSCRIPTASE; VIRAL INFECTIVITY; GENOMIC RNA; MUTATIONS; PRECURSOR; PARTICLES AB A series of deletions was introduced into the CA domain of the human immunodeficiency virus type 1 Gag polyprotein to examine its role in virus particle and core formation. The mutations resulted in two phenotypes, indicating the existence of two functionally distinct regions within the CA domain. Deletions within a conserved stretch of 20 amino acids referred to as the major homology region (MHR) and deletions C terminal to this region blocked virus replication and significantly reduced the ability to form viral particles. Deletions N terminal to the MHR also prevented virus replication, but the mutants retained the ability to assemble and release viral particles with the same efficiency as the wild type virus. The mutant particles contained circular rather than cone-shaped cores, and while they were of a density similar to that of wild-type particles, they were more heterogeneous in size. These results indicate that CA domain sequences N terminal to the MHR are essential for the morphogenesis of the mature cone-shaped core. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. BIOMED CTR,DEPT BIOCHEM,S-75123 UPPSALA,SWEDEN. FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI29873, AI28691] NR 48 TC 189 Z9 193 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1994 VL 68 IS 12 BP 8180 EP 8187 PG 8 WC Virology SC Virology GA PR432 UT WOS:A1994PR43200058 PM 7966609 ER PT J AU GORNY, MK MOORE, JP CONLEY, AJ KARWOWSKA, S SODROSKI, J WILLIAMS, C BURDA, S BOOTS, LJ ZOLLAPAZNER, S AF GORNY, MK MOORE, JP CONLEY, AJ KARWOWSKA, S SODROSKI, J WILLIAMS, C BURDA, S BOOTS, LJ ZOLLAPAZNER, S TI HUMAN ANTI-V2 MONOCLONAL-ANTIBODY THAT NEUTRALIZES PRIMARY BUT NOT LABORATORY ISOLATES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; GLYCOPROTEIN GP120; ENVELOPE GLYCOPROTEIN; SURFACE GLYCOPROTEIN; HIV-1 GP120; SOLUBLE CD4; BINDING; EPITOPES; DOMAIN; AFFINITY AB A human immunoglobulin G1 lambda monoclonal antibody (MAb), 697-D, was developed that recognizes the V2 region of human immunodeficiency virus type 1 (HIV-1) gp120. Substitutions at amino acid positions 176/177, 179/180, 183/184, and 192 to 194 in the V2 loop of gp120 each completely abolished the binding capacity of 697-D in an enzyme-linked immunosorbent assay format. Competition analysis with three different neutralizing murine anti-V2 MAbs confirmed the specificity of 697-D. The 697-D epitope is primarily conformation dependent, although there was weak reactivity of the MAb with a V2 peptide spanning residues 161 to 180. Treatment of recombinant gp120 HIVIIIB with sodium metaperiodate, which oxidizes carbohydrates, abolished the binding of the MAb, showing the dependence of the epitope on intact carbohydrates. The broad reactivity of 697-D was displayed by its binding to the gp120 molecules from four of four laboratory isolates and five of five primary isolates. The MAb 697-D neutralized three out of four primary isolates but failed to neutralize any of four laboratory strains of HIV-1, 697-D and a human anti-V3 MAb, 447-52-D, displayed similar potency in neutralizing primary isolates, indicating that the V2 region of gp120, like the V3 region and the CD4-binding domain, can induce potent neutralizing antibodies against HN-I in humans. C1 VET AFFAIRS MED CTR,NEW YORK,NY 10010. NYU,MED CTR,NEW YORK,NY. AARON DIAMOND AIDS RES CTR,NEW YORK,NY. MERCK SHARP & DOHME LTD,RES LABS,W POINT,PA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIROL,BOSTON,MA 02115. FU NIAID NIH HHS [AI 27742, AI 32424, AI 36085] NR 44 TC 151 Z9 153 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1994 VL 68 IS 12 BP 8312 EP 8320 PG 9 WC Virology SC Virology GA PR432 UT WOS:A1994PR43200075 PM 7525987 ER PT J AU FOUREL, I CULLEN, JM SAPUTELLI, J ALDRICH, CE SCHAFFER, P AVERETT, DR PUGH, J MASON, WS AF FOUREL, I CULLEN, JM SAPUTELLI, J ALDRICH, CE SCHAFFER, P AVERETT, DR PUGH, J MASON, WS TI EVIDENCE THAT HEPATOCYTE TURNOVER IS REQUIRED FOR RAPID CLEARANCE OF DUCK HEPATITIS-B VIRUS DURING ANTIVIRAL THERAPY OF CHRONICALLY INFECTED DUCKS SO JOURNAL OF VIROLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE; CARBOCYCLIC ANALOG; + ENANTIOMERS; DNA FRAGMENTS; REPLICATION; INHIBITION; 2'-DEOXYGUANOSINE; MECHANISM; INVITRO; ASSAY AB Duck hepatitis B virus (DHBV) DNA synthesis in congenitally infected ducks is inhibited by 2'-deoxycarbocyclic guanosine (2'-CDG). Three months of therapy reduces the number of infected hepatocytes at least 10 fold (W. S. Mason, J. Cullen, J. Saputelli, T.-T. Wu, C. Liu, W. T. London, E. Lustbader, P. Schaffer, A. P. O'Connell, I. Fourel, C. E. Aldrich, and A. R. Jilbert, Hepatology 19:393-411 1994). The present study was performed to determine the kinetics of disappearance of infected hepatocytes and to evaluate the role of hepatocyte turnover in this process. Essentially all hepatocytes were infected before drug therapy. Oral treatment with 2'-CDG resulted in a prompt reduction in the number of infected hepatocytes. After 2 weeks, only 30 to 50% appeared to still be infected, and less than 10% were detectably infected after 5 weeks of therapy. To assess the possible role of hepatocyte turnover in these changes, 5-bromo-2'-deoxyuridine (BUdR) was administered 8 h before liver biopsy to label host DNA in hepatocytes passing through S phase, and stained nuclei were detected in tissue sections by using an antibody reactive to BUdR. The extent of nuclear labeling after 5 weeks was the same as that before therapy (ca. 1%). However, biopsies taken after 2 weeks of therapy showed a ca. 10-fold elevation in the number of nuclei labeled with BUdR. This result suggested that a rapid clearance of infected hepatocytes by 2'-CDG was caused not just by the inhibition of viral replication but also by an acceleration of the rate of hepatocyte turnover. To test this possibility further, antiviral therapy was carried out with another strong inhibitor of DHBV DNA synthesis, 5-fluoro-2',3'-dideoxy-3'-thiacytidine (524W), which did not accelerate hepatocyte turnover in ducks. 524W administration led to a strong inhibition of virus production but to a slower rate oi decline in the number of infected hepatocytes, so that ca. 50% (and perhaps more) were still infected after 3 months of therapy. In addition, histopathologic evaluation of 2'-CDG-treated ducks revealed liver injury, especially at the start of therapy. No liver damage was observed during 524W therapy. These results imply that clearance of infected hepatocytes from the liver is correlated with hepatocyte turnover. Thus, in the absence of immune clearance or other sources for the accelerated elimination df infected hepatocytes, inhibitors of virus replication would have to be administered for a long period to substantially reduce the burden of infected hepatocytes in the liver. C1 FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. N CAROLINA STATE UNIV,COLL VET MED,DEPT MICROBIOL PATHOL & PARASITOL,RALEIGH,NC 27606. DANA FARBER CANC CTR,BOSTON,MA 02115. BURROUGHS WELLCOME CO,DIV EXPTL THERAPEUT,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA-57425, CA-40737]; NIAID NIH HHS [AI-18641] NR 33 TC 82 Z9 82 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1994 VL 68 IS 12 BP 8321 EP 8330 PG 10 WC Virology SC Virology GA PR432 UT WOS:A1994PR43200076 PM 7966625 ER PT J AU TADDEO, B HASELTINE, WA FARNET, CM AF TADDEO, B HASELTINE, WA FARNET, CM TI INTEGRASE MUTANTS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 WITH A SPECIFIC DEFECT IN INTEGRATION SO JOURNAL OF VIROLOGY LA English DT Note ID MURINE LEUKEMIA-VIRUS; PRODUCTIVE INFECTION; DNA-BINDING; POL GENE; IDENTIFICATION; MUTATIONS; PROTEIN; INVITRO; HIV-1; RECOMBINATION AB A previous genetic analysis of the human immunodeficiency virus type 1 integrase protein failed to identify single amino acid substitutions that only block the integration of viral DNA (C.-G. Shin, B. Taddeo, W. A. Haseltine, and C. M. Farnet, J. Virol. 68:1633-1642, 1994). Additional substitutions of amino acids that are highly conserved among retroviral integrases were constructed in human immunodeficiency virus type 1 and analyzed for their effects on viral protein synthesis and processing, virion morphology, and viral DNA synthesis and integration in an attempt to identify mutants with a specific defect in integration. Four single amino acid substitutions resulted in replication defective viruses. Conservative, single amino acid substitutions of the two invariant aspartic acid residues found in all retroviral integrases prevented the integration of viral DNA and had no detectable effect on the other stages in the viral replication cycle, indicating that these mutants exhibited a specific defect in integration. Mutations at two positions, S-81 and P-109, blocked the integration of viral DNA but also resulted in the production of viral particles that exhibited reduced reverse transcriptase activity, suggesting additional defects in viral replication. Substitution of the highly conserved amino acid T66 had no effect on viral replication in a CD4(+) human T-cell line. This analysis extends the range of possible phenotypes that may be produced by single amino acid substitutions in conserved residues of the integrase protein. C1 HARVARD UNIV,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HUMAN GENOME SCI INC,ROCKVILLE,MD 20850. IST SUPER SANITA,I-00161 ROME,ITALY. FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [U01 AI24845, P30 AI28691] NR 25 TC 75 Z9 76 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1994 VL 68 IS 12 BP 8401 EP 8405 PG 5 WC Virology SC Virology GA PR432 UT WOS:A1994PR43200086 PM 7966634 ER PT J AU BOLDT, DH KOPECKY, KJ HEAD, D GEHLY, G RADICH, JP APPELBAUM, FR AF BOLDT, DH KOPECKY, KJ HEAD, D GEHLY, G RADICH, JP APPELBAUM, FR TI EXPRESSION OF MYELOID ANTIGENS BY BLAST CELLS IN ACUTE LYMPHOBLASTIC-LEUKEMIA OF ADULTS - THE SOUTHWEST-ONCOLOGY-GROUP EXPERIENCE SO LEUKEMIA LA English DT Article ID ACUTE LYMPHOCYTIC-LEUKEMIA; IMMUNOLOGICAL MARKERS; CLASSIFICATION; DIAGNOSIS AB A subset of adult acute lymphoblastic leukemia (ALL) patients have blast cells which ce-express myeloid-associated antigens (MY+ ALL). We have analyzed 113 adult ALL cases for expression of MY-associated antigens (MAA). ALL was diagnosed by standard morphology, cytochemistry, and immunophenotype in central review. MY+ ALL was diagnosed when greater than or equal to 20% of lymphoblasts co-expressed CD13 and/or CD33. Overall incidence of MY+ was 31/113 (27%). MAA expression was not significantly correlated with WBC, blast count, hemoglobin, or hematocrit. MY+ cases were more likely to express B-associated antigens, especially CALLA, and to be FAB L2, Ph+, or to have the BCR-ABL translocation by PCR, but these differences were not statistically significant. All patients were induced with a L10M regimen, and 67 (59%) achieved CR: 43/66 (65%) of B MY neg; 14/29 (48%) of B MY+; 10/16 (63%) T MY neg; and 0/2 T MY+. In age-adjusted analyses CR rate did not differ significantly between MY+ and MY neg patients or between B- and T-cell patients. Of the 113 patients, 84 have died and the remaining 29 patients have been followed for a median of 49 months. In proportional hazards regression analyses adjusting for age and WBC, heterogeneity of survival among the four groups was statistically significant (p = 0.021), largely due to MY status. The mortality rate was 85% greater for MY+ patients compared to MY neg patients (two-tailed p = 0.013). By contrast, survival did not vary significantly between B- and T cell patients. The data indicate that MAA expression is useful for predicting overall survival of adult patients with ALL treated in a L10M protocol. As a predictive factor MAA expression is comparable to the WBC and superior to the more standard stratification by B- or T-cell markers for this group of patients. C1 AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. SW ONCOL GRP, CTR STAT, SEATTLE, WA USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. FRED HUTCHINSON CANC RES CTR, DIV CLIN RES, SEATTLE, WA 98104 USA. FRED HUTCHINSON CANC RES CTR, DIV EXPTL PATHOL, SEATTLE, WA 98104 USA. UNIV WASHINGTON, DEPT MED, SEATTLE, WA USA. SW ONCOL GRP, LEUKEMIA BIOL PROGRAM, SAN ANTONIO, TX USA. RP BOLDT, DH (reprint author), UNIV TEXAS, HLTH SCI CTR, DEPT MED, DIV HEMATOL, 7703 FLOYD CURL DR, SAN ANTONIO, TX 78284 USA. FU NCI NIH HHS [CA 32102] NR 31 TC 45 Z9 45 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 1994 VL 8 IS 12 BP 2118 EP 2126 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA QB451 UT WOS:A1994QB45100013 PM 7807999 ER PT J AU EISENBERG, PJ PAPANICOLAOU, N LEE, MJ YODER, IC AF EISENBERG, PJ PAPANICOLAOU, N LEE, MJ YODER, IC TI DIAGNOSTIC-IMAGING IN THE EVALUATION OF RENAL LYMPHOMA SO LEUKEMIA & LYMPHOMA LA English DT Review DE DIAGNOSTIC IMAGING; RENAL LYMPHOMA AB Renal lymphoma usually is a manifestation of disseminated disease and often is asymptomatic. Occasionally, the kidney(s) may be the major or only demonstrable site of disease, which may then present with a variety of urologic symptoms. The imaging studies should be tailored according to the presenting symptoms and prior history. Currently CT with intravenous contrast material enhancement is the study of choice for both the evaluation of renal involvement as well as staging of the disease. When necessary, CT or sonography may be used to guide percutaneous needle biopsy of suspicious masses. The role of the various imaging techniques, including MR and positron emission tomography, in the evaluation of renal lymphoma is discussed. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV GENITOURINARY RADIOL,BOSTON,MA 02114. NR 0 TC 12 Z9 12 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 1994 VL 16 IS 1-2 BP 37 EP 50 DI 10.3109/10428199409114138 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA PZ969 UT WOS:A1994PZ96900005 PM 7696930 ER PT J AU GLATT, CR AF GLATT, CR TI LETTERS AND DISPATCHES, 1924-1944 - WALLENDERG,R SO LIBRARY JOURNAL LA English DT Book Review RP GLATT, CR (reprint author), PHILADELPHIA VA MED CTR,PHILADELPHIA,PA, 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 1994 VL 119 IS 21 BP 104 EP 104 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA PX313 UT WOS:A1994PX31300134 ER PT J AU WHITE, RA GEISSLER, EN ADKISON, LR DOWLER, LL ALPER, SL LUX, SE AF WHITE, RA GEISSLER, EN ADKISON, LR DOWLER, LL ALPER, SL LUX, SE TI CHROMOSOMAL LOCATION OF THE MURINE ANION-EXCHANGER GENES ENCODING AE2 AND AE3 SO MAMMALIAN GENOME LA English DT Note ID MOUSE CHROMOSOME-5; MULTIDRUG RESISTANCE; LOCALIZATION; PROTEIN; LOCUS; DNA; MICE; EXPRESSION; MUTATION; CLONING C1 UNIV MISSOURI,SCH MED,KANSAS CITY,MO 64108. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MERCER UNIV,SCH MED,DIV BIOMED SCI,MACON,GA 31207. BETH ISRAEL HOSP,DEPT CELL & MOLEC PHYSIOL,MOLEC MED UNIT,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT CELL & MOLEC PHYSIOL,RENAL UNIT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP WHITE, RA (reprint author), CHILDRENS MERCY HOSP,GENET SECT,KANSAS CITY,MO 64108, USA. FU NIDDK NIH HHS [DK43495] NR 33 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD DEC PY 1994 VL 5 IS 12 BP 827 EP 829 DI 10.1007/BF00292027 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA PZ352 UT WOS:A1994PZ35200022 PM 7894173 ER PT J AU HALL, JA IRISH, JT ROTER, DL EHRLICH, CM MILLER, LH AF HALL, JA IRISH, JT ROTER, DL EHRLICH, CM MILLER, LH TI SATISFACTION, GENDER, AND COMMUNICATION IN MEDICAL VISITS SO MEDICAL CARE LA English DT Article DE GENDER; CONSUMER SATISFACTION; PHYSICIAN AND PATIENT COMMUNICATION ID SEX-DIFFERENCES; PATIENT SATISFACTION; META-ANALYSIS; PHYSICIAN; CARE; WOMEN; MEN; METAANALYSIS; PERFORMANCE; PREFERENCES AB The authors conducted two studies of routine medical visits, investigating the relation of physician gender; patient gender, and physician age to patient satisfaction, and the correlations between communication behaviors and satisfaction separately for different combinations of patient and physician gender. Study 1 was based on videotaped visits to a hospital-based internal medicine practice (n = 97 visits). Study 2 was based on audiotaped visits to 11 different community and hospital-based practices in the United States and Canada (n = 524 visits). In both studies, patients examined by younger physicians, especially younger female physicians, reported lower ratings of satisfaction. These findings were true for male and female patients; however, in both studies, the lowest satisfaction in absolute terms was among male patients examined by younger female physicians. The effects were not explained by patient and physician background characteristics or by measured communication during the visit. Correlations between verbal and nonverbal communication and satisfaction for different combinations of physician and patient gender suggested that gender-related values and expectations influence patients' reactions to physicians' behavior. There also was evidence that patient satisfaction is reflected in the patient's affective behavior during the visit. C1 JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT HLTH POLICY & MANAGEMENT, BALTIMORE, MD USA. MASSACHUSETTS GEN HOSP, DEPT MED, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. CUNY MT SINAI SCH MED, NEW YORK, NY 10029 USA. RP NORTHEASTERN UNIV, DEPT PSYCHOL, 125 NI, BOSTON, MA 02115 USA. RI Roter, Debra/N-8830-2014 FU NCRR NIH HHS [RR07143] NR 47 TC 206 Z9 208 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD DEC PY 1994 VL 32 IS 12 BP 1216 EP 1231 DI 10.1097/00005650-199412000-00005 PG 16 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA PV962 UT WOS:A1994PV96200005 PM 7967860 ER PT J AU SCHIFF, I UTIAN, W AF SCHIFF, I UTIAN, W TI THE GENESIS OF MENOPAUSE SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material C1 CASE WESTERN RESERVE UNIV HOSP,SCH MED,DEPT OBSTET & GYNECOL,CLEVELAND,OH 44106. RP SCHIFF, I (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV WOMEMS CARE,VINCENT MEM OBSTET & GYNECOL SERV,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 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD WIN PY 1994 VL 1 IS 4 BP 179 EP 180 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QB028 UT WOS:A1994QB02800001 ER PT J AU TOMERA, JF LILFORD, K AF TOMERA, JF LILFORD, K TI INDIRECT TALK OF SIGNALING SYSTEMS IN ENDOTOXICOSIS - CROSS-TALK ALTERNATIVES SO METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY LA English DT Article DE ADENOSINE 3'/5' CYCLIC MONOPHOSPHATE; CROSS-TALK; ENDOTOXICOSIS; GUANINE 3'/5' CYCLIC MONOPHOSPHATE; INDIRECT TALK; MOUSE MODEL; SIGNAL TRANSDUCTION; SKELETAL MUSCLE ID GASTROCNEMIUS-MUSCLE; TRAUMA AB This work evaluated indirect talk, a system of communication between two secondary messengers which uses a third modulating messenger/compound for communication. It expands on our previous report (6) of mean levels and univariate linear/non-linear relationships. It presents results using multivariate testing with vectorial modeling. The signal transduction systems (sts) studied through I-125-radioimmunoassay involved: adenosine 3':5'-cyclic monophosphate (cAMP); and the guanylate cyclase sts via guanine 3':5' -cyclic monophosphate (cGMP). Through multivariate testing, the dependency of a specified parameter was determined relative to two or more independent parameters. The contributing aspects of each of the independent variables were assigned to either 2- or 3-dimensional axes. Through the vector analyses the topic of indirect talk was well aspected. Multivariate equations showed that communication between two systems occurred. Vectorial analysis showed that the direct/indirect mechanism of that communication (namely, indirect talk) occurred. Such analysis leads to a greater understanding of endotoxemia that adversely affects skeletal muscle. C1 SHRINERS BURN INST,CLIN PHARMACOL LAB ANESTHESIA,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT ANESTHESIOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA. NR 10 TC 8 Z9 8 U1 0 U2 0 PU J R PROUS SA PI BARCELONA PA APARTADO DE CORREOS 540, 08080 BARCELONA, SPAIN SN 0379-0355 J9 METHOD FIND EXP CLIN JI Methods Find. Exp. Clin. Pharmacol. PD DEC PY 1994 VL 16 IS 10 BP 697 EP 716 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QE363 UT WOS:A1994QE36300003 PM 7723469 ER PT J AU STANLEY, J LINTON, D BURNENS, AP DEWHIRST, FE ON, SLW PORTER, A OWEN, RJ COSTAS, M AF STANLEY, J LINTON, D BURNENS, AP DEWHIRST, FE ON, SLW PORTER, A OWEN, RJ COSTAS, M TI HELICOBACTER PULLORUM SP-NOV - GENOTYPE AND PHENOTYPE OF A NEW SPECIES ISOLATED FROM POULTRY AND FROM HUMAN PATIENTS WITH GASTROENTERITIS SO MICROBIOLOGY-UK LA English DT Article DE HELICOBACTER PULLORUM SP NOV; POLYPHASIC TAXONOMY ID CAMPYLOBACTER-FENNELLIAE; DNA; IDENTIFICATION; CINAEDI; TESTS; DOGS AB Campylobacter-like organisms were isolated from the liver, duodenum and caecum of broiler and layer chickens, and from humans with gastroenteritis. They formed a unique DNA homology group and a polyphasic taxonomic analysis was made of 16 strains. Analysis of the nucleotide sequence of the 16S rRNA gene from seven of the strains identified them as belonging to a single species, within the genus Helicobacter. This conclusion was supported by the studies of relative DNA homology and of total protein electrophoretic patterns. The new species could be biochemically differentiated from other helicobacters and its ultrastructure in the electron microscope was typical of the genus except that the flagellum was not sheathed. We propose the name Helicobacter pullorum sp. nov. for this group. Like H. fennelliae or H. cinaedi it represents another non-gastric urease-negative Helicobacter species colonizing the lower bowel. Its isolation from the livers of chickens with vibrionic hepatitis is significant. We describe a species-specific PCR assay for H. pullorum sp. nov. which will facilitate its identification of further studies of its epidemiology. C1 CENT PUBL HLTH LAB,DIV VIRUS REFERENCE,LONDON NW9 5HT,ENGLAND. UNIV BERN,SWISS NATL REFERENCE LAB FOODBORNE DIS,INST VET BACTERIOL,CH-3012 BERN,SWITZERLAND. FORSYTH DENT CTR,DEPT MOLEC GENET,BOSTON,MA 02115. RP STANLEY, J (reprint author), CENT PUBL HLTH LAB,NATL COLLECT TYPE CULTURES,61 COLINDALE AVE,LONDON NW9 5HT,ENGLAND. FU NIDCR NIH HHS [DE 08303, DE 10374] NR 28 TC 193 Z9 196 U1 0 U2 3 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 1350-0872 J9 MICROBIOL-UK JI Microbiol.-UK PD DEC PY 1994 VL 140 BP 3441 EP 3449 PN 12 PG 9 WC Microbiology SC Microbiology GA PY759 UT WOS:A1994PY75900029 PM 7533595 ER PT J AU MOLNAR, A GEORGOPOULOS, K AF MOLNAR, A GEORGOPOULOS, K TI THE IKAROS GENE ENCODES A FAMILY OF FUNCTIONALLY DIVERSE ZINC-FINGER DNA-BINDING PROTEINS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RECEPTOR-ALPHA-GENE; NF-KAPPA-B; MYELOID-TRANSFORMING GENE; SEQUENCE-SPECIFIC BINDING; T-CELL DEVELOPMENT; TRANSCRIPTION FACTOR; INTERLEUKIN-2 ENHANCER; ONCOPROTEIN BCL-3; CRYSTAL-STRUCTURE; CD3-DELTA GENE AB We previously described the lymphocyte-restricted Ikaros gene encoding a zinc finger DNA-binding protein as a potential regulator of lymphocyte commitment and differentiation. Here, we report the isolation of four additional Ikaros transcripts, products of alternate splicing that encode functionally diverse proteins. The Ikaros proteins contain unique combinations of zinc finger modules that dictate their overall sequence specificity and affinity. The Ik-1 and Ik-2 proteins can both bind, albeit with different affinities, to the same recognition sequences present in a number of lymphocyte-specific regulatory elements. The Ik-3 and the Ik-4 proteins interact only with a subset of these motifs. The Ik-1 and Ik-2 proteins can strongly stimulate transcription, whereas Ik-3 and Ik-4 are weak activators. Significantly, the transcription activation potential of the Ikaros proteins correlates with their subcellular localization. Upon ectopic expression of the Ikaros isoforms in nonlymphoid cells, Ik-1 and Ik-2 localize to the nucleus, whereas Ik-3 and Ik-4 are predominantly found in the cytoplasm. The Ikaros isoforms are expressed differentially in lymphocytes: Ik-1 and Ik-2 mRNAs are the predominating forms, and Ik-4 is present in significant amounts only in early T-cell progenitors, whereas Ik-3 and Ik-5 transcripts are expressed at relatively low levels throughout lymphocyte development. The ability of the Ikaros gene to generate functionally diverse proteins that may participate in distinct regulatory pathways substantiates its role as a master regulator during lymphocyte development. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, CUTANEOUS BIOL RES CTR, BOSTON, MA 02129 USA. FU NIAID NIH HHS [R01AI33062] NR 49 TC 309 Z9 314 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1994 VL 14 IS 12 BP 8292 EP 8303 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PV674 UT WOS:A1994PV67400059 PM 7969165 ER PT J AU FLACH, J BOSSIE, M VOGEL, J CORBETT, A JINKS, T WILLINS, DA SILVER, PA AF FLACH, J BOSSIE, M VOGEL, J CORBETT, A JINKS, T WILLINS, DA SILVER, PA TI A YEAST RNA-BINDING PROTEIN SHUTTLES BETWEEN THE NUCLEUS AND THE CYTOPLASM SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; NUCLEOCYTOPLASMIC TRANSPORT; MESSENGER-RNA; TRANSLOCATION; MUTANT; PORES; LOCALIZATION; NUCLEOLUS; ENVELOPE; OOCYTES AB RNA-binding proteins have been suggested to move in association with RNA as it leaves the nucleus. The NPL3 gene of the yeast Saccharomyces cerevisiae encodes a nuclear protein with consensus RNA-binding motifs and similarity to heterogeneous nuclear ribonucleoproteins and members of the S/R protein family. We show that although Np13 is located in the nucleus, it can shuttle between nuclei in yeast heterokaryons. In contrast, other nucleus-targeted proteins do not leave the nucleus under similar conditions. Mutants missing the RNA-binding motifs or the N terminus are still capable of shuttling in and out of the nucleus. Np13 mutants missing the C terminus fail to localize to the nucleus. Overproduction of Np13 in wild-type cells slows cell growth. This toxicity depends on the presence of a series of unique repeats in the N terminus and localization to the nucleus. We suggest that the properties of Np13 are consistent,vith it being involved in export of RNAs from the nucleus. C1 CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. NR 36 TC 147 Z9 151 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1994 VL 14 IS 12 BP 8399 EP 8407 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PV674 UT WOS:A1994PV67400070 PM 7969175 ER PT J AU HOLLENBERG, AN PESTELL, RG ALBANESE, C BOERS, ME JAMESON, JL AF HOLLENBERG, AN PESTELL, RG ALBANESE, C BOERS, ME JAMESON, JL TI MULTIPLE PROMOTER ELEMENTS IN THE HUMAN CHORIONIC-GONADOTROPIN BETA-SUBUNIT GENES DISTINGUISH THEIR EXPRESSION FROM THE LUTEINIZING-HORMONE BETA-GENE SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE CHORIONIC GONADOTROPIN; LUTEINIZING HORMONE; PLACENTA; TISSUE-SPECIFIC EXPRESSION; GENE REGULATION; GENE EVOLUTION ID ADIPOSE-TISSUE; ALPHA-SUBUNIT; EVOLUTION; PLACENTA; CLUSTER; TRANSCRIPTION; IDENTIFICATION; MECHANISM; PLASMID; REGION AB The beta subunit of human chorionic gonadotropin (CG beta) is encoded by a cluster of six genes, which have developed through gene duplication from an ancestral LH beta gene. Despite approximately 90% sequence homology between the CG beta and LH beta promoters, the CG beta gene is expressed in the placenta, whereas the LH beta promoter is active only in the pituitary. The CG beta gene uses a TATA-less promoter that is located upstream of the transcriptional start site used by the homologous LH beta gene. The purpose of this study was to use the high degree of homology among members of the CG beta gene cluster and between the CG beta and LH beta promoters to localize regulatory elements that confer CG beta expression in the placenta. The 5'-flanking regions of the different CG beta genes were cloned and expressed in JEG-3 placental cells. Naturally occurring sequence variations were correlated with promoter activity and used to identify candidate regulatory elements. Exchanges of homologous sequences in the CG beta 5 and LH beta proximal promoters identified three separate regions between -362 and +104 that are necessary for full basal expression of the CG beta promoter. Site-directed mutagenesis of four evolutionarily divergent sequences near the CG beta transcription start site confirmed the importance of multiple distinct regulatory elements as each of these mutations resulted in an 80% decrease in promoter activity. These data support a model in which placental expression of the CG beta promoter has evolved from an ancestral LH beta promoter by the accumulation of multiple, combinatorial regulatory elements rather than by acquisition of single distinct tissue-specific enhancer. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,THYROID UNIT,BOSTON,MA. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [HD-23519, P-30 HD-23519] NR 36 TC 30 Z9 32 U1 0 U2 2 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD DEC PY 1994 VL 106 IS 1-2 BP 111 EP 119 DI 10.1016/0303-7207(94)90192-9 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA PZ341 UT WOS:A1994PZ34100014 PM 7534731 ER PT J AU SYMES, A LEWIS, S CORPUS, L RAJAN, P HYMAN, SE FINK, JS AF SYMES, A LEWIS, S CORPUS, L RAJAN, P HYMAN, SE FINK, JS TI STAT PROTEINS PARTICIPATE IN THE REGULATION OF THE VASOACTIVE-INTESTINAL-PEPTIDE GENE BY THE CILIARY NEUROTROPHIC FACTOR FAMILY OF CYTOKINES SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID LEUKEMIA-INHIBITORY FACTOR; SIGNAL-TRANSDUCTION PATHWAY; NEUROBLASTOMA CELL-LINE; LEUCINE ZIPPER PROTEINS; DNA-BINDING PROTEIN; TRANSCRIPTION FACTOR; TYROSINE PHOSPHORYLATION; INTERFERON-GAMMA; ONCOSTATIN-M; FACTOR RECEPTOR AB Ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) are members of a family of neuropoietic cytokines that have a broad range of actions on many different neuronal populations. In cultured sympathetic neurons, CNTF and LIF induce transcription of the VIP and other neuropeptide genes as part of a program of differentiation. To gain insight into the nuclear events involved in cytokine-mediated activation of the neuropeptide genes involved in neuronal differentiation, we have investigated the mechanisms of transcriptional activation of the vasoactive intestinal peptide (VIP) gene by the CNTF family of cytokines. In the neuroblastoma cell line NBFL, CNTF, LIF, and a related cytokine, oncostatin-M, activate VIP gene transcription through a 180-base pair cytokine response element (CyRE), Deletion analysis of the VIP CyRE showed that multiple regions within the 180 basepairs are important for cytokine-mediated transcriptional activation of the VIP gene. To one of these regions within the CyRE, cytokine treatment induces binding of a protein complex composed of members of the signal transducers and activators of transcription (STAT) transcription factor family. Mutation of this STAT-binding site attenuates cytokine-mediated transcriptional activation. LIF treatment of primary sympathetic neurons also induced binding of a STAT-containing protein complex to the VIP CyRE. Thus, activation of STAT transcription factors contributes to the induction of the VIP gene by the CNTF family of cytokines and may be involved in cytokine-mediated differentiation of sympathetic neurons. C1 MASSACHUSETTS GEN HOSP, DEPT NEUROL, MOLEC NEUROBIOL LAB, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT, MOLEC & DEV NEUROSCI LAB, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02114 USA. RI Symes, Aviva/S-7471-2016 OI Symes, Aviva/0000-0003-2557-9939 FU NIMH NIH HHS [MH-00892]; NINDS NIH HHS [NS-27514, NS-29767] NR 79 TC 98 Z9 98 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 1994 VL 8 IS 12 BP 1750 EP 1763 DI 10.1210/me.8.12.1750 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QA530 UT WOS:A1994QA53000017 PM 7708062 ER PT J AU MCALLISTER, KA GROGG, KM JOHNSON, DW GALLIONE, CJ BALDWIN, MA JACKSON, CE HELMBOLD, EA MARKEL, DS MCKINNON, WC MURRELL, J MCCORMICK, MK PERICAKVANCE, MA HEUTINK, P OOSTRA, BA HAITJEMA, T WESTERMAN, CJJ PORTEOUS, ME GUTTMACHER, AE LETARTE, M MARCHUK, DA AF MCALLISTER, KA GROGG, KM JOHNSON, DW GALLIONE, CJ BALDWIN, MA JACKSON, CE HELMBOLD, EA MARKEL, DS MCKINNON, WC MURRELL, J MCCORMICK, MK PERICAKVANCE, MA HEUTINK, P OOSTRA, BA HAITJEMA, T WESTERMAN, CJJ PORTEOUS, ME GUTTMACHER, AE LETARTE, M MARCHUK, DA TI ENDOGLIN, A TGF-BETA BINDING-PROTEIN OF ENDOTHELIAL-CELLS, IS THE GENE FOR HEREDITARY HEMORRHAGIC TELANGIECTASIA TYPE-1 SO NATURE GENETICS LA English DT Article ID RGD-CONTAINING GLYCOPROTEIN; HEMORRHAGIC TELANGIECTASIA; RECEPTOR SYSTEM; EXPRESSION; ULTRASTRUCTURE; IDENTIFICATION; BETAGLYCAN; COMPONENT; DISEASE AB Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystemic vascular dysplasia and recurrent haemorrhage. Linkage for some families has been established to chromosome 9q33-q34, In the present study, endoglin, a transforming growth factor beta (TGF-beta) binding protein, was analysed as a candidate gene for the disorder based on chromosomal location, expression pattern and function, We have identified mutations in three affected individuals: a C to G substitution converting a tyrosine to a termination codon, a 39 base pair deletion and a 2 basepair deletion which creates a premature termination codon, We have identified endoglin as the HHT gene mapping to 9q3 and have established HHT as the first human disease defined by a mutation in a member of the TGF-beta receptor complex. C1 DUKE UNIV,MED CTR,DEPT GENET,DURHAM,NC 27710. HENRY FORD HOSP,DIV CLIN & MOLEC GENET,DETROIT,MI 48202. UNIV MICHIGAN,MED CTR,CTR HUMAN GENOME,STUDIES FAMILY CORE,ANN ARBOR,MI 48109. UNIV VERMONT,COLL MED,DEPT PEDIAT,BURLINGTON,VT 05401. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BOSTON,MA 02129. DUKE UNIV,MED CTR,DIV NEUROL,DURHAM,NC 27710. ERASMUS UNIV ROTTERDAM,DEPT CLIN GENET,3000 DR ROTTERDAM,NETHERLANDS. ST ANTONIUS HOSP,3430 EM NIEUWEGEIN,NETHERLANDS. UNIV EDINBURGH,DEPT HUMAN GENET,EDINBURGH EH4 2XU,MIDLOTHIAN,SCOTLAND. HOSP SICK CHILDREN,DIV IMMUNOL & CANC,RES INST,TORONTO M5G 1X8,ON,CANADA. FU NHLBI NIH HHS [HL 49171] NR 36 TC 862 Z9 890 U1 4 U2 24 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1994 VL 8 IS 4 BP 345 EP 351 DI 10.1038/ng1294-345 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA PV682 UT WOS:A1994PV68200014 PM 7894484 ER PT J AU CASTILLA, LH COUCH, FJ ERDOS, MR HOSKINS, KF CALZONE, K GARBER, JE BOYD, J LUBIN, MB DESHANO, ML BRODY, LC COLLINS, FS WEBER, BL AF CASTILLA, LH COUCH, FJ ERDOS, MR HOSKINS, KF CALZONE, K GARBER, JE BOYD, J LUBIN, MB DESHANO, ML BRODY, LC COLLINS, FS WEBER, BL TI MUTATIONS IN THE BRCA1 GENE IN FAMILIES WITH EARLY-ONSET BREAST AND OVARIAN-CANCER SO NATURE GENETICS LA English DT Article ID CHROMOSOME-17Q21; LINKAGE; REGION; DNA AB We analysed 50 probands with a family history of breast and/or ovarian cancer for germline mutations in the coding region of the BRCA1 candidate gene, using single-strand conformation polymorphism (SSCP) analysis on PCR-amplified genomic DNA. A total Of eight putative disease-causing alterations were identified: four of these are frameshifts and two are nonsense mutations. In addition, we found two missense mutations, one of which changes the final cysteine of the BRCA1 zinc finger motif to glycine. These data are consistent with a tumour suppressor model, and support the notion that this candidate gene is in fact BRCA1. The heterogeneity of mutations, coupled with the large size of the gene, indicates that clinical application of BRCA1 mutation testing will be technically challenging. C1 UNIV PENN,DEPT INTERNAL MED,PHILADELPHIA,PA 19104. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV MICHIGAN,DEPT BIOL,ANN ARBOR,MI 48109. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. UNIV PENN,DEPT OBSTET & GYNECOL,PHILADELPHIA,PA 19104. STRANG CANC PREVENT CTR,NEW YORK,NY 10021. UNIV PENN,DEPT GENET,PHILADELPHIA,PA 19104. FU NCI NIH HHS [R01 CA-61231, R01-CA-57601] NR 26 TC 337 Z9 341 U1 1 U2 6 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1994 VL 8 IS 4 BP 387 EP 391 DI 10.1038/ng1294-387 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA PV682 UT WOS:A1994PV68200021 PM 7894491 ER PT J AU CHANCE, PF LENSCH, MW LIPE, H BROWN, RH BROWN, RH BIRD, TD AF CHANCE, PF LENSCH, MW LIPE, H BROWN, RH BROWN, RH BIRD, TD TI HEREDITARY NEURALGIC AMYOTROPHY AND HEREDITARY NEUROPATHY WITH LIABILITY TO PRESSURE PALSIES - 2 DISTINCT GENETIC-DISORDERS SO NEUROLOGY LA English DT Article ID TOOTH DISEASE TYPE-1A; BRACHIAL-PLEXUS NEUROPATHY; TOMACULOUS NEUROPATHY; DUPLICATION AB Hereditary neuralgic amyotrophy with predilection for the brachial plexus (HNA) and hereditary neuropathy with liability to pressure palsies (HNPP) are autosomal dominant disorders associated with episodic, recurrent brachial neuropathies. HNPP is associated with a deletion or abnormal structure of the PMP22 gene on chromosome 17p11.2-12. The genetic locus for HNA is unknown. To address the possibility that HNPP and HNA might be identical disorders or allelic variations at the same locus, we investigated three HNA pedigrees with markers from the HNPP region. We did not find the 17p11.2-12 deletion associated with HNPP, nor an abnormality in PMP22 structure with HNA. This analysis provides genetic evidence, in addition to that suggested by the clinical, electrophysiologic, and pathologic differences, that HNA and HNPP are distinct disorders. C1 UNIV PENN,SCH MED,DEPT NEUROL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104. UNIV WASHINGTON,SCH MED,DEPT MED,DIV NEUROL,SEATTLE,WA 98195. UNIV WASHINGTON,SCH MED,DEPT MED,DIV MED GENET,SEATTLE,WA 98195. VET ADM MED CTR,SEATTLE,WA 98108. USN,MED CORPS,BOSTON,MA. MASSACHUSETTS GEN HOSP EAST,NEUROMUSCULAR RES LAB,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RP CHANCE, PF (reprint author), UNIV PENN,DIV NEUROL RES,ROOM 6138,34TH & CIVIC CTR BLVD,PHILADELPHIA,PA 19104, USA. NR 27 TC 40 Z9 41 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 1994 VL 44 IS 12 BP 2253 EP 2257 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA PW548 UT WOS:A1994PW54800007 PM 7991108 ER PT J AU STERN, Y ALBERT, M BRANDT, J JACOBS, DM TANG, MX MARDER, K BELL, K SANO, M DEVANAND, DP BYLSMA, F LAFLECHE, G AF STERN, Y ALBERT, M BRANDT, J JACOBS, DM TANG, MX MARDER, K BELL, K SANO, M DEVANAND, DP BYLSMA, F LAFLECHE, G TI UTILITY OF EXTRAPYRAMIDAL SIGNS AND PSYCHOSIS AS PREDICTORS OF COGNITIVE AND FUNCTIONAL DECLINE, NURSING-HOME ADMISSION, AND DEATH IN ALZHEIMERS-DISEASE - PROSPECTIVE ANALYSES FROM THE PREDICTORS STUDY SO NEUROLOGY LA English DT Article ID DEMENTIA; MULTICENTER AB Objective: To examine whether either extrapyramidal signs or psychotic features are associated with more rapid progression of Alzheimer's disease. Background: It has been unclear whether extrapyramidal signs and psychosis are predictors of faster course or are simply late signs. Methods: Two hundred thirty-six patients with mild Alzheimer's disease were recruited in three cities and followed semiannually. Results: Using Cox proportional hazards models that adjusted for age, sex, disease severity, and estimated duration of illness at study entry, the presence of extrapyramidal signs at entry was associated with higher relative risk (RR) of reaching moderate cognitive (RR = 2.35, 95% CI = 1.12 to 4.92) or functional (RR = 2.31, 95% CI = 1.37 to 3.90) severity, nursing home entry (RR = 2.51, 95% CI = 1.32 to 4.76), or death (RR = 3.04, 95% CI = 1.31 to 7.05). Psychosis predicted only the functional end point (RR = 1.85, 95% CI = 1.18 to 2.90). Using regression models, modified Mini-Mental State scores declined 1.30 points (95% CI = 0.16 to 2.44) per 6-month interval, more among patients with than those without extrapyramidal signs; patients with psychosis declined 1.15 (95% CI = 0.52 to 1.77) more mMMS points per interval. Conclusions: This study confirms extrapyramidal signs and psychosis as robust predictors of disease end points and rapid progression in Alzheimer's disease. C1 COLUMBIA UNIV,COLL PHYS & SURG,DEPT NEUROL,NEW YORK,NY 10032. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY 10032. JOHNS HOPKINS UNIV,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. RP STERN, Y (reprint author), COLUMBIA UNIV,COLL PHYS & SURG,GERTRUDE H SERGIEVSKY CTR,630 W 168TH ST,NEW YORK,NY 10032, USA. OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [RR00645]; NIA NIH HHS [AG07370] NR 22 TC 165 Z9 166 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 1994 VL 44 IS 12 BP 2300 EP 2307 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA PW548 UT WOS:A1994PW54800015 PM 7991116 ER PT J AU CUMMINGS, JL MEGA, M GRAY, K ROSENBERGTHOMPSON, S CARUSI, DA GORNBEIN, J AF CUMMINGS, JL MEGA, M GRAY, K ROSENBERGTHOMPSON, S CARUSI, DA GORNBEIN, J TI THE NEUROPSYCHIATRIC INVENTORY - COMPREHENSIVE ASSESSMENT OF PSYCHOPATHOLOGY IN DEMENTIA SO NEUROLOGY LA English DT Article ID PROBABLE ALZHEIMERS-DISEASE; PSYCHIATRIC PHENOMENA; RATING-SCALE; PERSONALITY ALTERATIONS; DISORDERS; PSYCHOSIS; DELUSIONS; SYMPTOMS; PREDICTORS; DEPRESSION AB We developed a new instrument, the Neuropsychiatric Inventory (NPI), to assess 10 behavioral disturbances occurring in dementia patients: delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability/lability, apathy, and aberrant motor activity. The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions. Both the frequency and the severity of each behavior are determined. Information for the NPI is obtained from a caregiver familiar with the patient's behavior. Studies reported here demonstrate the content and concurrent validity as well as between-rater, test-retest, and internal consistency reliability; the instrument is both valid and reliable. The NPI has the advantages of evaluating a wider range of psychopathology than existing instruments, soliciting information that may distinguish among different etiologies of dementia, differentiating between severity and frequency of behavioral changes, and minimizing administration time. C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT BIOMATH,BIOMATH CONSULTING UNIT,LOS ANGELES,CA 90024. RP CUMMINGS, JL (reprint author), UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,SCH MED,DEPT NEUROL,PSYCHIAT SERV,LOS ANGELES,CA 90073, USA. FU NIA NIH HHS [AG10123] NR 37 TC 3502 Z9 3594 U1 17 U2 117 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1994 VL 44 IS 12 BP 2308 EP 2314 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA PW548 UT WOS:A1994PW54800016 PM 7991117 ER PT J AU LEIFER, D GOLDEN, J KOWALL, NW AF LEIFER, D GOLDEN, J KOWALL, NW TI MYOCYTE-SPECIFIC ENHANCER-BINDING FACTOR 2C EXPRESSION IN HUMAN BRAIN-DEVELOPMENT SO NEUROSCIENCE LA English DT Article ID TRANSCRIPTION FACTORS; ALZHEIMERS-DISEASE; CEREBRAL-CORTEX; GENE FAMILY; RAT-BRAIN; MUSCLE; ELEMENTS; SKELETAL; MEMBER; BOX AB Myocyte-specific enhancer binding factor 2C (MEF2C) activates transcription by binding to the myocyte-specific enhancer binding factor 2 (MEF2) regulatory element and has been shown previously to be expressed in muscle and in the brain. We have now studied MEF2C expression in human brain using an antiserum raised against amino acids 140-238 of MEF2C. Western blotting demonstrated that, in fetal brain. MEF2C-immunoreactive bands have the same apparent molecular weight as those in extracts of COS cells transfected with MEF2C complementary DNA. In adult brain, however, MEF2C-immunoreactive bands have a higher molecular weight. In the cerebral cortex; MEF2C immunoreactivity is present in the cortical plate, and is not found in the intermediate zone or ventricular zone. At 14 weeks of gestation, the earliest age examined, MEF2C immunoreactivity is present in cell nuclei throughout the cortical plate. Subsequently, MEF2C immunoreactivity develops a bilaminate and then a trilaminate distribution, and ultimately is expressed preferentially in layers II, IV and VI of mature neocortex. MEF2C immunoreactivity is also found in entorhinal cortex, hippocampus, claustrum, cerebellum and amygdala, and in scattered cells in the thalamus. These findings suggest a role for MEF2C in postmitotic neuronal differentiation, in particular, in the development of certain cortical layers, but also in differentiation of other neurons as well. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. CHILDRENS HOSP,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT NEUROPATHOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT NEUROPATHOL,BOSTON,MA. VET ADM MED CTR,DEPT NEUROL & PATHOL,BEDFORD,MA. BOSTON UNIV,SCH MED,BOSTON,MA 02118. RP LEIFER, D (reprint author), YALE UNIV,SCH MED,DEPT NEUROL,LCI 7,333 CEDAR ST,NEW HAVEN,CT 06510, USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NICHD NIH HHS [HD00888]; NINDS NIH HHS [NS10828, NS25588] NR 30 TC 64 Z9 64 U1 0 U2 1 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 1994 VL 63 IS 4 BP 1067 EP 1079 DI 10.1016/0306-4522(94)90573-8 PG 13 WC Neurosciences SC Neurosciences & Neurology GA PV921 UT WOS:A1994PV92100016 PM 7700509 ER PT J AU AIELLO, LP AVERY, RL ARRIGG, PG KEYT, BA JAMPEL, HD SHAH, ST PASQUALE, LR THIEME, H IWAMOTO, MA PARK, JE NGUYEN, HV AIELLO, LM FERRARA, N KING, GL AF AIELLO, LP AVERY, RL ARRIGG, PG KEYT, BA JAMPEL, HD SHAH, ST PASQUALE, LR THIEME, H IWAMOTO, MA PARK, JE NGUYEN, HV AIELLO, LM FERRARA, N KING, GL TI VASCULAR ENDOTHELIAL GROWTH-FACTOR IN OCULAR FLUID OF PATIENTS WITH DIABETIC-RETINOPATHY AND OTHER RETINAL DISORDERS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PIGMENT EPITHELIAL-CELLS; PERMEABILITY FACTOR; ANGIOGENESIS; NEOVASCULARIZATION; SECRETION; INSULIN; INVIVO AB Background. Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production is increased by hypoxia. Methods. We measured the concentration of VEGF in 210 specimens of ocular fluid obtained from 164 patients undergoing intraocular surgery, using both radioimmunoassays and radioreceptor assays. Vitreous proliferative potential was measured with in vitro assays of the growth of retinal endothelial cells and with VEGF-neutralizing antibody. Results. VEGF was detected in 69 of 136 ocular-fluid samples from patients with diabetic retinopathy, 29 of 38 samples from patients with neovascularization of the iris, and 3 of 4 samples from patients with ischemic occlusion of the central retinal vein, as compared with 2 of 31 samples from patients with no neovascular disorders (P<0.001, P<0.001, and P = 0.006, respectively). The mean (+/-SD) VEGF concentration in 70 samples of ocular fluid from patients with active proliferative diabetic retinopathy (3.6+/-6.3 ng per milliliter) was higher than that in 25 samples from patients with nonproliferative diabetic retinopathy (0.1+/-0.1 ng per milliliter, P = 0.008), 41 samples from patients with quiescent proliferative diabetic retinopathy (0.2+/-0.6 ng per milliliter, P<0.001), or 31 samples from nondiabetic patients (0.1+/-0.2 ng per milliliter, P = 0.003). Concentrations of VEGF in vitreous fluid (8.8+/-9.9 ng per milliliter) were higher than those in aqueous fluid (5.6+/-8.6 ng per milliliter, P = 0.033) in all 10 pairs of samples obtained simultaneously from the same patient; VEGF concentrations in vitreous fluid declined after successful laser photocoagulation. VEGF stimulated the growth of retinal endothelial cells in vitro, as did vitreous fluid containing measurable VEGF. Stimulation was inhibited by VEGF-neutralizing antibodies. Conclusions. Our data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT OPHTHALMOL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV CALIF SANTA BARBARA,NEUROSCI RES INST,SANTA BARBARA,CA 93106. GENENTECH INC,SAN FRANCISCO,CA. JOHNS HOPKINS UNIV HOSP,WILMER OPHTHALMOL INST,DEPT OPHTHALMOL,BALTIMORE,MD. RP AIELLO, LP (reprint author), JOSLIN DIABET CTR,BEETHAM EYE INST,DEPT OPHTHALMOL,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NEI NIH HHS [EY05110]; NIDCR NIH HHS [DERC36836-08] NR 38 TC 2267 Z9 2358 U1 9 U2 71 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 1 PY 1994 VL 331 IS 22 BP 1480 EP 1487 DI 10.1056/NEJM199412013312203 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA PU866 UT WOS:A1994PU86600003 PM 7526212 ER PT J AU WONG, TY MIHM, MC AF WONG, TY MIHM, MC TI PRIMARY SYPHILIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note RP WONG, TY (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 2 Z9 2 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 DEC 1 PY 1994 VL 331 IS 22 BP 1492 EP 1492 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PU866 UT WOS:A1994PU86600005 PM 7969299 ER PT J AU KISTLER, JP AF KISTLER, JP TI THE RISK OF EMBOLIC STROKE - ANOTHER PIECE OF THE PUZZLE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ATRIAL-FIBRILLATION; EMBOLIZATION RP KISTLER, JP (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 15 TC 26 Z9 27 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 DEC 1 PY 1994 VL 331 IS 22 BP 1517 EP 1519 DI 10.1056/NEJM199412013312211 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA PU866 UT WOS:A1994PU86600011 PM 7969305 ER PT J AU SCHMIDTERFURTH, U HASAN, T GRAGOUDAS, E MICHAUD, N FLOTTE, TJ BIRNGRUBER, R AF SCHMIDTERFURTH, U HASAN, T GRAGOUDAS, E MICHAUD, N FLOTTE, TJ BIRNGRUBER, R TI VASCULAR TARGETING IN PHOTODYNAMIC OCCLUSION OF SUBRETINAL VESSELS SO OPHTHALMOLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; SUBFOVEAL NEOVASCULAR MEMBRANES; RETINAL-DETACHMENT; PHOTORADIATION THERAPY; PLASMA-LIPOPROTEINS; ENDOTHELIAL-CELLS; HEMATOPORPHYRIN; THROMBOSIS; TISSUE; TUMORS AB Purpose: To evaluate the potential of photodynamic therapy (PDT) using benzoporphyrin derivative (BPD) for occlusion of subretinal neovascular membranes, the authors studied efficiency and collateral damage of PDT-induced photothrombosis in the rabbit choriocapillary layer. Method: Benzoporphyrin derivative, a new photosensitizer, currently in clinical trials for tumor therapy, was used. Low-density lipoprotein served as a carrier to enhance selective targeting of vascular endothelial cells. Results: Complete choriocapillary occlusion was achieved at a BPD dose of 2 mg/kg and a radiant exposure as low as 10 J/cm(2). When PDT was performed 3 hours after BPD application, damage to the neural retina was minimal. Only inner photoreceptor segments showed mitochondrial swelling probably secondary to choroidal ischemia. Bruch's membrane remained intact. Retinal pigment epithelium was invariably damaged as seen with other photosensitizers. Conclusion: Compared with photocoagulation BPD-PDT allows endothelial-bound intraluminal photothrombosis, sparing important structures such as neural retina and Bruch's membrane. It,may thus provide a more selective treatment of juxtafoveal and subfoveal neovascular membranes. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT RETINA,BOSTON,MA. MED LASERZENTRUM,LUBECK,GERMANY. RP SCHMIDTERFURTH, U (reprint author), UNIV LUBECK,AUGENKLIN,RATZEBURGER ALLEE 160,D-23538 LUBECK,GERMANY. RI Birngruber, Reginald/Q-2342-2016 NR 35 TC 160 Z9 169 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 1994 VL 101 IS 12 BP 1953 EP 1961 PG 9 WC Ophthalmology SC Ophthalmology GA PX412 UT WOS:A1994PX41200015 PM 7997334 ER PT J AU PERROTT, DH LU, YF POGREL, MA KABAN, LB AF PERROTT, DH LU, YF POGREL, MA KABAN, LB TI STABILITY OF SAGITTAL SPLIT OSTEOTOMIES - A COMPARISON OF 3 STABILIZATION TECHNIQUES SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID MANDIBULAR ADVANCEMENT SURGERY; RIGID FIXATION; SKELETAL STABILITY; MACACA-MULATTA; MAXILLOMANDIBULAR FIXATION; ORTHOGNATHIC SURGERY; NONRIGID FIXATION; RAMUS OSTEOTOMY; CLINICAL-TRIALS; WIRE FIXATION AB The objective of this study was to retrospectively evaluate stability of mandibular advancement after bilateral sagittal split osteotomies were performed. Three different fixation and immobilization protocols were examined. Thirty-three patients were evaluated with preoperative, immediate postoperative, and long-term (mean, 13 months) lateral cephalometric radiographs. The patients were divided into three groups: group 1 (n = 10) had nonrigid internal fixation and 6 weeks of maxillomandibular fixation, group 2 (n = 12) had rigid internal fixation and immediate postoperative function, and group 3 (n = 11) had rigid internal fixation with maxillomandibular fixation for a mean of 14 days. Group 3 had the least amount of sagittal and vertical relapse. Differences in sagittal relapse were statistically significant between groups 1 and 3. Group 2 demonstrated greater sagittal relapse than did group 3, although the result was not statistically significant. This study suggests that the use of rigid internal fixation with a period of maxillomandibular fixation appears to be more stable than nonrigid internal fixation with maxillomandibular fixation or rigid internal fixation without maxillomandibular fixation. C1 HARVARD UNIV,SCH DENT MED,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02114. RP PERROTT, DH (reprint author), UNIV CALIF SAN FRANCISCO,DEPT ORAL & MAXILLOFACIAL SURG,BOX 0440,SAN FRANCISCO,CA 94143, USA. FU NCRR NIH HHS [RR5305] NR 44 TC 20 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD DEC PY 1994 VL 78 IS 6 BP 696 EP 704 DI 10.1016/0030-4220(94)90083-3 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PY857 UT WOS:A1994PY85700005 PM 7898905 ER PT J AU LAZOR, JB CUNNINGHAM, MJ EAVEY, RD WEBER, AL AF LAZOR, JB CUNNINGHAM, MJ EAVEY, RD WEBER, AL TI COMPARISON OF COMPUTED-TOMOGRAPHY AND SURGICAL FINDINGS IN DEEP NECK INFECTIONS SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID RETROPHARYNGEAL ABSCESS; CERVICAL FASCIA; HEAD; MANAGEMENT; DIAGNOSIS AB Computed tomography is routinely used in the evaluation of patients suspected to have deep neck infections. This 10-year retrospective study compares preoperative computed tomography scan reports with intraoperative findings in 38 patients who underwent surgical exploration of the parapharyngeal or retropharyngeal space within 48 hours of their radiographic assessment. Overall, intraoperative findings confirmed computed tomography scan interpretation in 76.3% of the patients. The false-positive rate was 13.2%, and the false-negative rate was 10.5%. The sensitivity of computed tomography scan for detection of parapharyngeal space or retropharyngeal space abscess was 87.9%. This study's documentation of false-positive computed tomography scans in the evaluation of deep neck infections emphasizes the importance of correlating radiologic interpretation with clinical examination before surgical intervention. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA. NR 35 TC 83 Z9 85 U1 0 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD DEC PY 1994 VL 111 IS 6 BP 746 EP 750 DI 10.1016/S0194-5998(94)70562-3 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA PX413 UT WOS:A1994PX41300009 PM 7991254 ER PT J AU PERRIN, JM AF PERRIN, JM TI VARIATIONS IN PEDIATRIC HOSPITALIZATION RATES - WHY DO THEY OCCUR SO PEDIATRIC ANNALS LA English DT Article; Proceedings Paper CT Robert A Hoekelman Symposium on Community Pediatrics CY AUG 07, 1993 CL ROCHESTER, NY RP PERRIN, JM (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. FU AHRQ HHS [HS-06060] NR 0 TC 11 Z9 12 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD DEC PY 1994 VL 23 IS 12 BP 676 EP & PG 0 WC Pediatrics SC Pediatrics GA PX657 UT WOS:A1994PX65700005 PM 7892065 ER PT J AU TODRES, ID EARLE, M JELLINEK, MS AF TODRES, ID EARLE, M JELLINEK, MS TI ENHANCING COMMUNICATION - THE PHYSICIAN AND FAMILY IN THE PEDIATRIC INTENSIVE-CARE UNIT SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID PARENTS; CHILDREN; STRESS AB How well does the intensivist communicate with the parents of critically ill children? The authors' experience suggests that this process can be enhanced in a number of ways. The article reviews methods to improve communication by emphasizing the importance of the first meeting, trust, and understanding parental needs and coping mechanisms. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA. RP TODRES, ID (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PEDIAT INTENS CARE UNIT,32 FRUIT ST,BOSTON,MA 02114, USA. NR 24 TC 14 Z9 14 U1 0 U2 1 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 1994 VL 41 IS 6 BP 1395 EP 1404 PG 10 WC Pediatrics SC Pediatrics GA PW136 UT WOS:A1994PW13600013 PM 7984391 ER PT J AU DUGGAN, C KLEINMAN, RE AF DUGGAN, C KLEINMAN, RE TI HOMEOPATHY STUDY QUESTIONS - REPLY SO PEDIATRICS LA English DT Letter RP DUGGAN, C (reprint author), MASSACHUSETTS GEN HOSP,DIV PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02114, USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 1994 VL 94 IS 6 BP 963 EP 963 PN 1 PG 1 WC Pediatrics SC Pediatrics GA PU835 UT WOS:A1994PU83500047 PM 7971031 ER PT J AU KOLLIAS, N BAQER, A SADIQ, I AF KOLLIAS, N BAQER, A SADIQ, I TI MINIMUM ERYTHEMA DOSE DETERMINATION IN INDIVIDUALS OF SKIN TYPE-V AND TYPE-VI WITH DIFFUSE-REFLECTANCE SPECTROSCOPY SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE UVB; PUVA; MED; MPD; ERYTHEMA; MINIMAL ERYTHEMA DOSE; DIFFUSE REFLECTANCE; LASER DOPPLER; SKIN TYPE V ID LASER DOPPLER VELOCIMETRY; QUANTITATIVE ASSESSMENT; ULTRAVIOLET-RADIATION; QUANTIFICATION; INVIVO; FLOW AB Erythema induced by ultraviolet B radiation (UVB) or PUVA (psoralen+UVA) was meadured by diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LD) on patients receiving UV phototherapy and on healthy volunteers of skin type V and VI. The height of the 577 nm absorbance peak of oxyhemoglobin was taken as a measure of erythema intensity. DRS spectra from skin sites exposed to a series of doses were similar in shape. The dose necessary to produce a 0.05 difference in absorbance between 577 nm and 630 nm was determined to be a good indicator of minimal erythema dose (MED) in UVB. DRS measurements proved very reliable in the determination of MED or minimum phototoxic dose) of deeply pigmented subjects. In individuals with skin types V or VI, DRS detects and provides a measure for UVB and PUVA erythema and distinguishes it from melanin pigment, even when the erythema is not obvious. LD measurements lose sensitivity with increasing pigmentation and fail altogether in highly pigmented skin (types V and VI). Diffuse reflectance spectroscopic techniques also make possible the detection of sub-visual threshold reactions. DRS improved the accuracy of MED and MPD determination and the objective standardization of phototesting procedures irrespective of the subject's pigment level. C1 INT RES,NEW YORK,NY. MINIST PUBL HLTH KUWAIT,AL SABAH HOSP,DEPT DERMATOL,KUWAIT,KUWAIT. RP KOLLIAS, N (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. NR 21 TC 33 Z9 34 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD DEC PY 1994 VL 10 IS 6 BP 249 EP 254 PG 6 WC Dermatology SC Dermatology GA QF675 UT WOS:A1994QF67500004 PM 7727281 ER PT J AU SPIELMAN, AI HUQUE, T NAGAI, H WHITNEY, G BRAND, JG AF SPIELMAN, AI HUQUE, T NAGAI, H WHITNEY, G BRAND, JG TI GENERATION OF INOSITOL PHOSPHATES IN BITTER TASTE TRANSDUCTION SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE TASTE; BITTER; INOSITOL PHOSPHATES; G-PROTEINS; PHOSPHOLIPASE C; SIGNAL TRANSDUCTION; INOSITOL 1,4,5-TRISPHOSPHATE ID GTP-BINDING PROTEINS; PHOSPHOLIPASE-C; CELLS; CAFFEINE; CALCIUM; RELEASE; MICE; IDENTIFICATION; MECHANISMS; MEMBRANES AB It is probable that there is a diversity of mechanisms involved in the transduction of bitter taste. One of these mechanisms uses the second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Partial membrane preparations from circumvallate and foliate taste regions of mice tongues responded to the addition of known bitter taste stimuli by increasing the amount of inositol phosphates produced after 30 s incubation. Addition of both the bitter stimulus, sucrose octaacetate and the G-protein stimulant, GTP gamma S, led to an enhanced production of inositol phosphates compared with either alone. Pretreatment of the tissue samples with pertussis toxin eliminated all response to sucrose octaacetate plus GTP gamma S, whereas pretreatment with cholera toxin was without effect. Western blots of solubilized tissue from circumvallate and foliate regions probed with antibodies to the alpha-subunit of several types of G-proteins revealed bands reactive to antibodies against G alpha(i1-2), and G alpha(0),, with no apparent activity to antibodies against G alpha(i3). Given the results from the immunoblots and those of the toxin experiments, it is proposed that the transduction of the bitter taste of sucrose octaacetate in mice involves a receptor-mediated activation of a G(i)-type protein which activates a phospholipase C to produce the two second messengers, IP3 and DAG. C1 MONELL CHEM SENSES CTR, PHILADELPHIA, PA 19104 USA. NYU, COLL DENT, DIV BASIC SCI, NEW YORK, NY USA. SUNTORY LTD, INST FUNDAMENTAL RES, OSAKA, JAPAN. FLORIDA STATE UNIV, DEPT PSYCHOL, TALLAHASSEE, FL 32306 USA. DEPT VET AFFAIRS MED CTR, PHILADELPHIA, PA 19104 USA. UNIV PENN, SCH DENT MED, PHILADELPHIA, PA 19104 USA. NR 35 TC 55 Z9 55 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD DEC PY 1994 VL 56 IS 6 BP 1149 EP 1155 DI 10.1016/0031-9384(94)90359-X PG 7 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA PU103 UT WOS:A1994PU10300006 PM 7878084 ER PT J AU ZHANG, H WANG, J GOODMAN, HM AF ZHANG, H WANG, J GOODMAN, HM TI EXPRESSION OF THE ARABIDOPSIS GENE AKR COINCIDES WITH CHLOROPLAST DEVELOPMENT SO PLANT PHYSIOLOGY LA English DT Article ID ENCODING CHLOROPLAST; THALIANA; PROTEIN; NUCLEAR; BINDING; NOTCH; CAB; TRANSCRIPTION; REGULATORS; SIMILARITY AB Reduced expression of a nuclear gene of Arabidopsis thaliana, Akr, results in the formation of chlorotic plants due to a block in the proplastid-to-chloroplast developmental pathway (H. Zhang, D.C. Scheirer, W. Fowle, H.M. Goodman [1992] Plant Cell 4: 1575-1588). In an effort to discern the function of the Akr gene product in chloroplast development, transgenic plants containing an Akr::beta-glucuronidase gene fusion were constructed to monitor the spatial and temporal patterns of Akr expression. Akr is expressed only in chloroplast-containing tissues and maximal expression occurs during the seedling stage, coincident with chloroplast development. This result is consistent with the hypothesis that Akr is required at an early stage of chloroplast development. The effects of an AKR deficiency on the expression of nuclear and plastid genes required far photosynthetic activity were also examined. Within chloroplast-deficient leaves of plants in which Akr expression is limited by the presence of Akr antisense transgenes or truncated Akr sense transgenes, mRNAs for the nuclear genes Cab2, Cab4, RbcS, and GapA are present at wild-type levels; similarly, levels of mRNAs for the plastid genes rbcL and psbA are not affected by the AKR deficiency. Thus, although expression of these photosynthetic genes is tightly coordinated with the development and maintenance of chloroplasts in wild-type plants, their expression is unaffected in AKR-deficient chlorotic leaves. Therefore, we propose that Akr functions in a pathway different from the one controlling the expression and regulation of the photosynthetic genes during chloroplast development, and at a specific developmental stage after the putative plastid factor is made. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 26 TC 9 Z9 11 U1 0 U2 0 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD DEC PY 1994 VL 106 IS 4 BP 1261 EP 1267 PG 7 WC Plant Sciences SC Plant Sciences GA PY046 UT WOS:A1994PY04600004 ER PT J AU FRUMERSTYRON, N AF FRUMERSTYRON, N TI TEACHING MORE THAN MEDICINE - PSYCHOSOCIAL CONSIDERATIONS IN PEDIATRIC ONCOLOGY - VANEYS,J, COPELAND,DR, DAVIDSON,ER SO PSYCHO-ONCOLOGY LA English DT Book Review RP FRUMERSTYRON, N (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD DEC PY 1994 VL 3 IS 4 BP 333 EP 334 DI 10.1002/pon.2960030412 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA QB326 UT WOS:A1994QB32600010 ER PT J AU KURYLO, DD CORKIN, S GROWDON, JH AF KURYLO, DD CORKIN, S GROWDON, JH TI PERCEPTUAL ORGANIZATION IN ALZHEIMERS-DISEASE SO PSYCHOLOGY AND AGING LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 1993 CL SARASOTA, FL SP Assoc Res Vis & Ophthalmol ID VISUAL DISTURBANCES; AGE-DIFFERENCES; NOISE AB The ability of 16 AD patients and 16 age-matched control Ss to discriminate degraded forms was compared. Also examined were the effects of aging on perceptual organization by comparison of performance of normal Ss ranging in age from 20 to 86 years. Ss discriminated 2 forms, a circle and a square, each composed of randomly distributed dots concurrently embedded in visual noise. By means of a forced-choice procedure, the threshold signal-to-noise ratios at 4 levels of figure degradation were obtained, each presented at 3 durations. Performance by the normal Ss did not vary with age for long-duration stimuli, but did decline with age for briefly presented stimuli. Relative to age-matched control Ss, AD patients had significantly elevated thresholds at all form densities. Disruption of visual processing at the level of perceptual organization is likely a contributing factor to impairment of high-order visual function. C1 MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. MIT,CLIN RES CTR,CAMBRIDGE,MA 02139. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. FU NCRR NIH HHS [RR00088] NR 32 TC 21 Z9 21 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD DEC PY 1994 VL 9 IS 4 BP 562 EP 567 DI 10.1037/0882-7974.9.4.562 PG 6 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA QG007 UT WOS:A1994QG00700007 PM 7893427 ER PT J AU WEISSLEDER, R AF WEISSLEDER, R TI LIVER MR-IMAGING WITH IRON-OXIDES - TOWARD CONSENSUS AND CLINICAL-PRACTICE SO RADIOLOGY LA English DT Editorial Material DE EDITORIALS; IRON; LIVER NEOPLASMS; LIVER, MR; MAGNETIC RESONANCE (MR), CONTRAST ENHANCEMENT; RECEIVER OPERATING CHARACTERISTIC CURVE (ROC) RP WEISSLEDER, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,MR PHARMACEUT PROGRAM,BLDG 149 13TH ST,BOSTON,MA 02129, USA. NR 22 TC 102 Z9 108 U1 1 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1994 VL 193 IS 3 BP 593 EP 595 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PT553 UT WOS:A1994PT55300002 PM 7972790 ER PT J AU BROMLEY, B NADEL, AS PAUKER, S ESTROFF, JA BENACERRAF, BR AF BROMLEY, B NADEL, AS PAUKER, S ESTROFF, JA BENACERRAF, BR TI CLOSURE OF THE CEREBELLAR VERMIS - EVALUATION WITH 2ND-TRIMESTER US SO RADIOLOGY LA English DT Article DE FETUS, CENTRAL NERVOUS SYSTEM; FETUS, GROWTH AND DEVELOPMENT; FETUS, US,; PREGNANCY, US ID DANDY-WALKER MALFORMATION; FETAL CISTERNA MAGNA; SONOGRAPHIC DIAGNOSIS AB PURPOSE: To evaluate with sonography the normal development of the fetal cerebellum in the second trimester. MATERIALS AND METHODS: The study included all patients undergoing second trimester genetic amniocentesis who had structurally normal fetuses, in whom the posterior fossa was adequately seen and in whom the karyotype was later determined to be normal. Views of the cerebellum were obtained prospectively, and the inferior vermis was determined to be open or closed at the time of the initial scan. Follow-up was obtained by means of subsequent scans and review of the pediatric record. RESULTS: Of 897 fetuses that met the inclusion criteria, 147 had an open vermis at initial scanning. At 14 weeks gestation, 56% of fetuses had an open vermis, decreasing to 23% at 15 weeks and 6% at 17 weeks. In utero follow-up sonograms were obtained in 79% of fetuses with an initially open vermis and demonstrated closure in all but one fetus. The remaining 21%, without sonographic follow-up, were normal as newborns. CONCLUSION: The prenatal diagnosis of Dandy-Walker variant should not be made before 18 weeks gestation because the development of the cerebellar vermis may be incomplete at that time. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,COMMUNITY HLTH PLAN,DEPT GENET,BOSTON,MA. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. NR 14 TC 84 Z9 93 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 1994 VL 193 IS 3 BP 761 EP 763 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PT553 UT WOS:A1994PT55300035 PM 7972820 ER PT J AU GOLDBERG, SN PALMER, EL SCOTT, JA FISHER, R AF GOLDBERG, SN PALMER, EL SCOTT, JA FISHER, R TI PULMONARY-EMBOLISM - PREDICTION OF THE USEFULNESS OF INITIAL VENTILATION-PERFUSION SCANNING WITH CHEST RADIOGRAPHIC FINDINGS SO RADIOLOGY LA English DT Article DE EMBOLISM, PULMONARY; LUNG, RADIOGRAPHY; LUNG, RADIONUCLIDE STUDIES ID SCINTIGRAPHY; DIAGNOSIS AB PURPOSE: To evaluate the usefulness of ventilation-perfusion scanning when chest radiographic findings are abnormal to decide which patients should initially undergo angiography because of suspected pulmonary embolism. MATERIALS AND METHODS: The records of 951 patients who underwent examination between April 1, 1992,and August 24, 1993, were reviewed, and the: results of ventilation-perfusion scanning and chest radiography were correlated. RESULTS: Approximately 8% of patients with radiographic findings of no acute disease, pleural effusion, and linear atelectasis had high-probability ventilation-perfusion scans. Pulmonary edema and parenchymal consolidation categories had fewer high-probability studies (3% and 1%, respectively; P < .01). The chance of obtaining a nondiagnostic result was similar for the first three categories (12%) but was more likely for pleural effusion and parenchymal consolidation (36% and 82%, respectively; P < .01). CONCLUSION: The results of ventilation-perfusion scanning are not useful with focal radiographic consolidation. It may be appropriate to proceed directly to pulmonary angiography in many of these patients. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,NUCL MED SECT,BOSTON,MA 02114. NR 11 TC 29 Z9 29 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 1994 VL 193 IS 3 BP 801 EP 805 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PT553 UT WOS:A1994PT55300043 PM 7972828 ER PT J AU GENTILI, A SEEGER, LL YAO, L DO, HM AF GENTILI, A SEEGER, LL YAO, L DO, HM TI ANTERIOR CRUCIATE LIGAMENT TEAR - INDIRECT SIGNS AT MR-IMAGING SO RADIOLOGY LA English DT Article DE KNEE, LIGAMENTS, MENISCI, AND CARTILAGE; KNEE, MR; LIGAMENTS, INJURIES; LIGAMENTS, MR ID KNEE; PATTERNS; INJURY; TIBIA AB PURPOSE: To establish the sensitivity and specificity of indirect signs at magnetic resonance (MR) imaging of anterior cruciate ligament (ACL) tear. MATERIALS AND METHODS: MR images of the knees of 89 consecutive patients (54 with torn and 35 with normal ACLs) were reviewed. RESULTS: The indirect signs were as follows (first percentage is sensitivity; the second, specificity): angle between lateral tibial plateau and ACL less than 45 degrees (90%, 97%); angle between Blumenstaat line and ACL more than 15 degrees (89%, 100%); bone contusions in lateral compartment (54%, 100%); position of posterior cruciate ligament (PCL) line (52%, 91%); PCL angle less than 107 degrees (52%, 94%); PCL bowing ratio more than 0.39 (34%, 100%); posterior displacement of lateral meniscus more than 3.5 mm (44%, 94%); anterior displacement of tibia more than 7 mm (41%, 91%); and lateral femoral sulcus deeper than 1.5 mm (19%, 100%). CONCLUSION: Because the specificity is high, the presence of indirect signs corroborates the diagnosis of ACL tear. Because the sensitivity is low, the absence of these signs does not exclude the diagnosis of ACL tear. C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT RADIOL,LOS ANGELES,CA 90073. RP GENTILI, A (reprint author), UNIV CALIF LOS ANGELES,CTR HLTH SCI,DEPT RADIOL SCI,LOS ANGELES,CA 90073, USA. RI Gentili, Amilcare/G-1238-2013 OI Gentili, Amilcare/0000-0002-5623-7512 NR 20 TC 84 Z9 94 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1994 VL 193 IS 3 BP 835 EP 840 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PT553 UT WOS:A1994PT55300049 PM 7972834 ER PT J AU BRIDGES, AJ HSU, KC SINGH, A CHURCHILL, R MILES, J AF BRIDGES, AJ HSU, KC SINGH, A CHURCHILL, R MILES, J TI FIBRODYSPLASIA (MYOSITIS) OSSIFICANS PROGRESSIVA SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Article ID SOFT-TISSUE; DIPHOSPHONATE; ISOTRETINOIN; THERAPY; CT AB Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary connective tissue disorder. Patients with FOP develop progressive ossification of muscle and connective tissue associated with pain and disability. Onset is typically in childhood, and congenital anomalies of the feet are an early sign of this condition. Pain and stiffness of the spine or an inflammatory mass are common presenting features of FOP. Involvement of the spine often leads to complete fusion mimicking ankylosing spondylitis. Studies of twins and families suggest that FOP is a genetically inherited autosomal dominant trait with complete penetrance but variable expressivity. While radionuclide imaging and computed tomography are very sensitive for new bone formation and greatly assist the diagnosis of FOP, unfortunately, effective therapy is unavailable. We present twins with FOP and review the clinical, radiographic, and genetic manifestations of this disorder. Copyright (C) 1994 by W.B. Saunders Company C1 UNIV MISSOURI HOSP & CLIN,DEPT INTERNAL MED,COLUMBIA,MO. UNIV MISSOURI HOSP & CLIN,DEPT RADIOL,COLUMBIA,MO. UNIV MISSOURI HOSP & CLIN,DEPT NUCL MED,COLUMBIA,MO. UNIV MISSOURI HOSP & CLIN,DEPT PEDIAT,COLUMBIA,MO. RP BRIDGES, AJ (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT INTERNAL MED,MED SERV,2500 OVERLOOK TERRACE,MADISON,WI 53792, USA. NR 70 TC 29 Z9 30 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD DEC PY 1994 VL 24 IS 3 BP 155 EP 164 DI 10.1016/0049-0172(94)90071-X PG 10 WC Rheumatology SC Rheumatology GA PX513 UT WOS:A1994PX51300001 PM 7899873 ER PT J AU MUELLER, PR AF MUELLER, PR TI INTERVENTIONAL RADIOLOGY IN THE VENOUS SYSTEM - EDITORIAL SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Editorial Material RP MUELLER, PR (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD DEC PY 1994 VL 11 IS 4 BP 290 EP 290 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PY225 UT WOS:A1994PY22500001 ER PT J AU KAZANJIAN, SA KAUFMAN, JA AF KAZANJIAN, SA KAUFMAN, JA TI STRATEGIES FOR CENTRAL VENOUS CATHETER PLACEMENT IN PATIENTS WITH LIMITED ACCESS SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 0 TC 11 Z9 11 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD DEC PY 1994 VL 11 IS 4 BP 377 EP 387 DI 10.1055/s-2008-1074777 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PY225 UT WOS:A1994PY22500011 ER PT J AU ROSS, RJ BALL, WA DINGES, DF KRIBBS, NB MORRISON, AR SILVER, SM MULVANEY, FD AF ROSS, RJ BALL, WA DINGES, DF KRIBBS, NB MORRISON, AR SILVER, SM MULVANEY, FD TI MOTOR DYSFUNCTION DURING SLEEP IN POSTTRAUMATIC-STRESS-DISORDER SO SLEEP LA English DT Article DE POSTTRAUMATIC STRESS DISORDER; REM BEHAVIOR DISORDER; MUSCLE TWITCH BURSTS; PERIODIC LIMB MOVEMENTS; NIGHTMARES ID PERIODIC LEG MOVEMENTS; CORTISOL EXCRETION; REM-SLEEP; STARTLE; WAKEFULNESS; VETERANS; COMBAT AB A subjective disturbance of sleep, including the occurrence of repetitive, stereotypical anxiety dreams, is characteristic of posttraumatic stress disorder (PTSD). The phenomenology of the PTSD anxiety dream has seemed most consistent with an underlying rapid eye movement (REM.) sleep dysfunction. However, motor behavior reportedly can accompany PTSD dreams, and normal REM sleep typically involves a nearly total paralysis of the body musculature. As a means of understanding this discrepancy, anterior tibialis muscle activity during sleep was studied in a group of Vietnam combat veterans with current PTSD and in an age-matched normal control group. The PTSD subjects had a higher percentage of REM sleep epochs with at least one prolonged twitch burst; they also were more likely to have periodic limb movements in sleep, during nonrapid eye movement sleep. Both these forms of muscle activation also have been observed in REM behavior disorder (RED), a parasomnia characterized by the actual enactment of dream sequences during REM sleep. The identification of RED-like signs in PTSD adds to the evidence for a fundamental disturbance of REM sleep phasic mechanisms in PTSD. C1 PHILADELPHIA VET AFFAIRS MED CTR,RES SERV,PHILADELPHIA,PA. UNIV PENN,SCH MED,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. UNIV PENN,SCH VET MED,DEPT ANIM BIOL,PHILADELPHIA,PA 19104. COATESVILLE VET AFFAIRS MED CTR,COATESVILLE,PA. FU NIMH NIH HHS [F32-MH-09584-01, MH-42903] NR 46 TC 78 Z9 78 U1 0 U2 3 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 1994 VL 17 IS 8 BP 723 EP 732 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA QB731 UT WOS:A1994QB73100009 PM 7701184 ER PT J AU ABBOTT, RD BEHRENS, GR SHARP, DS RODRIGUEZ, BL BURCHFIELD, CM ROSS, W YANO, K CURB, JD AF ABBOTT, RD BEHRENS, GR SHARP, DS RODRIGUEZ, BL BURCHFIELD, CM ROSS, W YANO, K CURB, JD TI BODY MASS INDEX AND THROMBOEMBOLIC STROKE IN NONSMOKING MEN IN OLDER MIDDLE-AGE - THE HONOLULU-HEART-PROGRAM SO STROKE LA English DT Article DE BODY MASS INDEX; CEREBROVASCULAR DISORDERS RISK FACTORS; THROMBOEMBOLISM ID RISK-FACTORS; PHYSICAL-ACTIVITY; JAPANESE MEN; FOLLOW-UP; CARDIOVASCULAR-DISEASE; CIGARETTE-SMOKING; BLOOD-PRESSURE; MORTALITY; OBESITY; TRENDS AB Background and Purpose While evidence suggests that obesity has an independent relation to coronary artery disease, similar findings for stroke have not been established. The purpose of this study was to examine the relation between body mass index and the risk of thromboembolic stroke independently of other risk factors. Methods Since 1965, the Honolulu Heart Program has followed a cohort of men in a prospective study of cardiovascular disease. This article examines the relationship between the baseline measurement of body mass index and the risk of thromboembolic stroke in 1163 nonsmoking men in older middle age (55 to 68 years). Men who had an elevated risk of stroke due to hypertension, diabetes, and other risk factors were excluded from the analysis. Results After 22 years of follow-up, the rate of stroke increased significantly with increasing levels of body mass (P<.01). In the bottom tertile of the body mass index, the rate of thromboembolic stroke was 28.7 per 1000 (11/383). In the middle tertile, the rate was increased by 40% to 40.7 per 1000 (16/393), and in the top tertile, the rate of thromboembolic stroke was 55.4 per 1000 (21/387), a twofold excess compared with the bottom tertile. After adjustment for age and the residual effects of confounding risk factors, including systolic blood pressure and serum glucose, the estimated relative risk of stroke for the average body mass index in the top tertile (26.6 kg/m(2) compared with that in the bottom tertile (20.3 kg/m(2)) was 2.1 (95% confidence interval, 1.1 to 4.1). These findings were not affected by coronary events that occurred in the course of follow-up, nor did they appear to be influenced by deaths from other causes. Conclusions We conclude that elevated body mass is associated with an increased risk of thromboembolic stroke in nonsmoking men in older middle age who are free of commonly observed conditions related to cardiovascular disease. C1 HONOLULU HEART PROGRAM,HONOLULU,HI. NATL HEART LUNG & BLOOD INST,EPIDEMIOL & BIOMETRY PROGRAM,HONOLULU EPIDEMIOL RES SECT,HONOLULU,HI. UNIV HAWAII,JOHN A BURNS SCH MED,DEPT MED,HONOLULU,HI 96822. US DEPT VET AFFAIRS,KUAKINI MED CTR,HONOLULU ASIA AGING STUDY,HONOLULU,HI. RP ABBOTT, RD (reprint author), UNIV VIRGINIA,SCH MED,DEPT MED,DIV BIOSTAT,BOX 432,CHARLOTTESVILLE,VA 22908, USA. FU NCRR NIH HHS [RR-00847]; NHLBI NIH HHS [N01-HC-05102] NR 45 TC 64 Z9 67 U1 1 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 1994 VL 25 IS 12 BP 2370 EP 2376 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA PV675 UT WOS:A1994PV67500007 PM 7974575 ER PT J AU ABE, T BLACK, PM OJEMANN, RG HEDLEYWHITE, ET AF ABE, T BLACK, PM OJEMANN, RG HEDLEYWHITE, ET TI CEREBRAL EDEMA IN INTRACRANIAL MENINGIOMAS - EVIDENCE FOR LOCAL AND DIFFUSE PATTERNS AND FACTORS ASSOCIATED WITH ITS OCCURRENCE SO SURGICAL NEUROLOGY LA English DT Article DE BRAIN TUMORS; CEREBRAL EDEMA; MENINGIOMAS ID COMPUTED-TOMOGRAPHY; FEATURES AB In a review of 68 meningiomas with good quality computed tomography (CT) scans, 40% had significant CT edema, in the sense of having low absorption around tumor. Two distinct patterns of edema could be distinguished. One was a diffuse white matter process appearing to represent active transudation of water into white matter; this occurred in 43% of tumors with edema. The second, occurring in 57% of tumors with edema, was a localized peritumoral process. This distinction has important pathophysiologic and clinical implications. The diffuse pattern did not appear to reflect tumor size: it was found in 54.6% of tumors from 2 to 4 cm in diameter and 33% of tumors over 4 cm. It appeared more often in tumors of the lateral sphenoid wing or subfrontal region and was more often associated with atypical and syncytial histological type, (p < 0.05, two-tailed t test.). It occurred disproportionately often in atypical tumors and appeared to reflect some intrinsic property of the tumor rather than compression of surrounding structures. C1 BRIGHAM & WOMENS HOSP,NEUROSURG SERV,BOSTON,MA 02115. JIKEI UNIV,SCH MED,NEUROSURG SERV,TOKYO,JAPAN. CHILDRENS HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,NEUROPATHOL SERV,BOSTON,MA. NR 24 TC 29 Z9 31 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO 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 1994 VL 42 IS 6 BP 471 EP 475 DI 10.1016/0090-3019(94)90075-2 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA QB506 UT WOS:A1994QB50600003 PM 7825100 ER PT J AU LEXOW, N JOYCE, JN KIM, SJ PHILLIPS, J CASANOVA, MF BIRD, ED KLEINMAN, JE WINOKUR, A AF LEXOW, N JOYCE, JN KIM, SJ PHILLIPS, J CASANOVA, MF BIRD, ED KLEINMAN, JE WINOKUR, A TI ALTERATIONS IN TRH RECEPTORS IN TEMPORAL-LOBE OF SCHIZOPHRENICS - A QUANTITATIVE AUTORADIOGRAPHIC STUDY SO SYNAPSE LA English DT Article DE THYROTROPIN-RELEASING HORMONE; HUNTINGTONS DISEASE; ALZHEIMERS DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; AMYGDALA; HIPPOCAMPUS ID THYROTROPIN-RELEASING-HORMONE; MESOLIMBIC DOPAMINE SYSTEM; HUMAN-BRAIN; ALZHEIMERS-DISEASE; HIPPOCAMPAL-FORMATION; AMYGDALOID COMPLEX; HUNTINGTONS-DISEASE; MEMORY IMPAIRMENT; SUBSTANTIA NIGRA; CENTRAL NUCLEUS AB We utilized quantitative autoradiography to determine the distribution of receptors for thyrotropin-releasing hormone (TRH) throughout the human temporal lobe and to examine the distribution of these receptors in discrete subregions of the temporal lobe from patients diagnosed premortem with schizophrenia. When compared to non-neurologic controls, schizophrenic patients demonstrated an increase of 51% in the concentration of TRH receptors in the molecular layer of the dentate gyrus. Within nuclei of the schizophrenic amygdala, marked decreases were found in the central (44%), medial (38%), cortical (36%), accessory cortical (52%), lateral (54%), and medial basal (22%) nuclei. We also examined postmortem brain samples from patients with Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease for alterations in the distribution of TRH receptors. No significant differences from non-neuropsychiatric controls were noted within the hippocampus in any of these disease states; however, slight alterations were noted in the central and medial basal amygdala in Huntington's disease and in the cortical amygdala in Alzheimer's disease. These disease-specific findings suggest that TRH may play a role in the neurochemical dysfunction of schizophrenia. (C) 1994 Wiley-Liss, Inc. C1 UNIV PENN,DEPT PHARMACOL,PHILADELPHIA,PA 19104. NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,CTR NEUROSCI,NEUROPATHOL SECT,WASHINGTON,DC 20032. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL NEUROPATHOL,BOSTON,MA 02114. RP LEXOW, N (reprint author), UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104, USA. FU NCRR NIH HHS [2-S07-RR-05415-26]; NIMH NIH HHS [MH00044]; NINDS NIH HHS [R01 NS19597] NR 90 TC 8 Z9 8 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD DEC PY 1994 VL 18 IS 4 BP 315 EP 327 DI 10.1002/syn.890180407 PG 13 WC Neurosciences SC Neurosciences & Neurology GA QH899 UT WOS:A1994QH89900006 PM 7886624 ER PT J AU LIPINSKI, B FEDERMAN, SM KROLEWSKI, AS AF LIPINSKI, B FEDERMAN, SM KROLEWSKI, AS TI COMMENTS ON PLASMA-FIBRINOGEN LEVELS MEASURED BY FUNCTIONAL METHODS SO THROMBOSIS AND HAEMOSTASIS LA English DT Letter C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. RP LIPINSKI, B (reprint author), HS RES LAB,100 INMAN ST,CAMBRIDGE,MA 02139, USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD DEC PY 1994 VL 72 IS 6 BP 985 EP 985 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA PZ130 UT WOS:A1994PZ13000033 PM 7740472 ER PT J AU HERSHMAN, JM AF HERSHMAN, JM TI HIGHLIGHTS OF THIS ISSUE SO THYROID LA English DT Editorial Material RP HERSHMAN, JM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,BLDG 114,ROOM 200,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD WIN PY 1994 VL 4 IS 4 BP 397 EP 397 DI 10.1089/thy.1994.4.397 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QB897 UT WOS:A1994QB89700001 ER PT J AU BUTLER, RB AF BUTLER, RB TI MOOD DISORDERS AFTER NEUROLOGIC INJURY SO TOPICS IN GERIATRIC REHABILITATION LA English DT Article DE ATTENTIONAL DEFICITS; DEPRESSION; MOOD DISORDER ID CLOSED-HEAD INJURY; SELECTIVE ATTENTION; HEMISPHERE STROKE; PERFORMANCE; NEGLECT; BRAIN AB Mood disorders, attentional deficits, and their interrelationship in patients with neurologic injuries are discussed. Neurologic injuries, such as head trauma, stroke, parkinsonism, and Alzheimer's disease, often cause changes in mood. Mood alterations, including depression, mania, and compulsive behavior, are difficult to quantify. Attentional deficits, which are more easily quantified, often accompany mood alterations. The examiner can use tests of attention to identify mood alterations. Recommendations are provided for simple bedside testing of patients with neurologic impairments. C1 EMERSON HOSP,CONCORD,MA. BOSTON UNIV,SARGENT COLL ALLIED HLTH PROFESS,BOSTON,MA 02215. RP BUTLER, RB (reprint author), MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,DEPT PHYS THERAPY,BOSTON,MA 02114, USA. NR 43 TC 1 Z9 1 U1 1 U2 1 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 1994 VL 10 IS 2 BP 70 EP 81 PG 12 WC Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA QE264 UT WOS:A1994QE26400007 ER PT J AU GILLBODY, KM KREBS, DE AF GILLBODY, KM KREBS, DE TI USEFULNESS OF BIOMECHANICAL MEASUREMENT APPROACHES IN REHABILITATION SO TOPICS IN GERIATRIC REHABILITATION LA English DT Article DE BIOMECHANICAL ANALYSIS; MOVEMENT ANALYSIS; REHABILITATION OUTCOME ID POSITIONAL VERTIGO; MOVEMENTS; HABITUATION; CHAIR; POSTUROGRAPHY; BALANCE; ADULTS; AGE AB Several of the biomechanical measurement approaches that are currently used in rehabilitation are reviewed. The reliability and validity of each approach are identified. Selected areas in which clinicians and researchers have applied kinematics, kinetics, and electromyography in an attempt to further understanding of movement dysfunction, motor performance, and response to treatment in individuals with neurologic dysfunction are analyzed to illustrate the usefulness of these approaches. The advantages of whole-body biomechanical analysis, a sophisticated approach that combines kinematics and kinetics, are presented and discussed as they relate to recent findings in patients with vestibulopathy. Many of the current applications of biomechanical analyses are in the research rather than the clinical domain. Current limitations of biomechanical approaches are discussed including their lack of interpretation standards and clear understanding of how biomechanical measures relate to functional performance. C1 MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BIOMOT LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MIT,CAMBRIDGE,MA 02139. RP GILLBODY, KM (reprint author), MASSACHUSETTS GEN HOSP,PHYS THERAPY SERV,BOSTON,MA 02114, USA. NR 49 TC 2 Z9 2 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 1994 VL 10 IS 2 BP 82 EP 96 PG 15 WC Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA QE264 UT WOS:A1994QE26400008 ER PT J AU LEWIS, CB AF LEWIS, CB TI UNTITLED 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 8 TC 0 Z9 0 U1 3 U2 3 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 1994 VL 10 IS 2 BP R5 EP R6 PG 2 WC Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA QE264 UT WOS:A1994QE26400001 ER PT J AU SAKATA, J VACANTI, CA SCHLOO, B HEALY, GB LANGER, R VACANTI, JP AF SAKATA, J VACANTI, CA SCHLOO, B HEALY, GB LANGER, R VACANTI, JP TI TRACHEAL COMPOSITES TISSUE ENGINEERED FROM CHONDROCYTES, TRACHEAL EPITHELIAL-CELLS, AND SYNTHETIC DEGRADABLE SCAFFOLDING SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd International Congress of the Cell-Transplant-Society CY MAY 01-04, 1994 CL MINNEAPOLIS, MN SP Cell Transplant Soc ID RECONSTRUCTION C1 CHILDRENS HOSP,DEPT OTOLARYNGOL & COMMUN DISORDERS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02114. DEBORAH HEART & LUNG CTR,DEPT PATHOL,BROWNS MILLS,NJ. MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. RP SAKATA, J (reprint author), CHILDRENS HOSP,DEPT SURG,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 12 TC 47 Z9 55 U1 0 U2 3 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 1994 VL 26 IS 6 BP 3309 EP 3310 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA PW987 UT WOS:A1994PW98700091 PM 7998148 ER PT J AU STEELE, D WALLSTROM, A BLEIER, KJ TSANG, WG AUSTEN, W AUCHINCLOSS, H CHAPPEL, S AF STEELE, D WALLSTROM, A BLEIER, KJ TSANG, WG AUSTEN, W AUCHINCLOSS, H CHAPPEL, S TI TRANSPLANTATION OF PANCREATIC-ISLETS IN DIABETIC NONHUMAN-PRIMATES SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd International Congress of the Cell-Transplant-Society CY MAY 01-04, 1994 CL MINNEAPOLIS, MN SP Cell Transplant Soc ID T-CELL C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP STEELE, D (reprint author), DIACRIN INC,BOSTON,MA, USA. FU NHLBI NIH HHS [HL36372] NR 8 TC 4 Z9 4 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 1994 VL 26 IS 6 BP 3317 EP 3318 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA PW987 UT WOS:A1994PW98700095 PM 7998152 ER PT J AU CAO, Y VACANTI, JP MA, X PAIGE, KT UPTON, J CHOWANSKI, Z SCHLOO, B LANGER, R VACANTI, CA AF CAO, Y VACANTI, JP MA, X PAIGE, KT UPTON, J CHOWANSKI, Z SCHLOO, B LANGER, R VACANTI, CA TI GENERATION OF NEO-TENDON USING SYNTHETIC-POLYMERS SEEDED WITH TENOCYTES SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd International Congress of the Cell-Transplant-Society CY MAY 01-04, 1994 CL MINNEAPOLIS, MN SP Cell Transplant Soc C1 CHILDRENS HOSP,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. BETH ISRAEL HOSP,DEPT PLAST SURG,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PLAST SURG,BOSTON,MA. MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. DEBORAH HEART & LUNG CTR,DEPT PATHOL,BROWNS MILLS,NJ. RI Ma, Peter/E-4895-2011 NR 7 TC 86 Z9 112 U1 1 U2 3 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 1994 VL 26 IS 6 BP 3390 EP 3392 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA PW987 UT WOS:A1994PW98700135 PM 7998187 ER PT J AU BRUNICARDI, FC KLEINMAN, RM OHNING, G LLOYD, K GINGERICH, R WONG, H WALSH, J AF BRUNICARDI, FC KLEINMAN, RM OHNING, G LLOYD, K GINGERICH, R WONG, H WALSH, J TI THE INHIBITORY ROLE OF INTRAISLET SOMATOSTATIN ON GLUCAGON-SECRETION IN THE ISOLATED-PERFUSED HUMAN PANCREAS SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd International Congress of the Cell-Transplant-Society CY MAY 01-04, 1994 CL MINNEAPOLIS, MN SP Cell Transplant Soc ID MONOCLONAL-ANTIBODY; PARACRINE; INSULIN; INVITRO; INVIVO; CELL C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT SURG,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,CURE,LOS ANGELES,CA. WASHINGTON UNIV,SCH MED,DEPT PEDIAT,ST LOUIS,MO. RP BRUNICARDI, FC (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT SURG,CTR HLTH SCI,ROOM 72-244,10833 LE CONTE AVE,LOS ANGELES,CA 90024, USA. NR 14 TC 4 Z9 4 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 1994 VL 26 IS 6 BP 3451 EP 3452 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA PW987 UT WOS:A1994PW98700171 PM 7998217 ER PT J AU MALUF, HM KOERNER, FC AF MALUF, HM KOERNER, FC TI CARCINOMAS OF THE BREAST WITH ENDOCRINE DIFFERENTIATION - A REVIEW SO VIRCHOWS ARCHIV LA English DT Review DE BREAST CARCINOMA; NEUROENDOCRINE; CARCINOID ID INFILTRATING LOBULAR CARCINOMA; DENSE CORE GRANULES; NEURON-SPECIFIC ENOLASE; OAT-CELL CARCINOMA; ARGYROPHILIC CELLS; MAMMARY-CARCINOMA; FEMALE BREAST; CHROMOGRANIN; VARIANT; TUMORS AB The occurrence of endocrine differentiation in some mammary carcinomas seems well-established, but pathologists continue to debate its significance. Contemporary thinking suggests that endocrine tumours of the breast do not constitute a single clinicopathological entity with a consistent histogenesis but rather that ens docrine differentiation represents a pathway of neoplastic development available to a range of breast cancers. This pattern of differentiation occurs in tumours with vastly different morphological appearances, such as: ductal carcinoma in situ, mucinous carcinoma, a variant of lobular carcinoma, and low grade invasive ductal carcinoma. Although such tumours share some characteristics with intestinal endocrine neoplasms, the typical pattern of intestinal carcinoid virtually never occurs in mammary lesions. Conventional microscopy permits the diagnosis in most cases. Specialized techniques (histochemistry, immunohistochemistry, and electron microscopy) can serve as the basis for diagnosis in the absence of the appropriate morphological features. Although the system of nomenclature proposed by the World Health Organization for use with endocrine tumours in other organs can be used for endocrine tumours of the breast, only a minority of lesions will fit the established criteria. Most lesions are classifiable in the conventional categories of mammary carcinomas. No special prognostic significance is attached to these tumours at the present time. C1 MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. RP VET ADM MED CTR, DEPT PATHOL, 1030 JEFFERSON AVE, MEMPHIS, TN 38104 USA. NR 54 TC 68 Z9 75 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0945-6317 EI 1432-2307 J9 VIRCHOWS ARCH JI Virchows Arch. PD DEC PY 1994 VL 425 IS 5 BP 449 EP 457 PG 9 WC Pathology SC Pathology GA QD252 UT WOS:A1994QD25200001 PM 7850068 ER PT J AU NORGA, K PLESS, M STANULLA, M TEPAS, EC MATHEYPREVOT, B AF NORGA, K PLESS, M STANULLA, M TEPAS, EC MATHEYPREVOT, B TI MULTIPLE TRANSCRIPTION START SITES AND 5' ALTERNATE SPLICING OF MURINE IL-3 RECEPTOR BETA-CHAIN TRANSCRIPTS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID COLONY-STIMULATING FACTOR; PROGENITOR-CELL LINES; INTERLEUKIN-3; CLONING; EXPRESSION; SUBUNITS; GROWTH; GENES AB The murine interleukin-3 receptor beta-chain genes, IL-3R beta(IL-3) and IL-3R beta(C), encode the signal transducing chains of the high affinity receptors for IL-3 and IL-3, GM-CSF and IL-5 respectively. Little is known about the regulation of their expression. To enable the study of the promoters of IL-3R beta(IL-3) and IL-3R beta(C), we have characterized their respective 5' untranslated regions using a modified 5' RACE protocol. Four classes of alternatively spliced transcripts were isolated that initiate in a 400 nt region upstream from a previously reported start site(1). The initially reported partial IL-3R beta(IL-3) clone belongs to the first class of transcripts(2). The second class starts in the middle of an intron as defined by the first class. The 3rd and 4th class establish 2 novel. splice donor sites. These results were confirmed by RNAse-protection assay. The complex organization as evident from our data establishes an experimental framework for future experiments aimed at the study of the promoters for the murine IL-3R beta genes. (C) 1994 Academic Press, Inc. C1 CHILDRENS HOSP,BOSTON,MA 02115. RP NORGA, K (reprint author), HARVARD UNIV,DANA FARBER CANC INST,DIV PEDIAT ONCOL & HEMATOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Stanulla, Martin/D-2528-2010 FU NHLBI NIH HHS [2P01 HL32262] NR 14 TC 1 Z9 1 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 NOV 30 PY 1994 VL 205 IS 1 BP 886 EP 892 DI 10.1006/bbrc.1994.2747 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PW785 UT WOS:A1994PW78500128 PM 7999127 ER PT J AU KOROSHETZ, WJ BONVENTRE, JV AF KOROSHETZ, WJ BONVENTRE, JV TI HEAT-SHOCK RESPONSE IN THE CENTRAL-NERVOUS-SYSTEM SO EXPERIENTIA LA English DT Review DE EXCITOTOXICITY; STROKE; STRESS RESPONSE; NEURO PROTECTION; ISCHEMIA; BRAIN; NEURON ID GLUCOSE-REGULATED PROTEINS; ESCHERICHIA-COLI; CULTURED NEURONS; RAT HIPPOCAMPUS; HYPERTHERMIA PROTECTS; TRANSIENT ISCHEMIA; STATUS EPILEPTICUS; CELL-CULTURE; DNA-BINDING; STRESS AB The heat shock response is induced in nervous tissue in a variety of clinically significant experimental models including ischemic brain injury (stroke), trauma, thermal stress and status epilepticus. Excessive excitatory neurotransmission or the inability to metabolically support normal levels of excitatory neurotransmission may contribute to neuronal death in the nervous system in many of the same pathophysiologic circumstances. We demonstrated that in vitro glutamate-neurotransmitter induced excitotoxicity is attenuated by the prior induction of the heat shock response. A short thermal stress induced a pattern of protein synthesis characteristic of the highly conserved heat shock response and increased the expression of heat shock protein (HSP) mRNA. Protein synthesis was necessary for the neuroprotective effect. The study of the mechanisms of heat shock mediated protection may lead to important clues as to the basic mechanisms underlying the molecular actions of the HSP and the factors important for excitotoxic neuronal injury. The clinical relevance of these findings in vitro is suggested by experiments performed by others in vivo demonstrating that pretreatment of animals with a submaximal thermal or ischemic stress confers protection from a subsequent ischemic insult. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP E,SCH MED,MED SERV,BOSTON,MA 02129. RP KOROSHETZ, WJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL & MED SERV,KENNEDY 915,BOSTON,MA 02114, USA. NR 71 TC 28 Z9 31 U1 0 U2 1 PU BIRKHAUSER VERLAG AG PI BASEL PA PO BOX 133 KLOSTERBERG 23, CH-4010 BASEL, SWITZERLAND SN 0014-4754 J9 EXPERIENTIA JI Experientia PD NOV 30 PY 1994 VL 50 IS 11-12 BP 1085 EP 1091 DI 10.1007/BF01923465 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PV784 UT WOS:A1994PV78400015 PM 7988668 ER PT J AU HEYDARI, AR TAKAHASHI, R GUTSMANN, A YOU, S RICHARDSON, A AF HEYDARI, AR TAKAHASHI, R GUTSMANN, A YOU, S RICHARDSON, A TI HSP70 AND AGING SO EXPERIENTIA LA English DT Review DE AGING; LIVER; TRANSCRIPTION; HEAT SHOCK TRANSCRIPTION FACTOR; RAT; SENESCENCE ID HEAT-SHOCK PROTEINS; AGE-DEPENDENT RESPONSE; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVATION; DIPLOID FIBROBLASTS; STRESS; CELLS; THERMOSENSITIVITY; OLIGOMERIZATION; STIMULATION AB An alteration in the ability of cells to express heat shock proteins could be physiologically important in aging because all living organisms show a reduced ability to respond to stress with increasing age. Using hepatocytes freshly isolated from young adult and old rats, we have shown that the induction of hsp70 expression by heat shock is reduced approximately 50% with age. The decrease in hsp70 expression occurs at the level of transcription and appears to arise from a defect in the heat shock transcription factor. Other investigators have also shown that the induction of hsp70 expression by heat shock as well as other stresses declines significantly with age in a variety of tissues from rats as well as mononuclear cells from human subjects, In addition, a decrease in the inducibility of hsp70 is observed with cell senescence in cultured cells. Therefore, it appears that a reduced ability to express hsp70 in response to stress may be a common phenomenon underlying the aging process. C1 AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. FU NIA NIH HHS [AG01548] NR 43 TC 86 Z9 90 U1 0 U2 4 PU BIRKHAUSER VERLAG AG PI BASEL PA PO BOX 133 KLOSTERBERG 23, CH-4010 BASEL, SWITZERLAND SN 0014-4754 J9 EXPERIENTIA JI Experientia PD NOV 30 PY 1994 VL 50 IS 11-12 BP 1092 EP 1098 DI 10.1007/BF01923466 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PV784 UT WOS:A1994PV78400016 PM 7988669 ER PT J AU LI, SC DEBER, CM SHOELSON, SE AF LI, SC DEBER, CM SHOELSON, SE TI AN IRREGULARITY IN THE TRANSMEMBRANE DOMAIN HELIX CORRELATES WITH THE RATE OF INSULIN-RECEPTOR INTERNALIZATION SO BIOCHEMISTRY LA English DT Article ID M13 COAT PROTEIN; PROLINE RESIDUES; MEMBRANE ENVIRONMENTS; PEPTIDE CONFORMATION; CIRCULAR-DICHROISM; STRUCTURAL BASIS; HYPOTHESIS; MODEL; CELL AB Internalization of insulin and its receptor via receptor-mediated endocytosis is an important step in insulin-induced signal transduction. To investigate the structural determinants underlying the enhanced internalization rate observed for the insulin receptor transmembrane mutant Gly(933)-Pro(934) --> Ala-Ala (GP --> AA), we have designed and chemically synthesized two peptides, IR(TM)-GP and IR(TM)-AA, corresponding respectively to the N-terminal portion of the wild-type and the mutant insulin receptor TM segment containing these sites. Conformational studies by circular dichroism (CD) spectroscopy on these two peptides in their monomeric states revealed that peptide IR(TM)-GP forms an irregular helix in the membrane-mimetic environments of sodium dodecyl sulfate (SDS) micelles with a possible ''kink'' in the helix imposed by its Gly-Pro sequence, while peptide IR(TM)-AA assumes largely classical alpha-helical structure under corresponding conditions. The helical pattern of peptide IR(TM)-AA was maintained at elevated temperatures, while the shape of the CD curve for peptide IR(TM)-GP was found to alter as a function of temperature. At higher concentrations, both peptides formed high molecular weight aggregates in SDS micelles, as demonstrated by SDS-PAGE gels, but peptide IR(TM)-AA was shown to aggregate more readily and more extensively than peptide IR(TM)-GP. Fluorescent dye-leakage experiments indicated that peptide IR(TM)-GP produces an enhanced disruption of the membrane bilayer in phosphatidylglycerol vesicles vs that induced by IR(TM)-AA. The overall results are consistent with the notion that a Gly-Pro kink in the TM helix of the wild-type insulin receptor may submaximize the rate of its internalization by retarding its lateral movement through the plasma membrane and, accordingly, indicate an active role for the TM segment in receptor-mediated endocytosis. C1 HOSP SICK CHILDREN,RES INST,DIV BIOCHEM RES,TORONTO M5G 1X8,ON,CANADA. UNIV TORONTO,DEPT BIOCHEM,TORONTO M5S 1A8,ON,CANADA. BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. NR 36 TC 12 Z9 13 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 29 PY 1994 VL 33 IS 47 BP 14333 EP 14338 DI 10.1021/bi00251a047 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU760 UT WOS:A1994PU76000047 PM 7947843 ER PT J AU SHEA, JA BERLIN, JA ESCARCE, JJ CLARKE, JR KINOSIAN, BP CABANA, MD TSAI, WW HORANGIC, N MALET, PF SCHWARTZ, JS WILLIAMS, SV AF SHEA, JA BERLIN, JA ESCARCE, JJ CLARKE, JR KINOSIAN, BP CABANA, MD TSAI, WW HORANGIC, N MALET, PF SCHWARTZ, JS WILLIAMS, SV TI REVISED ESTIMATES OF DIAGNOSTIC-TEST SENSITIVITY AND SPECIFICITY IN SUSPECTED BILIARY-TRACT DISEASE SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ACUTE CHOLECYSTITIS; NATURAL-HISTORY; HEPATOBILIARY SCINTIGRAPHY; GALLBLADDER-DISEASE; CHOLESCINTIGRAPHY; ULTRASONOGRAPHY; GALLSTONE; CHOLECYSTOGRAPHY; CHOLELITHIASIS; TC-99M-PIPIDA AB Background: The purpose of this study was to estimate the sensitivity and specificity of diagnostic tests for gallstones and acute cholecystitis. Methods: All English-language articles published from 1966 through 1992 about tests used in the diagnosis of biliary tract disease were identified through MEDLINE. From 1614 titles, 666 abstracts were examined and 322 articles were read to identify 61 articles with information about sensitivity and specificity. Application of exclusion criteria based on clinical and methodologic criteria left 30 articles for analysis. Cluster-sampling methods were adapted to obtain combined estimates of sensitivities and specificities. Adjustments were made to estimates that were biased because the gold standard was applied preferentially to patients with positive test results. Results: Ultrasound has the best unadjusted sensitivity (0.97; 95% confidence interval, 0.95 to 0.99) and specificity (0.95; 95% confidence interval, 0.88 to 1.00) for evaluating patients with suspected gallstones. Adjusted values are 0.84 (0.76 to 0.92) and 0.99 (0.97 to 1.00), respectively. Adjusted and unadjusted results for oral cholecystogram were lower. Radionuclide scanning has the best sensitivity (0.97; 95% confidence interval, 0.96 to 0.98) and specificity (0.90; 95% confidence interval, 0.86 to 0.95) for evaluating patients with suspected acute cholecystitis; test performance is unaffected by delayed imaging. Unadjusted sensitivity and specificity of ultrasound in evaluating patients with suspected acute cholecystitis are 0.94 (0.92 to 0.96) and 0.78 (0.61 to 0.96); adjusted values are 0.88 (0.74 to 1.00) and 0.80 (0.62 to 0.98). Conclusions: Ultrasound is superior to oral cholecystogram for diagnosing cholelithiasis, and radionuclide scanning is the test of choice for acute cholecystitis. However, sensitivities and specificities are somewhat lower than commonly reported. We recommend estimates that are midway between the adjusted and unadjusted values. C1 UNIV PENN,CTR CLIN EPIDEMIOL & BIOSTAT,PHILADELPHIA,PA 19104. UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. UNIV PENN,DEPT MED,DIV GASTROENTEROL,PHILADELPHIA,PA 19104. MED COLL PENN,DEPT SURG,PHILADELPHIA,PA 19129. DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,PHILADELPHIA,PA 19107. RP SHEA, JA (reprint author), UNIV PENN,DEPT MED,DIV GEN INTERNAL MED,PHILADELPHIA,PA 19104, USA. FU AHRQ HHS [HS06481] NR 58 TC 102 Z9 103 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 28 PY 1994 VL 154 IS 22 BP 2573 EP 2581 DI 10.1001/archinte.154.22.2573 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA PU597 UT WOS:A1994PU59700006 PM 7979854 ER PT J AU RUBER, E GILBERT, A MONTAGNA, PA GILLIS, G CUMMINGS, E AF RUBER, E GILBERT, A MONTAGNA, PA GILLIS, G CUMMINGS, E TI EFFECTS OF IMPOUNDING COASTAL SALT-MARSH FOR MOSQUITO-CONTROL ON MICROCRUSTACEAN POPULATIONS SO HYDROBIOLOGIA LA English DT Article; Proceedings Paper CT 5th International Conference on Copepoda CY JUN 06-13, 1993 CL UNIV MARYLAND BALTIMORE CTY, BALTIMORE, MD SP UNIV MARYLAND BALTIMORE CTY, SMITHSONIAN INST HO UNIV MARYLAND BALTIMORE CTY DE COPEPODS; SALT MARSH; POOLS; IMPOUNDMENTS; DIVERSITY ID MASSACHUSETTS AB Populations of microcrustaceans were studied for 24 months in two New Jersey high salt marsh impoundments, and in three separate 14 month studies of high salt marsh pools in northeastern Massachusetts. In Massachusetts high marsh pools, dominants were all harpacticoids: Amphiascus pallidus, Cletocamptus deitersi, Harpacticus chelifer, Mesochra lilljeborgii, Metis jousseaumei, and Nitokra lacustris. The cyclopoids Apocyclops spartinus, Halicyclops sp. and the calanoid Eurytemora affinis were also numerically important. While there was extensive overlap, dominants varied to some extent from year to year and among the three studies. The New Jersey saline impoundment fauna showed extreme dominance (low equitability) in the first summer, somewhat less in the second and much less in the third. Total microcrustacean densities also declined each year. Variation in Apocyclops spartinus densities was the major factor, as this species comprised in three consecutive summers, 95, 85 and 51% of the total zooplankton at one station. Diversity as species richness was highest in a New Jersey freshwater impoundment which compared well with South Carolina salt marsh values. Impoundment diversity which was very low, and comparable with that found in a New Jersey Spartina patens marsh, increased each year becoming progressively more like that found in the Massachusetts pools. Vegetation changed significantly in the New Jersey impoundments over the three years. Spartina patens died-off in the first summer, while S. alterniflora gradually declined each year. A visit to the site twenty years later showed all emergent vegetation to be gone. These successional zooplankton and vegetation changes, together with the possible consequences of interrupted marsh-bay exchanges should be considered before undertaking any coastal mosquito control involving permanent flooding. C1 UNIV TEXAS,INST MARINE SCI,PORT ARANSAS,TX 78373. BUNKER HILL COMMUNITY COLL,DEPT NAT SCI,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CTR COMP SERV,BOSTON,MA 02129. RP RUBER, E (reprint author), NORTHEASTERN UNIV,DEPT BIOL,BOSTON,MA 02115, USA. NR 22 TC 3 Z9 3 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0018-8158 J9 HYDROBIOLOGIA JI Hydrobiologia PD NOV 25 PY 1994 VL 293 BP 497 EP 503 DI 10.1007/BF00229977 PG 7 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA QG902 UT WOS:A1994QG90200063 ER PT J AU SHAEFFER, JR AF SHAEFFER, JR TI HETEROGENEITY IN THE STRUCTURE OF THE UBIQUITIN CONJUGATES OF HUMAN ALPHA-GLOBIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEOLYSIS; MULTIUBIQUITIN CHAIN; PROTEIN LIGASE; RECOGNITION; MECHANISM; CLEAVAGE; SYSTEM AB Only monoubiquitinated (and to a much lesser extent diubiquitinated) I-125-alpha globin is observed as a conjugated intermediate in the ATP- and ubiquitin (Ub)-dependent proteolysis of I-122-alpha globin catalyzed by an unfractionated reticulocyte lysate (Shaeffer, J. R. (1994) J. Biol. Chem. 269, 22205-22210). A monoubiquitinated with a dilute acid reagent to selectively cleave the I-125-alpha globin moiety between residues 94 (Asp) and 95 (Pro). Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the resulting polypeptides showed that the Ub(1)-alpha conjugate consisted of a mixture of molecules in which 57% had Ub attached to the amino-terminal two-thirds and 43% had Ub attached to the carboxyl-terminal one-third of the I-125-alpha globin monomer. This amino- to carboxyl-terminal region ubiquitination ratio was essentially unchanged when a Ub(1)-alpha conjugate intermediate, pulse-labeled for 15 min in the presence of ubiquitin aldehyde to inhibit disassembly, was analyzed after (a) a 2-h chase incubation with excess nonradioactive alpha globin or (b) isolation and incubation separately as a proteolysis substrate. Similar analysis of the diubiquitinated I-125-alpha globin (Ub(2)-alpha) conjugate molecules showed that, after pulse labeling, 58% were diubiquitinated within the amino-terminal two-thirds and 42% were monoubiquitinated within both amino- and carboxyl-terminal regions of the I-125-alpha globin moiety (a small amount of molecules diubiquitinated within the carboxyl-terminal region may also be present) and that the relative amounts of these molecular types changed little, if any, during the chase incubation. This invariance in the amino- to carboxyl-terminal region ubiquitination ratio during degradation of the Ub(1)-alpha and Ub(2)-alpha conjugates suggests that I-125-alpha globin molecules ubiquitinated within either the amino- or carboxyl-terminal regions were both intermediates in the proteolysis of the unconjugated substrate. This heterogeneous pattern of Ub conjugation may also occur during the proteolysis of other long-lived intracellular proteins. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. RP SHAEFFER, JR (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL29379] NR 25 TC 7 Z9 7 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 25 PY 1994 VL 269 IS 47 BP 29530 EP 29536 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU284 UT WOS:A1994PU28400036 PM 7961937 ER PT J AU CHI, NW KOLODNER, RD AF CHI, NW KOLODNER, RD TI PURIFICATION AND CHARACTERIZATION OF MSH1, A YEAST MITOCHONDRIAL PROTEIN THAT BINDS TO DNA MISMATCHES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MUTS-ENCODED PROTEIN; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; PYRIMIDINE DIMERS; GENE CONVERSION; RIBOSOMAL-RNA; REPAIR; RECOMBINATION; SEQUENCES AB MSH1 is a homologue of the Escherichia coli MutS gene that is proposed to play an important role in the repair and maintenance of mitochondrial DNA in Saccharomyces cerevisiae (Reenan, R. A., and Kolodner, R. D. (1992) Genetics 132, 975-985). In this study, we demonstrate that msh1/MSH1 strains accumulate point mutations in mitochondria seven times faster than the wild-type. We also show that the MSH1 protein is targeted to the mitochondria where its mitochondrial-targeting sequence is removed. Purified MSH1 hydrolyzes ATP and recognizes DNA substrates containing nucleotide mismatches and unpaired nucleotides. The hierarchy of binding affinity of MSH1 among various mismatches is similar to that of MutS, suggesting that both proteins share a highly conserved scheme for recognizing mismatches. The specific binding of MSH1 to mismatches is more resistant to NaCl inhibition and has a slower dissociation rate as compared to the nonspecific binding to complementary DNA sequences. Our data support the idea that MSH1 plays a role in eliminating biosynthetic errors and homeologous recombination in mitochondrial genome by recognizing premutagenic DNA mismatches. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NHGRI NIH HHS [HG00305]; NIGMS NIH HHS [GM50006] NR 69 TC 118 Z9 121 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1994 VL 269 IS 47 BP 29984 EP 29992 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU284 UT WOS:A1994PU28400102 PM 7961998 ER PT J AU CHIT, NW KOLODNER, RD AF CHIT, NW KOLODNER, RD TI THE EFFECT OF DNA MISMATCHES ON THE ATPASE ACTIVITY OF MSH1, A PROTEIN IN YEAST MITOCHONDRIA THAT RECOGNIZES DNA MISMATCHES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; COLI UVRABC ENDONUCLEASE; BINDING; MUTATIONS; HOMOLOGS; CANCER; GENES AB MSH1 is a DNA-binding protein in yeast mitochondria that recognizes nucleotide mismatches in DNA and plays a role in mitochondrial mutation avoidance (Chi, W., and Kolodner, R. D. (1994) J. Biol. Chem. 269, 29984-29992). MSH1 exhibits an ATPase activity that hydrolyses similar to 1 ATP molecule/min in the absence of DNA, In this study, we show that DNA alters the pH dependence of the MSH1 ATPase and stimulates ATP hydrolysis at neutral pH. Using heteroduplex DNA containing mismatches with various affinity, we show an inverse correlation between the extent of ATPase stimulation by DNA and the binding affinity of MSH1 for the DNA effector. We also show that the presence of ATP increases the mismatch specificity of MSH1-DNA binding. Taken together, the observed interaction between the ATPase and the mismatch-binding activities suggests that MSH1 binds to ATP and mismatches with positive cooperativity. This interaction may provide a system for elucidating the role of ATP in mismatch recognition and repair. C1 DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. NR 31 TC 0 Z9 0 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 25 PY 1994 VL 269 IS 47 BP 29993 EP 29997 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU284 UT WOS:A1994PU28400103 ER PT J AU UMEZU, K KOLODNER, RD AF UMEZU, K KOLODNER, RD TI PROTEIN INTERACTIONS IN GENETIC-RECOMBINATION IN ESCHERICHIA-COLI - INTERACTIONS INVOLVING RECO AND RECR OVERCOME THE INHIBITION OF RECA BY SINGLE-STRANDED DNA-BINDING PROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HOMOLOGOUS RECOMBINATION; GENE-32 PROTEIN; UVSX-PROTEIN; SSB PROTEIN; BACTERIOPHAGE-T4; MUTANT; PURIFICATION; EXCHANGE; CLONING; CHROMATOGRAPHY AB RecA promotes homologous pairing of single-stranded DNA (ssDNA) with double-stranded DNA (dsDNA). This reaction occurs inefficiently if the ssDNA substrate is preincubated with Escherichia coli ssDNA-binding protein (SSB). However, RecO and RecR can act together as accessory factors for RecA to overcome this inhibition by SSB (Umezu, It., Chi, N.-W, and Kolodner, R. D. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 3875-3879). To elucidate the mechanism that underlies this process, we examined protein-protein interactions between Reck RecF, RecO, RecR, and SSB, and characterized the structure and activity of the ssDNA complexes formed with different combinations of these proteins. We obtained the following results. (i) RecO physically interacts with both RecR and SSB. The interaction between RecO and SSB is stronger than the RecO-RecR interaction. (ii) RecO and RecR do not remove SSB from SSB.ssDNA complexes, but instead bind to these complexes. The resulting RecO.RecR.SSB.ssDNA complexes were more active in Reck-mediated joint molecule formation than were SSB.ssDNA complexes. (iii) RecA can nucleate on the RecO.RecR.SSB.ssDNA complexes more efficiently than on SSB.ssDNA complexes. (iv) When RecA presynaptic filaments were formed in the presence of SSB, RecO, and RecR, the protein-DNA complexes obtained contained 70% of the amount of RecA required to saturate ssDNA These complexes, however, can mediate joint molecule formation and strand exchange as efficiently as presynaptic filaments which are fully saturated with Reck Based on these results, we propose dual roles for RecO and RecR in joint molecule formation. First, RecO and RecR bind to SSB.ssDNA complexes and modify their structure to allow RecA to nucleate on them efficiently. Second, RecO and RecR are retained in RecA presynaptic filaments and play a role in the subsequent homologous pairing process promoted by RecA. C1 DANA FARBER CANC INST,DIV CELL & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NIGMS NIH HHS [GM26017] NR 45 TC 186 Z9 188 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1994 VL 269 IS 47 BP 30005 EP 30013 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU284 UT WOS:A1994PU28400105 PM 7962001 ER PT J AU MYERS, AM CHARIFSON, PS OWENS, CE KULA, NS MCPHAIL, AT BALDESSARINI, RJ BOOTH, RG WYRICK, SD AF MYERS, AM CHARIFSON, PS OWENS, CE KULA, NS MCPHAIL, AT BALDESSARINI, RJ BOOTH, RG WYRICK, SD TI CONFORMATIONAL-ANALYSIS, PHARMACOPHORE IDENTIFICATION, AND COMPARATIVE MOLECULAR-FIELD ANALYSIS OF LIGANDS FOR THE NEUROMODULATORY SIGMA(3) RECEPTOR SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BINDING-SITES; DRUGS; REGRESSION; AFFINITY; CELLS; RAT AB Molecular modeling studies were carried out on a series of 1-phenyl-3-amino-1,2,3,4-tetrahydronaphthalenes (phenylaminotetralins, PATs), several PAT structural analogs, and various non-PAT ligands that demonstrate a range of affinities for a novel sigma(3) receptor linked to stimulation of tyrosine hydroxylase and dopamine synthesis in rodent brain. In an effort to develop a ligand-binding model for the sigma(3) receptor, a pharmacophore mapping program (DISCO) was used to identify structural features that are common to ligands that exhibit moderate to high binding affinity for sigma(3) sites. DISCO then was utilized to propose a common pharmacophoric region that included one low-energy conformation of each compound in the training set. The resulting alignment was utilized in a comparative molecular field analysis (CoMFA) study in an attempt to correlate the steric and electrostatic fields of the molecules with the respective binding affinities at the sigma(3) receptor. A suitably predictive model was obtained from the CoMFA analysis which will be employed in the development of additional PAT analogs that could potentially display high affinity and selectivity for the sigma(3) receptor. The excluded volumes which resulted from comparing molecular volumes of active and inactive compounds were visualized to examine the limits of steric tolerance imposed by the sigma(3) receptor. C1 UNIV N CAROLINA,SCH PHARM,DIV MED CHEM & NAT PROD,CHAPEL HILL,NC 27599. GLAXO INC,RES INST,RES TRIANGLE PK,NC 27709. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MCLEAN DIV,MAILMAN RES CTR,BELMONT,MA 02178. DUKE UNIV,DEPT CHEM,DURHAM,NC 27708. FU NIMH NIH HHS [MH-31154, MH-47370, MH-34006] NR 32 TC 44 Z9 44 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 25 PY 1994 VL 37 IS 24 BP 4109 EP 4117 DI 10.1021/jm00050a008 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PV283 UT WOS:A1994PV28300008 PM 7990111 ER PT J AU THALI, M BUKOVSKY, A KONDO, E ROSENWIRTH, B WALSH, CT SODROSKI, J GOTTLINGER, HG AF THALI, M BUKOVSKY, A KONDO, E ROSENWIRTH, B WALSH, CT SODROSKI, J GOTTLINGER, HG TI FUNCTIONAL ASSOCIATION OF CYCLOPHILIN-A WITH HIV-1 VIRIONS SO NATURE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CIS-TRANS ISOMERASE; BINDING-PROTEIN; CYCLOSPORINE-A; HISTOCOMPATIBILITY; REPLICATION; CELLS; GENE AB CYCLOPHILINS are a family of proteins that bind the immunosuppressant cyclosporin A, possess peptidyl-prolyl cis-trans isomerase activity, and assist in the folding of proteins(1-6). Human cyclophilins A and B are host cell proteins that bind specifically to the HIV-1 Gag polyprotein p55(gag) in vitro(7). Here we report that viral particles formed by p55(gag), in contrast to particles formed by the Gag polyproteins of other retroviruses, contain significant amounts of cyclophilin A. Sequences in the capsid domain of p55(gag) are both required and sufficient for the virion-association of cyclophilin A. The association of cyclophilin A with HIV-1 virions was inhibited in a dose-dependent manner by cyclosporin A as well as by SDZ NIM811 ([Melle-4] cyclosporin), a non-immunosuppressive analogue of cyclosporin A(8). Drug-induced reductions in virion-associated cyclophilin A levels were accompanied by reductions in virion infectivity, indicating that the association is functionally relevant. Moreover, SDZ NIM811 inhibited the replication of HIV-1 but was inactive against SIVIMAC, a primate immunodeficiency virus closely related to HIV-1, which does not incorporate cyclophilin A. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. SANDOZ GMBH,FORSCHUNGSINST,A-1235 VIENNA,AUSTRIA. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. OI Thali, Markus/0000-0001-8621-2095 NR 23 TC 506 Z9 514 U1 2 U2 10 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD NOV 24 PY 1994 VL 372 IS 6504 BP 363 EP 365 DI 10.1038/372363a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PU287 UT WOS:A1994PU28700056 PM 7969495 ER PT J AU SOLOMON, R WERNER, C MANN, D DELIA, J SILVA, P AF SOLOMON, R WERNER, C MANN, D DELIA, J SILVA, P TI EFFECTS OF SALINE, MANNITOL, AND FUROSEMIDE ON ACUTE DECREASES IN RENAL-FUNCTION INDUCED BY RADIOCONTRAST AGENTS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MAJOR ANGIOGRAPHY; CARDIAC-CATHETERIZATION; CONTRAST NEPHROPATHY; CORONARY ANGIOGRAPHY; RISK-FACTORS; FAILURE; DYSFUNCTION; INSUFFICIENCY; MEDIA; NEPHROTOXICITY AB Background. Injections of radiocontrast agents are a frequent cause of acute decreases in renal function, occurring most often in patients with chronic renal insufficiency and diabetes mellitus. Methods. We prospectively studied 78 patients with chronic renal insufficiency (mean [+/-SD] serum creatinine concentration, 2.1+/-0.6 mg per deciliter [186+/-53 mu mol per liter]) who underwent cardiac angiography. The patients were randomly assigned to receive 0.45 percent saline alone for 12 hours before and 12 hours after angiography, saline plus mannitol, or saline plus furosemide. The mannitol and furosemide were given just before angiography. Serum creatinine was measured before and far 48 hours after angiography, and urine was collected for 24 hours after angiography. An acute radiocontrast-induced decrease in renal function was defined as an increase in the base-line serum creatinine concentration of at least 0.5 mg per deciliter (44 mu mol per liter) within 48 hours after the injection of radiocontrast agents. Results. Twenty of the 78 patients (26 percent) had an increase in the serum creatinine concentration of at least 0.5 mg per deciliter after angiography. Among the 28 patients in the saline group, 3 (11 percent) had such an increase in serum creatinine, as compared with 7 of 25 in the mannitol group (28 percent) and 10 of 25 in the furosemide group (40 percent) (P = 0.05). The mean increase in serum creatinine 48 hours after angiography was significantly greater in the furosemide group (P = 0.01) than in the saline group. Conclusions. In patients with chronic renal insufficiency who are undergoing cardiac angiography, hydration with 0.45 percent saline provides better protection against acute decreases in renal function induced by radiocontrast agents than does hydration with 0.45 percent saline plus mannitol or furosemide. C1 NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. RP SOLOMON, R (reprint author), JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 33 TC 721 Z9 754 U1 1 U2 15 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 24 PY 1994 VL 331 IS 21 BP 1416 EP 1420 DI 10.1056/NEJM199411243312104 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA PU533 UT WOS:A1994PU53300004 PM 7969280 ER PT J AU LOGIGIAN, EL MURRAY, MB SCHAEFER, PW ADAMS, RD RORDORF, GA AF LOGIGIAN, EL MURRAY, MB SCHAEFER, PW ADAMS, RD RORDORF, GA TI A 19-YEAR-OLD MAN WITH RAPIDLY PROGRESSIVE LOWER-EXTREMITY WEAKNESS AND DYSESTHESIAS AFTER A RESPIRATORY-TRACT INFECTION - MYCOPLASMA-PNEUMONIAE INFECTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID ACUTE TRANSVERSE MYELOPATHY; POLYMERASE CHAIN-REACTION; CENTRAL-NERVOUS-SYSTEM; LYME-DISEASE; NEUROLOGIC MANIFESTATIONS; ANTIBODY-RESPONSE; MYELITIS; NEUROBORRELIOSIS; ABNORMALITIES; BORRELIOSIS C1 HARVARD UNIV, SCH MED, CAMBRIDGE, MA 02138 USA. RP LOGIGIAN, EL (reprint author), BRIGHAM & WOMENS HOSP, 75 FRANCIS ST, BOSTON, MA 02115 USA. NR 49 TC 8 Z9 8 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 24 PY 1994 VL 331 IS 21 BP 1437 EP 1444 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA PU533 UT WOS:A1994PU53300008 ER PT J AU CHANG, HC BAO, ZZ YAO, Y TSE, AGD GOYARTS, EC MADSEN, M KAWASAKI, E BRAUER, PP SACCHETTINI, JC NATHENSON, SG REINHERZ, EL AF CHANG, HC BAO, ZZ YAO, Y TSE, AGD GOYARTS, EC MADSEN, M KAWASAKI, E BRAUER, PP SACCHETTINI, JC NATHENSON, SG REINHERZ, EL TI A GENERAL-METHOD FOR FACILITATING HETERODIMERIC PAIRING BETWEEN 2 PROTEINS - APPLICATION TO EXPRESSION OF ALPHA-T-CELL AND BETA-T-CELL RECEPTOR EXTRACELLULAR SEGMENTS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTIGEN RECOGNITION; LEUCINE ZIPPER; PROTEIN ENGINEERING ID ANTIGEN RECEPTOR; ESCHERICHIA-COLI; H-2K(B) MOLECULE; TRANSGENIC MICE; CHAIN; RECOGNITION; PEPTIDE AB Generation of soluble T-cell receptor (TCR) molecules by a variety of genetic engineering methods has been hampered by inefficient pairing of alpha and beta subunits in the absence of their respective transmembrane regions and associated CD3 components. To overcome this obstacle, we have added 30-amino acid-long segments to the carboxyl termini of alpha and beta extracellular domains via a cleavable flexible linker. These peptide segments (BASE-p1 for alpha and ACID-p1 for beta) have been previously shown to selectively associate to form a stable heterodimeric coiled coil termed a leucine zipper. Homodimeric structures are not permitted due to electrostatic repulsion among amino acid side chains. Expression of a representative TCR-leucine zipper fusion protein in a baculovirus expression system results in production of alpha beta TCR heterodimer at 0.6-1.4 mg/liter. This yield is 5- to 10-fold greater than that of the TCR expressed in the absence of the synthetic leucine zipper sequence. The structure of the TCR component of the fusion heterodimer was judged to be native when probed with a panel of 17 mAbs specific for alpha and beta constant and variable domains. A mAb specific for the isolated BASE-p1/ACID-p1 coiled coil was also generated and shown to react with the TCR fusion protein. The above technology should be broadly useful in the efficient production and purification of TCRs as well as other heterodimeric proteins. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MICROBIOL & IMMUNOL,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT BIOCHEM,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT CELL BIOL,BRONX,NY 10461. PROCEPT INC,CAMBRIDGE,MA 02139. RP CHANG, HC (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. NR 25 TC 123 Z9 123 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 22 PY 1994 VL 91 IS 24 BP 11408 EP 11412 DI 10.1073/pnas.91.24.11408 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PU285 UT WOS:A1994PU28500026 PM 7972074 ER PT J AU PLATT, KA CLAFFEY, KP WILKISON, WO SPIEGELMAN, BM ROSS, SR AF PLATT, KA CLAFFEY, KP WILKISON, WO SPIEGELMAN, BM ROSS, SR TI INDEPENDENT REGULATION OF ADIPOSE TISSUE-SPECIFICITY AND OBESITY RESPONSE OF THE ADIPSIN PROMOTER IN TRANSGENIC MICE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SERINE PROTEASE HOMOLOG; MESSENGER-RNA; GENE; EXPRESSION; PROTEINS; CLONING AB Transcription of the adipocyte specific adipsin gene is dramatically reduced in the adipose tissue of a number of genetically and chemically-induced obese rodents. To map the region of the adipsin gene that confers this response to obesity transgenic mice were made containing -114, -250, -400, -700, and -938 base pairs (bp) to +35 bp of the promoter linked to the bacterial chloramphenicol acetyltransferase gene. Transgenic mice containing as few as 114 bp of the adipsin promoter had high levels of chloramphenicol acetyltransferase activity in adipose tissue. However, only those mice with 938 bp of the adipsin upstream regulatory region showed suppression of expression in adipose tissue in mice that were induced to become obese with monosodium glutamate. Using gel retardation assays, we showed that a 56-bp fragment of DNA mapping between -687 and -743 bp upstream from the start of adipsin expression was bound by protein factors in nuclear extracts prepared from adipose tissue. There was much greater retardation of this fragment with nuclear extracts prepared from adipose tissue of lean versus obese mice. These results indicate that a tissue-specific transcription factor(s) that regulates adipsin expression is less active in the adipose tissue of obese animals. C1 UNIV ILLINOIS,SCH MED,DEPT BIOCHEM MC 536,CHICAGO,IL 60612. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 01225. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 01225. FU NIDDK NIH HHS [DK 42539] NR 20 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 18 PY 1994 VL 269 IS 46 BP 28558 EP 28562 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU168 UT WOS:A1994PU16800010 PM 7961801 ER PT J AU FINI, ME BARTLETT, JD MATSUBARA, M RINEHART, WB MODY, MK GIRARD, MT RAINVILLE, M AF FINI, ME BARTLETT, JD MATSUBARA, M RINEHART, WB MODY, MK GIRARD, MT RAINVILLE, M TI THE RABBIT GENE FOR 92-KDA MATRIX METALLOPROTEINASE - ROLE OF AP1 AND AP2 IN CELL-TYPE-SPECIFIC TRANSCRIPTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IV COLLAGENASE GENE; FACTOR AP-2; GELATINOLYTIC ENZYMES; PHORBOL INDUCTION; HUMAN STROMELYSIN; MAMMALIAN-CELLS; BINDING-SITES; DNA-BINDING; HUMAN SKIN; EXPRESSION AB We isolated the rabbit gene for the 92-kDa matrix metalloproteinase, gelatinase B, and sequenced 1802 contiguous bases covering the first three exons and 522 bases of DNA upstream of the start site for transcription. The DNA between bases -519 and +19 is sufficient to drive expression of a reporter gene in early passage cultures of corneal fibroblasts or primary cultures of corneal epithelial cells. Basal activity of the gelatinase B promotor in fibroblasts is lower than a collagenase promotor of 1800 base pairs, but activity of both promoters is similarly stimulated by treatment of transfected cells with phorbol 12-myristate 13-acetate, and stimulation is enhanced by co-treatment with transforming growth factor-beta. In contrast, basal activity of the gelatinase B promotor in epithelial cells is higher than the collagenase promotor. Deletion analysis demonstrated that sequences upstream of base -330 confer cell type-specific activity to the gelatinase B promotor. Site-directed mutagenesis revealed that an AP1-like element within this region is specifically utilized by fibroblasts. This region also contains elements that confer the capacity for activation by AP2, a transcription factor found to be expressed by corneal epithelial cells but not by corneal fibroblasts. In contrast, AP2 does not activate the collagenase promotor. These results provide a molecular basis for the unique cell type-specific expression pattern of gelatinase B as compared to other matrix metalloproteinases. C1 HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02114. RP FINI, ME (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,CNY3,13TH ST,BOSTON,MA 02129, USA. FU NEI NIH HHS [R01-EY08408] NR 55 TC 99 Z9 100 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 18 PY 1994 VL 269 IS 46 BP 28620 EP 28628 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU168 UT WOS:A1994PU16800019 PM 7961810 ER PT J AU TAKAHASHI, S REDDY, SV CHIRGWIN, JM DEVLIN, R HAIPEK, C ANDERSON, J ROODMAN, GD AF TAKAHASHI, S REDDY, SV CHIRGWIN, JM DEVLIN, R HAIPEK, C ANDERSON, J ROODMAN, GD TI CLONING AND IDENTIFICATION OF ANNEXIN-II AS AN AUTOCRINE/PARACRINE FACTOR THAT INCREASES OSTEOCLAST FORMATION AND BONE-RESORPTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN MARROW CULTURES; MULTINUCLEATED CELLS; OSTEOTROPIC HORMONES; GROWTH-FACTOR; EXPRESSION; DEXAMETHASONE; STIMULATION; PRECURSORS; PHENOTYPE; ACID AB Autocrine products of osteoclasts such as interleukin-6 may play an important role in normal osteoclast formation and activity, To identify novel stimulatory factors for osteoclasts, we have prepared a mammalian cDNA expression library generated from highly purified human osteoclast-like multinucleated cells (MNC) formed in long term bone marrow cultures and screened this library for autocrine factors that enhance MNC formation. A candidate clone which stimulated MNC formation was isolated. Sequence analysis showed that this cDNA encoded annexin II (AXII). Purified recombinant AXII significantly increased MNC formation in human bone marrow cultures in the absence of 1,25-(OH)(2) vitamin D-3 and enhanced MNC formation in mouse bone marrow cultures treated with 10(-9) M 1,25-(OH)(2) vitamin D-3. The enhanced MNC formation in murine marrow cultures resulted in increased bone resorption. Treatment of fetal rat long bones with AXII and 1,25 (OH)(2) vitamin D-3 significantly increased bone resorption compared to 1,25-(OH)(2) vitamin D-3 alone. Reverse transcriptase polymerase chain reaction analysis demonstrated that AXII mRNA was expressed at high levels in RNA isolated from highly purified giant cells from osteoclastomas, human osteoclast-like MNC, and pagetic bone. Western blot analysis of conditioned media collected from human marrow cultures showed that AXII was present in the media. Furthermore, approximately 50% of total AXII produced by cells transfected with AXII cDNA was present in the conditioned media. These data suggest that the AXII is an autocrine factor that enhances osteoclast formation and bone resorption and demonstrate a previous unknown function for AXII. C1 VET ADM MED CTR,DEPT MED HEMATOL & ENDOCRINOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. FU NIADDK NIH HHS [AM 35188]; NIAMS NIH HHS [AR 41336, AR 39539] NR 24 TC 71 Z9 74 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 18 PY 1994 VL 269 IS 46 BP 28696 EP 28701 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU168 UT WOS:A1994PU16800030 PM 7961821 ER PT J AU MYERS, MG GRAMMER, TC WANG, LM SUN, XJ PIERCE, JH BLENIS, J WHITE, MF AF MYERS, MG GRAMMER, TC WANG, LM SUN, XJ PIERCE, JH BLENIS, J WHITE, MF TI INSULIN-RECEPTOR SUBSTRATE-1 MEDIATES PHOSPHATIDYLINOSITOL 3'-KINASE AND P70(S6K) SIGNALING DURING INSULIN, INSULIN-LIKE GROWTH-FACTOR-I, AND INTERLEUKIN-4 STIMULATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASES; HEMATOPOIETIC-CELLS; IRS-1; PHOSPHORYLATION; TRANSDUCTION; ASSOCIATION; EXPRESSION; ACTIVATION; 3-KINASE; PDGF AB Insulin Receptor Substrate-1 (IRS-1) is an endogenous cellular protein that is tyrosine phosphorylated during stimulation of cells with insulin, IGF-1, and interleukin 4 (IL-4). Phosphorylated IRS-1 regulates multiple regulatory pathways by recruiting signaling molecules containing Src homology 2 domains (SH2 proteins). The 32D myeloid progenitor cell line contains few insulin receptors and no detectable IRS-1. Expression of the insulin receptor alone partially mediates insulin-stimulated microtubule-associated protein (MAP) kinase activation, and the addition of IRS-1 enhances this effect (Myers, M. G., Jr., Wang, L.-M., Sun, X. J., Zhang, Y., Yenush, L. P., Schlessinger, J., Pierce, J. H., and White, M. F. (1994) Mol. Cell. Biol. 14, 3577-3587). Alone, insulin receptors mediate phosphatidylinositol (PI) 3'-kinase and p70(S6k) activation poorly if at all during insulin stimulation. Expression of IRS-1 alone in 32D cells mediates the stimulation of p70(S6k) by insulin, IGF-1, or IL 4; addition of insulin receptor to these cells increases the sensitivity of the insulin response. In contrast, full insulin stimulation of PI 3'-kinase requires both the insulin receptor and IRS-1, suggesting that a high level of IRS-1 phosphorylation is required for insulin-stimulated PI 3'-kinase activation, whereas a low level of IRS-1 tyrosine phosphorylation transmits an essential signal to p70(S6k). Both insulin receptors and IRS-1 are required for mitogenic signaling in 32D cells suggesting that MAP kinase or p70(S6k) alone are not sufficient, and that both or additional unknown IRS-1-mediated signals are necessary. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,PROGRAM CELL & DEV BIOL,BOSTON,MA 02215. NIH,CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 46595]; NIDDK NIH HHS [DK 38712, DK 43808] NR 40 TC 223 Z9 223 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 18 PY 1994 VL 269 IS 46 BP 28783 EP 28789 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU168 UT WOS:A1994PU16800043 PM 7961833 ER PT J AU WARREN, HS BAILEY, EM BHALLA, M AF WARREN, HS BAILEY, EM BHALLA, M TI A 57-YEAR-OLD MAN WITH CHRONIC ACTIVE HEPATITIS, A RAPIDLY PROGRESSIVE BULLOUS ERUPTION, AND SHOCK - NECROTIZING FASCIITIS DUE TO ESCHERICHIA-COLI, WITH UNDERLYING MYOSITIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID VIBRIO-VULNIFICUS INFECTIONS; SOFT-TISSUE INFECTIONS; AEROMONAS-HYDROPHILA; MALE GENITALIA; DOG BITE; SEPTICEMIA; DISEASE; SKIN; COMPLICATION; TETRACYCLINE C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP WARREN, HS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 52 TC 0 Z9 1 U1 1 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 17 PY 1994 VL 331 IS 20 BP 1362 EP 1368 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PR216 UT WOS:A1994PR21600009 ER PT J AU KOPANS, DB AF KOPANS, DB TI EFFICACY OF SCREENING MAMMOGRAPHY FOR WOMEN IN THEIR FORTIES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID BREAST-CANCER; FOLLOW RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,15 PARKMAN ST,RM 219,BOSTON,MA 02114, USA. NR 13 TC 4 Z9 4 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 NOV 16 PY 1994 VL 86 IS 22 BP 1721 EP 1722 DI 10.1093/jnci/86.22.1721 PG 2 WC Oncology SC Oncology GA PQ347 UT WOS:A1994PQ34700018 PM 7818698 ER PT J AU KOPANS, DB AF KOPANS, DB TI EFFICACY OF SCREENING MAMMOGRAPHY FOR WOMEN IN THEIR FORTIES - REPLY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID BREAST-CANCER; AGE; TRIAL; TIME RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,15 PARKMAN ST,RM 219,BOSTON,MA 02114, USA. NR 27 TC 0 Z9 0 U1 1 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 16 PY 1994 VL 86 IS 22 BP 1725 EP 1729 DI 10.1093/jnci/86.22.1725-a PG 5 WC Oncology SC Oncology GA PQ347 UT WOS:A1994PQ34700022 ER PT J AU BROOKS, R GARAN, H TORCHIANA, D VLAHAKES, GJ DZIUBAN, S NEWELL, J MCGOVERN, BA RUSKIN, JN AF BROOKS, R GARAN, H TORCHIANA, D VLAHAKES, GJ DZIUBAN, S NEWELL, J MCGOVERN, BA RUSKIN, JN TI 3-YEAR OUTCOME OF A NONTHORACOTOMY APPROACH TO CARDIOVERTER-DEFIBRILLATOR IMPLANTATION IN 189 CONSECUTIVE PATIENTS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MALIGNANT VENTRICULAR ARRHYTHMIAS; CLINICAL-EXPERIENCE; LEAD SYSTEM; SURVIVAL; COMPLICATIONS; THORACOTOMY; EFFICACY; THERAPY; DEVICE; PATCH AB To date, no long-term clinical data have been published in patients undergoing a nonthoracotomy approach to cardioverter-defibrillator system implantation. In the present report, 189 consecutive patients prospectively underwent a standardized approach to cardioverter-defibrillator system implantation in which the nonthoracotomy configurations were tested first. If satisfactory defibrillation thresholds were not obtained, thoracotomy was performed during the same intraoperative session. A nonthoracotomy system was successfully implanted in 149 of 189 patients (79%), with a higher success rate (90%) observed in patients who had more recent implantations, The overall rate of complications associated with these systems was low (11%). Over a mean follow up of 12.5 +/- 9.3 months, 17 patients (9%) died. Three-year total, cardiac, and sudden death-free actuarial survival for all patients was 83 +/- 11%, 88 +/- 7%, and 94 +/- 2%, respectively. Three-year sadden death-free actuarial survival was higher in the nonthoracotomy than in the thoracotomy patients (97 +/- 2% vs 87 +/- 6%, p = 0.047), although total survival was similar (77 +/- 11% vs 83 +/- 7%, p = 0.77). These data suggest that a majority of patients (>80%) requiring a cardioverter-defibrillator system can undergo implantation using a nonthoracotomy approach. Patients receiving nonthoracotomy systems have 3-year outcomes comparable to those implanted via thoracotomy. If these results are maintained, a nonthoracotomy approach will supplant thoracotomy-implanted systems as the preferred method because of the simpler implant procedure and lower overall cost involved. C1 ST PETERS HOSP,ALBANY,NY. RP BROOKS, R (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC ARRHYTHMIA SERV,CARDIAC UNIT,BOSTON,MA 02114, USA. NR 27 TC 16 Z9 16 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 NOV 15 PY 1994 VL 74 IS 10 BP 1011 EP 1015 DI 10.1016/0002-9149(94)90850-8 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PR334 UT WOS:A1994PR33400008 PM 7977038 ER PT J AU SOUKIASIAN, SH FOSTER, CS RAIZMAN, MB AF SOUKIASIAN, SH FOSTER, CS RAIZMAN, MB TI TREATMENT STRATEGIES FOR SCLERITIS AND UVEITIS ASSOCIATED WITH INFLAMMATORY BOWEL-DISEASE SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CROHNS-DISEASE; ULCERATIVE-COLITIS; EXTRAINTESTINAL MANIFESTATIONS; DOUBLE-BLIND; IMMUNE-COMPLEXES; COMPLICATIONS; THERAPY; CYCLOSPORINE; INDOMETHACIN; TRIAL AB We treated 19 patients with anterior uveitis, episcleritis, or scleritis associated with inflammatory bowel disease. Adequate control of ocular inflammation was achieved in 16 patients (84%). Ocular inflammation was adequately controlled with corticosteroids alone, without systemic adverse effects, in only three patients, all of whom had anterior uveitis associated with ulcerative colitis. Systemic nonsteroidal anti-inflammatory drugs proved beneficial in six of seven patients, and one additional patient benefited from another anti-inflammatory drug (hydroxychloroquine sulfate). Systemic cytotoxic immunosuppressive therapy was used in the remaining seven patients, six of whom had bilateral disease. Ocular inflammation was controlled in six of these patients. Azathioprine was beneficial for scleritis but was less effective for anterior uveitis, especially in Crohn's disease, thus necessitating the use of another cytotoxic agent. HLA-B27-positive anterior uveitis was more refractory to corticosteroid therapy and was more likely to require systemic cytotoxic immunosuppressive therapy. With the medical and surgical strategies described, vision was improved or maintained in all patients in the study group. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,SERV IMMUNOL,BOSTON,MA 02114. NR 43 TC 31 Z9 32 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV 15 PY 1994 VL 118 IS 5 BP 601 EP 611 PG 11 WC Ophthalmology SC Ophthalmology GA PQ077 UT WOS:A1994PQ07700005 PM 7977573 ER PT J AU XU, J CHEN, RS XIAO, ZX AF XU, J CHEN, RS XIAO, ZX TI ANALYSIS OF POTENTIAL FUNCTIONAL REGIONS USING LOCAL DEGENERACY - MUTATIONAL HOTSPOTS IN HUMAN FACTOR-IX ARE LOCALIZED IN HIGH-DEGENERACY REGIONS SO ANALYTICAL BIOCHEMISTRY LA English DT Article AB To study the relationship between the potential functional regions with the primary amino acid sequence, we introduced a new factor termed local degeneracy to analyze the degree of the degeneracy in a given segment of the protein. Using the defined local degeneracy, we have analyzed the human coagulation Factor IX (Christmas factor) which is an essential component of the clotting cascade. The mutational hotspots in Factor IX are primarily distributed in the high-degeneracy regions, suggesting a direct correlation of the functional regions with high degree of the degeneracy. This method may be useful to predict and to evaluate potential functional domains of a protein. (C) 1994 Academic Press, Inc. C1 ACAD SINICA,INST BIOPHYS,DEPT PROT ENGN,BEIJING 100101,PEOPLES R CHINA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RI Xu, Jun/B-7351-2012 NR 9 TC 1 Z9 1 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 15 PY 1994 VL 223 IS 1 BP 71 EP 73 DI 10.1006/abio.1994.1548 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PR654 UT WOS:A1994PR65400012 PM 7695104 ER PT J AU SILVER, MT ROSE, GA PAUL, SD ODONNELL, CJ OGARA, PT EAGLE, KA AF SILVER, MT ROSE, GA PAUL, SD ODONNELL, CJ OGARA, PT EAGLE, KA TI A CLINICAL RULE TO PREDICT PRESERVED LEFT-VENTRICULAR EJECTION FRACTION IN PATIENTS AFTER MYOCARDIAL-INFARCTION SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE MYOCARDIAL INFARCTION; VENTRICULAR FUNCTION, LEFT; STROKE VOLUME; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; PREDICTION RULES AB Objective: To derive and validate a clinical prediction rule that identifies patients after myocardial infarction who have preserved left ventricular systolic function. Design: Retrospective analysis of a prospective cohort study, with a derivation set to generate a clinical prediction rule and a validation set to test the prediction rule. Setting: Urban tertiary care hospital. Patients: 314 consecutive patients admitted with myocardial infarction who had one or more of the following tests to determine left ventricular ejection fraction: transthoracic echocardiography, contrast left ventriculography, or radionuclide ventriculography. Measurements: Left ventricular ejection fractions were determined by transthoracic echocardiography, contrast left ventriculography, and gated blood pool scan. Results: Multivariate analysis of patients in the derivation set yielded the following rule: The left ventricular ejection fraction is predicted to be 40% or more in patients who have 1) an interpretable electrocardiogram, 2) no previous Q-wave myocardial infraction, 3) no history of congestive heart failure, and 4) an index myocardial infarction that is not a Q-wave anterior infarction. In the derivation and the validation sets, the positive predictive value of the prediction rule was more than 0.98. Conclusions: A simple clinical prediction rule using easily obtained historical and electrocardiographic data reliably identifies a substantial percentage of patients after myocardial infarction (40% in our hospital) who are likely to have preserved left ventricular systolic function. If validated in other patient populations, application of this prediction rule in clinical practice could result in a substantial decrease in the cost of treating uncomplicated myocardial infarction. C1 MASSACHUSETTS GEN HOSP,CTR AMBULATORY CARE 475,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 16 TC 34 Z9 34 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 15 PY 1994 VL 121 IS 10 BP 750 EP 756 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PQ928 UT WOS:A1994PQ92800004 PM 7944052 ER PT J AU EMANUEL, EJ AF EMANUEL, EJ TI THE HISTORY OF EUTHANASIA DEBATES IN THE UNITED-STATES AND BRITAIN SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID ACTIVE EUTHANASIA; LIFE AB Debates about the ethics of euthanasia and physician-assisted suicide date from ancient Greece and Pome. After the development of ether, physicians began advocating the use of anesthetics to relieve the pains of death. In 1870, Samuel Williams first proposed using anesthetics and morphine to intentionally end a patient's life. Over the next 35 years, debates about the ethics of euthanasia raged in the United States and Britain,culminating in 1906 in an Ohio bill to legalize euthanasia, a bill that was ultimately defeated. The arguments propounded for and against euthanasia in the 19th century are identical to contemporary arguments. Such similarities suggest four conclusions: Public interest in euthanasia 1) is not linked with advances in biomedical technology; 2) it flourishes in times of economic recession, in which individualism and social Darwinism are invoked to justify public policy; 3) it arises when physician authority over medical decision making is challenged; and 4) it occurs when terminating life-sustaining medical interventions become standard medical practice and interest develops in extending such practices to include euthanasia. RP EMANUEL, EJ (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 111 TC 48 Z9 50 U1 5 U2 17 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 NOV 15 PY 1994 VL 121 IS 10 BP 793 EP 802 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA PQ928 UT WOS:A1994PQ92800010 PM 7944057 ER PT J AU CARTER, EA DEROJASWALKER, T TAMIR, S TANNENBAUM, SR YU, YM TOMPKINS, RG AF CARTER, EA DEROJASWALKER, T TAMIR, S TANNENBAUM, SR YU, YM TOMPKINS, RG TI NITRIC-OXIDE PRODUCTION IS INTENSELY AND PERSISTENTLY INCREASED IN TISSUE BY THERMAL-INJURY SO BIOCHEMICAL JOURNAL LA English DT Article ID MAMMALIAN NITRATE BIOSYNTHESIS; MOUSE AB NO is a major messenger molecule which regulates immunity and vascular tone, serves as a neurotransmitter and participates in wound healing. It has also been known to be increased in vivo by thermal injury. Urinary nitrate excretion and tissue levels of NO synthase activity were measured after a non-lethal thermal injury. Urinary nitrate excretion decreased by 90% 24-48 h after injury, but dramatically increased by 10-fold thereafter for 30-40 days after injury and remained elevated until the wound healed. This response was inhibited by a competitive inhibitor of NO synthase. These rates of urinary nitrate excretion suggest that NO production is dramatically affected by injury in a pattern that is distinct from that observed after lipopolysaccharide administration. On the basis of these findings, we suggest that the hyperdynamic cardiovascular and hypermetabolic responses seen to continue weeks after thermal injury could be a result of the autocrine and paracrine effects of NO generated locally within the tissues in addition to that generated by inflammatory cells. C1 SHRINERS BURN INST,BOSTON,MA 02144. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02144. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02144. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114. MIT,CAMBRIDGE,MA 02139. FU NCI NIH HHS [CA26731]; NIGMS NIH HHS [P50 GM21700] NR 16 TC 70 Z9 70 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 15 PY 1994 VL 304 BP 201 EP 204 PN 1 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU039 UT WOS:A1994PU03900031 PM 7528006 ER PT J AU GUINAN, EC GRIBBEN, JG BOUSSIOTIS, VA FREEMAN, GJ NADLER, LM AF GUINAN, EC GRIBBEN, JG BOUSSIOTIS, VA FREEMAN, GJ NADLER, LM TI PIVOTAL ROLE OF THE B7-CD28 PATHWAY IN TRANSPLANTATION TOLERANCE AND TUMOR-IMMUNITY SO BLOOD LA English DT Review ID T-CELL ACTIVATION; ANTIGEN-PRESENTING CELLS; BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; INTERLEUKIN-2 GENE-EXPRESSION; CHRONIC MYELOGENOUS LEUKEMIA; HLA-IDENTICAL SIBLINGS; SEVERE APLASTIC-ANEMIA; HUMAN LYMPHOCYTES-T; CLASS-II MOLECULES C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA 02115 USA. RP GUINAN, EC (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DEPT PEDIAT ONCOL, BOSTON, MA 02115 USA. NR 244 TC 339 Z9 346 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 1994 VL 84 IS 10 BP 3261 EP 3282 PG 22 WC Hematology SC Hematology GA PR221 UT WOS:A1994PR22100002 PM 7524733 ER PT J AU AIUTI, A FRIEDRICH, C GUTIERREZRAMOS, JC AF AIUTI, A FRIEDRICH, C GUTIERREZRAMOS, JC TI MOUSE STROMAL CELL CLONES WITH DIFFERENT CAPACITY TO SUPPORT LONG-TERM CULTURE OF PRIMITIVE HUMAN HEMATOPOIETIC-CELLS SO BLOOD LA English DT Meeting Abstract C1 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 1994 VL 84 IS 10 SU 1 BP A418 EP A418 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401652 ER PT J AU ALCANTARA, O REDDY, SV ROODMAN, GD BOLDT, DH AF ALCANTARA, O REDDY, SV ROODMAN, GD BOLDT, DH TI FUNCTIONAL-CHARACTERIZATION OF THE HEMIN RESPONSIVE ELEMENT OF THE MESSENGER TRAP GENE SO BLOOD LA English DT Meeting Abstract C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. NR 0 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A39 EP A39 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400145 ER PT J AU ALSINA, M BOYCE, B MUNDY, GR ROODMAN, GD AF ALSINA, M BOYCE, B MUNDY, GR ROODMAN, GD TI AN IN-VIVO MODEL OF HUMAN MULTIPLE-MYELOMA (MM) BONE-DISEASE (BD) SO BLOOD LA English DT Meeting Abstract C1 UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. VET ADM MED CTR, SAN ANTONIO, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A170 EP A170 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400664 ER PT J AU BACHIER, C CRAIG, F ROODMAN, GD AF BACHIER, C CRAIG, F ROODMAN, GD TI CD34+ STEM-CELL SELECTION AND IMMUNOMAGNETIC PURGING (IMP) TO REMOVE CHRONIC LYMPHOCYTIC-LEUKEMIA (CLL) CELLS FROM BONE-MARROW (BM) SO BLOOD LA English DT Meeting Abstract C1 VET ADM MED CTR, SAN ANTONIO, TX USA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A726 EP A726 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402884 ER PT J AU BACHIER, C FREYTES, CO SALZMAN, D CASTRO, J BOLDT, D ROODMAN, GD HARRIS, K CRAIG, F WIESNER, A LEMAISTRE, CF AF BACHIER, C FREYTES, CO SALZMAN, D CASTRO, J BOLDT, D ROODMAN, GD HARRIS, K CRAIG, F WIESNER, A LEMAISTRE, CF TI BONE-MARROW TRANSPLANTATION (BMT) FOR ADULT POOR-RISK HIGH-GRADE NON-HODGKINS-LYMPHOMA (HGNHL) SO BLOOD LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY VET ADM HOSP,SAN ANTONIO,TX 78284. S TEXAS CANC INST,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 1994 VL 84 IS 10 SU 1 BP A703 EP A703 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402794 ER PT J AU BALL, TC HIRAYAMA, F OGAWA, M AF BALL, TC HIRAYAMA, F OGAWA, M TI LYMPHOHEMATOPOIETIC PROGENITORS OF NORMAL MICE SO BLOOD LA English DT Meeting Abstract C1 RALPH H JOHNSON VET AFFAIRS MED CTR,CHARLESTON,SC. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. 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 1994 VL 84 IS 10 SU 1 BP A434 EP A434 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401716 ER PT J AU BARTLETTPANDITE, L SOIFFER, R GRIBBEN, JG ANDERSON, K ROBERTSON, M FREEDMAN, AS RITZ, J NEUBERG, D NADLER, LM AF BARTLETTPANDITE, L SOIFFER, R GRIBBEN, JG ANDERSON, K ROBERTSON, M FREEDMAN, AS RITZ, J NEUBERG, D NADLER, LM TI AUTOLOGOUS AND ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR B-CELL CLL - BALANCE BETWEEN TOXICITY AND EFFICACY 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 7 Z9 7 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 1994 VL 84 IS 10 SU 1 BP A536 EP A536 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402124 ER PT J AU BERENSON, J LICHTENSTEIN, A PORTER, L BORDONI, R GEORGE, S LIPTON, A KELLER, A SIMEONE, J HEFFERNAN, M SEAMAN, J KNIGHT, R AF BERENSON, J LICHTENSTEIN, A PORTER, L BORDONI, R GEORGE, S LIPTON, A KELLER, A SIMEONE, J HEFFERNAN, M SEAMAN, J KNIGHT, R TI PAMIDRONATE DISODIUM REDUCES THE OCCURRENCE OF SKELETAL-RELATED EVENTS (SRE) IN ADVANCED MULTIPLE-MYELOMA (MM) SO BLOOD LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES, DVA WLA, MYELOMA AREDIA STUDY GRP, LOS ANGELES, CA USA. ATLANTA CTR CANC RES, ATLANTA, GA USA. SW INST CLIN RES, RANCHO MIRAGE, CA USA. PENN STATE UNIV, MILTON S HERSHEY MED CTR, HERSHEY, PA 17033 USA. ST FRANCIS HOSP, TULSA, OK USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. CIBA GEIGY CORP, SUMMIT, NJ 07901 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A386 EP A386 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401525 ER PT J AU BOUSSIOTIS, VA HOUGHTON, A RITZ, J NADLER, LM SOIFFER, R AF BOUSSIOTIS, VA HOUGHTON, A RITZ, J NADLER, LM SOIFFER, R TI R24 ANTI-GD3 GANGLIOSIDE ANTIBODY CAN INDUCE COSTIMULATION AND PREVENT THE INDUCTION OF ALLOANTIGEN-SPECIFIC T-CELL CLONAL ANERGY SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. 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 1994 VL 84 IS 10 SU 1 BP A228 EP A228 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400895 ER PT J AU BOUSSIOTIS, VA BARBER, DL NAKARAI, T FREEMAN, GJ GRIBBEN, JG BERNSTEIN, GM DANDREA, AD RITZ, J NADLER, LM AF BOUSSIOTIS, VA BARBER, DL NAKARAI, T FREEMAN, GJ GRIBBEN, JG BERNSTEIN, GM DANDREA, AD RITZ, J NADLER, LM TI COMMON GAMMA-CHAIN SIGNALING IS SUFFICIENT TO PREVENT ALLOANTIGEN-SPECIFIC T-CELL CLONAL ANERGY SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES & 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 1994 VL 84 IS 10 SU 1 BP A111 EP A111 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400428 ER PT J AU BOUSSIOTIS, VA FREEMAN, GJ BERNSTEIN, GM GRAY, GS GRIBBEN, JG NADLER, LM AF BOUSSIOTIS, VA FREEMAN, GJ BERNSTEIN, GM GRAY, GS GRIBBEN, JG NADLER, LM TI B7 FAMILY COSTIMULATION CAN PREVENT BUT CANNOT REVERSE ALLOANTIGEN-SPECIFIC T-CELL CLONAL ANERGY SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. REPLIGEN CORP,CAMBRIDGE,MA. 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 1994 VL 84 IS 10 SU 1 BP A96 EP A96 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400373 ER PT J AU BROUNS, MC DELOUGHERY, TG NICHOLS, MJ AF BROUNS, MC DELOUGHERY, TG NICHOLS, MJ TI FATAL THROMBOSIS COMPLICATING ALL-TRANS-RETINOIC ACID (ATRA) THERAPY FOR ACUTE PROMYELOCYTIC LEUKEMIA (APL) SO BLOOD LA English DT Meeting Abstract C1 PORTLAND VET AFFAIRS MED CTR,PORTLAND,OR. 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 1994 VL 84 IS 10 SU 1 BP A616 EP A616 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402446 ER PT J AU BRUGNARA, C CAP, B DEMETRI, GD AF BRUGNARA, C CAP, B DEMETRI, GD TI RETICULOCYTE CELLULAR INDEXES IN PATIENTS WITH EARLY BREAST-CANCER TREATED WITH CHEMOTHERAPY PLUS COMBINATION CYTOKINES - EVIDENCE FOR IRON-DEFICIENT ERYTHROPOIESIS AND TRANSIENT MACROCYTOSIS SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 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 1994 VL 84 IS 10 SU 1 BP A580 EP A580 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402300 ER PT J AU CARDOSO, AA SCHULTZE, JL SEAMON, M PROVAN, A FREEMAN, GJ GRIBBEN, JG NADLER, LM AF CARDOSO, AA SCHULTZE, JL SEAMON, M PROVAN, A FREEMAN, GJ GRIBBEN, JG NADLER, LM TI EXPRESSION AND INDUCTION OF B7 COSTIMULATORY MOLECULES ON B-CELL PRECURSOR MALIGNANCIES - IMPLICATIONS FOR ANTITUMOR IMMUNITY SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,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 1994 VL 84 IS 10 SU 1 BP A378 EP A378 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401494 ER PT J AU CARROLL, M PLESS, M MATHEYPREVOT, B DANDREA, AD AF CARROLL, M PLESS, M MATHEYPREVOT, B DANDREA, AD TI ERYTHROPOIETIN STIMULATES ERYTHROID-DIFFERENTIATION BY PROLONGATION OF THE G1 PHASE OF THE CELL-CYCLE SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV HEMATOL ONCOL,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 1994 VL 84 IS 10 SU 1 BP A365 EP A365 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401440 ER PT J AU CASTRO, J BACHIER, C BOLDT, DH FREYTES, C HARRIS, K ROODMAN, D SALZMAN, D TAMI, J MENEGHETTI, C SHERIDANLEOS, N LEMAISTRE, CF AF CASTRO, J BACHIER, C BOLDT, DH FREYTES, C HARRIS, K ROODMAN, D SALZMAN, D TAMI, J MENEGHETTI, C SHERIDANLEOS, N LEMAISTRE, CF TI CRYOPRESERVED MATCHED RELATED DONOR MARROW ENGRAFTS PROMPTLY FOLLOWING ALLOGENEIC BONE-MARROW TRANSPLANTATION SO BLOOD LA English DT Meeting Abstract C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,S TEXAS CANC INST,SAN ANTONIO,TX 78284. NR 1 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 1994 VL 84 IS 10 SU 1 BP A93 EP A93 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400360 ER PT J AU CHAUHAN, D UCHIYAMA, H URASHIMA, M YAMAMOTO, K ANDERSON, KC AF CHAUHAN, D UCHIYAMA, H URASHIMA, M YAMAMOTO, K ANDERSON, KC TI NFKB REGULATES MULTIPLE-MYELOMA (MM) CELL ADHESION-RELATED INTERLEUKIN-6 (IL-6) TRANSCRIPTION IN BONE-MARROW STROMAL CELLS (BMSC) SO BLOOD LA English DT Meeting Abstract C1 KANAZAWA UNIV,CANC RES INST,DEPT MOLEC PATHOL,KANAZAWA,ISHIKAWA 920,JAPAN. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. NR 0 TC 3 Z9 3 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 1994 VL 84 IS 10 SU 1 BP A524 EP A524 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402076 ER PT J AU CLARET, EJ FREEMAN, GJ PROVAN, A BARTLETTPANDITE, L NADLER, LM AF CLARET, EJ FREEMAN, GJ PROVAN, A BARTLETTPANDITE, L NADLER, LM TI AUTOLOGOUS T-CELLS CAN EFFICIENTLY RECOGNIZE CD40 ACTIVATED MALIGNANT B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA CELLS IN AN ANTIGEN-SPECIFIC MANNER 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 1994 VL 84 IS 10 SU 1 BP A452 EP A452 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401789 ER PT J AU DEMETRI, GD BERENSON, RJ CAP, B BLUMSACK, R SHAPIRO, T AUSTIN, E SUGRUE, M HAYES, DF AF DEMETRI, GD BERENSON, RJ CAP, B BLUMSACK, R SHAPIRO, T AUSTIN, E SUGRUE, M HAYES, DF TI CD34+ SELECTED PERIPHERAL-BLOOD PROGENITOR CELLS (PBPCS) TO SUPPORT THE DELIVERY OF MULTIPLE CYCLES OF DOSE-INTENSIVE CYCLOPHOSPHAMIDE AND DOXORUBICIN (CD) WITH G-CSF PLUS ERYTHROPOIETIN (EPO) IN CHEMOTHERAPY-NAIVE BREAST-CANCER PATIENTS SO BLOOD LA English DT Meeting Abstract C1 CELLPRO INC,BOTHELL,WA. HARVARD UNIV,SCH MED,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 1994 VL 84 IS 10 SU 1 BP A207 EP A207 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400813 ER PT J AU DEMETRI, GD HAYES, DF MERICA, EA CAP, B SPARANO, J AF DEMETRI, GD HAYES, DF MERICA, EA CAP, B SPARANO, J TI CONCURRENT IL-6 PLUS G-CSF TO SUPPORT DOSE-INTENSIFIED CYCLOPHOSPHAMIDE DOXORUBICIN (CD) - POSSIBLE ACCELERATION OF HEMATOLOGIC RECOVERY FROM CHEMOTHERAPY-INDUCED THROMBOCYTOPENIA SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. MONTEFIORE MED CTR,BRONX,NY 10467. NR 2 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A29 EP A29 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400103 ER PT J AU DETRICH, HW STANIER, DYR WEINSTEIN, BM FISHMAN, MC ZON, LI AF DETRICH, HW STANIER, DYR WEINSTEIN, BM FISHMAN, MC ZON, LI TI CLOCHE, A GENE REQUIRED FOR GENERATION OF HEMATOPOIETIC STEM-CELL AND ENDOTHELIAL LINEAGES IN ZEBRAFISH SO BLOOD LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. 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 1994 VL 84 IS 10 SU 1 BP A365 EP A365 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401441 ER PT J AU DRACHMAN, JG GRIFFIN, JD KAUSHANSKY, K AF DRACHMAN, JG GRIFFIN, JD KAUSHANSKY, K TI THE C-MPL LIGAND (THROMBOPOIETIN) STIMULATES TYROSINE PHOSPHORYLATION SO BLOOD LA English DT Meeting Abstract C1 UNIV WASHINGTON,SCH MED,SEATTLE,WA 98195. HARVARD UNIV,SCH MED,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 1994 VL 84 IS 10 SU 1 BP A390 EP A390 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401540 ER PT J AU ELLIS, M FREEDMAN, A SOIFFER, R AF ELLIS, M FREEDMAN, A SOIFFER, R TI ABDOMINAL-PAIN AS THE INITIAL PRESENTATION OF DISSEMINATED VARICELLA-ZOSTER VIRUS (VZV) INFECTION AFTER BONE-MARROW TRANSPLANTATION (BMT) SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NEW ENGLAND DEACONESS 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 1994 VL 84 IS 10 SU 1 BP A491 EP A491 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401943 ER PT J AU ERNST, TJ WAMSLEY, S GOMEZZAERA, M GRIFFIN, JD AF ERNST, TJ WAMSLEY, S GOMEZZAERA, M GRIFFIN, JD TI ACTIVATION OF FES FPS INCREASES DRUG EFFLUX MEDIATED BY MDR WITHOUT INCREASING ITS CELL-SURFACE EXPRESSION 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 1994 VL 84 IS 10 SU 1 BP A222 EP A222 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400872 ER PT J AU ERNST, TJ CHA, S AF ERNST, TJ CHA, S TI HOMOHARRINGTONINE AND CYTARABINE ARE BOTH SELECTIVE AND SYNERGISTIC IN INHIBITING THE GROWTH OF CML CFU-S IN-VITRO SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,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 1994 VL 84 IS 10 SU 1 BP A151 EP A151 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400588 ER PT J AU FISHER, DE BODIS, S LOWE, S TAKEMOTO, C HOUSMAN, D JACKS, T AF FISHER, DE BODIS, S LOWE, S TAKEMOTO, C HOUSMAN, D JACKS, T TI RESTORATION OF APOPTOSIS IN P53 DEFICIENT TUMOR-CELLS SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. NR 0 TC 8 Z9 8 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 1994 VL 84 IS 10 SU 1 BP A111 EP A111 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400429 ER PT J AU FRANK, D SALGIA, R BHATT, A GRIFFIN, JD GREENBERG, M AF FRANK, D SALGIA, R BHATT, A GRIFFIN, JD GREENBERG, M TI IDENTIFICATION OF A 93KDA STAT PROTEIN PHOSPHORYLATED FOLLOWING TREATMENT BY GM-CSF OR IL-3 IN HEMATOPOIETIC-CELLS SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,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 1994 VL 84 IS 10 SU 1 BP A224 EP A224 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400878 ER PT J AU FREEDMAN, A NEUBERG, D GRIBBEN, J MAUCH, P ANDERSON, K SOIFFER, R PANDITE, L ROBERTSON, M KROON, M GROVER, J CORAL, F RITZ, J NADLER, L AF FREEDMAN, A NEUBERG, D GRIBBEN, J MAUCH, P ANDERSON, K SOIFFER, R PANDITE, L ROBERTSON, M KROON, M GROVER, J CORAL, F RITZ, J NADLER, L TI AUTOLOGOUS BONE-MARROW TRANSPLANTATION IN RELAPSED LOW-GRADE NON-HODGKINS-LYMPHOMA SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,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 1994 VL 84 IS 10 SU 1 BP A203 EP A203 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400796 ER PT J AU FREEMAN, GJ NG, J ANUMANTHAN, A GRIBBEN, JG BOUSSIOTIS, VA GREENFIELD, E RENNERT, PD GRAY, GS NADLER, LM AF FREEMAN, GJ NG, J ANUMANTHAN, A GRIBBEN, JG BOUSSIOTIS, VA GREENFIELD, E RENNERT, PD GRAY, GS NADLER, LM TI CTLA4 BINDING REQUIRES ONLY THE B7-1 IG-V DOMAIN BUT COSTIMULATION REQUIRES BOTH IG-V AND IG-C DOMAINS SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. REPLIGEN CORP,CAMBRIDGE,MA. NR 0 TC 1 Z9 1 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 1994 VL 84 IS 10 SU 1 BP A528 EP A528 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402094 ER PT J AU FREEMAN, GJ BOUSSIOTIS, VA GRIBBEN, JG BERNSTEIN, GM KE, XY RENNERT, PD GRAY, GS NADLER, LM AF FREEMAN, GJ BOUSSIOTIS, VA GRIBBEN, JG BERNSTEIN, GM KE, XY RENNERT, PD GRAY, GS NADLER, LM TI B7-1 AND B7-2 DO NOT DELIVER IDENTICAL COSTIMULATORY SIGNALS SINCE B7-2 BUT NOT B7-1 COSTIMULATES IL-4 PRODUCTION IN CD4+CD45RA+ (NAIVE) T-CELLS SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. REPLIGEN CORP,CAMBRIDGE,MA. 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 1994 VL 84 IS 10 SU 1 BP A511 EP A511 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402025 ER PT J AU FREEMAN, GJ EDELHOFF, S JELLIS, CL WANG, S RENNERT, PD GRAY, GS NG, JW DISTECHE, CM NADLER, LM AF FREEMAN, GJ EDELHOFF, S JELLIS, CL WANG, S RENNERT, PD GRAY, GS NG, JW DISTECHE, CM NADLER, LM TI B7-2 COLOCALIZES WITH B7-1 TO CHROMOSOME-3Q21 AND THE B7-2 GENOMIC STRUCTURE HAS ALTERNATIVE 5' EXONS SUGGESTING INDEPENDENT REGULATION SO BLOOD LA English DT Meeting Abstract C1 REPLIGEN CORP,CAMBRIDGE,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. 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 1994 VL 84 IS 10 SU 1 BP A446 EP A446 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401764 ER PT J AU FREYTES, CO BACHIER, C SALZMAN, D VUKELIA, S CASTRO, J BOLDT, D ROODMAN, GD CRAIG, F HARRIS, K TSAI, T SHERIDANLEOS, N HILSENBECK, S TAMI, J BURRELL, L LEMAISTRE, CF AF FREYTES, CO BACHIER, C SALZMAN, D VUKELIA, S CASTRO, J BOLDT, D ROODMAN, GD CRAIG, F HARRIS, K TSAI, T SHERIDANLEOS, N HILSENBECK, S TAMI, J BURRELL, L LEMAISTRE, CF TI HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM-CELL RESCUE IN RESISTANT OR RECURRENT LOW-GRADE LYMPHOMA SO BLOOD LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY VET ADM HOSP,S TEXAS CANC INST,SAN ANTONIO,TX 78284. BROOKE ARMY MED 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 1994 VL 84 IS 10 SU 1 BP A709 EP A709 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402816 ER PT J AU FRIEDRICH, C GUTIERREZRAMOS, JC AF FRIEDRICH, C GUTIERREZRAMOS, JC TI FUNCTIONAL-HETEROGENEITY OF STROMAL CELL CLONES DERIVED FROM THE FETAL LIVER AND THE BONE-MARROW OF THE MOUSE SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,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 1994 VL 84 IS 10 SU 1 BP A417 EP A417 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401651 ER PT J AU GERWIN, N AGUIRRE, V GUTIERREZRAMOS, JC AF GERWIN, N AGUIRRE, V GUTIERREZRAMOS, JC TI CLONING OF PROTEIN-TYROSINE KINASES INVOLVED IN EARLY HEMATOPOIESIS IN MOUSE FETAL LIVER SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,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 1994 VL 84 IS 10 SU 1 BP A415 EP A415 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401641 ER PT J AU GRABOWSKI, EF MICHAIL, HA FALLON, JT AF GRABOWSKI, EF MICHAIL, HA FALLON, JT TI TISSUE FACTOR EXPRESSION BY SUBENDOTHELIUM OF ENDOTHELIAL-CELL MONOLAYERS PRECONDITIONED BY LOW SHEAR-STRESS SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. MT SINAI MED CTR,NEW YORK,NY 10029. NR 0 TC 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 1994 VL 84 IS 10 SU 1 BP A192 EP A192 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400752 ER PT J AU GRABOWSKI, EF HEAD, C JANG, IK GOLD, H BENOIT, SE MICHELSON, AD AF GRABOWSKI, EF HEAD, C JANG, IK GOLD, H BENOIT, SE MICHELSON, AD TI PLATELETS ARE DEGRANULATED BY SOME BUT NOT ALL, CONTRAST-MEDIA SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA 01605. 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 1994 VL 84 IS 10 SU 1 BP A686 EP A686 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402726 ER PT J AU GRELLIER, PC ABBOUD, SL AF GRELLIER, PC ABBOUD, SL TI EXPRESSION AND REGULATION OF INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS (IGFBPS) IN MURINE PROGENITORS SO BLOOD LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,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 1994 VL 84 IS 10 SU 1 BP A125 EP A125 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400484 ER PT J AU GRIBBEN, JG BOUSSIOTIS, VA FREEMAN, GJ RENNERT, P JELLIS, CL GREENFIELD, E GRAY, GS NADLER, LM AF GRIBBEN, JG BOUSSIOTIS, VA FREEMAN, GJ RENNERT, P JELLIS, CL GREENFIELD, E GRAY, GS NADLER, LM TI ALLOANTIGEN AND CONCOMITANT CTLA4 SIGNALING INDUCES CLONAL DELETION OF ALLOREACTIVE T-CELLS - A NOVEL METHOD TO PREVENT GVHD SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. REPLIGEN CORP,CAMBRIDGE,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 1994 VL 84 IS 10 SU 1 BP A397 EP A397 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401569 ER PT J AU GRIBBEN, JG GUINAN, EC BOUSSIOTIS, VA KE, XY GRAY, GS FREEMAN, GJ NADLER, LM AF GRIBBEN, JG GUINAN, EC BOUSSIOTIS, VA KE, XY GRAY, GS FREEMAN, GJ NADLER, LM TI B7-2 IS THE MAJOR COSTIMULATORY SIGNAL RESPONSIBLE FOR THE INITIATION OF ALLOANTIGEN RECOGNITION LEADING TO GVHD SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. REPLIGEN CORP,CAMBRIDGE,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 1994 VL 84 IS 10 SU 1 BP A397 EP A397 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401568 ER PT J AU GUINAN, EC LOPEZ, KD MCKENZIE, SE LOBEL, J COHEN, P SINGER, D MCINTOSH, S CAMITTA, B KURTZBERG, J AF GUINAN, EC LOPEZ, KD MCKENZIE, SE LOBEL, J COHEN, P SINGER, D MCINTOSH, S CAMITTA, B KURTZBERG, J TI SUCCESSFUL TREATMENT (RX) OF PATIENTS (PTS) WITH REFRACTORY SEVERE APLASTIC-ANEMIA (SAA) WITH CONCOMITANT CYCLOSPORINE (CSA) AND COLONY-STIMULATING FACTORS (CSF) SO BLOOD LA English DT Meeting Abstract C1 PHOENIX CHILDRENS HOSP, PHOENIX, AZ USA. CHILDRENS HOSP WISCONSIN, MED COLL WISCONSIN, MILWAUKEE, WI USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HARVARD UNIV, CHILDRENS HOSP, BOSTON, MA 02115 USA. UNIV PENN, CHILDRENS HOSP, PHILADELPHIA, PA 19104 USA. GEISINGER MED CTR, DANVILLE, PA 17822 USA. UNIV CALIF LOS ANGELES, HARBOR GEN HOSP, LOS ANGELES, CA USA. DUKE UNIV, MED CTR, SCH MED, DURHAM, NC 27710 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A10 EP A10 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400028 ER PT J AU HALLEK, M WARMUTH, M DANHAUSERRIEDL, S HILDENBRAND, S GRIFFIN, JD DRUKER, BJ EMMERICH, B AF HALLEK, M WARMUTH, M DANHAUSERRIEDL, S HILDENBRAND, S GRIFFIN, JD DRUKER, BJ EMMERICH, B TI THE SRC-FAMILY KINASE P53/P56LYN ASSOCIATES WITH AND IS ACTIVATED BY THE P210BCR/ABL-KINASE SO BLOOD LA English DT Meeting Abstract C1 UNIV MUNICH,MED KLIN,W-8000 MUNICH 2,GERMANY. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. HARVARD UNIV,SCH MED,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 1994 VL 84 IS 10 SU 1 BP A294 EP A294 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401161 ER PT J AU HALLEK, M DANHAUSERRIEDL, S HERBST, R HILDENBRAND, S DRUKER, BJ EMMERICH, B GRIFFIN, JD ULLRICH, A AF HALLEK, M DANHAUSERRIEDL, S HERBST, R HILDENBRAND, S DRUKER, BJ EMMERICH, B GRIFFIN, JD ULLRICH, A TI THE RECEPTOR TYROSINE KINASE P145C-KIT INTERACTS WITH THE P210BCR/ABL-KINASE IN MYELOID CELLS SO BLOOD LA English DT Meeting Abstract C1 UNIV MUNICH,KLINIKUM INNENSTADT,MED KLIN,W-8000 MUNICH 2,GERMANY. MAX PLANCK INST BIOCHEM,W-8033 MARTINSRIED,GERMANY. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. HARVARD UNIV,SCH MED,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 1994 VL 84 IS 10 SU 1 BP A293 EP A293 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401155 ER PT J AU HARDY, L VOELLMY, R BOUSSIOTIS, V SPECTOR, NL AF HARDY, L VOELLMY, R BOUSSIOTIS, V SPECTOR, NL TI A POTENTIAL NOVEL MECHANISM OF PRIMARY RESISTANCE TO CHEMORADIOTHERAPY SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV MIAMI,SYLVESTER COMPREHENS CANC CTR,SCH MED,MIAMI,FL 33152. 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 1994 VL 84 IS 10 SU 1 BP A596 EP A596 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402364 ER PT J AU HEANEY, C ODA, T HAGOPIAN, JR OKUDA, K GRIFFIN, JD DRUKER, BJ AF HEANEY, C ODA, T HAGOPIAN, JR OKUDA, K GRIFFIN, JD DRUKER, BJ TI CRKL IS THE MAJOR TYROSINE-PHOSPHORYLATED PROTEIN IN NEUTROPHILS FROM PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA SO BLOOD LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 1 U2 3 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 1994 VL 84 IS 10 SU 1 BP A381 EP A381 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401504 ER PT J AU HO, CY OTTERUD, B VARVIL, T SAXENA, R DEHART, D KOHLER, S LI, F LEPPERT, M GILLILAND, DG AF HO, CY OTTERUD, B VARVIL, T SAXENA, R DEHART, D KOHLER, S LI, F LEPPERT, M GILLILAND, DG TI A FAMILIAL PLATELET DISORDER WITH PROPENSITY TO DEVELOP ACUTE MYELOID-LEUKEMIA IS LINKED TO HUMAN-CHROMOSOME 21Q22.1-22.2 SO BLOOD LA English DT Meeting Abstract C1 UNIV UTAH,HOWARD HUGHES MED INST,SALT LAKE CITY,UT 84112. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV UTAH,DEPT HUMAN GENET,SALT LAKE CITY,UT 84112. 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 1994 VL 84 IS 10 SU 1 BP A318 EP A318 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401256 ER PT J AU HUGHES, RT SANCHEZ, I MAYER, B YEE, K WOODGET, JR AVRUCH, J KYRIAKIS, JM ZON, LI AF HUGHES, RT SANCHEZ, I MAYER, B YEE, K WOODGET, JR AVRUCH, J KYRIAKIS, JM ZON, LI TI CLONING OF SEK1 DEFINES A STRESS-ACTIVATED, ABL-RESPONSIVE PROTEIN-KINASE CASCADE REGULATING C-JUN PHOSPHORYLATION SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,CHILDRENS HOSP,SCH MED,HHMI, DIV HEMATOL ONCOL, BOSTON, MA 02114 USA. ONTARIO CANC INST, TORONTO M4X 1K9, ONTARIO, CANADA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A293 EP A293 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401157 ER PT J AU ILARIA, RL VANETTEN, RA AF ILARIA, RL VANETTEN, RA TI THE SH2 DOMAIN OF P210 BCR/ABL IS NOT REQUIRED FOR TRANSFORMATION OF HEMATOPOIETIC GROWTH FACTOR-DEPENDENT CELL-LINES SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,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 1994 VL 84 IS 10 SU 1 BP A513 EP A513 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402033 ER PT J AU INHORN, RC EDER, M CARLESSO, N DURSTIN, M MATSUGUCHI, T GRIFFIN, JD AF INHORN, RC EDER, M CARLESSO, N DURSTIN, M MATSUGUCHI, T GRIFFIN, JD TI THE INITIAL STEPS OF GM-CSF RECEPTOR ASSEMBLY AND SIGNALING 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 1994 VL 84 IS 10 SU 1 BP A224 EP A224 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400881 ER PT J AU ISHIMARU, F SHIPP, MA AF ISHIMARU, F SHIPP, MA TI 2 SEPARATE PROMOTERS CONTROL TRANSCRIPTION OF CD10 NEUTRAL ENDOPEPTIDASE 24.11 IN HEMATOPOIETIC AND NONHEMATOPOIETIC CELLS SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,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 1994 VL 84 IS 10 SU 1 BP A434 EP A434 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401719 ER PT J AU JANICEK, M KAPLAN, W NEUBERG, D CANELLOS, GP SHULMAN, L SHIPP, MA AF JANICEK, M KAPLAN, W NEUBERG, D CANELLOS, GP SHULMAN, L SHIPP, MA TI EARLY RESTAGING GALLIUM SCANS IDENTIFY DURABLE RESPONSES TO INDUCTION THERAPY IN HIGH-RISK PATIENTS WITH AGGRESSIVE NON-HODGKINS-LYMPHOMA (NHL) SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,WOMENS HOSP,BOSTON,MA 02115. NR 0 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A233 EP A233 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400914 ER PT J AU JIA, GQ NICHOGIANNOPOULOU, A GUTIERREZRAMOS, JC AF JIA, GQ NICHOGIANNOPOULOU, A GUTIERREZRAMOS, JC TI REGULATION OF CYTOKINE RECEPTOR GENES DURING FETAL LIVER HEMATOPOIETIC DEVELOPMENT SO BLOOD LA English DT Meeting Abstract C1 CTR BLOOD RES INC,BOSTON,MA. HARVARD UNIV,SCH MED,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 1994 VL 84 IS 10 SU 1 BP A281 EP A281 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401106 ER PT J AU KAMEOKA, I DONG, RP HEGEN, M TANAKA, T XU, Y SLAYTER, HS SCHLOSSMAN, SF MORIMOTO, C AF KAMEOKA, I DONG, RP HEGEN, M TANAKA, T XU, Y SLAYTER, HS SCHLOSSMAN, SF MORIMOTO, C TI POSSIBLE REGULATORY ROLES OF CD26 ADENOSINE-DEAMINASE ADENOSINE IN T-CELL ACTIVATION SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. NR 1 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 1994 VL 84 IS 10 SU 1 BP A228 EP A228 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400894 ER PT J AU KAWASHIMA, I LAVER, JH LEARY, AG OGAWA, M AF KAWASHIMA, I LAVER, JH LEARY, AG OGAWA, M TI LOW C-KIT EXPRESSION BY PRIMITIVE HEMATOPOIETIC PROGENITORS IN UMBILICAL-CORD BLOOD SO BLOOD LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT PEDIAT,CHARLESTON,SC 29425. RALPH H JOHNSON DVA 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 1994 VL 84 IS 10 SU 1 BP A271 EP A271 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401069 ER PT J AU KULBACKI, R WEICH, N KOPF, M GUTIERREZRAMOS, JC AF KULBACKI, R WEICH, N KOPF, M GUTIERREZRAMOS, JC TI HYPERSENSITIVITY OF IL6 DEFICIENT MICE TO PHENYLHYDRAZINE INDUCED HEMOLYSIS SO BLOOD LA English DT Meeting Abstract C1 GENET INST INC, CAMBRIDGE, MA 02115 USA. MAX PLANCK INST IMMUNBIOL, FREIBURG, 02115, GERMANY. HARVARD UNIV, SCH MED, CTR BLOOD RES INC, BOSTON, MA USA. HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A549 EP A549 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402175 ER PT J AU LEGARE, R GRIBBEN, JG BUSQUE, L MARAGH, M NADLER, L GILLILAND, DG AF LEGARE, R GRIBBEN, JG BUSQUE, L MARAGH, M NADLER, L GILLILAND, DG TI CLONAL HEMATOPOIESIS IS PREDICTIVE OF SECONDARY MYELODYSPLASIA IN AUTOLOGOUS BONE-MARROW TRANSPLANT (ABMT) FOR NON-HODGKINS-LYMPHOMA (NHL) SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HOP MAISON NEUVE ROSEMONT, MONTREAL H1T 2M4, QUEBEC, CANADA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A495 EP A495 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401959 ER PT J AU LIN, GS FINGER, E GUTIERREZRAMOS, JC AF LIN, GS FINGER, E GUTIERREZRAMOS, JC TI NOVEL ANTI-MOUSE CD34 MONOCLONAL-ANTIBODIES THAT RECOGNIZE A SUBSET OF CD34 EXPRESSING CELLS IN THE FETAL LIVER SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT GENET,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 1994 VL 84 IS 10 SU 1 BP A273 EP A273 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401074 ER PT J AU LIU, K SANROMAN, J KAMALI, V NAUGHTON, BA KELLER, J RUSCETTI, FW ROODMAN, D BONEWALD, L MEAGHER, RM PURCHIO, AF TWARDZIK, DR AF LIU, K SANROMAN, J KAMALI, V NAUGHTON, BA KELLER, J RUSCETTI, FW ROODMAN, D BONEWALD, L MEAGHER, RM PURCHIO, AF TWARDZIK, DR TI PURIFICATION OF STEM-CELL PROLIFERATION FACTOR (SCPF), A CYTOKINE THAT STIMULATES THE EXPANSION OF HUMAN CD34+ CELLS IN-VITRO SO BLOOD LA English DT Meeting Abstract C1 ADV TISSUE SCI INC,LA JOLLA,CA. NCI,LEUKOCYTE BIOL LAB,FREDERICK,MD 21701. UNIV CINCINNATI,MED CTR,HOXWORTH BLOOD CTR,CINCINNATI,OH 45267. VET ADM MED CTR,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. 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 1994 VL 84 IS 10 SU 1 BP A275 EP A275 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401082 ER PT J AU LU, B CARROL, M FINCO, O ISHIMARU, F CARD, A GERARD, NP SHIPP, MA GERARD, C AF LU, B CARROL, M FINCO, O ISHIMARU, F CARD, A GERARD, NP SHIPP, MA GERARD, C TI TARGETED DISRUPTION OF CD10 NEUTRAL ENDOPEPTIDASE-24.11 SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP MED CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,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 1994 VL 84 IS 10 SU 1 BP A512 EP A512 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402027 ER PT J AU MANIE, SN WANG, D MORIMOTO, C PHIFER, JS FREEDMAN, A AF MANIE, SN WANG, D MORIMOTO, C PHIFER, JS FREEDMAN, A TI ACTIVATION OF THE TYROSINE KINASE PATHWAY FOLLOWING LIGATION OF THE BETA-1 INTEGRIN VLA-4 IN B-LYMPHOCYTES 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 1994 VL 84 IS 10 SU 1 BP A283 EP A283 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401115 ER PT J AU MATSUGUCHI, T INHORN, RC CARLESSO, N GRIFFIN, JD AF MATSUGUCHI, T INHORN, RC CARLESSO, N GRIFFIN, JD TI P95VAV IS TYROSINE-PHOSPHORYLATED BY GM-CSF, IL3, STEEL FACTOR AND P210BCR/ABL, AND IS ASSOCIATED WITH JAK KINASES IN MYELOID 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 1994 VL 84 IS 10 SU 1 BP A369 EP A369 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401459 ER PT J AU MATULONIS, U DOSIOU, C LAMONT, C FREEMAN, GJ MAUCH, P NADLER, LM GRIFFIN, JD AF MATULONIS, U DOSIOU, C LAMONT, C FREEMAN, GJ MAUCH, P NADLER, LM GRIFFIN, JD TI THE ROLE OF THE B7-1 AND B7-2 COSTIMULATORY MOLECULES IN GENERATING CELLULAR VACCINES FOR THE IMMUNOTHERAPY OF LEUKEMIA 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 1994 VL 84 IS 10 SU 1 BP A378 EP A378 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401493 ER PT J AU NEY, PA FARINA, SF BODINE, DM ANDREWS, NC ORKIN, SH NIENHUIS, AW AF NEY, PA FARINA, SF BODINE, DM ANDREWS, NC ORKIN, SH NIENHUIS, AW TI GENE-TRANSFER OF WILD-TYPE P45 NF-E2 INTO THE HEMATOPOIETIC-CELLS OF MK/MK MICE SO BLOOD LA English DT Meeting Abstract C1 ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38101 USA. ST JUDE CHILDRENS RES HOSP, DEPT EXPTL HEMATOL, MEMPHIS, TN 38101 USA. NCHGR, GENE TRANSFER LAB, HEMATOPOIESIS SECT, BETHESDA, MD USA. CHILDRENS HOSP MED CTR, DEPT PEDIAT, DIV HEMATOL ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HOWARD HUGHES MED INST, COCONUT GROVE, FL 33133 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A354 EP A354 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401398 ER PT J AU NICHOGIANNOPOULOU, A WANG, BP TERHORST, C GUTIERREZRAMOS, JC AF NICHOGIANNOPOULOU, A WANG, BP TERHORST, C GUTIERREZRAMOS, JC TI LONG-TERM ENGRAFTMENT OF FETAL HEMATOPOIETIC STEM-CELLS BY IN-UTERO TRANSPLANTATION INTO IMMUNODEFICIENT MOUSE EMBRYOS SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV IMMUNOL,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 1994 VL 84 IS 10 SU 1 BP A434 EP A434 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401718 ER PT J AU NORGA, K NATHAN, DG MATHEYPREVOT, B SADELAIN, M AF NORGA, K NATHAN, DG MATHEYPREVOT, B SADELAIN, M TI A SINGLE-COPY MINIMAL LOCUS-CONTROL REGION (LCR) FAITHFULLY UP-REGULATES HUMAN BETA-GLOBIN EXPRESSION IN RETROVIRALLY TRANSDUCED BA/F3-EPOR CELLS SO BLOOD LA English DT Meeting Abstract C1 MEM SLOAN KETTERING CANC CTR,DEPT HUMAN GENET,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. BOSTON CHILDRENS HOSP,BOSTON,MA. 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 1994 VL 84 IS 10 SU 1 BP A263 EP A263 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401035 ER PT J AU OKUDA, K GRIFFIN, JD ANDO, K AF OKUDA, K GRIFFIN, JD ANDO, K TI CDK4 IS A CRITICAL COMPONENT OF A CELL-CYCLE CHECKPOINT IN G1 REGULATED BY CAMP AND P21RAS 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 1994 VL 84 IS 10 SU 1 BP A366 EP A366 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401447 ER PT J AU PAIETTA, E ANDERSEN, J RACEVSKIS, J BENNETT, J ROWE, JM CASSILETH, P WIERNIK, PH AF PAIETTA, E ANDERSEN, J RACEVSKIS, J BENNETT, J ROWE, JM CASSILETH, P WIERNIK, PH TI MULTIDRUG-RESISTANCE GENE (MDR-1) TRANSCRIPT OR CD34 ANTIGEN EXPRESSION LEVELS DO NOT PREDICT FOR COMPLETE REMISSIONS IN DE-NOVO ADULT ACUTE MYELOID-LEUKEMIA (AML) - AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP STUDY SO BLOOD LA English DT Meeting Abstract C1 MONTEFIORE & ALBERT EINSTEIN CANC CTR,BRONX,NY. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV ROCHESTER,ROCHESTER,NY 14627. UNIV MIAMI,MIAMI,FL 33152. EASTERN COOPERAT ONCOL GRP,DENVER,CO. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A377 EP A377 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401490 ER PT J AU PICHERT, G ROY, D ALYEA, T SOIFFER, R RITZ, J AF PICHERT, G ROY, D ALYEA, T SOIFFER, R RITZ, J TI RT-PCR ANALYSIS OF BONE-MARROW IS MORE SENSITIVE FOR DETECTION OF RESIDUAL BCR-ABL MESSENGER-RNA EXPRESSING CELLS THAN ANALYSIS OF PERIPHERAL-BLOOD SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV HEMATOL MALIGNANCIES, BOSTON, MA 02115 USA. HOP MAISON NEUVE ROSEMONT, DIV HEMATOL IMMUNOL, MONTREAL H1T 2M4, QUEBEC, CANADA. OI Roy, Denis-Claude/0000-0002-5921-1692 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A342 EP A342 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401351 ER PT J AU PLESS, M CARROLL, M DANDREA, AD MATHEYPREVOT, B AF PLESS, M CARROLL, M DANDREA, AD MATHEYPREVOT, B TI STRUCTURAL REQUIREMENTS FOR RECEPTOR-MEDIATED ERYTHROID-DIFFERENTIATION OF BA/F3 CELLS SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT HEMATOL & ONCOL,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 1994 VL 84 IS 10 SU 1 BP A507 EP A507 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402009 ER PT J AU PROVAN, A BARTLETTPANDITE, L ANDERSON, K NADLER, LM GRIBBEN, JG AF PROVAN, A BARTLETTPANDITE, L ANDERSON, K NADLER, LM GRIBBEN, JG TI FEASIBILITY OF IDENTIFYING PATIENT-SPECIFIC PROBES TO ASSESS MINIMAL RESIDUAL DISEASE IN MALIGNANCIES OF B-CELL ORIGIN 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 1994 VL 84 IS 10 SU 1 BP A452 EP A452 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401790 ER PT J AU PROVAN, A BARTLETTPANDITE, L CORRADINI, P NADLER, LM GRIBBEN, JG AF PROVAN, A BARTLETTPANDITE, L CORRADINI, P NADLER, LM GRIBBEN, JG TI DETECTION OF MINIMAL RESIDUAL DISEASE IN PATIENTS WITH CLL UNDERGOING BMT USING CDRIII REGION-SPECIFIC OLIGONUCLEOTIDE PROBES SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV TURIN,DIV EMATOL,I-10124 TURIN,ITALY. 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 1994 VL 84 IS 10 SU 1 BP A203 EP A203 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400797 ER PT J AU RICE, GC TINO, W WEEKS, R BIERER, BE GALLIS, B CAI, F VALENTINE, M DESILVA, D JENKINS, M BIANCO, JA SINGER, JW BURSTEN, SL AF RICE, GC TINO, W WEEKS, R BIERER, BE GALLIS, B CAI, F VALENTINE, M DESILVA, D JENKINS, M BIANCO, JA SINGER, JW BURSTEN, SL TI DEVELOPMENT OF NOVEL AND SPECIFIC PHARMACOLOGICAL INHIBITORS OF INTERLEUKIN-2 SIGNAL-TRANSDUCTION SO BLOOD LA English DT Meeting Abstract C1 CELL THERAPEUT INC,SEATTLE,WA 98119. DANA FARBER INST,BOSTON,MA 02115. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. RI Jenkins, Marc/G-1063-2012 OI Jenkins, Marc/0000-0001-8009-7655 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 1994 VL 84 IS 10 SU 1 BP A227 EP A227 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400892 ER PT J AU ROGERS, WO FRIEDBERG, RC TILDEN, AB VAUGHAN, WP AF ROGERS, WO FRIEDBERG, RC TILDEN, AB VAUGHAN, WP TI TRANSFUSION-RELATED ACUTE LUNG INJURY (TRALI) DURING ALLOGENEIC HLA-IDENTICAL BONE-MARROW INFUSION SO BLOOD LA English DT Meeting Abstract C1 UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT INTERNAL MED,BIRMINGHAM,AL 35294. BIRMINGHAM VA MED CTR,DEPT PATHOL,BIRMINGHAM,AL. BIRMINGHAM VA MED CTR,MED SERV LAB,BIRMINGHAM,AL. 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 1994 VL 84 IS 10 SU 1 BP A491 EP A491 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401946 ER PT J AU SALGIA, R LI, JL LO, SH BRUNKHORST, B KANSAS, GS SUN, Y PISICK, E ERNST, T CHEN, LB GRIFFIN, JD AF SALGIA, R LI, JL LO, SH BRUNKHORST, B KANSAS, GS SUN, Y PISICK, E ERNST, T CHEN, LB GRIFFIN, JD TI MOLECULAR-CLONING OF PAXILLIN, A FOCAL ADHESION PHOSPHOPROTEIN INVOLVED IN GROWTH-FACTOR RECEPTOR AND ONCOGENE SIGNAL-TRANSDUCTION IN HEMATOPOIETIC-CELLS SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 1 Z9 1 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 1994 VL 84 IS 10 SU 1 BP A375 EP A375 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401480 ER PT J AU SCADDEN, DT BERARDI, AC WANG, A LOPEZ, P LEVINE, JD AF SCADDEN, DT BERARDI, AC WANG, A LOPEZ, P LEVINE, JD TI THE FUNCTIONAL ISOLATION AND CHARACTERIZATION OF HUMAN HEMATOPOIETIC STEM-CELLS SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEACONESS HOSP,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 1994 VL 84 IS 10 SU 1 BP A542 EP A542 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402147 ER PT J AU SCHULTZE, JL CARDOSO, AA SEAMON, M FREEMAN, GJ GRIBBEN, JG NADLER, LM AF SCHULTZE, JL CARDOSO, AA SEAMON, M FREEMAN, GJ GRIBBEN, JG NADLER, LM TI MOST FOLLICULAR LYMPHOMAS DO NOT STIMULATE AN ALLOGENEIC T-CELL PROLIFERATIVE RESPONSE SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 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 1994 VL 84 IS 10 SU 1 BP A521 EP A521 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402065 ER PT J AU SHIKAMA, Y DANDREA, A NATHAN, DG SIEFF, CA AF SHIKAMA, Y DANDREA, A NATHAN, DG SIEFF, CA TI A CONSTITUTIVELY ACTIVE MURINE ERYTHROPOIETIN HUMAN GM-CSF-ALPHA HYBRID RECEPTOR CONFERS FACTOR-INDEPENDENCE IN TRANS THROUGH THE MURINE COMMON BETA-SUBUNIT AIC2B SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP MED CTR,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,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 1994 VL 84 IS 10 SU 1 BP A507 EP A507 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402007 ER PT J AU SHIVDASANI, RA ROSENBLATT, MF VIGNALI, K ORKIN, SH AF SHIVDASANI, RA ROSENBLATT, MF VIGNALI, K ORKIN, SH TI ERYTHROPOIESIS IN P45 NF-E2 KNOCKOUT MICE SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,CHILDRENS HOSP,HOWARD HUGHES MED INST,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,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 1994 VL 84 IS 10 SU 1 BP A218 EP A218 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400855 ER PT J AU SHIVDASANI, RA ROSENBLATT, MF VIGNALI, K ZUCKERFRANKLIN, D ORKIN, SH AF SHIVDASANI, RA ROSENBLATT, MF VIGNALI, K ZUCKERFRANKLIN, D ORKIN, SH TI THE TRANSCRIPTION FACTOR NF-E2 IS REQUIRED IN-VIVO FOR NORMAL MEGAKARYOCYTE MATURATION AND PLATELET PRODUCTION SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,HOWARD HUGHES MED INST,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 1994 VL 84 IS 10 SU 1 BP A110 EP A110 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400424 ER PT J AU SOIFFER, R MURRAY, C FAIRCLOUGH, D ROBERTSON, M FREEDMAN, A ANDERSON, K PANDITE, L FREEMAN, A MARCUS, K MAUCH, P NADLER, L RITZ, J AF SOIFFER, R MURRAY, C FAIRCLOUGH, D ROBERTSON, M FREEDMAN, A ANDERSON, K PANDITE, L FREEMAN, A MARCUS, K MAUCH, P NADLER, L RITZ, J TI CD6-DEPLETED ALLOGENEIC BMT FOR ADULTS WITH ACUTE-LEUKEMIA 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 1994 VL 84 IS 10 SU 1 BP A332 EP A332 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401311 ER PT J AU SOIFFER, R MURRAY, C FAIRCLOUGH, D ALYEA, E RITZ, J AF SOIFFER, R MURRAY, C FAIRCLOUGH, D ALYEA, E RITZ, J TI LOW-DOSE INTERLEUKIN-2 FOLLOWING T-CELL DEPLETED ALLOGENEIC BMT FOR CHRONIC MYELOGENOUS LEUKEMIA (CML) 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 1994 VL 84 IS 10 SU 1 BP A213 EP A213 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400836 ER PT J AU SRIKANTH, S RADO, TA AF SRIKANTH, S RADO, TA TI ANALYSIS OF PU.1 INTERACTIONS IN DIFFERENTIATING MYELOID CELLS SO BLOOD LA English DT Meeting Abstract C1 UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. BIRMINGHAM VAMC,BIRMINGHAM,AL. 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 1994 VL 84 IS 10 SU 1 BP A133 EP A133 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400516 ER PT J AU SRIKANTH, S RADO, TA AF SRIKANTH, S RADO, TA TI PU.1 IS NECESSARY FOR TISSUE-SPECIFIC GENE-EXPRESSION FROM THE HNE PROMOTER SO BLOOD LA English DT Meeting Abstract C1 UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. BIRMINGHAM VAMC,BIRMINGHAM,AL. 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 1994 VL 84 IS 10 SU 1 BP A133 EP A133 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400515 ER PT J AU STONE, R MURRAY, C BERG, D MAYER, R RITZ, J SOIFFER, R AF STONE, R MURRAY, C BERG, D MAYER, R RITZ, J SOIFFER, R TI LOW-DOSE INTERLEUKIN-2 FOLLOWING INTENSIFICATION THERAPY WITH HIGH-DOSE ARA-C FOR ACUTE MYELOGENOUS LEUKEMIA IN 1ST COMPLETE REMISSION SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,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 1994 VL 84 IS 10 SU 1 BP A302 EP A302 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401190 ER PT J AU TAYLOR, DS NATHAN, DG PREVOT, BM AF TAYLOR, DS NATHAN, DG PREVOT, BM TI THE CORE BINDING-FACTOR (CBF) SITE WITHIN THE IL3 PROMOTER IS POSITION-SENSITIVE AND CBF ACTIVITY IS DEPENDENT ON THE ADJACENT ACT-1 (NFIL3) SITE SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL & ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,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 1994 VL 84 IS 10 SU 1 BP A428 EP A428 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401693 ER PT J AU TAYLOR, DS LAUBACH, J NATHAN, DG MATHEYPREVOT, B AF TAYLOR, DS LAUBACH, J NATHAN, DG MATHEYPREVOT, B TI THE HUMAN IL3 PROMOTER CONTAINS A CYCLOSPORINE-A SENSITIVE ELEMENT OTHER THAN NFAT SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL & ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,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 1994 VL 84 IS 10 SU 1 BP A236 EP A236 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400929 ER PT J AU TEPLER, I DEMETRI, G MCCAULEY, M GAYNES, L HARVEY, S SKARIN, A STRAUSS, G AYASH, L WHEELER, C SCHWARTZ, G SCHNIPPER, L FREI, E ELIAS, IA AF TEPLER, I DEMETRI, G MCCAULEY, M GAYNES, L HARVEY, S SKARIN, A STRAUSS, G AYASH, L WHEELER, C SCHWARTZ, G SCHNIPPER, L FREI, E ELIAS, IA TI OUTPATIENT-BASED TREATMENT WITH MULTIPLE CYCLES OF DOSE-INTENSIFIED IFOSFAMIDE, CARBOPLATIN AND ETOPOSIDE (ICE) CHEMOTHERAPY SUPPORTED BY PERIPHERAL-BLOOD PROGENITOR CELLS (PBPC) MOBILIZED BY G-CSF - EFFICIENT COLLECTION OF PROGENITOR CELLS WITH RAPID HEMATOLOGIC RECOVERY SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02215. 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 1994 VL 84 IS 10 SU 1 BP A211 EP A211 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400829 ER PT J AU URASHIMA, M CHAUHAN, D UCHIYAMA, H ANDERSON, KC AF URASHIMA, M CHAUHAN, D UCHIYAMA, H ANDERSON, KC TI CD40 TRIGGERED INTERLEUKIN-6 (IL-6) SECRETION BY MULTIPLE-MYELOMA (MM) AND BONE-MARROW STROMAL CELLS (BMSC) SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT 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 1994 VL 84 IS 10 SU 1 BP A524 EP A524 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402075 ER PT J AU VANDERWOUDE, AC PERRY, M MENU, E TSAI, B LEVY, S BIERER, BE AF VANDERWOUDE, AC PERRY, M MENU, E TSAI, B LEVY, S BIERER, BE TI ROLE OF CD81 (TAPA-1) IN T-LYMPHOCYTE ACTIVATION SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,SCH MED,BOSTON,MA 02115. STANFORD UNIV,MED CTR,STANFORD,CA 94305. RI MENU, Elisabeth/B-2886-2010 OI MENU, Elisabeth/0000-0001-8844-9328 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 1994 VL 84 IS 10 SU 1 BP A283 EP A283 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401117 ER PT J AU VANETTEN, RA DEBNATH, J ZHOU, H CASASNOVAS, JM AF VANETTEN, RA DEBNATH, J ZHOU, H CASASNOVAS, JM TI INTRODUCTION OF A LOSS-OF-FUNCTION POINT MUTATION FROM THE SH3 REGION OF THE CAENORHABDITIS-ELEGANS SEM-5 GENE ACTIVATES THE TRANSFORMING ABILITY OF C-ABL IN-VIVO AND ABOLISHES BINDING OF PROLINE-RICH LIGANDS IN-VITRO SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,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 1994 VL 84 IS 10 SU 1 BP A514 EP A514 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402037 ER PT J AU VOENA, C CORRADINI, P ASTOLFI, M LADETTO, M GRIBBEN, JG BOCCADORO, M PILERI, A AF VOENA, C CORRADINI, P ASTOLFI, M LADETTO, M GRIBBEN, JG BOCCADORO, M PILERI, A TI PCR AMPLIFICATION OF REARRANGED IMMUNOGLOBULIN HEAVY-CHAIN (IGH) GENES FOR MINIMAL RESIDUAL DISEASE DETECTION IN B-CELL MALIGNANCIES SO BLOOD LA English DT Meeting Abstract C1 UNIV TURIN,OSPED MOLINETTE,DIPARTIMENTO MED & ONCOL SPERIMENTALE,DIV EMATOL,I-10124 TURIN,ITALY. 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 1994 VL 84 IS 10 SU 1 BP A526 EP A526 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402083 ER PT J AU WAYNE, AS TAN, CTC ARCECI, RJ BARR, R HURWITZ, CA PITEL, PA WEINSTEIN, HJ FAVARA, BE AF WAYNE, AS TAN, CTC ARCECI, RJ BARR, R HURWITZ, CA PITEL, PA WEINSTEIN, HJ FAVARA, BE TI 2-CHLORODEOXYADENOSINE (2CDA) FOR DISORDERS OF MONO-HISTIOCYTIC (MO/HI) LINEAGE SO BLOOD LA English DT Meeting Abstract C1 UNIV SO FL,ALL CHILDRENS HOSP,ST PETE,FL. MAINE CHILDRENS CANC PROG,PORTLAND,ME. NEMOURS CHILDRENS CLIN,JACKSONVILLE,FL. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. MCMASTER UNIV,HAMILTON L8S 4L8,ONTARIO,CANADA. NR 0 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A57 EP A57 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400215 ER PT J AU WEBB, IJ AYASH, LJ EICKHOFF, CE WHEELER, C SCHWARTZ, G MAZANET, R DEMETRI, G ANTMAN, K SCHNIPPER, L FREI, E ELIAS, A AF WEBB, IJ AYASH, LJ EICKHOFF, CE WHEELER, C SCHWARTZ, G MAZANET, R DEMETRI, G ANTMAN, K SCHNIPPER, L FREI, E ELIAS, A TI STRATEGIES FOR MOBILIZATION OF PERIPHERAL-BLOOD STEM-CELLS FOR USE IN HIGH-DOSE CHEMOTHERAPY SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DANA FARBER CANC INST,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 1994 VL 84 IS 10 SU 1 BP A105 EP A105 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400407 ER PT J AU WETZLER, M TALPAZ, M YEE, G STASS, AS VANETTEN, RA ANDREEFF, M GOODACRE, AM KLEINE, HD MAHADEVIA, RK KURZROCK, R AF WETZLER, M TALPAZ, M YEE, G STASS, AS VANETTEN, RA ANDREEFF, M GOODACRE, AM KLEINE, HD MAHADEVIA, RK KURZROCK, R TI CELL CYCLE-RELATED SHIFTS IN SUBCELLULAR-LOCALIZATION OF BCR - ASSOCIATION WITH MITOTIC CHROMOSOMES AND WITH HETEROCHROMATIN SO BLOOD LA English DT Meeting Abstract C1 ROSWELL PK CANC INST,DEPT MED,BUFFALO,NY. UNIV MARYLAND MED SYST,DEPT PATHOL,BALTIMORE,MD. MD ANDERSON CANC CTR,DEPT CLIN INVEST,HOUSTON,TX. MD ANDERSON CANC CTR,DEPT HEMATOL,HOUSTON,TX. MD ANDERSON CANC CTR,DEPT LAB MED,HOUSTON,TX. CTR BLOOD RES,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 1994 VL 84 IS 10 SU 1 BP A139 EP A139 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400541 ER PT J AU WILLERFORD, DM PREFFER, F MCAFEE, S SCAVONE, M SPITZER, TR AF WILLERFORD, DM PREFFER, F MCAFEE, S SCAVONE, M SPITZER, TR TI MOBILIZATION OF EARLY AND LATE HEMATOPOIETIC PRECURSORS USING GMCSF, GCSF, OR COMBINED GMCSF AND GCSF FOLLOWING CHEMOTHERAPY SO BLOOD LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,HEMATOL ONCOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A90 EP A90 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400349 ER PT J AU YAMASHITA, T GROMPE, M WU, N CORLESS, C DANDREA, AD AF YAMASHITA, T GROMPE, M WU, N CORLESS, C DANDREA, AD TI IMMUNOLOGICAL SCREENING OF THE FANCONI-ANEMIA COMPLEMENTATION GROUP-C (FACC) POLYPEPTIDE IDENTIFIES CANDIDATE PATIENTS FOR GENE-THERAPY 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 & MOLEC BIOL,BOSTON,MA 02115. OREGON HLTH SCI UNIV,DEPT MOLEC & MED GENET,PORTLAND,OR 97201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A743 EP A743 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402953 ER PT J AU ZHAO, S CONSOLI, U ARCECI, R ANDREEFF, M AF ZHAO, S CONSOLI, U ARCECI, R ANDREEFF, M TI NEW SEMIAUTOMATED METHOD (QPCR(TM)) FOR QUANTITATING MULTIDRUG-RESISTANCE (MDR1) IN DRUG-RESISTANT CELL-LINES AND ACUTE MYELOID-LEUKEMIA SO BLOOD LA English DT Meeting Abstract C1 UNIV TEXAS,MD ANDERSON CANCER CTR,HOUSTON,TX 77030. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 2 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 1994 VL 84 IS 10 SU 1 BP A53 EP A53 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400202 ER PT J AU ZHU, Y HOCHSTRASSER, M DANDREA, AD AF ZHU, Y HOCHSTRASSER, M DANDREA, AD TI A HEMATOPOIETIC-SPECIFIC, INTERLEUKIN-3 (IL-3)-INDUCIBLE, IMMEDIATE-EARLY GENE ENCODING A DEUBIQUITINATING ENZYME 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 & MOLEC BIOL,BOSTON,MA 02115. UNIV CHICAGO,DEPT BIOCHEM & MOLEC BIOL,CHICAGO,IL 60637. NR 1 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 1994 VL 84 IS 10 SU 1 BP A222 EP A222 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400870 ER PT J AU ZUKERBERG, LR YANG, WI ARNOLD, A HARRIS, NL AF ZUKERBERG, LR YANG, WI ARNOLD, A HARRIS, NL TI CYCLIN-D1 (PRAD1/BCL-1) EXPRESSION IN NON-HODGKINS-LYMPHOMAS - DETECTION BY PARAFFIN-SECTION IMMUNOHISTOCHEMISTRY SO BLOOD LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 0 TC 1 Z9 1 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 1994 VL 84 IS 10 SU 1 BP A449 EP A449 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401779 ER PT J AU BOVIATSIS, EJ PARK, JS SENAESTEVES, M KRAMM, CM CHASE, M EFIRD, JT WEI, MX BREAKEFIELD, XO CHIOCCA, EA AF BOVIATSIS, EJ PARK, JS SENAESTEVES, M KRAMM, CM CHASE, M EFIRD, JT WEI, MX BREAKEFIELD, XO CHIOCCA, EA TI LONG-TERM SURVIVAL OF RATS HARBORING BRAIN NEOPLASMS TREATED WITH GANCICLOVIR AND A HERPES-SIMPLEX VIRUS VECTOR THAT RETAINS AN INTACT THYMIDINE KINASE GENE SO CANCER RESEARCH LA English DT Note ID THERAPY; GLIOMA; TUMOR; MODEL; CELLS; MUTANTS; BEARING; MOUSE AB Survival of rats harboring cerebral 9L, gliosarcomas can be significantly extended by an intratumoral inoculation with a herpes simplex virus vector, designated as hrR3. This vector, which bears the lacZ reporter gene, is defective in the gene encoding ribonucleotide reductase, allowing for replication in dividing tumor cells but not in postmitotic neural cells. It also possesses an intact viral thymidine kinase (TK) gene, which confers chemosensitivity to ganciclovir. In this study, the ability of ganciclovir to potentiate the antitumor effect of hrR3 was evaluated. In culture, there was a 23% decrease in the growth of 9L cells treated with hrR3 plus ganciclovir compared to hrR3 alone (P < 0.01). The combination of hrR3 plus ganciclovir led to the long-term survival of 48% of rats harboring intracerebral 91, gliosarcomas compared to 20% survival in the hrR3 group (P < 0.05). Ganciclovir treatment had no effect on the growth of tumor cells in vitro or in vivo when a herpes simplex virus vector with a defective TK gene was used. Immunocytochemistry confirmed selective expression of the TK gene in cells within the tumor. These findings indicate that the TK gene can potentiate the antitumor effect of the hrR3 herpes simplex virus vector and provide the basis for placing additional therapeutic genes in the genome of hrR3. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BIOSTAT UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,MOLEC NEUROGENET LAB,BOSTON,MA 02114. FU NINDS NIH HHS [NS 24279-08] NR 20 TC 155 Z9 158 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1994 VL 54 IS 22 BP 5745 EP 5751 PG 7 WC Oncology SC Oncology GA PR217 UT WOS:A1994PR21700002 PM 7954393 ER PT J AU PUGH, TD CHANG, CS UEMURA, H WEINDRUCH, R AF PUGH, TD CHANG, CS UEMURA, H WEINDRUCH, R TI PROSTATIC LOCALIZATION OF SPONTANEOUS EARLY INVASIVE-CARCINOMA IN LOBUND-WISTAR RATS SO CANCER RESEARCH LA English DT Note ID ANDROGEN RECEPTOR; CANCER; ANTIBODIES; NEOPLASIA; TUMORS AB Animal models of human prostate cancer are very limited in number but are of obvious importance to develop. Dr. Morris Pollard (M. Pollard, J. Natl. Cancer Inst., 51: 1235-1241, 1973) has reported that Lobund-Wistar rats develop spontaneous metastatic prostatic cancer when they become old(similar to 25% incidence after 25 months). A chemically-indnced form of the disease has also been described in Lobund-Wistar rats. However, recent reports suggest that most of the chemically induced adenocarcinomas are not prostatic in origin, with most arising in the seminal vesicle, and thereby raise questions about the origin of the spontaneous cancers. We herein report cancer spontaneously arising in the lateral lobes of the prostates in Lobund-Wistar rats. One of 8 rats killed at 16 months of age showed prostatic carcinoma in situ. Two of 39 rats killed at 20 months displayed early invasive adenocarcinomas with no signs of metastases. Because sectioning of the prostates in this study was limited to face sections from a single block for each rat, it is highly probable that the true incidence of dysplasias and carcinomas is underestimated by these data. Dysplastic or neoplastic changes were not seen in either the seminal vesicles or other portions of the prostatic complex. The nuclei of adenocarcinoma cells showed less labeling with antibody to the androgen hormone receptor than did normal cells. These data strongly support the validity of the Pollard model of spontaneous prostate cancer in Lobund-Wister rats. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,DEPT HUMAN ONCOL,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,MADISON,WI 53705. FU NIA NIH HHS [R01 AG 10536] NR 21 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1994 VL 54 IS 22 BP 5766 EP 5770 PG 5 WC Oncology SC Oncology GA PR217 UT WOS:A1994PR21700006 PM 7525050 ER PT J AU GINSBERG, D VAIRO, G CHITTENDEN, T XIAO, ZX XU, GF WYDNER, KL DECAPRIO, JA LAWRENCE, JB LIVINGSTON, DM AF GINSBERG, D VAIRO, G CHITTENDEN, T XIAO, ZX XU, GF WYDNER, KL DECAPRIO, JA LAWRENCE, JB LIVINGSTON, DM TI E2F-4, A NEW MEMBER OF THE E2F TRANSCRIPTION FACTOR FAMILY, INTERACTS WITH P107 SO GENES & DEVELOPMENT LA English DT Article DE E2F; CELL CYCLE; GROWTH CONTROL; TRANSCRIPTION; P107; TRANSFORMATION ID RETINOBLASTOMA GENE-PRODUCT; HUMAN MYC PROMOTER; CELL-CYCLE; TRANS-ACTIVATION; BINDING PROTEIN; DNA-BINDING; GROWTH-REGULATION; IDENTIFICATION; EXPRESSION; COMPLEX AB The E2F family of transcription factors has been implicated in the regulation of cell proliferation, and E2F-binding sites are present in the promoters of several growth-regulating genes. E2F family members are functionally regulated, in part, by complex formation with one or more members of the nuclear pocket protein family, RB, p107, and p130. Pocket protein regulation of E2F likely contributes to normal cellular growth control. While the three cloned species of E2F, E2F-1, E2F-2, and E2F-3, are known to be targets of RB interaction, no E2F species has yet been shown to be a specific p107 or p130 target. Here, we describe the cloning of a new member of the E2F family, E2F-4, which forms heterodimers with a member(s) of the DP family and, unlike some family members, is present throughout the cell cycle and appears to be a differentially phosphorylated p107-binding partner. p107 binding not only can be linked to the regulation of E2F-4 transcriptional activity, but also to suppression of the ability of E2F-4 to transform an immortalized rodent cell line. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV MASSACHUSETTS,MED CTR,DEPT CELL BIOL,WORCESTER,MA 01655. NR 64 TC 319 Z9 322 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 15 PY 1994 VL 8 IS 22 BP 2665 EP 2679 DI 10.1101/gad.8.22.2665 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA PU762 UT WOS:A1994PU76200001 PM 7958924 ER PT J AU BEIJERSBERGEN, RL KERKHOVEN, RM ZHU, LA CARLEE, L VOORHOEVE, PM BERNARDS, R AF BEIJERSBERGEN, RL KERKHOVEN, RM ZHU, LA CARLEE, L VOORHOEVE, PM BERNARDS, R TI E2F-4, A NEW MEMBER OF THE E2F GENE FAMILY, HAS ONCOGENIC ACTIVITY AND ASSOCIATES WITH P107 IN-VIVO SO GENES & DEVELOPMENT LA English DT Article DE E2F; P107; ONCOGENE; CELL CYCLE ID TRANSCRIPTION FACTOR E2F; RETINOBLASTOMA PROTEIN; CELL-CYCLE; BINDING PROTEIN; S-PHASE; C-MYC; RB; PRODUCT; REPRESSION; INHIBITION AB The E2F family of transcription factors controls the expression of genes that are involved in cell cycle regulation. E2F DNA-binding activity is found in complex with the retinoblastoma protein, pRb, and with the pRb-related p107 and p130. To date, cDNAs for three members of the E2F gene family have been isolated. However, all three E2Fs associate in vivo exclusively with pRb. We report here the cloning and functional analysis of a fourth E2F family member. E2F-4 encodes a 413-amino-acid protein with significant homology to E2F-1. E2F-4 antibodies recognize a 60-kD protein in anti-p107 immunoprecipitates, indicating that E2F-4 associates with p107 in vivo. Like the other E2Fs, E2F-4 requires DP-1 for efficient DNA binding and transcriptional activation of E2F site-containing promoters. Increased expression of E2F-4 and DP-1 in SaoS-a osteosarcoma cells causes a shift from G(1)-phase cells to S and G(2)/M-phase cells, suggesting a role for E2F-4 in regulation of cell-cycle progression. We show that expression of E2F-4 and DP-1 together with an activated ras oncogene in rat embryo fibroblasts, causes transformation, indicating that E2F-4 has oncogenic activity. C1 NETHERLANDS CANC INST,DIV MOLEC CARCINOGENESIS,1066 CX AMSTERDAM,NETHERLANDS. MASSACHUSETTS GEN HOSP,CTR CANC,DIV MOLEC ONCOL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. OI Bernards, Rene/0000-0001-8677-3423 NR 45 TC 326 Z9 331 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 15 PY 1994 VL 8 IS 22 BP 2680 EP 2690 DI 10.1101/gad.8.22.2680 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA PU762 UT WOS:A1994PU76200002 PM 7958925 ER PT J AU HEMESATH, TJ STEINGRIMSSON, E MCGILL, G HANSEN, MJ VAUGHT, J HODGKINSON, CA ARNHEITER, H COPELAND, NG JENKINS, NA FISHER, DE AF HEMESATH, TJ STEINGRIMSSON, E MCGILL, G HANSEN, MJ VAUGHT, J HODGKINSON, CA ARNHEITER, H COPELAND, NG JENKINS, NA FISHER, DE TI MICROPHTHALMIA, A CRITICAL FACTOR IN MELANOCYTE DEVELOPMENT, DEFINES A DISCRETE TRANSCRIPTION FACTOR FAMILY SO GENES & DEVELOPMENT LA English DT Article DE MICROPHTHALMIA; DIMERIZATION; DNA BINDING; M BOX; B-HLH-ZIP ID HELIX-LOOP-HELIX; DNA-BINDING ACTIVITY; C-MYC PROTEIN; LEUCINE-ZIPPER; NEGATIVE REGULATOR; MAST-CELLS; MAX; GENE; DIMERIZATION; HETERODIMERS AB The microphthalmia (mi) gene appears essential for pigment cell development and/or survival, based on its mutation in mi mice, It has also been linked to the human disorder Waardenburg Syndrome. The mi gene was recently cloned and predicts a basic/helix-loop-helix/leucine zipper (b-HLH-ZIP) factor with tissue-restricted expression. Here, we show that Mi protein binds DNA as a homo- or heterodimer with TEEB, TEE3, or TFEC, together constituting a new MiT family. Mi can also activate transcription through recognition of the M box, a highly conserved pigmentation gene promoter element, and may thereby determine tissue specific expression of pigmentation enzymes. Six mi mutations shown recently to cluster in the b-HLH-ZIP region produce surprising and instructive effects on DNA recognition and oligomerization. An alternatively spliced exon located outside of the b-HLH-ZIP region is shown to significantly modulate DNA recognition by the basic domain. These findings suggest that Mi's critical roles in melanocyte survival and pigmentation are mediated by MiT family interactions and transcriptional activities. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CO-74101] NR 58 TC 402 Z9 410 U1 1 U2 11 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 15 PY 1994 VL 8 IS 22 BP 2770 EP 2780 DI 10.1101/gad.8.22.2770 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA PU762 UT WOS:A1994PU76200009 PM 7958932 ER PT J AU WEWER, UM GERECKE, DR DURKIN, ME KURTZ, KS MATTEI, MG CHAMPLIAUD, MF BURGESON, RE ALBRECHTSEN, R AF WEWER, UM GERECKE, DR DURKIN, ME KURTZ, KS MATTEI, MG CHAMPLIAUD, MF BURGESON, RE ALBRECHTSEN, R TI HUMAN BETA-2 CHAIN OF LAMININ (FORMERLY S-CHAIN) - CDNA CLONING, CHROMOSOMAL LOCALIZATION, AND EXPRESSION IN CARCINOMAS SO GENOMICS LA English DT Article ID BASEMENT-MEMBRANES; NEUROMUSCULAR-JUNCTION; MULTIDOMAIN PROTEIN; SYNAPTIC CLEFT; SEQUENCE; SUBUNITS; REVEALS; MORPHOGENESIS; HETEROGENEITY; VARIANTS AB Overlapping cDNA clones that encode the full-length human laminin beta 2 chain, formerly called the S chain, were isolated, The cDNA of 5680 nt contains a 5391-nt open reading frame encoding 1797 amino acids, At the amino terminus is a 32-amino-acid signal peptide that is followed by the mature beta 2 chain polypeptide of 1765 amino acids with a calculated molecular mass of 192,389 Da. The human beta 2 chain is predicted to have all of the seven structural domains typical of the beta chains of laminin, including the short cysteine-rich alpha region. The amino acid sequence of human beta 2 chain showed 86.1% sequence identity to the rat beta 2 chain, 50.0% to the human beta 1 chain, and 36.3% to the human beta 3 chain. The greatest sequence identity was in domains VI, V, and III, The sequence of a 24-amino-acid peptide fragment isolated from the beta 2 chain of laminin purified from human amniotic basement membrane matched the sequence predicted from the cDNA, confirming that the cDNA encodes human beta 2 laminin. The cDNA was used to assign the gene (LAMB2) to human chromosome 3p21 by in situ hybridization. It is not linked to genes for human laminin chains alpha 1, beta 1, and gamma 1 or other known laminin genes. Immunostaining showed that the beta 2 chain is localized to the smooth muscle basement membranes of the arteries, while the homologous pi chain is confined to the subendothelial basement membranes. The beta 2 chain was found in the basement membranes of ovarian carcinomas but not colon carcinomas. These results indicate that the expression of the beta 2 chain gene is tightly regulated in normal human tissues and in disease, (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA. HOP ENFANTS LA TIMONE,INSERM,U242,F-13385 MARSEILLE,FRANCE. RP WEWER, UM (reprint author), UNIV COPENHAGEN,INST PATHOL ANAT,MOLEC PATHOL LAB,FREDERIK VS VEJ 11,DK-2100 COPENHAGEN,DENMARK. FU NIAMS NIH HHS [AR35689] NR 43 TC 42 Z9 43 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1994 VL 24 IS 2 BP 243 EP 252 DI 10.1006/geno.1994.1612 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PX512 UT WOS:A1994PX51200006 PM 7698745 ER PT J AU LI, ZG SUMIDA, M BIRCHBAUER, A SCHOTZ, MC REUE, K AF LI, ZG SUMIDA, M BIRCHBAUER, A SCHOTZ, MC REUE, K TI ISOLATION AND CHARACTERIZATION OF THE GENE FOR MOUSE HORMONE-SENSITIVE LIPASE SO GENOMICS LA English DT Article ID CHOLESTEROL ESTER HYDROLASE; ADIPOSE-TISSUE; CHROMOSOMAL LOCALIZATION; MESSENGER-RNA; RECEPTOR GENE; IDENTIFICATION; EXPRESSION; SEQUENCE; RAT; BINDING AB Hormone-sensitive lipase (HSL) is the rate-limiting enzyme in hydrolysis of triglycerides in adipose tissue and of cholesteryl esters in steroidogenic tissues and macrophages. The gene encoding mouse HSL has been isolated and characterized from two overlapping X clones, The gene spans approximately 10.4 kb and comprises 9 exons interrupted by 8 introns. The deduced amino acid sequence specifies a protein of 759 amino acids with a Mr of 83,297 in the absence of posttranslational modifications, The known functional domains of the HSL protein are encoded by discrete exons, with the putative catalytic site (Ser(423)) encoded by exon 6, and the basal and regulatory phosphorylation sites (Ser(557) and Ser(559)) encoded by exon 8, In addition, a putative lipid binding domain occurs in exon 9. The mouse protein shows 94% identity with the previously determined rat sequence and 85% identity with the recently determined human sequence. Interestingly, despite the high degree of similarity, the three species diverge significantly for a stretch of 16 amino acid residues upstream of the phosphorylation sites, In addition, an error was discovered in the carboxyl-terminal portion of the previously reported rat sequence, which produced a frame shift and premature termination of the coding sequence, The corrected rat sequence alters the identity of 12 amino acid residues and extends the protein an additional 11 residues, We have also examined the mouse HSL gene and 5' flanking region for nucleotide sequences that may modulate HSL gene transcription, Using primer extension, we identified a major transcription initiation site 593 nucleotides upstream of the protein coding sequence. Homologies with several known gene regulatory elements are present in the HSL 5' flanking region, including sequence motifs that appear to direct expression in adipose, testis, adrenal, and myeloid tissues. (C) 1994 Academic Press, Inc. C1 UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. RP LI, ZG (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,BLDG 113,ROOM 312,LOS ANGELES,CA 90073, USA. FU NHLBI NIH HHS [HL28481] NR 39 TC 41 Z9 44 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 1994 VL 24 IS 2 BP 259 EP 265 DI 10.1006/geno.1994.1614 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PX512 UT WOS:A1994PX51200008 PM 7698747 ER PT J AU PULKKINEN, L CHRISTIANO, AM GERECKE, D WAGMAN, DW BURGESON, RE PITTELKOW, MR UITTO, J AF PULKKINEN, L CHRISTIANO, AM GERECKE, D WAGMAN, DW BURGESON, RE PITTELKOW, MR UITTO, J TI A HOMOZYGOUS NONSENSE MUTATION IN THE BETA-3 CHAIN GENE OF LAMININ-5 (LAMB3) IN HERLITZ JUNCTIONAL EPIDERMOLYSIS-BULLOSA SO GENOMICS LA English DT Note ID BASEMENT-MEMBRANES; RNA AB Herlitz junctional epidermolysis bullosa (H-JEB) is a severe autosomal recessive disorder characterized by blister formation within the dermal-epidermal basement membrane, Based on immunofluorescence analysis recognizing laminin 5 epitopes (previously known as nicein/kalinin), the genes for this lamina lucida protein have been proposed as candidate genes in H-JEB. In this study, we examined the gene encoding the beta 3 polypeptide chain of laminin 5 (LAMB3) by Northern hybridization and RT-PCR analysis of keratinocyte mRNA from a proband in a family with H-JEB. Northern analysis revealed markedly reduced levels of the laminin beta 3 chain mRNA. Amplification of mRNA by RT-PCR, followed by direct nucleotide sequencing, revealed a homozygous C-to-T transition resulting in a premature termination codon (CGA --> TGA) on both alleles, This mutation was verified at the genomic DNA level, and both parents were shown to be heterozygous carriers of the same mutation. This is the first description of a mutation in the laminin beta 3 chain gene an H-JEB patient. (C) 1994 Academic Press, Inc. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT DERMATOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON INST MOLEC MED,MOLEC DERMATOL SECT,PHILADELPHIA,PA 19107. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. MAYO CLIN & MAYO FDN,DEPT DERMATOL,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,DEPT BIOCHEM & MOLEC BIOL,ROCHESTER,MN 55905. FU NIAMS NIH HHS [P01-AR38923, R01-AR35689, T32-AR07095] NR 15 TC 173 Z9 174 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 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1994 VL 24 IS 2 BP 357 EP 360 DI 10.1006/geno.1994.1627 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PX512 UT WOS:A1994PX51200021 PM 7698759 ER PT J AU GIANELLO, PR BLANCHO, G FISHBEIN, JF LORF, T NICKELEIT, V VITIELLO, D SACHS, DH AF GIANELLO, PR BLANCHO, G FISHBEIN, JF LORF, T NICKELEIT, V VITIELLO, D SACHS, DH TI MECHANISM OF CYCLOSPORINE-INDUCED TOLERANCE TO PRIMARILY VASCULARIZED ALLOGRAFTS IN MINIATURE SWINE - EFFECT OF ADMINISTRATION OF EXOGENOUS IL-2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; DISPARATE RENAL-ALLOGRAFTS; PERIPHERAL TOLERANCE; MONOCLONAL-ANTIBODY; T-CELLS; CLASS-I; INTERLEUKIN-2; INVIVO; TRANSPLANTATION; INDUCTION AB Indefinite tolerance to kidney allografts across a two-haplotype class I disparity can be induced in miniature swine in 100% of cases by a short course of cyclosporin A (CyA). Without CyA, all recipients reject kidney allografts within 2 wk. These animals therefore provide a unique opportunity to study the mechanisms of induction and maintenance of tolerance in a large animal model. Previous studies of cellular and humoral immunity suggested that a T cell help deficit at the time of the first exposure of the host's immune system to alloantigens was involved in tolerance induction. We have now studied the effect of exogenous T cell help in the form of an IL-2 infusion during both the induction and maintenance phases of tolerance. Lymphoid infiltrates were seen in class I mismatched renal allografts by day 8 in all animals whether treated with CyA or not. Administration of i.v. IL-2 on postoperative days 8, 9, and 10 to animals receiving the full CyA tolerizing regimen led to acute rejection in four of four animals. These rejecting animals showed induction of IL-2R expression on graft infiltrating cells in the kidney, suggesting that the infiltrates present before IL-2 administration were capable of causing rejection once T cell help was provided. Treatment with IL-2 did not abrogate long-term tolerance. Thus, limitation of T cell help at the time of first exposure to Ag in this model appears to be required to prevent rejection during the time required for active tolerance to develop. Once established, this tolerance does not appear to require continuous limitation of T cell help to be maintained, suggesting loss, inactivation, or suppression of the cells capable of causing rejection. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02129. FU NHLBI NIH HHS [HL18646]; NIAID NIH HHS [AI31046] NR 39 TC 38 Z9 40 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1994 VL 153 IS 10 BP 4788 EP 4797 PG 10 WC Immunology SC Immunology GA PR222 UT WOS:A1994PR22200046 PM 7963544 ER PT J AU HOLLANDER, GA FRUMAN, DA BIERER, BE BURAKOFF, SJ AF HOLLANDER, GA FRUMAN, DA BIERER, BE BURAKOFF, SJ TI DISRUPTION OF T-CELL DEVELOPMENT AND REPERTOIRE SELECTION BY CALCINEURIN INHIBITION IN-VIVO SO TRANSPLANTATION LA English DT Article ID CYCLOSPORINE-A; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; THYMIC MICROENVIRONMENT; PHOSPHATASE-ACTIVITY; POSITIVE SELECTION; THYMOCYTES; MICE; CYCLOPHILIN; ACTIVATION AB The microbial products FK506 and CsA are potent immunosuppressive agents that prevent early transcriptional events in TcR-mediated activation. Their mode of action is dependent upon the inhibition of calcineurin, a serine/threonine phosphatase positioned within the calcium-dependent signaling pathway. TcR-mediated activation of thymocytes constitutes an important prerequisite for their development and selection to mature T cells. Disruption of the cross-talk between thymic APC and thymocytes results in the loss of normal T cell ontogeny. To study the role of calcineurin in T cell maturation and repertoire selection in vivo, mice were treated with either FK506 or CsA. Administration of either drug inhibited the progression of CD4(+)CD8(+) positive thymocytes to mature single positive T cells. Furthermore, both drugs disrupted the process of negative thymic selection, causing an increased frequency of self-reactive cells among the few positively selected T cells. These effects correlated directly with the degree of inhibition of in vivo calcineurin enzyme activity. Blocking calcineurin activity appears to disrupt positive thymic selection and to prevent the deletion of self-reactive thymocytes. C1 BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP HOLLANDER, GA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,ROOM 1718,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [P01 CA39542-08A1]; PHS HHS [R01 A132514] NR 36 TC 23 Z9 23 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 1994 VL 58 IS 9 BP 1037 EP 1043 DI 10.1097/00007890-199411150-00011 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA PR964 UT WOS:A1994PR96400011 PM 7526495 ER PT J AU SCAGLIONI, PP MELEGARI, M WANDS, JR AF SCAGLIONI, PP MELEGARI, M WANDS, JR TI CHARACTERIZATION OF HEPATITIS-B VIRUS CORE MUTANTS THAT INHIBIT VIRAL REPLICATION SO VIROLOGY LA English DT Article ID GENOMIC RNA ENCAPSIDATION; ANTISENSE OLIGODEOXYNUCLEOTIDES; PREGENOME ENCAPSIDATION; REVERSE TRANSCRIPTION; SURFACE-ANTIGEN; GENE-PRODUCTS; DNA-SYNTHESIS; EXPRESSION; PARTICLES; HEPADNAVIRUS AB We have generated and functionally characterized dominant negative core protein variants of the hepadnaviruses to determine their effects on ''wild type'' viral replication. Plasmids expressing these constructs were introduced into hepatoma cell lines by transient transfection and effects on wild type woodchuck hepatitis virus (WHV) and hepatitis a virus (HBV) replication were evaluated by Southern blot analysis of purified viral core particles. WHV and HBV constructs expressing a truncated core protein fused in frame with the C-terminus of the small surface protein were found to inhibit viral replication by 90-95% due to disruption of the viral nucleocapsid assembly process and preventing encapsidation of pregenomic RNA. The antiviral effects were found to be specific for the targeted virus. These results demonstrate that mutants of hepadnaviral core protein may represent a novel class of antiviral agents. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. OI Scaglioni, Pier Paolo/0000-0002-6036-5138 FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-00048, AA-08169] NR 35 TC 51 Z9 59 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 0042-6822 J9 VIROLOGY JI Virology PD NOV 15 PY 1994 VL 205 IS 1 BP 112 EP 120 DI 10.1006/viro.1994.1625 PG 9 WC Virology SC Virology GA PQ623 UT WOS:A1994PQ62300013 PM 7975206 ER PT J AU ZITTEL, TT DEGIORGIO, R STERNINI, C RAYBOULD, HE AF ZITTEL, TT DEGIORGIO, R STERNINI, C RAYBOULD, HE TI FOS PROTEIN EXPRESSION IN THE NUCLEUS OF THE SOLITARY TRACT IN RESPONSE TO INTESTINAL NUTRIENTS IN AWAKE RATS SO BRAIN RESEARCH LA English DT Article DE NUCLEUS OF THE SOLITARY TRACT; FOS-LIKE IMMUNOREACTIVITY; IMMUNOCYTOCHEMISTRY; SMALL INTESTINE; LIPID; CARBOHYDRATE ID C-FOS; BRAIN-STEM; SPINAL-CORD; CHOLECYSTOKININ; REPRESENTATION; SUPPRESSION; STIMULATION; INDUCTION; STIMULUS; NEURONS AB Nutrients in the intestine inhibit food intake via an action on the vagal afferent pathway. The aim of the present study was to use immunochemical detection of Fos protein-like immunoreactivity (FLI) in the brainstem to trace the neuronal pathways activated by intestinal nutrients. Perfusion of the intestine of awake rats via an indwelling duodenal catheter with iso-osmotic mannitol, hydrochloric acid or casein hydrolysate had no effect on the number of FLI neurons in the nucleus of the solitary tract (NTS). Lipid emulsion (20%) and 2.7 M glucose significantly increased the number of immunopositive cells in the NTS. There was a significant increase in the number of immunopositive cells from caudal to rostral NTS. Nutrients effective at decreasing food intake (carbohydrate and fat) produced significant increases in Fos-like immunopositive cells in the NTS. C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,CTR GASTROCNTER BIOL,CURE,DEPT MED,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,CTR GASTROCNTER BIOL,CURE,DEPT PHYSIOL,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,CTR GASTROCNTER BIOL,CURE,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,BRAIN RES INST,LOS ANGELES,CA. OI De Giorgio, Roberto/0000-0003-0867-5873 FU NIDDK NIH HHS [DK41004, DK41301] NR 26 TC 58 Z9 58 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 14 PY 1994 VL 663 IS 2 BP 266 EP 270 DI 10.1016/0006-8993(94)91272-6 PG 5 WC Neurosciences SC Neurosciences & Neurology GA PQ749 UT WOS:A1994PQ74900011 PM 7874510 ER PT J AU OLSZEWSKI, S DEENEY, JT SCHUPPIN, GT WILLIAMS, KP CORKEY, BE RHODES, CJ AF OLSZEWSKI, S DEENEY, JT SCHUPPIN, GT WILLIAMS, KP CORKEY, BE RHODES, CJ TI RAB3A EFFECTOR DOMAIN PEPTIDES INDUCE INSULIN EXOCYTOSIS VIA A SPECIFIC INTERACTION WITH A CYTOSOLIC PROTEIN DOUBLET SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING PROTEIN; SYNAPTIC VESICLES; GUANINE-NUCLEOTIDES; SYNTHETIC PEPTIDE; EXCHANGE PROTEIN; TARGET PROTEIN; KINASE-C; SMG P25A; B-CELLS; SECRETION AB A key protein involved in the regulated exocytotic mechanism in neuroendocrine cells is the GTP-binding protein, Rab3A. Rab3A is thought to mediate exocytosis by an interaction of its effector domain with a putative effector protein. we demonstrate here that Rab3A effector domain peptides specifically stimulated insulin exocytosis in electroporated insulin-secreting cells (K-0.5 activation, 6-8 mu M) in a Ca2+-independent manner, although in the presence of Ca2+ insulin exocytosis was further potentiated. By using a I-125-radiolabeled photoactivated cross-linking Rab3A effector domain peptide, we identified a cytosolic protein doublet (REEF-1 and REEP-2), which specifically interacted with the Rab3A effector domain. Competitive inhibition studies revealed this protein-protein interaction to be at a concentration equivalent to that required for Rab3A effector domain peptides to trigger insulin exocytosis (K-i, 6-8 mu M) Furthermore, under basal secretory conditions REEF-1 and -2 were membrane associated, but upon stimulation of exocytosis they were released into a cytosolic fraction. Our results suggest that REEF-I and -2 are part of the regulated exocytotic machinery, and their dissociation upon stimulation of hormone release (likely from a protein complex) may be essential to the mechanism that triggers regulated exocytosis in pancreatic beta-cells. C1 BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,EP JOSLIN RES LAB,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. BOSTON UNIV,SCH MED,DEPT DIABET & METAB,BOSTON,MA 02118. OI Deeney, Jude/0000-0003-0988-9419 FU NIDDK NIH HHS [DK36836, DK35914, DK47919] NR 42 TC 40 Z9 41 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 11 PY 1994 VL 269 IS 45 BP 27987 EP 27991 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV772 UT WOS:A1994PV77200035 PM 7961732 ER PT J AU HO, AM JAIN, J RAO, A HOGAN, PG AF HO, AM JAIN, J RAO, A HOGAN, PG TI EXPRESSION OF THE TRANSCRIPTION FACTOR NFATP IN A NEURONAL CELL-LINE AND IN THE MURINE NERVOUS-SYSTEM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED T-CELLS; CIS-ACTING ELEMENT; NUCLEAR FACTOR; CYCLOSPORINE-A; GENE-EXPRESSION; SPINAL-CORD; NF-AT; FOS; PROTEIN; BINDING AB The transcription factor NFATp, which has a central role in cytokine gene induction in T cells, was previously thought to be expressed only in T cells and other immune cells. Here we report that NFATp, is also expressed in the rat PC12 pheochromocytoma cell line and in the murine nervous system. Antisera against T cell NFATp recognize proteins of similar apparent molecular weight in T cells, PC12 cells, and murine olfactory bulb. The immunoreactive proteins from PC12 cells and from olfactory bulb bind to an NFAT site of the murine interleukin-2 promoter with the same specificity as T cell NFATp. Immunohistochemical staining localizes NFATp to neurons, specifically to olfactory receptor neurons and to their terminals in the olfactory bulb. The presence of NFATp in the nervous system suggests that it has a role in the transcription of specific neuronal genes in response to increases in cytosolic calcium. C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA42471] NR 38 TC 114 Z9 115 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 11 PY 1994 VL 269 IS 45 BP 28181 EP 28186 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV772 UT WOS:A1994PV77200062 PM 7961754 ER PT J AU NISHIYAMA, T MCDONOUGH, AM BRUNS, RR BURGESON, RE AF NISHIYAMA, T MCDONOUGH, AM BRUNS, RR BURGESON, RE TI TYPE-XII AND TYPE-XIV COLLAGENS MEDIATE INTERACTIONS BETWEEN BANDED COLLAGEN-FIBERS IN-VITRO AND MAY MODULATE EXTRACELLULAR-MATRIX DEFORMABILITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANCHORING FIBRILS; GEL CONTRACTION; VII COLLAGEN; VONWILLEBRAND-FACTOR; GROWTH-FACTOR; IX COLLAGEN; FIBROBLASTS; IDENTIFICATION; FORM; REORGANIZATION AB Type XII and XIV collagens are very large molecules containing three extended globular domains derived from the amino terminus of each cu chain and an interrupted triple helix. Both collagens are genetically and immunologically unique and have distinct distributions in many tissues. These collagens localize near the surface of banded collagen fibrils. The function of the molecules is unknown. We have prepared a mixture of native type XII and XIV collagens that is free of contaminating proteins by electrophoretic criteria. In addition, we have purified the collagenase-resistant globular domains of type XII or XIV collagens (XII-NC-3 or XIV-NC-3). In this study, we have investigated the effect of intact type XII and XIV and XII-NC-3 or XIV-NC-3 on the interactions between fibroblasts and type I collagen fibrils. We find that both type XII and XIV collagens promote collagen gel contraction mediated by fibroblasts, even in the absence of serum, The activity is present in the NC-3 domains. The effect is dose-dependent and is inhibited by denaturation. The effect of type XII NC-3 is inhibited by the addition of anti-XII antiserum. To elucidate the mechanism underlying this phenomenon, we examined the effect of XII-NC-3 or XIV-NC-3 on deformability of collagen gels by centrifugal force. XII-NC-3 or XIV-NC-3 markedly promotes gel compression after centrifugation. The effect is also inhibited by denaturation, and the activity of type XII-NC3 is inhibited by the addition of anti-MT antiserum. The results indicate that the effect of XII-NC-3 or XIV-NC-3 on collagen gel contraction by fibroblasts is not due to activation of cellular events but rather results from the increase in mobility of hydrated collagen fibrils within the gel. These studies suggest that collagen types XII and XIV may modulate the biomechanical properties of tissues. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02129. RI Nishiyama, Toshio/C-5434-2013 FU NIADDK NIH HHS [AM35689] NR 29 TC 115 Z9 117 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 11 PY 1994 VL 269 IS 45 BP 28193 EP 28199 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV772 UT WOS:A1994PV77200064 PM 7961756 ER PT J AU BOYAN, BD SCHWARTZ, Z PARKSNYDER, S DEAN, DD YANG, FM TWARDZIK, D BONEWALD, LF AF BOYAN, BD SCHWARTZ, Z PARKSNYDER, S DEAN, DD YANG, FM TWARDZIK, D BONEWALD, LF TI LATENT TRANSFORMING GROWTH-FACTOR-BETA IS PRODUCED BY CHONDROCYTES AND ACTIVATED BY EXTRACELLULAR-MATRIX VESICLES UPON EXPOSURE TO 1,25-(OH)(2)D-3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VITAMIN-D METABOLITES; ARACHIDONIC-ACID TURNOVER; MOLECULAR-WEIGHT COMPLEX; CARTILAGE CELLS-INVITRO; RESTING ZONE; ALKALINE-PHOSPHATASE; PLATE CHONDROCYTES; FACTOR-BETA-1 GENE; MESSENGER-RNA; BONE CULTURES AB Resting zone and growth zone (GC) costochondral chondrocytes constitutively release latent, but not active, transforming growth factor-beta (TGF-beta) into the culture medium. When exogenous TGF-beta is added to the culture medium, no autocrine effect is observed. However, when 1,25-(OH)(2)D-3 is added, a dose-dependent inhibition of latent TGF-beta release is found. Messenger RNA levels for TGF-beta 1 are unchanged by treatment with either 1,25-(OH)(2)D-3 or TGF-beta 1. Since active growth factor was not observed in the conditioned medium, we tested the hypothesis that latent TGF-beta could be activated in the matrix. GC matrix vesicles, extracellular organelles associated with matrix calcification, were able to activate latent TGF-beta 1 and TGF-beta 2 when preincubated with 1,25-(OH)(2)D-3. In contrast, GC plasma membranes activated latent TGF-beta, and addition of 1,25-(OH)(2)D-3 inhibited this activation. The 1,25-(OH)(2)D-3-dependent decrease in latent TGF-beta in the medium, with no detectable change in mRNA level, and the inhibition of plasma membrane activation of latent TGF-beta by 1,25-(OH)(2)D-3 suggest that 1,25-(OH)(2)D-3 may act through post-transcriptional and/or nongenomic mechanisms. The results also suggest that latent TGF-beta is activated in the matrix and that 1,25-(OH)(2)D-3 regulates this activation by a direct, non-genomic action on the matrix vesicle membrane. C1 UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PERIODONT,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED ENDOCRINOL & METAB,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT STRUCT & CELLULAR BIOL,SAN ANTONIO,TX 78284. HEBREW UNIV JERUSALEM,HADASSAH FAC DENT MED,DEPT PERIODONT,JERUSALEM,ISRAEL. ADV TISSUE SCI,LA JOLLA,CA 92037. UNIV WASHINGTON,SCH MED,DEPT DERMATOL,SEATTLE,WA 98195. AUDIE MURPHY VET AFFAIRS MED CTR,SAN ANTONIO,TX 78284. RP BOYAN, BD (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT ORTHOPAED,SAN ANTONIO,TX 78284, USA. FU NIDCR NIH HHS [DE05937, DE08569, DE08603] NR 69 TC 81 Z9 82 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 11 PY 1994 VL 269 IS 45 BP 28374 EP 28381 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV772 UT WOS:A1994PV77200089 PM 7961777 ER PT J AU BOUSSIOTIS, VA BARBER, DL NAKARAI, T FREEMAN, GJ GRIBBEN, JG BERNSTEIN, GM DANDREA, AD RITZ, J NADLER, LM AF BOUSSIOTIS, VA BARBER, DL NAKARAI, T FREEMAN, GJ GRIBBEN, JG BERNSTEIN, GM DANDREA, AD RITZ, J NADLER, LM TI PREVENTION OF T-CELL ANERGY BY SIGNALING THROUGH THE GAMMA(C) CHAIN OF THE IL-2 RECEPTOR SO SCIENCE LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; CTLA-4 COUNTER-RECEPTOR; HUMAN LYMPHOCYTES-T; CLONAL ANERGY; FUNCTIONAL COMPONENT; INTERLEUKIN-2; INDUCTION; ANTIGEN; MICE; PROLIFERATION AB When stimulated through their antigen receptor without requisite costimulation, T cells enter a state of antigen-specific unresponsiveness, termed anergy. In this study, signaling through the common gamma chain of the interleukin-2 (IL-2), IL-4, and IL-7 receptors in the presence of antigen was found to be sufficient to prevent the induction of anergy. After culture with IL-2, IL-4, or IL-7, Jak3 kinase was tyrosine-phosphorylated, which correlated with the prevention of anergy. Therefore, a signal through the common gamma chain may regulate the decision of T cells to either clonally expand or enter a state of anergy. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP BOUSSIOTIS, VA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. RI Ain, Kenneth/A-5179-2012; Ritz, Jerome/C-7929-2009 OI Ain, Kenneth/0000-0002-2668-934X; Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA 40216]; NIAID NIH HHS [AI 35225] NR 51 TC 302 Z9 305 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 11 PY 1994 VL 266 IS 5187 BP 1039 EP 1042 DI 10.1126/science.7973657 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ924 UT WOS:A1994PQ92400043 PM 7973657 ER PT J AU CAMPBELL, LJ BORGES, LF HELDRICH, FJ AF CAMPBELL, LJ BORGES, LF HELDRICH, FJ TI MICROWAVE ACCELERATED PREPARATION OF ARYL 2-(N,N-DIETHYLAMINO)ETHYL ETHERS SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article AB A simple and expedient method for the preparation of the ubiquitous 2-(N,N-diethylamino)ethyl aryl ether moiety using a conventional microwave oven has been developed. The reactions are performed with pulsed microwave irradiation, to produce gram quantities of ethers in good yields. C1 COLL CHARLESTON,DEPT CHEM,CHARLESTON,SC 29424. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA 02114. NR 15 TC 14 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 10 PY 1994 VL 4 IS 21 BP 2627 EP 2630 DI 10.1016/S0960-894X(01)80297-3 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA PT379 UT WOS:A1994PT37900026 ER PT J AU ARAKI, E LIPES, MA PATTI, ME BRUNING, JC HAAG, B JOHNSON, RS KAHN, CR AF ARAKI, E LIPES, MA PATTI, ME BRUNING, JC HAAG, B JOHNSON, RS KAHN, CR TI ALTERNATIVE PATHWAY OF INSULIN SIGNALING IN MICE WITH TARGETED DISRUPTION OF THE IRS-1 GENE SO NATURE LA English DT Article ID GROWTH FACTOR-I; STIMULATES TYROSINE PHOSPHORYLATION; RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3-KINASE; HEMATOPOIETIC-CELLS; SIGNALING PATHWAYS; PROTEIN; MUSCLE; TRANSMISSION; EXPRESSION AB THE principal substrate for the insulin and insulin-like growth factor-1 (IGF-1) receptors is the cytoplasmic protein insulin-receptor substrate-1 (IRS-1/pp185)(1-7). After tyrosine phosphorylation at several sites, IRS-1 binds to and activates phosphatidylinositol-3'-OH kinase (PI(3)K)(8-11) and several other proteins containing SH2 (Src-homology 2) domains(12-14). To elucidate the role of IRS-1 in insulin/IGF-1 action, we created IRS-1-deficient mice by targeted gene mutation. These mice had no IRS-1 and shelved no evidence IRS-1 phosphorylation or IRS-1-associated PI(3)K activity. They also had a 50 per cent reduction in intrauterine growth, impaired glucose tolerance, and a decrease in insulin/IGF-1-stimulated glucose uptake in vivo and in vitro. The residual insulin/ IGF-1 action correlated with the appearance of a new tyrosine-phosphorylated protein (IRS-2) which binds to PI(3)K, but is slightly larger than and immunologically distinct from IRS-1. Our results provide evidence for IRS-1-dependent and IRS-1-independent pathways of insulin/IGF-1 signalling and for the existence of an alternative substrate of these receptor kinases. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. OI Johnson, Randall/0000-0002-4084-6639 NR 31 TC 949 Z9 965 U1 0 U2 29 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD NOV 10 PY 1994 VL 372 IS 6502 BP 186 EP 190 DI 10.1038/372186a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ688 UT WOS:A1994PQ68800058 PM 7526222 ER PT J AU BORSOOK, D FALKOWSKI, O ROSEN, H COMB, M HYMAN, SE AF BORSOOK, D FALKOWSKI, O ROSEN, H COMB, M HYMAN, SE TI OPIOIDS MODULATE STRESS-INDUCED PROENKEPHALIN GENE-EXPRESSION IN THE HYPOTHALAMUS OF TRANSGENIC MICE - A MODEL OF ENDOGENOUS OPIOID GENE-REGULATION BY EXOGENOUS OPIOIDS SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS ID MESSENGER-RNA; WITHDRAWAL AB Stressful stimuli strongly induce proenkephalin gene expression within the paraventricular nucleus (PVN) of the hypothalamus. A human proenkephalin-13-galactosidase fusion gene has previously been shown to give correct phenotypic expression and appropriate stress-regulation within the hypothalamus of transgenic mice; this model provides high sensitivity, cellular resolution, and ready quantification of levels of proenkephalin gene expression. Here we describe use of this transgenic model to study modulation of stress-regulated gene expression in the PVN by opiates. Acute or subacute morphine administration prior to a hypertonic saline stress produced marked superinduction of transgene expression compared with hypertonic saline stress alone. In contrast, chronic morphine administration decreased basal expression of the transgene, and inhibited stress-induced expression of the transgene. The endogenous proenkephalin mRNA was induced in parallel with the transgene as demonstrated by in situ hybridization; the immediate early gene, c-Fos was also regulated in parallel with the transgene. These data suggest that acute or subacute morphine administration sensitizes proenkephalin neurons within the PVN and other regions of the hypothalamus to stress and chronic morphine administration desensitizes this response. Because the molecular mechanisms regulating the expression of the transgene are well understood, this model provides a useful tool for investigating cellular and molecular effects of opioids on the hypothalamus. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT MOLEC VIROL,IL-91010 JERUSALEM,ISRAEL. RP BORSOOK, D (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,MOLEC & DEV NEUROSCI LAB,BOSTON,MA, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 29 EP 30 DI 10.1016/0167-0115(94)90373-5 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800016 ER PT J AU HYMAN, SE KONRADI, C COLE, RL AF HYMAN, SE KONRADI, C COLE, RL TI REGULATION OF STRIATAL PROENKEPHALIN AND PRODYNORPHIN GENE-EXPRESSION BY TRANSCRIPTION FACTOR CREB SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS AB There has been controversy over the precise mechanisms by which neural stimuli acting via cAMP and Ca2+ pathways regulate expression of the genes encoding the opioid peptide precursors proenkephalin and prodynorphin. Evidence has been adduced for both AP-1 proteins, including Fos, and CREB-like proteins as the key factors transducing signals to the DNA. Here we present evidence from in vivo systems that CREB, rather than Fos, is likely the key protein regulating cAMP responsiveness of these two opioid genes. In addition, we show that CREB is phosphorylated in vivo in response to stimuli known to regulate these opioid genes. RP HYMAN, SE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC & DEV NEUROSCI LAB,CNY-2 149,13TH ST,BOSTON,MA 02129, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 127 EP 128 DI 10.1016/0167-0115(94)90422-7 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800065 ER PT J AU SEDDON, JM AJANI, UA SPERDUTO, RD HILLER, R BLAIR, N BURTON, TC FARBER, MD GRAGOUDAS, ES HALLER, J MILLER, DT YANNUZZI, LA WILLETT, W AF SEDDON, JM AJANI, UA SPERDUTO, RD HILLER, R BLAIR, N BURTON, TC FARBER, MD GRAGOUDAS, ES HALLER, J MILLER, DT YANNUZZI, LA WILLETT, W TI DIETARY CAROTENOIDS, VITAMIN-A, VITAMIN-C, AND VITAMIN-E, AND ADVANCED AGE-RELATED MACULAR DEGENERATION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CIGARETTE SMOKERS; RETINA; PLASMA; ASCORBATE; LIGHT; RATS AB Objective.-To evaluate the relationships between dietary intake of carotenoids and vitamins A, C, and E and the risk of neovascular age-related macular degeneration (AMD), the leading cause of irreversible blindness among adults. Design.-The multicenter Eye Disease Case-Control Study. Setting.-Five ophthalmology centers in the United States. Patients.-A total of 356 case subjects who were diagnosed with the advanced stage of AMD within 1 year prior to their enrollment, aged 55 to 80 years, and residing near a participating clinical center. The 520 control subjects were from the same geographic areas as case subjects, had other ocular diseases, and were frequency-matched to cases according to age and sex. Main Outcome Measures.-The relative risk for AMD was estimated according to dietary indicators of antioxidant status, controlling for smoking and other risk factors, by using multiple logistic-regression analyses. Results.-A higher dietary intake of carotenoids was associated with a lower risk for AMD. Adjusting for other risk factors for AMD, we found that those in the highest quintile of carotenoid intake had a 43% lower risk for AMD compared with those in the lowest quintile (odds ratio, 0.57; 95% confidence interval, 0.35 to 0.92; P for trend=.02). Among the specific carotenoids, lutein and zeaxanthin, which are primarily obtained from dark green, leafy vegetables, were most strongly associated with a reduced risk for AMD (P for trend=.001). Several food items rich in carotenoids were inversely associated with AMD. In particular, a higher frequency of intake of spinach or collard greens was associated with a substantially lower risk for AMD (P for trend<.001). The intake of preformed vitamin A (retinol) was not appreciably related to AMD. Neither vitamin E nor total vitamin C consumption was associated with a statistically significant reduced risk for AMD, although a possibly lower risk for AMD was suggested among those with higher intake of vitamin C, particularly from foods. Conclusion.-Increasing the consumption of foods rich in certain carotenoids, in particular dark green, leafy vegetables, may decrease the risk of developing advanced or exudative AMD, the most visually disabling form of macular degeneration among older people. These findings support the need for further studies of this relationship. C1 MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. NEI,BETHESDA,MD 20892. UNIV ILLINOIS,DEPT OPHTHALMOL,CHICAGO,IL 60680. MED COLL WISCONSIN,DEPT OPHTHALMOL,MILWAUKEE,WI 53226. WILMER EYE INST,BALTIMORE,MD. CTR DIS CONTROL & PREVENT,DIV ENVIRONM HLTH LAB SCI,ATLANTA,GA 30341. MANHATTAN EYE EAR & THROAT HOSP,NEW YORK,NY 10021. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RP SEDDON, JM (reprint author), MASSACHUSETTS EYE & EAR INFIRM,EPIDEMIOL UNIT,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY09972] NR 27 TC 842 Z9 870 U1 6 U2 78 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 9 PY 1994 VL 272 IS 18 BP 1413 EP 1420 DI 10.1001/jama.272.18.1413 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA PP690 UT WOS:A1994PP69000028 PM 7933422 ER PT J AU WEG, JG BALK, RA THARRATT, RS JENKINSON, SG SHAH, JB ZACCARDELLI, D HORTON, J PATTISHALL, EN AF WEG, JG BALK, RA THARRATT, RS JENKINSON, SG SHAH, JB ZACCARDELLI, D HORTON, J PATTISHALL, EN TI SAFETY AND POTENTIAL EFFICACY OF AN AEROSOLIZED SURFACTANT IN HUMAN SEPSIS-INDUCED ADULT-RESPIRATORY-DISTRESS-SYNDROME SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Note ID SYNTHETIC SURFACTANT; PULMONARY SURFACTANT; EXOGENOUS SURFACTANT; LUNG INJURY; MORTALITY; FAILURE; DELIVERY; SYSTEM AB Objective.-To evaluate the safety and potential efficacy of aerosolized surfactant in intubated patients with adult respiratory distress syndrome (ARDS). Design.-A prospective, double-blind, placebo-controlled, randomized, parallel, mutlicenter pilot clinical trial. Patients.-A total of 51 patients with sepsis-induced ARDS were entered into the study within 18 hours of developing sepsis or sepsis syndrome. Intervention.-Patients were randomized into four treatment groups in a 2:1:2:1 ratio, as follows: 12 hours of surfactant per day, 12 hours of 0.6% saline per day, 24 hours of surfactant per day, and 24 hours of 0.6% saline per day. Surfactant or saline was aerosolized continuously for up to 5 days using an in-line nebulizer that aerosolized only during inspiration. Main Outcome Measures.-Ventilatory data, arterial blood gases, and hemodynamic parameters were measured at baseline, every 4 or 8 hours during the 5 days of treatment, 24 hours after treatment, and 30 days after treatment, at which time mortality was also assessed. Safety was evaluated throughout the 30 days of the study. Results.-Surfactant was administered safely in ventilated patients when given continuously throughout the 5 days using the nebulizer system. Although there were no differences in any physiological parameter between the treatment groups, there was a dose-dependent trend in reduction of mortality from 47% in the combined placebo group to 41% and 35% in the groups treated with 12 hours and 24 hours of surfactant per day, respectively. Conclusions-Aerosolized surfactant was well tolerated when administered on a continuous basis for up to 5 days; however, at the doses given, it did not result in significant improvements in patients with sepsis-induced ARDS. C1 RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT PULM & CRIT CARE MED,CHICAGO,IL 60612. UNIV CALIF DAVIS,CTR MED,DIV PULM & CRIT CARE MED,SACRAMENTO,CA. AUDIE L MURPHY VET AFFAIRS HOSP,PULM DIS SECT,SAN ANTONIO,TX. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT ANESTHESIOL,RICHMOND,VA 23298. BURROUGHS WELLCOME CO,DIV CLIMATE RES,RES TRIANGLE PK,NC 27709. RP WEG, JG (reprint author), UNIV MICHIGAN,CTR MED,DEPT INTERNAL MED,DIV PULM & CRIT CARE MED,ROOM B1H245-0026,ANN ARBOR,MI 48109, USA. NR 37 TC 102 Z9 104 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 9 PY 1994 VL 272 IS 18 BP 1433 EP 1438 DI 10.1001/jama.272.18.1433 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PP690 UT WOS:A1994PP69000031 PM 7933425 ER PT J AU LEE, LA GRITSCH, HA SERGIO, JJ ARN, JS GLASER, RM SABLINSKI, T SACHS, DH SYKES, M AF LEE, LA GRITSCH, HA SERGIO, JJ ARN, JS GLASER, RM SABLINSKI, T SACHS, DH SYKES, M TI SPECIFIC TOLERANCE ACROSS A DISCORDANT XENOGENEIC TRANSPLANTATION BARRIER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANTIGEN-PRESENTING CELLS; CLONAL DELETION; T-CELLS; SUPRALETHAL IRRADIATION; MOUSE; INDUCTION AB Successful induction of tolerance across disparate (discordant) species barriers could overcome the organ shortage that presently limits clinical transplantation. We demonstrate here that xenogeneic swine thymic transplants can induce tolerance to swine antigens in mice, while positively selecting functional host CD4(+) T cells. Immunologically normal C57BL/10 mice were thymectomized and depleted of T and natural killer cells; then they received transplants of fetal pig thymus and liver fragments. Mature mouse CD4(+) T cells developed in the pig thymus grafts and migrated to the periphery. Swine grafts grew markedly and no anti-pig IgG response was produced. Mixed lymphocyte reactions confirmed that the new T cells were functional and were tolerant to pig antigens. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. BIOTRANSPLANT INC,BOSTON,MA 02129. FU NCI NIH HHS [T32-CA09216-14]; NHLBI NIH HHS [HL49915] NR 12 TC 89 Z9 91 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 8 PY 1994 VL 91 IS 23 BP 10864 EP 10867 DI 10.1073/pnas.91.23.10864 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ938 UT WOS:A1994PQ93800023 PM 7971974 ER PT J AU QIN, XQ LIVINGSTON, DM KAELIN, WG ADAMS, PD AF QIN, XQ LIVINGSTON, DM KAELIN, WG ADAMS, PD TI DEREGULATED TRANSCRIPTION FACTOR E2F-1 EXPRESSION LEADS TO S-PHASE ENTRY AND P53-MEDIATED APOPTOSIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; WILD-TYPE P53; LARGE T-ANTIGEN; C-MYC; GROWTH SUPPRESSION; BINDING PROTEIN; CELL-CYCLE; TRANSACTIVATION; IDENTIFICATION; INHIBITION AB E2F-1 is a transcription factor suspected of activating genes required for S phase and a known target for the action of RB, the retinoblastoma gene product. Its induction in quiescent fibroblasts led to S-phase entry followed by apoptosis. E2F-1-mediated apoptosis was suppressed by coexpression of wild-type RB or a transdominant negative mutant species of p53. In contrast, coexpression of a naturally occurring loss-of-function RB mutant or wild-type p53 did not suppress the induction of apoptosis under these conditions. Thus, deregulated E2F-1 activity gives rise to proliferative and apoptotic signals. p53 appears to participate in the execution of the latter. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA 02115. NR 53 TC 685 Z9 688 U1 3 U2 5 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 8 PY 1994 VL 91 IS 23 BP 10918 EP 10922 DI 10.1073/pnas.91.23.10918 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ938 UT WOS:A1994PQ93800034 PM 7971984 ER PT J AU FURUKAWA, T ITOH, M KRUEGER, NX STREULI, M SAITO, H AF FURUKAWA, T ITOH, M KRUEGER, NX STREULI, M SAITO, H TI SPECIFIC INTERACTION OF THE CD45 PROTEIN-TYROSINE-PHOSPHATASE WITH TYROSINE-PHOSPHORYLATED CD3 ZETA-CHAIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE T-CELL ACTIVATION; DEPHOSPHORYLATION ID LEUKOCYTE-COMMON ANTIGEN; T-CELL RECEPTOR; ALTERNATIVELY SPLICED EXONS; DIFFERENTIAL EXPRESSION; EXTRACELLULAR REGION; CATALYTIC DOMAINS; ESCHERICHIA-COLI; MURINE CD45; KINASE; FAMILY AB The CD45 transmembrane protein-tyrosine phosphatase (PTPase, EC 3.1.3.48) plays an essential role in T-cell activation by activating the Lck and/or Fyn protein-tyrosine kinases. However, numerous experiments have indicated that CD45 may have both stimulatory and inhibitory roles in T-cell activation. Thus, it is unlikely that the two kinases are the sole substrates of the CD45 PTPase. Furthermore, the complex regulation of the alternative splicing of the extracellular domain in various leukocyte lineages also suggests additional roles for the CD45 PTPase. To identify such functions, it is necessary to identify physiologically relevant substrates of the CD45 PTPase other than the two protein-tyrosine kinases. To this end, we searched for high-affinity substrates of the CD45 PTPase among the tyrosine-phosphorylated T-cell proteins by using purified glutathione S-transferase-CD45 fusion molecules. The enzymatically inactive CD45 C828S mutant protein, in which the cysteine residue at the catalytic center was changed to a serine residue, bound tightly to the phosphorylated CD3 zeta chain. This binding was specific to CD45 PTPase, as neither the leukocyte common antigen-related molecule (LAR) PTPase nor the CD45-LAR hybrid PTPases bound the phosphorylated CD3 zeta chain. Furthermore, phosphorylated CD3 zeta chain was preferentially dephosphorylated by the wild-type CD45 PTPase under conditions that did not significantly dephosphorylate other cellular proteins. Thus, the phosphorylated CD3 zeta chain is a specific and high-affinity substrate of the CD45 PTPase. These results suggest that CD45 is involved in the termination of the T-cell response via dephosphorylation of CD3 zeta chain. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI26598] NR 49 TC 136 Z9 139 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 8 PY 1994 VL 91 IS 23 BP 10928 EP 10932 DI 10.1073/pnas.91.23.10928 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ938 UT WOS:A1994PQ93800036 PM 7526385 ER PT J AU GULICK, T CRESCI, S CAIRA, T MOORE, DD KELLY, DP AF GULICK, T CRESCI, S CAIRA, T MOORE, DD KELLY, DP TI THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR REGULATES MITOCHONDRIAL FATTY-ACID OXIDATIVE ENZYME GENE-EXPRESSION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE FATTY ACID OXIDATION; MITOCHONDRIAL ENZYMES; NUCLEAR HORMONE RECEPTOR; TRANSCRIPTIONAL REGULATION ID ACYL-COA DEHYDROGENASE; TISSUE-SPECIFIC EXPRESSION; OMEGA-HYDROXYLASE; BINDING-PROTEIN; BETA-OXIDATION; CLOFIBRIC ACID; RAT; INDUCTION; ELEMENT; LIVER AB Medium-chain acyl-CoA dehydrogenase (MCAD) catalyzes a pivotal reaction in mitochondrial fatty acid (FA) beta-oxidation. To examine the potential role of FAs and their metabolites in the regulation of MCAD gene expression, we measured MCAD mRNA levels in animals fed inhibitors of mitochondrial long-chain FA import. Administration of carnitine palmitoyltransferase I inhibitors to mice or rats resulted in tissue-limited increases in steady-state MCAD mRNA levels. HepG2 cell cotransfection experiments with MCAD promoter reporter plasmids demonstrated that this was a transcriptional effect mediated by the peroxisome proliferator-activated receptor (PPAR). The activity mapped to a nuclear receptor response element that functioned in a heterologous promoter context and specifically bound immunoreactive PPAR in rat hepatic nuclear extracts, confirming an in vivo interaction. PPAR-mediated transactivations of this promoter and element were also induced by exogenously added FA and fibric acid derivatives. Induction of PPAR transactivation by perturbation of this discrete metabolic step is unusual and indicates that intracellular FA metabolites that accumulate during such inhibition can regulate MCAD expression and are likely candidates for PPAR ligand(s). These results dictate an expanded role for the PPAR in the regulation of FA metabolism. C1 WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MOLEC BIOL & PHARMACOL,ST LOUIS,MO 63110. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. FU NIDDK NIH HHS [DK43382-02, DK45416] NR 30 TC 401 Z9 408 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 1994 VL 91 IS 23 BP 11012 EP 11016 DI 10.1073/pnas.91.23.11012 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ938 UT WOS:A1994PQ93800053 PM 7971999 ER PT J AU KUTER, DJ BEELER, DL ROSENBERG, RD AF KUTER, DJ BEELER, DL ROSENBERG, RD TI THE PURIFICATION OF MEGAPOIETIN - A PHYSIOLOGICAL REGULATOR OF MEGAKARYOCYTE GROWTH AND PLATELET PRODUCTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BLOOD PLATELET; HEMATOPOIETIC GROWTH FACTOR; THROMBOCYTOPENIA; BUSULFAN ID RAT; PLOIDY AB The circulating blood platelet is produced by the bone marrow megakaryocyte. In response to a decrease in the platelet count, megakaryocytes increase in number and ploidy. Although this feedback loop has long been thought to be mediated by a circulating hematopoietic Factor, no such factor has been purified. Using a model of thrombocytopenia in sheep, we have identified an active substance called megapoietin, which stimulated an increase in the number and ploidy of megakaryocytes in bone marrow culture. Circulating levels of this factor could be quantified with this assay and were found to be inversely proportional to the platelet count of the sheep. Levels increased from <0.26 pM in normal sheep to 25-40 pM in thrombocytopenic sheep. From large amounts of thrombo cytopenic sheep plasma we have purified a 31,200-Da protein and found that it retained the ability to stimulate both megakaryocyte number and ploidy in vitro. Injection of partially purified megapoietin into rats stimulated a 24% increase in megakaryocyte number and a 60% increase in mean ploidy as well as a 77% increase in the platelet count. Sheep platelets bound megapoietin and the amount of platelets required to eliminate half the activity in vitro was close to the amount associated with this same level of activity in vivo. We believe that megapoietin is the physiologically relevant mediator of megakaryocyte growth and platelet production. Moreover, our data suggest that the level of megapoietin is directly determined by the ability of platelets to remove megapoietin from the circulation. C1 MASSACHUSETTS GEN HOSP,HEMATOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. RP KUTER, DJ (reprint author), MIT,DEPT BIOL,BLDG 68-495,100 MASSACHUSETTS AVE,CAMBRIDGE,MA 02139, USA. FU NHLBI NIH HHS [HL 39753] NR 12 TC 336 Z9 341 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 1994 VL 91 IS 23 BP 11104 EP 11108 DI 10.1073/pnas.91.23.11104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ938 UT WOS:A1994PQ93800072 PM 7972018 ER PT J AU CORNFORD, EM HYMAN, S LANDAW, EM AF CORNFORD, EM HYMAN, S LANDAW, EM TI DEVELOPMENTAL MODULATION OF BLOOD-BRAIN-BARRIER GLUCOSE-TRANSPORT IN THE RABBIT SO BRAIN RESEARCH LA English DT Article DE BLOOD-BRAIN BARRIER GLUCOSE TRANSPORTER; KINETIC CONSTANT; GLUT1 ISOFORM; QUANTITATIVE IMMUNOGOLD ELECTRON MICROSCOPY; LUMINAL AND ABLUMINAL MEMBRANE; NEONATE; SUCKLING; WEANLING AND ADULT; DEVELOPMENTAL UP-REGULATION; CEREBRAL BLOOD FLOW; PERMEABILITY SURFACE AREA PRODUCT ID RAT CEREBRAL-CORTEX; FLOW; METABOLISM; KINETICS; ACID; PHOSPHORYLATION; 2-DEOXYGLUCOSE; TRANSLOCATION; CAPILLARIES; EXPRESSION AB Blood-brain barrier (BBB) glucose transport rates were measured using the intracarotid injection method in newborn, 14-day-old suckling, 28-day-old weanling and adult rabbits, and compared with membrane transporter density. Light microscope immunochemistry confirmed the presence of the GLUT1 glucose transporter isoform in these rabbits. Quantitative electron microscopic immunogold analyses of GLUT1-immunoreactive sites per micrometer of capillary membrane indicated GLUT1 density increased with age, and correlated with in vivo measurements of V-max. Maximal transport velocities (V-max) of glucose transfer (an indicator of the activity and relative number of transporter proteins) increased significantly (P = 0.05) with age: in neonates V-max = 0.61 mu mol.min(-1).g(-1), in sucklings V-max = 0.68 mu mol.min(-1).g(-1), in weanlings V-max = 0.88 mu mol.min(-1).g(-1), and in adults Vmax = 1.01 mu mol.min(-1) g(-1). Cerebral blood flow (CBF) rates, increased with age from 0.19 and 0.26 ml.min(-1).g(-1) in neonates and sucklings to 0.51 (weanlings) and 0.70 (adults) ml.min(-1).g(-1). Non-linear regression analyses indicated the half-saturation constant (K-m) for glucose transport ranged from 13 mM in adult rabbits to 19 mM in 14-day-old sucklings: differences in K-m were not significant. Age-related changes in the Permeability-Surface Area product (PS +/-S.E.) of both water and glucose were also seen. At all ages studied, the diffusion component (K-d) of glucose uptake was not distinguishable from zero. We conclude developmental up-regulation of the rabbit BBB glucose transporter is characterized by no changes in transporter affinity, and provide the first demonstration of increased membrane transporter proteins correlating with an age-related increase (65%) in glucose transporter maximal velocity. C1 VET ADM MED CTR, W LOS ANGELES VET AFFAIRS MED CTR, SW REG VA EPILEPSY CTR, NEUROL SERV, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT NEUROL, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT BRAIN RES INST, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT BIOMATH, LOS ANGELES, CA 90024 USA. RP CORNFORD, EM (reprint author), VET ADM MED CTR, W LOS ANGELES VET AFFAIRS MED CTR, SW REG VA EPILEPSY CTR, RES SERV, LOS ANGELES, CA 90073 USA. FU NCI NIH HHS [CA-16042]; NINDS NIH HHS [NS 25554] NR 60 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD NOV 7 PY 1994 VL 663 IS 1 BP 7 EP 18 DI 10.1016/0006-8993(94)90457-X PG 12 WC Neurosciences SC Neurosciences & Neurology GA PP616 UT WOS:A1994PP61600002 PM 7850472 ER PT J AU KINANE, TB FINDER, JD KAWASHIMA, A BROWN, D ABBATE, M SHANG, C FREDERICKS, WJ RAUSCHER, FJ SUKHATME, VP ERCOLANI, L AF KINANE, TB FINDER, JD KAWASHIMA, A BROWN, D ABBATE, M SHANG, C FREDERICKS, WJ RAUSCHER, FJ SUKHATME, VP ERCOLANI, L TI GROWTH OF LLC-PK1 RENAL-CELLS IS MEDIATED BY EGR-1 UP-REGULATION OF G-PROTEIN ALPHA-I-2 PROTOONCOGENE TRANSCRIPTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ZINC FINGER PROTEIN; MULTICELLULAR DEVELOPMENT; SIGNAL TRANSDUCTION; GENE PROMOTER; SUBUNIT; IDENTIFICATION; DICTYOSTELIUM; PRODUCT; DIFFERENTIATION; LOCALIZATION AB The early growth response zinc finger transcription factor (EGR-1) and the heterotrimeric guanine nucleotide binding protein encoded by the protooncogene G alpha i-2 each play pivotal roles in signaling pathways that control cell growth and differentiation. The G alpha i-2 gene 5'-flanking region contains a putative binding site (5'-CGCCCCCGC-3') for EGR-1 that may allow it to be a target gene for EGR-1 mitogenic signaling. We now demonstrate in LLC-PK1 renal cells the temporal expression of EGR-1 protein by immunoblotting and immunocytochemistry coincident with the maximal activation of the G alpha i-2 gene during cell growth. To determine whether G alpha i-2 or EGR-1 influence epithelial cell growth, LLC-PK1 cells were transiently transfected with plasmids encoding cDNAs for G alpha i-2 (pRSV G alpha i-2) or EGR-1 (pRSV EGR-1) driven by a viral Rous sarcoma promoter enhancer to overexpress each protein. Following transfection, cell growth was examined in media containing either 10 or 0.1% fetal bovine serum. Only cells transfected with plasmids encoding G alpha i-2 and EGR-1 had growth rates greater than that of serum replete cohorts. To assess whether EGR-1 was contributing to the transcriptional activation of the G alpha i-2 gene, cells were cotransfected with pRSV EGR-1 and plasmids encoding firefly luciferase reporter genes fused to 5'-flanking areas of the G alpha i-2 gene containing either the EGR-1 binding site or a mutated EGR-1 binding site (5'-AAAAACCGC-3'). A 320% enhancement of G alpha i-2 transcription was found only in LLC-PK1 cells following their transfection with plasmids that contained both the EGR-1 binding site and overexpressed EGR-1 protein. Utilizing mobility shift assays, which compared nuclear extracts from cells before and after cell polarization, a probe containing the EGR-1 motif detected induced nuclear protein complexes during transcriptional activation of the G alpha i-2 gene. An anti-EGR-1 antibody specifically retarded the mobility of the induced nuclear complexes, indicating that the EGR-1 protein was a component of these complexes. These data provide direct evidence for a novel mitogenic signaling pathway coupling proximal signaling events that activate EGR-1 gene expression to a target protooncogene G alpha i-2 that is participatory for growth and differentiation in renal cells. C1 WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,PEDIAT PULM UNIT,BOSTON,MA 02114. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,RENAL UNIT,BOSTON,MA 02114. FU NIDDK NIH HHS [DK-42543, DK-02271, F32 DK-08838] NR 30 TC 23 Z9 23 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 4 PY 1994 VL 269 IS 44 BP 27503 EP 27509 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV771 UT WOS:A1994PV77100055 PM 7961665 ER PT J AU SLOAN, IS HOROWITZ, PM CHIRGWIN, JM AF SLOAN, IS HOROWITZ, PM CHIRGWIN, JM TI RAPID SECRETION BY A NONCLASSICAL PATHWAY OF OVEREXPRESSED MAMMALIAN MITOCHONDRIAL RHODANESE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN CATHEPSIN-D; MOLECULAR CHAPERONES; LIVER RHODANESE; PROTEINS; CELL; EXPRESSION; CDNA; THIOREDOXIN; MEMBRANES; SEQUENCE AB Rhodanese is a small (33 kDa) monomeric sulfurtransferase which is synthesized on cytoplasmic ribosomes and imported into the mitochondrial matrix without cleavage of its amino terminus. When we transfected mammalian cell lines with rhodanese cDNA under the control of an efficient viral promoter, up to 40% of the overexpressed protein was secreted into the medium. This secretion was not the result of cell lysis, did not occur via the endoplasmic reticulum, and did not require the amino-terminal mitochondrial import signal. Addition of a carboxyl-terminal peptide extension did not block secretion, nor did a number of inhibitors of cellular sorting processes. Rhodanese polypeptide is known to associate with chaperonin proteins. In the absence of available mitochondrial import sites, such a complex in the cytoplasm of transfected cells could deliver unfolded rhodanese to export pores on the inner surface of the plasma membrane. This mechanism could contribute to the nonclassical secretion of cytoplasmically synthesized interleukins, growth factors, and lectins. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV ENDOCRINOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,RES SERV,SAN ANTONIO,TX 78284. FU NIEHS NIH HHS [ES 05729]; NIGMS NIH HHS [GM 25177] NR 46 TC 17 Z9 17 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 4 PY 1994 VL 269 IS 44 BP 27625 EP 27630 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV771 UT WOS:A1994PV77100072 PM 7961679 ER PT J AU CHUANG, LM HAUSDORFF, SF MYERS, MG WHITE, MF BIRNBAUM, MJ KAHN, CR AF CHUANG, LM HAUSDORFF, SF MYERS, MG WHITE, MF BIRNBAUM, MJ KAHN, CR TI INTERACTIVE ROLES OF RAS, INSULIN-RECEPTOR SUBSTRATE-1, AND PROTEINS WITH SRC HOMOLOGY-2 DOMAINS IN INSULIN SIGNALING IN XENOPUS OOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; SH3 DOMAINS; BETA-SUBUNIT; MAP KINASE; ACTIVATION; BINDING; DISTINCT; TRANSDUCTION AB Insulin receptor substrate-1 (IRS-1) serves as the major immediate substrate of insulin/insulin-like growth factor (IGF)-1 receptors and following tyrosine phosphorylation binds to specific Src homology-2 (SH2) domain-containing proteins including the p85 subunit of phosphatidylinositol (PI) 3-kinase and GRB2, a molecule believed to link IRS-1 to the Ras pathway. To investigate how these SH2-containing signaling molecules interact to regulate insulin/IGF-1 action, IRS-1, glutathione S-transferase (GST)-SH2 domain fusion proteins and Ras proteins were microinjected into Xenopus oocytes. We found that pleiotropic insulin actions are mediated by IRS-1 through two independent, but convergent, pathways involving PI 3-kinase and GRB2. Thus, microinjection of GST-fusion proteins of either p85 or GRB2 inhibited IRS-1-dependent activation of mitogen-activated protein (MAP) and S6 kinases and oocyte maturation, although only the GST-SH2 of p85 reduced insulin-stimulated PI 3-kinase activation. Co-injection of a dominant negative Ras (S17N) with IRS-1 inhibited insulin-stimulated MAP and S6 kinase activation. Microinjection of activated [Arg(12),Thr(59)]Ras increased basal MAP and S6 kinase activities and sensitized the oocytes to insulin-stimulated maturation without altering insulin-stimulated PI 3-kinase. The Ras-enhanced oocyte maturation response, but not the elevated basal level of MAP and S6 kinase, was partially blocked by the SH2-p85, but not SH2-GRB2. These data strongly suggest that IRS-1 can mediate many of insulin's actions on cellular enzyme activation and cell cycle progression requires binding and activation of multiple different SH2-domain proteins. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DEPT MED,DIV RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. OI CHUANG, LEE-MING/0000-0003-0978-2662; Birnbaum, Morris/0000-0001-9972-8680 FU NIDDK NIH HHS [DK 33201, DK 39519, DK 43808] NR 50 TC 33 Z9 33 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 4 PY 1994 VL 269 IS 44 BP 27645 EP 27649 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV771 UT WOS:A1994PV77100076 PM 7961682 ER PT J AU LOWE, SW BODIS, S MCCLATCHEY, A REMINGTON, L RULEY, HE FISHER, DE HOUSMAN, DE JACKS, T AF LOWE, SW BODIS, S MCCLATCHEY, A REMINGTON, L RULEY, HE FISHER, DE HOUSMAN, DE JACKS, T TI P53 STATUS AND THE EFFICACY OF CANCER-THERAPY IN-VIVO SO SCIENCE LA English DT Article ID PROGRAMMED CELL-DEATH; C-MYC; GENE; MUTATIONS; INDUCTION; APOPTOSIS; MOUSE; TUMOR AB The therapeutic responsiveness of genetically defined tumors expressing or devoid of the p53 tumor suppressor gene was compared in immunocompromised mice. Tumors expressing the p53 gene contained a high proportion of apoptotic cells and typically regressed after treatment with gamma radiation or adriamycin. In contrast, p53-deficient tumors treated with the same regimens continued to enlarge and contained few apoptotic cells. Acquired mutations in p53 were associated with both treatment resistance and relapse in p53-expressing tumors. These results establish that defects in apoptosis, here caused by the inactivation of p53, can produce treatment-resistant tumors and suggest that p53 status may be an important determinant of tumor response to therapy. C1 MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. VANDERBILT UNIV,SCH MED,DEPT IMMUNOL & MICROBIOL,NASHVILLE,TN 37232. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. FU NCI NIH HHS [R01CA40602, CA14051, 5R27CA17575] NR 25 TC 1390 Z9 1411 U1 4 U2 26 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 4 PY 1994 VL 266 IS 5186 BP 807 EP 810 DI 10.1126/science.7973635 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP753 UT WOS:A1994PP75300041 PM 7973635 ER PT J AU CONNOR, EM SPERLING, RS GELBER, R KISELEV, P SCOTT, G OSULLIVAN, MJ VANDYKE, R BEY, M SHEARER, W JACOBSON, RL JIMENEZ, E ONEILL, E BAZIN, B DELFRAISSY, JF CULNANE, M COOMBS, R ELKINS, M MOYE, J STRATTON, P BALSLEY, J AF CONNOR, EM SPERLING, RS GELBER, R KISELEV, P SCOTT, G OSULLIVAN, MJ VANDYKE, R BEY, M SHEARER, W JACOBSON, RL JIMENEZ, E ONEILL, E BAZIN, B DELFRAISSY, JF CULNANE, M COOMBS, R ELKINS, M MOYE, J STRATTON, P BALSLEY, J TI REDUCTION OF MATERNAL-INFANT TRANSMISSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 WITH ZIDOVUDINE TREATMENT SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CLINICAL-TRIALS GROUP; RETROVIRAL DISEASE; HIV-1 INFECTION; PREGNANCY; VIREMIA; EMBRYOS; THERAPY; 3'-AZIDO-3'-DEOXYTHYMIDINE; PHARMACOKINETICS; PREIMPLANTATION AB Background and Methods. Maternal-infant transmission is the primary means by which young children become infected with human immunodeficiency virus type 1 (HIV). We conducted a randomized, double-blind, placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission. HIV-infected pregnant women (14 to 34 weeks' gestation) with CD4+ T-lymphocyte counts above 200 cells per cubic millimeter who had not received antiretroviral therapy during the current pregnancy were enrolled. The zidovudine regimen included antepartum zidovudine (100 mg orally five times daily), intrapartum zidovudine (2 mg per kilogram of body weight given intravenously over a one-hour period, then 1 mg per kilogram per hour until delivery), and zidovudine for the newborn (2 mg per kilogram orally every six hours for six weeks). Infants with at least one positive HIV culture of peripheral-blood mononuclear cells were classified as HIV-infected. Results. From April 1991 through December 20, 1993, the cutoff date for the first interim analysis of efficacy, 477 pregnant women were enrolled; during the study period, 409 gave birth to 415 live-born infants. HIV-infection status was known for 363 births (180 in the zidovudine group and 183 in the placebo group). Thirteen infants in the zidovudine group and 40 in the placebo group were HIV-infected. The proportions infected at 18 months, as estimated by the Kaplan-Meier method, were 8.3 percent (95 percent confidence interval, 3.9 to 12.8 percent) in the zidovudine group and 25.5 percent (95 percent confidence interval, 18.4 to 32.5 percent) in the placebo group. This corresponds to a 67.5 percent (95 percent confidence interval, 40.7 to 82.1 percent) relative reduction in the risk of HIV transmission (Z = 4.03, P = 0.00006). Minimal short-term toxic effects were observed. The level of hemoglobin at birth in the infants in the zidovudine group was significantly lower than that in the infants in the placebo group. By 12 weeks of age, hemoglobin values in the two groups were similar. Conclusions. In pregnant women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy, a regimen consisting of zidovudine given ante partum and intra partum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two thirds. C1 UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT PEDIAT,NEWARK,NJ 07103. CUNY MT SINAI SCH MED,DEPT OBSTET GYNECOL & REPROD SCI,NEW YORK,NY 10029. HARVARD UNIV,SCH PUBL HLTH,AIDS CLIN TRIALS GRP,CTR STAT & DATA ANAL,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA. UNIV MIAMI,SCH MED,DEPT PEDIAT,MIAMI,FL. UNIV MIAMI,SCH MED,DEPT OBSTET & GYNECOL,MIAMI,FL 33101. TULANE UNIV,SCH MED,DEPT PEDIAT,NEW ORLEANS,LA 70112. LOUISIANA STATE UNIV,SCH MED,DEPT OBSTET & GYNECOL,NEW ORLEANS,LA. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. UNIV TEXAS,SCH MED,DEPT OBSTET & GYNECOL,HOUSTON,TX. SAN JUAN CITY HOSP,DEPT PEDIAT,SAN JUAN,PR. SAN JUAN CITY HOSP,DEPT OBSTET & GYNECOL,SAN JUAN,PR. AGENCE NATL RECH SIDA,PARIS,FRANCE. UNIV WASHINGTON,SCH MED,SEATTLE,WA. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. NICHHD,BETHESDA,MD. NIAID,DIV AIDS,PEDIAT MED BRANCH,BETHESDA,MD 20892. RI Sandall, Jane/D-4146-2009; OI Sandall, Jane/0000-0003-2000-743X; moye, john/0000-0001-9976-8586 NR 39 TC 2459 Z9 2571 U1 10 U2 80 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 3 PY 1994 VL 331 IS 18 BP 1173 EP 1180 DI 10.1056/NEJM199411033311801 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA PN806 UT WOS:A1994PN80600001 PM 7935654 ER PT J AU MILLS, JA AF MILLS, JA TI SYSTEMIC LUPUS-ERYTHEMATOSUS - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP MILLS, JA (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 3 PY 1994 VL 331 IS 18 BP 1235 EP 1235 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PN806 UT WOS:A1994PN80600026 ER PT J AU ELKIN, PL AF ELKIN, PL TI LOW-BACK-PAIN - A PATIENTS GUIDE TO LOW-BACK-PAIN - A COMPLETE INTERACTIVE COMPUTER SOFTWARE PROGRAM FOR PATIENT EDUCATION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Software Review ID HYPERTEXT RP ELKIN, PL (reprint author), MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 2 PY 1994 VL 272 IS 17 BP 1387 EP 1388 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PP020 UT WOS:A1994PP02000036 ER PT J AU CHANG, CYY SHIH, H JEFFREY, PD MARGOLIES, MN SHERIFF, S AF CHANG, CYY SHIH, H JEFFREY, PD MARGOLIES, MN SHERIFF, S TI CRYSTALLIZATION AND PRELIMINARY-X-RAY ANALYSIS OF ANTIDIGOXIN ANTIBODIES SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Note ID 3-DIMENSIONAL STRUCTURE; FAB FRAGMENT; CRYSTAL-STRUCTURE; MONOCLONAL-ANTIBODY; PEPTIDE ANTIGEN; STRANDED-DNA; COMPLEX; RECOGNITION; RESOLUTION; AFFINITY AB The Fab fragments of several monoclonal antibodies that bind digoxin and other cardiac glycosides have been screened for crystallization conditions. We have crystallized two of these in forms suitable for X-ray analysis. The anti-digoxin antibody 40-50 in complex with ouabain crystallizes with symmetry consistent with space group C2, with a = 92.6, b = 85.0, c = 73.0 Angstrom and beta = 131.7 degrees. This crystal form shows considerable non-isomorphism between crystals. A second anti-digoxin antibody, 49-10, crystallizes with symmetry consistent with space group P2(1)2(1)2, with a = 95.3, b = 147.1 and c = 76.2 Angstrom. C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 37 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD NOV 1 PY 1994 VL 50 BP 915 EP 917 DI 10.1107/S0907444994004841 PN 6 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA PR048 UT WOS:A1994PR04800017 PM 15299362 ER PT J AU GOODWIN, TM HERSHMAN, JM COLE, L AF GOODWIN, TM HERSHMAN, JM COLE, L TI INCREASED CONCENTRATION OF THE FREE BETA-SUBUNIT OF HUMAN CHORIONIC-GONADOTROPIN IN HYPEREMESIS GRAVIDARUM SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE FREE BETA HCG; HYPEREMESIS GRAVIDARUM ID HCG; PREGNANCY; NICKS AB Objective. The amount of free beta subunit hCG (free beta) has been reported to be increased in trophoblast disease and Down's syndrome, conditions also associated with high total hCG. increased total hCG has been reported in hyperemesis gravidarum. We sought to determine if sera from singleton gestations with hyperemesis gravidarum contained a higher proportion of free beta hCG compared to controls of comparable gestational age. Methods. Sera from 39 patients with hyperemesis gravidarum was compared with that from 23 control subjects of comparable gestational age with respect to beta hCG and its subunits (free beta and free alpha). Results. Hyperemesis patients and controls were comparable with respect to age, weight and gestational age. The concentration of hCG was greater in hyperemesis patients (9237 +/- 3613 ng/ml, mean +/- s.d.) compared to controls (5543 +/- 2290, p < 0.005) as was the concentration of free beta hCG (101 +/- 70 ng/ml vs. 31 + 31, p < 0.001). Free alpha did not differ between hyperemesis patients and controls (399 +/- 231 ng/ml vs. 377 +/- 214). A percent free beta greater than 0.6 was found in 33/39 hyperemesis patients (85%) compared to 5/23 controls (22%), p < 0.001. Conclusion. Increased free beta hCG is found in hyperemesis gravidarum. This finding strengthens the association of hyperemesis with abnormal metabolism of hCG. C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,LOS ANGELES,CA. YALE UNIV,DEPT OBSTET & GYNECOL,NEW HAVEN,CT 06520. RP GOODWIN, TM (reprint author), UNIV SO CALIF,WOMENS HOSP,DEPT OBSTET & GYNECOL,ROOM 5K-10,1240 N MISS RD,LOS ANGELES,CA 90033, USA. NR 12 TC 47 Z9 50 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PD NOV PY 1994 VL 73 IS 10 BP 770 EP 772 DI 10.3109/00016349409072502 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QA070 UT WOS:A1994QA07000006 PM 7817726 ER PT J AU DEMERS, P ROBILLARD, A LAFLECHE, G NASH, F HEYMAN, A FILLENBAUM, G AF DEMERS, P ROBILLARD, A LAFLECHE, G NASH, F HEYMAN, A FILLENBAUM, G TI TRANSLATION OF CLINICAL AND NEUROPSYCHOLOGICAL INSTRUMENTS INTO FRENCH - THE CERAD EXPERIENCE SO AGE AND AGEING LA English DT Article AB The increasing number of international and epidemiological studies of Alzheimer's disease points to the need for linguistically equivalent translations of measures for identifying the presence, types, and severity of dementia in cross-cultural populations. In translating the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuropsychological instruments into French, several linguistic issues have emerged such as semantic, phonetic, and word-frequency equivalences. In verbal memory tests, these problems, though minor in appearance, can be major pitfalls in studies comparing cognitive function in populations differing in language. Description of the translation procedure and examples of problems encountered are presented, with measures taken to resolve them. C1 HOP MAISON NEUVE ROSEMONT, DEPT NEUROL, MONTREAL H1T 2M4, PQ, CANADA. MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT, BOSTON, MA 02114 USA. DUKE UNIV, MED CTR, DURHAM, NC 27710 USA. RP DEMERS, P (reprint author), HOP MAISON NEUVE ROSEMONT, DEPT PSYCHOL, 5415 BOUL ASSOMPT, MONTREAL H1T 2M4, PQ, CANADA. NR 3 TC 14 Z9 14 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0002-0729 EI 1468-2834 J9 AGE AGEING JI Age Ageing PD NOV PY 1994 VL 23 IS 6 BP 449 EP 451 DI 10.1093/ageing/23.6.449 PG 3 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA PT038 UT WOS:A1994PT03800003 PM 9231936 ER PT J AU HISNANICK, JJ AF HISNANICK, JJ TI CHANGES OVER TIME IN THE ADL STATUS OF ELDERLY US VETERANS SO AGE AND AGEING LA English DT Article ID ALL-CAUSE MORTALITY; COMPRESSION; MORBIDITY; DYNAMICS; POLICY; HEALTH AB The ageing of the US veteran population has greatly out-paced that of the general US population in the last decade and the demographics of this subgroup have changed relative to the US general population. To address the concerns of policy makers within the US Department of Veterans' Affairs (VA), data on elderly US male veterans and non-veterans from the Longitudinal Survey on Aging in 1984, 1986, 1988, and 1990 were used in a prospective study. Health status or well-being was assessed through changes over time in ADL status, according to the following five categories; (I) the presence of no ADL dependence and not developing a dependence between survey periods, (II) no change in ADL dependence between survey periods, (III) an increase in ADL dependence status between survey periods, (IV) a decrease in ADL dependence between survey periods, and (V) the occurrence of death between survey periods. Using a polytomous logistic regression model, these five categories were assessed in relation to a set of variables representing social, health-care utilization, and socioeconomic characteristics. The estimated coefficients from the model indicate that family income, having worked in the last 12 months, having an increase or no change in levels of physical activity in the past 12 months and the presence of Medicare coverage are inversely associated with moving, over time, into a lower state of health status or wellbeing. The prior existence of an ADL limitation, the number of doctor and hospital visits in the past 12 months, level of education, having been widowed in the past 12 months and veteran status were all proportionally associated with the likelihood of moving into a lower state of health status or well-being. These findings lead to the conclusion that being a veteran in the US does make a difference in regard to moving into various states of health status or well-being. This difference is supported by the estimated coefficient for veteran status being significant at a p value of 0.01 and through an evaluation of the estimated transition likelihood, controlling for veteran status. Veterans are less likely to die than their non-veteran counterparts, but have a greater likelihood of transition into levels of ADL dependence. Similarly, given the existence of a prior ADL limitation, over time, veterans are less likely to die, but more likely to move into a state of increased ADL limitations. RP HISNANICK, JJ (reprint author), US DEPT VET AFFAIRS,NATL CTR VET ANAL & STAT 008C12,810 VERMONT AVE NW,WASHINGTON,DC 20420, USA. NR 34 TC 9 Z9 9 U1 2 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0002-0729 J9 AGE AGEING JI Age Ageing PD NOV PY 1994 VL 23 IS 6 BP 505 EP 511 DI 10.1093/ageing/23.6.505 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA PT038 UT WOS:A1994PT03800013 PM 9231946 ER PT J AU ANTIMISIARIS, M SARMA, JSM SCHOENBAUM, MP SHARMA, PP VENKATARAMAN, K SINGH, BN CHRISTENSON, P AF ANTIMISIARIS, M SARMA, JSM SCHOENBAUM, MP SHARMA, PP VENKATARAMAN, K SINGH, BN CHRISTENSON, P TI EFFECTS OF AMIODARONE ON THE CIRCADIAN-RHYTHM AND POWER SPECTRAL CHANGES OF HEART-RATE AND QT INTERVAL - SIGNIFICANCE FOR THE CONTROL OF SUDDEN CARDIAC DEATH SO AMERICAN HEART JOURNAL LA English DT Article ID III ANTIARRHYTHMIC AGENTS; VENTRICULAR ARRHYTHMIAS; MYOCARDIAL-INFARCTION; THYROID-FUNCTION; LONG; TERM; ADRENOCEPTORS; MORTALITY; MUSCLE; DRUG AB Effects of chronic amiodarone therapy on the circadian rhythmicity and power spectral changes of heart rate and QT intervals from Holter recordings were evaluated in three groups of patients: group 1 baseline (n = 10); group 2, treated for 3 to 8 months (n = 11); and group 3, treated for >1 year(n = 13). Amiodarone reduced heart rate, which reached steady state at 3 to 6 months; bradycardia was evident during the entire 24 hours. The corrected QT (QT(c)) interval increased as a function of treatment duration. It was 457 +/- 39, 530 + 28 (p < 0.001), and 581 +/- 36 (p < 0.0002) msec for groups 1, 2, and 3, after 6 months, respectively. The circadian rhythmicity of QT, was abolished in group 3. Power spectral analysis showed a tendency for amiodarone to reduce both R-R and QT interval variabilities, suggesting inhibition of autonomic control on the heart by the drug. The effectiveness of amiodarone against ventricular arrhythmias may result in part from the sustained bradycardia in concert with continuous uniform prolongation of myocardial repolarization. C1 W LOS ANGELES VET AFFAIRS MED CTR,DIV CARDIOL,LOS ANGELES,CA 90073. CITY HOPE NATL MED CTR,DUARTE,CA 91010. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT BIOMATH,LOS ANGELES,CA. NR 36 TC 15 Z9 16 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 1994 VL 128 IS 5 BP 884 EP 891 DI 10.1016/0002-8703(94)90584-3 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PN864 UT WOS:A1994PN86400006 PM 7942479 ER PT J AU RIVERA, JM MELE, D VANDERVOORT, PM MORRIS, E WEYMAN, AE THOMAS, JD AF RIVERA, JM MELE, D VANDERVOORT, PM MORRIS, E WEYMAN, AE THOMAS, JD TI EFFECTIVE REGURGITANT ORIFICE AREA IN TRICUSPID REGURGITATION - CLINICAL IMPLEMENTATION AND FOLLOW-UP-STUDY SO AMERICAN HEART JOURNAL LA English DT Article ID PROXIMAL FLOW CONVERGENCE; DOPPLER ECHOCARDIOGRAPHIC METHOD; MITRAL REGURGITATION; VALVULAR REGURGITATION; BLOOD-FLOW; REAL-TIME; QUANTIFICATION; VALIDATION; MOMENTUM; CONSERVATION AB Analysis of the flow-convergence zone proximal to a regurgitant orifice permits the noninvasive, quantitative measurement of clinically useful parameters of valvular insufficiency. However, many indexes such as flow rate reflect not only the size of the regurgitant lesion but are also highly dependent on the hemodynamic loading conditions. The effective regurgitant orifice area (ROA) in contrast is a more fundamental parameter, less dependent on hemodynamics and more reflective of real changes in the geometry of the valve, making it a promising index for serial assessment of patients. In this study, the measurement of regurgitant orifice area by the flow-convergence method was tested in tricuspid regurgitation and then used to monitor patients noninvasively over time. The effective ROA was calculated in 45 patients with tricuspid regurgitation by means of the flow-convergence method and compared with the ROA obtained with pulsed Doppler echocardiographic methods. An excellent correlation was obtained between the two assessments of ROA (r = 0.96, Delta ROA = -0.09 +/- 6.5 mm(2)). ROA also showed an excellent correlation with other indexes of valvular insufficiency such as regurgitant stroke volume (r = 0.89) and regurgitant fraction (r = 0.88). In a subgroup of 22 patients thought to be clinically stable, ROA was calculated serially over a mean follow-up period of 2 months and its variability compared with that of other flow-based parameters obtainable from proximal acceleration. The variation between the two studies in regurgitant stroke volume end regurgitant flow rate was 5% +/- 20.6% and 5.2% +/- 35.7%, respectively. The effective ROA showed significantly less variability at 1.8% +/- 15%. It is concluded that the effective ROA is an excellent parameter to monitor in the serial assessment of valvular insufficiency because it is less dependent on hemodynamic conditions and correlates well with traditional indexes of regurgitation. C1 MASSACHUSETTS GEN HOSP,NONINVAS CARDIAC LAB,BOSTON,MA 02114. CLEVELAND CLIN FDN,DEPT CARDIOL,CLEVELAND,OH 44195. RI rivera, miguel/D-5026-2014 NR 26 TC 23 Z9 23 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 1994 VL 128 IS 5 BP 927 EP 933 DI 10.1016/0002-8703(94)90591-6 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PN864 UT WOS:A1994PN86400013 PM 7942486 ER PT J AU CUI, GG SEN, LY SAGER, P UPPAL, P SINGH, BN AF CUI, GG SEN, LY SAGER, P UPPAL, P SINGH, BN TI EFFECTS OF AMIODARONE, SEMATILIDE, AND SOTALOL ON QT DISPERSION SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIAL-INFARCTION; ELECTROPHYSIOLOGY; PHARMACOLOGY; PROLONGATION; CHANNELS; CELLS AB To study the effects of class III agents on QT/QTc dispersion in patients with heart disease and cardiac arrhythmias, QT dispersion and QRS and RR intervals were compared in patients before and after treatment with amiodarone (n = 26), sematilide (n = 26), and sotalol (n = 26). QT, QRS, and RR intervals, and QTc values were calculated for each complex, and their mean values were calculated for each lead. QT and QTc dispersions were defined as differences between the minimal and maximal QT or QTc values in each of the 12 leads studied. Amiodarone, sematilide, and sotalol all significantly prolonged the QT interval and the QTc value. Significant reductions in QT and QTc dispersions were only found in the amiodarone group (QT dispersions: 79 +/- 13 vs 49 +/- 14 ms; p <0.001; QTc dispersions: 0.08 +/- 0.02 vs 0.05 +/- 0.01 s(1/2); p <0.001). The mean RR interval was significantly increased in patients after treatment with amiodarone (p <0.001) and sotalol (p <0.001), but not in patients receiving sematilide treatment (p >0.2). The baseline QT and QTc dispersions were significantly greater in patients with than without myocardial infarction before treatment (p <0.001). The mean baseline values for QT/QTc dispersions were not significantly different among all 3 groups. However, only amiodarone significantly reduced the QT dispersion (from 76 +/- 10 to 46 +/- 11 ms; p <0.001) and QTc dispersion (from 0.09 +/- 0.02 to 0.05 +/- 0.01 s(1/2); p <0.001) in patients with myocardial infarction. The reduction in the QT/QTc dispersion was significantly greater than that in patients without myocardial infarction (p <0.01). It is concluded that (1) antiarrhythmic agents that get by lengthening repolarization have differing effects on QT/QTc dispersion, most likely reflecting differences in their fundamental mechanisms whereby they prolong myocardial repolarization, and (2) the low reported incidence of torsades de pointes with amiodarone may in part be due to reduced dispersion of QT and QTc compared with other class III cents. C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,DIV CARDIOVASC,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. NR 22 TC 81 Z9 85 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 1994 VL 74 IS 9 BP 896 EP 900 DI 10.1016/0002-9149(94)90582-7 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP130 UT WOS:A1994PP13000010 PM 7526675 ER PT J AU DEUTSCH, JC KOLLI, VR SANTHOSHKUMAR, CR KOLHOUSE, JF AF DEUTSCH, JC KOLLI, VR SANTHOSHKUMAR, CR KOLHOUSE, JF TI SERUM XYLOSE ANALYSIS BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE XYLOSE; INTESTINAL MALABSORPTION; GAS CHROMATOGRAPHY; MASS SPECTROMETRY; SERUM ID MASS-SPECTROMETRY; ALPHA-TOCOPHEROL; MALABSORPTION; PLASMA; BLOOD; URINE AB A gas chromatography/mass spectrometric (GC/MS) isotope dilution assay for xylose was developed using tertbutyldimethylsilyl-derivatized xylose and [C-13](1) xylose, and applied to human serum samples. A calibration curve in serum using this assay showed <3% variation (<10 mg/L) for any given point. The correlation coefficient for xylose measurements made on 27 sera between a colorimetric method performed by a national commercial reference laboratory and the GC/MS method developed here was .952. However, xylose determinations of 10 of 27 samples differed by >10% (up to 150 mg/L) when colorimetric values were compared to GC/MS. Two of these samples had borderline-low xylose values by GC/MS, but were well within the normal range by colorimetric analysis. gas chromatography/mass spectrometric isotope dilution assay appears to be an accurate method to measure xylose in serum. These data also suggest that further prospective studies comparing GC/MS to colorimetric methods are indicated for subjects undergoing oral xylose testing. C1 DENVER VET AFFAIRS HOSP,DEPT MED,DIV GASTROENTEROL,DENVER,CO. DENVER VET AFFAIRS HOSP,DEPT MED,DIV HEMATOL,DENVER,CO. UNIV COLORADO,HLTH SCI CTR,DIV HEMATOL,DENVER,CO. RP DEUTSCH, JC (reprint author), UNIV COLORADO,HLTH SCI CTR,DIV GASTROENTEROL,4200 E 9TH AVE,DENVER,CO 80262, USA. NR 19 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD NOV PY 1994 VL 102 IS 5 BP 595 EP 599 PG 5 WC Pathology SC Pathology GA PQ162 UT WOS:A1994PQ16200008 PM 7942623 ER PT J AU KUPRYJANCZYK, J BELL, DA YANDELL, DW SCULLY, RE THOR, AD AF KUPRYJANCZYK, J BELL, DA YANDELL, DW SCULLY, RE THOR, AD TI P53 EXPRESSION IN OVARIAN BORDERLINE TUMORS AND STAGE-I CARCINOMAS SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE ENDOMETRIOSIS; OVARIAN BORDERLINE TUMORS; OVARIAN CARCINOMAS; P53 PROTEIN ACCUMULATION ID CLINICOPATHOLOGIC ANALYSIS; PAPILLARY CYSTADENOMAS; SUPPRESSOR GENE; UNIFOCAL ORIGIN; MUCINOUS TUMORS; CANCER; PROTEIN; MUTATIONS; OVEREXPRESSION; ACCUMULATION AB Seventy-nine ovarian serous and mucinous borderline tumors, 36 stage I carcinomas and 39 stage II-IV carcinomas were studied for p53 protein accumulation with monoclonal antibody PAb1801. p53 protein was expressed in 14% of borderline tumors, 36% of stage I carcinomas, and 64% of higher stage carcinomas. All immunopositive carcinomas accumulated p53 protein in the primary tumor, and 95% of them showed concordance in staining among different tissue blocks. A difference in frequency of p53 protein accumulation between stage I and higher stage serous carcinomas was not statistically significant. p53 positivity was associated with microinvasion, microcarcinoma and coexistent carcinoma in mucinous borderline tumors (P = .025). An association between p53 protein expression and poor tumor differentiation in Stage I carcinomas was statistically significant (P = .03). p53 positivity was observed in a poorly differentiated endometrioid carcinoma as well as in adjacent benign endometriotic tissue. These results suggest that p53 abnormalities may be early events in ovarian cancer, possibly contributing to malignant transformation of some borderline tumors, endometriosis and other carcinoma precursors. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT LABS,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,MOLEC GENET RES LAB,BOSTON,MA 02114. FU NCI NIH HHS [P01 CA44768] NR 40 TC 72 Z9 73 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD NOV PY 1994 VL 102 IS 5 BP 671 EP 676 PG 6 WC Pathology SC Pathology GA PQ162 UT WOS:A1994PQ16200021 PM 7942635 ER PT J AU MCCABE, CJ AF MCCABE, CJ TI TRAUMA - AN ANNOTATED-BIBLIOGRAPHY OF THE RECENT LITERATURE SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Bibliography RP MCCABE, CJ (reprint author), MASSACHUSETTS GEN HOSP,EMERGENCY SERV,FRUIT ST,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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 1994 VL 12 IS 6 BP 668 EP 682 DI 10.1016/0735-6757(94)90037-X PG 15 WC Emergency Medicine SC Emergency Medicine GA PT456 UT WOS:A1994PT45600014 PM 7945611 ER PT J AU LICHTENSTEIN, MJ GRIFFIN, MR CORNELL, JE MALCOLM, E RAY, WA AF LICHTENSTEIN, MJ GRIFFIN, MR CORNELL, JE MALCOLM, E RAY, WA TI RISK-FACTORS FOR HIP-FRACTURES OCCURRING IN THE HOSPITAL SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ACCIDENTAL FALLS; AGED; HIP FRACTURES; HOSPITALS; PSYCHOTROPIC DRUGS; WOUNDS AND INJURIES ID FALLS; LONG; BENZODIAZEPINES; PREVENTION; ACCIDENTS; RESIDENTS; INJURIES AB Risk factors for in-hospital hip fractures among patients aged greater than or equal to 65 years were evaluated in a population-based case-control study conducted in the Canadian province of Saskatchewan from 1983 through 1985. There were 129 cases with confirmed in-hospital hip fractures and 234 controls, who were those controls from a previous study in this setting hospitalized on their assigned index date. Study variables were abstracted from the hospital chart. Six factors were independently associated with a significantly increased risk of in-hospital hip fracture: impaired vision (odds ratio = 1.97, 95% confidence interval (CI)1.18-3.30), assisted ambulation (odds ratio = 2.12, 95% CI 1.25-3.59), confusion (odds ratio = 2.48, 95% CI 1.37-4.48), psychotropic drug use (odds ratio = 2.02, 95% CI 1.22-3.33), lowest weight tertile (odds ratio = 2.86, 95% CI 1.38-5.92), and prior in-hospital fall (odds ratio = 2.71, 95% CI 1.52-4.82). The risk increased substantially with the number of factors present, from an odds ratio of 4.08 (95% CI 1.56-10.67) for one factor (reference group, no factors) to 82.84 (95% CI 18.6-368.7) for four or more factors (p < 0.001, test for trend). These data underscore the multifactorial etiology of in-hospital hip fracture and suggest that prevention programs need to target multiple risk factors. C1 VANDERBILT UNIV,SCH MED,DEPT PREVENT MED,DIV PHARMACOEPIDEMIOL,NASHVILLE,TN 37232. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DIV GERIATR & GERONTOL,SAN ANTONIO,TX. LAB & DIS CONTROL SERV,REGINA,SK,CANADA. FU FDA HHS [FD-U-000073]; PHS HHS [CCR407306] NR 36 TC 50 Z9 50 U1 6 U2 9 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 1994 VL 140 IS 9 BP 830 EP 838 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PQ069 UT WOS:A1994PQ06900008 PM 7977293 ER PT J AU ROTH, D SMITH, RD SCHULMAN, G STEINMAN, TI HATCH, FE RUDNICK, MR SLOAND, JA FREEDMAN, BI WILLIAMS, WW SHADUR, CA BENZ, RL TEEHAN, BP REVICKI, DA SAROKHAN, BJ ABELS, RI AF ROTH, D SMITH, RD SCHULMAN, G STEINMAN, TI HATCH, FE RUDNICK, MR SLOAND, JA FREEDMAN, BI WILLIAMS, WW SHADUR, CA BENZ, RL TEEHAN, BP REVICKI, DA SAROKHAN, BJ ABELS, RI TI EFFECTS OF RECOMBINANT-HUMAN-ERYTHROPOIETIN ON RENAL-FUNCTION IN CHRONIC-RENAL-FAILURE PREDIALYSIS PATIENTS SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE ERYTHROPOIETIN; PREDIALYSIS; ANEMIA; GLOMERULAR FILTRATION RATE ID PLACEBO-CONTROLLED TRIAL; PRE-DIALYSIS PATIENTS; ANEMIA; INJURY; HYPERTENSION; PROGRESSION; EFFICACY; THERAPY; DISEASE AB A study was undertaken to ascertain the effects of recombinant human erythropoietin (r-HuEPO) on renal function in chronic renal failure predialysis patients. The effect of improvement of anemia by r-HuEPO on the rate of decline in renal function in predialysis patients has not been previously studied prospectively in a large number of patients using reliable measures of glomerular filtration rate (GFR). To investigate the efficacy, safety, and impact of r-HuEPO therapy in chronic renal insufficiency patients, a 48-week, randomized, open-label, multicenter study was initiated in 83 anemic, predialysis (serum creatinine 3 to 8 mg/dL) patients. Serial GFRs were measured using I-125-iothalamate clearance. Forty patients were randomized to the untreated arm and 43 patients to the treatment arm (50 U/kg r-HuEPO subcutaneously three times weekly). Baseline characteristics were comparable for the r-HuEPO-treated and untreated groups. During this 48-week study, GFR, mean arterial blood pressure, and daily protein intake were not significantly different between the two groups. There was a statistically significant increase in hematocrit for the r-HuEPO-treated group that was not associated with acceleration of deterioration in residual renal function. This was demonstrated by the lack of a significant (P = 0.376) between-group difference in mean change in GFR from baseline to last available value for the r-HuEPO-treated (-2.1 +/- 3.2 mL/min) and untreated (-2.8 +/- 3.5 mL/min) groups. This study concludes that r-HuEPO therapy improves anemia in predialysis patients and does not accelerate the rate of progression to end-stage renal disease. (C) 1994 by the National Kidney Foundation, Inc. C1 LANKENAU HOSP,MED RES CTR,DIV NEPHROL,WYNNEWOOD,PA 19097. UNIV MIAMI,SCH MED,DEPT MED & SURG,MIAMI,FL. UNIV TEXAS,SW MED CTR,SCH MED,DALLAS,TX. VET ADM MED CTR,DEPT MED,SALSBERG,NC. VET ADM MED CTR,DEPT NEPHROL,SALSBERG,NC. VANDERBILT UNIV,CTR MED,END STAGE RENAL DIS PROGRAM,NASHVILLE,TN 37232. VANDERBILT UNIV,CTR MED,DEPT MED,DIV NEPHROL,NASHVILLE,TN 37232. BETH ISRAEL HOSP,DIALYSIS UNIT,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV TENNESSEE,DEPT MED,DIV NEPHROL,MEMPHIS,TN 38104. UNIV PENN,GRAD HOSP,SCH MED,DEPT MED,DIV NEPHROL,PHILADELPHIA,PA 19104. UNIV ROCHESTER,HIGHLAND HOSP,DEPT MED,NEPHROL UNIT,ROCHESTER,NY. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT INTERNAL MED,NEPHROL SECT,WINSTON SALEM,NC. IOWA METHODIST MED CTR,DEPT NEPHROL & INTERNAL MED,DES MOINES,IA. LANKENAU HOSP,HAVERFORD DIALYSIS UNIT,WYNNEWOOD,PA. BATTELLE CTR PUBL HLTH RES & EVALUAT,ARLINGTON,VA. ORTHO BIOTECH INC,RARITAN,NJ. RW JOHNSON PHARMACEUT RES INST,RARITAN,NJ 08869. NR 26 TC 149 Z9 157 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 1994 VL 24 IS 5 BP 777 EP 784 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA PR329 UT WOS:A1994PR32900005 PM 7977319 ER PT J AU BARNWELL, SL CLARK, WM NGUYEN, TT ONEILL, OR WYNN, ML COULL, BM AF BARNWELL, SL CLARK, WM NGUYEN, TT ONEILL, OR WYNN, ML COULL, BM TI SAFETY AND EFFICACY OF DELAYED INTRAARTERIAL UROKINASE THERAPY WITH MECHANICAL CLOT DISRUPTION FOR THROMBOEMBOLIC STROKE SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE THROMBOLYSIS; THROMBOSIS, CEREBRAL; DRUGS, INTRAARTERIAL INJECTION; BRAIN, INFARCTION; INTERVENTIONAL NEURORADIOLOGY ID TISSUE PLASMINOGEN-ACTIVATOR; MIDDLE CEREBRAL-ARTERY; THROMBOLYTIC THERAPY; TERRITORY STROKE; ISCHEMIC STROKE AB PURPOSE: To evaluate safety and efficacy of delayed intraarterial urokinase therapy with mechanical disruption of clot to treat thromboembolic stroke. METHODS: Thirteen patients with cerebral thrombolic disease (10 carotid territory, 3 basilar territory) were treated with catheter-directed intraarterial urokinase therapy with mechanical disruption of the clots. All patients were excluded from a 6-hour multicenter thrombolytic trial by either time, recent surgery, age, seizure, or myocardial infarction. Time elapsed before treatment ranged from 3.5 to 48 hours (12 +/- 13 hours), with 200 000 to 900 000 U of urokinase used. RESULTS: Ten patients had successful vessel recanalization, confirmed by repeat angiography. Cases with distal branch vessel occlusions were less likely to recanalize. Asymptomatic hemorrhagic conversion occurred in 2 patients on repeat scans. Both acute neurologic and functional outcomes were assessed with significant improvement occurring in 9 (69%) of 13 patients at 48 hours (greater than four-point change on the National Institutes of Health scale) and in 100% of 3-month survivors. All patients who improved had normal initial CT scans. CONCLUSIONS: Intraarterial cerebral thrombolysis with mechanical disruption of clot seems to be a useful therapy in selected stroke cases even after 6 hours. C1 OREGON HLTH SCI UNIV,DEPT RADIOL,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DOTTER INTERVENT INST,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,OREGON STROKE CTR,PORTLAND,OR 97201. PORTLAND VET AFFAIRS MED CTR,NEUROL SERV,PORTLAND,OR. RP BARNWELL, SL (reprint author), OREGON HLTH SCI UNIV,DEPT NEUROSURG,L-472,3181 SW SAM JACKSON PK RD,PORTLAND,OR 97201, USA. NR 18 TC 133 Z9 136 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV PY 1994 VL 15 IS 10 BP 1817 EP 1822 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA PQ991 UT WOS:A1994PQ99100004 PM 7863929 ER PT J AU PROVENZALE, JM BARBORIAK, DP GAENSLER, EHL ROBERTSON, RL MERCER, B AF PROVENZALE, JM BARBORIAK, DP GAENSLER, EHL ROBERTSON, RL MERCER, B TI LUPUS-RELATED MYELITIS - SERIAL MR FINDINGS SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE MYELITIS; LUPUS ERYTHEMATOSUS; SPINAL CORD, MAGNETIC RESONANCE ID ACUTE TRANSVERSE MYELITIS; MULTIPLE-SCLEROSIS; SPINAL-CORD; ERYTHEMATOSUS; MYELOPATHY; DISEASE AB PURPOSE: To correlate the MR findings in transverse myelitis secondary to systemic lupus erythematosus with clinical findings during disease exacerbation and remission. METHODS: Four patients (ages 33 to 47 years) with episodes of transverse myelitis secondary to systemic lupus erythematosus were identified. Three patients had recurrent transverse myelitis episodes (one patient with two recurrences), for a total of eight episodes. MR examinations (six after contrast administration) were performed during each transverse myelitis episode, as well as during four periods of remission (in three patients) after therapy with steroids and/or immunosuppressive agents. MR examinations were reviewed for the presence of spinal cord enlargement, intramedullary signal abnormality, and contrast enhancement. RESULTS: Prolongation of T1 or T2 signal (or both) was seen in eight episodes (100%). Spinal cord enlargement was seen in six (75%) of eight transverse myelitis episodes, although it was mild during two episodes. Contrast enhancement was seen in three of six transverse myelitis episodes (dense, inhomogeneous enhancement during two episodes in one patient, and a small focus of enhancement in one patient). During periods of remission, spinal cord diameter returned to normal, and no contrast enhancement was seen, although abnormal signal was present in three examinations performed within 2 months of a transverse myelitis episode. CONCLUSION: Spinal cord widening and signal abnormalities are common MR findings during episodes of transverse myelitis related to systemic lupus erythematosus, and contrast enhancement is less frequently seen. Improvement or resolution of these findings correlates with clinical improvement. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. ALTA BATES MED CTR,DEPT RADIOL,BERKELEY,CA. HARVARD UNIV,COMMUNITY HLTH PLAN,DEPT NEURORADIOL,BOSTON,MA 02115. SHIELDS HEALTHCARE,BROCKTON,MA. OI Robertson, Richard/0000-0001-8811-4405 NR 32 TC 51 Z9 52 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV PY 1994 VL 15 IS 10 BP 1911 EP 1917 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA PQ991 UT WOS:A1994PQ99100016 PM 7863941 ER PT J AU PEDROSA, CA AHERN, DK MCKENNA, MJ OJEMANN, RG ACQUADRO, MA AF PEDROSA, CA AHERN, DK MCKENNA, MJ OJEMANN, RG ACQUADRO, MA TI DETERMINANTS AND IMPACT OF HEADACHE AFTER ACOUSTIC NEUROMA SURGERY SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article ID PAIN; BIOFEEDBACK; EXCISION AB Headache after acoustic neuroma surgery is known to occur clinically, but has not been studied systematically until recently. In the present study, 155 patients were surveyed regarding their experience of headache and associated symptoms following resection of an acoustic neuroma: 73 percent (n = 98) of patients undergoing suboccipital resection of an acoustic neuroma and 53 percent (n = 8) of patients undergoing translabyrinthine resection of acoustic neuroma complained of headache following surgery. The average pain intensity was greater for the suboccipital approach. Only 9 percent(n = 14) reported troublesome or frequent headaches preoperatively. Headache was described most often as tension type, with episodic acute exacerbations mimicking migraine. Clinical observations suggest that most patients are treated successfully with various combinations of reassurance, tricyclic antidepressants, nonsteroidal anti-inflammatory medications, trigger-point injections, adjunctive stress management techniques (relaxation), and physical therapy. The impact of recurrent headache on work and recreational function is notable. Several possible pathophysiological and biopsychosocial models are proposed to account for the prevalent headache problem. Although spontaneous resolution usually occurs over time, additional study is needed to determine the natural history of postoperative headache once it occurs. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV BEHAV MED PSTCHIAT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG,BOSTON,MA. NR 15 TC 31 Z9 31 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD NOV PY 1994 VL 15 IS 6 BP 793 EP 797 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA PQ076 UT WOS:A1994PQ07600017 PM 8572094 ER PT J AU MARATHIAS, K PINTO, C RODBERG, G PREFFER, F WONG, J KRADIN, R AF MARATHIAS, K PINTO, C RODBERG, G PREFFER, F WONG, J KRADIN, R TI THE T-CELL ANTIGEN RECEPTOR CD3-CD4 MOLECULAR-COMPLEX IS DIMINISHED ON THE SURFACE OF PULMONARY LYMPHOCYTES SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4 MOLECULE; MONOCLONAL-ANTIBODIES; CLASS-II; HUMAN-LUNG; HIV GP120; ACTIVATION; BINDING; EXPRESSION; PROLIFERATION AB CD4, a 55-kd cell surface glycoprotein, binds to class II major histocompatibility complex (MHC) (Ia) antigens and functions as a coreceptor for the T cell antigen receptor (Ti alpha beta)-CD3 complex. We have observed that critical elements of the T cell antigen multireceptor complex, including Ti alpha beta, CD3, CD4, but not CD8, were diminished on CD45RO(+) pulmonary T lymphocytes but not CD45RO(+) peripheral blood T lymphocytes (PBL). Epitopes mapping from the first (D1) to the fourth (D4) extracytoplasmic Ig-like domains of CD4 were expressed to a lesser degree on pulmonary T cells than on PBL (P = 0.002). CD4 expression on pulmonary T cells did not increase after 72 hours of ex vivo culture in complete medium but was restored toward control levels by stimulation with phytohemagglutinin, anti-CD3, or interleukin-2 CD4 mRNA isolated from lung T cells and PBL co-migrated on Northern blots and the total levels of CD4 mRNA were comparable, suggesting that diminished CD4 expression by pulmonary T cells might reflect a posttranscriptional change. To determine whether CD4(bright) T cells convert with mitogen stimulation to CD4(dim) cells, PBLs were stimulated with immobilized anti-CD3, anti-CD4, or a molecularly engineered anti-CD3:CD4 bispecific monoclonal antibody and the ratio of the CD4:CD3 mean fluorescence staining intensities was calculated at days 3 and 13. The CD4:CD3 ratio decreased primarily for cells stimulated with anti-CD3:CD4, suggesting that co-ligation of CD3 and CD4 is required for the generation of CD4(dim) cells. We conclude that diminished Ti alpha beta CD3:CD4 expression is a characteristic of T cells in lung that is not shared by peripheral blood T cells in vivo, and speculate that this change reflects T cell activation in a millieu of limited interleukin-2 availability. C1 MASSACHUSETTS GEN HOSP, DEPT MED, IMMUNOPATHOL UNIT COX 5, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. FU NHLBI NIH HHS [HL-48385, HL-43827] NR 45 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1994 VL 145 IS 5 BP 1219 EP 1227 PG 9 WC Pathology SC Pathology GA PQ086 UT WOS:A1994PQ08600026 PM 7977652 ER PT J AU CHANG, A HAMMOND, TG SUN, TT ZEIDEL, ML AF CHANG, A HAMMOND, TG SUN, TT ZEIDEL, ML TI PERMEABILITY PROPERTIES OF THE MAMMALIAN BLADDER APICAL MEMBRANE SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE WATER PERMEABILITY; UREA; ENDOCYTOSIS; FLOW CYTOMETRY ID RABBIT URINARY-BLADDER; TRANSITIONAL EPITHELIAL-CELLS; EXPANSION-CONTRACTION CYCLE; PLASMA-MEMBRANE; NONELECTROLYTE PERMEABILITIES; SURFACE GLYCOSAMINOGLYCANS; WATER PERMEABILITY; LUMINAL MEMBRANE; COLLECTING DUCT; TRANSLOCATION AB The luminal surface of mammalian bladder is exposed to urine with a composition widely different from that of plasma that bathes the basolateral surface of epithelium. Therefore we predict that the bladder permeability barrier, which is likely located in the apical membrane (AM), will exhibit low permeabilities to water, urea, NH3, H+, and small nonelectrolytes. AM surface area increases as the bladder fills with urine and decreases during emptying, a process that involves cyclical endocytosis and reinsertion of membrane from a pool of AM endosomes (AME). Rigid-appearing plaques composed of three proteins, uroplakins, have been identified acid occupy 70-90% of AM surface area. To determine permeability properties of the AM permeability barrier, we purified AME and measured their permeabilities. Rabbit urinary bladders were removed, and their apical surface was exposed to carboxyfluorescein (CF) or horseradish peroxidase (HRP). Exposure to hypotonic and then isotonic basolateral solutions induced endocytosis of luminal CF or HRP into AME. Electron microscopy of bladders after this treatment revealed HRP entrapped within AME bordered by plaques. AME were purified by differential and sucrose-gradient centrifugation, and CF-containing AME were purified 17.0 +/- 3-fold (SD) with respect to homogenate. Analysis of purified AME by flow cytometry showed that > 95% of vesicles contained CF entrapped from luminal solution and were selectively labeled with anti-uroplakin antibody. AME osmotic water permeability averaged 2.3 +/- 0.66 x 10(-4) cm/s and exhibited a high activation energy, indicating that AM contains no water channels. Permeability to urea and NH3 averaged 7.8 +/- 3.7 x 10(-7) and 1.5 +/- 0.3 x 10(-3) cm/s, respectively, which are exceptionally low and similar to permeabilities of other water-tight membranes, including toad urinary bladder and gastric mucosa. AME behaved as a single population in all permeability studies, which will permit future characterization of protein and lipid structure responsible for these unique permeability properties. C1 VET AFFAIRS MED CTR, RES SERV, BOSTON, MA 02132 USA. UNIV WISCONSIN, DEPT MED, MADISON, WI 53706 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, MADISON, WI 53706 USA. NYU, MED CTR, DEPT DERMATOL, NEW YORK, NY 10003 USA. UNIV PITTSBURGH, SCH MED, DIV RENAL & ELECTROLYTE, PITTSBURGH, PA 15213 USA. UNIV PITTSBURGH, SCH MED, EPITHELIAL CELL BIOL LAB, PITTSBURGH, PA 15213 USA. VET AFFAIRS MED CTR, MED SERV, BOSTON, MA 02132 USA. FU NIDDK NIH HHS [DK-43955, R0-1-DK-47547, DK-46117] NR 42 TC 77 Z9 77 U1 2 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD NOV PY 1994 VL 267 IS 5 BP C1483 EP C1492 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA PW518 UT WOS:A1994PW51800037 PM 7977709 ER PT J AU OGUCHI, S WALKER, WA SANDERSON, IR AF OGUCHI, S WALKER, WA SANDERSON, IR TI PROFILE OF IGF-BINDING PROTEINS SECRETED BY INTESTINAL EPITHELIAL-CELLS CHANGES WITH DIFFERENTIATION SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE CACO-2 CELLS; GROWTH FACTORS; TRANSFORMING GROWTH FACTOR-ALPHA ACTIVITY; INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN; INSULIN-LIKE GROWTH FACTOR ID GROWTH FACTOR-I; MOLECULAR-CLONING; EXPRESSION; IDENTIFICATION; RAT; CACO-2; SERUM AB Profile of IGF-binding proteins secreted by intestinal epithelial cells changes with differentiation. Am. J. Physiol. 267 (Gastrointest. Liver Physiol. 30): G843-G850, 1994.-Previous reports have shown that gastrointestinal epithelial cells produce insulin-like growth factor-binding proteins (IGF-BP), which modulate the actions of IGF. This study aims to examine the relationship between differentiation and IGF-BP secretion by human intestinal epithelial cells and the effect of growth factors on their production. Caco-2 cells were cultured in serum-free media. IGF-BP secretion into the incubation media was analyzed by Western ligand blotting and immunoblotting. Caco-2 cells produced IGF-BP-2, IGF-BP-3, and IGF-BP-4. Secretion of IGF-BP-2 and IGF-BP-3 increased with differentiation, but IGF-BP-4 secretion diminished. The effect of exogenous growth factors on IGF-BP secretion was maximal at earlier stages of differentiation. IGF-I stimulated mainly IGF-BP-3 production, but epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) stimulated predominantly IGF-BP-4 secretion. Adding an anti-EGF receptor antibody to block autocrine TGF-alpha activity inhibited IGF-BP-4 production but stimulated IGF-BP-S and IGF-BP-3. In conclusion, the profile of IGF-BP secretion changes with differentiation. IGF-I and EGF (or TGF-alpha) stimulate different types of IGF-BP, with autocrine TGF-alpha activity being a factor affecting IGF-BP production during differentiation. C1 MASSACHUSETTS GEN HOSP, DEV GASTROENTEROL LAB, COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02129 USA. FU NICHD NIH HHS [HD-12437, HD-31852] NR 33 TC 42 Z9 42 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 1994 VL 267 IS 5 BP G843 EP G850 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA PX275 UT WOS:A1994PX27500013 PM 7526702 ER PT J AU GIORDANO, M CASTELLINO, P MCCONNELL, EL DEFRONZO, RA AF GIORDANO, M CASTELLINO, P MCCONNELL, EL DEFRONZO, RA TI EFFECT OF AMINO-ACID INFUSION ON RENAL HEMODYNAMICS IN HUMANS - A DOSE-RESPONSE STUDY SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE AMINO ACIDS; GLOMERULAR FILTRATION RATE; RENAL PLASMA FLOW; RENAL FUNCTIONAL RESERVE; GLUCAGON ID GLOMERULAR-FILTRATION RATE; GROWTH FACTOR-I; MEAT MEAL; INDUCED HYPERFILTRATION; GLUCAGON; INSULIN; PROTEIN; SOMATOMEDIN; KIDNEY; PROSTAGLANDINS AB We evaluated the dose-response relationship between the plasma amino acid (AA) concentration and renal hemodynamics in eight normal subjects. After an overnight fast, a balanced 10% AA solution was infused for 180 min at five separate infusion rates: 0.5 (group I), 1.0 (group 11), 2.0 (group III), 4.0 (group IV), and 6.0 (group V) ml.kg(-1).min(-1) on separate days. Basal plasma AA concentration was 1.87 +/- 0.1 mmol/l and increased to 2.26 +/- 0.1 (group 1), 2.66 +/- 0.2 (group II), 3.79 +/- 0.5 (group III), 5.81 +/- 0.4 (group IV), and 7.41 +/- 0.4 mmol/l (group V). Basal glomerular filtration rate (GFR) and renal plasma flow (RPF) averaged 95 +/- 4 and 476 +/- 29 ml.1.73 m(-2).min(-1), respectively, and rose to 98 +/- 5 and 506 +/- 40 (group I) [P = not significant (NS)], 102 +/- 3 and 533 +/- 30 (group II) (P < 0.05 vs. basal), 110 +/- 4 and 567 +/- 29 (group III), 115 +/- 7 and 610 +/- 55 (group IV), and 117 +/- 7 and 614 +/- 66 ml.1.73 m(-2).min(-1) (group V) (P = NS vs, group TV). Basal plasma glucagon concentration averaged 68 +/- 10 pg/ml and increased to 74 +/- 10 (group I), 83 +/- 11 (group II) (P < 0.05 vs. basal), 100 +/- 14 (group III), 121 +/- 14 (group IV), and 229 +/- 35 pg/ml (group V) (P < 0.01 vs. basal). Increases in plasma growth hormone (GH) and insulin levels were observed only during groups IV and V. Plasma insulin-like growth factor I (IGF-I) did not change significantly during AA infusion. These results indicate the following: 1) increases in plasma AA concentrations within the physiological range cause a dose-related rise in GFR and RPF (r = 0.94, P < 0.001); 2) pharmacological increases in plasma AA levels are not associated with any further rise in GFR and RPF above that observed with physiological hyperaminoacidemia; and 3) within the physiological range the increases in GFR and RPF are closely correlated with the elevation in plasma glucagon concentration (r = 0.98, P < 0.001) but not with changes in insulin, GH, or IGF-I levels. C1 UNIV TEXAS, HLTH SCI CTR, DEPT MED, DIV DIABET, SAN ANTONIO, TX 78284 USA. AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. RP GIORDANO, M (reprint author), UNIV NAPLES 2, IST MED INTERNA & NEFROL, DIV POLICLIN, CAPPELLA CANGIANI, VIA PANSINI, I-80131 NAPLES, ITALY. NR 33 TC 22 Z9 24 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrol. Physiol. PD NOV PY 1994 VL 267 IS 5 BP F703 EP F708 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA PW546 UT WOS:A1994PW54600001 PM 7977774 ER PT J AU CHRISTIANI, DC YE, TT WEGMAN, DH EISEN, EA DAI, HL LU, PL AF CHRISTIANI, DC YE, TT WEGMAN, DH EISEN, EA DAI, HL LU, PL TI COTTON DUST EXPOSURE, ACROSS-SHIFT DROP IN FEV(1), AND 5-YEAR CHANGE IN LUNG-FUNCTION SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID TEXTILE WORKERS; RESPIRATORY-DISEASE; EPIDEMIOLOGY; BYSSINOSIS; MILLS AB To evaluate chronic loss of lung function in cotton dust-exposed workers, a 5-yr follow-up study was performed in Shanghai, China from 1981 to 1986. Workers at a nearby silk thread manufacturing mill were used as a control population. There were 384 cotton textile workers restudied from an original group of 446, and 403 silk workers restudied from the original 468. The presence of byssinosis among retested cotton workers at the time of first survey was 7.3%. The prevalence of byssinosis was 9.7% at the initial survey among those lost to follow-up. No byssinosis was found among control subjects. The mean annual decline in FEV(1) was 39.5 mi among cotton workers and 30.6 mi for silk workers (p < 0.05). The greatest annual decrements were found among smoking cotton workers, but nonsmoking cotton workers also lost lung function at a faster rate than silk nonsmokers (annual loss = 33.3 mt versus 24.4 mi, respectively). Autoregressive modeling revealed that after adjustments for age, sex, height, and smoking, cotton dust exposure was significantly associated with decline in FEV(1). Moreover, across-shift drop of 5% or more at the time of first survey was predictive of 5-yr decline in FEV(1). Cotton workers who had an acute response (5% or greater drop in FEV(1) at the time of first survey) suffered a 57.0 ml/yr FEV(1) drop compared with a 35.1-ml drop among cotton workers with less acute response at baseline (p < 0.01). Silk workers with or without 5% across-shift drops had similar annual rates of decline (-33.8 mt and -36.1 mi, respectively). After adjusting for appropriate confounders, we found that continued exposure to cotton dust in the cotton textile industry is associated with progressive impairment of lung function and that modest across-shift decrements in FEV(1) are strongly predictive of long term impairment of lung function. Workers chronically exposed to cotton dust are at risk of developing chronic airflow obstruction. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,PULM & CRIT CARE UNIT,BOSTON,MA. SHANGHAI MED UNIV,SCH PUBL HLTH,INST PREVENT MED,SHANGHAI,PEOPLES R CHINA. UNIV MASSACHUSETTS,DEPT WORK ENVIRONM,LOWELL,MA. FIRST HOSP SHANGHAI TEXT BUR,SHANGHAI,PEOPLES R CHINA. RP CHRISTIANI, DC (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,OCCUPAT HLTH PROGRAM,665 HUNTINGTON AVE,I-1405,BOSTON,MA 02115, USA. FU NIEHS NIH HHS [ES00002]; NIOSH CDC HHS [R01OH02421] NR 25 TC 70 Z9 73 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV PY 1994 VL 150 IS 5 BP 1250 EP 1255 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PR664 UT WOS:A1994PR66400007 PM 7952548 ER PT J AU SILMAN, JB PETERS, JI LEVINE, SM JENKINSON, SG AF SILMAN, JB PETERS, JI LEVINE, SM JENKINSON, SG TI DEVELOPMENT OF INTRACRANIAL TUBERCULOMAS WHILE RECEIVING THERAPY FOR PULMONARY FIBROSIS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Note ID CHEMOTHERAPY; MENINGITIS AB Development of tuberculomas on adequate tuberculosis therapy is an uncommon event. This case report describes a patient who developed multiple intracranial tuberculomas while receiving adequate supervised outpatient therapy for sensitive pulmonary tuberculosis who was documented to have no intracranial lesions prior to initiation of treatment. C1 AUDIE L MURPHY MEM VET ADM MED CTR,PULM DIS SECT,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. NR 17 TC 9 Z9 9 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV PY 1994 VL 150 IS 5 BP 1439 EP 1440 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PR664 UT WOS:A1994PR66400034 PM 7695703 ER PT J AU GLIKLICH, RE METSON, R AF GLIKLICH, RE METSON, R TI A COMPARISON OF SINUS COMPUTED-TOMOGRAPHY (CT) STAGING SYSTEMS FOR OUTCOMES RESEARCH SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article ID PARANASAL SINUSES; CATEGORICAL DATA; SURGERY; ETHMOIDECTOMY; INTRANASAL; EXPERIENCE AB The success of outcomes research for sinus disease will depend in part on the utilization of a computed tomography (CT) staging system that meets rigorous statistical criteria. Such a staging system must demonstrate an even distribution of population by scale, a high inter-rater and intra-rater agreement, and a low percentage of unclassifiable scans. Four proposed sinus CT classification systems were evaluated for these parameters. Each system was used by four masked racers to rate 42 consecutive preoperative CT scans on two separate occasions. One of these systems is based on the sire of disease rather than the degree of sinus opacification and gives a clear definition of sinus disease (2 mm or greater of mucosal thickening). This system had the highest inter-rater agreement (kappa = 0.61, range = 0.38 to 0.61) and the lowest percentage of unclassifiable scans (0.6%, range = 0.6 to 14.2%). The statistical attributes of this particular sinus CT staging system support its use for outcomes research in sinus disease. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP GLIKLICH, RE (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 18 TC 54 Z9 56 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD NOV-DEC PY 1994 VL 8 IS 6 BP 291 EP 297 DI 10.2500/105065894781874197 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA QB700 UT WOS:A1994QB70000005 ER PT J AU GREENE, R AF GREENE, R TI AN IMPERCEPTIBLE SLOW DRIP MAY LEAD TO DEATH SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note ID PNEUMONIA; DIAGNOSIS C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 7 TC 2 Z9 2 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 1994 VL 163 IS 5 BP 1036 EP 1037 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PQ817 UT WOS:A1994PQ81700004 PM 7976872 ER PT J AU KOPANS, DB AF KOPANS, DB TI THE SINE-QUA-NON OF BREAST-CANCER - REPLY SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter RP KOPANS, DB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 1994 VL 163 IS 5 BP 1266 EP 1266 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PQ817 UT WOS:A1994PQ81700054 ER PT J AU YOUNG, RH OLIVA, E SCULLY, RE AF YOUNG, RH OLIVA, E SCULLY, RE TI SMALL-CELL CARCINOMA OF THE OVARY, HYPERCALCEMIC TYPE - A CLINICOPATHOLOGICAL ANALYSIS OF 150 CASES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE OVARY; SMALL CELL CARCINOMA; HYPERCALCEMIA ID HORMONE-RELATED PROTEIN; PARA-NEOPLASTIC HYPERCALCEMIA; PARATHYROID-HORMONE; HUMORAL HYPERCALCEMIA; TUMORS; ADENOCARCINOMA; YOUNG; DYSGERMINOMA; METASTASES; DIAGNOSIS AB The clinical and pathological features of 150 cases of ovarian small cell carcinoma of the hypercalcemic type are described. The patients ranged from 9 to 43 (average 23.9) years of age. The serum calcium level was known to be elevated in 49 of the 79 patients (62%) whose preoperative calcium levels were measured. Four of these patients had symptoms of hypercalcemia, and one of them had undergone neck exploration with negative results before the ovarian tumor was discovered. At laparotomy the tumor was unilateral in 148 cases (99%). Extraovarian spread was present in approximately half the cases. The tumors ranged from 6 to 26 (average 15.3) cm in greatest dimension. Microscopic examination disclosed various patterns, the most common of which was diffuse sheets of cells punctured by variable numbers of follicle-like spaces; the tumor cells also grew in nests, cords, clusters, and singly. The follicle-like spaces, which were present in 80% of the cases, contained fluid that was almost always eosinophilic and rarefy basophilic. Glands or cysts lined by mucinous epithelial cells were present in 12% of the neoplasms. The neoplastic cells were typically small and round with hyperchromatic nuclei and brisk mitotic activity. Fifty percent of the tumors, however, also had a variable component of cells with moderate to abundant amounts of eosinophilic cytoplasm, which sometimes contained large hyaline globules and large nuclei that were typically paler and had more prominent nucleoli than the small cells. Immunohistochemical staining confirmed the epithelial nature of the tumors, as did electron microscopy, which characteristically showed abundant dilated rough endoplasmic reticulum. Five of seven tumors investigated by immunohistochemical staining for parathyroid hormone-related protein showed positive results. All 23 tumors examined by flow cytometry with interpretable results were diploid. Fourteen of 42 patients (33%) with stage IA disease for whom follow-up information is available remained well and free of disease 1-13 (average 5.7) years postsurgery; 23 died of their disease, usually within 2 years; and five had recurrences but were alive at last follow-up. Almost all the patients with tumors of a stage higher than IA died of disease, but one patient with stage IIB disease who received intensive chemotherapy and radiation therapy is alive and apparently free of disease at 7 years. Features in stage IA tumors that appeared to be associated with a more favorable outcome included an age > 30 years, a normal preoperative calcium determination, a tumor size < 10 cm, and an absence of large cells. The tumors in this series were frequently misinterpreted initially as a variety of other ovarian neoplasms, most commonly adult or juvenile granulosa cell tumors or a primitive germ cell tumor, but the characteristic microscopic features of the small cell carcinoma facilitate its distinction from those tumors and others with which it may be confused. Analysis of the various types of therapy in the present series suggests that a procedure that includes bilateral salpingo-oophorectomy may be optimal for patients with stage IA tumors. The role of adjuvant therapy is unclear. Combination chemotherapy and radiation therapy for high-stage and recurrent tumors has been generally disappointing, but it has occasionally resulted in long-term survival and possible cure. 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,BOSTON,MA 02114, USA. NR 79 TC 178 Z9 193 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 1994 VL 18 IS 11 BP 1102 EP 1116 DI 10.1097/00000478-199411000-00004 PG 15 WC Pathology; Surgery SC Pathology; Surgery GA PN368 UT WOS:A1994PN36800003 PM 7943531 ER PT J AU CHEUNG, ANY YOUNG, RH SCULLY, RE AF CHEUNG, ANY YOUNG, RH SCULLY, RE TI PSEUDOCARCINOMATOUS HYPERPLASIA OF THE FALLOPIAN-TUBE ASSOCIATED WITH SALPINGITIS - A REPORT OF 14 CASES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE PSEUDOCARCINOMATOUS HYPERPLASIA; FALLOPIAN TUBE; CHRONIC SALPINGITIS ID LESIONS; TUMORS AB We describe 14 cases of pseudocarcinomatous changes in the fallopian tube characterized by florid epithelial hyperplasia and in half the cases mesothelial hyperplasia and associated with chronic salpingitis. The patients' ages ranged from 17 to 40 years. Seven had clinical evidence of pelvic inflammatory disease. Tubal enlargement or thickening were observed in 12 cases and pyosalpinx, tuboovarian abscesses, or hydrosalpinx, in six cases. All cases showed no gross evidence of tumor. The reactive atypical hyperplasia mimicked carcinoma microscopically because of a cribriform pattern, penetration of the tubal wall by hyperplastic epithelium, florid mesothelial hyperplasia, or a combination of these findings; epithelial papillae were present in the lymphatics in two cases. In five cases, an erroneous microscopic diagnosis of carcinoma had been made or seriously entertained initially, and one patient underwent a radical hysterectomy as a result. The typically young age of the patients, absence of a gross tumor, presence of severe chronic inflammation, lack of solid epithelial proliferation, mildness of nuclear atypia, and paucity of mitotic figures facilitated the differential diagnosis. Nine patients for whom follow-up information was available had no recurrence of tubal disease. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. NR 18 TC 25 Z9 27 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 1994 VL 18 IS 11 BP 1125 EP 1130 DI 10.1097/00000478-199411000-00006 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA PN368 UT WOS:A1994PN36800005 PM 7943533 ER PT J AU PELLEGRIN, KL FRUEH, BC AF PELLEGRIN, KL FRUEH, BC TI WHY PSYCHOLOGISTS DONT THINK LIKE PHILOSOPHERS SO AMERICAN PSYCHOLOGIST LA English DT Note C1 RALPH H JOHNSON VET AFFAIRS MED CTR,CHARLESTON,SC. RP PELLEGRIN, KL (reprint author), MED UNIV S CAROLINA,CHARLESTON,SC 29425, USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD NOV PY 1994 VL 49 IS 11 BP 970 EP 970 PG 1 WC Psychology, Multidisciplinary SC Psychology GA PQ622 UT WOS:A1994PQ62200010 ER PT J AU EDWARDS, MA LECLERC, N CRANDALL, JE YAMAMOTO, M AF EDWARDS, MA LECLERC, N CRANDALL, JE YAMAMOTO, M TI PURKINJE-CELL COMPARTMENTS IN THE REELER MUTANT MOUSE AS REVEALED BY ZEBRIN-II AND 90-ACETYLATED GLYCOLIPID ANTIGEN EXPRESSION SO ANATOMY AND EMBRYOLOGY LA English DT Article DE CEREBELLUM; NEUROLOGICAL MUTANT; GANGLIOSIDE; IMMUNOHISTOCHEMISTRY; NEURON MIGRATION ID RAT CEREBELLAR CORTEX; OLIVOCEREBELLAR PROJECTION; ORGANIZATION; BANDS; MICE; MIGRATION; ZONATION; COMPLEX AB The cerebellum is organized into a series of parasagittally aligned bands that may be revealed histologically in the adult mouse by largely complementary immunostaining of Purkinje cell sets with the monoclonal antibodies Zebrin II (ZII; antigen:aldolase C) and P-path (PP; antigen:90-acetyl glycolipids). We compared the normal staining pattern using these markers and an antibody to calbindin with that found in the reeler mutants (rl/rl), in which most Purkinje cell migration is halted beneath the cerebellar white matter. The results revealed that Purkinje cells in reeler mutants, despite their ectopic location in large subcortical masses, show a clear tendency to distribute into alternating zones that either stain for Zebrin II or for P-path, with variable transition zones of mixed labeling. However, the estimated number of zones was fewer than in the normal adult cortex: roughly 7-9 zones are revealed per side in the mutant compared with 14 major divisions in wild type mice. These results raise the possibility that neurons destined to express these markers are segregated during their migration and that the final phase of migration into the cortex might involve further splitting or interdigitation between cell sets expressing the two antigens. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. RP EDWARDS, MA (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DEPT BIOMED SCI,200 TRAPELO RD,WALTHAM,MA 02254, USA. FU NICHD NIH HHS [HD21018]; NINDS NIH HHS [NS24386, NS18381] NR 49 TC 25 Z9 25 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-2061 J9 ANAT EMBRYOL JI Anat. Embryol. PD NOV PY 1994 VL 190 IS 5 BP 417 EP 428 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA PU794 UT WOS:A1994PU79400002 PM 7887492 ER PT J AU RYAN, JF LOPEZ, JR SANCHEZ, VB SRETER, FA ALLEN, PD AF RYAN, JF LOPEZ, JR SANCHEZ, VB SRETER, FA ALLEN, PD TI MYOPLASMIC CALCIUM CHANGES PRECEDE METABOLIC AND CLINICAL SIGNS OF PORCINE MALIGNANT HYPERTHERMIA SO ANESTHESIA AND ANALGESIA LA English DT Article ID PIG RYANODINE RECEPTOR; SKELETAL-MUSCLE; SUSCEPTIBLE SWINE; DANTROLENE; CA-2+; MUTATION; INVIVO AB This study examines the chronologic relationship of the biochemical and clinical development of malignant hyperthermia (MH) in susceptible swine. Four pigs previously established by challenge to be susceptible to MH were studied. Monitors included end-tidal CO2 (ETco(2)), transcutaneous oxygen saturation (Spo(2)), intraarterial blood pressure, rectal temperature, electrocardiogram (ECG), and train-of-four twitch measurements. Calcium-selective microelectrodes were used to monitor changes in the concentration of free myoplasmic calcium ([Ca2+](i)). The animals were studied in the resting state, during the development of the syndrome, and after treatment with dantrolene sodium. The increase in [Ca2+](i) preceded the increase in ETco(2) that preceded a decrease in Spo(2) that preceded the classic first sign, tachycardia, and all preceded the increase in rectal temperature. Dantrolene reversed all of these physiologic changes in the same order of precedence as the increase. C1 INST VENEZOLANO INVEST CIENT,CTR BIOFIS & BIUOQUIM,CARACAS,VENEZUELA. BRIGHAM & WOMENS HOSP,DEPT ANESTHESIA,BOSTON,MA. BOSTON BIOMED RES INST,DEPT MUSCLE RES,BOSTON,MA. RP RYAN, JF (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. FU NIGMS NIH HHS [GM 15904] NR 21 TC 10 Z9 10 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD NOV PY 1994 VL 79 IS 5 BP 1007 EP 1011 PG 5 WC Anesthesiology SC Anesthesiology GA PN578 UT WOS:A1994PN57800033 PM 7978379 ER PT J AU HESS, D HIRSCH, C MARQUISDAMICO, C KACMAREK, RM AF HESS, D HIRSCH, C MARQUISDAMICO, C KACMAREK, RM TI IMPOSED WORK AND OXYGEN DELIVERY DURING SPONTANEOUS BREATHING WITH ADULT DISPOSABLE MANUAL VENTILATORS SO ANESTHESIOLOGY LA English DT Article DE BREATHING, IMPOSED WORK; EQUIPMENT, MANUAL VENTILATION DEVICES, RESUSCITATORS; VENTILATION, EMERGENCY, MECHANICAL, OXYGEN ADMINISTRATION, POSITIVE END-EXPIRATORY PRESSURE ID POSITIVE AIRWAY PRESSURE; END-EXPIRATORY PRESSURE; VOLUMES AB Background: Manual ventilators (resuscitators) are used primarily to ventilate the lungs of patients lacking spontaneous ventilatory effort. However, in many settings patients are allowed to breathe through the manual ventilator. Although many aspects of manual ventilator function have been studied, very little has been reported on the use of manual ventilators during spontaneous breathing. The purpose of this study was to evaluate inspiratory and expiratory imposed work Of breathing and oxygen delivery during spontaneous breathing through disposable manual ventilators. Methods: Simulated spontaneous breathing was established with a two-chambered test lung, with one chamber serving as the test chamber and the other as the driving chamber. Imposed work of breathing was evaluated with decelerating inspiratory now at a rate of 20 breaths/min at tidal volume (V-T) 0.25 l and peak now 40 l/min, at V-T 0.5 l and peak flow 80 l/min, and V-T 0.8 l and peak flow 120 l/min. Flow (integrated to volume) and pressure were measured between the manual ventilator and test lung, and inspiratory and expiratory imposed work of breathing were calculated by integration of the volume-pressure curve. Oxygen concentration was measured with an oxygen analyzer placed between the manual ventilator and the test lung at 20 breaths/min, V-T 0.5 l, and flow 45 l/min. An oxygen flow of 15 l/min was added to the device for all evaluations. Two of the manual ventilators had built-in positive end-expiratory pressure valves, and Imposed work was evaluated at 10 cmH(2)O with these. Results: There were significant differences in imposed work between inspiration and expiration (P < 0.001) and among the three levels of ventilatory demand (P < 0.001). For each ventilatory demand, there was a significant difference in work between manual ventilator brands for inspiratory work and expiratory work (P < 0.001). At a V-T of 0.5 l and peak flow of 80 l/min, the pooled inspiratory imposed work for all manual ventilators was 0.44 +/- 0.12 J/l, and the pooled expiratory imposed work was 0.23 +/- 0.05 J/l. With 10 cmH(2)O positive end-expiratory pressure, the inspiratory imposed work was very high (> 1 J/l). Four of the devices were unable to deliver more than 0.85 oxygen concentration at the spontaneous ventilatory pattern evaluated. Conclusions: Adult disposable manual ventilators produce a substantial imposed work of spontaneous breathing, which is increased with the addition of positive end-expiratory pressure. With some manual ventilators, a high oxygen concentration may not be delivered during spontaneous breathing. We recommend that patients not be allowed to spontaneously breathe through disposable manual ventilators. C1 HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115. RP HESS, D (reprint author), MASSACHUSETTS GEN HOSP,DEPT RESP CARE,ELLISON 401,BOSTON,MA 02114, USA. NR 19 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 1994 VL 81 IS 5 BP 1256 EP 1263 DI 10.1097/00000542-199411000-00020 PG 8 WC Anesthesiology SC Anesthesiology GA PP715 UT WOS:A1994PP71500023 PM 7978485 ER PT J AU CROSBY, G MAROTA, JJA GOTO, T UHL, GR AF CROSBY, G MAROTA, JJA GOTO, T UHL, GR TI SUBARACHNOID MORPHINE REDUCES STIMULATION-INDUCED BUT NOT BASAL EXPRESSION OF PREPROENKEPHALIN IN RAT SPINAL-CORD SO ANESTHESIOLOGY LA English DT Article DE ANALGESIA; ANALGESICS, OPIOID, MORPHINE; ANESTHETICS, INTRATHECAL, MORPHINE; CELLS, METABOLISM; METABOLISM, DNA, RNA; PAIN, EXPERIMENTAL; POLYPEPTIDES, ENKEPHALINS; SPINAL CORD, MORPHINE ID NUCLEUS CAUDALIS NEURONS; DORSAL HORN NEURONS; GENE-EXPRESSION; C-FOS; MESSENGER-RNA; AFFERENT-FIBERS; NERVOUS-SYSTEM; SUBSTANCE-P; PROENKEPHALIN; INFLAMMATION AB Background: To evaluate directly the possibility that the potent exogenous opioid analgesic morphine may alter neuronal expression of opioid peptide genes, we assessed the effect of subarachnoid morphine on basal and noxious stimulation-induced expression of preproenkephalin in spinal cord neurons. Methods: Twenty male Sprague-Dawley rats were prepared 48 h in advance with lumbar subarachnoid catheters. In the first phase, basal expression was evaluated in rats that received morphine 10 mu g or saline intrathecally (n = 5 per group). Subsequently, the experiment was repeated (n = 5 per group), except that 10 min after morphine or saline administration rats received a hindpaw footpad injection of 50 mu l 5% formalin. Rats were killed during pentobarbital anesthesia 2 h later, and messenger RNA transcribed from preproenkephalin was measured in lumbar spinal cord with quantitative in situ hybridization with a complementary sulfur 35-labeled oligonucleotide probe and emulsion autoradiography. Results: In control (nonstimulated) rats, 20% of the neurons in laminae I-II and 10% of those in laminae III-IV expressed preproenkephalin. Injection of formalin increased the fraction of positive neurons by 34% (P < 0.05) and 20% (P < 0.05) in laminae I-II and V-VI, respectively, but had no effect on expression in laminae III-IV. Subarachnoid morphine did not alter basal expression of preproenkephalin but markedly attenuated the noxious stimulation-induced increase in laminae I-II (P < 0.01) and V-VI (P < 0.05) by preventing the stimulation-evoked recruitment of preproenkephalin-expressing neurons that otherwise would have occurred. Conclusions: Subarachnoid morphine does not acutely alter basal expression of preproenkephalin in spinal cord neurons but inhibits the increase in preproenkephalin expression that would otherwise occur after noxious stimulation. C1 HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115. NIDA,ADDICT RES CTR,MOLEC NEUROBIOL LAB,LEXINGTON,KY. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21218. RP CROSBY, G (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. FU NIGMS NIH HHS [R01-GM42466] NR 39 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 1994 VL 81 IS 5 BP 1270 EP 1276 DI 10.1097/00000542-199411000-00022 PG 7 WC Anesthesiology SC Anesthesiology GA PP715 UT WOS:A1994PP71500025 PM 7978486 ER PT J AU THOMAS, SH STONE, CK RAY, VG WHITLEY, TW AF THOMAS, SH STONE, CK RAY, VG WHITLEY, TW TI INTRAVENOUS VERSUS RECTAL PROCHLORPERAZINE IN THE TREATMENT OF BENIGN VASCULAR OR TENSION HEADACHE - A RANDOMIZED, PROSPECTIVE, DOUBLE-BLIND TRIAL SO ANNALS OF EMERGENCY MEDICINE LA English DT Article AB Study objective: To compare the effectiveness of IV and PR prochlorperazine for treatment of acute benign vascular or tension headache. Design: Prospective, randomized, double-blind trial. Setting: University emergency department with 50,000 annual census. Participants: Forty-five adult patients enrolled on 46 visits. Interventions: Patients received 10 mg prochlorperazine IV and placebo suppository or 25 mg prochlorperazine PR and placebo injection. Pain assessment was made using a 10-cm visual-analog scale; scores were analyzed using Wilcoxon/Kruskal-Wallis rank-sum tests (alpha of .01). Results: Mean 60-minute pain scores for IV and PR groups were 0.6 and 3.5, respectively (P=.0002). Two patients (8.7%) in the IV group and six patients (26.1%) in the PR group required rescue analgesia (P=.12). Conclusion: IV prochlorperazine appears to provide more effective relief than PR prochlorperazine for benign vascular or tension headaches. RP THOMAS, SH (reprint author), MASSACHUSETTS GEN HOSP,DEPT EMERGENCY SERV,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 15 Z9 15 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD NOV PY 1994 VL 24 IS 5 BP 923 EP 927 DI 10.1016/S0196-0644(54)00222-3 PG 5 WC Emergency Medicine SC Emergency Medicine GA PP225 UT WOS:A1994PP22500013 PM 7978566 ER PT J AU KINOSIAN, B GLICK, H GARLAND, G AF KINOSIAN, B GLICK, H GARLAND, G TI CHOLESTEROL AND CORONARY HEART-DISEASE - PREDICTING RISKS BY LEVELS AND RATIOS SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE CORONARY DISEASE; CHOLESTEROL; LIPOPROTEINS, HDL CHOLESTEROL; LIPOPROTEINS, LDL CHOLESTEROL; PRACTICE GUIDELINES ID DENSITY LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR-DISEASE; PREVALENCE; WOMEN; FAT AB Objective: Comparison of four measures of cholesterol for predicting men and women who will develop coronary heart disease within 8 to 10 years. Design: Cohort study. Patients: 1898 men who received placebo (the placebo group of the Lipid Research Clinics [LRC] Coronary Primary Prevention Trial [CPPT]), 1025 men and 1442 women who participated in the 1970-1971 Framingham Heart Study biennial examination, and 1911 men and 1767 women without coronary heart disease who were from the LRC Population Prevalence Study. Measurements: Total cholesterol, low-density lipoprotein (LDL) cholesterol, ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol, and the ratio of LDL to HDL. Outcomes were coronary heart disease in the CPPT and Framingham studies and death from coronary heart disease in the Prevalence Study. Results: independent information in the total cholesterol/HDL ratio added risk-discriminating ability to total Cholesterol and LDL cholesterol measures (P < 0.02), but the reverse was not true. Among women, a high-risk threshold of 5.6 for the total cholesterol/HDL ratio identified a 0% to 15% larger group at 25% to 45% greater risk in the Prevalence and Framingham studies, respectively, than did current guidelines. Among men in the same studies, a risk threshold of 6.4 for the total cholesterol/HDL ratio identified a 69% to 95% larger group at 2% to 14% greater risk than did LDL cholesterol levels alone. Eight-year likelihood ratios for coronary heart disease ranged from 0.32 to 3.11 in men and from 0.59 to 2.98 in women for total cholesterol/HDL ratios (grouped from < 3 to greater than or equal to 9). Conclusions: The total cholesterol/HDL ratio is a superior measure of risk for coronary heart disease compared with either total cholesterol or LDL cholesterol levels. Current practice guidelines could be more efficient if risk stratification was based on this ratio rather than primarily on the LDL cholesterol level. C1 UNIV PENN,DEPT ECON,PHILADELPHIA,PA 19104. DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. RP KINOSIAN, B (reprint author), UNIV PENN,RALSTON PENN CTR,DIV GEN INTERNAL MED,ROOM 230,3615 CHESTNUT ST,PHILADELPHIA,PA 19104, USA. FU NIA NIH HHS [NIA R29-AG09837-03] NR 27 TC 301 Z9 312 U1 1 U2 5 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 NOV 1 PY 1994 VL 121 IS 9 BP 641 EP 647 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PN450 UT WOS:A1994PN45000002 PM 7944071 ER PT J AU COX, M HADDAD, JG AF COX, M HADDAD, JG TI LYMPHOMA, HYPERCALCEMIA, AND THE SUNSHINE VITAMIN SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID HORMONE-RELATED PROTEIN; CELL LEUKEMIA-LYMPHOMA; CULTURED ALVEOLAR MACROPHAGES; D ENDOCRINE SYSTEM; PARATHYROID-HORMONE; HUMORAL HYPERCALCEMIA; 1,25-DIHYDROXYVITAMIN-D3 PRODUCTION; TRANSFORMED LYMPHOCYTES; CALCITRIOL LEVELS; SERUM LEVELS C1 HOSP UNIV PENN,PHILADELPHIA,PA 19104. RP COX, M (reprint author), DEPT VET AFFAIRS MED CTR,MED SERV 111,UNIV & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. NR 44 TC 4 Z9 4 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 1 PY 1994 VL 121 IS 9 BP 709 EP 712 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA PN450 UT WOS:A1994PN45000012 PM 7944081 ER PT J AU HENSON, JW SCHNITKER, BL CORREA, KM VONDEIMLING, A FASSBENDER, F XU, HJ BENEDICT, WF YANDELL, DW LOUIS, DN AF HENSON, JW SCHNITKER, BL CORREA, KM VONDEIMLING, A FASSBENDER, F XU, HJ BENEDICT, WF YANDELL, DW LOUIS, DN TI THE RETINOBLASTOMA GENE IS INVOLVED IN MALIGNANT PROGRESSION OF ASTROCYTOMAS SO ANNALS OF NEUROLOGY LA English DT Article ID DINUCLEOTIDE REPEAT POLYMORPHISM; ALTERED EXPRESSION; TUMORS; HETEROZYGOSITY; CARCINOMA; PRODUCT; PROTEIN AB Loss of chromosome 13q occurs in up to 50% of human astrocytomas, suggesting the presence of an astrocytoma tumor suppressor gene on that chromosome. To determine whether the retinoblastoma susceptibility gene (Rb) on 13q14 contributes to the formation of astrocytomas, we examined 85 tumors for loss of heterozygosity (LOH) at the intragenic Rb 1.20 locus. LOH was detected in 16 of 54 informative high-grade astrocytomas (30%), but was not detected in 12 low-grade gliomas. Deletion mapping with flanking markets on 13q revealed that the Rb 1.20 region was preferentially targeted by the deletions. Tumors with LOH at Rb 1.20 were examined for mutations in the remaining Rb allele using single-strand conformational polymorphism (SSCP) analysis and direct DNA sequencing. Mutations were detected in exon 8 (1 tumor), exon 24 (2 tumors), and intron 24 (1 tumor). Rb protein expression, as assessed by immunohistochemistry, was altered in 3 of 9 cases with LOH and in 1 tumor without LOH. Our results demonstrate that Rb inactivation contributes to the formation of high-grade astrocytomas, and therefore implicate a second, known tumor suppressor gene in astrocytoma tumorigenesis. C1 MASSACHUSETTS GEN HOSP E,MOLEC NEUROONCOL LAB,NEUROSURG SERV,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP E,DEPT PATHOL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,HOWE LAB OPHTHALMOL,BOSTON,MA 02114. UNIV BONN,INST NEUROPATHOL,W-5300 BONN,GERMANY. BAYLOR COLL MED,CTR BIOTECHNOL,THE WOODLANDS,TX 77381. RP HENSON, JW (reprint author), MASSACHUSETTS GEN HOSP E,MOLEC NEUROONCOL LAB,NEUROL SERV,149 13TH ST,BOSTON,MA 02129, USA. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X FU NCI NIH HHS [CA 54672, CA 57683]; NINDS NIH HHS [NS 01650] NR 30 TC 181 Z9 183 U1 0 U2 3 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1994 VL 36 IS 5 BP 714 EP 721 DI 10.1002/ana.410360505 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PR051 UT WOS:A1994PR05100004 PM 7979217 ER PT J AU MECOCCI, P MACGARVEY, U BEAL, MF AF MECOCCI, P MACGARVEY, U BEAL, MF TI OXIDATIVE DAMAGE TO MITOCHONDRIAL-DNA IS INCREASED IN ALZHEIMERS-DISEASE SO ANNALS OF NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; DEGENERATIVE DISEASES; CYTOCHROME-OXIDASE; BRAIN; 8-HYDROXY-2'-DEOXYGUANOSINE; MUTATIONS; STRESS; OXYGEN; AMYLOIDOGENICITY; PEROXIDATION AB Oxidative damage to DNA may play a role in both normal aging and in neurodegenerative diseases. We examined whether Alzheimer's disease (AD) is associated with increased oxidative damage to both nDNA and mtDNA in postmortem brain tissue. We measured the oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (OH(8)dG), in DNA isolated from three regions of cerebral cortex and cerebellum in 13 AD and 13 age-matched controls. There was a significant threefold increase in the amount of OH(8)dG in mtDNA in parietal cortex of AD patients compared with controls. In the entire group of samples there was a small significant increase in oxidative damage to nDNA and a highly significant threefold increase in oxidative damage to mtDNA in AD compared with age-matched controls. These results confirm that mitochondrial DNA is particularly sensitive to oxidative damage, and they show that there is increased oxidative damage to DNA in AD, which may contribute to the neurodegenerative process. C1 MASSACHUSETTS GEN HOSP,NEUROCHEM LAB,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIA NIH HHS [5P50AG05134, P01AG11337] NR 45 TC 668 Z9 691 U1 3 U2 23 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1994 VL 36 IS 5 BP 747 EP 751 DI 10.1002/ana.410360510 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PR051 UT WOS:A1994PR05100009 PM 7979220 ER PT J AU BRESSMAN, SB DELEON, D KRAMER, PL OZELIUS, LJ BRIN, MF GREENE, PE FAHN, S BREAKEFIELD, XO RISCH, NJ AF BRESSMAN, SB DELEON, D KRAMER, PL OZELIUS, LJ BRIN, MF GREENE, PE FAHN, S BREAKEFIELD, XO RISCH, NJ TI DYSTONIA IN ASHKENAZI JEWS - CLINICAL CHARACTERIZATION OF A FOUNDER MUTATION SO ANNALS OF NEUROLOGY LA English DT Article ID IDIOPATHIC TORSION DYSTONIA; AUTOSOMAL DOMINANT INHERITANCE; SEGREGATION ANALYSIS; LINKAGE MAP; GENE; EXCLUSION AB A gene (DYT1) for idiopathic torsion dystonia maps to chromosome 9q34 in Ashkenazi Jewish families with early onset of symptoms. Further, there is linkage disequilibrium between DYT1 and a particular haplotype of alleles at 9q34 loci in this population. This implies that a large proportion of early-onset idiopathic torsion dystonia in Ashkenazi Jews is due to a founder mutation in DYT1. To characterize the phenotypic range of this mutation, we studied 174 Ashkenazi Jewish individuals affected with idiopathic torsion dystonia. We used GT(n) markers on chromosome 9q34 (D9S62, D9S63, and ASS) and classified individuals as having (''carriers''), not having (''noncarriers''), or being ambiguous with respect to a DYT1-associated haplotype. We assessed clinical features and found marked clinical differences between haplotype carriers and noncarriers. There were 90 carriers, 70 noncarriers, and 14 ambiguous individuals. The mean age at onset of symptoms was significantly lower in carriers than in noncarriers (12.5 +/- 8.2 vs 36.5 +/- 16.4 years). In 94% of carriers, symptoms began in a limb (arm or leg equally); rarely the disorder started in the neck (3.3%) or larynx (2.2%). In contrast, the neck, larynx, and other cranial muscles were the sites of onset in 79% of noncarriers; onset in the arms occurred in 21% and onset in the legs never occurred. Limb onset, leg involvement in the course of disease, and age at onset distinguished haplotype carriers from noncarriers with 90% accuracy. In conclusion, there are clinical differences between Ashkenazi Jewish individuals with idiopathic torsion dystonia who do or do not have a unique DYT1 mutation, as determined by a DYT1-associated haplotype of 9q34 alleles. These differences suggest that early, limb-onset idiopathic torsion dystonia and late, cervical cranial-onset idiopathic torsion dystonia are genetically distinct entities. C1 OREGON HLTH SCI UNIV,DEPT NEUROL,PORTLAND,OR 97201. MASSACHUSETTS GEN HOSP,CTR NEUROSCI,MOLEC NEUROGENET UNIT,E CHARLESTOWN,MA. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. RP BRESSMAN, SB (reprint author), COLUMBIA PRESBYTERIAN MED CTR,INST NEUROL,DEPT NEUROL,710 W 168TH ST,NEW YORK,NY 10032, USA. FU NHGRI NIH HHS [HG00348]; NINDS NIH HHS [NS26656, NS28384] NR 28 TC 125 Z9 128 U1 0 U2 5 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1994 VL 36 IS 5 BP 771 EP 777 DI 10.1002/ana.410360514 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PR051 UT WOS:A1994PR05100013 PM 7979224 ER PT J AU MONTGOMERY, WW HILLMAN, RE VARVARES, MA AF MONTGOMERY, WW HILLMAN, RE VARVARES, MA TI COMBINED THYROPLASTY TYPE-I AND INFERIOR CONSTRICTOR MYOTOMY SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE CRANIAL NERVE PARALYSIS; INFERIOR CONSTRICTOR; LARYNX; MYOTOMY; PHONOSURGERY; THYROPLASTY AB The preoperative evaluation and technique of combined thyroplasty and inferior constrictor myotomy are described and illustrated. The results in cases in which thyroplasty type I and inferior constrictor myotomy were done as separate procedures are compared to those in cases in which thyroplasty and inferior constrictor myotomy were combined in the same operation. The end results obtained with these two approaches did not differ significantly; however, with the exception of brain stem disease, patients undergoing the combined procedure at an early date are more likely to be spared gastrostomy and aspiration pneumonia. Diseases of the brain stem (ie, stroke and metastatic disease such as breast cancer) respond poorly to an inferior constrictor myotomy. In such cases the patient can best be rehabilitated with a thyroplasty type I along with a gastrostomy or laryngeal closure procedure. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP MONTGOMERY, WW (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 6 TC 16 Z9 16 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD NOV PY 1994 VL 103 IS 11 BP 858 EP 862 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA PQ995 UT WOS:A1994PQ99500006 PM 7978999 ER PT J AU MADDIX, DS TALLIAN, KB MEAD, PS AF MADDIX, DS TALLIAN, KB MEAD, PS TI RIFABUTIN - A REVIEW WITH EMPHASIS ON ITS ROLE IN THE PREVENTION OF DISSEMINATED MYCOBACTERIUM-AVIUM COMPLEX INFECTION SO ANNALS OF PHARMACOTHERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; ANTIMICROBIAL AGENTS; PROPHYLAXIS; ANSAMYCIN; INVITRO; INTRACELLULARE; CYCLOSPORINE; INHIBITION; ABSORPTION AB OBJECTIVE: To discuss the mechanism of action, in vitro and in vivo activity, pharmacokinetics, clinical trials, adverse effects, drug interactions, and dosage guidelines of rifabutin. DATA SOURCES: Pertinent literature published between 1982 and 1993 was identified via a MEDLINE search. Published proceedings of selected conferences were also reviewed. STUDY SELECTION: Selected basic science, microbiologic, and pharmacokinetic articles were evaluated. Because only limited data regarding rifabutin were available in the literature, all clinical trials involving the use of rifabutin in the prevention of Mycobacterium avium complex (MAC) infection in AIDS patients were reviewed. DATA SYNTHESIS: Rifabutin is a rifamycin derivative that was approved recently for the prevention of disseminated MAC disease in patients with advanced HIV infection. The drug has in vitro and in vivo activity against gram-positive bacteria, gram-negative bacteria, and mycobacteria. Two prospective, randomized, double-blind, placebo-controlled, multicenter trials demonstrated that rifabutin decreased the progression to MAC bacteremia in AIDS patients by about 50 percent. Adverse effects that resulted in the discontinuation of rifabutin prophylaxis occurred in 16 percent of patients. Rifabutin induces hepatic enzymes to a lesser extent than does rifampin, but dosage adjustment of drugs that are known to interact with rifampin may be required. CONCLUSIONS: Rifabutin is the only drug shown to be effective in the prevention of MAC bacteremia in AIDS patients; therefore, it should be made available as a formulary agent. It may be reasonable to delay initiation of rifabutin prophylaxis until CD4 lymphocyte counts are less than 75-50/mm3. C1 UNIV CALIF SAN FRANCISCO,SCH PHARM,SAN FRANCISCO,CA 94143. SAN FRANCISCO VET AFFAIRS MED CTR,MED SERV,INFECT DIS SECT,SAN FRANCISCO,CA. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. RP MADDIX, DS (reprint author), SAN FRANCISCO VET AFFAIRS MED CTR,PHARM SERV 119,4150 CLEMENT ST,SAN FRANCISCO,CA 94121, USA. NR 33 TC 9 Z9 9 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD NOV PY 1994 VL 28 IS 11 BP 1250 EP 1254 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PT259 UT WOS:A1994PT25900010 PM 7849340 ER PT J AU GRILLO, HC AF GRILLO, HC TI ESOPHAGOPLEURAL FISTULA - AN EARLY AND LONG-TERM COMPLICATION AFTER PNEUMONECTOMY - INVITED COMMENTARY SO ANNALS OF THORACIC SURGERY LA English DT Note RP GRILLO, HC (reprint author), MASSACHUSETTS GEN HOSP,DEPT THORAC SURG,THORAC SURG UNIT,WARREN 1101,55 FRUIT ST,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 1994 VL 58 IS 5 BP 1441 EP 1441 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PQ159 UT WOS:A1994PQ15900031 ER PT J AU HENDREN, WG OKEEFE, DD GEFFIN, GA DENENBERG, AG LOVE, TR DAGGETT, WM AF HENDREN, WG OKEEFE, DD GEFFIN, GA DENENBERG, AG LOVE, TR DAGGETT, WM TI MAXIMAL OXYGENATION OF DILUTE BLOOD CARDIOPLEGIC SOLUTION SO ANNALS OF THORACIC SURGERY LA English DT Article ID MYOCARDIAL PROTECTION; ARREST AB The content of dissolved O-2 (the major source of O-2 for the myocardium) of dilute blood cardioplegic solution (dBCS) varied widely when oxygenated at 4 degrees C by surface flow of O-2 in a Bentley BCR-3500 cardiotomy reservoir. We have modified the system to consistently deliver maximally oxygenated dBCS to the heart. Laboratory studies indicated that bubbling O-2 through a 16-gauge intravenous catheter in a central Luer-Lok port of the cardiotomy reservoir provided contents of dissolved O-2 that were consistently near maximal. We then studied 17 patients in the operating room. The first 6 patients received dBCS oxygenated with 100% O-2 with a high dissolved O-2 content of 3.2 +/- 0.2 ml/dl. However, the pH of the dBCS became highly alkaline (7.83 +/- 0.11 at 37 degrees C). Therefore, in the remaining 11 patients, 2% CO2 was added to the O-2. The dissolved O-2 content remained high (3.3 +/- 0.1 mI/dl), and the pH was in a more physiological range (7.35 +/- 0.09 at 37 degrees C). We conclude that consistently maximal oxygenation of a dBCS at a more physiological pH can be achieved by this method. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,CARDIAC SURG UNIT,BOSTON,MA 02114. NR 11 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 1994 VL 58 IS 5 BP 1558 EP 1559 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PQ159 UT WOS:A1994PQ15900063 PM 7979702 ER PT J AU FURLONG, ST SAMIA, JA ROSE, RM FISHMAN, JA AF FURLONG, ST SAMIA, JA ROSE, RM FISHMAN, JA TI PHYTOSTEROLS ARE PRESENT IN PNEUMOCYSTIS-CARINII SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID STEROL; FUNGI; HOMOLOGY; IDENTIFICATION; INHIBITORS; METABOLISM; MEMBRANES; SEQUENCES; PLANTS; GENE AB Although originally classified as a protozoan, Pneumocystis carinii is now considered to have fungal characteristics. Drugs typically used for the treatment of fungal infections target ergosterol. Because P. carinii is an important pathogen in AIDS and other immunocompromised patients, knowledge of the sterol content of this organism may be useful as a basis for developing new treatment strategies or for improving diagnosis. P. canna organisms were harvested from infected rat lungs and were purified by filtration. Control preparations from uninfected animals were identically prepared. Lipids were extracted from the organisms and control preparations and were separated into neutral lipid, glycolipid, and phospholipid fractions by silicic acid chromatography. The neutral lipid fraction was further treated by alkaline hydrolysis and was analyzed by reversed-phase high-pressure liquid chromatography (HPLC), gas chromatography (GC), and CC-mass spectrometry (GC-MS). As shown hy HPLC, the neutral lipid fraction from infected rats contained a minimum of six peaks, while in control preparations a single peak with a retention time identical to that of cholesterol was observed. The predominant sterol in these preparations was positively identified by CC-MS as cholesterol and constituted 80 to 90% of the total. The remaining peaks had relative retention times similar to those of phytosterols by both HPLC and GC, and the similarity of these sterols to those derived from plants and fungi was confirmed by MS. Ergosterol, however, was not present. These results provide further evidence for a close phylogenetic relationship between P. carinii and fungi and suggest that these sterols could be used as targets for drug development and for improving diagnosis. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT RHEUMATOL IMMUNOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. NEW ENGLAND DEACONESS HOSP,DIV PULM MED,BOSTON,MA 02215. FU NHLBI NIH HHS [HL34510] NR 38 TC 37 Z9 37 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 1994 VL 38 IS 11 BP 2534 EP 2540 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA PP222 UT WOS:A1994PP22200004 PM 7872743 ER PT J AU BARCHIESI, F COLOMBO, AL MCGOUGH, DA FOTHERGILL, AW RINALDI, MG AF BARCHIESI, F COLOMBO, AL MCGOUGH, DA FOTHERGILL, AW RINALDI, MG TI IN-VITRO ACTIVITY OF A NEW ANTIFUNGAL TRIAZOLE, D0870, AGAINST CANDIDA-ALBICANS ISOLATES FROM ORAL CAVITIES OF PATIENTS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AZOLE-RESISTANT; IN-VITRO; FLUCONAZOLE RESISTANCE; LIPID-COMPOSITION; EMERGENCE; GLABRATA; THERAPY; STRAINS; AIDS AB We investigated the in vitro activity of a new antifungal triazole, D0870, against 100 Candida albicans isolates from the oral cavities of patients infected,vith human immunodeficiency virus by using a broth macrodilution method following the recommendations provided by the National Committee for Clinical Laboratory Standards (document M27-P). All of the isolates were chosen from C. albicans isolates already tested for fluconazole susceptibility by the procedure of the National Committee for Clinical Laboratory Standards. Fifty isolates were considered fluconazole susceptible (MICs, less than or equal to 4 mu g/ml), and 50 isolates were considered fluconazole resistant (MICs, greater than or equal to 8 mu g/ml). The in vitro data demonstrated that D0870 had good activity against isolates tested; for 90% of all strains of C. albicans, MICs were 0.5 mu g/ml. However, the D0870 MICs for the fluconazole-susceptible isolates were lower than those for the fluconazole-resistant isolates; MICs for 50 and 90% of the isolates tested were less than or equal to 0.0078 and 0.06 mu g/ml, respectively, for fluconazole-susceptible isolates and 0.25 and 2 mu g/ml, respectively, for fluconazole-resistant isolates (P < 0.001). Our data suggest that this new triazole could represent a valid alternative in the treatment of oral candidiasis in human immunodeficiency virus-infected patients. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. ESCOLA PAULISTA MED,SAO PAULO,BRAZIL. UNIV ANCONA,IST MALATTIE INFETT & MED PUBBL,ANCONA,ITALY. RP BARCHIESI, F (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,FUNGUS TESTING LAB,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 21 TC 14 Z9 15 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 NOV PY 1994 VL 38 IS 11 BP 2553 EP 2556 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA PP222 UT WOS:A1994PP22200007 PM 7872746 ER PT J AU VALERO, G MORENO, F GRAYBILL, JR AF VALERO, G MORENO, F GRAYBILL, JR TI ACTIVITIES OF CLARITHROMYCIN, OFLOXACIN, AND CLARITHROMYCIN PLUS ETHAMBUTOL AGAINST MYCOBACTERIUM-SIMIAE IN MURINE MODEL OF DISSEMINATED INFECTION SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID INTRACELLULAR ACTIVITIES; AVIUM COMPLEX; ENHANCEMENT AB After 2 weeks of intravenous challenge with Mycobacterium simiae, ICR outbred mice were treated with clarithromycin, ofloxacin, or clarithromycin pins ethambutol for 4 weeks. All three therapy groups demonstrated a decrease in the level of infection in both the lungs and the spleen. There were no significant differences among the three treated groups in decreasing mycobacterial counts in the lungs; however, both ofloxacin and clarithromycin plus ethambutol were superior to clarithromycin alone in reducing the level of infection in the spleen. Results of the study suggest a potential role for these agents in the treatment of human M. simiae infection. C1 AUDIE L MURPHY MEM VET ADM MED CTR,DEPT INFECT DIS,SAN ANTONIO,TX 78284. NR 12 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 1994 VL 38 IS 11 BP 2676 EP 2677 PG 2 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA PP222 UT WOS:A1994PP22200031 PM 7872769 ER PT J AU BARSKY, AJ BARNETT, MC CLEARY, PD AF BARSKY, AJ BARNETT, MC CLEARY, PD TI HYPOCHONDRIASIS AND PANIC DISORDER - BOUNDARY AND OVERLAP SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; DSM-III HYPOCHONDRIASIS; PRIMARY CARE; SOMATOSENSORY AMPLIFICATION; MEDICAL OUTPATIENTS; ANXIETY; SOMATIZATION; DEPRESSION; BELIEFS; ILLNESS AB Background: To determine the nosological and phenomenological overlap and boundaries between panic disorder and hypochondriasis, we compared the symptoms, disability, comorbidity, and medical care of primary care patients with each diagnosis. Methods: Patients with DSM-LII-R panic disorder were recruited by screening consecutive primary care clinic attenders and then administering a structured diagnostic interview for panic disorder. Patients also completed self-report questionnaires, and their primary care physicians completed questionnaires about them. They were then compared with patients with DSM-III-R hypochondriasis from the same setting who had been studied previously. Results: One thousand six hundred thirty-four patients were screened; 135 (71.0% of the 190 eligible patients) completed the research battery; 100 met lifetime panic disorder criteria. Twenty-five of these had comorbid hypochondriasis. Those without comorbid hypochondriasis (n=75) were then compared with patients with hypochondriasis without comorbid panic disorder (n=51). Patients with panic disorder were less hypochondriacal(P<.001), somatized less (P<.05), were less disabled (P<.001), were more satisfied with their medical care (P<.001), and were rated by their physicians as less help rejecting (P<.05) and less demanding (P<.01). Major depression was more prevalent in the group with panic disorder (66.7% vs 45.1 %; P<.05), as were phobias (76.0% vs 37.3%; P<.001), but somatization disorder symptoms (P<.0001) and generalized anxiety disorder were less prevalent (74.5% vs 16.0%; P<.001) in panic disorder than was hypochondriasis. Conclusions: While hypochondriasis and panic disorder co-occur to some extent in a primary care population, the overlap is by no means complete. These patients are phenomenologically functionally differentiable and distinct and are viewed differently by their primary care physicians. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BOSTON,MA 02114. RP BARSKY, AJ (reprint author), BRIGHAM & WOMENS HOSP,DIV PSYCHIAT,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NIMH NIH HHS [MH-40487] NR 55 TC 60 Z9 62 U1 2 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 1994 VL 51 IS 11 BP 918 EP 925 PG 8 WC Psychiatry SC Psychiatry GA PQ612 UT WOS:A1994PQ61200009 PM 7944880 ER PT J AU MANGIONE, CM PHILLIPS, RS LAWRENCE, MG SEDDON, JM ORAV, EJ GOLDMAN, L AF MANGIONE, CM PHILLIPS, RS LAWRENCE, MG SEDDON, JM ORAV, EJ GOLDMAN, L TI IMPROVED VISUAL FUNCTION AND ATTENUATION OF DECLINES IN HEALTH-RELATED QUALITY-OF-LIFE AFTER CATARACT-EXTRACTION SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID SHORT-FORM; LENS IMPLANTATION; MEDICAL OUTCOMES; ELDERLY PATIENTS; SURVEY SF-36; SURGERY; VISION; PREVALENCE; ARTHRITIS; VALIDITY AB Objective: To measure the effect of cataract extraction and lens implantation on elderly persons' health-related quality of life and on their ability to perform visual activities. Design: Evaluations of health status were conducted preoperatively and at 3 and 12 months after surgery on patients scheduled for cataract extraction. Setting: Patients were enrolled from the General Eye Service of the Massachusetts Eye and Ear Infirmary and 33 Boston practices. Patients: The cohort consisted of 464 patients aged 65 years or older who were identified from the surgical schedule of the Massachusetts Eye and Ear Infirmary. At 3 to 12 months after surgery, 458 (99%) of the participants were successfully contacted. Health-related quality of life data were available for 419 (90%) to assess changes after surgery. Main Outcome Measures: Ophthalmologic examinations were performed preoperatively and during the follow-up period. The Activities of Daily Vision Scale (ADVS) and the Medical Outcomes Study 36-item short form (SF-36) were administered before surgery and at 3 and 12 months postoperatively to assess changes in health Status. Results: At 12 months after surgery, 95% of patients had improved Snellen visual acuity, 80% had improved ADVS scores, but only 36% had improved SF-36 physical functioning. Average scores on seven of eight SF-36 subscales worsened at 12 months. Patients with improved ADVS scores had significantly smaller declines across an SF-36 dimensions except for role limitations due to emotional problems. Conclusion: Improved visual function after cataract surgery was associated with better health-related quality of life, suggesting that age-related declines in health may be attenuated by improvements in visual function. C1 BRIGHAM & WOMENS HOSP,DEPT MED,DEPT CLIN EPIDEMIOL,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT MED,DEPT GEN MED,BOSTON,MA. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,GEN EYE SERV,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,CATARACT CONSULTAT SERV,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,EPIDEMIOL UNIT,BOSTON,MA. RP MANGIONE, CM (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,DIV GEN INTERNAL MED & HLTH SERV RES,LOS ANGELES,CA 90024, USA. FU AHRQ HHS [FS32 HS00048-01]; BHP HRSA HHS [2-T32 PE 11001]; NIA NIH HHS [1K08-AG00605] NR 29 TC 181 Z9 184 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD NOV PY 1994 VL 112 IS 11 BP 1419 EP 1425 PG 7 WC Ophthalmology SC Ophthalmology GA PQ702 UT WOS:A1994PQ70200011 PM 7980131 ER PT J AU MOSCICKI, RA AF MOSCICKI, RA TI IMMUNE-MEDIATED INNER-EAR DISORDERS SO BAILLIERES CLINICAL NEUROLOGY LA English DT Article ID SENSORINEURAL HEARING-LOSS; COGANS SYNDROME; II COLLAGEN; RELAPSING POLYCHONDRITIS; ENDOLYMPHATIC SAC; SERUM ANTIBODIES; DISEASE; ANTIGEN; IMMUNOGLOBULINS; AUTOANTIBODIES C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. GENZYME CORP,CAMBRIDGE,MA 02159. RP MOSCICKI, RA (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 64 TC 8 Z9 8 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0961-0421 J9 BAILLIERE CLIN NEUR JI Baillieres Clin. Neurol. PD NOV PY 1994 VL 3 IS 3 BP 547 EP 563 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA PV259 UT WOS:A1994PV25900008 PM 7874408 ER PT J AU BROWNE, SE BEAL, MF AF BROWNE, SE BEAL, MF TI OXIDATIVE DAMAGE AND MITOCHONDRIAL DYSFUNCTION IN NEURODEGENERATIVE DISEASES SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 56th Meeting of the Biochemical-Society CY JUL 13-14, 1994 CL LANCASTER, ENGLAND SP BIOCHEM SOC ID AMYOTROPHIC-LATERAL-SCLEROSIS; TOXIN 3-NITROPROPIONIC ACID; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; ENERGY-METABOLISM; PROTEIN OXIDATION; COMPLEX-I; BRAIN; LESIONS C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 50 TC 30 Z9 31 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD NOV PY 1994 VL 22 IS 4 BP 1002 EP 1006 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX715 UT WOS:A1994PX71500033 PM 7698395 ER PT J AU DERESIEWICZ, RL WOO, JH CHAN, M FINBERG, RW KASPER, DL AF DERESIEWICZ, RL WOO, JH CHAN, M FINBERG, RW KASPER, DL TI MUTATIONS AFFECTING THE ACTIVITY OF TOXIC SHOCK SYNDROME TOXIN-1 SO BIOCHEMISTRY LA English DT Article ID STAPHYLOCOCCUS-AUREUS; MONOCLONAL-ANTIBODIES; SECONDARY STRUCTURE; CIRCULAR-DICHROISM; IDENTIFICATION; NUCLEOTIDE; FRAGMENTS; CELLS AB Toxic shock syndrome toxin-1 (TSST-1), the potent staphylococcal exoprotein linked to most cases of the toxic shock syndrome, is a V-beta-restricted T-cell mitogen (a so-called ''superantigen''). TSST-ovine (TSST-O) is a natural variant of TSST-1, and is produced by certain ovine mastitis-associated strains of Staphylococcus aureus. Compared to TSST-1, TSST-O is only weakly mitogenic for leporine or murine splenocytes. It differs from TSST-1 at 7 amino acid residues over its 194 amino acid length. Terminus shuffling between the two proteins has suggested that their C-terminal differences (T69, Y80, E132, and I140 in TSST-1; I69, W80, K132, and T140 in TSST-O) are in part responsible for their discrepant mitogenic properties. In order to explore further the functional consequences of altering TSST-1 at residues 132 and 140, we engineered point mutants of TSST-1 at those positions. The mutant proteins were purified to homogeneity from culture supernatants of a nontoxigenic strain of S. aureus using a combination of ultrafiltration, liquid-phase isoelectric focusing, and ion-exchange chromatography. The mutants retained global structural integrity as evidenced by circular dichroism spectroscopy, their preserved resistance to trypsin digestion, and their preserved binding to a neutralizing murine monoclonal antibody. The mutants were then tested for mitogenicity for human T-cells: The mutant I140T was approximately as active as wild-type TSST-1, while the mutant E132D was about 10-fold attenuated. On the other hand, the mutants E132A or E132K were each at least 1000-fold attenuated. We conclude that the mitogenic activity of TSST-1 for human T-cells depends critically on the presence and precise position of the negative charge at residue 132. C1 BRIGHAM & WOMENS HOSP,DIV INFECT DIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,DIV INFECT DIS,BOSTON,MA 02115. RP DERESIEWICZ, RL (reprint author), HARVARD UNIV,SCH MED,CHANNING LAB,180 LONGWOOD AVE,BOSTON,MA 02115, USA. RI Finberg, Robert/E-3323-2010 NR 21 TC 23 Z9 23 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 NOV 1 PY 1994 VL 33 IS 43 BP 12844 EP 12851 DI 10.1021/bi00209a016 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PP527 UT WOS:A1994PP52700016 PM 7947690 ER PT J AU LO, SH WEISBERG, E CHEN, LB AF LO, SH WEISBERG, E CHEN, LB TI TENSIN - A POTENTIAL LINK BETWEEN THE CYTOSKELETON AND SIGNAL-TRANSDUCTION SO BIOESSAYS LA English DT Review ID TYROSINE-PHOSPHORYLATED PROTEIN; END-BOUND INSERTIN; CELL-ADHESION; ERYTHROPOIETIN RECEPTOR; EXTRACELLULAR-MATRIX; ACTIN POLYMERIZATION; SMOOTH-MUSCLE; SH3 DOMAINS; STABLE ASSOCIATION; TRANSFORMED-CELLS AB Cytoskeletal proteins provide the structural foundation that allows cells to exist in a highly organized manner. Recent evidence suggests that certain cytoskeletal proteins not only maintain structural integrity, but might also be associated with signal transduction and suppression of tumorigenesis. Since the time of the discovery of tensin, a fair amount of data has been gathered which supports the notion that tensin is one such protein possessing these characteristics. In this review, we discuss recent studies that: (1) elucidate a role for tensin in maintenance of cellular structure and signal transduction; (2) implicate tensin as the anchor for actin filaments at the focal adhesion; (3) describe the phosphorylation of tensin; (4) describe potential targets for its Src homology region 2 domain; (5) describe the association between tensin and the nuclear protein p130; and (6) demonstrate that increased tensin expression in a cell line appears to reduce its transformation potential. RP LO, SH (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 61 TC 111 Z9 111 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 0265-9247 J9 BIOESSAYS JI Bioessays PD NOV PY 1994 VL 16 IS 11 BP 817 EP 823 DI 10.1002/bies.950161108 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA PU045 UT WOS:A1994PU04500007 PM 7840759 ER PT J AU NORLING, LL VONGELDERN, T CHEVALIER, RL AF NORLING, LL VONGELDERN, T CHEVALIER, RL TI MATURATION OF A71915-DEPENDENT INHIBITION OF ATRIAL NATRIURETIC PEPTIDE-STIMULATED CYCLIC-GMP PRODUCTION IN ISOLATED RAT GLOMERULI SO BIOLOGY OF THE NEONATE LA English DT Article DE MATURATION; CYCLIC GMP; GLOMERULI; ATRIAL NATRIURETIC FACTOR; ATRIAL NATRIURETIC PEPTIDE ANALOG; INHIBITION ID ANP; RECEPTORS; INFUSION; YOUNG; CGMP AB Atrial natriuretic peptide (ANP) regulates glomerular hemodynamics by interaction with biologic receptors (GC-A/ANP) that possess particulate guanylyl cyclase activity. In a previous study we have shown a developmental difference in glomerular response to ANP where preweaned glomeruli produced significantly less extracellular cGMP in response to ANP. Because of the possibility that functional differences in the ANP biologic receptor might exist during development, further characterization of GC-A/ANP receptor response in glomeruli of developing rats was done using a structural analogue of ANP. A71915 (Abbott Laboratories) is a structural analogue of ANP which has been shown to inhibit activation of ANP receptor-associated guanylyl cyclase in vascular smooth muscle cells. The purpose of this study was to investigate the ability of A71915 to inhibit ANP-stimulated cGMP response in isolated glomeruli of adult and pre weaned rats. Isolated glomeruli from preweaned or adult rat kidneys were preincubated for 15 min with A71915 (10(-5) M) prior to addition of ANP (up to 10(-6) M). Glomerular response of production of intracellular and extracellular cGMP was measured by radioimmunoassay. Adult glomeruli produced significantly greater amounts of extracellular cGMP compared to preweaned glomeruli for concentrations of ANP greater than or equal to 10(-9) M. Infant glomeruli had a significant decrease in the production of ANP-stimulated intracellular cGMP in the presence of A71915 (10(-5) M), whereas extracellular cGMP production was unchanged. In contrast both ANP-stimulated intracellular and extracellular cGMP were significantly decreased by A71915 in adult glomeruli. These results demonstrate the maturation of the glomerular response to ANP. The lack of effect of A71915 on extracellular release of cGMP by glomeruli from preweaned rats is likely due to immaturity of the cGMP extrusion mechanism rather than a reduced GC-A/ANP receptor response or signal transduction. C1 ABBOTT LABS,ABBOTT PK,IL 60064. UNIV VIRGINIA,HLTH SCI CTR,DEPT PEDIAT,CHARLOTTESVILLE,VA. RP NORLING, LL (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT NEPHROL UNIT,ACC 709,15 PARKMAN ST,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [P50DK44756-01, P50DK45179-02] NR 10 TC 4 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0006-3126 J9 BIOL NEONATE JI Biol. Neonate PD NOV PY 1994 VL 66 IS 5 BP 294 EP 301 PG 8 WC Pediatrics SC Pediatrics GA QD992 UT WOS:A1994QD99200007 PM 7873695 ER PT J AU JURMAN, ME BOLAND, LM LIU, Y YELLEN, G AF JURMAN, ME BOLAND, LM LIU, Y YELLEN, G TI VISUAL IDENTIFICATION OF INDIVIDUAL TRANSFECTED CELLS FOR ELECTROPHYSIOLOGY USING ANTIBODY-COATED BEADS SO BIOTECHNIQUES LA English DT Note ID EXPRESSION AB Electrophysiological study of transiently transfected cells requires the identification of individual cells that express the protein of interest. We describe a simple, quick and inexpensive methods for visually identifying cells that have been co-transfected with an expression plasmid for a lymphocyte surface antigen (CD8-alpha). Transfected cells are incubated briefly with polystyrene microspheres (4.5 mu m diameter) that have been precoated with antibody to CD8. Cells expressing CD8 on their surface are decorated with many beads and are thus readily distinguishable from untransfected cells. Beads already coated with antibody are available commercially. The method rakes less than five minutes and requires no reagent preparation or special equipment for visualization of the beads. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,MOLEC PHYSIOL LAB,BOSTON,MA 02114. FU NINDS NIH HHS [R01 NS029693] NR 6 TC 269 Z9 270 U1 0 U2 3 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD NOV PY 1994 VL 17 IS 5 BP 876 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ504 UT WOS:A1994PQ50400016 PM 7840967 ER PT J AU GOLDMACHER, VS BOURRET, LA LEVINE, BA RASMUSSEN, RA POURSHADI, M LAMBERT, JM ANDERSON, KC AF GOLDMACHER, VS BOURRET, LA LEVINE, BA RASMUSSEN, RA POURSHADI, M LAMBERT, JM ANDERSON, KC TI ANTI-CD38-BLOCKED RICIN - AN IMMUNOTOXIN FOR THE TREATMENT OF MULTIPLE-MYELOMA SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; PLASMA-CELL MYELOMA; PHASE-I TRIAL; MONOCLONAL-ANTIBODY; BLOCKED RICIN; ANTI-B4-BLOCKED RICIN; PERIPHERAL-BLOOD; STEM-CELLS; B-CELLS; INTERLEUKIN-6 AB We report the development of a potent anti-CD38 immunotoxin capable of killing human myeloma and lymphoma cell lines. The immunotoxin is composed of an anti-CD38 antibody HB7 conjugated to a chemically modified ricin molecule wherein the binding sites of the B chain have been blocked by covalent attachment of affinity ligands (blocked ricin). Conjugation of blocked ricin to the HB7 antibody has minimal effect on the apparent affinity of the antibody and no effect on the ribosome-inactivating activity of the ricin A-chain moiety. Four to six logs of CD38(+) tumor cell line kill was achieved at concentrations of HB7-blocked ricin in the range of 0.1 to 3 nmol/L. Low level of toxicity for normal bone marrow (BM) granulocyte-macrophage colony-forming units (CFU-GM), burst-forming units-erythroid (BFU-E). colony-forming units-granulocyte/erythroid/monocyte/macrophage (CFU-GEMM) cells was observed. Greater than two logs of CD38(+) multiple myeloma cells were depleted from a 10-fold excess of normal BM mononuclear cells (BMMCs) after an exposure to HB7-blocked ricin under conditions (0.3 nmol/L) that were not very toxic for the normal BM precursors. HB7-blocked ricin was tested for its ability to inhibit protein synthesis in fresh patients' multiple myeloma cells and in normal BMMCs isolated from two healthy volunteers; tumor cells from four of five patients were 100-fold to 500-fold more sensitive to the inhibitory effect of HB7-blocked ricin than the normal BM cells. HB7 antibody does not activate normal resting peripheral blood lymphocytes, and HB7-blocked ricin is not cytotoxic toward these cells at concentrations of up to 1 nmol/L. The potent killing of antigen-bearing tumor cells coupled with a lack of effects on peripheral blood T cells or on hematopoietic progenitor cells suggests that HB7-blocked ricin may have clinical utility for the in vivo or in vitro purging of human multiple myeloma cells. (C) 1994 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA. RP GOLDMACHER, VS (reprint author), IMMUNOGEN INC,148 SIDNEY ST,CAMBRIDGE,MA 02139, USA. FU NCI NIH HHS [CA50947] NR 64 TC 69 Z9 71 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1994 VL 84 IS 9 BP 3017 EP 3025 PG 9 WC Hematology SC Hematology GA PP021 UT WOS:A1994PP02100024 PM 7524764 ER PT J AU SLAPAK, CA MIZUNUMA, N KUFE, DW AF SLAPAK, CA MIZUNUMA, N KUFE, DW TI EXPRESSION OF THE MULTIDRUG-RESISTANCE ASSOCIATED PROTEIN AND P-GLYCOPROTEIN IN DOXORUBICIN-SELECTED HUMAN MYELOID-LEUKEMIA CELLS SO BLOOD LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; MDR1 GENE-EXPRESSION; ASCITES TUMOR-CELLS; INDUCED DNA DAMAGE; RED-BLOOD-CELLS; HL-60 CELLS; VINCRISTINE RESISTANCE; ERYTHROLEUKEMIA-CELLS; DRUG ACCUMULATION; CROSS-RESISTANCE AB Drug-resistant sublines of the human U-937 myeloid leukemia cell line were selected in doxorubicin concentrations of 10, 40, and 200 ng/mL (designated U-A10, U-A40, and U-A200, respectively). Northern blot analysis showed overexpression of the multidrug resistance-associated protein (MRP) gene, but not MDR1, in U-A10 cells as compared with parental U-937 eels. Prolonged passage of U-A10 cells in 10 ng/mL of doxorubicin had little effect on MRP RNA levels, but increased MDR1 expression. The U-A40 and U-A200 cells, derived by selection of U-A10 cells, showed high levels of both MRP and MDR1 expression. None of the drug-resistant cell lines showed MRP or MDR1 gene amplification as judged by Southern blot analysis. U-A10 cells exhibited minimal decreased net accumulation of anthracycline, whereas U-A40 and U-A200 cells showed more significantly decreased drug accumulation as compared with U-937 cells. Subcellular anthracycline accumulation in U-937 cells as determined by fluorescence microscopy showed daunorubicin fluorescence predominately in the nucleus, However, the drug-resistant cell lines showed minimal nuclear drug accumulation with marked redistribution of drug into a vesicular compartment. Treatment with sodium azide/2-deoxyglucose. 2,4-dinitrophenol, or monensin, but not verapamil, abolished the vesicular accumulation. These studies in doxorubicin-selected U-937 cells indicate that induction of MRP overexpression occurs before that for the MDR1 gene. In addition, the drug-resistant cells possess an energy-dependent redistribution of anthracyclines into a nonnuclear vesicular compartment. (C) 1994 by The American Society of Hematology. RP SLAPAK, CA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,44 BINNEY ST,NO D1730,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-01613, CA-29431, CA-31483] NR 65 TC 90 Z9 90 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 1 PY 1994 VL 84 IS 9 BP 3113 EP 3121 PG 9 WC Hematology SC Hematology GA PP021 UT WOS:A1994PP02100036 PM 7949184 ER PT J AU SHUHART, MC MYERSON, D CHILDS, BH FINGEROTH, JD PERRY, JJ SNYDER, DS SPURGEON, CL BEVAN, CA MCDONALD, GB AF SHUHART, MC MYERSON, D CHILDS, BH FINGEROTH, JD PERRY, JJ SNYDER, DS SPURGEON, CL BEVAN, CA MCDONALD, GB TI MARROW TRANSPLANTATION FROM HEPATITIS-C VIRUS-SEROPOSITIVE DONORS - TRANSMISSION RATE AND CLINICAL COURSE SO BLOOD LA English DT Article ID POLYMERASE CHAIN-REACTION; NON-B-HEPATITIS; BLOOD MONONUCLEAR-CELLS; CHRONIC NON-A; IMMUNOSUPPRESSIVE THERAPY; VIRAL-INFECTION; LIVER-DISEASE; LONG-TERM; RNA; REPLICATION AB Bone marrow transplant recipients are at risk for acquiring hepatitis C infection from the donated marrow. Twelve pa patients who were hepatitis C virus (HCV) RNA-negative pretransplant received marrow from anti-HCV seropositive donors. HCV RNA was present in the sera of seven of these donors. After transplant, serial serum specimens were obtained from all marrow recipients for determination of HCV RNA and aminotransferase levels. All seven recipients of marrow from HCV RNA-positive donors were HCV RNA-positive after marrow infusion; none cleared virus from the serum. All five recipients of marrow from anti-HCV seropositive. HCV RNA-negative donors remained free of HCV RNA in serum up to day 100. Abnormal serum aminotransferases were common in both HCV RNA-negative and HCV RNA-positive marrow recipients, One HCV-infected recipient developed marked elevation in aminotransferases after immunosuppressive drugs were stopped. We conclude that the presence of HCV RNA in the serum of marrow donors is an accurate predictor of HCV infection in marrow recipients. The acute infection was subclinical in all patients. The longterm risk of chronic hepatitis C virus infection in these patients remains to be determined. (C) 1994 by The American Society of Hematology. C1 FRED HUTCHINSON CANC RES CTR,PATHOL SECT,SEATTLE,WA 98104. MEM SLOAN KETTERING CANC CTR,HEMATOL ONCOL SECT,NEW YORK,NY 10021. DANA FARBER CANC INST,INFECT DIS SECT,BOSTON,MA. WAKE FOREST UNIV,CTR COMPREHENS CANC,WINSTON SALEM,NC 27109. CITY HOPE NATL MED CTR,DEPT HEMATOL & BONE MARROW TRANSPLANTAT,DUARTE,CA 91010. RP SHUHART, MC (reprint author), FRED HUTCHINSON CANC RES CTR,GASTROENTEROL HEPATOL SECT SC113,1124 COLUMBIA ST,SEATTLE,WA 98104, USA. FU NCI NIH HHS [CA18029, CA15704] NR 36 TC 46 Z9 48 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 1 PY 1994 VL 84 IS 9 BP 3229 EP 3235 PG 7 WC Hematology SC Hematology GA PP021 UT WOS:A1994PP02100050 PM 7949194 ER PT J AU GOUDSOUZIAN, NG SAVARESE, JJ AF GOUDSOUZIAN, NG SAVARESE, JJ TI ANTAGONIZING RESIDUAL NEUROMUSCULAR BLOCK WITH NEOSTIGMINE AND ATROPINE SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Letter C1 NEW YORK HOSP,CORNELL MED CTR,DEPT ANESTHESIA,NEW YORK,NY 10021. RP GOUDSOUZIAN, NG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU PROF SCI PUBL PI LONDON PA TAVISTOCK HOUSE EAST, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD NOV PY 1994 VL 73 IS 5 BP 725 EP 725 DI 10.1093/bja/73.5.725 PG 1 WC Anesthesiology SC Anesthesiology GA PP065 UT WOS:A1994PP06500061 PM 7826807 ER PT J AU FREI, E AF FREI, E TI RANDOMIZED CLINICAL-TRIALS AND OTHER APPROACHES IN CLINICAL RESEARCH SO CANCER LA English DT Article; Proceedings Paper CT American-Cancer-Society National Conference on Clinical Trials CY NOV 03-05, 1993 CL ATLANTA, GA SP AMER CANC SOC, AMER COLL SURGEONS COMMISS CANC, AMER ACAD FAMILY PHYSICIANS, ONCOL NURSING SOC DE CLINICAL TRIALS; CANCER; CHEMOTHERAPY; EXPERIMENTAL DESIGN; BIOSTATISTICS; TUMOR BIOLOGY ID BREAST-CANCER; CHEMOTHERAPY AB Phase III randomized clinical trials have greatly contributed to our understanding of the pathobiology of neoplastic disease and, particularly, to therapeutic progress. However, randomized Phase III studies are no better than or are critically dependent on Phase I and Phase II studies for positive therapeutic leads that are compelling enough to test in the Phase III arena. The variables involved in the series of randomized trials that led to the curative treatment of acute lymphocytic leukemia also resulted in an understanding of the principles of cancer therapy in therapeutic research. These principles, when applied to Hodgkin's disease in non-Hodgkin's lymphoma, testis cancer, childhood solid tumors, and others, resulted in a substantial cure rate for those diseases. However, for the adult epithelial common solid tumors, a second strategy, adjuvant chemotherapy, was required. This has resulted in a 20% reduction in mortality in patients with node positive and node negative breast cancer. Tamoxifen has been similarly effective in patients with postmenopausal breast cancer. In colon cancer, adjuvant chemotherapy with fluorouracil plus levamisole has decreased mortality to a comparable degree. New agents, modulations, combination chemotherapy, and biotherapeutics are being addressed to the adjuvant situation which has proven effective in a variety of neoplastic diseases. A third strategy is neoadjuvant chemotherapy. This involves the use of chemotherapy first for patients with solid tumors, designed to down-stage the primary tumor, thus making it more susceptible to less radical surgery and to organ- or limb-sparing procedures in osteogenetic sarcoma and in head and neck cancer. For example, neoadjuvant chemotherapy has not resulted in an increased survival as compared with the appropriate control but has allowed for important quality-of-life contributions, such as limb-sparing and radical surgery-sparing procedures. In addition to new agents and combination chemotherapy, dose is a critical variable. This is most evident clinically in the transplantation arena. Comparative studies recently completed, for example, in patients with adjuvant breast cancer and with acute leukemia indicate that dose is a significant factor in tumor control. RP FREI, E (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 8 TC 0 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 1994 VL 74 IS 9 SU S BP 2610 EP 2613 DI 10.1002/1097-0142(19941101)74:9+<2610::AID-CNCR2820741804>3.0.CO;2-C PG 4 WC Oncology SC Oncology GA PQ269 UT WOS:A1994PQ26900003 PM 7954273 ER PT J AU CHENG, JQ JHANWAR, SC KLEIN, WM BELL, DW LEE, WC ALTOMARE, DA NOBORI, T OLOPADE, OI BUCKLER, AJ TESTA, JR AF CHENG, JQ JHANWAR, SC KLEIN, WM BELL, DW LEE, WC ALTOMARE, DA NOBORI, T OLOPADE, OI BUCKLER, AJ TESTA, JR TI P16 ALTERATIONS AND DELETION MAPPING OF 9P21-P22 IN MALIGNANT MESOTHELIOMA SO CANCER RESEARCH LA English DT Note ID TUMOR-SUPPRESSOR GENE; HOMOZYGOUS DELETIONS; INTERFERON GENES; CRITICAL REGION; ABNORMALITIES; MELANOMA; CANCER; MODEL; P53; 9P AB To determine whether p16 is altered in human malignant mesothelioma (MM), molecular analysis of multiple 9p loci was performed on 40 cell lines and 23 primary tumors from 42 MM patients. We identified homozygous deletions of p16 in 34 (85%) cell lines and a point mutation in 1 line. Down-regulation of p16 was observed in 4 of the remaining cell lines, 1 of which displayed a DNA rearrangement of p16. Homozygous deletions of p16 were identified in 5 of 23 (22%) primary tumors; no mutations or rearrangements were found in these specimens. Pour cell lines displayed a single homozygous deletion proximal to or distal to p16; 4 others had 2 nonoverlapping deletions, one involving p16 and the other involving a region proximal to this locus. These data indicate that alterations of p16 are a common occurrence in MM cell lines and, to a lesser extent, in primary tumors. Furthermore, deletions of 9p21-p22 outside of the p16 locus may reflect the involvement of other putative tumor suppressor genes that could also contribute to the pathogenesis of some MMs. C1 FOX CHASE CANC CTR,DEPT MED ONCOL,PHILADELPHIA,PA 19111. MEM SLOAN KETTERING CANC CTR,DEPT PATHOL,NEW YORK,NY 10021. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. MASSACHUSETTS GEN HOSP,MOLEC & NEUROL UNIT,BOSTON,MA 02129. FU NCI NIH HHS [CA-45745, CA-06927, P30 CA006927, R01 CA045745] NR 34 TC 282 Z9 297 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1994 VL 54 IS 21 BP 5547 EP 5551 PG 5 WC Oncology SC Oncology GA PP190 UT WOS:A1994PP19000012 PM 7923195 ER PT J AU SLAPAK, CA FRACASSO, PM MARTELL, RL TOPPMEYER, DL LECERF, JM LEVY, SB AF SLAPAK, CA FRACASSO, PM MARTELL, RL TOPPMEYER, DL LECERF, JM LEVY, SB TI OVEREXPRESSION OF THE MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN (MRP) GENE IN VINCRISTINE BUT NOT DOXORUBICIN-SELECTED MULTIDRUG-RESISTANT MURINE ERYTHROLEUKEMIA-CELLS SO CANCER RESEARCH LA English DT Article ID BACTERIAL TRANSPORT PROTEINS; P-GLYCOPROTEIN EXPRESSION; BREAST-CANCER-CELLS; ADRIAMYCIN; MDR1; LINES; DNA; PHENOTYPE; APOPTOSIS; HOMOLOGY AB Multidrug-resistant sublines of the murine erythroleukemia cell line PC4 were sequentially selected in increasing vincristine concentrations (5-160 ng/ml). The low- and intermediate-level resistant cell lines, selected in less than or equal to 40 ng/ml of vincristine, demonstrated resistance to Vinca alkaloids and to an epipodophyllotoxin but little or none to an anthracycline. The expression of murine mdr genes, as analyzed by Northern blotting, revealed a baseline expression of murine mdr2 in parental cells that was unchanged in the drug-resistant cell lines. Overexpression of mdr3 was observed only in the highest-level resistant fell line, PC-V160, whereas mdr1 mRNA was not detected in any of the cell fines. The polymerase chain reaction, using mdr3-specific primers, excluded the possibility that low levels of P-glycoprotein expression contributed to the resistance phenotype in the low and intermediate-level resistant cell lines. Northern blot analysis using a human complementary DNA probe for the multidrug resistance-associated protein (MRP) demonstrated overexpression of murine mrp in each of the vincristine-selected sublines. Genomic amplification of the mrp gene was coincident with mrp overexpression. The expression of mrp was also examined in two series of previously characterized doxorubicin-selected cell lines derived from parental PC4 and C7D murine erythroleukemia cells. In contrast to the vincristine-selected cell lines, overexpression of mrp was not detected. These studies demonstrate that,in murine erythroleukemia cells selected for vincristine resistance, overexpression of murine mrp occurred prior to that for murine mdr. In contrast to human MRP, selection for vincristine, but not doxorubicin resistance, resulted in the overexpression of murine mrp. C1 TUFTS UNIV,SCH MED,CTR ADAPT GENET & DRUG RESISTANCE,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT MOLEC BIOL & MICROBIOL,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT MED,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV CANCER PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA-01613, 1F32-CA08553, T32-CA09429] NR 39 TC 50 Z9 50 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1994 VL 54 IS 21 BP 5607 EP 5613 PG 7 WC Oncology SC Oncology GA PP190 UT WOS:A1994PP19000023 PM 7923205 ER PT J AU MARTIN, GR JAIN, RK AF MARTIN, GR JAIN, RK TI NONINVASIVE MEASUREMENT OF INTERSTITIAL PH PROFILES IN NORMAL AND NEOPLASTIC TISSUE USING FLUORESCENCE RATIO IMAGING MICROSCOPY SO CANCER RESEARCH LA English DT Article ID INTRACELLULAR PH; TUMORS; INVIVO; HYPERGLYCEMIA; CARCINOMA; DIFFUSION; CELLS; ACID; FLOW AB The tumor interstitial pH and its modification play a significant role in cancer treatment. Current in vivo pH measurement techniques are invasive and/or provide poor spatial resolution. Therefore, there are no data on perivascular interstitial pH gradients in normal or tumor tissue. We have optically measured interstitial pH gradients with high resolution in normal and tumor (VX2 carcinoma) tissue in vivo by combining a fluorescence ratio imaging microscopy technique and the rabbit ear chamber preparation. The strengths of our approach include the ability to follow pH in the same location for several weeks and to relate these measurements to local blood flow and vascular architecture. Our results show: (a) tumor interstitial pH (6.75 units; N = 6 animals, n = 324 measurements) is significantly (P < 0.001) less than normal interstitial pH (7.23; N = 5, n = 274). This increased acidity in the tumor interstitium is in agreement with the previously reported data on this tumor; (b) with respect to pH spatial gradients in normal tissue, the interstitial pH decreased by approximately 0.32 pH units over a distance of 50 mu m away from the blood vessel, while in tumor tissue, interstitial pH decreased by approximately 0.13 units over the same distance. Although the pH gradient near the vessel wall was steeper in normal tissue compared to tumor, the proton concentration gradient in normal tissue was less than that in the tumor. The approximate increase in proton concentration from 0 to 50 mu m from the vessel was 4.5 x 10(-8) M in normal versus 5.7 x 10(-8) M in tumor tissue; (c) a simple one-dimensional diffusion-reaction model suggested that tumor tissue was producing protons at a rate 65-100% greater than normal tissue; (d) feasibility studies of temporal dynamics resulting from hyperglycemia (6 g/kg) or hypercapnia (10% CO2) led to significant (P < 0.05) interstitial pH reductions. During hyperglycemia, pH dropped by more than 0.2 pH units in about 90 min in tumor tissue but remained constant in normal tissue. Hypercapnia dramatically reduced pH by approximately 0.3 pH units in tumor tissue. Our limited studies on hyperglycemia and hypercapnia are in agreement with the previously published studies and demonstrate the capability of fluorescence ratio imaging microscopy to measure spatial as well as temporal changes in interstitial pH. Fluorescence ratio imaging microscopy should permit noninvasive evaluation of new pa-modifying agents and offer unique mechanistic information about tumor pathophysiology in tissue preparations where the surface of the tissue can be observed. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114. CARNEGIE MELLON UNIV,DEPT CHEM ENGN,PITTSBURGH,PA 15213. FU NCI NIH HHS [R35-CA-56591] NR 29 TC 226 Z9 236 U1 0 U2 21 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 1 PY 1994 VL 54 IS 21 BP 5670 EP 5674 PG 5 WC Oncology SC Oncology GA PP190 UT WOS:A1994PP19000033 PM 7923215 ER PT J AU COLSTON, JT KUMAR, P CHAMBERS, JP FREEMAN, GL AF COLSTON, JT KUMAR, P CHAMBERS, JP FREEMAN, GL TI ALTERED SARCOLEMMAL CALCIUM-CHANNEL DENSITY AND CA2+-PUMP ATPASE ACTIVITY IN TACHYCARDIA HEART-FAILURE SO CELL CALCIUM LA English DT Article ID DIHYDROPYRIDINE RECEPTOR; MYOCARDIUM; BINDING; CA-2+; MODEL; DESENSITIZATION; NOREPINEPHRINE; DEPENDENCE; ACTIVATION; DOGS AB Whether sarcolemmal (SL) calcium handling is altered in endstage heart failure produced by chronic rapid pacing is not known. To investigate this we paced 7 rabbits at a rate of 400 beats/min for 35 +/- 11 days. 6 animals served as non-paced controls. Purified left ventricular SL membranes were then prepared and tested for [H-3]-nitrendipine binding and (Ca2++Mg2+)-dependent ATPase (Ca2+-pump) activity. Results show a 50% reduction in calcium channel antagonist binding sites with B-max values reduced from 450 +/- 40 to 230 +/- 8 fmoles/mg protein in response to chronic rapid pacing (P < 0.01). This change was accompanied by a modest decrease in K-d from 0.29 +/- 0.09 to 0.22 +/- 0.03 nM (not significant). V-max values for the SL Ca2+-pump ATPase were decreased from 387 to 164 nmoles/mg protein/min (P < 0.01) with K-Ca(2+) values reduced from 0.91 to 0.28 mu M Ca2+ (P < 0.05) in response to tachycardia induced failure as compared to controls. ATPase activity in both groups was very sensitive to 25 mu M calmidazolium and 5 mu M vanadate. Results from this study indicate that both a reduction in SL calcium channel density and decrease in SL Ca2+-pump ATPase activity are evident in tachycardia heart failure. We conclude that sarcolemmal calcium handling is altered in heart failure induced by chronic rapid pacing and that such changes may contribute to systolic dysfunction associated with this model of heart failure. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,DIV LIFE SCI,BRAIN RES LAB BIOCHEM,SAN ANTONIO,TX 78285. NR 28 TC 23 Z9 23 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD NOV PY 1994 VL 16 IS 5 BP 349 EP 356 DI 10.1016/0143-4160(94)90028-0 PG 8 WC Cell Biology SC Cell Biology GA PR183 UT WOS:A1994PR18300002 PM 7859249 ER PT J AU FOY, BD ROTEM, A TONER, M TOMPKINS, RG YARMUSH, ML AF FOY, BD ROTEM, A TONER, M TOMPKINS, RG YARMUSH, ML TI A DEVICE TO MEASURE THE OXYGEN-UPTAKE RATE OF ATTACHED CELLS - IMPORTANCE IN BIOARTIFICIAL ORGAN DESIGN SO CELL TRANSPLANTATION LA English DT Article DE OXYGEN UPTAKE RATE; ANCHORAGE-DEPENDENT CELLS; HEPATOCYTES ID MULTICELLULAR SPHEROIDS; ADULT-RAT; HEPATOCYTES; DEPENDENCE; CULTURE; BIOREACTORS; RESPIRATION; METABOLISM; TRANSPORT; DIFFUSION AB Quantification of the dependence of cellular oxygen uptake rate (OUR) on oxygen partial pressure is useful for the design and testing of bioartificial devices which utilize cells. Thus far, this information has only been obtained from suspended tells and from cells attached to microcarriers. In this work, a device was developed to obtain the dependence of OUR on oxygen partial pressure for anchorage-dependent cells cultured in standard culture dishes. The device is placed and sealed on the top of the culture dish, and holds a Clark polarographic mini-electrode flush with the bottom surface of the device. It also houses a motor to spin a magnetic stir bar within the cell chamber to insure that the medium is well-mixed. Several characteristics of the device - such as oxygen leakage into the device chamber, electrode-lag time, and linearity of the electrode at low oxygen partial pressures-were quantified and their potential effect on the values of V-m, (maximal OUR) and K-0.5 (oxygen partial pressure at which OUR is half-maximal) were evaluated. Comparison of V-m and K-0.5 values obtained with this device with previously published values for suspended rat hepatocytes, Bacillus cei eus, and E. coli indicated that the technique provides values accurate within 30% as long as the cell under study has a K-0.5 greater than approximately 1.0 mmHg. For hepatocytes cultured on 0.05 min thickness collagen gel for 1 day (n = 4) and 3 days (n = 6), V-m was found to be 0.38 +/- 0.12 and 0.25 +/- 0.09 nmol O-2/s/10(6) cells, respectively, and K-0.5 was found to be 5.6 +/- 0.5 and 3.3 +/- 0.6 mmHg, respectively. This technique should aid in predicting bioreactor conditions such as flow rate, cell density, distance of cell from flow, and gas phase oxygen partial pressure which can lead to oxygen limitations. In addition, further studies of the effect of factors such as extracellular matrix composition, metabolic substrate, and drugs on the dependence of OUR on oxygen partial pressure for many anchorage-dependent cell types can be pursued with this technique. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,SURG SERV,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. FU NIDDK NIH HHS [DK-41709, DK-43371] NR 35 TC 72 Z9 74 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD NOV-DEC PY 1994 VL 3 IS 6 BP 515 EP 527 PG 13 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA PR945 UT WOS:A1994PR94500008 PM 7881763 ER PT J AU CANNON, MB VINE, AJ KANTOR, HL LAHORRA, JA NICKELL, SA HAHN, CW ALLYN, JW TEPLICK, RS TITUS, JS TORCHIANA, DF GEFFIN, GA DAGGETT, WM AF CANNON, MB VINE, AJ KANTOR, HL LAHORRA, JA NICKELL, SA HAHN, CW ALLYN, JW TEPLICK, RS TITUS, JS TORCHIANA, DF GEFFIN, GA DAGGETT, WM TI WARM AND COLD BLOOD CARDIOPLEGIA - COMPARISON OF MYOCARDIAL-FUNCTION AND METABOLISM USING P-31 MAGNETIC-RESONANCE SPECTROSCOPY SO CIRCULATION LA English DT Article; Proceedings Paper CT 66th Scientific Sessions of the American-Heart-Association:Cardiovascular Surgery 1993 CY NOV 08-11, 1993 CL ATLANTA, GA SP AMER HEART ASSOC DE CARDIOPLEGIA; SPECTROSCOPY; DOGS ID HEART-SURGERY; RAT-HEART; SARCOPLASMIC-RETICULUM; CARDIOPULMONARY BYPASS; TEMPERATURE; CALCIUM; ISCHEMIA; PH; PHOSPHORYLATION; PRESERVATION AB Background Standard myocardial protection during cardiac surgery uses hypothermic arrest, but warm heart surgery, recently introduced, is now used in many centers. We hypothesized that warm continuous blood cardioplegia (WCBC) would provide better myocardial preservation than cold continuous blood cardioplegia (CCBC). Methods and Results In isolated cross-perfused canine hearts, left ventricular (LV) function and myocardial O-2 consumption (MVo(2)) were measured at constant LV volume, coronary perfusion pressure, and heart rate before and after 75 minutes of arrest at 37 degrees C or 10 degrees C. Metabolism was evaluated by P-31 nuclear magnetic resonance spectroscopy. LV resting tone increased transiently after arrest by CCBC but not WCBC (38+/-3.9 versus 2.9+/-0.5 mm Hg, P<.0005). Myocardiai ATP changed over time differently in the groups (P<.001), declining at the outset of CCBC and returning to control levels during the recovery period after CCBC or WCBC. Intracellular pH rose from 7.17+/-0.03 to 7.85+/-0.05 during CCBC (P<.0005 versus WCBC), MVo(2) declined dramatically during arrest at either temperature but to a lower value during CCBC (P<.0005). LV pressure recovered to 86.1+/-5.1% of its prearrest value after CCBC and to 97.2+/-7.8% following WCBC (P=NS). After CCBC but not WCBC, there were small but significant increases in LV end-diastolic pressure (by 1.3 mm Hg, P<.05) and in the LV relaxation constant, tau (from 37.3+/-1.5 to 42.3+/-2.4 milliseconds, P<.05). Conclusions The increase in intracellular pH during CCBC is largely accounted for by physicochemical factors. Group differences in ATP over time may be related to rapid cooling contracture during CCBC. The data suggest that CCBC mildly impairs LV function but that WCBC preserves function and metabolism at or near prearrest levels. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,SURG CARDIOVASC UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 52 TC 16 Z9 17 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 PY 1994 VL 90 IS 5 BP 328 EP 338 PN 2 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PR287 UT WOS:A1994PR28700058 ER PT J AU LEAF, A JORGENSEN, MB JACOBS, AK COTE, G SCHOENFELD, DA SCHEER, J WEINER, BH SLACK, JD KELLETT, MA RAIZNER, AE WEBER, PC MAHRER, PR ROSSOUW, JE AF LEAF, A JORGENSEN, MB JACOBS, AK COTE, G SCHOENFELD, DA SCHEER, J WEINER, BH SLACK, JD KELLETT, MA RAIZNER, AE WEBER, PC MAHRER, PR ROSSOUW, JE TI DO FISH OILS PREVENT RESTENOSIS AFTER CORONARY ANGIOPLASTY SO CIRCULATION LA English DT Article DE RESTENOSIS; ANGIOPLASTY; FISH OIL; FATTY ACIDS ID EICOSAPENTAENOIC ACID; GREENLAND ESKIMOS; FATTY-ACIDS; SUPPLEMENTS; DISEASE; TRIAL; DIET; ATHEROSCLEROSIS; THROMBOLYSIS; THROMBOXANE AB Background The omega-3 polyunsaturated fatty acids derived from fish oils have been shown to modulate many factors believed to affect the pathogenesis of atherosclerosis. Because certain features of restenosis following angioplasty mimic some of the early changes of atherogenesis, some researchers have suggested that fish oil might prevent restenosis following angioplasty. We report the effects of omega-3 fatty acids on the rate of restenosis following percutaneous intraluminal coronary angioplasty (PTCA). Methods and Results From August 1989 through September 1992, 551 patients were randomized to start receiving a daily dietary supplement of ten 1.0-g capsules containing 80.6% ethyl esters of omega-3 fatty acids providing 4.1 g eicosapentaenoic acid (EPA) and 2.8 g docosahexaenoic acid (DHA) for 6 months or an equal amount of an ethyl ester of corn oil. Four hundred seventy subjects who were well matched for risk factors completed successful angioplasty of one or multiple lesions in native coronary vessels and constituted the study cohort, of whom 447 were evaluable at 6 months after PTCA. The criteria for restenosis were that the quantitative coronary angiography at 6 months show a >30% increase in narrowing at the stenosis site or loss of at least half of the gain achieved at the time of PTCA and final restenosis with <50% luminal diameter remaining, In 93% of the patients, the end point was determined by angiography and in all except 1% of these by quantitative coronary angiography. Compliance with the fish oil supplement was good as judged by incorporation of EPA and DHA in plasma and red blood cell phospholipids. The restenosis rate among analyzable patients was 46% for corn oil and 52% for fish oil (P=.37). The addition of 200 mg alpha-tocopherol for all subjects during the study had no effect on restenosis rates. Conclusions This was the largest of such trials to date, and a supplement of 8 g/d of omega-3 fatty acids failed to prevent the usual high rate of restenosis after PTCA. No adverse effects were attributable to this large daily supplement of omega-3 fatty acids. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. KAISER PERMANENTE, LOS ANGELES, CA USA. UNIV BOSTON HOSP, MED CTR, BOSTON, MA 02118 USA. MONTREAL HEART INST, MONTREAL H1T 1C8, PQ, CANADA. UNIV MASSACHUSETTS, MED CTR, WORCESTER, MA USA. SMITH & PINKERTON CARDIOL INC, INDIANAPOLIS, IN USA. MAINE MED CTR, PORTLAND, ME 04102 USA. METHODIST HOSP, HOUSTON, TX 77030 USA. BAYLOR COLL MED, HOUSTON, TX 77030 USA. UNIV MUNICH, INST PROPHYLAXE & EPIDEMIOL KREISLAUFKRANKHEITEN, MUNICH, GERMANY. NHLBI, LIPID METAB ATHEROGENESIS BRANCH, BETHESDA, MD 20892 USA. FU NHLBI NIH HHS [UO1-HL-40548] NR 34 TC 171 Z9 173 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV PY 1994 VL 90 IS 5 BP 2248 EP 2257 PN 1 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PR286 UT WOS:A1994PR28600013 PM 7955181 ER PT J AU ISSELBACHER, EM CIGARROA, JE EAGLE, KA AF ISSELBACHER, EM CIGARROA, JE EAGLE, KA TI CARDIAC-TAMPONADE COMPLICATING PROXIMAL AORTIC DISSECTION - IS PERICARDIOCENTESIS HARMFUL SO CIRCULATION LA English DT Article DE AORTA; TAMPONADE; PERICARDIOCENTESIS; PERICARDIUM AB Background Cardiac tamponade frequently complicates acute proximal aortic dissection and is one of the most common causes of death from aortic dissection. Well-defined strategies for the management of acute aortic dissection now exist; however, little is known about how best to manage the hemopericardium that may complicate it. Methods and Results Using a computer-based review, we retrospectively identified 10 patients presenting to our hospital over a 13-year period who were diagnosed with both aortic dissection and cardiac tamponade. All 10 had proximal dissections. Three of the 10 presented as the sudden onset of fatal electromechanical dissociation, 6 presented with hypotension, and 1 was normotensive on presentation. Of the 7 hypotensive or normotensive patients diagnosed with cardiac tamponade, 4 underwent successful pericardiocentesis while awaiting surgery. At time intervals of 5 to 40 minutes after their pericardiocenteses, 3 of the 4 patients experienced sudden onset of electromechanical dissociation and death; the fourth patient survived and underwent surgical repair. Of the 3 hypotensive or normotensive patients who had either no pericardiocentesis or an unsuccessful pericardiocentesis, all 3 underwent successful surgical repair and survived. Conclusions In this study, patients with an aortic dissection complicated by cardiac tamponade have an early mortality of 60%. While 3 of the 10 died from electromechanical dissociation immediately upon presentation, the 3 other deaths all occurred shortly after successful pericardiocentesis, a procedure undertaken to stabilize them. While the number of patients in this series is small, the observations do raise the possibility that in patients with cardiac tamponade complicating aortic dissection pericardiocentesis could be harmful rather than beneficial. Possible mechanisms for why the performance of pericardiocentesis might destabilize such patients are proposed. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. NR 8 TC 70 Z9 73 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV PY 1994 VL 90 IS 5 BP 2375 EP 2378 PN 1 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PR286 UT WOS:A1994PR28600028 PM 7955196 ER PT J AU MEYER, BJ BADIMON, JJ MAILHAC, A FERNANDEZORTIZ, A CHESEBRO, JH FUSTER, V BADIMON, L AF MEYER, BJ BADIMON, JJ MAILHAC, A FERNANDEZORTIZ, A CHESEBRO, JH FUSTER, V BADIMON, L TI INHIBITION OF GROWTH OF THROMBUS ON FRESH MURAL THROMBUS - TARGETING OPTIMAL THERAPY SO CIRCULATION LA English DT Article DE THROMBOSIS; ATHEROSCLEROSIS; REOCCLUSION; ANTITHROMBOTICS; HIRUDIN ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; COLLAGEN TYPE-I; UNSTABLE ANGINA; VONWILLEBRAND-FACTOR; PLATELET DEPOSITION; VESSEL WALL; RECOMBINANT HIRUDIN; RECURRENT ISCHEMIA; ARTERY DISEASE AB Background Residual mural thrombus on severely damaged arterial wall is very thrombogenic. We tested the hypothesis that direct thrombin inhibition will block thrombus growth on fresh thrombus better than indirect thrombin inhibition, cyclooxygenase inhibition, or both. Methods and Results A fresh mural thrombus was formed by directly perfusing fresh porcine blood for 5 minutes over severely damaged arterial wall at a high shear rate in a well-characterized ex vivo perfusion system. The average platelet (P) and fibrinogen (F) deposition (D) achieved in 5 minutes were 382+/-32x10(6) platelets/cm(2) and 296+/-36x10(12) fibrinogen molecules/cm(2), respectively. Thrombus growth on the fresh mural thrombus was quantitated by directly perfusing blood from pigs with In-111-labeled platelets and I-125-labeled fibrinogen for an additional 5 minutes over the preformed mural thrombus. Treatment included recombinant hirudin (1 mg/kg per hour IV) as a probe for thrombin, aspirin (5 mg/kg IV) as a platelet inhibitor of cyclooxygenase, heparin (moderate, 100 IU/kg per hour IV; high-dose, 250 IU/kg per hour IV) as an indirect thrombin inhibitor, and heparin (100 IU/kg per hour) plus aspirin (5 mg/kg IV). Thrombus growth as measured by labeled PD (x10(6)/cm(2)) and FD (x10(12) molecules/cm(2)) was mildly but not significantly reduced by aspirin (1034+/-92 and 436+/-78, respectively) compared with baseline (1113+/-67 and 545+/-52, respectively). Inhibition of thrombus growth with heparin was dose dependent. A regression analysis showed an inverse correlation of PD and FD with mean plasma heparin concentrations (r=-.81, P=.0001 and r=-.49, P=.0007, respectively). Recombinant hirudin led to a profound inhibition of thrombus growth (PD, 30+/-12; FD, 109+/-21), which was significant compared with all groups, even the highest dosage of heparin (250 IU/kg per hour). Conclusions Specific thrombin inhibition markedly inhibits platelet and fibrinogen deposition onto fresh mural thrombus at a high shear rate. Aspirin alone or in combination with heparin has little effect on evolving thrombosis. Heparin dose dependently reduces thrombus growth, but,even the highest dosage is less effective than hirudin. Thrombin appears to be the primary activator of platelets by fresh thrombus. C1 CSIC,H ST PAU,CARDIOVASC RES CTR,BARCELONA,SPAIN. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CARDIOVASC BIOL RES LAB,BOSTON,MA 02114. RI BADIMON, LINA/O-4711-2014; Fuster, Valentin/H-4319-2015; Fernandez-Ortiz, Antonio/B-2227-2017 OI BADIMON, LINA/0000-0002-9162-2459; Fuster, Valentin/0000-0002-9043-9986; Fernandez-Ortiz, Antonio/0000-0002-3239-1910 FU NHLBI NIH HHS [HL-38933] NR 42 TC 69 Z9 69 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 PY 1994 VL 90 IS 5 BP 2432 EP 2438 PN 1 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PR286 UT WOS:A1994PR28600035 PM 7955200 ER PT J AU MEYER, BJ FERNANDEZORTIZ, A MAILHAC, A FALK, E BADIMON, L MICHAEL, AD CHESEBRO, JH FUSTER, V BADIMON, JJ AF MEYER, BJ FERNANDEZORTIZ, A MAILHAC, A FALK, E BADIMON, L MICHAEL, AD CHESEBRO, JH FUSTER, V BADIMON, JJ TI LOCAL-DELIVERY OF R-HIRUDIN BY A DOUBLE-BALLOON PERFUSION CATHETER PREVENTS MURAL THROMBOSIS AND MINIMIZES PLATELET DEPOSITION AFTER ANGIOPLASTY SO CIRCULATION LA English DT Article DE ANGIOPLASTY; R-HIRUDIN; THROMBOSIS; CATHETERS; PLATELETS ID CORONARY-ARTERY DISEASE; CLOT-BOUND THROMBIN; INJURY; HEPARIN; INHIBITION; MODEL; RESTENOSIS; WALL; PATHOGENESIS; INACTIVATION AB Background The major morbidity of percutaneous transluminal coronary angioplasty is acute thrombosis and restenosis of the dilated lesion. Platelet-thrombus deposition occurs within minutes after injury, is primarily mediated by thrombin, causes acute occlusion, and contributes to late restenosis. Experimentally, specific thrombin inhibitors have prevented mural thrombosis. However, local therapy may be more effective than systemic treatment. We tested the hypothesis that high local concentrations of an antithrombin drug at the site of arterial injury following balloon angioplasty inhibit platelet thrombus formation equally or better than conventional systemic treatment and at lower systemic anticoagulant levels. Methods and Results Balloon angioplasty of the carotid arteries of 29 pigs was performed using systemic intravenous treatment with heparin (100 U/kg, groups I and II), suboptimal r-hirudin (0.3 mg/kg, group III), and higher-dose r-hirudin (0.7 mg/kg, group TV), which is the lowest dose that completely inhibited arterial thrombosis in the pig. Immediately after balloon angioplasty of the first carotid, additional local therapy with placebo (group I) or r-hirudin (groups II, III, and IV; 0.3 mg/kg in 1 mt) was administered with distal perfusion through a new percutaneous double-balloon catheter. After 1 hour of local drug delivery, angioplasty of the contralateral carotid was performed. Reflow for 1 hour was permitted to both carotids to compare the short-term effect of local plus systemic treatment with systemic treatment on quantitative In-111-labeled platelet deposition and macroscopic mural thrombus formation on deeply injured carotid segments. Local drug delivery of placebo compared with systemic heparin treatment resulted in no change of platelet deposition (x10(6)/cm(2), mean+/-SEM) in controls (group I, 91.0+/-23.5 versus 80.8+/-19.4), but local delivery of r-hirudin resulted in a significant reduction in group II (15+/-2.5 versus 71.3+/-14.5; P<.02) and group III (11.4+/-2.5 versus 80.5+/-11.4; P<.01) and was borderline in group IV (7.4-+/-1.8 versus 14.1+/-7.4; P=.05), respectively. The incidence of macroscopic mural thrombus formation with local and systemic treatment was 86% and 75% in group I, 16% and 70% in group II, 14% and 71% in group III, and 0% and 16% in group IV, respectively. Conclusions Local therapy with the specific thrombin inhibitor r-hirudin significantly reduces short-term quantitative platelet deposition and macroscopic mural thrombus formation following balloon angioplasty compared with systemic treatment of conventional doses of heparin and hirudin and requires a significantly smaller amount of the recombinant drug. C1 CUNY MT SINAI SCH MED,INST CARDIOVASC,NEW YORK,NY 10029. MASSACHUSETTS GEN HOSP,CARDIOVASC BIOL RES LAB,CARDIAC UNIT,BOSTON,MA. RI BADIMON, LINA/O-4711-2014; Falk, Erling/A-7475-2015; Fuster, Valentin/H-4319-2015; Fernandez-Ortiz, Antonio/B-2227-2017 OI BADIMON, LINA/0000-0002-9162-2459; Falk, Erling/0000-0001-8566-9974; Fuster, Valentin/0000-0002-9043-9986; Fernandez-Ortiz, Antonio/0000-0002-3239-1910 NR 31 TC 65 Z9 65 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 PY 1994 VL 90 IS 5 BP 2474 EP 2480 PN 1 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PR286 UT WOS:A1994PR28600040 PM 7955205 ER PT J AU OSSWALD, S TROUTON, TG ONUNAIN, SS HOLDEN, HB RUSKIN, JN GARAN, H AF OSSWALD, S TROUTON, TG ONUNAIN, SS HOLDEN, HB RUSKIN, JN GARAN, H TI RELATION BETWEEN SHOCK-RELATED MYOCARDIAL INJURY AND DEFIBRILLATION EFFICACY OF MONOPHASIC AND BIPHASIC SHOCKS IN A CANINE MODEL SO CIRCULATION LA English DT Article DE SHOCK; MYOCARDIUM; DEFIBRILLATION ID TRANS-THORACIC COUNTERSHOCK; SAFETY FACTOR; CARDIOVERTER-DEFIBRILLATORS; RABBIT HEART; LEAD SYSTEM; DOGS; WAVEFORMS; THRESHOLD; HUMANS; DAMAGE AB Background Certain biphasic waveforms with specific time ratios of positive and negative components require less energy for successful defibrillation of the fibrillating ventricles than monophasic waveforms. However, if more efficient waveforms were also to be associated with more injurious effects on myocardial function, they might not provide a true biological advantage. This study investigates the relation between defibrillation efficacy and potential toxicity of monophasic and asymmetric, single capacitor, biphasic waveforms with equal durations of positive and negative components. Methods and Results The myocardial lactate extraction rate (LER) was used to measure the injurious effects on myocardial oxidative metabolism of two synchronized 35-J shocks in sinus rhythm. LER, mean arterial pressure (MAP) and, in a subset of experiments, cardiac output (CO) and coronary blood flow (CBF) were measured at baseline, 30 seconds, 60 seconds, 90 seconds, 150 seconds, 300 seconds, and 600 seconds after the shocks. In 12 dogs, three different waveforms (M 10: monophasic 10 milliseconds; BI 10: biphasic 10 milliseconds; BI 20: biphasic 20 milliseconds) were tested as series of two consecutive shocks (60 seconds apart) resulting in a total of 36 sets of data. At baseline, LER was 25+/-11%. After monophasic shocks, LER decreased significantly more than after biphasic shocks (LER at 150 seconds: M 10: -6+/-31% versus BI 10: 21+/-15% versus BI 20: 21+/-16%; M 10 versus BI 10 and M 10 versus BI 20, P<.05) and showed also a slower recovery (LER at 300 seconds: M 10: 1+/-24% versus BI 10: 20+/-11% versus BI 20: 20+/-15%; M 10 versus BI 10 and M 10 versus BI 20, P<.05). The maximal decrease in LER was 41+/-27% for M 10 compared with 18+/-15% for BI 10 and 15+/-11% for BI 20 (both, M 10 versus BI 10 and M 10 versus BI 20, P<.05). There was a similar decrease in CO and MAP, with the lowest MAP after monophasic shocks. The maximal decrease in MAP was significantly greater after M 10 compared with BI 20 (-29+/-15 mm Hg versus -13+/-11 mm Hg, P<.05). The defibrillation threshold was 18.6+/-8 J for M 10 compared with 11.5+/-4.0 J for BI 10 (P<.05) and 15.0+/-6.1 J for BI 20, respectively (P=NS). Conclusions Our results suggest that these specific biphasic waveforms are associated with less injurious effects on myocardial oxidative metabolism and hemodynamic performance. Given their higher defibrillation efficacy as well, biphasic waveforms may provide important long-term benefits in patients receiving frequent shocks from implantable cardioverter-defibrillators. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,BOSTON,MA 02114. NR 41 TC 61 Z9 62 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 PY 1994 VL 90 IS 5 BP 2501 EP 2509 PN 1 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PR286 UT WOS:A1994PR28600043 PM 7955208 ER PT J AU BRAUNWALD, E AF BRAUNWALD, E TI COST-EFFECTIVENESS OF TIMI IIIB STRATEGIES - REPLY SO CIRCULATION LA English DT Letter RP BRAUNWALD, E (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,TIMI STUDY GRP,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV PY 1994 VL 90 IS 5 BP 2569 EP 2569 PN 1 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PR286 UT WOS:A1994PR28600071 ER PT J AU PURNER, MB BERENS, RL KRUG, EC CURIEL, TJ AF PURNER, MB BERENS, RL KRUG, EC CURIEL, TJ TI EPSTEIN-BARR VIRUS-TRANSFORMED B-CELLS, A POTENTIALLY CONVENIENT SOURCE OF AUTOLOGOUS ANTIGEN-PRESENTING CELLS FOR THE PROPAGATION OF CERTAIN HUMAN CYTOTOXIC T-LYMPHOCYTES SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN; REVERSE-TRANSCRIPTASE; VIRAL HEMAGGLUTININ; SEQUENCE VARIATION; SOLUBLE-ANTIGEN; INFECTED CELLS; HLA-ANTIGEN; CLONES; LINES; INDUCTION AB Antigen-specific cytotoxic T cells (CTL) are generally elicited in vitro by incubation of effector cells with an appropriate major histocompatibility complex-matched antigen-presenting cell (APC). In the case of CTL derived from inbred rodents, spleen cells from an animal of the same strain serve as a ready source of autologous major histocompatibility complex-identical APC. In outbred human populations, however, a convenient source of human leukocyte antigen-matched APC is ordinarily difficult to obtain, and for that reason human antigen-specific CTL may be difficult to propagate. We describe a method whereby Epstein-Barr virus-transformed human B cells (B-LCL) serve as a convenient source of efficient APC for the propagation of human antigen-specific CTL. B-LCL are produced by using B cells from the donor under study and are thus human leukocyte antigen identical to the donor. Using this method, we have propagated human CD4+ Toxoplasma gondii-specific CTL for up to 9 months in vitro, during which time the cells retained their functional capability. C1 UNIV COLORADO,HLTH SCI CTR,DIV INFECT DIS,BOX B-168,4200 E 9TH AVE,DENVER,CO 80262. DENVER VET AFFAIRS MED CTR,DIV INFECT DIS,DENVER,CO 80220. NR 39 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD NOV PY 1994 VL 1 IS 6 BP 696 EP 700 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PV209 UT WOS:A1994PV20900014 PM 8556523 ER EF