FN Thomson Reuters Web of Science™ VR 1.0 PT J AU CHAPMAN, KB SZOSTAK, JW AF CHAPMAN, KB SZOSTAK, JW TI ISOLATION OF A RIBOZYME WITH 5'-5' LIGASE ACTIVITY SO CHEMISTRY & BIOLOGY LA English DT Article DE EVOLUTION; IN VITRO SELECTION; ORIGIN OF LIFE; RNA WORLD ID MESSENGER-RNA; DIADENOSINE 5',5'''-P1,P4-TETRAPHOSPHATE; INVITRO SELECTION; OLIGOMERIZATION; TETRAHYMENA; NUCLEOTIDES; POLYMERASE; SEQUENCES; ADENOSINE; APPPPA AB Background: Many new ribozymes, including sequence-specific nucleases, ligases and kinases, have been isolated by in vitro selection from large pools of random-sequence RNAs. We are attempting to use in vitro selection to isolate new ribozymes that have, or can be evolved to have, RNA polymerase-like activities. As phosphorimidazolide-activated nucleosides are extensively used to study non-enzymatic RNA replication, we wished to select for a ribozyme that would accelerate the template-directed ligation of 5'-phosphorimidazolide-activated oligonucleotides. Results: Ribozymes selected to perform the desired template-directed ligation reaction instead ligated themselves to the activated substrate oligonucleotide via their 5'-triphosphate, generating a 5'-5' P-1,P-4-tetraphosphate linkage. Deletion analysis of one of the selected sequences revealed that a 54-nucleotide RNA retained activity; this small ribozyme folds into a pseudoknot secondary structure with an internal binding site for the substrate oligonucleotide. The ribozyme can also synthesize 5'-5' triphosphate and 5'-5' pyrophosphate linkages. Conclusions: The emergence of ribozymes that accelerate an unexpected 5'-5' ligation reaction from a selection designed to yield template-dependent 3'-5' ligases suggests that it may be much easier for RNA to catalyze the synthesis of 5'5' Linkages than 3'5' linkages. 5'-5' linkages are found in a variety of contexts in present-day biology. The ribozyme-catalyzed synthesis of such linkages raises the possibility that these 5'-5' linkages originated in the biochemistry of the RNA world. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 32 TC 42 Z9 43 U1 0 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD MAY PY 1995 VL 2 IS 5 BP 325 EP 333 DI 10.1016/1074-5521(95)90051-9 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RB384 UT WOS:A1995RB38400009 PM 9383434 ER PT J AU NEYA, K LEE, R GUERRERO, JL LANG, P VLAHAKES, GJ AF NEYA, K LEE, R GUERRERO, JL LANG, P VLAHAKES, GJ TI EXPERIMENTAL ABLATION OF OUTFLOW TRACT MUSCLE WITH A THERMAL BALLOON CATHETER SO CIRCULATION LA English DT Article DE CATHETER ABLATION; RADIOFREQUENCY ID RADIOFREQUENCY ENERGY; THERMODYNAMIC MODEL; TETRALOGY; FALLOT; ANGIOPLASTY; TISSUE; SIZE; VALVULOPLASTY; TEMPERATURE; OPERATIONS AB Background Pulmonary balloon valvuloplasty has been performed in selected patients with tetralogy of Fallot as an alternative to surgical palliation; this technique is limited, however, by the fact that the balloon has little effect on the dynamic, muscular contribution to outflow tract obstruction, In an experimental model, we used a new thermal balloon catheter to ablate right ventricular outflow tract muscle. We evaluated the acute efficacy and muscle ablation parameters of this technology and its effects after myocardial healing. Methods and Results A prototype electrolyte-filled balloon catheter, heated by radiofrequency energy, was constructed. Studies were conducted to determine the optimum electrolyte solution needed to minimize balloon heating time with an unmodified, commercially available radiofrequency generator. In vivo ablations of right ventricular outflow tract muscle with the thermal balloon were performed in lambs that were divided into three groups (n=5 each) according to the duration of thermal energy delivery (20, 40, and 60 seconds, respectively). Ablated lesion volume increased (460+/-63 to 1156+/-256 mm(3)) as the energy delivery time increased (20 to 60 seconds) and was correlated with delivered energy, temperature integral, and maximum epicardial surface temperature (r=.85, .82, and .72, respectively). All five lesions in the 60-second group showed an acute decrease of the wall thickness. Additional in vivo ablations were performed in 6 animals in which survival studies showed muscle thinning, healing by fibrosis, and no evidence of aneurysm formation. Conclusions Thermal energy can be used with a balloon catheter delivery system to ablate myocardium. This study suggests that this energy delivery technology might be useful for relief of muscular outflow tract obstruction and that further studies are warranted. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,CARDIAC SURG UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,PEDIAT CARDIOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 34 TC 3 Z9 3 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 1 PY 1995 VL 91 IS 9 BP 2445 EP 2453 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QV251 UT WOS:A1995QV25100022 PM 7729032 ER PT J AU LOH, E BARNETT, JV FELDMAN, AM COUPER, GS VATNER, DE COLUCCI, WS GALPER, JB AF LOH, E BARNETT, JV FELDMAN, AM COUPER, GS VATNER, DE COLUCCI, WS GALPER, JB TI DECREASED ADENYLATE-CYCLASE ACTIVITY AND EXPRESSION OF G(S-ALPHA) IN HUMAN MYOCARDIUM AFTER ORTHOTOPIC CARDIAC TRANSPLANTATION SO CIRCULATION RESEARCH LA English DT Article DE CARDIAC TRANSPLANTATION; ADENYLATE CYCLASE; GUANINE NUCLEOTIDE REGULATORY PROTEINS ID FAILING HUMAN-HEART; CHICK ATRIAL CELLS; POLYMERASE CHAIN-REACTION; LOW-DENSITY LIPOPROTEINS; G-PROTEIN; GENE-EXPRESSION; REGULATORY PROTEINS; MESSENGER-RNA; SUBUNITS; ALPHA AB We studied several aspects of guanine nucleotide-stimulated adenylate cyclase function in patients after orthotopic cardiac transplantation. In 28 patients, adenylate cyclase activity was measured in endomyocardial biopsy samples obtained just before and at monthly intervals after cardiac transplantation. In biopsies obtained greater than or equal to 6 months after transplantation, basal adenylate cyclase activity was decreased by 67% (n=12; P<.05), GTP gamma S-stimulated adenylate cyclase activity was decreased by 78% (n=12; P<.05), Mn+2+forskolin-stimulated adenylate cyclase activity was decreased by 80% (n=8; P<.05), and Mn+2-stimulated adenylate cyclase activity (a measure of activity of the catalytic subunit of adenylate cyclase) was decreased by 83% (n=8, P<.05). Western blot analysis demonstrated that 6 months after cardiac transplantation, the level of G(s alpha) protein was decreased by 61+/-12% (n=8; P<.001). There was no change in the level of G(i alpha) as assessed by pertussis toxin-catalyzed ADP-ribosylation (n=4; P=NS). With the use of the quantitative polymerase chain reaction, a 50+/-10% (n=6; P<.001) reduction in the steady-state level of G(s alpha) mRNA was observed. There was no change in the level of mRNA for G(i-3 alpha) Thus, after orthotopic cardiac transplantation in humans, guanine nucleotide-stimulated adenylate cyclase activity is decreased in parallel with decreased levels of G(s alpha) protein and mRNA. C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV CARDIOVASC,BOSTON,MA 02115. VANDERBILT UNIV,MED CTR,DEPT MED,DIV CARDIOVASC,NASHVILLE,TN. UNIV PITTSBURGH,DIV CARDIOL,PITTSBURGH,PA. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP LOH, E (reprint author), HOSP UNIV PENN,DEPT MED,DIV CARDIOVASC,3400 SPRUCE ST,PHILADELPHIA,PA 19104, USA. FU NHLBI NIH HHS [HL-42539, HL-39719, HL-36014] NR 43 TC 8 Z9 8 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAY PY 1995 VL 76 IS 5 BP 852 EP 860 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA QU898 UT WOS:A1995QU89800019 PM 7729002 ER PT J AU DAQUILA, RT AF DAQUILA, RT TI HIV-1 CHEMOTHERAPY AND DRUG-RESISTANCE SO CLINICAL AND DIAGNOSTIC VIROLOGY LA English DT Review DE HIV-1; ANTIRETROVIRALS; ZIDOVUDINE (AZT) RESISTANCE; REVERSE TRANSCRIPTASE; PROTEASE; DRUG-RESISTANCE MUTATIONS; DRUG-RESISTANCE ASSAYS; HIV-1 PLASMA RNA ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 REVERSE-TRANSCRIPTASE; HIGH-LEVEL RESISTANCE; SYNCYTIUM-INDUCING PHENOTYPE; POLYMERASE CHAIN-REACTION; BLOOD MONONUCLEAR-CELLS; ZIDOVUDINE-RESISTANCE; REDUCED SENSITIVITY; IN-VITRO; MUTATIONS AB Background: Therapy with inhibitors of human immunodeficiency virus' type 1 (HIV-1) replication has had only transient clinical benefit to date. It has been speculated that drug-resistant virus mutants may contribute to therapeutic failure. Objective: To extrapolate from the biology of drug-resistant HIV-1 to improve antiretroviral chemotherapeutic strategies. Study design: The literature was reviewed in regard to clinical and virologic correlates of HIV-1 drug resistance, methodology for detection of resistant virus, and chemotherapeutic strategies for prolonging suppression of virus replication. Results: HIV-1 isolates resistant to different nucleoside reverse transcriptase (RT) inhibitors, nonnucleoside RT inhibitors, and protease inhibitors have been implicated to different extents with virologic or clinical failure of therapeutic effectiveness. The in vivo antiviral effect of certain nonnucleoside RT inhibitors as monotherapy is lost coincident with emergence of a dominant population of resistant virus. Disease Progression is more rapid among patients at advanced stages of HIV-1 disease with highly zidovudine (AZT)-resistant virus (50% inhibitory concentration less than or equal to 1.0 mu M AZT) and is not attributable to effects of other baseline predictors of progression studied to date. However, there is no definitive evidence that high level AZT resistance causes the loss of therapeutic benefit of AZT. Several of the research methods used for detection of drug-resistant mutants could be developed for future use as screening assays in clinical virology laboratories. Conclusions: Strategies for individualizing therapy based on switching, or adding, drugs at first detection of drug-resistant HIV-1 aim to minimize replication of viruses that are drug-resistant, as well as those that remain susceptible to the drug. If clinical investigation reveals that such approaches extend duration of antiretroviral: therapeutic benefit, HIV-1 drug-resistance assessment may be increasingly requested from, clinical virology laboratories. Monitoring antiviral suppression by quantifying plasma HIV-1 RNA appears more practical at present, however. Different combination regimens are also being studied to see if some regimens delay emergence of resistant virus longer than others. In the future, sequential empiric changes to new combination regimens every few months may also bear investigation to attempt to ''pre-empt'' HIV-1 resistance development. RP DAQUILA, RT (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,149 13TH ST,BOSTON,MA 02129, USA. NR 95 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0197 J9 CLIN DIAGN VIROL JI Clin. Diagn. Virol. PD MAY PY 1995 VL 3 IS 4 BP 299 EP 316 DI 10.1016/0928-0197(94)00064-2 PG 18 WC Virology SC Virology GA RC051 UT WOS:A1995RC05100001 PM 15566811 ER PT J AU Merajver, SD Frank, TS Xu, JZ Pham, TM Calzone, KA BennettBaker, P Chamberlain, J Boyd, J Garber, JE Collins, FS Weber, BL AF Merajver, SD Frank, TS Xu, JZ Pham, TM Calzone, KA BennettBaker, P Chamberlain, J Boyd, J Garber, JE Collins, FS Weber, BL TI Germline BRCA1 mutations and loss of the wild-type allele in tumors from families with early onset breast and ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID GENETIC-ANALYSIS; CHROMOSOME-17Q21; LINKAGE; REGION AB The BRCA1 gene on human chromosome 17q21 is responsible for an autosomal dominant syndrome of inherited early onset breast/ovarian cancer, It is estimated that women harboring a germline BRCA1 mutation incur an 85% lifetime risk of breast cancer and a greatly elevated risk of ovarian cancer. The BRCA1 gene has recently been isolated and mutations have been found in the germline of affected individuals in linked families. Previous studies of loss of heterozygosity (LOH) in breast tumors have been carried out on sporadic tumors derived from individuals without known linkage to BRCA1 and on tumors from linked families, Loss of large regions of chromosome 17 has been observed, but these LOH events could not be unequivocally ascribed to BRCA1. We have studied 28 breast and 6 ovarian tumors from families with strong evidence for linkage between breast cancer and genetic markers flanking BRCA1. These tumors were examined for LOH using genetic markers flanking and within BRCA1, including THRA1, D17S856, EDH17B1, EDH17B2, and D17S183, Forty-six percent (16/34) of tumors exhibit LOH which includes BRCA1, In 8 of 16 tumors the parental origin of the deleted allele could be determined by evaluation of haplotypes of associated family members; in 100% of these cases, the wild-type allele was lost. In some of these families germline mutations in BRCA1 have been determined; analyses of tumors with LOH at BRCA1 have revealed that only the disease-related allele of BRCA1 was present. These data strongly support the hypothesis that BRCA1 is a tumor suppressor gene. C1 DANA FARBER CANC INST,BOSTON,MA 02115. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV PENN,DEPT OBSTET & GYNECOL,PHILADELPHIA,PA 19104. UNIV PENN,DEPT INTERNAL MED,PHILADELPHIA,PA 19104. UNIV PENN,DEPT GENET,PHILADELPHIA,PA 19104. UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109. UNIV MICHIGAN,CTR HUMAN GENOME,ANN ARBOR,MI 48109. RP Merajver, SD (reprint author), UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,5510 MSRB I,ANN ARBOR,MI 48109, USA. FU NCI NIH HHS [R01 CA57601-01]; NCRR NIH HHS [3MO1RR00042-34S1]; NHGRI NIH HHS [P30 HG00209] NR 23 TC 68 Z9 71 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 1995 VL 1 IS 5 BP 539 EP 544 PG 6 WC Oncology SC Oncology GA TL080 UT WOS:A1995TL08000009 PM 9816013 ER PT J AU Ichige, K Perey, L Vogel, CA Buchegger, F Kufe, D AF Ichige, K Perey, L Vogel, CA Buchegger, F Kufe, D TI Expression of the DF3-P epitope in human ovarian carcinomas SO CLINICAL CANCER RESEARCH LA English DT Article ID POLYMORPHIC EPITHELIAL MUCIN; MONOCLONAL-ANTIBODY NDOG2; SURFACE-ANTIGENS; BREAST; TUMORS; REACTIVITY; PROTEIN; CANCER; CELLS; SERUM AB Recent studies have described the generation of a mAb, designated DF3-P, which reacts with underglycosylated precursors of the DF3/MUC1 mucin-like glycoprotein. The present work demonstrates that the epitope recognized by mAb DF3-P is expressed by cell lines derived from human epithelial ovarian carcinomas and not a teratocarcinoma. Indirect immunofluorescence assays of single-cell suspensions support expression of the DF3-P epitope on the surface of ovarian carcinomas. Immunofluorescence studies on chamber slides further demonstrate that the mAb DF3-P-reactive cells are present in clusters, We also demonstrate that I-125-labeled mAb DF3-P selectively localizes to human ovarian carcinoma xenografts in athymic mice. The percentage of injected I-125 dose/g tissue ranged between 10 and 17% for implanted CAOV-3 and OVCAR-3 tumors. Finally, the results of immunoperoxidase staining studies demonstrate that the DF3-P epitope is detectable in formalin-fixed sections of ovarian tumors and that mAb DF3-P exhibits little if any reactivity with normal surrounding tissues, Selective expression of the DF3-P epitope may be useful as a target for radioimaging or immunotherapeutic approaches to ovarian cancer. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PHARMACOL,BOSTON,MA 02115. CHU VAUDOIS,DIV NUCL MED,CTR PLURIDISCIPLINAIRE ONCOL,CH-1011 LAUSANNE,SWITZERLAND. NR 29 TC 22 Z9 22 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 1995 VL 1 IS 5 BP 565 EP 571 PG 7 WC Oncology SC Oncology GA TL080 UT WOS:A1995TL08000013 PM 9816017 ER PT J AU DISALVO, TG OGARA, PT AF DISALVO, TG OGARA, PT TI TORSADE-DE-POINTES CAUSED BY HIGH-DOSE INTRAVENOUS HALOPERIDOL IN CARDIAC PATIENTS SO CLINICAL CARDIOLOGY LA English DT Note DE HALOPERIDOL; TORSADE DE POINTES ID DE-POINTES; VENTRICULAR TACHYARRHYTHMIA AB Intravenous haloperidol is the agent of choice for controlling severe agitated delirium in seriously ill cardiac patients in many institutions. Prior reports have proposed that high-dose intravenous haloperidol may be without untoward effects in these patients. Recently, however, a few reports of significant QTc prolongation and torsade de pointes as complications of high-dose intravenous haloperidol therapy have appeared. The present report describes three patients with definite haloperidol-induced QTc prolongation and torsade. In each case, QTc prolongation preceded the arrhythmia and disappeared following the discontinuation of haloperidol. Neither electrolyte imbalance, therapy with other cardiac drugs, bradycardia, ischemia, left ventricular dysfunction, nor other known cause of torsade was present in these patients. It is hypothesized that QTc prolongation and torsade likely are idiosyncratic, unpredictable reactions to high-dose haloperidol in select patients. Careful serial electrocardiographic monitoring and prompt discontinuation of the drug should suffice to prevent this relatively uncommon, life-threatening complication of high-dose intravenous haloperidol. RP DISALVO, TG (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC FELLOWS OFF,CARDIAC UNIT,BULFINCH BASEMENT,FRUIT ST,BOSTON,MA 02114, USA. NR 18 TC 38 Z9 38 U1 0 U2 0 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA JBI BUILDING, MAHWAH, NJ 07430 SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAY PY 1995 VL 18 IS 5 BP 285 EP 290 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QW008 UT WOS:A1995QW00800011 PM 7628136 ER PT J AU VIRELLA, G MUNOZ, JF GALBRAITH, GMP GISSINGER, C CHASSEREAU, C LOPESVIRELLA, MF AF VIRELLA, G MUNOZ, JF GALBRAITH, GMP GISSINGER, C CHASSEREAU, C LOPESVIRELLA, MF TI ACTIVATION OF HUMAN MONOCYTE-DERIVED MACROPHAGES BY IMMUNE-COMPLEXES CONTAINING LOW-DENSITY-LIPOPROTEIN SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; SMOOTH-MUSCLE CELLS; HUMAN-ENDOTHELIAL-CELLS; HUMAN MONONUCLEAR-CELLS; POLYMORPHONUCLEAR LEUKOCYTES; VASCULAR ENDOTHELIUM; FATTY STREAKS; AORTIC INTIMA; FACTOR-ALPHA; TNF-ALPHA AB Human monocyte-derived macrophages are transformed into foam cells upon incubation with immune complexes containing low-density lipoprotein (LDL-IC), which are internalized predominantly through Fc gamma receptor-mediated phagocytosis. We investigated whether the FcR gamma-mediated ingestion of LDL-IC is associated with functional and metabolic activation of the ingesting cells. As end points we used the assay of released interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) and the reduction of nitroblue tetrazolium, which measures the respiratory burst. LDL-IC, added to the macrophages in concentrations known to induce intracellular accumulation of cholesterol esters and foam cell transformation, stimulated both the cytokine release and the respiratory burst more efficiently than control immune complexes. Time course studies of cytokine release and mRNA expression suggest that the synthesis and release of these two cytokines is under independent control. TNF alpha was released almost immediately after addition of LDL-IC to the macrophages, coinciding with increased early expression of TNF alpha mRNA, detectable 30 min after stimulation. In contrast, IL-1 beta was only increased in stimulated cell supernatants after 8 hr, and the onset of expression of IL-1 beta mRNA was also delayed in comparison to that of TNF alpha mRNA. We noted wide variations in the amounts of TNF alpha released by monocyte-derived macrophages from different donors. We also found that those macrophages which released higher levels of TNF alpha also took up higher amounts of I-125-labeled LDL, suggesting that the expression of LDL receptors by LDL-IC-stimulated macrophages is somehow linked to the degree of activation of these cells. Experiments using the measurement of the oxidative burst as end point corroborated that LDL-IC cause a general activation of macrophage functions. In conclusion, human macrophages are efficiently activated by LDL-IC, as reflected by the release of IL-1 beta and TNF alpha and by the release of oxygen active radicals. Thus, the presentation of LDL-IC to human macrophages induces a variety of metabolic and functional changes which are likely to contribute, directly or indirectly, to endothelial damage and progression of the atheromatous lesion. (C) 1995 Academic Press, Inc. C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. UNIV VIENNA,DEPT MED,VIENNA,AUSTRIA. RALPH H JOHNSON VET ADM MED CTR,CHARLESTON,SC 29425. RP VIRELLA, G (reprint author), MED UNIV S CAROLINA,DEPT MICROBIOL & IMMUNOL,CHARLESTON,SC 29425, USA. FU NHLBI NIH HHS [HL46815] NR 69 TC 55 Z9 60 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 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD MAY PY 1995 VL 75 IS 2 BP 179 EP 189 DI 10.1006/clin.1995.1069 PG 11 WC Immunology; Pathology SC Immunology; Pathology GA QT379 UT WOS:A1995QT37900012 PM 7704977 ER PT J AU STOLAR, MW AF STOLAR, MW TI CLINICAL MANAGEMENT OF THE NIDDM PATIENT - IMPACT OF THE AMERICAN-DIABETES-ASSOCIATION PRACTICE GUIDELINES, 1985-1993 SO DIABETES CARE LA English DT Article ID PHYSICIANS AB OBJECTIVE- To assess the impact of the American Diabetes Association's (ADA's) standards of care for patients with non-insulin-dependent diabetes mellitus (NIDDM) on practice patterns among university-based endocrine physicians and fellows. RESEARCH DESIGN AND METHODS- This study represents a retrospective chart-based review of 790 patients with NIDDM conducted by endocrine fellows in training at 42 academic institutions. By using an ADA guidelines-based questionnaire, patient management and adherence to the guidelines were assessed by reviewing charts dating greater than or equal to 3 years before, the year of, and 3 years after the guidelines' publication. All calculations were performed using the McNemar test, and all P values are two-sided. RESULTS- The ADA standards of care have not had the significant impact in the clinical training setting that was anticipated. Deficiencies were noted in all aspects of the diabetic patient encounter and did not improve significantly following publication of the guidelines, except in the areas of foot care, eye examination, and lipid screening. Major deficiencies exist in areas of quality assurance and chart documentation, and these did not improve over time. CONCLUSIONS- New strategies must be devised to increase awareness and implementation of these guidelines, both to enhance patient care and to improve the training of future diabetes caregivers. C1 NASSAU CTY MED CTR,E MEADOW,NY 11554. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,NEWARK,NJ 07103. UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. LOYOLA UNIV,MED CTR,CHICAGO,IL. WAYNE STATE UNIV,SCH MED,DETROIT,MI 48202. CLEVELAND CLIN FDN,CLEVELAND,OH. WILFORD HALL USAF MED CTR,LACKLAND AFB,TX. OREGON HLTH SCI UNIV,PORTLAND,OR. METROHLTH MED CTR,CLEVELAND,OH. BROWN UNIV,RHODE ISL HOSP,PROVIDENCE,RI. UNIV ALABAMA,BIRMINGHAM,AL. UNIV KENTUCKY,MED CTR,LEXINGTON,KY 40506. CEDARS SINAI MED CTR,LOS ANGELES,CA. MARSHALL UNIV,SCH MED,HUNTINGTON,WV. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA. UNIV MIAMI,SCH MED,CORAL GABLES,FL 33124. LOUISIANA STATE UNIV,MED CTR,NEW ORLEANS,LA. ST LOUIS UNIV,MED CTR,ST LOUIS,MO. SHADYSIDE HOSP,PITTSBURGH,PA. UNIV ARIZONA,TUCSON,AZ 85721. UNIV MINNESOTA,MINNEAPOLIS,MN. DUKE UNIV,MED CTR,DURHAM,NC 27706. TEMPLE UNIV,PHILADELPHIA,PA. INTERFAITH MED CTR,BROOKLYN,NY. UNIV SO CALIF,LOS ANGELES,CA 90089. UNIV MISSOURI,COLUMBIA,MO. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX. MAINE MED CTR,PORTLAND,ME. INDIANA UNIV,BLOOMINGTON,IN 47405. UNIV MASSACHUSETTS,MED CTR,AMHERST,MA 01003. BETH ISRAEL HOSP,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA. UNIV IOWA,IOWA CITY,IA 52242. UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR. JOHN L MCCLELLAN MEM VET ADM MED CTR,LITTLE ROCK,AR. LOUISIANA STATE UNIV,MED CTR,SHREVEPORT,LA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV KANSAS,MED CTR,LAWRENCE,KS 66045. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. CHICAGO MED CTR,CHICAGO,IL. UNIV CALIF DAVIS,DAVIS,CA 95616. PENN STATE UNIV,MILTON S HERSHEY MED CTR,HERSHEY,PA 17033. MED COLL WISCONSIN,MILWAUKEE,WI. TEMPLE UNIV HOSP & MED SCH,PHILADELPHIA,PA. BAYLOR COLL MED,HOUSTON,TX. SAN JUAN CITY HOSP,SAN JUAN,PR. NEW ENGLAND DEACONESS HOSP,JOSLIN DIABET CTR,BOSTON,MA. SUNY STONY BROOK,STONY BROOK,NY 11794. UNIV FLORIDA,HLTH SCI CTR,GAINESVILLE,FL 32611. OCHSNER MED FDN,NEW ORLEANS,LA. OHIO STATE UNIV HOSP,COLUMBUS,OH. EMORY UNIV,SCH MED,ATLANTA,GA. COLUMBIA UNIV,COLL PHYS & SURG,NEW YORK,NY 10027. UNIV WISCONSIN,MADISON,WI 53706. SCOTT & WHITE MEM HOSP & CLIN,TEMPLE,TX. HOSP UNIV PENN,PHILADELPHIA,PA. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. NR 9 TC 44 Z9 45 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 1995 VL 18 IS 5 BP 701 EP 707 DI 10.2337/diacare.18.5.701 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QW299 UT WOS:A1995QW29900017 PM 8586012 ER PT J AU PITMAN, MB SZYFELBEIN, WM AF PITMAN, MB SZYFELBEIN, WM TI SIGNIFICANCE OF ENDOTHELIUM IN THE FINE-NEEDLE ASPIRATION BIOPSY DIAGNOSIS OF HEPATOCELLULAR-CARCINOMA SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE LIVER; CYTOLOGY; METASTASES; CIRRHOSIS AB We reviewed fine-needle aspiration biopsies (FNAB) of hepatocellular carcinoma (HCC) (n = 35), benign hepatic processes (n = 35), cholangiocarcinoma (CC) (n = 6), and metastatic tumors (n = 100) to evaluate the significance of endothelium present either peripherally-wrapping around groups of cells, (peripheral endothelium (PE)), or transgressing sheets of cells (transgressing endothelium (TE)), in distinguishing these lesions. These patterns were assessed as absent, focal, or prominent. Thirty-three of 35 (94%) HCCs contained either focal or prominent PE or TE, compared to only 3 of 35 (9%) benign hepatocytic lesions. Only one benign lesion contained a prominent endothelial component (TE only). Two cases of HCC failed to contain endothelium, one fibrolamellar variant and one well-differentiated HCC. These differences were statistically significant (P < 10(-5), sensitivity 94%, specificity 91%, and positive predictive value [PPV] 92%). Neither pattern of endothelium was present in any CC or metastatic tumor. These differences were also statistically significant (P < 10(-5), sensitivity 94%, and specificity and PVP 100%). We conclude that the presence of endothelium, at least focally in either one or both distinctive patterns, is highly sensitive and specific for HCC and aides in distinguishing it from benign hepatocytic lesions, CC, and metastases. Diagn Cytopathol 1995;12:208-214. (C) 1995 Wiley-Liss, Inc. RP PITMAN, MB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,FRUIT STR,BOSTON,MA 02114, USA. NR 0 TC 32 Z9 32 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 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD MAY PY 1995 VL 12 IS 3 BP 208 EP 214 DI 10.1002/dc.2840120304 PG 7 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA QU911 UT WOS:A1995QU91100003 PM 7621715 ER PT J AU CRAIG, WA AF CRAIG, WA TI INTERRELATIONSHIP BETWEEN PHARMACOKINETICS AND PHARMACODYNAMICS IN DETERMINING DOSAGE REGIMENS FOR BROAD-SPECTRUM CEPHALOSPORINS SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article ID GRAM-NEGATIVE BACTEREMIA; THIGH-INFECTION; TISSUE-LEVELS; ANTIBIOTICS; CEFOTAXIME AB The broad-spectrum cephalosporins exhibit time-dependent bactericidal activity and produce prolonged postantibiotic effects only with staphylococci. The duration of time that serum levels exceed the minimum inhibitory concentration (MIG) is the important pharmacodynamic parameter correlating with efficacy for these drugs. Maximal efficacy for cephalosporins in several animal infection models is approached when serum levels are above the MIC for 60%-70% of the dosing interval for Enterobacteriaceae and streptococci and for 40%-50% of the dosing interval for Staphylococcus aureus. Based on MIC(90) values of 0.5 mu g/ml for enteric bacilli and 4 mu g/ml for S. aureus, these time above MIC goals can be easily met in infected and/or elderly patients following 1-2 g of cefotaxime at 12-h intervals. Full knowledge of the interrelationships between pharmacokinetics and pharmacodynamics is important for determining effective dosage regimens for the broad-spectrum cephalosporins. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR, DEPT MED, MADISON, WI USA. UNIV WISCONSIN, DEPT MED, MADISON, WI USA. NR 31 TC 388 Z9 408 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 EI 1879-0070 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD MAY-JUN PY 1995 VL 22 IS 1-2 BP 89 EP 96 DI 10.1016/0732-8893(95)00053-D PG 8 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA RL195 UT WOS:A1995RL19500012 PM 7587056 ER PT J AU SCHMIDT, J COMPTON, CC RATTNER, DW LEWANDROWSKI, K WARSHAW, AL AF SCHMIDT, J COMPTON, CC RATTNER, DW LEWANDROWSKI, K WARSHAW, AL TI LATE HISTOPATHOLOGIC CHANGES AND HEALING IN AN IMPROVED RODENT MODEL OF ACUTE NECROTIZING PANCREATITIS SO DIGESTION LA English DT Article DE PANCREATITIS; HISTOPATHOLOGY; MODEL; RAT; HEALING; INJURY ID ACUTE HEMORRHAGIC-PANCREATITIS; RAT; NECROSIS; ABSCESS; THERAPY; LIGHT AB Studies of experimental pancreatitis have generally focussed on early time points rather than the stages of healing and resolution or scarring. We recently characterized a new pancreatitis model of moderate severity by combining intraductal infusion of very low concentrations of glycodeoxycholic acid with intravenous caerulein. This study evaluates late histopathologic changes and gross complications in this pancreatitis model compared to the traditionally used high-dose bile salt model in rats. After 14 days, histopathologic features of caerulein pancreatitis were not different from saline controls. High-dose intraductal bile salt infusion resulted in widespread chronic inflammation, acinar dilation and atrophy, marked reactive stromal proliferation, and ductular budding with periductal fibrosis. In contrast, animals receiving low-dose intraductal bile salt infusion combined with intravenous caerulein demonstrated a moderate degree of chronic inflammation and acinar atrophy along with an intermediate degree of periductal fibrosis and stromal reaction. We conclude that due to its moderate degree of injury, this model may be useful for the study of tissue injury and repair following acute pancreatitis. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. NR 38 TC 9 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0012-2823 J9 DIGESTION JI Digestion PD MAY-JUN PY 1995 VL 56 IS 3 BP 246 EP 252 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RF260 UT WOS:A1995RF26000012 PM 7544747 ER PT J AU DEWS, S KAPLAN, J WINNER, E AF DEWS, S KAPLAN, J WINNER, E TI WHY NOT SAY IT DIRECTLY - THE SOCIAL FUNCTIONS OF IRONY SO DISCOURSE PROCESSES LA English DT Article ID VERBAL IRONY; PRETENSE AB In three experiments, we investigated the social payoffs of speaking ironically. In Experiment 1, participants rated videotaped ironic remarks (criticisms and compliments) as funnier than literal remarks, but no more or less status enhancing. In Experiment 2, participants listened to audiotaped ironic criticisms and compliments. Ironic compliments were rated as more insulting than literal compliments, but ironic criticisms were found to be less insulting than literal criticisms. In Experiment 3, participants read literal or ironic criticisms. Ironic comments were rated as more amusing than literal ones. When irony was directed at the addressee's poor performance, it served to protect the addressee's face by softening the criticism. When irony was directed at the addressee's offensive behavior, it served to protect the speaker's face by showing the speaker as less angry and more in control. In addition, irony damaged the speaker-addressee relationship less than did literal criticism. Taken together, these studies suggest that speakers choose irony over literal language in order to be funny, to soften the edge of an insult, to show themselves to be in control of their emotions, and to avoid damaging their relationship with the addressee. C1 UNIV CALIF BERKELEY,BERKELEY,CA 94720. BOSTON COLL,CHESTNUT HILL,MA 02167. HARVARD UNIV,PROJECT ZERO,CAMBRIDGE,MA 02138. RP DEWS, S (reprint author), MASSACHUSETTS GEN HOSP,PSYCHIAT GERONTOL 149-9124,BLDG 149 13TH ST,BOSTON,MA 02129, USA. NR 18 TC 105 Z9 105 U1 0 U2 15 PU ABLEX PUBL CORP PI NORWOOD PA 355 CHESTNUT ST, NORWOOD, NJ 07648 SN 0163-853X J9 DISCOURSE PROCESS JI Discl. Process. PD MAY-JUN PY 1995 VL 19 IS 3 BP 347 EP 367 PG 21 WC Psychology, Educational; Psychology, Experimental SC Psychology GA RL189 UT WOS:A1995RL18900002 ER PT J AU ZHU, L ENDERS, G LEES, JA BEIJERSBERGEN, RL BERNARDS, R HARLOW, E AF ZHU, L ENDERS, G LEES, JA BEIJERSBERGEN, RL BERNARDS, R HARLOW, E TI THE PRB-RELATED PROTEIN P107 CONTAINS 2 GROWTH SUPPRESSION DOMAINS - INDEPENDENT INTERACTIONS WITH E2F AND CYCLIN CDK COMPLEXES SO EMBO JOURNAL LA English DT Article DE CELL CYCLE; FUNCTIONAL DOMAINS; GROWTH SUPPRESSION; P107 ID TRANSCRIPTION FACTOR E2F; RETINOBLASTOMA PROTEIN; CELL-CYCLE; GENE-PRODUCT; MAMMALIAN FIBROBLASTS; VIRAL ONCOPROTEINS; BINDING; RB; TRANSACTIVATION; EXPRESSION AB Unregulated expression of either the retinoblastoma protein (pRB) or the related protein p107 can cause growth arrest of sensitive cells in the G(1) phase of the cell cycle. However, growth arrests mediated by p107 and pRB are not identical. Through structure - function and co-expression analyses we have dissected the p107 molecule into two domains that independently are able to block cell cycle progression. One domain corresponds to the sequences needed for interaction with the transcription factor E2F, and the other corresponds to the interaction domain for cyclin A or cyclin E complexes. In cervical carcinoma cell line C33A, which was previously shown to be sensitive to p107 but resistant to pRB growth suppression, only the cyclin binding domain is active as a growth suppressor. Furthermore, we show that these two independent domains are functional in untransformed mouse fibroblasts. Together, these results provide experimental evidence for the presence of two functional domains in p107 and pinpoint an important functional difference between p107 and pRB. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MIT,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA 02139. NETHERLANDS CANC INST,DIV MOLEC CARCINOGENESIS,1066 CX AMSTERDAM,NETHERLANDS. RP ZHU, L (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 50 TC 126 Z9 127 U1 0 U2 0 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 MAY 1 PY 1995 VL 14 IS 9 BP 1904 EP 1913 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QX744 UT WOS:A1995QX74400007 PM 7743997 ER PT J AU XIONG, YT XIE, LY ABOUSAMRA, AB AF XIONG, YT XIE, LY ABOUSAMRA, AB TI SIGNALING PROPERTIES OF MOUSE AND HUMAN CORTICOTROPIN-RELEASING FACTOR (CRP) RECEPTORS - DECREASED COUPLING EFFICIENCY OF HUMAN TYPE-II CRF RECEPTOR SO ENDOCRINOLOGY LA English DT Article ID ADENYLATE-CYCLASE ACTIVITY; ANTERIOR-PITUITARY-CELLS; HORMONE-RELATED PEPTIDE; EXPRESSION CLONING; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; CYCLIC-AMP; INOSITOL TRISPHOSPHATE; CALCITONIN RECEPTOR; PARATHYROID-HORMONE AB CRF is the primary neuroregulator of the function of the hypothalamic-pituitary-adrenal axis. We have recently cloned a mouse CRF receptor (mCRF-R) complementary DNA (cDNA) from an AtT-20 cell cDNA library by polymerase chain reaction. To compare the functions of mCRF-R to those of the human type I and type II CRF receptors (hCRF-RI and hCRF-RII), cDNAs were cloned into the expression vector pcDNA1 and transfected into COS-7 cells. CRF binding and CRF-stimulated cAMP accumulation as well as phosphoinositide hydrolysis were measured. Scatchard analysis of the binding of I-125-labeled [Tyr(0)]r/hCRF ([I-125]CRF) to, COS-7 cells expressing mCRF-R and hCRF-RI cDNAs revealed the same apparent K-d (9 nM). In contrast, the apparent binding K-d for hCRF-RII was 20 nM CRF. Maximal stimulatory concentrations (1 mu M) of rat/human CRF-(1-41) (r/hCRF) increased cAMP accumulation in COS-7 cells transfected with mCRF-R, hCRF-RI, and hCRF-RII cDNA. plasmid (10 mu g each) from basal values of 8-19 pmol/10(5) cells . 15 min to 84 +/- 10, 87 +/- 16, and 45 +/- 16 pmol/10(5) cells . 15 min, respectively The EC(50) values of r/hCRF-stimulated cAMP accumulation in COS-7 cells expressing mCRF-R and hCRF-RI cDNAs were similar at 0.4 +/- 0.2 and 0.7 +/- 0.2 nM, respectively. Conversely, the EC(50) of r/hCRF-stimulated cAMP accumulation in hCRF-RII-transfected COS-7 cells was 47.5 +/- 18.9 nM. As the level of expression of hCRF-RII was lower than that of hCRF-RI, we compared r/hCRF-stimulated cAMP accumulation in COS-7 cells expressing low and high levels of hCRF-RI. The EC(50) for r/hCRF-stimulated cAMP accumulation in COS-7 cells transfected with hCRF-RI did not change when receptor expression was varied by a factor of 1- to 8.4-fold. In contrast, the EC(50) for r/hCRF-stimulated cAMP accumulation mediated by hCRF-RII was at least 100-fold higher than that mediated by the hCRF-RI in COS-7 cells, which suggests poor coupling between hCRF-RII and adenylate cyclase. Inositol phosphate (IF) levels were also determined in mCRF-R, hCRF-RI, and hCRF-RII cDNA-transfected COS-7 cells stimulated with increasing concentrations of r/hCRF. r/hCRF-stimulated IPs accumulation was dose dependent in COS-7 cells expressing mCRF-R and hCRF-RI using 100 and 1000 nM r/hCRF. Concentrations of 10 (or less) nM r/hCRF had no effect on IP generation. hCRF-RII did not mediate stimulation of IP even at 1000 nar r/hCRF. These data indicate that mCRF-R and hCRF-RI have similar binding and signaling properties. In contrast, hCRF-RII did not increase phosphoinositide tw?lover. Additionally, hCRF-RII had a 1.8-fold lower expression level, 2.1-fold lower apparent binding affinity, and at least 100-fold lower coupling to stimulation of cAMP accumulation in COS-7 cells. C1 MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [NIDDK 45020] NR 32 TC 60 Z9 61 U1 0 U2 1 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 MAY PY 1995 VL 136 IS 5 BP 1828 EP 1834 DI 10.1210/en.136.5.1828 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QU628 UT WOS:A1995QU62800003 PM 7720627 ER PT J AU CINCOTTA, AH KNISELY, TL LANDRY, RJ MIERS, WR GUTIERREZ, PJA ESPERANZA, P MEIER, AH AF CINCOTTA, AH KNISELY, TL LANDRY, RJ MIERS, WR GUTIERREZ, PJA ESPERANZA, P MEIER, AH TI THE IMMUNOREGULATORY EFFECTS OF PROLACTIN IN MICE ARE TIME OF DAY DEPENDENT SO ENDOCRINOLOGY LA English DT Article ID ANTERIOR-PITUITARY-CELLS; TUMOR-NECROSIS-FACTOR; GROWTH-HORMONE; TEMPORAL SYNERGISM; BROMOCRIPTINE TREATMENT; PROTEIN-PHOSPHORYLATION; MESOCRICETUS-AURATUS; STIMULATES PROLACTIN; SEASONAL CONDITIONS; PROTHYMOSIN-ALPHA AB The effects of timed administration of PRL on immune activities were investigated in male BALB/c mice. Ten daily injections of PRL (1 mg/kg) were made 0/24, 4, 8, 12, 16, or 20 h after light onset (HALO). On day II, spleen cells were harvested between 1-3 HALO and cocultured with gamma-irradiated C57BL/6 spleen cells for 5 days, and proliferative responses to alloantigen were assayed (mixed lymphocyte reaction). When given in vivo at 4-12 HALO, PRL strongly stimulated proliferation by more than a-fold, whereas PRL injections when given at 24 HALO substantially inhibited proliferation and had no effect when given at 16-20 HALO. When endogenous PRL secretion was stimulated for 7 days with injections of domperidone or 5-hydroxytryptophan, the splenocyte response increased by 48% and 64%, respectively, when injections were given at 9-10 HALO, but did not increase when they were given at 23-0 HALO. Inhibition of endogenous PRL secretion for 7 days with bromocriptine (2.5 mg/kg . day) inhibited splenocyte responsiveness by 40% when injected at 9 HALO, but had no effect when administered at 0 HALO. Furthermore, such bromocriptine treatment inhibited T- and B-cell mitogenic responses to Concanavalin-A (by 48%) and lipopolysaccharide (38%) when administered at 10, but not 0, HALO. In a manner similar to mixed lymphocyte reaction responses, daily PRL injections for 10 days at 11 HALO stimulated (40%) the in vivo delayed-type hypersensitivity response to antigen (azobenzenearsonate), whereas injections at 0 HALO were nonstimulatory. Bromocriptine treatment (1.5 mg/kg . day) suppressed the delayed-type hypersensitivity response (43% less than the control value) when administered at 10-12 HALO, but had no effect when administered at light onset. Timed PRL injections for 28 days in adult mice increased (42%) the total thymic cell number when administered at 11 HALO, but had no effect when injected at 0 HALO. Together, these results show that immunocyte responsiveness to PRL is time of day dependent. Thus, these findings support an essential and heretofore unrecognized circadian role in PRL regulation of immunity. C1 MASSACHUSETTS GEN HOSP, WELLMAN LABS PHOTOMED, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT DERMATOL, BOSTON, MA 02114 USA. LOUISIANA STATE UNIV, DEPT ZOOL & PHYSIOL, BATON ROUGE, LA 70803 USA. NR 71 TC 15 Z9 15 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 MAY PY 1995 VL 136 IS 5 BP 2163 EP 2171 DI 10.1210/en.136.5.2163 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QU628 UT WOS:A1995QU62800049 PM 7720666 ER PT J AU EMMONS, KM THOMPSON, B FENG, Z HEBERT, JR HEIMENDINGER, J LINNAN, L AF EMMONS, KM THOMPSON, B FENG, Z HEBERT, JR HEIMENDINGER, J LINNAN, L TI DIETARY-INTAKE AND EXPOSURE TO ENVIRONMENTAL TOBACCO-SMOKE IN A WORKSITE POPULATION SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE DIET; ENVIRONMENTAL TOBACCO SMOKE; NUTRITION WORKSITES ID LUNG-CANCER; ALPHA-TOCOPHEROL; PASSIVE SMOKING; BETA-CAROTENE; VITAMIN-A; RISK; NONSMOKERS AB Objectives: Nonsmokers who live with smokers have poorer dietary habits than those who live in nonsmoking households. This relationship may be due to shared lifestyle patterns by spouses and family members. However, in order to fully understand the nature of this relationship, it is also important to examine the association between diet and exposure to environmental tobacco smoke (ETS) at the workplace. Further, blue collar workers' patterns of exposure to ETS both at work and at home have not been studied. The goal of this study is to examine the dietary intake of manufacturing workers as it relates to exposure to ETS at work and at home. Methods: The Working Well Trial surveyed 10 833 nonsmokers about a variety of health behaviors, including smoking, dietary behaviors, and ETS exposure. Results. Nonsmokers who had ETS exposure in their household had significantly lower intake of all target micronutrients, compared to those without household exposure. Exposure to ETS at the workplace was associated with lower intakes of vitamin C and fruits and vegetables, but not the other micronutrients examined. Conclusions: Exposure to ETS was associated with poorer dietary habits. Household exposure was a stronger predictor of intake than was workplace exposure. Because of the antagonistic effects of many components of a healthful diet in relation to the harmful effects of tobacco smoke, these findings have relevance larger than either ETS exposure or diet considered singly. C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98101. UNIV MASSACHUSETTS,SCH MED,WORCESTER,MA 01655. NCI,ROCKVILLE,MD 20852. MIRIAM HOSP,PROVIDENCE,RI 02906. RP EMMONS, KM (reprint author), HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,DIV COMMUNITY BASED RES,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [U01CA51686, U01CA5A51671, U01 CA51687] NR 38 TC 24 Z9 26 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD MAY PY 1995 VL 49 IS 5 BP 336 EP 345 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA QY954 UT WOS:A1995QY95400004 PM 7664719 ER PT J AU CHEW, FS BROWN, JH PALMER, WE KATTAPURAM, SV AF CHEW, FS BROWN, JH PALMER, WE KATTAPURAM, SV TI CT-GUIDED ASPIRATION IN POTENTIALLY INFECTED TOTAL HIP REPLACEMENTS COMPLICATED BY HETEROTOPIC BONE SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Note DE HIP, ARTHROGRAPHY; ARTHROGRAPHY, TECHNIQUE AB Aspiration of the hip joint in the setting of a potentially infected total hip replacement is occasionally unsuccessful under fluoroscopic guidance because of periarticular heterotopic bone. Of 136 consecutive patients with total hip replacements who were referred to the radiology department for hip aspiration because of suspected infection, successful intraarticular needle placement was achieved in 132 (97%) under fluoroscopic guidance. In four (3%) cases, the attempted aspiration was unsuccessful because heterotopic bone prevented the needle tip from reaching the joint; a second attempt was performed successfully under CT guidance. CT confirmed that the anterior approach was completely blocked by heterotopic bone and that there was a gap in this bone elsewhere through which a needle could be passed into the joint. The increased cost of CT was modest because it was necessary in only a small percentage of patients. RP CHEW, FS (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. OI Chew, Felix/0000-0003-2711-2013 NR 0 TC 8 Z9 8 U1 0 U2 4 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAY PY 1995 VL 20 IS 1 BP 72 EP 74 DI 10.1016/0720-048X(95)00606-Q PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RK783 UT WOS:A1995RK78300017 PM 7556260 ER PT J AU PAHLAVANI, MA HARRIS, MD MOORE, SA WEINDRUCH, R RICHARDSON, A AF PAHLAVANI, MA HARRIS, MD MOORE, SA WEINDRUCH, R RICHARDSON, A TI THE EXPRESSION OF HEAT-SHOCK PROTEIN-70 DECREASES WITH AGE IN LYMPHOCYTES FROM RATS AND RHESUS-MONKEYS SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVATION; DIETARY RESTRICTION; MITOGEN STIMULATION; DIPLOID FIBROBLASTS; IMMUNE FUNCTION; MESSENGER-RNA; T-CELLS; STRESS; HSP70 AB The ability of cells to express heat shock proteins in response to a stress such as heat is universal to all organisms and is believed to play a critical protective role. Therefore, it was of interest to determine the influence of aging on the ability of lymphocytes to express the heat shock protein hsp70 in response to a heat shock (42.5 degrees C for 1 h). Splenic lymphocytes isolated from old (24-26 months) rats showed a marked decrease in the induction of hsp70 protein levels or hsp70 synthesis when compared to lymphocytes isolated from young (4-5 months) rats. An age-related decrease in the induction of hsp70 levels by heat also was observed in peripheral lymphocytes isolated from rhesus monkeys, The decline with age in the induction of hsp70 by lymphocytes from rats was paralleled by a decrease in the induction of hsp70 mRNA and the nuclear transcription of hsp70. In addition, it was found that the ability of extracts from heat-shocked lymphocytes to bind the heat shock element (HSE) decreased approximately 50% with age. Therefore, it appears that the reduced ability of lymphocytes from old rats to express hsp70 in response to a heat shock occurs at the level of transcription because of an alteration in the ability of the heat shock transcription factor to bind the HSE on the promoter of the hsp70 gene. The age-related decrease in the induction of hsp70 appears to be physiologically important because the viability of spleen lymphocytes exposed to high temperatures decreases significantly with age. (C) 1995 Academic Press, Inc. C1 AUDIE L MURPHY MEM VET ADM MED CTR, CTR GERIATR RES EDUC & CLIN 182, SAN ANTONIO, TX 78284 USA. UNIV TEXAS, HLTH SCI CTR, DEPT MED, SAN ANTONIO, TX 78284 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, CTR GERIATR RES EDUC & CLIN, MADISON, WI 53705 USA. UNIV WISCONSIN, DEPT MED, MADISON, WI 53705 USA. FU NIA NIH HHS [AG00165, AG00205, AG01548] NR 43 TC 48 Z9 48 U1 0 U2 0 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 EI 1090-2422 J9 EXP CELL RES JI Exp. Cell Res. PD MAY PY 1995 VL 218 IS 1 BP 310 EP 318 DI 10.1006/excr.1995.1160 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA QW998 UT WOS:A1995QW99800037 PM 7737368 ER PT J AU RAVID, K KUTER, DJ ROSENBERG, RD AF RAVID, K KUTER, DJ ROSENBERG, RD TI RMIL-6 STIMULATES THE TRANSCRIPTIONAL ACTIVITY OF THE RAT PF4 GENE SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE INTERLEUKIN-6; PLATELET FACTOR 4; MEGAKARYOCYTES ID ERYTHROLEUKEMIA CELL-LINE; PLATELET PRODUCTION; HUMAN INTERLEUKIN-6; FACTOR-II; MEGAKARYOCYTES; ERYTHROPOIETIN; EXPRESSION; PROMOTER; GROWTH; HEL AB We have examined the effect of recombinant murine interleukin-6 (rmIL-6) on megakaryocytopoiesis in a liquid rat bone marrow culture system. At concentrations of IL-6 up to 100 ng/mL, no stimulation of megakaryocyte ploidy was observed. However, transient expression studies revealed that IL-6 did have a significant effect on the transcriptional activity of the platelet factor four (PF4) gene, a platelet alpha-granule protein gene uniquely expressed in megakaryocytes. Furthermore, when the amount of PF4 message was directly measured in megakaryocytes, it was increased three-fold in response to IL-6. We also note that the PF4 promoter contains a hexamer, CTGGGA, described as the IL-6-responsive element in other genes. Our results suggest that the platelet progeny of IL-6-stimulated megakaryocytes may have altered alpha-granule constituents. C1 MIT,DEPT BIOL,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,HEMATOL UNIT,BOSTON,MA 02114. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. FU NHLBI NIH HHS [HL 39753] NR 32 TC 2 Z9 2 U1 0 U2 0 PU CARDEN JENNINGS PUBL COLTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAY PY 1995 VL 23 IS 5 BP 397 EP 401 PG 5 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA QW623 UT WOS:A1995QW62300003 PM 7720812 ER PT J AU CARDOSO, AA WATT, SM BATARD, P LI, ML HATZFELD, A GENEVIER, H HATZFELD, J AF CARDOSO, AA WATT, SM BATARD, P LI, ML HATZFELD, A GENEVIER, H HATZFELD, J TI AN IMPROVED PANNING TECHNIQUE FOR THE SELECTION OF CD34(+) HUMAN BONE-MARROW HEMATOPOIETIC-CELLS WITH HIGH RECOVERY OF EARLY PROGENITORS SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE CD34; HEMATOPOIETIC STEM CELLS; PANNING; CLONOGENIC ASSAY; PURIFICATION ID HUMAN GENE-THERAPY; MONOCLONAL-ANTIBODY; POSITIVE SELECTION; EXPRESSION; GLYCOPROTEIN; QUIESCENCE; COLONIES; BINDING; RELEASE AB The human hematopoietic pluripotent repopulating ''stem cell'' is thought to be present within a minor subpopulation of CD34(+) cells. This has not been definitively shown, although the more primitive CD34(+) cell subset contains precursors for all lymphoid and nonlymphoid cell lineages. When purifying CD34(+) cells, it is important to recover these early progenitors, which are more strongly immunoadsorbent to the separation devices. Using a commercialized panning system (AIS CELLector flasks), we observed that a high degree of purity requires a thorough washing procedure so that cells not binding or weakly binding to CD34 antibodies are removed. High recoveries can be obtained if the adherent cells are then efficiently detached by a 2-hour incubation in culture medium without added cytokines. In this way, we can routinely obtain 93.5 +/- 3.4% purity of CD34(+) cells with a 74% yield of the multipotent colony-forming units (CFU-GEMM). Complete recovery of the putative ''stem cell,'' or at least the early progenitor cell compartment (CD34 CD38(low/-) CD34(+) Thy-1(+) cells), is also obtained. More than 30% of these cells can generate day-ldr colonies in vitro. Comparable results were obtained when the separation was scaled up for clinical application using appropriate large-scale devices. The various incubation times of the procedure can be easily adjusted to the work schedule. This renders the procedure easy to handle, efficient, safe, and, because the cells can be observed under light microscopy, easy to control. C1 JOHN RADCLIFFE HOSP,INST MOLEC MED,MRC,MOLEC HAEMATOL UNIT,OXFORD OX3 9DU,ENGLAND. IRSC,BIOL CELLULAIRE & MOLEC FACTEURS CROISSANCE LAB,CNRS,UPR 272,VILLEJUIF,FRANCE. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. INST CHILD HLTH,CELLULAR IMMUNOL UNIT,LONDON,ENGLAND. RI HATZFELD, Antoinette/I-2341-2013; HATZFELD, Jacques/I-2346-2013 OI HATZFELD, Antoinette/0000-0002-9147-533X; HATZFELD, Jacques/0000-0002-3468-6659 NR 26 TC 32 Z9 32 U1 0 U2 3 PU CARDEN JENNINGS PUBL COLTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAY PY 1995 VL 23 IS 5 BP 407 EP 412 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA QW623 UT WOS:A1995QW62300005 PM 7536682 ER PT J AU BONVENTRE, JV WITZGALL, R AF BONVENTRE, JV WITZGALL, R TI KID-1, A KIDNEY TRANSCRIPTION FACTOR SO EXPERIMENTAL NEPHROLOGY LA English DT Review DE TRANSCRIPTION FACTORS; KRUPPEL ASSOCIATED BOXES; KID-1; ACUTE RENAL FAILURE; RENAL DEVELOPMENT; KIDNEY ZINC FINGERS RP BONVENTRE, JV (reprint author), MASSACHUSETTS GEN HOSP EAST,MED SERV,149-4002 13TH STR,BOSTON,MA 02129, USA. FU NIDDK NIH HHS [DK 38452, DK 39773] NR 0 TC 6 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-7782 J9 EXP NEPHROL JI Exp. Nephrol. PD MAY-JUN PY 1995 VL 3 IS 3 BP 159 EP 164 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA QZ669 UT WOS:A1995QZ66900002 PM 7620854 ER PT J AU MOSER, AJ ABEDIN, MZ GIURGIU, DIN ROSLYN, JJ AF MOSER, AJ ABEDIN, MZ GIURGIU, DIN ROSLYN, JJ TI OCTREOTIDE PROMOTES GALLBLADDER ABSORPTION IN PRAIRIE DOGS - A POTENTIAL CAUSE OF GALLSTONES SO GASTROENTEROLOGY LA English DT Article ID LONG-TERM TREATMENT; SOMATOSTATIN ANALOG; BILIARY CALCIUM; ION-TRANSPORT; CYCLIC-AMP; CHOLESTEROL; SECRETION; BILE; SMS-201-995; NUCLEATION AB Background/Aims: Gallstone formation during octreotide administration has been causally linked to increased biliary concentrations of calcium, protein, and total lipids, all purported prolithogenic factors. These changes may be caused by octreotide-induced gallbladder stasis or a direct effect of octreotide on gallbladder absorption. We tested the hypothesis that octreotide stimulates gallbladder ion and water transport. Methods: Prairie dog gallbladders were mounted in Ussing chambers and bathed in oxygenated Ringer's solution. Electrophysiological parameters were recorded, and unidirectional Na+, Cl-, and H2O fluxes were measured before and after serosal exposure to 50 nmol/L octreotide. Results: Octreotide exposure caused a significant decrease in transepithelial short-circuit current and potential difference and an increase in tissue resistance compared with baseline. These alterations in electrophysiological parameters coincided with changes in ion transport. Octreotide stimulated net Na+ and H2O absorption and converted the gallbladder from a state of Cl- secretion to one of Cl- absorption by increasing mucosal to serosal fluxes. Octreotide effects on ion transport were blocked by 4,4'-diisothiocynostilbene-2,2'-disulfonic acid and amiloride and reversed by theophylline. Conclusions: Octreotide may promote gallstone formation by inducing gallbladder stasis and by directly increasing gallbladder absorption, which may act synergistically to increase the concentration of prolithogenic factors in bile and to facilitate nucleation and stone growth. C1 MED COLL PENN,DEPT SURG,PHILADELPHIA,PA 19129. UNIV CALIF LOS ANGELES,SCH MED,DEPT SURG,LOS ANGELES,CA 90024. VET AFFAIRS MED CTR,RES SERV,SEPULVEDA,CA. HAHNEMANN UNIV,PHILADELPHIA,PA 19102. VET AFFAIRS MED CTR,PHILADELPHIA,PA. NR 36 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 1995 VL 108 IS 5 BP 1547 EP 1555 DI 10.1016/0016-5085(95)90705-X PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QV545 UT WOS:A1995QV54500027 PM 7729647 ER PT J AU PETEET, J GREENBERG, B AF PETEET, J GREENBERG, B TI MARITAL CRISES IN ONCOLOGY PATIENTS - AN APPROACH TO INITIAL INTERVENTION BY PRIMARY CLINICIAN SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID CANCER-PATIENTS; THERAPY; FAMILIES; ILLNESS; COUPLES AB Life-threatening illnesses such as cancer may precipitate marital crises in vulnerable relationships, and oncology clinicians often feel uncertain about how to approach them. This paper presents a framework for initial intervention based on the nature of the principal threat to the relationship. Immature relationships need distance and support for their identity as a couple; hostile dependent couples need to find consensus in order to structure communication; physically abusive relationships require monitoring in order to promote safety; and estranged couples need help in understanding their disappointment and identifying available support. Clinicians working in oncology can help couples in crisis by promoting a realistic balance of independence and dependence, clarifying the complexity of factors contributing to the crisis, considering referral for couples treatment, communicating with the ream while respecting patients' confidences, and by choosing clear and compatible clinical roles. Primary clinicians can stabilize and treat marital crises, but need access to medically knowledgeable couples' therapists. C1 BRIGHAM & WOMENS HOSP,DEPT PSYCHOSOCIAL SERV & SOCIAL WORK,DANA FARBER CANC INST,BOSTON,MA 02115. RP PETEET, J (reprint author), BRIGHAM & WOMENS HOSP,DIV PSYCHIAT,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 36 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD MAY PY 1995 VL 17 IS 3 BP 201 EP 207 DI 10.1016/0163-8343(95)00028-P PG 7 WC Psychiatry SC Psychiatry GA RA373 UT WOS:A1995RA37300008 PM 7649464 ER PT J AU CRYNS, VL YI, SM TAHARA, H GAZ, RD ARNOLD, A AF CRYNS, VL YI, SM TAHARA, H GAZ, RD ARNOLD, A TI FREQUENT LOSS OF CHROMOSOME ARM IP DNA IN PARATHYROID ADENOMAS SO GENES CHROMOSOMES & CANCER LA English DT Article ID DINUCLEOTIDE REPEAT POLYMORPHISM; ENDOCRINE NEOPLASIA TYPE-2; LINKAGE MAP; HUMAN NEUROBLASTOMAS; CANDIDATE ONCOGENE; TUMOR-SUPPRESSOR; BREAST-CANCER; 1P DELETION; N-MYC; GENE AB Two molecular defects have been described in parathyroid adenomas: rearrangement and overexpression of the PRADI/cyclin DI oncogene and allelic loss of chromosome II DNA, often including the multiple endocrine neoplasia type 1 (MENI) putative tumor suppressor gene region. In an effort to identify additional parathyroid tumor suppressor genes, we examined 25 parathyroid adenomas for tumor-specific allelic loss of polymorphic DNA loci located near known or candidate tumor suppressor genes. Control leukocyte DNA from all 25 patients was heterozygous for 1 or more of the 9 chromosome markers examined. Allelic loss at 1 or more of these informative loci on chromosome was observed in 10 of 25 (40%) adenomas. Although many tumors lost extensive regions on chromosome I, all but one of these tumors had allelic loss of distal Ip (Ip32-pter); four tumors also lost loci on Iq. Allelic loss at IIq13, the site of the MENI gene, was detected in 5 of 21 (24%) informative cases, including 3 with Ip loss. In contrast, allelic loss was rarely observed at loci on 9q and 10p and was not observed at loci on 3p, 3q, 4p, 5q, 12q, 14q, 18q, 22q, or Xp. In summary, clonal allelic loss of loci on chromosome arm Ip is a frequent feature of parathyroid adenomas, implying that inactivation of a tumor suppressor gene(s) on Ip commonly contributes to their pathogenesis. (C) 1995 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE ONCOL LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [1F32CA-0938101, 1K08CA-0172-01A1]; NIDDK NIH HHS [DK-11794] NR 63 TC 93 Z9 93 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 1995 VL 13 IS 1 BP 9 EP 17 DI 10.1002/gcc.2870130103 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA QW163 UT WOS:A1995QW16300002 PM 7541648 ER PT J AU WU, CT HOWE, M AF WU, CT HOWE, M TI A GENETIC-ANALYSIS OF THE SUPPRESSOR-2 OF ZESTE COMPLEX OF DROSOPHILA-MELANOGASTER SO GENETICS LA English DT Review ID POSITION-EFFECT VARIEGATION; POSTERIOR-SEX COMBS; HETEROCHROMATIN-ASSOCIATED PROTEIN; DOSAGE-DEPENDENT MODIFIERS; POLYCOMB-GROUP GENE; CHROMOSOME-BINDING-SITES; BETA-TUBULIN GENE; BITHORAX COMPLEX; WHITE GENE; HOMEOTIC GENES AB The zeste(1) (z(1)) mutation of Drosophila melanogaster produces a mutant yellow eye color instead of the wild-type red. Genetic and molecular data suggest that z(1) achieves this change by altering expression of the wild-type white gene in a manner that exhibits transvection effects. There exist suppressor and enhancer mutations that modify the z(1) eye color, and this paper summarizes our studies of those belonging to the Suppressor 2 of zeste complex [Su(z)2-C]. The Su(z)2-C consists of at least three subregions called Psc (Posterior sex combs), Su(z)2 and Su(z)2D (Distal). The products of these subregions are proposed to act at the level of chromatin. Complementation analyses predict that the products are functionally similar and interacting. The alleles of Psc define two overlapping phenotypic classes, the hopeful and hapless. The distinctions between these two classes and the intragenic complementation seen among some of the Psc alleles are consistent with a multidomain structure for the product of Psc. Psc is a member of the homeotic Polycomb group of genes. A general discussion of the Polycomb and trithorax group of genes, position-effect variegation, transvection, chromosome pairing and chromatin structure is presented. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RP WU, CT (reprint author), HARVARD UNIV,SCH MED,DEPT GENET,200 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 190 TC 56 Z9 57 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 1995 VL 140 IS 1 BP 139 EP 181 PG 43 WC Genetics & Heredity SC Genetics & Heredity GA QV521 UT WOS:A1995QV52100013 PM 7635282 ER PT J AU RACHMILEWITZ, D STAMLER, JS BACHWICH, D KARMELI, F ACKERMAN, Z PODOLSKY, DK AF RACHMILEWITZ, D STAMLER, JS BACHWICH, D KARMELI, F ACKERMAN, Z PODOLSKY, DK TI ENHANCED COLONIC NITRIC-OXIDE GENERATION AND NITRIC-OXIDE SYNTHASE ACTIVITY IN ULCERATIVE-COLITIS AND CROHNS-DISEASE SO GUT LA English DT Article DE ULCERATIVE COLITIS; CROHNS DISEASE; NITRIC OXIDE ID MOUSE MACROPHAGES; L-ARGININE; PEROXYNITRITE; INHIBITION; INFLAMMATION; EXPRESSION; CLONING; INJURY; DAMAGE; CELLS AB Recent studies have suggested that nitric oxide (NO .), the product of nitric oxide synthase in inflammatory cells, may play a part in tissue injury and inflammation through its oxidative metabolism. In this study the colonic generation of oxides of nitrogen (NOx) and nitric oxide synthase determined in ulcerative Crohn's disease. Colonic biopsy specimens were obtained from inflammatory bowel disease patients and from normal controls. Mucosal explants were cultured in vitro for 24 hours and NOx generation was determined. Nitric oxide synthase activity was monitored by the conversion of [H-3]-L-arginine to citrulline. Median NOx generation by inflamed colonic mucosa of patients with active ulcerative colitis and Crohn's colitis was 4.2- and 8.1-fold respectively higher than that by normal human colonic mucosa. In ulcerative colitis and Crohn's colitis nitric oxide synthase activity was 10.0- and 3.8-fold respectively higher than in normal subjects. Colonic NOx generation is significantly decreased by methylprednisolone and ketotifen. The decrease in NOx generation by cultured colonic mucosa induced by methylprednisolone suggests that NO synthase activity is induced during the culture and the steroid effect may contribute to its therapeutic effect. Enhanced colonic NOx generation by stimulated nitric oxide synthase activity in ulcerative colitis and Crohn's disease may contribute to tissue injury. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DIV RESP & CARDIOVASC,BOSTON,MA 02115. RP RACHMILEWITZ, D (reprint author), HADASSAH UNIV HOSP,DEPT MED,POB 24035,IL-91240 JERUSALEM,ISRAEL. FU NIDDK NIH HHS [5P30 DK 43351] NR 29 TC 276 Z9 280 U1 0 U2 4 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 MAY PY 1995 VL 36 IS 5 BP 718 EP 723 DI 10.1136/gut.36.5.718 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QX126 UT WOS:A1995QX12600017 PM 7541008 ER PT J AU COPELAND, PM ANDERSON, B AF COPELAND, PM ANDERSON, B TI DIABETES-MELLITUS AND EATING DISORDERS SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID BULIMIA; WOMEN C1 JOSLIN DIABET CTR,BOSTON,MA 02115. N SHORE MED CTR,EATING DISORDERS PROGRAM,SALEM,MA. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. NR 16 TC 1 Z9 1 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 1995 VL 3 IS 1 BP 36 EP 40 DI 10.3109/10673229509017162 PG 5 WC Psychiatry SC Psychiatry GA RA048 UT WOS:A1995RA04800004 PM 9384926 ER PT J AU MURPHY, JM AF MURPHY, JM TI WHAT HAPPENS TO DEPRESSED MEN SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID GENERAL-POPULATION; STIRLING COUNTY; ANXIETY; DISORDERS; PREVALENCE; DIAGNOSIS; MORTALITY; SEX RP MURPHY, JM (reprint author), MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PSYCHIAT EPIDEMIOL UNIT,705 WARREN BLDG,BOSTON,MA 02114, USA. NR 17 TC 20 Z9 20 U1 8 U2 8 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 1995 VL 3 IS 1 BP 47 EP 49 DI 10.3109/10673229509017165 PG 3 WC Psychiatry SC Psychiatry GA RA048 UT WOS:A1995RA04800007 PM 9384928 ER PT J AU LOPEZ, CA OLSON, ES ADAMS, JC MOU, K DENHARDT, DT DAVIS, RL AF LOPEZ, CA OLSON, ES ADAMS, JC MOU, K DENHARDT, DT DAVIS, RL TI OSTEOPONTIN EXPRESSION DETECTED IN ADULT COCHLEAE AND INNER-EAR FLUIDS SO HEARING RESEARCH LA English DT Article DE INNER EAR; CHOROID PLEXUS; IN SITU HYBRIDIZATION; IMMUNOHISTOCHEMISTRY; WESTERN BLOT ID SECRETED PHOSPHOPROTEIN-1 SPP-1; INSITU HYBRIDIZATION; NEOPLASTIC TRANSFORMATION; BONE PHOSPHOPROTEIN; MOLECULAR-CLONING; TUMOR PROMOTER; MESSENGER-RNA; RAT BONE; PROTEIN; KIDNEY AB Localization of protein epitopes and mRNA expression showed that there was a wide-spread distribution of osteopontin (OPN) within the membranous labyrinth of the adult mammalian cochlea. Immunoreaction product and mRNA were found within the stria vascularis, VIIIth cranial nerve, spiral ligament and limbus. Only specific cell types within these regions contained abundant OPN mRNA or protein, the main cell type being fibrocytes that populate the spiral limbus and spiral ligament. Epithelial cells that line the luminal surface of the stria vascularis (marginal cells) and neurons that compose the vestibular and auditory ganglia also showed high opn expression. The pattern of anti-OPN staining within the membranous labyrinth was comparable to that observed in tissues such as gall bladder, breast and kidney. In those tissues, luminal epithelial cells, corresponding to the marginal cells of the stria vascularis, may be responsible for manufacturing and secreting OPN into the luminal fluids. Consistent with those observations, we detected OPN epitopes in cochlear fluids withdrawn from the scala media and tympani of the cochlea. We found that the protein species in cochlear fluid differed from those present in cerebrospinal fluid (CSF) suggesting that OPN exists in tissue-specific isoforms that may correspond to particular cellular functions. C1 RUTGERS STATE UNIV,DEPT BIOL SCI,PISCATAWAY,NJ 08855. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. FU NIDCD NIH HHS [DC01295] NR 50 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 1995 VL 85 IS 1-2 BP 210 EP 222 DI 10.1016/0378-5955(95)00046-7 PG 13 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA RE527 UT WOS:A1995RE52700021 PM 7559176 ER PT J AU NG, LL SWEENEY, FP SICZKOWSKI, M DAVIES, JE QUINN, PA KROLEWSKI, B KROLEWSKI, AS AF NG, LL SWEENEY, FP SICZKOWSKI, M DAVIES, JE QUINN, PA KROLEWSKI, B KROLEWSKI, AS TI NA+-H+ ANTIPORTER PHENOTYPE, ABUNDANCE, AND PHOSPHORYLATION OF IMMORTALIZED LYMPHOBLASTS FROM HUMANS WITH HYPERTENSION SO HYPERTENSION LA English DT Article DE HYPERTENSION, ESSENTIAL; SODIUM-HYDROGEN EXCHANGER; PROTONS; PHOSPHORYLATION ID SODIUM-PROTON EXCHANGE; SMOOTH-MUSCLE CELLS; MOLECULAR-CLONING; SKELETAL-MUSCLE; GROWTH-FACTOR; OKADAIC ACID; RAT; EXPRESSION; MEMBRANE; ACTIVATION AB Previous studies have demonstrated an elevated Na+-H+ exchanger activity in various cell types from patients with essential hypertension. The phenotype of an increased maximal transport capacity is preserved in Epstein-Barr virus immortalized lymphoblasts from hypertensive patients. The mechanisms underlying this abnormality are unclear. In this study, we used lymphoblasts from hypertensive patients and normotensive control subjects with and without a family history of hypertension to determine (1) Na+-H+ exchanger activity using fluorometry with the pH indicator 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein, (2) Nac-Hc exchanger isoform 1 abundance with specific polyclonal antibodies, and (3) Na+-H+ exchanger phosphorylation by immunoprecipitation of the P-32-labeled transporter. Na+-H+ exchanger activity (in millimoles per liter per minute) measured when pH(i) was clamped at 6.0 was significantly higher in cells from hypertensive patients (18.8+/-0.6, P<.001) and those subjects with a family history of hypertension (16.4+/-0.6, P<.001) compared with normotensive control subjects (12.9+/-0.6). Exchanger abundance was identical in all three groups of subjects, indicating that increased activity in the hypertensive group was due to an elevated turnover number of the exchanger. Na+-H+ exchanger phosphorylation in quiescent cells was significantly elevated in cells from hypertensive patients (1.58+/-0.16, P<.001) compared with control subjects (1.00+/-0.07), and cells from normotensive subjects with a hypertensive family history showed intermediate values (1.23+/-0.14). Identical changes in Na+-H+ exchanger function and phosphorylation have been demonstrated in vascular smooth muscle cells from spontane ously hypertensive rats. Our findings suggest that the elevated Na+-H+ exchanger activity in cells from human hypertensive patients is not associated with an increased exchanger abundance but may be related to increased exchanger phosphorylation. C1 LEICESTER ROYAL INFIRM,DEPT MED & THERAPEUT,LEICESTER,LEICS,ENGLAND. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA. JOSLIN DIABET CTR,BOSTON,MA. FU NIDDK NIH HHS [DK 41526, DK 36836]; Wellcome Trust NR 26 TC 55 Z9 55 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 1995 VL 25 IS 5 BP 971 EP 977 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QY005 UT WOS:A1995QY00500010 PM 7737735 ER PT J AU FREEMAN, GJ BOUSSIOTIS, VA ANUMANTHAN, A BERNSTEIN, GM KE, XY RENNERT, PD GRAY, GS GRIBBEN, JG NADLER, LM AF FREEMAN, GJ BOUSSIOTIS, VA ANUMANTHAN, A BERNSTEIN, GM KE, XY RENNERT, PD GRAY, GS GRIBBEN, JG NADLER, LM TI B7-1 AND B7-2 DO NOT DELIVER IDENTICAL COSTIMULATORY SIGNALS, SINCE B7-2 BUT NOT B7-1 PREFERENTIALLY COSTIMULATES THE INITIAL PRODUCTION OF IL-4 SO IMMUNITY LA English DT Article ID T-CELL ACTIVATION; ANTIGEN-PRESENTING CELL; DIFFERENTIAL REGULATION; CYTOKINE PRODUCTION; COUNTER-RECEPTOR; LYMPHOCYTES-T; INTERLEUKIN-4; EXPRESSION; CD28; MOLECULES AB The functional necessity for two CD28 counterreceptors (B7-1 and B7-2) is presently unknown. B7-1 and B7-2 equivalently costimulate IL-2 and interferon-gamma (IFN gamma) production and IL-2 receptor alpha and gamma chain expression. B7-2 induces significantly more IL-4 production than B7-1, with the greatest difference seen in naive T cells. Repetitive costimulation of CD4(+) CD45RA(+) T cells with B7-2 results in moderate levels of both IL-4 and IL-2, whereas repetitive costimulation with B7-1 results in high levels of IL-2 and low levels of IL-4. Therefore, B7-1 and B7-2 costimulation mediate distinct outcomes, since B7-2 provides an initial signal to induce naive T cells to become IL-4 producers, thereby directing the immune response more towards Th0/Th2, whereas B7-1 is a more neutral differentiative signal. C1 REPLIGEN CORP,CAMBRIDGE,MA 02139. RP FREEMAN, GJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 34183, CA 40416] NR 61 TC 509 Z9 514 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 1995 VL 2 IS 5 BP 523 EP 532 DI 10.1016/1074-7613(95)90032-2 PG 10 WC Immunology SC Immunology GA QZ430 UT WOS:A1995QZ43000009 PM 7538442 ER PT J AU MARASCO, WA AF MARASCO, WA TI INTRACELLULAR ANTIBODIES (INTRABODIES) AS RESEARCH REAGENTS AND THERAPEUTIC MOLECULES FOR GENE-THERAPY SO IMMUNOTECHNOLOGY LA English DT Review DE INTRACELLULAR IMMUNIZATION; AIDS; GENE TRANSFER; TARGETED GENE DISRUPTION; CANCER THERAPY; HIV-1; T CELL ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; MURINE MONOCLONAL-ANTIBODIES; TAT-MEDIATED TRANSACTIVATION; PHAGE DISPLAY LIBRARIES; BY-PASSING IMMUNIZATION; AMINO-ACID SUBSTITUTION; HIV-1 MATRIX PROTEIN; MESSENGER-RNA; BINDING-PROTEIN C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [P30 AI28691, AI28785] NR 182 TC 69 Z9 70 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1380-2933 J9 IMMUNOTECHNOLOGY JI Immunotechnology PD MAY PY 1995 VL 1 IS 1 BP 1 EP 19 DI 10.1016/1380-2933(95)00001-1 PG 19 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA TF482 UT WOS:A1995TF48200002 PM 9373329 ER PT J AU GOLLI, SJ TSAI, M WERSHIL, BK TAM, SY COSTA, JJ AF GOLLI, SJ TSAI, M WERSHIL, BK TAM, SY COSTA, JJ TI REGULATION OF MOUSE AND HUMAN MAST-CELL DEVELOPMENT, SURVIVAL AND FUNCTION BY STEM-CELL FACTOR, THE LIGAND FOR THE C-KIT RECEPTOR SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 20th Symposium of the Collegium-Internationale-Allergologicum on Molecular and Clinical Implications for Allergy in the 21st-Century CY SEP 25-29, 1994 CL NANTUCKET, MA SP Collegium Int Allergologicum DE ALLERGY; ANAPHYLAXIS; APOPTOSIS; BCL-2; C-KIT; IGE ANTIBODY; MAST-CELL-DEFICIENT MICE; MAST CELLS; MASTOCYTOSIS; PROTOONCOGENES ID HEMATOPOIETIC GROWTH-FACTOR; TYROSINE KINASE RECEPTOR; CONNECTIVE-TISSUE-TYPE; MEDIATOR RELEASE; SI-LOCUS; INVIVO; EXPRESSION; APOPTOSIS; IL-3 AB Stem cell factor (SCF), the ligand for the receptor (SCFR) that is encoded by the c-kit proto-oncogene, has many important effects in mouse and human mast cell development, survival, and function. SCF can promote mast cell survival by suppressing apoptosis, induce mast cell hyperplasia in murine rodents, experimental primates and humans, directly induce SCFR-dependent mast cell mediator release, and significantly modulate the extent of mast cell activation by Fc epsilon RI-dependent mechanisms. These findings raise several clinical issues and, in some cases, point to potentially significant therapeutic opportunities. C1 BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. CHILDRENS HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL,BOSTON,MA. RP GOLLI, SJ (reprint author), BETH ISRAEL HOSP,DEPT PATHOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 21 TC 2 Z9 2 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD MAY-JUL PY 1995 VL 107 IS 1-3 BP 51 EP 53 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA RM261 UT WOS:A1995RM26100012 ER PT J AU DVORAK, AM MORGAN, ES MONAHANEARLEY, RA ESTRELLA, P SCHLEIMER, RP WELLER, PF TEPPER, RI LICHTENSTEIN, LM GALLI, SJ AF DVORAK, AM MORGAN, ES MONAHANEARLEY, RA ESTRELLA, P SCHLEIMER, RP WELLER, PF TEPPER, RI LICHTENSTEIN, LM GALLI, SJ TI ANALYSIS OF MAST-CELL ACTIVATION USING DIAMINE OXIDASE-GOLD ENZYME-AFFINITY ULTRASTRUCTURAL CYTOCHEMISTRY SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 20th Symposium of the Collegium-Internationale-Allergologicum on Molecular and Clinical Implications for Allergy in the 21st-Century CY SEP 25-29, 1994 CL NANTUCKET, MA SP Collegium Int Allergologicum DE MAST CELL; PIECEMEAL DEGRANULATION; HISTAMINASE; DIAMINE OXIDASE; ENZYME-AFFINITY CYTOCHEMISTRY; ULTRASTRUCTURE; HUMAN; INTERLEUKIN-4 TRANSGENIC MOUSE; HISTAMINE; HISTAMINE SECRETION IN VIVO ID BASOPHILIC LEUKOCYTES; DEGRANULATION; DISEASE AB We review a new technique - diamine oxidase (DAO)-gold ultrastructural enzyme-affinity labeling - which we developed to localize histamine in subcellular sites of mast cells. The DAO-gold method showed that isolated human lung mast cells contained abundant histamine in their cytoplasmic granules, a conclusion which was verified by a large number of specificity controls. We also studied mast-cell-rich eyelid lesions which developed in interleukin-4 transgenic mice. The DAO-gold method demonstrated histamine in the electron-dense granules of mast cells in these lesions, but little or no histamine was detected in the swollen, empty granules of mast cells undergoing piecemeal degranulation. This new enzyme-affinity-gold method has permitted the first ultrastructural localization of histamine in subcellular sites of routinely prepared electron microscopy samples. The method has also permitted the first morphological studies of histamine secretion in vivo and has demonstrated that such secretion can be associated with the ultrastructural changes of piecemeal degranulation. C1 BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. JOHNS HOPKINS ASTHMA & ALLERGY CTR,DIV CLIN IMMUNOL & ALLERGY,BALTIMORE,MD. RP DVORAK, AM (reprint author), BETH ISRAEL HOSP,DEPT PATHOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NIAID NIH HHS [AI-33372] NR 15 TC 9 Z9 9 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD MAY-JUL PY 1995 VL 107 IS 1-3 BP 87 EP 89 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA RM261 UT WOS:A1995RM26100023 PM 7542108 ER PT J AU WERSHIL, BK FURUTA, GT LAVIGNE, JA CHOUDHURY, AR WANG, ZS GALLI, SJ AF WERSHIL, BK FURUTA, GT LAVIGNE, JA CHOUDHURY, AR WANG, ZS GALLI, SJ TI DEXAMETHASONE AND CYCLOSPORINE-A SUPPRESS MAST CELL-LEUKOCYTE CYTOKINE CASCADES BY MULTIPLE MECHANISMS SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 20th Symposium of the Collegium-Internationale-Allergologicum on Molecular and Clinical Implications for Allergy in the 21st-Century CY SEP 25-29, 1994 CL NANTUCKET, MA SP Collegium Int Allergologicum DE CYCLOSPORINE A; CYTOKINES; DEXAMETHASONE; HISTAMINE; INFLAMMATION, CUTANEOUS; MAST CELLS; TUMOR NECROSIS FACTOR-ALPHA ID MEDIATOR RELEASE; INHIBITION; ASTHMA; FK506; MOUSE; IGE AB Based on in vitro findings with mouse mast cells and in vivo findings in mice, we report that dexamethasone or cyclosporin A can have at least three actions which interfere with the pathogenesis IgE-, mast-cell-, and cytoltine-dependent inflammatory reactions: suppression of the IgE-dependent increase in tumor necrosis factor (TNF)-alpha mRNA by mast cells, inhibition of the IgE-dependent production of TNF-alpha protein by mast cells, and diminution of the responsiveness of target cells to TNF-alpha. Our findings in mice raise the possibility that similar actions of these agents in humans may account for some of the clinical efficacy of corticosteroids and cyclosporin A in allergic diseases. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. CHILDRENS HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL,BOSTON,MA. RP WERSHIL, BK (reprint author), BETH ISRAEL HOSP,DEPT PATHOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NIAID NIH HHS [AI22674, AI23990]; NIDDK NIH HHS [P01 DK 33506] NR 13 TC 19 Z9 19 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD MAY-JUL PY 1995 VL 107 IS 1-3 BP 323 EP 324 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA RM261 UT WOS:A1995RM26100099 PM 7613160 ER PT J AU SANDERSON, IR WALKER, WA AF SANDERSON, IR WALKER, WA TI ESTABLISHMENT OF A HUMAN FETAL SMALL-INTESTINAL EPITHELIAL-CELL LINE SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 20th Symposium of the Collegium-Internationale-Allergologicum on Molecular and Clinical Implications for Allergy in the 21st-Century CY SEP 25-29, 1994 CL NANTUCKET, MA SP Collegium Int Allergologicum DE HUMAN ENTEROCYTES; KARYOTYPE; NONMALIGNANT; KERATIN; MATRIGEL ID RAT SMALL-INTESTINE; DIFFERENTIATION RP SANDERSON, IR (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEV GASTROENTEROL LAB,BOSTON,MA 02129, USA. FU FIC NIH HHS [F06-TWO 1865]; NICHD NIH HHS [R01-HD12437]; NIDDK NIH HHS [P01-DK33506] NR 7 TC 6 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD MAY-JUL PY 1995 VL 107 IS 1-3 BP 396 EP 397 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA RM261 UT WOS:A1995RM26100135 PM 7542092 ER PT J AU SUGIE, K NAKAMURA, K TESHIGAWARA, K DIAMOND, MS SPRINGER, TA NAKAMURA, Y LEONARD, WJ UCHIDA, A YODOI, J AF SUGIE, K NAKAMURA, K TESHIGAWARA, K DIAMOND, MS SPRINGER, TA NAKAMURA, Y LEONARD, WJ UCHIDA, A YODOI, J TI ACTIVATION OF NATURAL-KILLER-CELLS BY THE MAB YTA-1 THAT RECOGNIZES LEUKOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE LFA-1; NATURAL KILLER; YT CELL LINE ID LARGE GRANULAR LYMPHOCYTES; T-CELLS; MONOCLONAL-ANTIBODY; ALPHA-SUBUNIT; INTERLEUKIN-2 RECEPTOR; ADHESION GLYCOPROTEIN; COUNTER-RECEPTOR; NK CLONES; INTEGRIN; MOLECULES AB The mAb YTA-1, which brightly stains CD3(-)CD16(+) large granular lymphocytes (LGL)/natural killer (NK) cells and CD8(+) T cells by immunofluorescence, is specific for leukocyte function-associated antigen (LFA)-1. Some mAbs recognizing the LFA-1 alpha chain (CD11a) or LFA-1 beta chain (CD18) inhibited the binding of YTA-1 to peripheral blood mononuclear cells, YTA-1 mAb could be chemically cross-linked to 170 and 96 kDa molecules, whose molecular weights correspond to those of LFA-1 alpha and beta respectively, YTA-1 bound to COS-7 cells co-transfected with CD11a and CD18 cDNAs, but not to untransfected cells, Reactivities of YTA-1 to K562 cells transfected with LFA-1 alpha and beta (CD11a/CD18) cDNAs and to CHO cells transfected with Mac-1 (CD11b/CD18) or p150, 95 (CD11c/CD18) cDNAs strongly suggest that YTA-1 recognizes either LFA-1 alpha or an epitope formed by a combination of LFA-1 alpha and beta. Treatment of fresh CD3(-)CD16(+) LGL with YTA-1 augmented cytolytic activity and induced proliferation. F(ab')(2) fragments of YTA-1 augmented NK cytotoxicity, indicating that the NK activating signal was transmitted through LFA-1 without involvement of Fc gamma receptor III, In contrast, the other mAbs against LFA-1 could not activate NK cells. These results collectively indicate that YTA-1 recognizes a unique epitope of LFA-1, which is involved in activation of fresh NK cells. C1 KYOTO UNIV,CTR RADIAT BIOL,DEPT LATE EFFECT STUDIES,SAKYO KU,KYOTO 60601,JAPAN. KYOTO UNIV,INST VIRUS RES,DEPT BIOL RESPONSES,SAKYO KU,KYOTO 60601,JAPAN. KYOTO UNIV,CHEST DIS RES INST,DEPT IMMUNOL,SAKYO KU,KYOTO 60601,JAPAN. HARVARD UNIV,SCH MED,DEPT PATHOL,CTR BLOOD RES,BOSTON,MA 02115. NHLBI,IRP,OD,PULM & MOLEC IMMUNOL SECT,BETHESDA,MD 20892. NR 34 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 1995 VL 7 IS 5 BP 763 EP 769 PG 7 WC Immunology SC Immunology GA QZ064 UT WOS:A1995QZ06400006 PM 7547703 ER PT J AU WONG, TY SUSTER, S BOUFFARD, D FLYNN, SD JOHNSON, RA BARNHILL, RL MIHM, MC AF WONG, TY SUSTER, S BOUFFARD, D FLYNN, SD JOHNSON, RA BARNHILL, RL MIHM, MC TI HISTOLOGIC SPECTRUM OF CUTANEOUS INVOLVEMENT IN PATIENTS WITH MYELOGENOUS LEUKEMIA INCLUDING THE NEUTROPHILIC DERMATOSES SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID SWEETS SYNDROME; GRANULOCYTIC SARCOMA; MYELOPROLIFERATIVE DISORDERS; MYELOMONOCYTIC LEUKEMIA; PYODERMA GANGRENOSUM; CUTIS; SKIN AB Background. Cutaneous manifestations of myeloid leukemia can be specific or nonspecific. The study was designed to determine the prevalence and histologic appearance of cutaneous lesions in patients with myeloid leukemia acid various myeloproliferative disorders. Methods. The histologic changes of cutaneous lesions in 52 patients with myelodysplastic syndrome, polycythemia vera, and myeloid, myelomonocytic, or monocytic leukemia are presented in this study. Results. Two types of cellular infiltrates were identified. In the first group, the mast common pattern was a diffuse involvement by the leukemic cells through the entire dermis with preservation of a ''grenz zone'' in the superficial dermis. Two cases exhibited a Kaposi's sarcoma-like pattern, with prominent slit-like blood-filled spaces lined by myeloblasts against a fibrocellular stroma. The second group of lesions was characterized by dense, neutrophilic dermal infiltrates resembling acute neutrophilic dermatosis (Sweet's syndrome) or pyoderma gangrenosum. In two of these cases, scattered immature blast cells admired with the mature neutrophilic elements were identified. Conclusions. Awareness of these different morphologic features and application of special stains are of value in the evaluation of suspicious cutaneous infiltrates in patients with myeloid leukemia and various myeloproliferative disorders. C1 MASSACHUSETTS GEN HOSP,DIV DERMATOPATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MT SINAI MED CTR,DEPT PATHOL,MIAMI,FL. UNIV MIAMI,SCH MED,MIAMI,FL. YALE NEW HAVEN MED CTR,DEPT PATHOL,NEW HAVEN,CT 06504. YALE UNIV,SCH MED,NEW HAVEN,CT. NEW ENGLAND DEACONESS HOSP,DEPT DERMATOL,BOSTON,MA 02215. RP WONG, TY (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 27 TC 25 Z9 26 U1 0 U2 1 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON ST, PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD MAY PY 1995 VL 34 IS 5 BP 323 EP 329 DI 10.1111/j.1365-4362.1995.tb03612.x PG 7 WC Dermatology SC Dermatology GA QW655 UT WOS:A1995QW65500006 PM 7607792 ER PT J AU HETH, CA MARESCALCHI, PA YE, LY AF HETH, CA MARESCALCHI, PA YE, LY TI IP3 GENERATION INCREASES ROD OUTER SEGMENT PHAGOCYTOSIS BY CULTURED ROYAL-COLLEGE OF SURGEONS RETINAL-PIGMENT EPITHELIUM SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE RETINAL PIGMENT EPITHELIUM; PHAGOCYTOSIS; ROD OUTER SEGMENTS; INOSITOL TRIPHOSPHATE; IP3; RCS RATS ID RAT RETINA; CELLS; PHOSPHORYLATION; DYSTROPHY; INGESTION; BOVINE AB Purpose. To measure outer segment phagocytosis in cultures of Royal College of Surgeons (RCS) rat retinal pigment epithelium (RPE) that have been treated with carbachol. Carbachol treatment of RCS RPE results in an increase in the second messenger inositol triphosphate, which mimics that observed in normal RPE after interaction with rod outer segments (ROS). Methods. Cultures of RCS RPE were phagocytically challenged with isolated rat ROS for 2 hours. Carbachol (1 mM) was added to some cultures to stimulate inositol triphosphate synthesis, and incubation continued for 30 minutes at 37 degrees C. Inositol triphosphate concentration was measured by radioreceptor assay. Bound and ingested outer segments were quantified by double immunofluorescent staining. Ingestion of outer segment membranes was confirmed by electron microscopy and immunogold staining. Results. Carbachol treatment was associated with a rapid and temporary increase in inositol triphosphate levels. Royal College of Surgeons rat RPE phagocytically challenged with outer segments and treated with carbachol showed significantly higher ingestion (34%) compared to untreated RCS RPE (9%)(P < 0.05). Conclusions. Exposure of cultured RCS RPE to carbachol increases the intracellular concentration of inositol triphosphate and enhances phagocytosis of bound ROS. These results support the hypothesis that the phagocytic defect in RCS RPE is related to an abnormality in the generation of inositol triphosphate as a second messenger after outer segment recognition and binding. RP HETH, CA (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY08091] NR 25 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1995 VL 36 IS 6 BP 984 EP 989 PG 6 WC Ophthalmology SC Ophthalmology GA QW241 UT WOS:A1995QW24100004 PM 7730032 ER PT J AU FARAONE, SV CHEN, WJ WARBURTON, R BIEDERMAN, J MILBERGER, S TSUANG, MT AF FARAONE, SV CHEN, WJ WARBURTON, R BIEDERMAN, J MILBERGER, S TSUANG, MT TI GENETIC-HETEROGENEITY IN ATTENTION-DEFICIT HYPERACTIVITY DISORDER (ADHD) - GENDER, PSYCHIATRIC COMORBIDITY, AND MATERNAL ADHD SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID CONDUCT DISORDER; SEX-DIFFERENCES; FAMILIAL ASSOCIATION; RISK-FACTORS; CHILDREN; CHILDHOOD; PSYCHOPATHOLOGY; PARENTS; BOYS; TRANSMISSION AB The authors examined the siblings of 140 attention-deficit hyperactivity disorder(ADHD) and 120 control probands and classified families as antisocial if the proband had conduct disorder or a parent had antisocial personality. Partial support was found for the hypothesis that the ADHD gender effect would be limited to antisocial families. Boys had an increased risk for ADHD compared with girls, but only among siblings from antisocial families. The effect size for predicting ADHD in siblings of probands was greater for maternal compared with paternal ADHD, but only for families exhibiting antisocial disorders. Strong support was found for the hypothesis that, compared with siblings from nonantisocial families, those from antisocial families would have more psychopathology (ADHD, depression, substance use, and conduct disorders). The presence of antisocial disorders signals a distinct subtype of ADHD. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. MASSACHUSETTS MENTAL HLTH CTR,HARVARD MED SCH,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP FARAONE, SV (reprint author), MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT ACC725,FRUIT ST,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-41314-01A2] NR 68 TC 122 Z9 125 U1 2 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 1995 VL 104 IS 2 BP 334 EP 345 DI 10.1037//0021-843X.104.2.334 PG 12 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA QW681 UT WOS:A1995QW68100009 PM 7790635 ER PT J AU KERN, RS GREEN, MF GOLDSTEIN, MJ AF KERN, RS GREEN, MF GOLDSTEIN, MJ TI MODIFICATION OF PERFORMANCE ON THE SPAN OF APPREHENSION, A PUTATIVE MARKER OF VULNERABILITY TO SCHIZOPHRENIA SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Note ID CARD SORTING TEST; CHILDREN; REMEDIATION; DEFICITS AB The present study examined the effectiveness of 2 types of intervention (contingent monetary reinforcement and enhanced instruction) on span of apprehension performance. Forty chronic schizophrenia inpatients (26 men, 14 women) received a 3- and 12-letter array version of the span of apprehension task 4 times: baseline, intervention, immediate posttest, and 1-week follow-up. All patients were randomly assigned to 1 of 4 groups that differed according to method of intervention: repeat administration, monetary reinforcement only, instruction only, and monetary reinforcement plus instruction. The combination of monetary reinforcement plus instruction yielded significantly greater improvement in span accuracy than the other methods of intervention. These findings suggest that performance on this putative vulnerability indicator can be modified through certain interventions. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BEHAV SCI,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PSYCHOL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. FU NIMH NIH HHS [MH 43292, MH 14584] NR 24 TC 47 Z9 48 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 1995 VL 104 IS 2 BP 385 EP 389 DI 10.1037//0021-843X.104.2.385 PG 5 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA QW681 UT WOS:A1995QW68100015 PM 7790641 ER PT J AU LYONS, MJ TOOMEY, R KREMEN, WS FARAONE, SV YEUNG, AS TSUANG, MT AF LYONS, MJ TOOMEY, R KREMEN, WS FARAONE, SV YEUNG, AS TSUANG, MT TI CORRELATES OF PSYCHOSIS PRONENESS IN RELATIVES OF SCHIZOPHRENIC-PATIENTS SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Note ID PERSONALITY-DISORDERS; SCHIZOTYPY; BORDERLINE; INDICATORS; VALIDITY; FAMILY AB The Magical Ideation Scale (MIS), Perceptual Aberration Scale (PABS), Social Anhedonia Scale (SAS), and Physical Anhedonia Scale (PAS) were administered to 98 relatives of schizophrenic patients along with a measure of personality disorders (the Personality Diagnostic Questionnaire-Revised). Hierarchical regression analysis indicated that the schizotypal and borderline personality disorder (PD) scales explained significant variance in both the MIS and PABS; the avoidant PD scale also explained significant variance in the PABS. The schizoid, paranoid, and avoidant PD scales explained significant variance in the SAS. Sibling intraclass correlations indicated a significant heritability of 0.62 for the PABS. C1 HARVARD INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA. BROCKTON W ROXBURY VET AFFAIRS MED CTR,HARVARD MED SCH,DEPT PSYCHIAT,BROCKTON,MA. MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP LYONS, MJ (reprint author), BOSTON UNIV,DEPT PSYCHOL,64 CUMMINGTON ST,BOSTON,MA 02401, USA. RI Lyons, Michael/B-6119-2011; OI Lyons, Michael/0000-0001-6516-9219; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH43518, MH41874, MH47353] NR 33 TC 27 Z9 27 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 1995 VL 104 IS 2 BP 390 EP 394 DI 10.1037/0021-843X.104.2.390 PG 5 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA QW681 UT WOS:A1995QW68100016 PM 7790642 ER PT J AU ATKINSON, BA BOUTHET, C BOCANEGRA, R CORREA, A LUTHER, MF GRAYBILL, JR AF ATKINSON, BA BOUTHET, C BOCANEGRA, R CORREA, A LUTHER, MF GRAYBILL, JR TI COMPARISON OF FLUCONAZOLE, AMPHOTERICIN-B AND FLUCYTOSINE IN TREATMENT OF A MURINE MODEL OF DISSEMINATED INFECTION WITH CANDIDA-GLABRATA IN IMMUNOCOMPROMISED MICE SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID TORULOPSIS-GLABRATA; RESISTANCE; EPIDEMIOLOGY; YEASTS AB Candida glabrata is an emerging opportunist pathogen in immunosuppressed patients. C. glabrata is resistant to many antifungal agents and until recently, there have been no standard treatment regimens for this organism. A mouse model was established using mice immunosuppressed with 5 fluorouracil to evaluate amphotericin B, flucytosine, fluconazole and their combinations to treat an intravenously induced C. glabrata infection. Treatment with fluconazole, flucytosine, amphotericin B or a combination was begun one day after infection. Following 5 days of treatment, the mice were killed for fungal counts in kidneys and spleen. At the doses used, amphotericin B was superior to fluconazole or flucytosine alone in the treatment of C. glabrata infections. Flucytosine reduced the fungal burden in the kidney for only two of four isolates of C. glabrata. The combination of fluconazole and flucytosine was superior to these agents alone in reducing the tissue burden in the kidney for one isolate of C. glabrata. High doses of fluconazole alone produced modest reductions in kidney counts but did not reduce spleen tissue counts. There was poor correlation between in-vitro MICs and in-vivo results. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MICROBIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 23 TC 22 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD MAY PY 1995 VL 35 IS 5 BP 631 EP 640 DI 10.1093/jac/35.5.631 PG 10 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA RD066 UT WOS:A1995RD06600009 PM 7592176 ER PT J AU BADR, MS TOIBER, F SKATRUD, JB DEMPSEY, J AF BADR, MS TOIBER, F SKATRUD, JB DEMPSEY, J TI PHARYNGEAL NARROWING OCCLUSION DURING CENTRAL SLEEP-APNEA SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE UPPER AIRWAY OBSTRUCTION; NON RAPID EYE MOVEMENT SLEEP; HYPOCAPNIA; PHARYNGEAL AIRWAY; PATHOGENESIS OF SLEEP APNEA SYNDROME ID UPPER AIRWAY PATENCY; NREM SLEEP; PULMONARY RESISTANCE; HUMAN INFANT; PRESSURE; PATHOGENESIS; WAKEFULNESS; OBSTRUCTION; VENTILATION; MECHANISM AB We hypothesized that subatmospheric intraluminal pressure is not required for pharyngeal occlusion during sleep. Six normal subjects and six subjects with sleep apnea or hypopnea (SAH) were studied during non-rapid-eye-movement sleep. Pharyngeal patency was determined by using fiber-optic nasopharyngoscopy during spontaneous central sleep apnea (n = 4) and induced hypocapnic central apnea via nasal mechanical ventilation (n = 10). Complete pharyngeal occlusion occurred in 146 of 160 spontaneously occurring central apneas in patients with central sleep apnea syndrome. During induced hypocapnic central apnea, gradual progressive pharyngeal narrowing occurred. More pronounced narrowing was noted at the velopharynx relative to the oropharynx and in subjects with SAH relative to normals. Complete pharyngeal occlusion frequently occurred in subjects with SAH (31 of 44 apneas) but rarely occurred in normals (3 of 25 apneas). Resumption of inspiratory effort was associated with persistent narrowing or complete occlusion unless electroencephalogram signs of arousal were noted. Thus pharyngeal cross-sectional area is reduced during central apnea in the absence of inspiratory effort. Velopharyngeal narrowing consistently occurs during induced hypocapnic central apnea even in normal subjects. Complete pharyngeal occlusion occurs during spontaneous or induced central apnea in patients with SAH. We conclude that subatmospheric intraluminal pressure is not required for pharyngeal occlusion to occur. Pharyngeal narrowing or occlusion during central apnea may be due to passive collapse or active constriction. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MED SERV,MADISON,WI 53705. UNIV WISCONSIN,SCH MED,DEPT MED,JOHN RANKIN LAB PREVENT MED,MADISON,WI 53705. UNIV WISCONSIN,SCH MED,DEPT PREVENT MED,JOHN RANKIN LAB PREVENT MED,MADISON,WI 53705. FU NCRR NIH HHS [RR-03186]; NHLBI NIH HHS [HL-02588, HL-42242] NR 41 TC 171 Z9 174 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAY PY 1995 VL 78 IS 5 BP 1806 EP 1815 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA QY605 UT WOS:A1995QY60500027 PM 7649916 ER PT J AU PINS, MR MANKIN, HJ XAVIER, RJ ROSENTHAL, DI DICKERSIN, GR ROSENBERG, AE AF PINS, MR MANKIN, HJ XAVIER, RJ ROSENTHAL, DI DICKERSIN, GR ROSENBERG, AE TI MALIGNANT EPITHELIOID HEMANGIOENDOTHELIOMA OF THE TIBIA ASSOCIATED WITH A BONE INFARCT IN A PATIENT WHO HAD GAUCHER DISEASE - A CASE-REPORT SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Note ID SOFT-TISSUE; ANGIOSARCOMA; HYPERPLASIA; EOSINOPHILIA; MISTAKEN; SARCOMA; SKIN C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. RP PINS, MR (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,FRUIT ST,BOSTON,MA 02114, USA. NR 22 TC 16 Z9 18 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. vol. PD MAY PY 1995 VL 77A IS 5 BP 777 EP 781 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA QY970 UT WOS:A1995QY97000015 PM 7744904 ER PT J AU SCHLENSTEDT, G HARRIS, S RISSE, B LILL, R SILVER, PA AF SCHLENSTEDT, G HARRIS, S RISSE, B LILL, R SILVER, PA TI A YEAST DNAJ HOMOLOG, SCJ1P, CAN FUNCTION IN THE ENDOPLASMIC-RETICULUM WITH BIP/KAR2P VIA A CONSERVED DOMAIN THAT SPECIFIES INTERACTIONS WITH HSP70S SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HEAT-SHOCK PROTEINS; LUMINAL ER PROTEINS; KAR2 BIP GENE; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; MITOCHONDRIAL PROTEIN; SECRETORY PROTEINS; UNFOLDED PROTEINS; MEMBRANE-PROTEIN; TRANSLOCATION AB Eukaryotic cells contain multiple Hsp70 proteins and DnaJ homologues. The partnership between a given Hsp10 and its interacting DnaJ could, in principle, be determined by their cellular colocalization or by specific protein-protein interactions. The yeast SCJ1 gene encodes one of several homologues of the bacterial chaperone DnaJ. We show that Scj1p is located in the lumen of the endoplasmic reticulum (ER), where it can function with Kar2p (the ER-lumenal BiP/Hsp70 of yeast). The region common to all DnaJ homologues (termed the J domain) from Scj1p can be swapped for a similar region in Sec63p, which is known to interact with Kar2p in the ER lumen, to form a functional transmembrane protein component of the secretory machinery. Thus, Kar2p can interact with two different DnaJ proteins. On the other hand, J domains from two other non-ER DnaJs, Sis1p and Mdj1p, do not function when swapped into Sec63p. However, only three amino acid changes in the Sis1p J domain render the Sec63 fusion protein fully functional in the ER lumen. These results indicate that the choice of an Hsp10 partner by a given DnaJ homologue is specified by the J domain. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08544. UNIV MUNICH,INST PHYSIOL CHEM,D-80336 MUNICH,GERMANY. NR 59 TC 124 Z9 128 U1 0 U2 0 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 MAY PY 1995 VL 129 IS 4 BP 979 EP 988 DI 10.1083/jcb.129.4.979 PG 10 WC Cell Biology SC Cell Biology GA QY118 UT WOS:A1995QY11800008 PM 7744969 ER PT J AU FORTENBERRY, SC SCHOREY, JS CHIRGWIN, JM AF FORTENBERRY, SC SCHOREY, JS CHIRGWIN, JM TI ROLE OF GLYCOSYLATION IN THE EXPRESSION OF HUMAN PROCATHEPSIN-D SO JOURNAL OF CELL SCIENCE LA English DT Article DE PROCATHEPSIN D; PROTEIN GLYCOSYLATION; LYSOSOMAL TARGETING ID CATHEPSIN-D; LYSOSOMAL-ENZYMES; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; HUMAN RENIN; CELLS; SECRETION; PROTEIN; EVOLUTION; PROTEASES AB Human procathepsin D carries two N-linked glycosylation sites at asparagine residues 70 and 199, widely separated on the surface of the folded protein. We created monoglycosylated procathepsin D molecules by site-directed mutagenesis in vitro of the individual glycosylation sites. With only two exceptions, all 12 mutants of this type were expressed efficiently in mammalian cells. The expressed proteins were stable, targeted to the lysosome, and partially secreted into the medium. When both glycosylation sites were eliminated, however, the expressed proteins (9 different mutants) were stable but most were not secreted and targeted poorly to the lysosome. Mammalian fibroblasts appear to sort nascent procathepsin D efficiently only if it is N-glycosylated. Procathepsin D monoglycosylated at N70 is readily distinguished from the endogenous protein in transfected human cells and thus provides an excellent substrate for studying lysosomal targeting in an homologous system. C1 UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV ENDOCRINOL & METAB,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,RES SERV,SAN ANTONIO,TX 78284. NR 35 TC 18 Z9 21 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY PY 1995 VL 108 BP 2001 EP 2006 PN 5 PG 6 WC Cell Biology SC Cell Biology GA QY172 UT WOS:A1995QY17200017 PM 7657720 ER PT J AU SCHOREY, JS FORTENBERRY, SC CHIRGWIN, JM AF SCHOREY, JS FORTENBERRY, SC CHIRGWIN, JM TI LYSINE RESIDUES IN THE C-TERMINAL LOBE AND LYSOSOMAL TARGETING OF PROCATHEPSIN-D SO JOURNAL OF CELL SCIENCE LA English DT Article DE PROCATHEPSIN D; LYSOSOMAL TARGETING; PROTEIN SORTING ID HUMAN CATHEPSIN-D; PROTEIN RECOGNITION DETERMINANTS; HAMSTER KIDNEY-CELLS; BREAST-CANCER CELLS; ENZYME PHOSPHORYLATION; CARBOXYPEPTIDASE-Y; OLIGOSACCHARIDES; BIOSYNTHESIS; EXPRESSION; PROPEPTIDE AB A major pathway to the lysosome for soluble hydrolases involves the 6-phosphorylation of mannose residues. The initial step in this reaction is catalyzed by a phosphotransferase which recognizes lysosomal precursors. We constructed mutants of human procathepsin D whose targeting to the lysosome could be assayed directly in intact cells. Eight lysine residues were individually converted to glutamic acid on the surface of the carboxyl terminal lobe of the protein. Mutants with as many as four Lys to Glu mutations were normally targeted to the lysosome and processed to the mature form of the enzyme in transfected cells. We conclude that the C-terminal lobe of procathepsin D may not carry a determinant essential for lysosomal targeting in intact fibroblasts. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV ENDOCRINOL & METAB,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 NCI NIH HHS [CA40035] NR 60 TC 12 Z9 12 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY PY 1995 VL 108 BP 2007 EP 2015 PN 5 PG 9 WC Cell Biology SC Cell Biology GA QY172 UT WOS:A1995QY17200018 PM 7657721 ER PT J AU AMES, A MAYNARD, KI KAPLAN, S AF AMES, A MAYNARD, KI KAPLAN, S TI PROTECTION AGAINST CNS ISCHEMIA BY TEMPORARY INTERRUPTION OF FUNCTION-RELATED PROCESSES OF NEURONS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE RETINA; ENERGY METABOLISM; STROKE; PROTECTION; HYPOXIA; HYPOGLYCEMIA ID CEREBRAL-ARTERY OCCLUSION; ENERGY-REQUIREMENTS; BLOOD-FLOW; GLUCOSE DEPRIVATION; CORTICAL CULTURE; MILD HYPOTHERMIA; RABBIT RETINA; BRAIN; INJURY; AMILORIDE AB Previous studies have shown that most of the energy consumption of CNS tissue is used for processes that subserve signaling functions of the cells. Since these function-related processes are probably not essential to cell viability, blocking them reversibly with a combination of pharmacologic agents should protect cells from a reduction in energy metabolism. Preliminary experiments to test this hypothesis were performed on isolated rabbit retinas. They were maintained in a newly devised chamber that permitted continuous monitoring of electrophysiological function for greater than or equal to 8 h. Ischemia was simulated by a 6-fold reduction in both O-2, and glucose. This caused a rapid (t(1/2) 75 s) and complete loss of the light-evoked response in the optic nerve. Untreated retinas showed full recovery after 1/2 h of deprivation, but only 50% recovery after 1 h and little or no recovery after 2 or 3 h. Retinas exposed during 3 h of deprivation to a combination of six agents that abolished electrophysiologic function and reduced glucose utilization [tetrodotoxin (TTX), 2-amino-4-phosphonobutyric acid (APB), 2-amino-5-phosphonovaleric acid (APV), amiloride, Mg2+, and Li+] showed full recovery. We conclude that reducing energy requirements by blocking functional processes can prevent ischemic damage. RP AMES, A (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,EDWARDS 414,BOSTON,MA 02114, USA. NR 39 TC 32 Z9 32 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 1995 VL 15 IS 3 BP 433 EP 439 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA QT257 UT WOS:A1995QT25700011 PM 7714001 ER PT J AU CHAPMAN, CA WABER, DP BERNSTEIN, JH POMEROY, SL LAVALLY, B SALLAN, SE TARBELL, N AF CHAPMAN, CA WABER, DP BERNSTEIN, JH POMEROY, SL LAVALLY, B SALLAN, SE TARBELL, N TI NEUROBEHAVIORAL AND NEUROLOGIC OUTCOME IN LONG-TERM SURVIVORS OF POSTERIOR-FOSSA BRAIN-TUMORS - ROLE OF AGE AND PERIOPERATIVE FACTORS SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID CHILDREN; MEDULLOBLASTOMA; CHILDHOOD; DEFICITS AB We evaluated the neuropsychological and neurologic outcome of 15 long-term survivors of posterior fossa tumors who were treated between 1970 and 1984 with cranial irradiation (n = 15) and surgery (n = 14). The interval between diagnosis and evaluation ranged from 4 to 20 years (median = 10 years). Earlier age at diagnosis (< 6 years) was associated with an increased incidence of severe neurologic and neuropsychological sequelae. Hydrocephalus, obtundation, and tumor extension outside the vermis also were more prevalent in the younger group. Poor neurobehavioral outcomes in young children with posterior fossa tumors may be related to more aggressive tumor growth or complications of the initial therapy and not solely due to toxicity from craniospinal irradiation. C1 CHILDRENS HOSP,DIV PSYCHOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA. RP CHAPMAN, CA (reprint author), CHILDRENS HOSP,DEPT NEUROL,FEGAN 11,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 18 TC 58 Z9 58 U1 1 U2 1 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON ST, PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD MAY PY 1995 VL 10 IS 3 BP 209 EP 212 PG 4 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA QX383 UT WOS:A1995QX38300006 PM 7642890 ER PT J AU LERMAN, P LERMANSAGIE, T AF LERMAN, P LERMANSAGIE, T TI SULTHIAME REVISITED SO JOURNAL OF CHILD NEUROLOGY LA English DT Note ID CHILDHOOD; EPILEPSY C1 BEILINSON MED CTR,PEDIAT SEIZURE CLIN,PETAH TIQWA,ISRAEL. TEL AVIV UNIV,SACKLER SCH MED,TEL AVIV,ISRAEL. MASSACHUSETTS GEN HOSP,DIV PEDIAT NEUROL,BOSTON,MA. RP LERMAN, P (reprint author), BEILINSON MED CTR,EEG LAB,PETAH TIQWA,ISRAEL. NR 13 TC 16 Z9 16 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON ST, PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD MAY PY 1995 VL 10 IS 3 BP 241 EP 242 PG 2 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA QX383 UT WOS:A1995QX38300015 PM 7642898 ER PT J AU HERSHMAN, JM AF HERSHMAN, JM TI DOES THYROXINE THERAPY PREVENT RECURRENCE OF GRAVES HYPERTHYROIDISM SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID MEDICAL-TREATMENT; DISEASE; RISK RP HERSHMAN, JM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR, 11301 WILSHIRE BLVD, LOS ANGELES, CA 90073 USA. NR 13 TC 8 Z9 8 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1995 VL 80 IS 5 BP 1479 EP 1480 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QW611 UT WOS:A1995QW61100002 PM 7744988 ER PT J AU TAYLOR, AE WHITNEY, H HALL, JE MARTIN, K CROWLEY, WF AF TAYLOR, AE WHITNEY, H HALL, JE MARTIN, K CROWLEY, WF TI MIDCYCLE LEVELS OF SEX STEROIDS ARE SUFFICIENT TO RECREATE THE FOLLICLE-STIMULATING-HORMONE BUT NOT THE LUTEINIZING-HORMONE MIDCYCLE SURGE - EVIDENCE FOR THE CONTRIBUTION OF OTHER OVARIAN FACTORS TO THE SURGE IN NORMAL WOMEN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; LUTEAL PHASE DEFICIENCY; HUMAN MENSTRUAL-CYCLE; PROGESTERONE SECRETION; RHESUS MACAQUES; ESTRADIOL; OVULATION; RECEPTORS; GNRH; LH AB The midcycle surge of LH and FSH is critical for final oocyte maturation and ovulation. In normal women, this gonadotropin surge follows a gradual increase in estradiol levels (E) and is concomitant with a small increase in progesterone (P) levels. However, whether sex steroids alone are sufficient to induce the complex neuroendocrine interactions underlying this switch from negative to positive feedback is unknown. In this study, physiological midcycle levels off, with and without periovulatory levels of P (E+P and E, respectively) were infused into 18 normally cycling women in their early to midfollicular phases. The resulting sex-steroid-induced gonadotropin responses were then compared with 118 spontaneous midcycle surges in 81 normal women. The sex steroid levels achieved by the infusions were within the normal ranges;for the spontaneous midcycle surge. However, neither women who received E alone nor those who received E+P had LH responses that achieved those of spontaneous LH surges in the normal menstral cycle (NMC) [82.7 +/- 16.3 IU/L E (mean +/- SEM), 69.7 +/- 12.01 IU/L E+P vs. 121.7 +/- 6.23 IU/L NMC, P < 0.05 E and P < 0.005 E+P vs. NMC]. In contrast, peak FSH levels evoked by E and P matched the spontaneous FSH peaks (19.0 +/- 2.1 IU/L E, 24.5 +/- 4.0 IU/L E+P us. 23.3 +/- 0.9 IU/L NMC, P = 0.07 E and P = 0.71 E+P vs. NMC). In conclusion, sex steroids alone do not seem to be sufficient to stimulate the normal midcycle LH surge. We hypothesize that other ovarian factors, which are missing in the midfollicular phase, are required for the generation of the normal midcycle surge of LH. C1 MASSACHUSETTS GEN HOSP, REPROD ENDOCRINE UNIT, BOSTON, MA 02114 USA. RP TAYLOR, AE (reprint author), MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, DEPT MED, 511 FRUIT ST, BOSTON, MA 02114 USA. FU NICHD NIH HHS [R01HD-15080, U54HD-29164, P30HD-28138] NR 40 TC 36 Z9 36 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1995 VL 80 IS 5 BP 1541 EP 1547 DI 10.1210/jc.80.5.1541 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QW611 UT WOS:A1995QW61100017 PM 7744998 ER PT J AU SCHIPANI, E WEINSTEIN, LS BERGWITZ, G IIDAKLEIN, A KONG, XF STUHRMANN, M KRUSE, K WHYTE, MP MURRAY, T SCHMIDTKE, J VANDOP, C BRICKMAN, AS CRAWFORD, JD POTTS, JT KRONENBERG, HM ABOUSAMRA, AB SEGRE, GV JUPPNER, H AF SCHIPANI, E WEINSTEIN, LS BERGWITZ, G IIDAKLEIN, A KONG, XF STUHRMANN, M KRUSE, K WHYTE, MP MURRAY, T SCHMIDTKE, J VANDOP, C BRICKMAN, AS CRAWFORD, JD POTTS, JT KRONENBERG, HM ABOUSAMRA, AB SEGRE, GV JUPPNER, H TI PSEUDOHYPOPARATHYROIDISM TYPE IB IS NOT CAUSED BY MUTATIONS IN THE CODING EXONS OF THE HUMAN PARATHYROID-HORMONE (PTH)/PTH-RELATED PEPTIDE RECEPTOR GENE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; NEPHROGENIC DIABETES-INSIPIDUS; VASOPRESSIN V2-RECEPTOR GENE; POLYMERASE CHAIN-REACTION; COMMON RECEPTOR; DNA FRAGMENTS; PROTEIN; RESISTANCE; CELLS; FIBROBLASTS AB Pseudohypoparathyroidism type Ib (PHP-Ib) is thought to be caused by a PTH/PTH-related peptide (PTHrP) receptor defect. To search for receptor mutations in genomic DNA from 17 PHP-Ib patients, three recently isolated human genomic DNA clones were further characterized by restriction enzyme mapping and nucleotide sequencing across intron/exon borders. Regions including all 14 coding exons and their splice junctions were amplified by polymerase chain reaction, and the products were analyzed by either temperature gradient gel electrophoresis or direct nucleotide sequencing. Silent polymorphisms were identified in exons G (1 of 17), M4 (1 of 17), and M7 (15 of 17). Two base changes were found in introns, 1 at the splice-donor site of the intron between exons E2 and E3 (1 of 17) and the other between exons G and M1 (2 of 17), Total ribonucleic acid from COS-7 cells expressing minigenes with or without the base change between exons E2 and E3 showed no difference by either Northern blot analysis or reverse transcriptase-polymerase chain reaction. Radioligand binding was indistinguishable for both transiently expressed constructs. A missense mutation (E546 to K546) in the receptor's cytoplasmic tail (3 of 17) was also found in 1 of 60 healthy individuals, and PTH/PTHrP receptors with this mutation were functionally indistinguishable from wild-type receptors. PHP-Ib thus appears to be rarely, if ever, caused by mutations in the coding exons of the PTH/PTHrP receptor gene. C1 MASSACHUSETTS GEN HOSP, MED & CHILDRENS SERV, PEDIAT ENDOCRINE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, MED & CHILDRENS SERV, ENDOCRINE UNIT, BOSTON, MA 02114 USA. NIDDK, METAB DIS BRANCH, BETHESDA, MD 20892 USA. HANNOVER MED SCH, HUMANGENET ABT, D-30114 HANNOVER, GERMANY. UNIV CALIF LOS ANGELES, LOS ANGELES, CA 90024 USA. UNIV LUBECK, PADIAT KLIN, D-23538 LUBECK, GERMANY. VET ADM MED CTR, DEPT ENDOCRINOL, SEPULVEDA, CA 91343 USA. SHRINERS HOSP CRIPPLED CHILDREN, METAB RES UNIT, ST LOUIS, MO 63131 USA. WASHINGTON UNIV, JEWISH HOSP ST LOUIS, SCH MED, DIV BONE & MINERAL DIS, ST LOUIS, MO 63130 USA. ST MICHAELS HOSP, BONE MINERAL GRP, TORONTO, ON M5B 1A6, CANADA. OI Weinstein, Lee/0000-0002-1899-5152; Abou-Samra, Abdul/0000-0001-8735-1142 FU PHS HHS [R01-46718] NR 58 TC 88 Z9 89 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1995 VL 80 IS 5 BP 1611 EP 1621 DI 10.1210/jc.80.5.1611 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QW611 UT WOS:A1995QW61100028 PM 7745008 ER PT J AU YIP, I PANG, XP BERG, L HERSHMAN, JM AF YIP, I PANG, XP BERG, L HERSHMAN, JM TI ANTITUMOR ACTIONS OF INTERFERON-GAMMA AND INTERLEUKIN-1-BETA ON HUMAN PAPILLARY THYROID-CARCINOMA CELL-LINES SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TUMOR-NECROSIS-FACTOR; RECONSTITUTED BASEMENT-MEMBRANE; FACTOR-ALPHA; PROGNOSTIC FACTORS; RECOMBINANT ALPHA-2-INTERFERON; IMMUNE INTERFERON; INVITRO ASSAY; CANCER; INVASION; INHIBITION AB To test the hypothesis that interferon-gamma (IFN gamma) and interleukin-1 beta (IL-1 beta) possess antitumor activity on human papillary thyroid carcinoma cells, we studied the in vitro effects of IFN gamma and IL-1 beta on the proliferation and invasiveness of two human PTC cell lines, TPC-1 (TP) and NPA (NP) cells. TP and NP cells were treated with various concentrations ofIFN gamma and IL-1 beta alone and in combination. Cell proliferation was assessed by [H-3]thymidine incorporation and cell number measurement. Tumor cell invasion was assessed by the ability of cells to penetrate through a Matrigel membrane. Both IFN gamma and IL-1 beta inhibited [H-3]thymidine incorporation into TP cells in a dose-dependent manner and decreased TP cell number. In NP cells, treatment with IFN gamma and IL-1 beta also decreased [H-3]thymidine incorporation and cell number. The inhibitory effects of IFN gamma and IL-1 beta on tumor cell proliferation were additive in both cell lines. In the invasion experiments, IFN gamma and IL-1 beta reduced the invasiveness of TP and NP cells. Again, the inhibitory effects of IFN gamma and IL-1 beta on tumor cell invasion were additive in both cell lines. In summary, the results showed that both IFN gamma and IL-1 beta are potent inhibitors of the proliferation and invasiveness of TP and NP cells. The additive effects of IFN gamma and IL-1 beta are evidence that they act through different pathways. Our findings suggest that IFN gamma and IL-1 beta are two of the anticancer factors that act to suppress the proliferation and reduce the invasive potential of human papillary thyroid carcinoma cells. C1 W LOS ANGELES VET AFFAIRS MED CTR, ENDOCRINE RES LAB, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90073 USA. FU NCI NIH HHS [CA-61863] NR 48 TC 30 Z9 31 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1995 VL 80 IS 5 BP 1664 EP 1669 DI 10.1210/jc.80.5.1664 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QW611 UT WOS:A1995QW61100035 PM 7745015 ER PT J AU WAGNER, DD AF WAGNER, DD TI P-SELECTIN CHASES A BUTTERFLY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,DEPT PATHOL,CAMBRIDGE,MA. RP WAGNER, DD (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,CAMBRIDGE,MA, USA. NR 8 TC 4 Z9 5 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1995 VL 95 IS 5 BP 1955 EP 1956 DI 10.1172/JCI117878 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QW205 UT WOS:A1995QW20500001 PM 7537752 ER PT J AU ARNOLD, A BROWN, MF URENA, P GAZ, RD SARFATI, E DRUEKE, TB AF ARNOLD, A BROWN, MF URENA, P GAZ, RD SARFATI, E DRUEKE, TB TI MONOCLONALITY OF PARATHYROID TUMORS IN CHRONIC-RENAL-FAILURE AND IN PRIMARY PARATHYROID HYPERPLASIA SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE UREMIA; PRIMARY HYPERPARATHYROIDISM; SECONDARY HYPERPARATHYROIDISM; TERTIARY HYPERPARATHYROIDISM; NEOPLASIA-PARATHYROID ID ENDOCRINE NEOPLASIA TYPE-1; HYPERVARIABLE DXS255 LOCUS; CLONAL ORIGIN; PITUITARY-ADENOMAS; CUSHINGS-DISEASE; X-CHROMOSOME; DIFFERENTIAL METHYLATION; CANDIDATE ONCOGENE; UREMIC PATIENTS; HYPERPARATHYROIDISM AB The pathogeneses of parathyroid disease in patients with uremia and nonfamilial primary parathyroid hyperplasia are poorly understood, Because of multigland involvement, it has been assumed that these common diseases predominantly involve polyclonal (non-neoplastic) cellular proliferations, but an overall assessment of their clonality has not been done. We examined the clonality of these hyperplastic parathyroid tumors using X-chromosome inactivation analysis with the M27 beta (DXS255) DNA polymorphism and by searching for monoclonal allelic losses at M27 beta and at loci on chromosome band 11q13. Fully 7 of 11 informative hemodialysis patients (64%) with uremic refractory hyperparathyroidism harbored at least one monoclonal parathyroid tumor (with a minimum of 12 of their 19 available glands being monoclonal), Tumor monoclonality was demonstrable in 6 of 16 informative patients (38%) with primary parathyroid hyperplasia, Histopathologic categories of nodular versus generalized hyperplasia were not useful predictors of clonal status, These observations indicate that monoclonal parathyroid neoplasms are common in patients with uremic refractory hyperparathyroidism and also develop in a substantial group of patients with sporadic primary parathyroid hyperplasia, thereby changing our concept of the pathogenesis of these diseases, Neoplastic transformation of preexisting polyclonal hyperplasia, apparently due in large part to genes not yet implicated in parathyroid tumorigenesis and possibly including a novel X-chromosome tumor suppressor gene, is likely to play a central role in these disorders. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HOP NECKER ENFANTS MALAD,DEPT NEPHROL,INSERM,U90,PARIS,FRANCE. HOP ST LOUIS,SERV CHIRURG GEN,PARIS,FRANCE. RP ARNOLD, A (reprint author), MASSACHUSETTS GEN HOSP,ENDOCRINE ONCOL LAB,GRJ 1021,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-55909]; NIDDK NIH HHS [DK-11794] NR 42 TC 299 Z9 301 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1995 VL 95 IS 5 BP 2047 EP 2053 DI 10.1172/JCI117890 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QW205 UT WOS:A1995QW20500013 PM 7738171 ER PT J AU GUZMAN, NJ FANG, MZ TANG, SS INGELFINGER, JR GARG, LC AF GUZMAN, NJ FANG, MZ TANG, SS INGELFINGER, JR GARG, LC TI AUTOCRINE INHIBITION OF NA+/K+-ATPASE BY NITRIC-OXIDE IN MOUSE PROXIMAL TUBULE EPITHELIAL-CELLS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE EPITHELIAL TRANSPORT; SODIUM NITROPRUSSIDE; CYCLIC GUANOSINE MONOPHOSPHATE; L-ARGININE; PEROXYNITRITE ID PROTEIN-KINASE-C; NA-K-ATPASE; NEPHRON SEGMENTS; MESANGIAL CELLS; CANINE KIDNEY; SYNTHASE; RAT; TRANSPORT; MYOINOSITOL; INFLAMMATION AB An inducible nitric oxide synthase has recently been described in proximal tubule epithelium To investigate the effects of proximal tubule NO on Na+/K+-ATPase, we induced NO production in mouse proximal tubule epithelial cells by treatment with lipopolysaccharide (LPS) and interferon-gamma (IFN gamma) followed by determinations of ouabain-sensitive ATPase activity, Na+/K+-ATPase activity decreased after 4 h of IPS/IFN gamma treatment, reaching maximal inhibition after 24 h (34% reduction in activity), The inhibition of Na+/K+-ATPase activity by LPS/IFN gamma was prevented by simultaneous incubation with N-omega-nitro L-arginine and markedly blunted by removal of L-arginine from the medium, The NO donors sodium nitroprusside and SIN-1 also inhibited Na+/K+-ATPase activity to a similar extent than LPS/IFN gamma. However, treatment with 8-pCPT-cGMP only modestly reduced Na+/K+-ATPase activity. Interestingly, superoxide dismutase prevented the inhibitory effects of NO on Na+/K+-ATPase activity, suggesting a role for peroxynitrite in this inhibition, We conclude that NO generated by mouse proximal tubule epithelial cell iNOS inhibits Na/K ATPase activity in an autocrine fashion and that this inhibition is accompanied by a reduction in Na-dependent solute transport. C1 UNIV FLORIDA, COLL MED, DIV NEPHROL HYPERTENS & TRANSPLANTAT, GAINESVILLE, FL 32610 USA. MASSACHUSETTS GEN HOSP, DIV PEDIAT NEPHROL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. RP GUZMAN, NJ (reprint author), UNIV FLORIDA, COLL MED, J HILLIS MILLER HLTH CTR, DEPT PHARMACOL, POB 100267, GAINESVILLE, FL 32610 USA. FU NHLBI NIH HHS [HL-48455, HL-43131]; NIAAA NIH HHS [AA-09888] NR 43 TC 137 Z9 142 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1995 VL 95 IS 5 BP 2083 EP 2088 DI 10.1172/JCI117895 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QW205 UT WOS:A1995QW20500018 PM 7537754 ER PT J AU GOODYEAR, LJ GIORGINO, F SHERMAN, LA CAREY, J SMITH, RJ DOHM, GL AF GOODYEAR, LJ GIORGINO, F SHERMAN, LA CAREY, J SMITH, RJ DOHM, GL TI INSULIN-RECEPTOR PHOSPHORYLATION, INSULIN-RECEPTOR SUBSTRATE-1 PHOSPHORYLATION, AND PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY ARE DECREASED IN INTACT SKELETAL-MUSCLE STRIPS FROM OBESE SUBJECTS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE INSULIN ACTION; INSULIN RESISTANCE; OBESITY; INSULIN RECEPTOR SUBSTRATE; TYROSINE PHOSPHORYLATION ID TYROSINE KINASE-ACTIVITY; GROWTH FACTOR-I; GLUCOSE TRANSPORTER; RESISTANT PATIENTS; DIABETIC SUBJECTS; MORBIDLY OBESE; PROTEIN-KINASE; RAT; BINDING; IRS-1 AB To determine whether the impaired insulin-stimulated glucose uptake in obese individuals is associated with altered insulin receptor signaling, we measured both glucose uptake and early steps in the insulin action pathway in intact strips of human skeletal muscle. Biopsies of rectus abdominus muscle were taken from eight obese and eight control subjects undergoing elective surgery (body mass index 52.9 +/- 3.6 vs 25.7 +/- 0.9). Insulin-stimulated 2-deoxyglucose uptake was 53% lower in muscle strips from obese subjects, Additional muscle strips were incubated in the basal state or with 10(-7) M insulin for 2, 15, or 30 min. In the lean subjects, tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 (IRS-1), measured by immunoblotting with anti-phosphotyrosine antibodies, was significantly increased by insulin at all time points. In the skeletal muscle from the obese subjects, insulin was less effective in stimulating tyrosine phosphorylation (maximum receptor and IRS-1 phosphorylation decreased by 35 and 38%, respectively), Insulin stimulation of IRS-1 immunoprecipitable phosphatidylinositol 3-kinase (PI 3-kinase) activity also was markedly lower in obese subjects compared with controls (10- vs 35-fold above basal, respectively). In addition, the obese subjects had a lower abundance of the insulin receptor, IRS-1, and the p85 subunit of PI 3-kinase (55, 54, and 64% of nonobese, respectively). We conclude that impaired insulin-stimulated glucose uptake in skeletal muscle from severely obese subjects is accompanied by a deficiency in insulin receptor signaling, which may contribute to decreased insulin action. C1 BETH ISRAEL HOSP,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. E CAROLINA UNIV,SCH MED,DEPT BIOCHEM,GREENVILLE,NC 27858. RI Giorgino, Francesco/K-7262-2016 OI Giorgino, Francesco/0000-0001-7372-2678 FU NIDDK NIH HHS [DK36836, DK46121]; NIGMS NIH HHS [GM36428] NR 59 TC 389 Z9 401 U1 0 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1995 VL 95 IS 5 BP 2195 EP 2204 DI 10.1172/JCI117909 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QW205 UT WOS:A1995QW20500032 PM 7537758 ER PT J AU HOTAMISLIGIL, GS ARNER, P CARO, JF ATKINSON, RL SPIEGELMAN, BM AF HOTAMISLIGIL, GS ARNER, P CARO, JF ATKINSON, RL SPIEGELMAN, BM TI INCREASED ADIPOSE-TISSUE EXPRESSION OF TUMOR-NECROSIS-FACTOR-ALPHA IN HUMAN OBESITY AND INSULIN-RESISTANCE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE CYTOKINES; FAT; NON-INSULIN-DEPENDENT DIABETES MELLITUS; WEIGHT LOSS; INSULIN ACTION ID RECEPTOR SUBSTRATE-1; MUSCLE; PHOSPHORYLATION; PENTOXIFYLLINE; LYMPHOTOXIN; CLONING; LIVER AB Obesity is frequently associated with insulin resistance and abnormal glucose homeostasis. Recent studies in animal models have indicated that TNF-alpha plays an important role in mediating the insulin resistance of obesity through its overexpression in fat tissue, However, the mechanisms linking obesity to insulin resistance and diabetes in humans remain largely unknown, In this study we examined the expression pattern of TNF-alpha mRNA in adipose tissues from 18 control and 19 obese premenopausal women by Northern blot analysis, TNF-alpha protein concentrations in plasma and in conditioned medium of explanted adipose tissue were measured by ELISA. Furthermore, the effects of weight reduction by dietary treatment of obesity on the adipose expression of TNF-alpha mRNA were also analyzed in nine premenopausal obese women, before and after a controlled weight-reduction program. These studies demonstrated that obese individuals express 2.5-fold more TNF-alpha mRNA in fat tissue relative to the lean controls (P < 0.001), Similar increases were also observed in adipose production of TNF-alpha protein but circulating TNF-alpha levels were extremely low or undetectable, A strong positive correlation was observed between TNF-alpha mRNA expression levels in fat tissue and the level of hyperinsulinemia (P < 0.001), an indirect measure of insulin resistance, Finally, body weight reduction in obese subjects which resulted in improved insulin sensitivity was also associated with a decrease in TNF-alpha mRNA expression (45%, P < 0.001) in fat tissue, These results suggest a role for the abnormal regulation of this cytokine in the pathogenesis of obesity-related insulin resistance. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HUDDINGE UNIV HOSP,KAROLINSKA INST,DEPT MED,S-14186 HUDDINGE,SWEDEN. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT MED,PHILADELPHIA,PA 19107. MED COLL WISCONSIN,DEPT MED,MADISON,WI 53706. FU NIDDK NIH HHS [DK 42539, DK 45592] NR 30 TC 2092 Z9 2173 U1 11 U2 87 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1995 VL 95 IS 5 BP 2409 EP 2415 DI 10.1172/JCI117936 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QW205 UT WOS:A1995QW20500059 PM 7738205 ER PT J AU PFALLER, MA BALE, M BUSCHELMAN, B LANCASTER, M ESPINELINGROFF, A REX, JH RINALDI, MG COOPER, CR MCGINNIS, MR AF PFALLER, MA BALE, M BUSCHELMAN, B LANCASTER, M ESPINELINGROFF, A REX, JH RINALDI, MG COOPER, CR MCGINNIS, MR TI QUALITY-CONTROL GUIDELINES FOR NATIONAL COMMITTEE FOR CLINICAL LABORATORY STANDARDS RECOMMENDED BROTH MACRODILUTION TESTING OF AMPHOTERICIN-B, FLUCONAZOLE, AND FLUCYTOSINE SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SUSCEPTIBILITY TESTS AB Amphotericin B, fluconazole, and flucytosine (5FC) were tested in a multilaboratory study to establish quality control (QC) guidelines far yeast antifungal susceptibility testing. Ten candidate QC strains were tested in accordance with National Committee for Clinical Laboratory Standards M27-P guidelines against the three antifungal agents in each of six laboratories. Each laboratory was assigned a unique lot of RPMI 1640 broth medium as well as a lot of RPMI 1640 common to all of the laboratories. The candidate QC strains were tested 20 times each against the three antifungal agents in bath unique and common lots of RPMI 1640. A minimum of 220 MICs per drug per organism were generated during the study. Overall, 95% of the MICs of amphotericin B, fluconazole, and 5FC fell within the desired 3 log(2)-dilution range (mode +/- 1 log(2) dilution), Excellent performance with all three drugs was observed for Candida parapsilosis ATCC 22019 and C. krusei ATCC 6258. With these strains, an-scale 3 log(2)-dilution ranges encompassing 96 to 99% of the MICs of all three drugs were established. These two strains are recommended for QC testing of amphotericin B, fluconazole, and 5FC. Reference ranges were also established for an additional four strains for use in method development and for training. Four strains failed to perform adequately for recommendation as either QC or reference strains. C1 ALAMAR BIOSCI INC,SACRAMENTO,CA 95834. VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,RICHMOND,VA 23298. UNIV TEXAS,SCH MED,HOUSTON,TX 77030. UNIV TEXAS,AUDIE L MURPHY MEM VET HOSP,HLTH SCI CTR,LAB SERV,SAN ANTONIO,TX 78284. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77555. RP PFALLER, MA (reprint author), UNIV IOWA,COLL MED,IOWA CITY,IA 52242, USA. NR 14 TC 106 Z9 108 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1995 VL 33 IS 5 BP 1104 EP 1107 PG 4 WC Microbiology SC Microbiology GA QT306 UT WOS:A1995QT30600012 PM 7615713 ER PT J AU KIRBY, R RUOFF, KL AF KIRBY, R RUOFF, KL TI COST-EFFECTIVE, CLINICALLY RELEVANT METHOD FOR RAPID IDENTIFICATION OF BETA-HEMOLYTIC STREPTOCOCCI AND ENTEROCOCCI SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GROUP-A STREPTOCOCCI; PRESUMPTIVE IDENTIFICATION; GROUP-C; ESCHERICHIA-COLI; THROAT-CULTURES; GROUP-B; DIFFERENTIATION; GLUCURONIDASE; TESTS AB Currently popular agglutination and coagglutination methods for the identification of beta-hemolytic streptococci, although rapid and simple to perform, are costly. Furthermore, they fail to distinguish between clinically relevant species and normal flora of the same serogroup. We investigated the use of a series of four physiologic tests to differentiate beta-hemolytic streptococci and enterococci into five clinically relevant groups. We also investigated the use of a new product, Visi-Spot, and evaluated an alternate method for the detection of beta-D-glucuronidase production. Our results suggest that for most routine processing of beta-hemolytic streptococci, physiologic tests are sufficiently rapid, more accurate, and far less costly to perform than serologic methods. The facility of our scheme is enhanced by the use of the Visi-Spot test and the substitution of a commercially available product for more traditional methods of detecting beta-D-glucuronidase. C1 MASSACHUSETTS GEN HOSP,MICROBIOL LABS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,JAMES HOLMER WRIGHT PATHOL LABS,BOSTON,MA 02114. NR 21 TC 5 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1995 VL 33 IS 5 BP 1154 EP 1157 PG 4 WC Microbiology SC Microbiology GA QT306 UT WOS:A1995QT30600021 PM 7615721 ER PT J AU EMANUEL, EJ AF EMANUEL, EJ TI A PHASE-I TRIAL ON THE ETHICS OF PHASE-I TRIALS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CLINICAL-TRIALS; AGENTS RP EMANUEL, EJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 8 TC 33 Z9 33 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 MAY PY 1995 VL 13 IS 5 BP 1049 EP 1051 PG 3 WC Oncology SC Oncology GA QV951 UT WOS:A1995QV95100001 PM 7738609 ER PT J AU VOGEL, CL SCHOENFELDER, J SHEMANO, I HAYES, DF GAMS, RA AF VOGEL, CL SCHOENFELDER, J SHEMANO, I HAYES, DF GAMS, RA TI WORSENING BONE-SCAN IN THE EVALUATION OF ANTITUMOR RESPONSE DURING HORMONAL-THERAPY OF BREAST-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TAMOXIFEN; METASTASES; FLARE; HYPERCALCEMIA AB Purpose: Scintigraphic flare in association with response to therapy has been well described in the medical literature. During the course of a recent breast cancer trial, it became apparent that several patients with worsening bone scan but no other clinical evidence of disease progression might have potentially benefited from continued therapy, but had therapy discontinued. A retrospective analysis of this issue was performed to assess the magnitude and scope of this problem. Materials and Methods: A total of 648 patients with hormone receptor-positive or unknown advanced breast cancer were treated as part of a large-scale trial of first-line hormonal therapy. Patients were assessed for response to therapy, including response duration, progression-free interval (PFI), overall survival, and quality of life. The retrospective analysis presented here was performed to assess whether patients with a possible scintigraphic flare within the first 16 weeks of therapy might have had therapy discontinued prematurely due to a worsening bone scan attributable to tumor flare, rather than due to disease progression. Results: Analysis of the hormonal trial showed that of 376 assessable patients 108 (29%) with bone disease had a possible scintigraphic flare by week 8 or 16 of the trial, based on data on the case report forms and radiology reports (bone scans and x-rays). Of these, 69 patients (64%) were continued on study therapy, which resulted in clinical benefit in 50 (72%) of those patients. In contrast, 39 patients (36%) with possible scintigraphic flare were removed from the trial. Conclusion: We conclude that changes in bone scintigraphy that mimic progressive disease early in the course of hormonal treatment of patients with breast cancer metastatic to bone may represent scintigraphic flare associated with response. Thus, clinicians must be cognizant of the phenomenon of scintigraphic flare to avoid premature discontinuation of a potentially beneficial treatment. (C) 1995 by American Society of Clinical Oncology. C1 COMPREHENS CANC RES GRP INC,MIAMI BEACH,FL. PHARM ADRIA INC,MED RES CTR,COLUMBUS,OH. DANA FARBER CANC INST,CTR BREAST EVALUAT,BOSTON,MA 02115. NR 25 TC 65 Z9 67 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1995 VL 13 IS 5 BP 1123 EP 1128 PG 6 WC Oncology SC Oncology GA QV951 UT WOS:A1995QV95100011 PM 7537797 ER PT J AU STRAUSS, GM KWIATKOWSKI, DJ HARPOLE, DH LYNCH, TJ SKARIN, AT SUGARBAKER, DJ AF STRAUSS, GM KWIATKOWSKI, DJ HARPOLE, DH LYNCH, TJ SKARIN, AT SUGARBAKER, DJ TI MOLECULAR AND PATHOLOGICAL MARKERS IN STAGE-I NON-SMALL-CELL CARCINOMA OF THE LUNG SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID NUCLEOLAR ORGANIZER REGIONS; BLOOD-VESSEL INVASION; PRIMARY BREAST-CANCER; PROGNOSTIC FACTORS; DNA CONTENT; POSTSURGICAL STAGE; SHORTENED SURVIVAL; SURGICAL-TREATMENT; POOR-PROGNOSIS; P53 GENE AB Purpose: Although standard treatment of stage I non-small-cell lung cancer (NSCLC) consists of surgical resection alone, approximately 50% of clinical stage I and 30% to 40% of pathologic stage I patients have disease recurrence and die following curative resection. A large number of traditional pathologic and newer molecular markers have been identified, which appear to have important prognostic significance in this population. This review attempts to summarize these data comprehensively. Methods: Criteria for study selection were English-language reports, identified using Medline and Cancerline, through the fall of 1994. Abstracts from the American Society of Clinical Oncology (ASCO) and the International Association for the Study of Lung Cancer (IASLG) were also reviewed. Results: Molecular markers are classified as molecular genetic markers, differentiation markers, proliferation markers, and markers of metastatic propensity. A number of these markers have been reported to be highly predictive of outcome in stage I NSCLC, and several reports conclude that a specific biomarker may be, aside from clinical stage, the most powerful determinant of prognosis in NSCLC. However, little has been done to clarify the relationships between these newer biologic markers, classic clinicopathologic variables, and clinical outcome. Conclusion: At present, a firm conclusion regarding which biomarkers are most important in predicting outcome is not possible, and a model that reliably integrates all independent prognostic variables cannot be developed. A prospective trial is mandatory to address this issue, and a study design is suggested that would facilitate the development of a prognostic index, while simultaneously asking a therapeutic question. The development of a prognostic index would facilitate future trials in which only high-risk stage I patients could be targeted for investigation of postresection adjuvant treatment strategies. (C) 1995 by American Society of Clinical Oncology. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV EXPTL MED,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV THORAC SURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,HEMATOL ONCOL UNIT,BOSTON,MA 02114. RP STRAUSS, GM (reprint author), DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 85 TC 110 Z9 112 U1 0 U2 2 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 MAY PY 1995 VL 13 IS 5 BP 1265 EP 1279 PG 15 WC Oncology SC Oncology GA QV951 UT WOS:A1995QV95100031 PM 7738631 ER PT J AU FAVA, M LABBATE, LA ABRAHAM, ME ROSENBAUM, JF AF FAVA, M LABBATE, LA ABRAHAM, ME ROSENBAUM, JF TI HYPOTHYROIDISM AND HYPERTHYROIDISM IN MAJOR DEPRESSION REVISITED SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 146th Annual Meeting of the American-Psychiatric-Association CY MAY 22-27, 1993 CL SAN FRANCISCO, CA SP Amer Psychiat Assoc ID THYROID-FUNCTION; ANTITHYROID ANTIBODIES; DYSFUNCTION AB Background: The aim of our study was to evaluate the prevalence of thyroid abnormalities among depressed outpatients and to examine the response to treatment of those subjects with relatively low or high thyroid hormone levels. Method: Outpatients (N = 200) 18 to 65 years of age who met DSM-III-R criteria for major depression were screened for the presence of thyroid abnormalities using a number of thyroid indices. Of these patients, 166 were then treated openly with the antidepressant fluoxetine for 12 weeks. We assessed whether patients with relatively low or high thyroid hormone levels had a different response to treatment compared with other patients. The 17-item Hamilton Rating Scale for Depression (HAM-D-17) was administered during the study to assess changes in depressive symptoms. Thyroid function was assessed by measuring T-3, T-4, free T-4 index (FT4I), T-3 uptake (T3U), and serum thyroid-stimulating hormone (TSH) levels. Results: No clinical cases of hyperthyroidism or hypothyroidism were detected. Of the patients examined, 5 (2.6%) had slightly elevated TSH levels (range, 4.7-8.2); none of these had T-4 or FT4I levels below the normal range. Subnormal levels of T-4 or FT4I were found in 1 subject (0.5%). T-3 and T3U levels were below the normal range in a larger number of patients (7.6% and 15.0% respectively), but only 1 of these patients had elevated TSH levels. None of the patients had levels of TSH below the normal range, and only 3 subjects (1.5%) had T-4 levels above the normal range. No relationship was found between response rate (assessed as either change in HAM-D-17 score or as remission of depressive symptoms with a HAM-D-17 score less than or equal to 7 for 3 consecutive weeks) and each of the thyroid tests, even after adjusting for baseline severity of depression. Conclusion: In depressed outpatients, it appears that hypothyroidism and hyperthyroidism are extremely uncommon and that the presence of subtle thyroid function abnormalities does not have an impact on treatment outcome. RP FAVA, M (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESSION RES PROGRAM,WAC 815,BOSTON,MA 02114, USA. NR 22 TC 53 Z9 57 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 1995 VL 56 IS 5 BP 186 EP 192 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA QY850 UT WOS:A1995QY85000004 PM 7737957 ER PT J AU PERROTT, DH VARGERVIK, K TABAN, LB AF PERROTT, DH VARGERVIK, K TABAN, LB TI COSTOCHONDRAL RECONSTRUCTION OF MANDIBULAR CONDYLES IN NONGROWING PRIMATES SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE TMJ RECONSTRUCTION; COSTOCHONDRAL GRAFT ID TEMPOROMANDIBULAR-JOINT ANKYLOSIS; UNPREDICTABLE GROWTH-PATTERN; MACACA-MULATTA; GRAFTS; AGE AB The aim of this study was to develop a reproducible model in nongrowing animals to document morphological and histological changes after costochondral reconstruction of the mandibular condyle. Seven adult monkeys underwent a unilateral condylectomy followed by costochondral reconstruction Dimensional changes of the thorax and reconstructed ramus-condyle unit were documented by in situ and radiographic analysis. Morphological and histological analysis were completed after removal at 4 (n = 2), 8 (n = 2), and 12 months (n = 3). In situ measurements demonstrated no dimensional changes of the thorax, but the reconstructed ramus-condyle unit decreased in height an average of 3.2 +/- 1.4 mm. The original graft remained unchanged morphologically, but new bone and cartilage progressively encompassed it, creating a form similar to the native condyle. Histologically, the transplanted cartilage remained unchanged. However, the articulating surface progressively took the appearance of the native condyle. Results of this study indicated that, in nongrowing animals, the reconstructed ramus-condyle unit decreases in height slightly but remodels to a size and shape morphologically and histologically similar to the native condyle. C1 UNIV CALIF SAN FRANCISCO,DEPT GROWTH & DEV,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,CTR CRANIOFACIAL ANOMALIES,SAN FRANCISCO,CA 94143. 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,521 PARNASSUS AVE,BOX 0440,SAN FRANCISCO,CA 94143, USA. FU NCRR NIH HHS [RR 5305] NR 41 TC 15 Z9 15 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD MAY PY 1995 VL 6 IS 3 BP 227 EP 237 DI 10.1097/00001665-199505000-00010 PG 11 WC Surgery SC Surgery GA QY847 UT WOS:A1995QY84700009 PM 9020694 ER PT J AU SKODA, RC TSAI, SF ORKIN, SH LEDER, P AF SKODA, RC TSAI, SF ORKIN, SH LEDER, P TI EXPRESSION OF C-MYC UNDER THE CONTROL OF GATA-1 REGULATORY SEQUENCES CAUSES ERYTHROLEUKEMIA IN TRANSGENIC MICE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ERYTHROID TRANSCRIPTION FACTOR; LEUKEMIA-INHIBITORY FACTOR; ERYTHROPOIETIN RECEPTOR; ALPHA-GLOBIN; GENE FAMILY; CELLS; MOUSE; BINDING; DIFFERENTIATION; ONCOGENE AB To study oncogenesis in the erythroid lineage, we have generated transgenic mice carrying the human c-MYC proto-oncogene under the control of mouse GATA-1 regulatory sequences. Six transgenic lines expressed the transgene and displayed a clear oncogenic phenotype. Of these, five developed an early onset, rapidly progressive erythroleukemia that resulted in death of the founder animals 30-50 d after birth. Transgenic progeny of the sixth founder, while also expressing the transgene, remained asymptomatic for more than 8 mo, whereupon members of this line began to develop late onset erythroleukemia. The primary leukemic cells were transplantable into nude mice and syngeneic hosts. Cell lines were established from five of the six leukemic animals and these lines, designated erythroleukemia/c-MYC (EMY), displayed proerythroblast morphology and expressed markers characteristic of the erythroid lineage, including the erythropoietin receptor and beta-globin. Moreover, they also manifested a limited potential to differentiate in response to erythropoietin. Studies in the surviving transgenic line indicated that, contrary to our expectations, the transgene was not expressed in the mast cell lineage. That, coupled with the exclusive occurrence of erythroleukemia in all the transgenic lines, suggests that the GATA-1 promoter construct we have used includes regulatory sequences necessary for in vivo erythroid expression only. Additional sequences would appear to be required for expression in mast cells. Further, our results show that c-MYC can efficiently transform erythroid precursors if expressed at a vulnerable stage of their development. C1 HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT GENET,BOSTON,MA 02115. CHILDRENS HOSP,HOWARD HUGHES MED INST,DIV HEMATOL ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. RI Tsai, Shih-Feng/E-3997-2010 NR 51 TC 18 Z9 18 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1995 VL 181 IS 5 BP 1603 EP 1613 DI 10.1084/jem.181.5.1603 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA QV929 UT WOS:A1995QV92900002 PM 7722440 ER PT J AU LEONG, GB SILVA, JA AF LEONG, GB SILVA, JA TI A PSYCHIATRIC-LEGAL ANALYSIS OF PSYCHOTIC CRIMINAL DEFENDANTS CHARGED WITH MURDER SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE PSYCHIATRY; PSYCHOSIS; HOMICIDE; MURDER; MENTAL DISORDER; VIOLENCE; AGGRESSION AB A sample of 25 criminal defendants charged with murder and suffering from psychosis from a large urban multi-ethnic, multi-cultural community pool was studied. Subject characteristics and information about the homicide and decedents are described. Suggestions for further study are briefly discussed. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP LEONG, GB (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV 116AA,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 19 TC 10 Z9 10 U1 2 U2 3 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD MAY PY 1995 VL 40 IS 3 BP 445 EP 448 PG 4 WC Medicine, Legal SC Legal Medicine GA RB239 UT WOS:A1995RB23900017 PM 7782749 ER PT J AU BAMEZAI, A PALLISER, D BEREZOVSKAYA, A MCGREW, J HIGGINS, K LACY, E ROCK, KL AF BAMEZAI, A PALLISER, D BEREZOVSKAYA, A MCGREW, J HIGGINS, K LACY, E ROCK, KL TI REGULATED EXPRESSION OF LY-6A.2 IS IMPORTANT FOR T-CELL DEVELOPMENT SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MULTIGENE FAMILY; ALPHA-BETA; MONOCLONAL-ANTIBODIES; ACTIVATING PROTEIN; INTERFERON-GAMMA; TRANSGENIC MICE; DOWN-REGULATION; LYMPHOCYTES-T; TAP; RECEPTOR AB Ly-6A.2 is a surface protein on T cells that may play a role in lymphocyte activation. The regulation of Ly-6A.2 expression during T cell lymphopoiesis has been intriguing. It is one of the earliest markers expressed on pluripotent hemopoietic stem cells and is present on both primitive and mature T cells, but its expression is extinguished in the thymus during key developmental stages. To determine whether Ly-6A.2 is active on developing T cells, as well as the significance of its developmental regulation, Ly-6A.2 was expressed throughout T cell development under control of the T cell-specific human CD2 enhancer in transgenic mice. The constitutive overexpression of Ly-6A.2 in vivo led to a marked impairment in the generation of thymocytes. Development was arrested at the time in thymic development when Ly-6A.2 expression is normally turned off. These results indicate that the regulated expression of Ly-6A.2 in thymocytes may be important for normal development. Moreover, these findings demonstrate that Ly-6A.2 is active in the thymic microenvironment. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MEM SLOAN KETTERING CANC CTR,PROGRAM MOLEC BIOL,NEW YORK,NY 10021. CORNELL UNIV,GRAD SCH MED SCI,NEW YORK,NY 10021. RP BAMEZAI, A (reprint author), DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,ROOM 1018,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI 30502]; NIGMS NIH HHS [GM 38515] NR 37 TC 41 Z9 41 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 MAY 1 PY 1995 VL 154 IS 9 BP 4233 EP 4239 PG 7 WC Immunology SC Immunology GA QU825 UT WOS:A1995QU82500001 PM 7722283 ER PT J AU JAPOUR, AJ WELLES, S DAQUILA, RT JOHNSON, VA RICHMAN, DD COOMBS, RW REICHELDERFER, PS KAHN, JO CRUMPACKER, CS KURITZKES, DR AF JAPOUR, AJ WELLES, S DAQUILA, RT JOHNSON, VA RICHMAN, DD COOMBS, RW REICHELDERFER, PS KAHN, JO CRUMPACKER, CS KURITZKES, DR TI PREVALENCE AND CLINICAL-SIGNIFICANCE OF ZIDOVUDINE RESISTANCE MUTATIONS IN HUMAN-IMMUNODEFICIENCY-VIRUS ISOLATED FROM PATIENTS AFTER LONG-TERM ZIDOVUDINE TREATMENT SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HIGH-LEVEL RESISTANCE; REVERSE-TRANSCRIPTASE; THERAPY; SENSITIVITY; DIDANOSINE; HIV; AZT AB Zidovudine resistance mutations at reverse transcriptase codons 215 or 41 were found in two-thirds of human immunodeficiency virus type 1 (HIV-1) isolates obtained at baseline from patients enrolled in an AIDS Clinical Trials Group (ACTG) protocol that compared didanosine with continued zidovudine in patients with greater than or equal to 16 weeks of previous zidovudine therapy (ACTG 116B/117). The combined presence of mutations at both codons 215 and 41 conferred an increased risk for progression (relative hazard, 1.82; 95% confidence interval [CI], 1.02-3.26) and an increased risk for death (RH, 5.42; 95% CI, 1.92-15.30) in analyses that controlled for other factors predictive of progression. However, the benefit of switching to didanosine compared with continued zidovudine therapy was independent of the presence of these mutations. Although this information is not helpful in determining when to alter therapy, detection of zidovudine resistance mutations provides prognostic information in patients with advanced HIV disease. C1 UNIV COLORADO,HLTH SCI CTR,DIV INFECT DIS,DENVER,CO 80206. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,CTR STAT DATA ANAL,BOSTON,MA 02115. UNIV ALABAMA,BIRMINGHAM,AL. VET ADM MED CTR,BIRMINGHAM,AL. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV WASHINGTON,SEATTLE,WA 98195. NIAID,DIV AIDS,MED BRANCH,BETHESDA,MD 20892. VET ADM MED CTR,DENVER,CO. UNIV COLORADO,HLTH SCI CTR,DENVER,CO. FU NIAID NIH HHS [AI-27659, AI-29193, AI-32794] NR 24 TC 122 Z9 123 U1 0 U2 0 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 MAY PY 1995 VL 171 IS 5 BP 1172 EP 1179 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QU640 UT WOS:A1995QU64000014 PM 7538548 ER PT J AU HE, Q SPIRO, MJ AF HE, Q SPIRO, MJ TI ISOLATION OF RAT-HEART ENDOTHELIAL-CELLS AND PERICYTES - EVALUATION OF THEIR ROLE IN THE FORMATION OF EXTRACELLULAR-MATRIX COMPONENTS SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE RAT MYOCARDIAL ENDOTHELIAL CELLS; PERICYTES; TYPE VI COLLAGEN; TYPE IV COLLAGEN; TYPE I COLLAGEN; EXTRACELLULAR MATRIX, GLUT1; GLUT4 ID SMOOTH-MUSCLE CELLS; CDNA CLONES; MESANGIAL CELLS; VI COLLAGEN; GLUCOSE; IV; MYOCYTES; CULTURE; DIFFERENTIATION; TRANSPORTERS AB In order to facilitate investigation of the cells responsible for overproduction of type VI collagen in the extracellular matrix surrounding the capillaries of diabetic rat myocardium, procedures have been developed for the isolation from this tissue of endothelial cells as well as a cell type identified as pericytes. This was accomplished by enzymatic and mechanical disruption of ventricles from young rats (125 g) followed by removal of myocytes through their nonadherence to tissue culture surfaces. Endothelial cells were separated by fluorescence-activated cell sorting after staining with rhodamine-labeled acetylated low density lipoprotein and were identified by their monolayer growth pattern, reaction with anti-von Willebrand factor and the ability to form capillary-like tubes induced by low serum concentration. Pericytes were purified by selective scraping for removal of other cell types and were identified by their irregular shape, overlapping growth pattern at confluence, reaction with anti-smooth muscle actin and content of GLUT4 glucose transporter. Fibroblasts, visualized after staining with rhodamine-labeled alpha 2-macroglobulin, were only rarely detected. Analysis of collagen by immunoblotting indicated formation by both cell types of alpha 1(IV) collagen as well as the three subunits of type VI (alpha 3 at 205 kDa and alpha 1 plus alpha 2 at 150 kDa). Both endothelial cells and pericytes demonstrated transcripts for types VI, IV and I collagen, as well as fibronectin, but while the level of the mRNA for type IV collagen was higher in pericytes than in endothelial cells, the reverse was true for collagens VI and I and fibronectin. These observations suggest that both endothelial cells and pericytes contribute to formation of the myocardial capillary matrix, but that changes involving only type VI collagen, such as occur in diabetic cardiomyopathy, may reflect a response primarily of endothelial cells. C1 JOSLIN DIABET CTR, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM, BOSTON, MA USA. FU NHLBI NIH HHS [HL31315]; NIDDK NIH HHS [DK36836] NR 40 TC 20 Z9 20 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 1995 VL 27 IS 5 BP 1173 EP 1183 DI 10.1016/0022-2828(95)90053-5 PG 11 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA QY363 UT WOS:A1995QY36300008 PM 7473775 ER PT J AU ROSS, BM KIM, DK BONVENTRE, JV KISH, SJ AF ROSS, BM KIM, DK BONVENTRE, JV KISH, SJ TI CHARACTERIZATION OF A NOVEL PHOSPHOLIPASE A(2) ACTIVITY IN HUMAN BRAIN SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE PHOSPHOLIPASE A(2); HUMAN BRAIN; PHOSPHOGLYCERIDES ID CALCIUM-INDEPENDENT PHOSPHOLIPASE-A2; MAGNETIC-RESONANCE SPECTROSCOPY; CYTOSOLIC PHOSPHOLIPASE-A2; PLATELET PHOSPHOLIPASE-A2; SUBSTRATE-SPECIFICITY; PURIFICATION; MEMBRANE; RAT; IDENTIFICATION; CELLS AB Phospholipases A(2) (PLA(2)) are a family of enzymes that catalyze the removal of fatty acid residues from phosphoglycerides. The enzyme is postulated to be involved in several human brain disorders, although little is known regarding the status of PLA(2) activity in human CNS. We therefore have characterized some aspects of the PLA(2) activity present in the temporal cortex of human brain. More PLA(2) activity was found in the membrane (particulate) fraction than in the cytosolic fraction. The enzyme could be solubilized from particulate material using 1 M potassium chloride, and was capable of hydrolyzing choline phosphoglyceride (CPG) and ethanolamine phosphoglyceride (EPG), with a preference (approximately eightfold) for EPG over CPG. When the solubilized particulate enzyme was subjected to gel filtration chromatography, PLA(2) activity eluted in a high molecular mass fraction (similar to 180 kDa). PLA(2) activity was weakly stimulated by dithiothreitol, strongly stimulated by millimolar concentrations of calcium ions, and inhibited by brief heat treatment at 57 degrees C, bromophenacyl bromide, the arachidonic acid derivative AACOCF(3), gamma-linolenoyl amide, and N-methyl gamma-linolenoyl amide. Thus, whereas the human brain enzyme(s) characterized in our study displays some of the characteristics of previously characterized PLA(2)s, it differs in several key features. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. MASSACHUSETTS GEN HOSP, MED SERV, BOSTON, MA 02114 USA. RP CLARKE INST PSYCHIAT, HUMAN NEUROCHEM PATHOL LAB, 250 COLL ST, TORONTO, ON M5T 1R8, CANADA. FU NINDS NIH HHS [NS26034] NR 55 TC 41 Z9 42 U1 0 U2 1 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1995 VL 64 IS 5 BP 2213 EP 2221 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA QU384 UT WOS:A1995QU38400038 PM 7722506 ER PT J AU SCHULZ, JB HENSHAW, DR SIWEK, D JENKINS, BG FERRANTE, RJ BENCIPOLLONI, P KOWALL, NW ROSEN, BR BEAL, MF AF SCHULZ, JB HENSHAW, DR SIWEK, D JENKINS, BG FERRANTE, RJ BENCIPOLLONI, P KOWALL, NW ROSEN, BR BEAL, MF TI INVOLVEMENT OF FREE-RADICALS IN EXCITOTOXICITY IN-VIVO SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE FREE RADICALS; EXCITOTOXICITY; MITOCHONDRIA; SPIN TRAPS; NEURODEGENERATIVE DISEASES; HUNTINGTONS DISEASE; PARKINSONS DISEASE ID AMYOTROPHIC-LATERAL-SCLEROSIS; MITOCHONDRIAL ENERGY-METABOLISM; BUTYL-ALPHA-PHENYLNITRONE; SUPEROXIDE-DISMUTASE; HUNTINGTONS-DISEASE; REPERFUSION INJURY; CEREBELLAR NEURONS; OXIDATIVE STRESS; RAT STRIATUM; KAINIC ACID AB Recent evidence has linked excitotoxicity with the generation of free radicals. We examined whether free radical spin traps can attenuate excitotoxic lesions in vivo, Pretreatment with N-fert-butyl-alpha-(2-sulfophenyl)-nitrone (S-PBN) significantly attenuated striatal excitotoxic lesions in rats produced by N-methyl-D-aspartate (NMDA), kainic acid, and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). In a similar manner, striatal lesions produced by 1-methyl-4-phenylpyridinium (MPP(+)), malonate, and 3-acetylpyridine were significantly attenuated by either S-PBN or alpha-phenyl-N-tert-butylnitrone (PBN) treatment. Administration of S-PBN in combination with the NMDA antagonist MK-801 produced additive effects against malonate and 3-acetylpyridine toxicity. Malonate injections resulted in increased production of hydroxyl free radicals ((OH)-O-.) as assessed by the conversion of salicylate to 2,3- and 2,5-dihydroxybenzoic acid (DHBA). This increase was significantly attenuated by S-PBN, consistent with a free radical scavenging effect. S-PBN had no effects on malonate-induced ATP depletions and had no significant effect on spontaneous striatal electrophysiologic activity. These results provide the first direct in vivo evidence for the involvement of free radicals in excitotoxicity and suggest that antioxidants may be useful in treating neurologic illnesses in which excitotoxic mechanisms have been implicated. C1 MASSACHUSETTS GEN HOSP,NMR CTR,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. BOSTON UNIV,SCH MED,BEDFORD VA MED CTR,CTR GERIATR RES EDUC & CLIN,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02118. RP SCHULZ, JB (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,WARREN 408,BOSTON,MA 02114, USA. RI Schulz, Jorg/D-9786-2012; Kowall, Neil/G-6364-2012 OI Schulz, Jorg/0000-0002-8903-0593; Kowall, Neil/0000-0002-6624-0213 FU NINDS NIH HHS [NS 10828, NS 31579]; PHS HHS [16367] NR 51 TC 283 Z9 283 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1995 VL 64 IS 5 BP 2239 EP 2247 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA QU384 UT WOS:A1995QU38400041 PM 7536809 ER PT J AU BOWLING, AC BARKOWSKI, EE MCKENNAYASEK, D SAPP, P HORVITZ, HR BEAL, MF BROWN, RH AF BOWLING, AC BARKOWSKI, EE MCKENNAYASEK, D SAPP, P HORVITZ, HR BEAL, MF BROWN, RH TI SUPEROXIDE-DISMUTASE CONCENTRATION AND ACTIVITY IN FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE AMYOTROPHIC LATERAL SCLEROSIS; NEURODEGENERATION; FREE RADICALS; OXIDATIVE DAMAGE; SUPEROXIDE DISMUTASE ID MUTATIONS AB Some cases of autosomal-dominant familiar amyotrophic lateral sclerosis (FALS) have been associated with mutations in SOD1, the gene that encodes Cu/Zn superoxide dismutase (Cu/Zn SOD). We determined the concentrations (mu g of Cu/Zn SOD/mg of total protein), specific activities (U/mu g of total protein), and apparent turnover numbers (U/mu mol of Cu/ Zn SOD) of Cu/Zn SOD in erythrocyte lysates from patients with known SOD1 mutations. We also measured the concentrations and activities of Cu/Zn SOD in FALS patients with no identifiable SOD1 mutations, sporadic ALS (SALS) patients, and patients with other neurologic disorders. The concentration and specific activity of Cu/Zn SOD were decreased in all patients with SOD1 mutations, with mean reductions of 51 and 46%, respectively, relative to controls. In contrast, the apparent turnover number of the enzyme was not altered in these patients. For the six mutations studied, there was no correlation between enzyme concentration or specific activity and disease severity, expressed as either duration of disease or age of onset. No significant alterations in the concentration, specific activity, or apparent turnover number of Cu/Zn SOD were detected in the FALS patients with no identifiable SOD1 mutations, SALS patients, or patients with other neurologic disorders. That Cu/Zn SOD concentration and specific activity are equivalently reduced in erythrocytes from patients with SOD1 mutations suggests that mutant Cu/Zn SOD is unstable in these cells. That concentration and specific activity do not correlate with disease severity suggests that an altered, novel function of the enzyme, rather than reduction of its dismutase activity, may be responsible for the pathogenesis of FALS. C1 MASSACHUSETTS GEN HOSP,NEUROMUSCULAR RES CTR,NEUROL SERV,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,NEUROCHEM LAB,BOSTON,MA 02129. MIT,HOWARD HUGHES MED INST,DEPT BIOL,CAMBRIDGE,MA 02139. FU NIA NIH HHS [AG05134]; NINDS NIH HHS [1PO1NS31248-01, K08-NS01780] NR 18 TC 102 Z9 102 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 MAY PY 1995 VL 64 IS 5 BP 2366 EP 2369 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA QU384 UT WOS:A1995QU38400059 PM 7722523 ER PT J AU KOWALL, N FERRANTE, R SCHULZ, J BROWN, R BEAL, MF AF KOWALL, N FERRANTE, R SCHULZ, J BROWN, R BEAL, MF TI INTRACISTERNAL INFUSION OF SUPEROXIDE DISMUTASE-1 (SOD1) ANTISENSE OLIGODEOXYNUCLEOTIDE CAUSES ANTERIOR HORN CELL DEGENERATION IN-VIVO SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 BEDFORD VET ADM MED CTR,BEDFORD,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BOSTON UNIV,SCH MED,BOSTON,MA 02118. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1995 VL 54 IS 3 BP 417 EP 417 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA QX385 UT WOS:A1995QX38500039 ER PT J AU DELAMONTE, SM BLOCH, KD WANDS, JR AF DELAMONTE, SM BLOCH, KD WANDS, JR TI ABNORMAL NTP AND CENOS GENE-EXPRESSION CORRELATE WITH DENDRITIC PATHOLOGY IN AD SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1995 VL 54 IS 3 BP 430 EP 430 DI 10.1097/00005072-199505000-00091 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA QX385 UT WOS:A1995QX38500090 ER PT J AU YONG, WH CHOU, D UEKI, K VONDEIMLING, A LOUIS, DN AF YONG, WH CHOU, D UEKI, K VONDEIMLING, A LOUIS, DN TI THE CHROMOSOME 19Q GLIOMA TUMOR-SUPPRESSOR GENE - DELETION MAPPING AND CANDIDATE GENES SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. INST NEUROPATHOL,BONN,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1995 VL 54 IS 3 BP 439 EP 439 DI 10.1097/00005072-199505000-00130 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA QX385 UT WOS:A1995QX38500129 ER PT J AU HSU, DW KOERNER, FC EFIRD, JT HEDLEYWHYTE, ET AF HSU, DW KOERNER, FC EFIRD, JT HEDLEYWHYTE, ET TI ESTROGEN AND PROGESTERONE RECEPTORS IN MENINGIOMAS - PROGNOSTIC CONSIDERATIONS SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1995 VL 54 IS 3 BP 455 EP 455 DI 10.1097/00005072-199505000-00194 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA QX385 UT WOS:A1995QX38500193 ER PT J AU JOSEPH, JT LISLE, DK LOUIS, DN AF JOSEPH, JT LISLE, DK LOUIS, DN TI NF2 GENE ANALYSIS IN HEMANGIOPERICYTOMAS AND MENINGIOMAS SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1995 VL 54 IS 3 BP 467 EP 467 DI 10.1097/00005072-199505000-00241 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA QX385 UT WOS:A1995QX38500240 ER PT J AU CANNON, SC HAYWARD, LJ BEECH, J BROWN, RH AF CANNON, SC HAYWARD, LJ BEECH, J BROWN, RH TI SODIUM-CHANNEL INACTIVATION IS IMPAIRED IN EQUINE HYPERKALEMIC PERIODIC PARALYSIS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SKELETAL-MUSCLE; QUARTER HORSES; ALPHA-SUBUNIT; MYOTONIA; MUTATION AB 1. Equine hyperkalemic periodic paralysis (E-HPP) is a dominantly inherited disorder of muscle that causes recurrent episodes of stiffness (myotonia) and weakness in association with elevated serum K+. Affected horses carry a mutant allele of the skeletal muscle isoform of the Na channel alpha-subunit. To understand how this mutation may cause the disease phenotype, the functional defect in Na channel behavior was defined physiologically by recording unitary currents from cell-attached patches on normal and affected equine myotubes. 2. The presence of the mutation was confirmed in our cell line by restriction digest of polymerase chain reaction (PCR)-amplified genomic DNA. Myotubes from the affected horse were heterozygous for the point mutation that codes for a Phe to Leu substitution in S-3 of domain IV. This assay provides a rapid technique to screen for the mutation in horses at risk. 3. The primary physiological defect in mutant Na channels was an impairment of inactivation. This defect was manifest as bursts of persistent activity during which the channel closed and reopened throughout a maintained depolarization. Disrupted inactivation slowed the decay of the ensemble-averaged current and produced an eightfold increase in the steady-state open probability measured at the end of a 40-ms pulse. This point mutation identifies a new region of the alpha subunit that is important for rapid inactivation of the channel. 4. The persistent Na current was produced by a distinct mode of gating. Failure of a mutant channel to inactivate was infrequent and occurred in groups of consecutive trials. Furthermore, the open time distributions for mutant Na channels contained a second, slow component (tau(s) = 1-2 ms) in addition to a fast component (tau(f) = 0.4 ms), which by itself was sufficient to represent the distribution in normal channels. These observations are consistent with the notion that channels slowly switch between two modes of inactivation: rapid versus noninactivating. Although the variance was high, for mutant channels there was a trend toward more frequent bursts of noninactivating behavior when extracellular K+ was increased. For Na channels in E-HPP myotubes, the ratio of steady-state to peak open probability increased threefold (0.024 from 0.008) in 10 versus 0 mM [K+](o). Conversely, in normal Na channels the steady-state to peak P P-open was 0.003 and invariant with [K+](o). C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. UNIV PENN,SCH VET MED,DEPT CLIN STUDIES,KENNETT SQ,PA 19348. RP CANNON, SC (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,EDWARDS BLDG,RM 413A,50 BLOSSOM ST,BOSTON,MA 02114, USA. FU NIAMS NIH HHS [AR-41025, AR-42703] NR 29 TC 30 Z9 30 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 1995 VL 73 IS 5 BP 1892 EP 1899 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA QY833 UT WOS:A1995QY83300015 PM 7623088 ER PT J AU SRIDHAR, TS LIBERMAN, MC BROWN, MC SEWELL, WF AF SRIDHAR, TS LIBERMAN, MC BROWN, MC SEWELL, WF TI A NOVEL CHOLINERGIC SLOW EFFECT OF EFFERENT STIMULATION ON COCHLEAR POTENTIALS IN THE GUINEA-PIG SO JOURNAL OF NEUROSCIENCE LA English DT Article DE ACH; COCHLEA; OUTER HAIR CELL; OLIVOCOCHLEAR EFFERENTS; IN VIVO PHARMACOLOGY ID CROSSED-OLIVOCOCHLEAR-BUNDLE; OUTER HAIR-CELLS; NERVE-FIBER RESPONSES; ELECTRICAL-STIMULATION; CAT COCHLEA; ACETYLCHOLINE; NEURONS; INNERVATION; MORPHOLOGY; AFFERENT AB This report documents slow changes in cochlear responses produced by electrical stimulation of the olivocochlear bundle (OCB), which provides efferent innervation to the hair cells of the cochlea, These slow changes have time constants of 25-50 sec, three orders of magnitude slower than those reported previously, Such ''slow effects'' are similar to classically described ''fast effects'' in that (1) they comprise a suppression of the compound action potential (CAP) of the auditory nerve, mirrored by an enhancement of the cochlear microphonic potential (CM) generated largely by the outer hair cells; (2) the magnitude of suppression decreases as the intensity of the acoustic stimulus increases; (3) they share the same dependence on OCB stimulation rate; (4) both are extinguished upon cutting the OCB; and (5) both are blocked with similar concentrations of a variety of cholinergic antagonists as well as with strychnine and bicuculline, These observations suggest that both fast and slow effects are mediated by the same receptor and are produced by conductance changes in outer hair cells, Slow effects differ from fast effects in that (1) fast effects are greatest for acoustic stimulus frequencies between 6 and 10 kHz, whereas slow effects peak for frequencies from 12 to 16 kHz, and (2) fast effects persist over long periods of OCB stimulation, whereas slow effects diminish after 60 sec of stimulation, The time course of the slow effects can be described mathematically by assuming that each shock-burst produces, in addition to a fast effect, a small decrease in CAP amplitude that decays exponentially with a time constant that is long relative to the intershock interval, The long time constant of the slow effect compared to the fast effect suggests that it may arise from a distinct intracellular mechanism, possibly mediated by second-messenger systems. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,EATON PEABODY LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. FU NIDCD NIH HHS [DC00119, DC00188, DC0076] NR 48 TC 118 Z9 121 U1 0 U2 2 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 MAY PY 1995 VL 15 IS 5 BP 3667 EP 3678 PN 1 PG 12 WC Neurosciences SC Neurosciences & Neurology GA QY982 UT WOS:A1995QY98200040 PM 7751937 ER PT J AU CHAPMAN, PH FRIM, DM AF CHAPMAN, PH FRIM, DM TI SYMPTOMATIC SYRINGOMYELIA FOLLOWING SURGERY TO TREAT RETETHERING OF LIPOMYELOMENINGOCELES SO JOURNAL OF NEUROSURGERY LA English DT Article DE LIPOMYELOMENINGOCELE; TETHERED SPINAL CORD; SYRINGOMYELIA; SPINAL LIPOMA; HYDROMYELIA ID SURGICAL-TREATMENT; MANAGEMENT; CHILDREN; LIPOMAS; LESIONS AB The authors report the cases of three children in whom symptomatic syringomyelia occurred de novo following an operation to relieve retethering of a previously treated lipomyelomeningocele. No patient had a Chiari malformation. In two cases, magnetic resonance imaging performed before the first operation did not show a syrinx. At the time of surgery to relieve retethering, it was discovered that one of these patients had a minor degree of terminal hydromyelia and the other had a prominent central canal within the conus medullaris. The third patient was initially studied by means of myelography, which gave no indication of a syrinx, and one was not found at the time of the surgery to release the retethering. Neurological deficits appeared abruptly within several months of operation in two children, and insidiously after 12 to 18 months in the other symptomatic individual. In all three cases, the syrinx involved the distal spinal cord adjacent to the site of the lipoma. Treatment consisted of syringosubarachnoid shunting, which arrested the progression of deficits but only partially reversed them. The details of each case are presented and the possible mechanism of syrinx formation discussed. Early recognition and treatment of this unusual but important problem are emphasized. RP CHAPMAN, PH (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV NEUROSURG,NEUROSURG SERV,BOSTON,MA 02114, USA. NR 13 TC 28 Z9 29 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 MAY PY 1995 VL 82 IS 5 BP 752 EP 755 DI 10.3171/jns.1995.82.5.0752 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA QU325 UT WOS:A1995QU32500006 PM 7714598 ER PT J AU MAYNARD, KI OGILVY, CS AF MAYNARD, KI OGILVY, CS TI PATTERNS OF PEPTIDE-CONTAINING PERIVASCULAR NERVES IN THE CIRCLE OF WILLIS - THEIR ABSENCE IN INTRACRANIAL ARTERIOVENOUS-MALFORMATIONS SO JOURNAL OF NEUROSURGERY LA English DT Article DE CALCITONIN GENE-RELATED PEPTIDE; NEUROPEPTIDE Y; CEREBRAL ARTERY; VASOACTIVE INTESTINAL POLYPEPTIDE; PERIVASCULAR NERVE; ARTERIOVENOUS MALFORMATION ID VASOACTIVE INTESTINAL POLYPEPTIDE; GENE-RELATED PEPTIDE; HUMAN CEREBRAL-ARTERIES; CENTRAL EAR ARTERY; NEUROPEPTIDE-Y; SUBSTANCE-P; CEREBROVASCULAR NERVES; IMMUNOHISTOCHEMICAL LOCALIZATION; TEMPORAL ARTERIES; INNERVATION AB Using standard immunohistochemical techniques and an improved procedure for whole-mount vascular preparations, the authors describe the pattern and density of innervation of calcitonin gene-related peptide (CGRP)-like, neuropeptide Y (NPY)-like and vasoactive intestinal polypeptide (VIP)-like immunoreactivity in major arteries of postmortem adult human circles of Willis. Calcitonin gene-related peptide-, NPY-, and VIP-LI exhibited a variety of varicose and nonvaricose single axons, and small and large perivascular nerve bundles. Although the density of innervation within each vascular segment was highly variable, the pattern of innervation for each neuropeptide observed was consistent throughout the circle of Willis. With the use of human and rat circles of Willis as positive control preparations, the lack of CGRP-LI, NPY-LI, and VIP-LI in vessel segments taken from five cases of intracranial arteriovenous malformations (AVMs) is also reported. It is concluded that adult human circles of Willis exhibit CGRP-LI, NPY-LI, and VIP-LI perivascular nerves. in addition, intracranial AVMs do not possess these peptide-containing nerves that, in animals, normally mediate neurogenic control in the cerebrovasculature. It is hypothesized that this lack of innervation, and hence neurotrophic influence, may contribute to the development of AVMs. RP MAYNARD, KI (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,EDWARDS 414,32 FRUIT ST,BOSTON,MA 02114, USA. NR 41 TC 11 Z9 12 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 MAY PY 1995 VL 82 IS 5 BP 829 EP 833 DI 10.3171/jns.1995.82.5.0829 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA QU325 UT WOS:A1995QU32500017 PM 7714609 ER PT J AU YOKOTA, M PETERSON, JW KAOUTZANIS, MC YAMAKAWA, K SIBILIA, R ZERVAS, NT AF YOKOTA, M PETERSON, JW KAOUTZANIS, MC YAMAKAWA, K SIBILIA, R ZERVAS, NT TI PROTEIN-KINASE-C AND DIACYLGLYCEROL CONTENT IN BASILAR ARTERIES DURING EXPERIMENTAL CEREBRAL VASOSPASM IN THE DOG SO JOURNAL OF NEUROSURGERY LA English DT Article DE VASOSPASM; SUBARACHNOID HEMORRHAGE; DIACYLGLYCEROL; PROTEIN KINASE C; VASCULAR SMOOTH MUSCLE; DOG ID SMOOTH-MUSCLE CONTRACTION; SUBARACHNOID HEMORRHAGE; PATHOGENESIS; ACTIVATION; MEMBRANE; CELLS AB Sixteen dogs were entered into a study of the double subarachnoid hemorrhage (SAH) model of cerebral vasospasm. Six animals were sacrificed 72 hours after the first experimental SAH, and the remaining 10 animals were killed 72 hours after the second experimental SAH; ten additional animals served as controls. Basilar arteries were rapidly excised from the dogs and frozen. Multiple segments of the frozen arteries were analyzed independently for total protein and 1,2-diacylglycerol (DAG) content, which averaged 3.17 (+/- 0.27 standard error of the mean; SEM) pmol DAG/mu g protein for all 25 arteries analyzed. A slight decreasing trend in DAG content relative to that of control vessels was found in vessels chronically constricted in situ by subarachnoid blood clot; however, this trend did not attain statistical significance. Two segments of the same vessels were assayed independently for protein kinase C (PKC) activity, which averaged 1.21 (+/- 0.08 SEM) pmol phosphate incorporation per minute per mu g protein for all 24 arteries analyzed. A small decrease in PKC content was noted in vessels that experienced a single SAH; however, PKC returned to near control value in vessels subjected to double SAH. The ratio of particulate (membrane bound) to soluble PKC activity, an indicator of PKC translocation to the membrane and hence PKC activation, showed a small but statistically significant trend to increase with experimental SAH. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,CEREBROVASC BIOPHYS LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HYOGO MED UNIV,DEPT NEUROSURG,HYOGO,JAPAN. FU NHLBI NIH HHS [HL22573, HL44554] NR 16 TC 16 Z9 16 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 MAY PY 1995 VL 82 IS 5 BP 834 EP 840 DI 10.3171/jns.1995.82.5.0834 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA QU325 UT WOS:A1995QU32500018 PM 7714610 ER PT J AU CLINTON, SK LI, PS MULLOY, AL IMREY, PB NANDKUMAR, S VISEK, WJ AF CLINTON, SK LI, PS MULLOY, AL IMREY, PB NANDKUMAR, S VISEK, WJ TI THE COMBINED EFFECTS OF DIETARY-FAT AND ESTROGEN ON SURVIVAL, 7,12-DIMETHYLBENZ(A)ANTHRACENE-INDUCED BREAST-CANCER AND PROLACTIN METABOLISM IN RATS SO JOURNAL OF NUTRITION LA English DT Article DE RATS; ESTROGEN; PROLACTIN; DIETARY FAT; BREAST CANCER ID SPRAGUE-DAWLEY RATS; MAMMARY-TUMORS; POSTMENOPAUSAL WOMEN; FISH OIL; CORN-OIL; GROWTH; PROTEIN; TUMORIGENESIS; BINDING; MICE AB The relationships between dietary fat concentration (10 or 40% of energy), fat source (corn oil or beef tallow) and estrogen (control, ovariectomy or ovariectomy with estrogen replacement) to 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast carcinogenesis and survival in rats were studied in a 2 x 2 x 3 factorial experiment. Female Sprague-Dawley rats given DMBA (2.5 mg/100 g body wt, intragastric) at 55 d of age were randomly allocated to three groups 48 h later: sham ovariectomy (control), ovariectomy (OVX) or ovariectomy with a subcutaneous estrogen implant (OVX+E). Each group was subdivided into dietary groups fed 10 and 40% of energy as corn oil or beef tallow for 70 wk. OVX+E rats exhibited serum estrogen concentrations in excess of physiologic values. Survival at 70 wk for the 3 hormonal groups was control 51%, OVX 67% and OVX+E 13%. Mortality in controls was doubled by feeding a high fat diet; no diet effect was detected in OVX or OVX+E rats. Palpable tumors developed in 74, 14 and 60% of control, OVX and OVX+E rats, respectively. High fat diets approximately doubled the hazard of developing a palpable tumor. Adenocarcinoma prevalence was 58, 12 and 63% in control, OVX and OVX+E rats, respectively. The odds of having any tumor, an adenocarcinoma or an adenoma were multiplied by 3.6, 2.8 and 2.3, respectively, for rats fed high vs. low fat. Additional studies showed that diet had no effect on serum prolactin or estrogen concentrations or metabolism and clearance of intravenously administered radiolabeled prolactin. We demonstrated that high dietary fat concentration enhances breast carcinogenesis independently of cyclic ovarian function, although the presence of estrogen may be a prerequisite for significant dietary modulation. The effect of fat on breast cancer is not mediated by major changes in systemic prolactin metabolism. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CLIN ONCOL,BOSTON,MA 02115. NATL CHENG KUNG UNIV,COLL MED,DEPT PHYSIOL,TAINAN 70101,TAIWAN. MED COLL GEORGIA,DEPT MED,AUGUSTA,GA 30912. UNIV ILLINOIS,COLL MED,DEPT MED INFORMAT SCI,URBANA,IL 61801. UNIV ILLINOIS,COLL MED,DEPT COMMUNITY HLTH,URBANA,IL 61801. UNIV ILLINOIS,COLL MED,DEPT STAT,URBANA,IL 61801. UNIV ILLINOIS,COLL MED,DEPT PATHOL,URBANA,IL 61801. UNIV ILLINOIS,COLL MED,DEPT INTERNAL MED,DIV NUTR SCI,URBANA,IL 61801. RP CLINTON, SK (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,44 BINNEY ST,BOSTON,MA 02115, USA. OI Imrey, Peter/0000-0002-0533-4603 FU NCI NIH HHS [CA23326, CA29629, K07 CA01680] NR 57 TC 17 Z9 17 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 1995 VL 125 IS 5 BP 1192 EP 1204 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA QX169 UT WOS:A1995QX16900008 PM 7738679 ER PT J AU DAVIES, JP TSE, MK HARRIS, WH AF DAVIES, JP TSE, MK HARRIS, WH TI IN-VITRO EVALUATION OF BONDING OF THE CEMENT-METAL INTERFACE OF A TOTAL HIP FEMORAL COMPONENT USING ULTRASOUND SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID INITIATION; FAILURE AB Debonding of the cement-metal interface of a cemented femoral component is one mechanism associated with loosening of total hip replacement. An ultrasonic pulse-echo technique was developed to determine, nondestructively, the integrity of the cement-metal interface in vitro. The characteristics of the ultrasonic reflections of bonded and debonded interfaces were obtained by using a physical model that consisted of a flat slab of cement and a flat cobalt alloy plate with known conditions of bonded and debonded interfaces. The same model was used to establish that the ultrasonic technique could distinguish between two surfaces that were in direct apposition but not bonded and those that were actually bonded. This technique then was shown to be useful in nondestructively detecting bonded and debonded cement-metal interfaces of femoral prostheses cemented into fiberglass femurs and femurs from human cadavera. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. QUAL ENGN ASSOCIATES,BURLINGTON,MA. NR 7 TC 9 Z9 9 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD MAY PY 1995 VL 13 IS 3 BP 335 EP 338 DI 10.1002/jor.1100130306 PG 4 WC Orthopedics SC Orthopedics GA RG920 UT WOS:A1995RG92000005 PM 7602394 ER PT J AU AMIEL, D HARWOOD, FL GELBERMAN, RH CHU, CR SEILER, JG ABRAHAMSSON, S AF AMIEL, D HARWOOD, FL GELBERMAN, RH CHU, CR SEILER, JG ABRAHAMSSON, S TI AUTOGENOUS INTRASYNOVIAL AND EXTRASYNOVIAL TENDON GRAFTS - AN EXPERIMENTAL-STUDY OF PRO ALPHA-1(I) COLLAGEN MESSENGER-RNA EXPRESSION IN DOGS SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Note AB On the basis of recent evidence that the healing processes of tendon grafts are donor-tissue specific, in situ hybridization, using a 372 bp cDNA fragment complementary to a portion of pro alpha 1(I) collagen mRNA, was utilized to compare the cellular responses to transplantation exhibited by autogenous intrasynovial and extrasynovial flexor tendon grafts. Intrasynovial and extrasynovial tendons from the hindpaw were transferred to synovial sheaths in the forepaw of 12 mongrel dogs (24 tendons) and treated with immediate controlled passive motion. The tendon grafts were harvested at 2, 4, and 6 weeks, and each was divided into a proximal, central (8 mm), and distal portion. Sections from the central portion were embedded in paraffin and subjected to in situ hybridization, autoradiography, and staining levels of procollagen mRNA then were assessed by microscopic examination. The two types of tendon grafts exhibited different levels of pro alpha 1(I) collagen mRNA expression at all three time points. Intrasynovial tendon grafts displayed no areas of increased type-I procollagen mRNA at 2, 4, and 6 weeks. The extrasynovial tendon grafts displayed increased surface levels of type-I procollagen mRNA at 2 and 4 weeks; the levels decreased to background levels by 6 weeks. The high levels of procollagen mRNA exhibited by the extrasynovial grafts suggest increased collagen synthetic activity, indicative of a cellular response to injury: whereas the preservation of low levels of expression in the intrasynovial grafts may signify a less inflammatory cellular response. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114. RP AMIEL, D (reprint author), UNIV CALIF SAN DIEGO,DEPT ORTHOPAED,9500 GILMAN DR,LA JOLLA,CA 92093, USA. FU NIAMS NIH HHS [AR33097] NR 10 TC 17 Z9 18 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD MAY PY 1995 VL 13 IS 3 BP 459 EP 463 DI 10.1002/jor.1100130321 PG 5 WC Orthopedics SC Orthopedics GA RG920 UT WOS:A1995RG92000020 PM 7602408 ER PT J AU YU, YM YOUNG, VR TOMPKINS, RG BURKE, JF AF YU, YM YOUNG, VR TOMPKINS, RG BURKE, JF TI COMPARATIVE-EVALUATION OF THE QUANTITATIVE UTILIZATION OF PARENTERALLY AND ENTERALLY ADMINISTERED LEUCINE AND L-[1-13C,15N]LEUCINE WITHIN THE WHOLE-BODY AND THE SPLANCHNIC REGION SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article ID BIRTH-WEIGHT INFANTS; GUT MASS; NUTRITION; KINETICS; PROTEIN; PHENYLALANINE; METABOLISM; TPN; L-<1-C-13,N-15>LEUCINE; TRAUMA AB Background: The purpose of this study was to quantify the kinetic aspects of leucine metabolism in the whole body and within the splanchnic region when an amino acid mixture is administered by the enteral route as compared with administration by the parenteral route. Methods: Seven chronically catheterized dogs were studied during an intragastric infusion of L-[1-C-13,-15-N]leucine with 0.24 g of complete amino acid mixture (kg-1.h-1) for 6 hours. The results are compared with those previously reported for nine dogs studied under essentially identical experimental conditions except that the tracer and amino acid mixtures were given by vein. Results: At the whole body level, the various parameters of leucine metabolism (flux, oxidation, and disappearance into and release from proteins) were not significantly different among animals that were infused enterally and those that were infused parenterally. Leucine metabolism within the splanchnic region and gut was more extensive for enteral administration than for parenteral administration. For the splanchnic region, 31.4%, 27.9%, and 6.0% of enterally administered leucine was used for protein synthesis, deamination, and oxidization, respectively, compared with respective mean values of 19.5% (p < .001), 13.4% (p < .001), and 4.1% (p < .05) for parenterally administered leucine. For liver, 4.8% of enterally administered leucine was oxidized compared with 2.3% (p < .001) of parenterally administered leucine. These findings are qualitatively similar to those reported previously by us when comparing enteral and parenteral amino acid intakes but with an IV tracer infusion. Conclusion: Enteral administration seems to be more effective than an acute parenteral feeding regimen, at least in maintaining leucine (protein) balance in gut tissues. C1 MASSACHUSETTS GEN HOSP,TRAUMA SERV,BOSTON,MA 02114. MIT,HUMAN NUTR LAB,CAMBRIDGE,MA 02139. RP YU, YM (reprint author), SHRINERS BURNS INST,51 BLOSSOM ST,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK 15856]; NIGMS NIH HHS [GM02700] NR 31 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD MAY-JUN PY 1995 VL 19 IS 3 BP 209 EP 215 DI 10.1177/0148607195019003209 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RB810 UT WOS:A1995RB81000008 PM 8551649 ER PT J AU CREAGH, TM BAIN, BJ EVANS, DJ REID, CDL YOUNG, RH FLANAGAN, AM AF CREAGH, TM BAIN, BJ EVANS, DJ REID, CDL YOUNG, RH FLANAGAN, AM TI ENDOMETRIAL EXTRAMEDULLARY HEMATOPOIESIS SO JOURNAL OF PATHOLOGY LA English DT Article DE ENDOMETRIUM; EXTRAMEDULLARY HEMATOPOIESIS; HEMATOLOGICAL ABNORMALITIES; MYELOPROLIFERATIVE DISORDER ID AGNOGENIC MYELOID METAPLASIA; HEMATOPOIESIS AB Four cases of endometrial extramedullary haemopoiesis are reported, all with associated haematological disease. The diagnoses of a myeloproliferative disorder and thalassaemia trait were made as a consequence of the histological observations and subsequent haematological investigations in two cases. The third case occurred in a patient with an established diagnosis of chronic myeloid leukaemia. The diagnosis of extramedullary haemopoiesis in the final case was made on autopsy material from a patient with multiple myeloma. The endometrium from five other women with known myelofibrosis was examined but extramedullary haemopoiesis was not found. Endometrium from 32 fetuses did not contain haemopoietic elements, excluding the likelihood of the endometrium being a common site for extramedullary haemopoiesis in development. Endometrial extramedullary haemopoiesis is an uncommon finding, but it is worthy of note, as it may herald the presence of an underlying haematological abnormality. C1 UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,ST MARYS HOSP,SCH MED,DEPT HISTOPATHOL,LONDON W2 1PG,ENGLAND. NORTHWICK PK HOSP & CLIN RES CTR,DEPT HAEMATOL,HARROW HA1 3UJ,MIDDX,ENGLAND. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 23 TC 15 Z9 15 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAY PY 1995 VL 176 IS 1 BP 99 EP 104 DI 10.1002/path.1711760114 PG 6 WC Oncology; Pathology SC Oncology; Pathology GA QY940 UT WOS:A1995QY94000013 PM 7616362 ER PT J AU HE, HD MCKAY, G WIRSHING, B MIDHA, KK AF HE, HD MCKAY, G WIRSHING, B MIDHA, KK TI DEVELOPMENT AND APPLICATION OF A SPECIFIC AND SENSITIVE RADIOIMMUNOASSAY FOR TRIHEXYPHENIDYL TO A PHARMACOKINETIC STUDY IN HUMANS SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID CHROMATOGRAPHIC METHOD; PARKINSONS-DISEASE; GAS-CHROMATOGRAPHY; BENZHEXOL; PLASMA; HYDROCHLORIDE; QUANTITATION; MEMORY AB A radioimmunoassay (RIA) for trihexyphenidyl was developed through the use of a bovine thyroglobulin conjugate of trihexyphenidyl hemisuccinate. Immunization of New Zealand white rabbits with this drug-protein conjugate yielded antisera, for which the antibody titer and specificity were evaluated. An antiserum that had the highest titer and minimal cross-reactivities to major metabolites of trihexyphenidyl, such as trihexyphenidyl N-oxide (2%), hydroxytrihexyphenidyl (1%), and the antipsychotic drugs fluphenazine (<1%), flupenthixol (<1%), chlorpromazine (<1%), and haloperidol (<1%), was selected for development of a RIA. The described RIA enables the quantitation of 7.8 pg of trihexyphenidyl in 200 mu L of human plasma with a mean coefficient of variation of <6% across the range of the standard curve. Assay specificity was further demonstrated by comparison of results obtained directly and after selective extraction of trihexyphenidyl from replicate samples. This RIA procedure was applied to the analysis of steady state plasma samples obtained from patients undergoing treatment with trihexyphenidyl (2-8 mg) and plasma samples obtained from eight healthy male volunteers after administration of a single 4 mg oral dose of the drug. The results of the latter single dose studies demonstrated that the mean +/-SD for the peak concentration (C-max), the time to C-max (T-max), the rate of absorption (K-a), and the area under the curve from 0 to 72 h (AUC(0-72)) were found to be 7.15 +/- 2.58 ng/mL, 1.32 +/- 0.58 h, 2.07 +/- 0.93 1/h, and 201 +/- 71 ng h/mL, respectively. The human subjects had a biphasic plot of mean plasma concentration Versus time consisting of an initially rapid distribution phase (T-alpha 1/2 = 5.33 +/- 3.23 h) and a later slower elimination phase (T-beta 1/2 = 32.7 +/- 6.35 h). C1 UNIV SASKATCHEWAN,COLL PHARM & NUTR,SASKATOON,SK S7N 0W0,CANADA. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. NR 29 TC 6 Z9 6 U1 0 U2 1 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD MAY PY 1995 VL 84 IS 5 BP 561 EP 567 DI 10.1002/jps.2600840509 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA QX151 UT WOS:A1995QX15100008 PM 7658345 ER PT J AU KAUFMANN, MA CASTELLI, I PARGGER, H DROP, LJ AF KAUFMANN, MA CASTELLI, I PARGGER, H DROP, LJ TI NITRIC-OXIDE DOSE-RESPONSE STUDY IN THE ISOLATED-PERFUSED RAT-KIDNEY AFTER INHIBITION OF ENDOTHELIUM-DERIVED RELAXING FACTOR SYNTHESIS - THE ROLE OF SERUM-ALBUMIN SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID L-ARGININE; BLOOD-VESSELS; SMOOTH-MUSCLE; RELEASE; RELAXATION; ACETYLCHOLINE; RESISTANCE; MECHANISMS; PRESSURE; ADDUCT AB The dose-response relationship of steady-state nitric oxide (NO) administration on renal vascular resistance in isolated rat kidneys (IPRK) perfused at constant pressure was investigated after inhibition of NO synthesis with N-G-monomethyl-L-arginine (L-NMMA). To study the influence of biological thiols on renovascular NO effects, experiments were carried out with Krebs-Henseleit (KH) perfusate solutions alone, and in combination with bovine serum albumin (KH-ALB). Steady-state administration of NO by gassing the perfusate with 0 to 340 ppm NO led to graded decreases in renovascular tone. The minimal effective NO perfusate concentration in the absence of endogenous NO synthesis was about 6 to 8 nM, whereas a near-maximal effect was observed with similar to 200 nM. The presence of albumin reduced the speed of onset of renal vasodilation and the maximal effect at a given concentration of NO, After termination of NO administration, NO-induced vasodilation persisted in KH-ALB perfused kidneys for 30 min, whereas KH-perfused kidneys showed a rapid reconstriction. These findings suggest that the prolonged, potent renal vasodilation was caused by a reaction of bovine serum albumin (BSA) with oxides of nitrogen to form S-nitroso-BSA. Nitrosothiol levels in the KH-ALB perfusate were found to be proportional to the concentration of NO administered. The above-mentioned findings, confirmed in identical experiments with diethylamine NONOate, a novel NO-liberating substance, support the biological importance of S-nitrosothiols (RS-NO) in the action and metabolism of endothelium-derived relaxing factor (EDRF) in the IPRK. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BEECHER LAB,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA. UNIV BASEL,DEPT ANAESTHESIA & RES,BASEL,SWITZERLAND. NR 29 TC 35 Z9 36 U1 0 U2 2 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 MAY PY 1995 VL 273 IS 2 BP 855 EP 862 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QX925 UT WOS:A1995QX92500040 PM 7752090 ER PT J AU BARSKY, AJ BRENER, J COEYTAUX, RR CLEARY, PD AF BARSKY, AJ BRENER, J COEYTAUX, RR CLEARY, PD TI ACCURATE AWARENESS OF HEARTBEAT IN HYPOCHONDRIACAL AND NON-HYPOCHONDRIACAL PATIENTS SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article ID SOMATOSENSORY AMPLIFICATION; SELF-PERCEPTION; DISCRIMINATION; PATTERNS; EXERCISE; ANXIETY; PAIN AB We measured the accurate awareness of resting heartbeat in a sample of medical outpatients meeting DSM-III-R criteria for hypochondriasis (n = 60), and in a comparison group of non-hypochondriacal patients (n = 60) from the same general medical clinic. Patients also completed subjective self-report ratings of their sensitivity to benign bodily sensation and of functional somatic symptoms. Hypochondriacal patients did not differ significantly from non-hypochondriacal patients in their accurate awareness of heartbeat. They did, however, consider themselves more sensitive to benign bodily sensation and report more functional somatic symptoms. Within each sample, the only statistically significant association found was a negative correlation (r = -0.32, p = 0.025) between heartbeat awareness and the severity of hypochondriacal symptoms among the hypochondriacal patients. These results suggest that hypochondriacs may not be more accurately aware of normal cardiac activity, and therefore that hypochondriacal somatic complaints may not result from an unusually fine discriminative ability to detect normal physiological sensations that non-hypochondriacal individuals do not perceive. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. SUNY STONY BROOK,DEPT PSYCHOL,STONY BROOK,NY 11794. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. RP BARSKY, AJ (reprint author), BRIGHAM & WOMENS HOSP,DIV PSYCHIAT,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NIMH NIH HHS [MH40487] NR 38 TC 30 Z9 30 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD MAY PY 1995 VL 39 IS 4 BP 489 EP 497 DI 10.1016/0022-3999(94)00166-3 PG 9 WC Psychiatry SC Psychiatry GA RG059 UT WOS:A1995RG05900009 PM 7562678 ER PT J AU YOUNG, JA SIEGEL, IM AF YOUNG, JA SIEGEL, IM TI 3-DIMENSIONAL DIGITAL SUBTRACTION MODELING OF CORNEAL TOPOGRAPHY SO JOURNAL OF REFRACTIVE SURGERY LA English DT Article AB BACKGROUND: The introduction of a system of classification of color-coded computerized topography has proved of great clinical value but may be misinterpreted by some who assume that the color plots represent actual corneal contour. METHODS: A three-dimensional system of contour modeling is used to plot equivalents of each category of corneal shape. The round, oval, symmetric bowtie, and asymmetric bowtie of the widely used classification schema are each translated into contour equivalents. Digital subtraction of an appropriate sphere from the contour data is central to the transformation. RESULTS: While round- and oval-type color-coded refractive power plots translate into fairly intuitive contour images, symmetric and asymmetric bowties produce surprising results. We demonstrated that the bowtie appearance is a result of the changing curvatures present between the two principal meridia of the toroidal surface. CONCLUSION: The shape characteristics of the corneal surface dictate the familiar color-coded dioptric plots. C1 NYU,DEPT OPHTHALMOL,NEW YORK,NY 10016. RP YOUNG, JA (reprint author), MASSACHUSETTS EYE & EAR INFIRM,CORNEA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 11 TC 5 Z9 5 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0883-0444 J9 J REFRACT SURG JI J. Refractive Surg. PD MAY-JUN PY 1995 VL 11 IS 3 BP 188 EP 193 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA RG908 UT WOS:A1995RG90800011 PM 7553089 ER PT J AU GARITI, P ALTERMAN, AI HOLUBBEYER, E VOLPICELLI, JR PRENTICE, N OBRIEN, CP AF GARITI, P ALTERMAN, AI HOLUBBEYER, E VOLPICELLI, JR PRENTICE, N OBRIEN, CP TI EFFECTS OF AN APPOINTMENT REMINDER CALL ON PATIENT SHOW RATES SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE WAITING LISTS; DROPOUT; TREATMENT RETENTION; INITIAL APPOINTMENTS; SHOW RATES; SUBSTANCE ABUSERS ID ABUSE TREATMENT; WAITING LIST; RETENTION; DISORDERS AB A pilot study (N = 80) was conducted to determine if (I) prospective substance-dependent patients randomly selected to be reminded (TC) of their scheduled intake evaluation the day before their first appointment would have a higher show rate than those not contacted (NC) and (2) if TC subjects administered a satisfaction questionnaire 1-3 days after intake would exhibit higher treatment retention rates at one week and one month posttreatment entry than NC subjects not exposed to the questionnaire. The findings suggest that reminding prospective patients of their initial scheduled appointments and following up with phone calls to those who fail to show can improve the rate at which patients will initiate treatment, provided initial appointments are scheduled in a timely manner (7 days or less). Similarly, the combination of the reminder call and the satisfaction questionnaire were associated with higher treatment retention rates for those whose initial appointments were scheduled in a timely manner. C1 UNIV PENN,SCH MED,DIV ADDICT STUDIES,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. FU NIDA NIH HHS [DA05186] NR 25 TC 28 Z9 28 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD MAY-JUN PY 1995 VL 12 IS 3 BP 207 EP 212 DI 10.1016/0740-5472(95)00019-2 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA RP285 UT WOS:A1995RP28500006 PM 7474028 ER PT J AU BIEDERMAN, J FARAONE, S MICK, E LELON, E AF BIEDERMAN, J FARAONE, S MICK, E LELON, E TI PSYCHIATRIC COMORBIDITY AMONG REFERRED JUVENILES WITH MAJOR DEPRESSION - FACT OR ARTIFACT SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE MAJOR DEPRESSION; COMORBIDITY; ATTENTION-DEFICIT HYPERACTIVITY DISORDER ID ATTENTION-DEFICIT DISORDER; CO-MORBIDITY; RISK-FACTORS; HYPERACTIVITY DISORDER; FLUOXETINE TREATMENT; UNIPOLAR DEPRESSION; ANXIETY DISORDERS; ANGER ATTACKS; FOLLOW-UP; CHILDREN AB Objective: The high levels of psychiatric comorbidity reported in juveniles meeting operational definitions of depressive disorders raise both substantive and methodological concerns about whether depression with comorbid disorders should be classified as two disorders or as different manifestations of the same condition. Our purpose was to clarify issues of diagnostic heterogeneity and diagnostic overlap in juvenile depression. Method: The sample consisted of consecutively referred children and adolescents (N = 424) comprehensively evaluated with structured diagnostic interviews and psychosocial assessments. Results: A clinical picture compatible with the diagnosis of major depression was identified in 40% of these referred youths. Children meeting criteria for major depression had prototypical symptoms of the disorder, a chronic course, and severe psychosocial dysfunction. In addition, they frequently met criteria for attention-deficit hyperactivity disorder, conduct disorder, and anxiety disorders. These comorbidity findings were not due to symptom overlap among major depression and the cc-occurring disorders. For the most part, comorbid disorders preceded the onset of major depression by several years. Conclusions: juvenile depression has a chronic course, severe dysfunction, and high levels of psychiatric comorbidity. Despite symptom overlap, our work suggests that major depression and other conditions may represent different disorders. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP BIEDERMAN, J (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,WACC 725,15 PARKMAN ST,BOSTON,MA 02114, USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 57 TC 144 Z9 146 U1 2 U2 10 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1995 VL 34 IS 5 BP 579 EP 590 DI 10.1097/00004583-199505000-00010 PG 12 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA QV536 UT WOS:A1995QV53600010 PM 7775353 ER PT J AU ZIELSTORFF, RD AF ZIELSTORFF, RD TI CAPTURING AND USING CLINICAL OUTCOME DATA - IMPLICATIONS FOR INFORMATION-SYSTEMS DESIGN SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Informatics: The Infrastructure for Quality Assessment and Improvement in Nursing CY JUN 22-25, 1994 CL AUSTIN, TX ID HEALTH-CARE; INDICATORS; PATIENT AB There is an urgent need to capture and record data related to clinical outcomes, but there are many barriers. The range of problems includes lack of agreement on conceptualization of the term ''outcome,'' inadequate measures of outcomes, and inadequate information systems to capture and manipulate data that would reflect outcomes. This article focuses on information system requirements to capture, store, and utilize clinical outcome data. For greatest accuracy, outcome data should be captured as close to the source as possible, including direct data capture from patients themselves and from their families. To make maximum use of outcome data, systems must be designed to 1) store data in multipurpose databases; 2) share data across different platforms; 3) link outcome data to other data that might influence or explain outcomes; 4) allow querying of the data by authorized personnel; and 5) protect patient confidentiality. C1 MASSACHUSETTS GEN HOSP,DEPT MED,COMP SCI LAB,BOSTON,MA 02114. RP ZIELSTORFF, RD (reprint author), MASSACHUSETTS GEN HOSP,DEPT NURSING,WHITE 116,BOSTON,MA 02114, USA. NR 36 TC 22 Z9 22 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY-JUN PY 1995 VL 2 IS 3 BP 191 EP 196 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA QW173 UT WOS:A1995QW17300006 PM 7614120 ER PT J AU GHIKA, J TENNIS, M GROWDON, J HOFFMAN, E JOHNSON, K AF GHIKA, J TENNIS, M GROWDON, J HOFFMAN, E JOHNSON, K TI ENVIRONMENT-DRIVEN RESPONSES IN PROGRESSIVE SUPRANUCLEAR PALSY SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE PROGRESSIVE SUPRANUCLEAR PALSY; FRONTAL; UTILIZATION BEHAVIORS; ENVIRONMENT; DRIVEN BEHAVIOR; VISUAL GRASP ID POSITRON EMISSION TOMOGRAPHY; ATTENTION; BRAIN; LOBE AB The neurological signs and behaviors that accompany degenerative diseases associated with fronto-striatal dysfunction are incompletely described. We observed several novel environmentally-driven behaviors in seven patients with progressive supranuclear palsy (PSP). All patients had cognitive deficits with greatest impairments on tests of frontal lobe function, and frontal lobe cerebral perfusion was significantly reduced in 4 of the 5 who had single photon emission computed tomography (SPECT) brain scans. Visual grasping, in which a patient's gaze was attracted to an incidental object in the environment such as a TV set or mirror, was preeminent. Once fixed, there was inability to release the gaze and shift to another object. In other instances, removing a table placed in front of a patient or unbuckling of his seat belt would make him stand up, which was impossible on command. Similarly, playing music would induce rhythmic foot beating, which was never obtained on command. There were compulsive utilization behaviors, such as repetitively picking up and replacing the telephone for no apparent reason. As expected, there were signs of heightened facial reflexes, grasp reflexes, apraxia of eyelid opening, echolalia and echopraxia. We postulate that these stimuli-oriented behaviors stem from parietal lobe disinhibition due to fronto-striatal dysfunction. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 41 TC 23 Z9 23 U1 0 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 MAY PY 1995 VL 130 IS 1 BP 104 EP 111 DI 10.1016/0022-510X(95)00015-T PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA QX742 UT WOS:A1995QX74200015 PM 7650525 ER PT J AU TAM, SKC GU, W NADALGINARD, B AF TAM, SKC GU, W NADALGINARD, B TI MOLECULAR CARDIOMYOPLASTY - POTENTIAL CARDIAC GENE-THERAPY FOR CHRONIC HEART-FAILURE SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 74th Annual Meeting of the American-Association-for-Thoracic-Surgery CY APR 24-27, 1994 CL NEW YORK, NY SP Amer Assoc Thorac Surg ID LATISSIMUS-DORSI; MUSCLE; EXPRESSION; MYOD AB In this study, we evaluated the feasibility of converting cardiac fibroblasts into skeletal muscle cells by forced expression of the MyoD gene, one of the basic helix-loop-helix myogenic factors. Primary cardiac fibroblasts, isolated from newborn rats, were infected with retrovirus-carrying sense or antisense MyoD gene. Ten days after infection, expression of MyoD protein was demonstrated in 95% of cells infected with sense MyoD virus by intense nuclear immunostaining with a MyoD polyclonal antibody. In contrast, none of the cells infected with antisense MyoD virus showed staining. On withdrawal of serum, 95% of MyoD positive cells became elongated and, in the presence of appropriate cell density, fused to form multinucleated myotubes, morphologically similar to striated muscle cell. Expression of downstream myogenic differentiation markers, myosin heavy chain and myocyte-specific enhancer factor 2, in 95% of these myotubes were detected by intense cytoplasmic and nuclear immunostaining, respectively, with specific antibodies. In contrast, no detectable staining was noted in MyoD negative cells. Spontaneous contractile movements were noted in a few clusters of myotubes. In summary, cardiac fibroblasts were able to be converted into bonafide potentially functional skeletal myocytes as shown by definitive morphologic and biochemical changes. Further studies with in vivo models are needed to explore this unique molecular strategy to treat patients with chronic heart failure. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,CHILDRENS HOSP,SCH MED,DEPT CARDIOL,CARDIAC SURG UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. NR 15 TC 25 Z9 28 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 1995 VL 109 IS 5 BP 918 EP 924 DI 10.1016/S0022-5223(95)70317-9 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA QX368 UT WOS:A1995QX36800014 PM 7739253 ER PT J AU PUSKAS, JD MATHISEN, DJ GRILLO, HC WAIN, JC WRIGHT, CD MONCURE, AC AF PUSKAS, JD MATHISEN, DJ GRILLO, HC WAIN, JC WRIGHT, CD MONCURE, AC TI TREATMENT STRATEGIES FOR BRONCHOPLEURAL FISTULA SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 74th Annual Meeting of the American-Association-for-Thoracic-Surgery CY APR 24-27, 1994 CL NEW YORK, NY SP Amer Assoc Thorac Surg ID POSTPNEUMONECTOMY EMPYEMA; BRONCHIAL OMENTOPEXY; OMENTAL PEDICLE; MANAGEMENT; MUSCLE; PNEUMONECTOMY; THORACOPLASTY; TRANSPOSITION; EXPERIENCE; CLOSURE AB Successful management of chronic postoperative bronchopleural fistula remains a challenge for thoracic surgeons. Forty-two patients (33 referred from other institutions) were treated for major postoperative bronchopleural fistula since 1978. Factors associated with bronchopleural fistula included right pneumonectomy (n 23), left pneumonectomy (n = 8), long bronchial stump (n = 16), pneumonia (n 13), radiation therapy (n = 12), stapled bronchial closure (n = 8), prolonged mechanical ventilation (n = 7), recurrent carcinoma (n = 6), and tuberculosis (n 2). Patients had undergone an average of 3.3 surgical procedures to correct their bronchopleural fistulas during a mean interval of 24 months before our treatment. Bronchopleural fistulas were located in the right main bronchial stump (n = 23), left main bronchial stump (n = 8), right lobar bronchial stumps (n = 10), and tracheobronchial anastomosis (n = 1). Thirty-five patients were treated by suture closure of the bronchial stump, buttressed with vascularized pedicle flaps of omentum (n = 19), muscle (n = 13), or pleura (n = 2). In seven cases, direct suture closure was not possible, and omental (n = 6) or muscle (n = 1) flaps were sutured over the bronchopleural fistula. Suture closure without pedicle coverage was performed successfully in one case. Initial repair of the fistula was successful in 23 of 25 patients treated with omentum, in nine of 14 patients treated with muscle and in neither of two patients treated with pleural flaps. In nine patients with persistent or recurrent bronchopleural fistula after our initial repair, four underwent a second procedure (three successful) and five were managed with drainage only. The fistula was successfully closed in 11 of 12 patients who had received high-dose radiation therapy (nine with omentum). Overall, successful closure of bronchopleural fistula was achieved in 36 of 42 patients (86%). Four in-hospital deaths resulted from pneumonia and sepsis, two in patients with recurrent bronchopleural fistula after pleural flap closure. In 16 patients the empyema cavity was obliterated during definitive repair of the fistula. The cavity resolved with drainage in four others, nine had draining cavities at follow-up, and one was lost to follow-up. Ten patients required a total of 17 Clagett procedures and one had a delayed myoplasty. Direct surgical repair of chronic bronchopleural fistula may be achieved in most patients after adequate pleural drainage by suture closure and aggressive transposition of vascularized pedicle flaps. Omentum is particularly effective in buttressing the closure of bronchopleural fistulas. C1 MASSACHUSETTS GEN HOSP,THORAC SERV SURG,BOSTON,MA 02114. NR 35 TC 64 Z9 71 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 1995 VL 109 IS 5 BP 989 EP 996 DI 10.1016/S0022-5223(95)70325-X PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA QX368 UT WOS:A1995QX36800022 PM 7739261 ER PT J AU GODLEY, CD MCCABE, CJ WARREN, RL ROSENBERG, WS AF GODLEY, CD MCCABE, CJ WARREN, RL ROSENBERG, WS TI TRAUMATIC SUBARACHNOID-PLEURAL FISTULA - CASE REPORT SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Note AB Traumatic subarachnoid-pleural fistula was recently diagnosed in an 18-year-old male after a gunshot wound in the chest and spinal column, The diagnosis was suggested by persistent pleural drainage and headache in the setting of signs of spinal injury at the thoracic level. Computed tomographic myelography delineated the dural injury. The fistulous connection was defined and repaired at operation. This paper describes the diagnostic and therapeutic features encountered in the management of this: rare disorder. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,NEUROSURG SERV,BOSTON,MA 02115. NR 21 TC 8 Z9 8 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Inf. Crit. Care PD MAY PY 1995 VL 38 IS 5 BP 808 EP 811 DI 10.1097/00005373-199505000-00023 PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA RD569 UT WOS:A1995RD56900023 PM 7760414 ER PT J AU SHERIDAN, RL STEWART, B TOMPKINS, RG AF SHERIDAN, RL STEWART, B TOMPKINS, RG TI SOLID-ORGAN PROCUREMENT FROM BURN PATIENTS SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Note ID THERMAL INJURY; UNITED-STATES; AVAILABILITY; BACTEREMIA; DISEASE; DONORS; CARE AB With the increasing success or organ transplantation and the consequent increasing scarcity of suitable organs, many traditional contraindications to organ procurement are being reconsidered. One such traditional contraindication to organ procurement is burn injury. We report a case of successful multiorgan procurement from a child with an extensive burn and propose guidelines for solid organ harvest from burn patients. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP SHERIDAN, RL (reprint author), SHRINERS BURN INST,51 BLOSSOM ST,BOSTON,MA 02114, USA. NR 18 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Inf. Crit. Care PD MAY PY 1995 VL 38 IS 5 BP 824 EP 825 DI 10.1097/00005373-199505000-00029 PG 2 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA RD569 UT WOS:A1995RD56900029 PM 7760420 ER PT J AU KONDO, E MAMMANO, F COHEN, EA GOTTLINGER, HG AF KONDO, E MAMMANO, F COHEN, EA GOTTLINGER, HG TI THE P6(GAG) DOMAIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IS SUFFICIENT FOR THE INCORPORATION OF VPR INTO HETEROLOGOUS VIRAL PARTICLES SO JOURNAL OF VIROLOGY LA English DT Article ID OPEN READING FRAME; VIRION-ASSOCIATED PROTEIN; PRODUCTIVE INFECTION; MUTATIONAL ANALYSIS; HUMAN MACROPHAGES; MATURE VIRIONS; GAG PROTEINS; GENE; IDENTIFICATION; RELEASE AB The vpr gene of human immunodeficiency virus type 1 (HIV-1) encodes a virion-associated regulatory protein. Mutagenesis has shown that the virion association of Vpr requires sequences near the C terminus of the HIV-1 Gag polyprotein Pr55(gag). To investigate whether Vpr incorporation is mediated by a specific domain of Pr55(gag), we examined the ability of chimeric HIV-1/Moloney murine leukemia virus (MLV) Gag polyproteins to direct the incorporation of Vpr. Vpr expressed in trans did not associate with particles formed by the authentic MLV Gag polyprotein or with particles formed by chimeric Gag polyproteins that had the matrix (MA) or,capsid (CA) domain of MLV precisely replaced by the corresponding domain of HIV-1(HXB2). By contrast, Vpr was efficiently incorporated upon replacement of the C-terminal nucleocapsid (NC) domain of the MLV Gag polyprotein with HIV-1 p15 sequences. Vpr was also efficiently incorporated into particles formed by a MLV Gag polyprotein that had the HIV-1 p6 domain fused to its C terminus. Furthermore, a deletion analysis revealed that a conserved region near the C terminus of the p6 domain is essential for Vpr incorporation, whereas sequences downstream of the conserved region are dispensable. These results show that a virion association motif for Vpr is located within residues 1 to 46 of p6. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV MONTREAL,DEPT MICROBIOL & IMMUNOL,MONTREAL,PQ H3C 3J7,CANADA. FU NIAID NIH HHS [AI28691, AI29873, AI34267] NR 37 TC 136 Z9 137 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1995 VL 69 IS 5 BP 2759 EP 2764 PG 6 WC Virology SC Virology GA QR784 UT WOS:A1995QR78400006 PM 7707498 ER PT J AU CHOE, HR SODROSKI, J AF CHOE, HR SODROSKI, J TI ADAPTATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TO CELLS EXPRESSING A BINDING-DEFICIENT CD4 MUTANT (LYSINE-46 TO ASPARTIC-ACID) SO JOURNAL OF VIROLOGY LA English DT Review ID HUMAN MONOCLONAL-ANTIBODY; ENVELOPE GLYCOPROTEIN FUNCTION; RECOMBINANT SOLUBLE CD4; SYNCYTIUM FORMATION; T-CELL; RECEPTOR-BINDING; HTLV-III; TRANSMEMBRANE GLYCOPROTEIN; NEUTRALIZING ANTIBODIES; MEMBRANE-FUSION AB Human immunodeficiency virus (HIV-1) was adapted to replicate efficiently in cells expressing an altered form of the CD4 viral receptor. The mutant CD4 (46 K/D) contained a single amino acid change (lysine 46 to aspartic acid) in the CDR2 loop of domain 1, which results in a 15-fold reduction in affinity for the viral gp120 glycoprotein. The ability of the adapted virus to replicate in CD4 46 K/D-expressing cells was independently enhanced by single amino acid changes in the V2 variable loop, the V3 variable loop, and the fourth conserved (C4) region of the gp120 glycoprotein. Combinations of these amino acids in the same envelope glycoprotein resulted in additive enhancement of virus replication in cells expressing the CD4 46 K/D molecule. In cells expressing the wild-type CD4 glycoproteins, the same V2 and V3 residue changes also increased the efficiency of replication of a virus exhibiting decreased receptor-binding ability due to an amino acid change (aspartic acid 368 to glutamic acid) in the gp120 glycoprotein. In neither instance did the adaptive changes restore the binding ability of the monomeric gp120 glycoprotein or the oligomeric envelope glycoprotein complex for the mutant or wild-type CD4 glycoproteins, respectively. Thus, particular conformations of the gp120 V2 and V3 variable loops and of the C4 region allow postreceptor binding events in the membrane fusion process to occur in the context of less than optimal receptor binding. These results suggest that the fusion-related functions of the V2, V3, and C4 regions of gp120 are modulated by CD4 binding. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI28691, AI24845] NR 115 TC 16 Z9 16 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1995 VL 69 IS 5 BP 2801 EP 2810 PG 10 WC Virology SC Virology GA QR784 UT WOS:A1995QR78400011 PM 7707502 ER PT J AU KING, SL CUNNINGHAM, JA FINBERG, RW BERGELSON, JM AF KING, SL CUNNINGHAM, JA FINBERG, RW BERGELSON, JM TI ECHOVIRUS-1 INTERACTION WITH THE ISOLATED VLA-2 I-DOMAIN SO JOURNAL OF VIROLOGY LA English DT Note ID EXTRACELLULAR-MATRIX; ALPHA-2 SUBUNIT; INTEGRIN VLA-2; BINDING-SITE; PROTEINS; MECHANISMS; RECEPTOR AB The isolated I domain of the integrin VLA-2, produced as a bacterial fusion protein, specifically bound echovirus 1 and prevented virus attachment to cells. These results demonstrate that the receptor structures critical for virus attachment are contained solely within the VLA-2 I domain and that soluble receptor fragments are capable of preventing infection. RP KING, SL (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,44 BINNEY ST,BOSTON,MA 02115, USA. RI Finberg, Robert/E-3323-2010 FU NIAAA NIH HHS [2T32AAI0724511]; NIAID NIH HHS [1R01AI31628] NR 18 TC 30 Z9 31 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1995 VL 69 IS 5 BP 3237 EP 3239 PG 3 WC Virology SC Virology GA QR784 UT WOS:A1995QR78400070 PM 7535868 ER PT J AU MARTIN, P FRIEDMAN, LS AF MARTIN, P FRIEDMAN, LS TI CHRONIC VIRAL-HEPATITIS AND THE MANAGEMENT OF CHRONIC-RENAL-FAILURE SO KIDNEY INTERNATIONAL LA English DT Review ID NON-B-HEPATITIS; C VIRUS-INFECTION; DIALYSIS-ASSOCIATED HEPATITIS; PLACEBO-CONTROLLED TRIAL; CHRONIC LIVER-DISEASE; FRENCH HEMODIALYSIS UNITS; CHRONIC ACTIVE HEPATITIS; SURFACE-ANTIGEN VACCINE; CHRONIC NON-A; TRANSPLANT RECIPIENTS C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP MARTIN, P (reprint author), UNIV CALIF LOS ANGELES,SCH MED,ROOM 77-123D CHS,10833 LE CONTE AVE,LOS ANGELES,CA 90024, USA. NR 124 TC 50 Z9 52 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1995 VL 47 IS 5 BP 1231 EP 1241 DI 10.1038/ki.1995.177 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA QV942 UT WOS:A1995QV94200001 PM 7637252 ER PT J AU IMAMURA, A MACKENZIE, HS LACY, ER HUTCHISON, FN FITZGIBBON, WR PLOTH, DW AF IMAMURA, A MACKENZIE, HS LACY, ER HUTCHISON, FN FITZGIBBON, WR PLOTH, DW TI EFFECTS OF CHRONIC TREATMENT WITH ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR OR AN ANGIOTENSIN RECEPTOR ANTAGONIST IN 2-KIDNEY, ONE-CLIP HYPERTENSIVE RATS SO KIDNEY INTERNATIONAL LA English DT Article ID ACTIVE ANTIHYPERTENSIVE AGENT; BILATERAL RENAL-FUNCTION; RENOVASCULAR HYPERTENSION; INDUCED PROTEINURIA; 2-KIDNEY; RESPONSES; BLOCKADE; THERAPY; DUP-753; INJURY AB The effects of chronic angiotensin II (Ang II) receptor blockade (losartan) or converting enzyme inhibition (enalapril) on blood pressure (BP), urinary albumin excretion (UalbV), renal histology and the hemodynamic and excretory function of the clipped and nonclipped kidneys were studied in two-kidney, one-clip (2-K 1-C) rats. One day after clipping the right renal artery, male Wistar rats were divided into three groups receiving: (1) losartan, 20 mg/kg/day (N = 7), (2) enalapril, 20 mg/kg/day (N = 8), or (3) no treatment (controls, N = 9) for three weeks. Both losartan and enalapril treatments maintained conscious BP at comparably lowered levels compared to control animals (116 +/- 6 mm Hg and 113 +/- 2 mm Hg vs. 188 +/- 11 mm Hg, respectively, P < 0.01). Treatment also prevented the increase in UalbV, observed for the untreated group, three weeks after clipping (1.7 +/- 0.5 and 0.7 +/- 0.1 mg/24 hr vs. 17.5 +/- 7 mg/24 hr, respectively, P < 0.01). After three weeks of treatment, acute study of renal function during pentobarbital anesthesia revealed higher values of GFR and RPF and lowered vascular resistance for nonclipped kidneys from the losartan and enalapril groups compared to the corresponding kidneys from control animals. Despite the lower BP of both treated groups, clipped kidney GFR and RPF were unchanged compared to the control group. UalbV for nonclipped kidneys from untreated rats was approximately 5- to 10-fold higher than in the nonclipped kidneys from the treated groups. Histological evaluation revealed evidence of early glomerulosclerosis in the nonclipped kidneys from the untreated but not the treated groups, and decreased indices of glomerular size and mesangial expansion in clipped kidneys for the treated groups compared to the untreated group. These data support a primary role for Ang II modulation of blood pressure and renal function in the nonclipped kidney of the 2-K 1-C rat. C1 MED UNIV S CAROLINA,DEPT MED,DIV NEPHROL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT CELL BIOL & ANAT,CHARLESTON,SC 29425. RALPH H JOHNSON VET ADM MED CTR,CHARLESTON,SC 29403. FU NIDDK NIH HHS [DK 43186] NR 33 TC 44 Z9 46 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1995 VL 47 IS 5 BP 1394 EP 1402 DI 10.1038/ki.1995.196 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA QV942 UT WOS:A1995QV94200020 PM 7637269 ER PT J AU WANG, CC MONTGOMERY, W EFIRD, J AF WANG, CC MONTGOMERY, W EFIRD, J TI LOCAL-CONTROL OF OROPHARYNGEAL CARCINOMA BY IRRADIATION ALONE SO LARYNGOSCOPE LA English DT Article ID SQUAMOUS-CELL-CARCINOMA; TUMOR VOLUME RELATIONSHIPS; TONSILLAR FOSSA; RADIATION-THERAPY; TONGUE; BASE; SURGERY; SCHEMES; REGION; TIME AB The authors of this study reviewed the management of 402 patients with squamous cell carcinomas of the faucial tonsil. and the base of the tongue. These patients received radiation therapy at Massachusetts General Hospital and the Massachusetts Eye and Ear Infirmary from 1970 through 1993. Radiation therapy remains the treatment of choice for these lesions. Although the data from this review were not randomized, the accelerated hyperfractionated radiation therapy twice-daily program was shown to achieve significantly higher B-year local tumor control rates and disease-specific survival rates than the conventional once-daily radiation therapy program (historical control). In patients with early tumors of the faucial tonsil (cancer stages T1 and T2), the 5-year actuarial local tumor control and disease-specific survival rates following the twice-daily radiation therapy program were 91% and 77%, respectively. In patients with advanced tumors (T3), the corresponding rates following twice-daily radiation therapy showed marked improvement and were 80% and 68%. While the treatment results for carcinoma of the base of the tongue generally were inferior to those for carcinoma of the faucial tonsil, they were still much better after the twice-daily program than after conventional once-daily irradiation. For patients with carcinoma of the base of the tongue, the local tumor control and disease-specific survival rates for T1 and T2 lesions were 85% and 76%, respectively. For T3 lesions, the corresponding rates were 54% and 53%. Extensive T4 tumors are better managed by combined surgery and postoperative irradiation. Residual metastatic nodal disease is managed by neck dissection. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA. RP WANG, CC (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 20 TC 25 Z9 26 U1 0 U2 0 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 1995 VL 105 IS 5 BP 529 EP 533 DI 10.1288/00005537-199505000-00016 PN 1 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA QW365 UT WOS:A1995QW36500019 PM 7760672 ER PT J AU CHAUHAN, D KHARBANDA, SM UCHIYAMA, H URASHIMA, M ANDERSON, KC AF CHAUHAN, D KHARBANDA, SM UCHIYAMA, H URASHIMA, M ANDERSON, KC TI ACTIVATION OF PP90(RSK) AND EARLY GROWTH RESPONSE-1 GENE-EXPRESSION BY POKEWEED MITOGEN IN HUMAN B-CELLS SO LEUKEMIA RESEARCH LA English DT Article DE EARLY GROWTH RESPONSE-1 GENE; B CELLS; POKEWEED MITOGEN; PP90(RSK); SERUM RESPONSE ELEMENT ID PROTEIN TYROSINE PHOSPHORYLATION; MEDIATED SIGNAL TRANSDUCTION; COLONY-STIMULATING FACTOR; MYELOID-LEUKEMIA CELLS; IMMEDIATE-EARLY GENES; FINGER-ENCODING GENE; MURINE LYMPHOCYTES-B; SWISS 3T3 CELLS; ANTIGEN RECEPTOR; C-FOS AB The present studies have examined the effects of pokeweed mitogen (PWM) on the induction of early growth response-1 gene (EGR-1) in normal human B cells. PWM regulates EGR-1 gene expression by both transcriptional and post-transcriptional mechanisms. Transient transfection assays with EGR-1 promoter fragments linked to the chloramphenicol acetyltransferase (CAT) gene demonstrated that PWM induced EGR-1 transcription is conferred by the CArG motif (C C[AT](6)GG) in the EGR-1 promoter. The results further demonstrated the activation of S6 kinase (pp90(rsk)), evidenced by phosphorylation of S6 and serum response factor (SRF) peptides, in PWM treated B cells. Taken together, these findings suggest that PWM is able to initiate an intracytoplasmic signalling cascade and EGR-1 induction in normal human B cells. C1 HARVARD UNIV,DEPT MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,DEPT MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 50947] NR 61 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAY PY 1995 VL 19 IS 5 BP 337 EP 344 DI 10.1016/0145-2126(94)00132-T PG 8 WC Oncology; Hematology SC Oncology; Hematology GA RA965 UT WOS:A1995RA96500006 PM 7769834 ER PT J AU CRAIG, WA ANDES, DR AF CRAIG, WA ANDES, DR TI PARENTERAL VERSUS ORAL ANTIBIOTIC-THERAPY SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID RESPIRATORY-TRACT INFECTIONS; INTRAVENOUS CEFTAZIDIME; CHRONIC OSTEOMYELITIS; CYSTIC-FIBROSIS; SKIN STRUCTURE; CIPROFLOXACIN; EFFICACY; ENDOCARDITIS; CEFTRIAXONE; ARTHRITIS AB The past decade has seen increased use of oral therapy for a variety of infections previously treated exclusively by the parenteral route. Clinical trials exhibit similar efficacy between parenteral and oral or step-down therapy. Much of the success is because of the availability of new oral agents with enhanced activity against gram-negative bacilli and improved pharmacokinetics. Oral therapy can reduce the cost of antimicrobial therapy significantly. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI. UNIV WISCONSIN,DEPT INTERNAL MED,MADISON,WI. RP CRAIG, WA (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT INFECT DIS,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 39 TC 38 Z9 38 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 1995 VL 79 IS 3 BP 497 EP 508 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA QX447 UT WOS:A1995QX44700004 PM 7752724 ER PT J AU MA, MY RHO, JP AF MA, MY RHO, JP TI CONSIDERATIONS IN ANTIMICROBIAL PRESCRIBING SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID MEDICATION; THERAPY; FREQUENCY; AGENTS; IMPACT; TWICE AB Factors important to the clinician in prescribing an antimicrobial regimen include the selection of the most effective agent(s), avoidance of adverse drug reactions, and the ensurance of patient compliance. This article discusses various strategies that can be used by physicians and hospitals to improve cost-effective use of antimicrobial drugs. C1 UNIV CALIF SAN FRANCISCO,SCH PHARM,SAN FRANCISCO,CA. UNIV SO CALIF,SCH PHARM,LOS ANGELES,CA. RP MA, MY (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,PHARM SERV 119,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 29 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 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 1995 VL 79 IS 3 BP 537 EP 549 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA QX447 UT WOS:A1995QX44700007 PM 7752727 ER PT J AU YOSHIKAWA, TT NORMAN, DC AF YOSHIKAWA, TT NORMAN, DC TI TREATMENT OF INFECTIONS IN ELDERLY PATIENTS SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; NERVOUS-SYSTEM INFECTIONS; URINARY-TRACT INFECTIONS; BACTERIAL-MENINGITIS; REQUIRING HOSPITALIZATION; CONSECUTIVE EPISODES; OLMSTED COUNTY; DIAGNOSIS; EPIDEMIOLOGY; BACTEREMIA AB Infections are common in elderly persons. The clinical manifestations of infection may be atypical or absent in the elderly. The microbial cause for many common infections may be more diverse in elderly patients, and obtaining diagnostic clinical specimens often is more difficult. Aging is associated with changes in pharmacokinetics and a higher rate of adverse drug reactions. These factors impact on the approach to treating infections in the elderly. C1 GEORGE WASHINGTON UNIV,DEPT HLTH CARE SCI,WASHINGTON,DC. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA. RP YOSHIKAWA, TT (reprint author), US DEPT VET AFFAIRS,OFF GERIATR & EXTENDED CARE 114,810 VERMONT AVE NW,WASHINGTON,DC 20420, USA. NR 62 TC 22 Z9 22 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 1995 VL 79 IS 3 BP 651 EP 661 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA QX447 UT WOS:A1995QX44700013 PM 7752733 ER PT J AU YU, YM YOUNG, VR CASTILLO, L CHAPMAN, TE TOMPKINS, RG RYAN, CM BURKE, JF AF YU, YM YOUNG, VR CASTILLO, L CHAPMAN, TE TOMPKINS, RG RYAN, CM BURKE, JF TI PLASMA ARGININE AND LEUCINE KINETICS AND UREA PRODUCTION-RATES IN BURN PATIENTS SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID WHOLE-BODY PROTEIN; INDISPENSABLE AMINO-ACIDS; NITRIC-OXIDE; OROTIC ACIDURIA; SEVERE TRAUMA; ADULT HUMANS; METABOLISM; TURNOVER; INFUSION; CHILDREN AB We measured plasma arginine and leucine kinetics and rates of urea production (appearance) in 12 severely burned patients (mean body surface burn area, 48%) during a basal state (low-dose intravenous glucose) and while receiving routine, total parenteral nutrition ([TPN] fed state) including an L-amino acid mixture, supplying a generous level of nitrogen (mean, 0.36 g N . kg(-1) . d(-1)). The two nutritional states were studied in random order using a primed 4-hour constant intravenous tracer infusion protocol. Stable-nuclide-labeled tracers were L-[guanidino-C-13]arginine, L-[1-C-13]leucine, [O-18]urea, and (NaHCO3)-C-13 (prime only), with blood and expired air samples drawn at intervals to determine isotopic abundance of arginine, citrulline, ornithine, alpha ketoisocaproate ([KIC] for leucine), and urea in plasma and (CO2)-C-13 in breath. Results are compared with data obtained in these laboratories in healthy adults. Leucine kinetics (flux and disappearance into protein synthesis) indicated the expected higher turnover in burn patients than in healthy controls. Mean leucine oxidation rates are also higher and compared well with values predicted from urea production rates, provided that urea nitrogen recycling via intestinal hydrolysis is taken into account, The plasma urea flux was also higher than for normal subjects. Arginine fluxes as measured in the systemic whole body, via the plasma pool, were correspondingly higher in burned patients than in healthy controls and were in good agreement with values predicted from leucine-KIC kinetics. However, systemic whole-body arginine flux measured via the plasma pool was only 20% of the arginine flux estimated from the urea flux plus the rate of protein synthesis. This finding is strong evidence that there is a significant synthesis of arginine (probably via recycling of ornithine) occurring in a sequestered pool (presumably in the hepatocyte) that is not in close communication with the plasma pool. Further, these data for plasma arginine flux suggest that the net rate of arginine degradation is increased in burn trauma, while there also appears to be a continued low and possibly unchanged net rate of de novo arginine synthesis contributing arginine to the plasma pool. This interpretation leads to the conclusion that there are at least two significant metabolic pools of arginine, one highly sequestered related specifically to urea synthesis and the other a systemic pool in equilibrium with the plasma, Because the hepatic urea arginine cycle does not contribute substantially to making arginine available for protein synthesis, we propose from these findings that arginine is a conditionally essential (indispensable) amino acid in the nutrition of severely burned patients and that an exogenous arginine source is needed to maintain arginine balance. Copyright (C) 1995 by W.B. Saunders Company C1 MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,TRAUMA SERV,BOSTON,MA 02114. MIT,HUMAN NUTR LAB,CAMBRIDGE,MA 02139. FU NCRR NIH HHS [RR88]; NIDDK NIH HHS [DK 15856]; NIGMS NIH HHS [GM 02700] NR 68 TC 52 Z9 53 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAY PY 1995 VL 44 IS 5 BP 659 EP 666 DI 10.1016/0026-0495(95)90125-6 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QW979 UT WOS:A1995QW97900016 PM 7752916 ER PT J AU WENG, QP ANDRABI, K KOZLOWSKI, MT GROVE, JR AVRUCH, J AF WENG, QP ANDRABI, K KOZLOWSKI, MT GROVE, JR AVRUCH, J TI MULTIPLE INDEPENDENT INPUTS ARE REQUIRED FOR ACTIVATION OF THE P70 S6 KINASE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-KINASES; PHOSPHORYLATION; PURIFICATION; EXPRESSION; P70(S6K); SITES AB Previous studies have shown that the noncatalytic carboxy-terminal tail of the p70 S6 kinase (amino acids 422 to 525) contains an autoinhibitory pseudosubstrate domain that is phosphorylated in situ during activation and in vitro by mitogen-activated protein kinases, The present study shows that a recombinant p70 deleted of the carboxy-terminal tail (p70 Delta CT104) nevertheless exhibits a basal and serum-stimulated 40S kinase activity and susceptibility to inhibition by wortmannin very similar to those of the parent, full-length p70 kinase, Carboxy-terminal deletion reduces the extent of maximal inhibition produced by rapamycin, from >95% in the full-length p70 to 60 to 80% in p70 Delta CT104, without altering the sensitivity to rapamycin inhibition (50% inhibitory concentration of 2 nM), Serum activation of p70 Delta CT104, as with the parent, full-length p70, is accompanied by an increase in P-32 content (about twofold) in situ and a slowing in electrophoretic mobility; both modifications are inhibited by pretreatment with wortmannin or rapamycin, P-32-peptide maps of p70 Delta CT104 show multisite phosphorylation, and wortmannin and rapamycin appear to cause preferential dephosphorylation of the same subset of sites, Thus, it is likely that activation of the kinase requires phosphorylation of p70 at sites in addition to those previously identified in the carboxy-terminal tail. Evidence that the carboxy-terminal tail actually functions as a potent intramolecular inhibitor of kinase activity in situ is uncovered by deletion of a short acidic segment (amino acids 29 to 46) from the p70 amino-terminal noncatalytic region, Deletion of amino acids 29 to 46 causes a >95% inhibition of p70 activity despite continued phosphorylation of the carboxy-terminal tail in situ; additional deletion of the carboxy-terminal tail (yielding p70 Delta 29-46/Delta CT104) increases activity 10 fold, to a level approaching that of p70 Delta CT101. Deletion of residues 29 to 46 also abolishes completely the sensitivity of p70 to inhibition by rapamycin but does not alter the susceptibility to activation by serum or inhibition by wortmannin. Although the mechanisms underlying the effects of the Delta 29-46 deletion are not known, they are not attributable to loss of the major in situ p70 phosphorylation site at Ser-40, Thus, activation of the p70 S6 kinase involves multiple, independent inputs directed at different domains of the p70 polypeptide, Disinhibition from the carboxy-terminal tail requires, in addition to its multisite phosphorylation, an activating input dependent on the presence of amino acids 29 to 46; this p70-activating input may be the same as that inhibited by rapamycin but is distinct from that arising from the wortmannin-inhibitable phosphatidylinositol 3-kinase, In addition, as exemplified by the rapamycin-resistant but mitogen- and wortmannin-sensitive p70 Delta 29-46/Delta CT104 mutant, a further activating input, which probably involves site-specific phosphorylation in the segment between amino acids 46 to 421, is necessary. C1 MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIABET UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. FU NIDDK NIH HHS [DK17776] NR 17 TC 186 Z9 188 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1995 VL 15 IS 5 BP 2333 EP 2340 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QU665 UT WOS:A1995QU66500001 PM 7739516 ER PT J AU MERIKA, M ORKIN, SH AF MERIKA, M ORKIN, SH TI FUNCTIONAL SYNERGY AND PHYSICAL INTERACTIONS OF THE ERYTHROID TRANSCRIPTION FACTOR GATA-1 WITH THE KRUPPEL FAMILY PROTEINS SP1 AND EKLF SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DOMINANT CONTROL REGION; LOCUS-CONTROL REGION; BETA-GLOBIN LOCUS; PORPHOBILINOGEN DEAMINASE GENE; LEUCINE ZIPPER PROTEIN; DNA-BINDING; MAMMALIAN-CELLS; DEVELOPMENTAL REGULATION; HYPERSENSITIVE SITE-3; MULTIGENE FAMILY AB An unresolved aspect of current understanding of erythroid cell-specific gene expression relates to how a limited number of transcriptional factors cooperate to direct high level expression mediated by cis-regulatory elements separated over large distances within globin loci, In this report, we provide evidence that GATA-1, the major erythroid transcription factor, activates transcription in a synergistic fashion with two Kruppel family factors, the ubiquitous protein Sp1 and the erythroid-restricted factor EKLF (erythroid Kruppel-like factor), which recognize GC and/or GT/CACC motifs. Binding sites for both GATA-1 and these Kruppel proteins (especially Sp1) are found in close association in the promoters and enhancers of numerous erythroid cell-expressed genes and appear to cooperate in directing their expression. We have shown that GATA-1 interacts physically with Sp1 and EKLF and that interactions are mediated through their respective DNA-binding domains. Moreover, we show that GATA-1 and Sp1 synergize from a distance in constructs designed to mimic the architecture of globin locus control regions and downstream globin promoters. Finally, the formation of GATA-1-Sp1 complexes was demonstrated in vivo by the ability of Sp1 to recruit GATA-1 to a promoter in the absence of GATA-binding sites. These experiments provide the first evidence for functionally important protein-protein interactions involved in erythroid cell-specific expression and suggest a mechanism by which DNA loops between locus control regions and globin promoters (or enhancers) might be formed or stabilized. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. NR 63 TC 419 Z9 421 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1995 VL 15 IS 5 BP 2437 EP 2447 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QU665 UT WOS:A1995QU66500013 PM 7739528 ER PT J AU CROSSLEY, M MERIKA, M ORKIN, SH AF CROSSLEY, M MERIKA, M ORKIN, SH TI SELF-ASSOCIATION OF THE ERYTHROID TRANSCRIPTION FACTOR GATA-1 MEDIATED BY ITS ZINC-FINGER DOMAINS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GLOBIN GENE-TRANSCRIPTION; DNA-BINDING SPECIFICITIES; PROTEIN-KINASE-C; DEVELOPMENTAL REGULATION; MEGAKARYOCYTIC DIFFERENTIATION; MAMMALIAN-CELLS; TRANSGENIC MICE; EXPRESSION; SP1; ACTIVATION AB GATA-1, the founding member of a distinctive family of transcription factors, is expressed predominantly in erythroid cells and participates in the expression of numerous erythroid cell-expressed genes. GATA-binding sites are found in the promoters and enhancers of globin and nonglobin erythroid genes as well as in the alpha-and beta-globin locus control regions. To elucidate how GATA-1 may function in a variety of regulatory contexts, we have examined its protein-protein interactions. Here we show that GATA-1 self-associates in solution and in whole-cell extracts and that the zinc finger region of the molecule is sufficient to mediate this interaction, This physical interaction can influence transcription, as GATA-1 self-association is able to recruit a transcriptionally active but DNA-binding-defective derivative of GATA-1 to promoter-bound GATA-1 and result in superactivation. Through in vitro studies with bacterially expressed glutathione S-transferase fusion proteins, we have localized the minimal domain required for GATA-1 self-association to 40 amino acid residues within the C-terminal zinc finger region. Finally, we have detected physical interaction of GATA-1 with other GATA family members (GATA-2 and GATA-3) also mediated through the zinc finger domain. These findings have broad implications for the involvement of GATA factors in transcriptional control. In particular, the interaction of GATA-1 with itself and with other transcription factors may facilitate its function at diverse promoters in erythroid cells and also serve to bring together, or stabilize, loops between distant regulatory elements, such as the globin locus control regions and downstream globin promoters. We suggest that the zinc finger region of GATA-1, and related proteins, is multifunctional and mediates not only DNA binding but also important protein-protein interactions. C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. RI Crossley, Merlin/D-7888-2011 OI Crossley, Merlin/0000-0003-2057-3642 NR 59 TC 148 Z9 148 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1995 VL 15 IS 5 BP 2448 EP 2456 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QU665 UT WOS:A1995QU66500014 PM 7739529 ER PT J AU WU, CL ZUKERBERG, LR NGWU, C HARLOW, E LEES, JA AF WU, CL ZUKERBERG, LR NGWU, C HARLOW, E LEES, JA TI IN-VIVO ASSOCIATION OF E2F AND DP FAMILY PROTEINS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; TRANSCRIPTION FACTOR E2F; ADENOVIRUS E1A; CYCLIN-A; CELL-PROLIFERATION; BINDING PROTEIN; TRANSACTIVATION; P107; RB; INHIBITION AB The mammalian transcription factor E2F plays an important role in regulating the expression of genes that are required for passage through the cell cycle. This transcriptional activity is inhibited by association with the retinoblastoma tumor suppressor protein (pRB) or its relatives p107 and p130. The first cDNA from the E2F family to be cloned was designated E2F-1, and multiple E2F family members have now been identified. They bind to DNA as heterodimers, interacting with proteins known as DP. Here we demonstrate that DP is also a family of polypeptides with at least two members (hDP-1 and hDP-2). Both hDP-1 and hDP-2 bind to all E2F family members in vivo, and each complex is capable of activating transcription. However, the various E2F/DP complexes display strong differences in the ability to bind to either pRB or p107 in vivo, and the specificity of PRE or p107 binding is mediated by the E2F subunit. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP WU, CL (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 57 TC 199 Z9 205 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 MAY PY 1995 VL 15 IS 5 BP 2536 EP 2546 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QU665 UT WOS:A1995QU66500024 PM 7739537 ER PT J AU KIM, JB SPOTTS, GD HALVORSEN, YD SHIH, HM ELLENBERGER, T TOWLE, HC SPIEGELMAN, BM AF KIM, JB SPOTTS, GD HALVORSEN, YD SHIH, HM ELLENBERGER, T TOWLE, HC SPIEGELMAN, BM TI DUAL DNA-BINDING SPECIFICITY OF ADD1/SREBP1 CONTROLLED BY A SINGLE AMINO-ACID IN THE BASIC HELIX-LOOP-HELIX DOMAIN SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTIONAL ACTIVATION; NEGATIVE REGULATOR; ZIPPER PROTEIN; ACHAETE-SCUTE; HIGH-AFFINITY; MYC PROTEINS; ENHANCER; SEQUENCE; MYOD; GENE AB Adipocyte determination- and differentiation-dependent factor 1 (ADD1), a member of the basic helix-loop-helix (bHLH) family of transcription factors, has been associated with both adipocyte differentiation and cholesterol homeostasis (in which case it has been termed SREBP1). Using PCR-amplified binding analysis, we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC). The ADD1/SREBP1 consensus E-box site is similar to a regulatory sequence designated the carbohydrate response element, defined by its ability to regulate transcription in response to carbohydrate in genes involved in fatty acid and triglyceride metabolism in liver and fat. When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1. Substitution of an atypical tyrosine in the basic region of ADD1/SREBP1 to an arginine found in most bHLH protein causes a restriction to only E-box binding. Conversely, substitution of a tyrosine for the equivalent arginine in another bHLH protein, upstream stimulatory factor, allows this factor to acquire a dual binding specificity similar to that of ADD1/SREBP1. Promoter activation by ADD1/SREBP1 through the carbohydrate response element E box is not sensitive to the tyrosine-to arginine mutation, while activation through SRE-1 is completely suppressed. These data illustrate that ADD1/SREBP1 has dual DNA sequence specificity controlled by a single amino acid residue; this dual specificity may provide a novel mechanism to coordinate different pathways of lipid metabolism. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. UNIV MINNESOTA,DEPT BIOCHEM,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,INST HUMAN GENET,MINNEAPOLIS,MN 55455. FU NCI NIH HHS [5T32CA09361]; NIDDK NIH HHS [DK 31405] NR 37 TC 263 Z9 277 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 MAY PY 1995 VL 15 IS 5 BP 2582 EP 2588 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QU665 UT WOS:A1995QU66500028 PM 7739539 ER PT J AU AYTE, J LEIS, JF HERRERA, A TANG, E YANG, H DECAPRIO, JA AF AYTE, J LEIS, JF HERRERA, A TANG, E YANG, H DECAPRIO, JA TI THE SCHIZOSACCHAROMYCES-POMBE MBF COMPLEX REQUIRES HETERODIMERIZATION FOR ENTRY INTO S-PHASE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-SYNTHESIS GENES; CELL-CYCLE CONTROL; PROTEIN SECONDARY STRUCTURE; FISSION YEAST; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; TRANSCRIPTION FACTOR; START; SWI4; EXPRESSION AB In Schizosaccharamyces pombe, MBF is a DNA-binding complex suspected to activate the transcription of genes necessary for entry into S phase. The MBF complex contains both p85(cdc10) and p72(res1/sct1). To obtain a better understanding of how the MBF complex regulates gene expression at the G(1)/S transition, we have performed a genetic analysis of p72(res1). We determined that p72(res1) can bind specifically to the cdc22 promoter, when analyzed by gel mobility shift assay, and that the N-terminal 157 amino acids of p72(res1) are sufficient for this specific binding. When overexpressed in vivo, a fragment of p72(res1) containing this DNA-binding domain could rescue a strain carrying a temperature-sensitive cdc10 allele at the restrictive temperature as well as a strain with a cdc10 null allele. We also determined that the C-terminal region of p72(res1) is necessary and sufficient for binding to p85(cdc10). Overexpression of the cdc10-binding domain of p72(res1) leads to a G(1) arrest with a cde phenotype and a decrease on MBF activity. Overexpression of full-length p72(res1) also leads to a growth arrest that can be rescued by overexpression of p85(cdc10). These results imply that the MBF activity in vivo is dependent on the interaction of p85(cdc10) With p72(res1). C1 HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RP HARVARD UNIV, DANA FARBER CANC INST, DIV NEOPLAST DIS MECH, 44 BINNEY ST, BOSTON, MA 02115 USA. RI Ayte, Jose/L-5217-2014 OI Ayte, Jose/0000-0002-6354-0536 NR 57 TC 28 Z9 29 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1995 VL 15 IS 5 BP 2589 EP 2599 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QU665 UT WOS:A1995QU66500029 PM 7739540 ER PT J AU JOHNSON, AW KOLODNER, RD AF JOHNSON, AW KOLODNER, RD TI SYNTHETIC LETHALITY OF SEP1 (XRN1) SKI2 AND SEP1 (XRN1) SKI3 MUTANTS OF SACCHAROMYCES-CEREVISIAE IS INDEPENDENT OF KILLER VIRUS AND SUGGESTS A GENERAL ROLE FOR THESE GENES IN TRANSLATION CONTROL SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LACKING 5'->3' EXORIBONUCLEASE-1; TRANSFER PROTEIN-BETA; DOUBLE-STRANDED-RNA; MESSENGER-RNA; YEAST-CELLS; EXCHANGE; DNA; EXPRESSION; MUTATIONS; RECOMBINATION AB Strand exchange protein 1 (Sep1) (also referred to as exoribonuclease I [Xrn1]) from Saccharomyces cerevisiae has been implicated in DNA recombination, RNA turnover, karyogamy, and G4 DNA pairing among other disparate cellular processes. Using a genetic approach to study the role of SEP1/XRN1 in mitotic yeast cells, we identified mutations in the genes superkiller 2 (SKI2) and superkiller 3 (SKI3) as synthetically lethal with an sep1 null mutation. The SKI genes are thought to comprise an intracellular antiviral system controlling the expression of killer toxin from double-stranded RNA virus found in many yeast strains. However, the lethality of sep1 ski2 and sep1 ski3 mutants was independent of the L-A and M viruses, suggesting that the SKI genes act in a general cellular process in addition to virus control. We propose that Sep1/Xrn1 and Ski2 both act to block translation on transcripts targeted for degradation. Using a temperature-sensitive allele of SEP1/XRN1, we show that double mutants display a synthetic cell cycle arrest in late G(1) at Start. 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. RP JOHNSON, AW (reprint author), UNIV TEXAS,DEPT MICROBIOL,AUSTIN,TX 78712, USA. FU NCI NIH HHS [CA06516]; NIGMS NIH HHS [GM13594, GM29383] NR 62 TC 63 Z9 66 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 MAY PY 1995 VL 15 IS 5 BP 2719 EP 2727 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QU665 UT WOS:A1995QU66500042 PM 7739552 ER PT J AU HEYER, WD JOHNSON, AW REINHART, U KOLODNER, RD AF HEYER, WD JOHNSON, AW REINHART, U KOLODNER, RD TI REGULATION AND INTRACELLULAR-LOCALIZATION OF SACCHAROMYCES-CEREVISIAE STRAND EXCHANGE PROTEIN-1 (SEP1/XRN1/KEM1), A MULTIFUNCTIONAL EXONUCLEASE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LACKING 5'->3' EXORIBONUCLEASE-1; MESSENGER-RNA; ESSENTIAL GENE; MEIOTIC CELLS; YEAST-CELLS; DNA; MUTATIONS; RECOMBINATION; BETA; RENATURATION AB The Saccharomyces cerevisiae strand exchange protein 1 (Sep1; also referred to as Xrn1, Kem1, Rar5, or Stp beta) catalyzes the formation of hybrid DNA from model substrates in vitro. The protein is also a 5'-to-3' exonuclease active on DNA and RNA. Multiple roles for the in vivo function of Sep1, ranging from DNA recombination and cytoskeleton to RNA turnover, have been proposed. We show that Sep1 is an abundant protein in vegetative S. cerevisiae cells, present at about 80,000 molecules per diploid cell. Protein levels were not changed during the cell cycle or in response to DNA-damaging agents but increased twofold during meiosis. Cell fractionation and indirect immunofluorescence studies indicated that >90% of Sep1 was cytoplasmic in vegetative cells, and indirect immunofluorescence indicated a cytoplasmic localization in meiotic cells as well. The localization supports the proposal that Sep1 has a role in cytoplasmic RNA metabolism. Anti-Sep1 monoclonal antibodies detected cross-reacting antigens in the fission yeast Schizosaccharomyces pombe, in Drosophila melanogaster embryos, in Xenopus laevis, and in a mouse pre-B-cell line. C1 UNIV BERN, INST GEN MICROBIOL, CH-3012 BERN, SWITZERLAND. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV CELLULAR & MOLEC BIOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02115 USA. FU NIGMS NIH HHS [GM29383, GM13594] NR 66 TC 64 Z9 67 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1995 VL 15 IS 5 BP 2728 EP 2736 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QU665 UT WOS:A1995QU66500043 PM 7739553 ER PT J AU PERSICHETTI, F AMBROSE, CM GE, P MCNEIL, SM SRINIDHI, J ANDERSON, MA JENKINS, B BARNES, GT DUYAO, MP KANALEY, L WEXLER, NS MYERS, RH BIRD, ED VONSATTEL, JP MACDONALD, ME GUSELLA, JF AF PERSICHETTI, F AMBROSE, CM GE, P MCNEIL, SM SRINIDHI, J ANDERSON, MA JENKINS, B BARNES, GT DUYAO, MP KANALEY, L WEXLER, NS MYERS, RH BIRD, ED VONSATTEL, JP MACDONALD, ME GUSELLA, JF TI NORMAL AND EXPANDED HUNTINGTONS-DISEASE GENE ALLELES PRODUCE DISTINGUISHABLE PROTEINS DUE TO TRANSLATION ACROSS THE CAG REPEAT SO MOLECULAR MEDICINE LA English DT Article ID REGION; SEQUENCE; TISSUES AB Background: An expanded CAG trinudeotide repeat is the genetic trigger of neuronal degeneration in Huntington's disease (HD), but its mode of action has yet to be discovered. The sequence of the HD gene places the CAG repeat near the 5' end in a region where it may be translated as a variable polyglutamine segment in the protein product, huntingtin. Materials and Methods: Antisera directed at amino acid stretches predicted by the DNA sequence upstream and downstream of the CAG repeat were used in Western blot and immunohistochemical analyses to examine huntingtin expression from the normal and the HD allele in lymphoblastoid cells and postmortem brain tissue. Results: CAG repeat segments of both normal and expanded IID alleles are indeed translated, as part of a discrete similar to 350-kD protein that is found primarily in the cytosol. The difference in the length of the N-terminal polyglutamine segment is sufficient to distinguish normal and HD huntingtin in a Western blot assay. Conclusions: The HD mutation does not eliminate expression of the HD gene but instead produces an altered protein with an expanded polyglutamine stretch near the N terminus. Thus, HD pathogenesis is probably triggered by an effect at the level of huntingtin protein. C1 MASSACHUSETTS GEN HOSP, MOLEC NEUROGENET UNIT, BOSTON, MA 02129 USA. MASSACHUSETTS GEN HOSP, MOLEC NEUROPATHOL LAB, BOSTON, MA 02129 USA. MCLEAN HOSP, BRAIN TISSUE RESOURCE CTR, BELMONT, MA 02178 USA. HEREDITARY DIS FDN, SANTA MONICA, CA USA. BOSTON UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02118 USA. HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA USA. FU NINDS NIH HHS [NS16367, NS22031, NS32765] NR 29 TC 72 Z9 74 U1 0 U2 2 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 EI 1528-3658 J9 MOL MED JI Mol. Med. PD MAY PY 1995 VL 1 IS 4 BP 374 EP 383 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA QZ097 UT WOS:A1995QZ09700006 PM 8521295 ER PT J AU VANHOESEN, GW SOLODKIN, A HYMAN, BT AF VANHOESEN, GW SOLODKIN, A HYMAN, BT TI NEUROANATOMY OF ALZHEIMERS-DISEASE - HIERARCHICAL VULNERABILITY AND NEURAL SYSTEM COMPROMISE - COMMENTARY SO NEUROBIOLOGY OF AGING LA English DT Note ID PATHOLOGICAL-CHANGES; HIPPOCAMPAL-FORMATION; NEUROFIBRILLARY TANGLES; SENILE PLAQUES; PATTERN C1 UNIV IOWA,COLL MED,DEPT NEUROL,IOWA CITY,IA 52242. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,BOSTON,MA 02114. RP VANHOESEN, GW (reprint author), UNIV IOWA,COLL MED,DEPT ANAT,IOWA CITY,IA 52242, USA. NR 18 TC 3 Z9 3 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 1995 VL 16 IS 3 BP 278 EP 280 DI 10.1016/0197-4580(95)00019-B PG 3 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA QZ922 UT WOS:A1995QZ92200013 ER PT J AU SIMONIAN, NA HYMAN, BT AF SIMONIAN, NA HYMAN, BT TI FUNCTIONAL ALTERATIONS IN NEURAL CIRCUITS IN ALZHEIMERS-DISEASE SO NEUROBIOLOGY OF AGING LA English DT Article; Proceedings Paper CT Schmitt Symposium - The Cytoskeleton and Alzheimers Disease CY MAY 21-23, 1994 CL ROCHESTER, NY DE ALZHEIMERS DISEASE; CYTOCHROME OXIDASE; MITOCHONDRIA; ENERGY METABOLISM ID CYTOCHROME-OXIDASE; OXIDATIVE-PHOSPHORYLATION; ENERGY-METABOLISM; PERFORANT PATHWAY; VISUAL-CORTEX; MITOCHONDRIAL; BRAIN; EXPRESSION; HISTOCHEMISTRY; HIPPOCAMPUS AB While a correlation exists at the regional level between the distribution of neurofibrillary tangles and the predicted sites of brain dysfunction based on clinical and functional neuroimaging studies, the relationship between neurofibrillary tangles and neuronal dysfunction is poorly understood. Using cytochrome oxidase activity as a marker of neuronal functional activity, we found reductions in metabolic activity both in a hippocampal subfield with a high density of neurofibrillary tangles (CAI) as well as in subfields relatively spared (CA3, dentate granule cells). In contrast, we found no reduction in activity in primary visual cortex. Using in situ hybridization, we found a selective reduction in a mitochondrial-encoded cytochrome oxidase mRNA transcript with sparing of a nuclear-encoded transcript. These results suggest that the reduction in cytochrome oxidase activity in Alzheimer's disease brain may be related to an alteration in mitochondrial gene expression. The absence of a direct correlation between structural pathology and cytochrome oxidase activity suggests that neurons that remain structurally intact in Alzheimer's disease may nonetheless undergo substantial changes in metabolic activity. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. FU NIA NIH HHS [AG08487]; NINDS NIH HHS [NS07009-18] NR 38 TC 12 Z9 12 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 1995 VL 16 IS 3 BP 305 EP 309 DI 10.1016/0197-4580(95)00034-C PG 5 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA QZ922 UT WOS:A1995QZ92200021 PM 7566339 ER PT J AU DIFIGLIA, M SAPP, E CHASE, K SCHWARZ, C MELONI, A YOUNG, C MARTIN, E VONSATTEL, JP CARRAWAY, R REEVES, SA BOYCE, FM ARONIN, N AF DIFIGLIA, M SAPP, E CHASE, K SCHWARZ, C MELONI, A YOUNG, C MARTIN, E VONSATTEL, JP CARRAWAY, R REEVES, SA BOYCE, FM ARONIN, N TI HUNTINGTIN IS A CYTOPLASMIC PROTEIN ASSOCIATED WITH VESICLES IN HUMAN AND RAT-BRAIN NEURONS SO NEURON LA English DT Article ID DISEASE GENE; CONSTITUENT; GLUTAMATE; MEMBRANE; TISSUES AB The gene defective in Huntington's disease encodes a protein, huntingtin, with unknown function. Antisera generated against three separate regions of huntingtin identified a single high molecular weight protein of similar to 320 kDa on immunoblots of human neuroblastoma extracts. The same protein species was detected in human and rat cortex synaptosomes and in sucrose density gradients of vesicle-enriched fractions, where huntingtin immunoreactivity overlapped with the distribution of vesicle membrane proteins (SV2, transferrin receptor, and synaptophysin). Immunohistochemistry in human and rat brain revealed widespread cytoplasmic labeling of huntingtin within neurons, particularly cell bodies and dendrites, rather than the more selective pattern of axon terminal labeling characteristic of many vesicle-associated proteins. At the ultrastructural level, immunoreactivity in cortical neurons was detected in the matrix of the cytoplasm and around the membranes of the vesicles. The ubiquitous cytoplasmic distribution of huntingtin in neurons and its association with vesicles suggest that huntingtin may have a role in vesicle trafficking. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG,BOSTON,MA 02114. UNIV MASSACHUSETTS,MED CTR,DEPT MED,WORCESTER,MA 01655. UNIV MASSACHUSETTS,MED CTR,DEPT PHYSIOL,WORCESTER,MA 01655. UNIV MASSACHUSETTS,MED CTR,DEPT CELL BIOL,WORCESTER,MA 01655. RP DIFIGLIA, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114, USA. FU NINDS NIH HHS [NS31579, NS16367] NR 24 TC 497 Z9 505 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD MAY PY 1995 VL 14 IS 5 BP 1075 EP 1081 DI 10.1016/0896-6273(95)90346-1 PG 7 WC Neurosciences SC Neurosciences & Neurology GA QY935 UT WOS:A1995QY93500020 PM 7748555 ER PT J AU RAFFEL, C UEKI, K HARSH, GR LOUIS, DN AF RAFFEL, C UEKI, K HARSH, GR LOUIS, DN TI THE MULTIPLE TUMOR-SUPPRESSOR-1 CYCLIN-DEPENDENT KINASE INHIBITOR-2 GENE IN HUMAN CENTRAL-NERVOUS-SYSTEM PRIMITIVE NEUROECTODERMAL TUMOR SO NEUROSURGERY LA English DT Article DE MULTIPLE TUMOR SUPPRESSOR 1/CYCLIN DEPENDENT KINASE INHIBITOR 2; ONCOGENESIS; PRIMITIVE NEUROECTODERMAL TUMOR; TUMOR SUPPRESSOR GENES ID 17P; P53; MUTATIONS; CHILDHOOD; CANCER; LOSSES AB THE RECENTLY DESCRIBED multiple tumor suppressor 1/cyclin-dependent kinase inhibitor 2 (MTS1/CDKN2) gene, encoding the cyclin-dependent kinase 4 inhibitor p16, is mutated in a wide variety of tumor cell lines, including gliomas. To investigate the possible role of this gene in the genesis of the central nervous system primitive neuroectodermal tumor (PNET), four established PNET cell lines and 18 PNET surgical specimens were studied for deletions and mutations of the MTS1/CDKN2 gene. One of the four cell lines had homozygous deletion of the gene. No mutation in any of the three MTS1/CDKN2 exons was detected in the other three cell lines by single strand conformational polymorphism analysis. Eighteen surgical PNET specimens were studied for allelic and homozygous deletion at chromosome 9p21, the location of the MTS1/CDKN2 gene. No loss of heterozygosity was noted in 11 of the tumors, and no homozygous loss was noted in any tumor. Single strand conformational polymorphism analysis of the entire coding region of the MTS1/CDKN2 gene revealed no mutation within MTS1/CDKN2 in any tumor, Although deletion of MTS1/CDKN2 may occur in some PNET cell lines, neither deletion nor mutation of the gene is found in tumors before culture. The genesis of the human central nervous system PNET does not involve deletion or mutation of the MTS1/CDKN2 gene. C1 CHILDRENS HOSP LOS ANGELES,DIV PEDIAT NEUROSURG,LOS ANGELES,CA 90027. UNIV SO CALIF,SCH MED,DEPT NEUROL SURG,LOS ANGELES,CA 90033. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,MOLEC NEUROONCOL LAB,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA57683] NR 20 TC 14 Z9 14 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAY PY 1995 VL 36 IS 5 BP 971 EP 974 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA QV351 UT WOS:A1995QV35100045 PM 7791990 ER PT J AU BORGES, LF ZERVAS, NT LEHRICH, JR AF BORGES, LF ZERVAS, NT LEHRICH, JR TI IDIOPATHIC SPINAL-CORD HERNIATION - A TREATABLE CAUSE OF THE BROWN-SEQUARD SYNDROME - CASE-REPORT SO NEUROSURGERY LA English DT Note DE BROWN-SEQUARD SYNDROME; DURA; HERNIATION; SPINAL CORD AB SYMPTOMATIC HERNIATION OF the spinal cord through the dura is an uncommon clinical problem. Since 1989, we have encountered three patients who each presented with an unexplained, longstanding Brown-Sequard syndrome and were found to have idiopathic herniation of the thoracic spinal cord. This report describes the clinical, radiographic, and surgical findings in these three patients and reviews the five previously reported patients with this syndrome. Idiopathic herniation of the spinal cord is a treatable cause of the Brown-Sequard syndrome that may be more common than is currently recognized and should be known to all surgeons managing spinal disorders. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,BOSTON,MA 02114. RP BORGES, LF (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROSURG SERV,WHITE 1205,FRUIT ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY08264] NR 10 TC 81 Z9 84 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAY PY 1995 VL 36 IS 5 BP 1028 EP 1032 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA QV351 UT WOS:A1995QV35100075 PM 7791969 ER PT J AU WEISSKOFF, RM AF WEISSKOFF, RM TI FUNCTIONAL MRI - ARE WE ALL MOVING TOWARDS ARTIFACTUAL CONCLUSIONS - OR FMRI FACT OR FANCY SO NMR IN BIOMEDICINE LA English DT Editorial Material ID VISUAL-CORTEX; STIMULATION C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP WEISSKOFF, RM (reprint author), MASSACHUSETTS GEN HOSP,CTR NMR,DEPT RADIOL,BLDG 149 2301,13TH ST,BOSTON,MA 02129, USA. NR 10 TC 12 Z9 12 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD MAY PY 1995 VL 8 IS 3 BP 101 EP 103 DI 10.1002/nbm.1940080304 PG 3 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA RZ485 UT WOS:A1995RZ48500002 PM 8579996 ER PT J AU FLANZ, J DURLACHER, S GOITEIN, M LEVINE, A REARDON, P SMITH, A AF FLANZ, J DURLACHER, S GOITEIN, M LEVINE, A REARDON, P SMITH, A TI OVERVIEW OF THE MGH NORTHEAST-PROTON-THERAPY-CENTER PLANS AND PROGRESS SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS LA English DT Article; Proceedings Paper CT 13th International Conference on the Application of Accelerators in Research and Industry CY NOV 07-10, 1994 CL DENTON, TX SP US DOE, Natl Sci Fdn, Univ N Texas AB The Northeast Proton Therapy Center (NPTC) is currently being designed and is scheduled for completion in 1998. The goal of the project is to provide the northeast region of the United States with a first class proton therapy facility which has the capabilities needed for the conduct of innovative research, and proven treatments using proton therapy. The NPTC will be built on the Massachusetts General Hospital (MGH) campus. MGH has contracted Bechtel Corporation to coordinate the design and building of the civil construction. Ion Beam Applications (IBA) who is teamed with General Atomics, is responsible for the equipment. The specifications for the facility are written in terms of the clinical performance requirements and will be presented. Aspects of the facility design, status and plans will also be presented. RP FLANZ, J (reprint author), MASSACHUSETTS GEN HOSP,NE PROTON THERAPY CTR,75 BLOSSOM COURT,BOSTON,MA 02114, USA. NR 5 TC 30 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-583X J9 NUCL INSTRUM METH B JI Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms PD MAY PY 1995 VL 99 IS 1-4 BP 830 EP 834 DI 10.1016/0168-583X(94)00586-9 PG 5 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA RK760 UT WOS:A1995RK76000219 ER PT J AU HAUSER, R ELREEDY, S HOPPIN, JA CHRISTIANI, DC AF HAUSER, R ELREEDY, S HOPPIN, JA CHRISTIANI, DC TI UPPER AIRWAY RESPONSE IN WORKERS EXPOSED TO FUEL-OIL ASH - NASAL LAVAGE ANALYSIS SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE NASAL LAVAGE; FUEL OIL ASH; VANADIUM ID COTTON DUST; OZONE; INFLAMMATION; POLLUTANTS; ADAPTATION; NOSE AB Objectives-Among other constituents fuel oil ash contains vanadium pentoxide, a known respiratory irritant. Exposure to ambient vanadium pentoxide dust has been shown to produce irritation of the eyes, nose, and throat. The usefulness of nasal lavage in detecting an inflammatory response to exposure to fuel oil ash among 37 boilermakers and utility workers was investigated. Methods-A baseline lavage was performed on the morning of the first day back to work after an average of 114 days away from work (range 36 hours to 1737 days). A lavage was performed after exposure on the morning three days after the baseline lavage. Exposure to respirable particulate matter of diameter less than or equal to 10 mu m (PM(10)) and respirable vanadium dust were estimated with daily work diaries and a personal sampling device for respirable particulates. These estimates were made for each subject on each workday during the three days between lavages. For each subject, the adjusted change in polymorphonuclear cells was calculated by dividing the change in polymorphonuclear cell counts by the average of the counts before and after exposure. The association between the adjusted polymorphonuclear cell counts and exposure was assessed with multiple linear regression, adjusted for age and current smoking. Results-Personal sampling (one to 10 hour time weighted average) showed a range of PM(10) concentrations of 50 to 4510 mu g/m,3 and respirable vanadium dust concentration of 0.10 to 139 mu g/m(3). In smokers the adjusted polymorphonuclear cell count was not significantly different from zero (-0.1%, P > 0.5), but in nonsmokers it was significantly greater than zero (+50%, P < 0.05). In both non-smokers and smokers, there was considerable variability in adjusted polymorphonuclear cell counts and a dose-response relation between these adjusted cell counts and either PM(10) or respirable vanadium dust exposure could not be found. Conclusion-A significant increase in polymorphonuclear cells in non-smokers but not smokers was found. This suggests that in non-smokers, exposure to fuel oil ash is associated with upper airway inflammation manifested as increased polymorphonuclear cell counts. The lack of an increase in polymorphonuclear cells in smokers may reflect either a diminished inflammatory response or may indicate that smoking masks the effect of exposure to fuel oil ash. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,ENVIRONM SCI & ENGN PROGRAM,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,PULM & CRIT CARE UNIT,BOSTON,MA. RP HAUSER, R (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,OCCUPAT HLTH PROGRAM,BLDG 1,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NIEHS NIH HHS [ES07069, ES00002, ES05947] NR 28 TC 50 Z9 51 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD MAY PY 1995 VL 52 IS 5 BP 353 EP 358 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QX139 UT WOS:A1995QX13900011 PM 7795759 ER PT J AU PARK, SS MARCUS, DM DUKER, JS PESAVENTO, RD TOPPING, TM FREDERICK, AR DAMICO, DJ AF PARK, SS MARCUS, DM DUKER, JS PESAVENTO, RD TOPPING, TM FREDERICK, AR DAMICO, DJ TI POSTERIOR SEGMENT COMPLICATIONS AFTER VITRECTOMY FOR MACULAR HOLE SO OPHTHALMOLOGY LA English DT Article ID RETINAL-PIGMENT EPITHELIOPATHY; PARS-PLANA VITRECTOMY; VITREOUS SURGERY; PNEUMATIC RETINOPEXY; DETACHMENT; MEMBRANES; BREAKS AB Purpose: The purpose of this study is to assess the rate of posterior segment complications after vitreous surgery for macular holes and to evaluate the effect of such complications on final visual outcome. Methods: The authors reviewed retrospectively all cases of vitreous surgery for macular holes performed between June 1990 and October 1993. Among 98 patients with a followup of 3 months or more, all patients with posterior segment complications during the postoperative course were identified. The rate of complications was compared with that seen after vitreous surgery for macular pucker performed by the same surgeons. Results: Posterior segment complications were noted in 23 (23%) of 98 patients. These included peripheral retinal breaks (3%), rhegmatogenous retinal detachment from a peripheral retinal break (14%), enlargement of the hole (2%), late reopening of the hole (2%), retinal pigment epithelium loss under the hole (1%), photic toxicity (1%), and endophthalmitis (1%). In 40% of these eyes, the final visual acuity was two lines or more below preoperative visual acuity. When compared with the macular pucker group, the rate of posterior segment complications, in particular the rate of peripheral retinal tears and detachments, was significantly higher (P less than or equal to 0.05). Conclusions: The authors conclude that visually significant posterior segment complications may occur after vitrectomy for macular hole, and the rate of these complications appears to be higher than expected. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,RETINA SERV,BOSTON,MA. OPHTHALM CONSULTANTS BOSTON,BOSTON,MA. TUFTS UNIV,SCH MED,NEW ENGLAND EYE CTR,DEPT OPHTHALMOL,RETINA SERV,BOSTON,MA 02111. NR 32 TC 132 Z9 135 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 1995 VL 102 IS 5 BP 775 EP 781 PG 7 WC Ophthalmology SC Ophthalmology GA QY827 UT WOS:A1995QY82700013 PM 7777277 ER PT J AU ROELKE, M ONUNAIN, SS OSSWALD, S GARAN, H HARTHORNE, JW RUSKIN, JN AF ROELKE, M ONUNAIN, SS OSSWALD, S GARAN, H HARTHORNE, JW RUSKIN, JN TI SUBCLAVIAN CRUSH SYNDROME COMPLICATING TRANSVENOUS CARDIOVERTER-DEFIBRILLATOR SYSTEMS SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE LEAD COMPRESSION; TRANSVENOUS IMPLANTABLE CARDIOVERTER DEFIBRILLATORS ID PACEMAKER LEAD; AXILLARY VEIN; EXPERIENCE; FAILURE; DAMAGE AB Subclavian crush syndrome, described with pacemaker leads implanted via subclavian puncture, may occur when conductor fractures and insulation breaches develop by compression of a lead between the first rib and clavicle. We reviewed our experience in 164 patients who underwent intended implantation of transvenous defibrillator systems to determine the clinical relevance of subclavian crush syndrome in defibrillator patients. Venous access was obtained via subclavian puncture in 114 patients (70%) and via cephalic cut-down in 50 patients (30%). Nonthoracotomy lead systems, with or without subcutaneous patch, were successfully implanted in 131 of 164 patients (79.9%). Thoracotomy was required in 32 patients (19.5%) and subxiphoid patch in 1 patient (0.6%). Over a mean of 12.9 months (range 1-62 months), 3 patients (1.8%) required revision of the rate sensing lead/coil or superior vena caria coil after development of lead compression fractures in the region of the clavicle and first rib. In all 3 patients the leads had been implanted via subclavian puncture (2.6% of patients in whom the subclavian technique was utilized). Two patients presented with spurious shocks. One patient was asymptomatic. Conclusions: When venous access is obtained via subclavian puncture, subclavian crush syndrome may develop in patients with transvenous defibrillator systems. Patients may be asymptomatic and lead fractures may go unrecognized. When implanting transvenous defibrillator systems? strong consideration should be given to obtaining venous access primarily via the cephalic cut-down technique. C1 MASSACHUSETTS GEN HOSP,CARDIAC ARRHYTHMIA SERV,CARDIAC UNIT,BOSTON,MA 02114. NEWARK BETH ISRAEL MED CTR,DIV CARDIOL,NEWARK,NJ. NEWARK BETH ISRAEL MED CTR,CTR PACEMAKER,NEWARK,NJ. NR 24 TC 69 Z9 69 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD MAY PY 1995 VL 18 IS 5 BP 973 EP 979 DI 10.1111/j.1540-8159.1995.tb04737.x PN 1 PG 7 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA QY231 UT WOS:A1995QY23100005 PM 7659570 ER PT J AU YONG, WH SOUTHERN, JF PINS, MR WARSHAW, AL COMPTON, CC LEWANDROWSKI, KB AF YONG, WH SOUTHERN, JF PINS, MR WARSHAW, AL COMPTON, CC LEWANDROWSKI, KB TI CYST FLUID NB/70K CONCENTRATION AND LEUKOCYTE ESTERASE - 2 NEW MARKERS FOR DIFFERENTIATING PANCREATIC SEROUS TUMORS FROM PSEUDOCYSTS SO PANCREAS LA English DT Article DE CYSTIC FLUID NB/70K; LEUKOCYTE ESTERASE; PSEUDOCYSTS; SEROUS TUMORS ID OVARIAN-CANCER; CYSTADENOCARCINOMA; CYSTADENOMAS; NEOPLASMS; SERUM AB Cystic lesions of the pancreas include inflammatory pseudocysts, serous cystadenomas, and mucinous tumors, some of which are malignant. Preoperative clinical and radiological parameters are unreliable and may result in incorrect diagnosis and inappropriate treatment. Cyst fluid analysis for cytology, viscosity, carcinoembryonic antigen, CA 72-4, and CA 15-3 will distinguish mucinous from nonmucinous lesions and usually help in determining malignancy. Currently, there is no reliable method to differentiate inflammatory pseudocysts from serous cystadenomas. This distinction is important because the treatment of these two lesions is different; pseudocysts are either observed or drained, whereas serous tumors are usually resected. The tumor marker NB/70K was measured in aspirated cyst fluid from 13 inflammatory pseudocysts and 11 serous cystadenomas by a commercial immunoassay. Leukocyte esterase was measured using Chemstrip SG urine test strips and amylase and lipase on a routine chemistry analyzer. The cyst fluid NB/70K concentration was significantly higher in pseudocysts (mean, 555 U/ml; range, 42-1,926 U/ml) than in serous cystadenomas (mean, 12 U/ml; range, 0-130 U/ml) and this difference was significant (p < 0.0002). Leukocyte esterase was detected in 7 of 11 pseudocysts but was absent in 10 of 10 serous tumors (p = 0.002). Amylase and lipase values were generally higher in pseudocysts but these markers were unreliable due to marked outliers. Cyst fluid NB/70K and leukocyte esterase are promising markers to help differentiate pseudocysts from serous tumors on percutaneous aspirates. When combined with previously reported cyst fluid parameters (amylase, lipase, cytology, and amylase isoenzymes), these two cystic lesions can be reliably distinguished. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 15 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0885-3177 J9 PANCREAS JI Pancreas PD MAY PY 1995 VL 10 IS 4 BP 342 EP 346 DI 10.1097/00006676-199505000-00004 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QU157 UT WOS:A1995QU15700004 PM 7792290 ER PT J AU WINSTON, KR OGILVY, CS MCGRAIL, K AF WINSTON, KR OGILVY, CS MCGRAIL, K TI REDUCTION CRANIOPLASTY SO PEDIATRIC NEUROSURGERY LA English DT Article DE HYDROCEPHALUS; MACROCEPHALY; REDUCTION CRANIOPLASTY; RISKS; SURGICAL TECHNIQUE ID ADVANCED HYDROCEPHALUS AB Reduction cranioplasty can greatly improve the quality of life for selected patients with severe macrocephaly and can significantly diminish some of the difficulties in the long-term chronic care of others. Because of differences in age, cranial morphology and surgical goals, the surgical plan must be tailored to the individual patient. Three techniques for reduction cranioplasty, with the advantages and disadvantages of each, are described. Four patients, representing the spectrum of severe macrocephaly and also the problems associated with reduction cranioplasty, are presented. Surgical indications, tactical considerations and risks are discussed. C1 UNIV COLORADO,CTR HLTH SCI,DEPT NEUROSURG,DENVER,CO. CHILDRENS HOSP,DENVER,CO 80218. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. GEORGETOWN UNIV,DEPT NEUROSURG,WASHINGTON,DC 20057. NR 10 TC 11 Z9 11 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1016-2291 J9 PEDIATR NEUROSURG JI Pediatr. Neurosurg. PD MAY PY 1995 VL 22 IS 5 BP 228 EP 234 DI 10.1159/000120906 PG 7 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA RE321 UT WOS:A1995RE32100002 PM 7547453 ER PT J AU CAHALIN, LP SADOWSKY, HS AF CAHALIN, LP SADOWSKY, HS TI PULMONARY MEDICATIONS SO PHYSICAL THERAPY LA English DT Review DE BRONCHODILATOR AGENTS; PHARMACOLOGY; PULMONARY, GENERAL RESPIRATION; VENTILATION ID OBSTRUCTIVE LUNG-DISEASE; INHALED NITRIC-OXIDE; BRONCHIAL RESPONSIVENESS; CARDIOVASCULAR ADJUSTMENTS; GLUCOCORTICOID TREATMENT; EXERCISE PERFORMANCE; AIRWAY INFLAMMATION; RESPIRATORY MUSCLES; ENDOTHELIAL-CELLS; SKELETAL-MUSCLE AB Many of the patients seen by physical therapists have primary or secondary diagnoses for which cardiovascular- or pulmonary-active medications may be prescribed. There is a need therefore, for physical therapists to understand the pharmacologic treatment of such patients. This article discusses medications commonly used in the treatment of pulmonary disorders. These medications are typically divided into the following categories: bronchodilators, anti-inflammatory agents, decongestants, antihistamines, antitussives, mucokinetics, respiratory stimulants and depressants, and paralyzing and antimicrobial agents. Regardless of which group a particular medication belongs to, the rationale for its prescription centers on promoting bronchodilation or relieving bronchoconstriction, facilitating the removal of secretions from the lungs, improving alveolar ventilation or oxygenation or optimizing the breathing pattern. The relative importance of each of these goals depends on the specific disease process involved and the resultant respiratory problem(s). C1 INST HLTH PROFESS,BOSTON,MA 02114. CALIF STATE UNIV FRESNO,DEPT PHYS THERAPY,FRESNO,CA 93740. RP CAHALIN, LP (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 128 TC 0 Z9 0 U1 0 U2 0 PU AMER PHYS THER ASSN PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD MAY PY 1995 VL 75 IS 5 BP 397 EP 414 PG 18 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA QW072 UT WOS:A1995QW07200009 PM 7732084 ER PT J AU TAGUE, BW GOODMAN, HM AF TAGUE, BW GOODMAN, HM TI CHARACTERIZATION OF A FAMILY OF ARABIDOPSIS ZINC-FINGER PROTEIN CDNAS SO PLANT MOLECULAR BIOLOGY LA English DT Article DE ARABIDOPSIS THALIANA; C2H2 ZINC FINGER PROTEIN; TRANSCRIPTION FACTOR; ORGAN-SPECIFIC EXPRESSION ID NUCLEAR-LOCALIZATION; TRANSCRIPTION FACTORS; XENOPUS-LAEVIS; PHOSPHORYLATION; BINDING; GENES; EXPRESSION; SEQUENCES; OPA; ORGANIZATION AB Work from animal systems indicates that C2H2 zinc finger proteins play an important role in development, and this is likely true for plant systems as well. To address this question we have used the sequence information from a previously isolated Arabidopsis thaliana C2H2 zinc finger protein gene to isolate additional cDNAs belonging to this gene family. While zinc finger genes isolated from other organisms encode multiple copies of this domain, the eight cDNAs isolated from Arabidopsis each contain only a single zinc finger. Outside of the finger region there is little sequence identity or similarity, although features characteristic of transcription factors are evident. While these genes are related, hybridization analysis indicates that each of them is a unique gene in the Arabidopsis genome. Analysis of mRNA demonstrates that the genes are expressed in different but overlapping sets of organs in the plant. These results are discussed in the light of recent analysis of zinc finger genes from other plant systems. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 41 TC 43 Z9 59 U1 0 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-4412 J9 PLANT MOL BIOL JI Plant Mol.Biol. PD MAY PY 1995 VL 28 IS 2 BP 267 EP 279 DI 10.1007/BF00020246 PG 13 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA RH500 UT WOS:A1995RH50000006 PM 7599312 ER PT J AU SNIDMAN, N KAGAN, J RIORDAN, L SHANNON, DC AF SNIDMAN, N KAGAN, J RIORDAN, L SHANNON, DC TI CARDIAC-FUNCTION AND BEHAVIORAL REACTIVITY DURING INFANCY SO PSYCHOPHYSIOLOGY LA English DT Article DE HEART PERIOD; AUTONOMIC NERVOUS SYSTEM; INFANT DEVELOPMENT; TEMPERAMENT ID HEART-RATE-VARIABILITY; TEMPERAMENT; NEWBORN; LIFE AB Longitudinal cardiac data from the end of the fetal period to 21 months of age were examined for change and stability over age and relations to the temperamental characteristics of high and low reactivity at 4 months of age and fear to the unfamiliar in the second year. Heart period and power in the cardiac spectra changed dramatically over the first 2 years, and individual differences were not preserved until 9-14 months of age. Sleep heart period at 2 weeks of age and low frequency power at 2 months of age were better predictors of the temperamental categories than later measures of the same variables, suggesting that cardiac function early in life may be an especially sensitive index of temperamental qualities. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP SNIDMAN, N (reprint author), HARVARD UNIV,DEPT PSYCHOL,33 KIRKLAND ST,CAMBRIDGE,MA 02138, USA. NR 29 TC 71 Z9 71 U1 1 U2 7 PU SOC PSYCHOPHYSIOL RES PI WASHINGTON PA 1010 VERMONT AVE NW SUITE 1100, WASHINGTON, DC 20005 SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD MAY PY 1995 VL 32 IS 3 BP 199 EP 207 DI 10.1111/j.1469-8986.1995.tb02949.x PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA QV891 UT WOS:A1995QV89100001 PM 7784528 ER PT J AU CREMENS, MC CALABRESE, LV SHUSTER, JL STERN, TA AF CREMENS, MC CALABRESE, LV SHUSTER, JL STERN, TA TI THE MASSACHUSETTS GENERAL-HOSPITAL ANNOTATED-BIBLIOGRAPHY - FOR RESIDENTS TRAINING IN CONSULTATION-LIAISON PSYCHIATRY SO PSYCHOSOMATICS LA English DT Article AB The annotated bibliography for the resident's division of the Avery D. Weisman Psychiatry Consultation Service at the Massachusetts General Hospital (MGH) equips the residents with a practical knowledge in consultation-liaison (C-L) psychiatry for their forays onto the floors of the general hospital. As an annotated bibliography, it is not intended to be a comprehensive source for C-L training. However, the basic fund of knowledge prepares MGH's psychiatric residents in a practical way for the variety of questions posed to the C-L service. The authors present this annotated bibliography as a guide for future efforts to establish a core content of knowledge for residents training in C-L psychiatry. C1 HARVARD UNIV,SCH MED,PSYCHIAT CONSULTAT SERV,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP CREMENS, MC (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,WARREN BLDG,606 FRUIT ST,BOSTON,MA 02114, USA. NR 13 TC 7 Z9 7 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1995 VL 36 IS 3 BP 217 EP 235 PG 19 WC Psychiatry; Psychology SC Psychiatry; Psychology GA QW930 UT WOS:A1995QW93000001 PM 7638309 ER PT J AU PETEET, JR AF PETEET, JR TI FORCED INTO TREATMENT - THE ROLE OF COERCION IN CLINICAL-PRACTICE SO PSYCHOSOMATICS LA English DT Book Review C1 BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. RP PETEET, JR (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1995 VL 36 IS 3 BP 311 EP 311 PG 1 WC Psychiatry; Psychology SC Psychiatry; Psychology GA QW930 UT WOS:A1995QW93000013 ER PT J AU FISCHER, CP BODE, BP ABCOUWER, SF LUKASZEWICZ, GC SOUBA, WW AF FISCHER, CP BODE, BP ABCOUWER, SF LUKASZEWICZ, GC SOUBA, WW TI HEPATIC-UPTAKE OF GLUTAMINE AND OTHER AMINO-ACIDS DURING INFECTION AND INFLAMMATION SO SHOCK LA English DT Editorial Material ID TUMOR NECROSIS FACTOR; ACUTE-PHASE RESPONSE; PLASMA-MEMBRANE VESICLES; ADAPTIVE REGULATION; PROTEIN-SYNTHESIS; HUMAN HEPATOCYTES; RAT HEPATOCYTES; GENE-EXPRESSION; TRANSPORT; METABOLISM AB Catabolic illness such as sepsis and injury induce profound changes in host amino acid metabolism, including increased hepatic amino acid uptake. Because many amino acid-dependent pathways such as gluconeogenesis and acute-phase protein synthesis are activated in the liver during severe infection, this review will focus on the control of hepatic plasma membrane amino acid transport by specific inflammatory mediators. We specifically review the role of cytokines, eicosanoids, and glucorticoids in this response. Collectively, these signaling molecules act in a concerted manner to exert local control of hepatic function including the stimulation of amino acid transport. In particular, we review the role of glutamine and its transport in the liver, as it occupies a unique role in interorgan ammonia metabolism during critical illness. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG, DIV SURG ONCOL, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG, NUTR SUPPORT UNIT, BOSTON, MA 02114 USA. OI Abcouwer, Steven F/0000-0003-2580-1288 NR 52 TC 32 Z9 33 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD MAY PY 1995 VL 3 IS 5 BP 315 EP 322 PG 8 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA QY848 UT WOS:A1995QY84800001 PM 7648331 ER PT J AU LIU, VF BOUBNOV, NV WEAVER, DT AF LIU, VF BOUBNOV, NV WEAVER, DT TI CELL-CYCLE CHECKPOINTS AND REPAIR OF IONIZING-RADIATION DAMAGE SO STEM CELLS LA English DT Article; Proceedings Paper CT International-Searle-Foundation Workshop on Assessment of Radiation Effects by Molecular and Cellular Approaches CY SEP, 1994 CL SCHLOSS REISENSBURG, ULM, GERMANY SP Int Searle Fdn, Int Inst Sci Cooperat HO SCHLOSS REISENSBURG DE IONIZING RADIATION; REPAIR; CHECKPOINTS; ATAXIA TELANGIECTASIA; P53; P21(WAF1/CLP1); KU; DNA-PK; V(D)J RECOMBINATION; RPA ID ACTIVATED PROTEIN-KINASE; VIRUS-40 DNA-REPLICATION; STRAND BREAK REPAIR; COMBINED IMMUNE-DEFICIENCY; CHINESE-HAMSTER OVARY; WILD-TYPE P53; V(D)J RECOMBINATION; ATAXIA-TELANGIECTASIA; T-ANTIGEN; GENE AMPLIFICATION AB Following exposure to ionizing radiation (IR), normal cells activate a delay in any phase of the cell cycle in conjunction with DNA repair mechanisms. Cell cycle delay or arrest is a programmed response that is mutable by a variety of genetic changes. DNA repair mechanisms that are responsible for the repair of otherwise lethal IR-induced double-strand breaks (DSBs) operate in a parallel pathway. The formulation of this pathway has recently been investigated, and new information regarding several mutant cell lines that are unable to execute IR-induced DSB repair are summarized. The scid mutation and defects in Ku proteins have been characterized. Molecular readouts of the properties of IR repair have been identified, including the hyperphosphorylation of the 34 kDa subunit of replication protein A. In addition, we have identified features of the G(1)/S IR-induced checkpoint that can be influenced by p53 status, genetic background or the levels of cell cycle proteins, A further understanding of the players in these pathways is expected to lead to the identification of molecular markers for ionizing radiation damage. Examination of the changes in these proteins may be valuable in a clinical setting for documenting radiation exposure. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. NR 93 TC 25 Z9 26 U1 0 U2 0 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PD MAY PY 1995 VL 13 SU 1 BP 117 EP 128 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA RQ185 UT WOS:A1995RQ18500016 PM 7488937 ER PT J AU TATTER, SB BUONANNO, FS OGILVY, CS AF TATTER, SB BUONANNO, FS OGILVY, CS TI ACUTE LACUNAR STROKE IN ASSOCIATION WITH ANGIOGRAM-NEGATIVE SUBARACHNOID HEMORRHAGE - MECHANISTIC IMPLICATIONS OF 2 CASES SO STROKE LA English DT Note DE ANGIOGRAPHY; ARTERIAL OCCLUSIVE DISEASES; CEREBRAL ARTERIES; CEREBRAL INFARCTION; SUBARACHNOID HEMORRHAGE ID UNKNOWN ETIOLOGY; INTRACEREBRAL HEMORRHAGE; CEREBRAL-HEMORRHAGE; ANEURYSMS; HYPERTENSION; RUPTURE; PATTERN; ORIGIN; CT AB Background and Purpose Although there is much speculation regarding the source of bleeding in patients with subarachnoid hemorrhage when no angiographic abnormality is found, little direct evidence has been obtained to document a cause. We report two cases of stroke in the distribution of a perforating or lenticulostriate artery occurring at the time of angiogram-negative subarachnoid hemorrhage. Case Descriptions A 68- and a 60-year-old man each presented with acute onset of headache and meningismus. Computed tomography (CT) revealed subarachnoid hemorrhage in a perimesencephalic pattern and in the left sylvian fissure, respectively. In both instances, immediate CT revealed evidence of an early infarction in the distribution of a perforating artery originating at the site of the subarachnoid blood. Both of these strokes were demonstrated to be acute by evolution on serial imaging studies. No source for the subarachnoid blood could be found in either patient in cerebral angiograms repeated at 2 weeks. Conclusions These observations suggest that in some cases of angiogram-negative subarachnoid hemorrhage the source of blood may be a small artery that is obliterated at the time of hemorrhage. This observation provides an explanation for the low rate of rehemorrhage among patients with angiogram-negative subarachnoid hemorrhage. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. NR 36 TC 18 Z9 18 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 1995 VL 26 IS 5 BP 891 EP 895 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA QV877 UT WOS:A1995QV87700033 PM 7740585 ER PT J AU SELVAKUMAR, A GRANJA, CB SALAZAR, M ALOSCO, SM YUNIS, EJ DUPONT, B AF SELVAKUMAR, A GRANJA, CB SALAZAR, M ALOSCO, SM YUNIS, EJ DUPONT, B TI A NOVEL SUBTYPE OF A2 (A-ASTERISK-0217) ISOLATED FROM THE SOUTH-AMERICAN INDIAN B-CELL LINE AMALA SO TISSUE ANTIGENS LA English DT Note DE A2; A-ASTERISK-0217; SOUTH AMERICAN INDIAN; B-CELL; AMALA ID HLA-A; RESOLUTION; ANTIGEN; MHC C1 AMER RED CROSS,DEDHAM,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. RP SELVAKUMAR, A (reprint author), MEM SLOAN KETTERING CANC CTR,PROGRAM IMMUNOL,1275 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA 22507, CA 08748] NR 18 TC 26 Z9 27 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD MAY PY 1995 VL 45 IS 5 BP 343 EP 347 DI 10.1111/j.1399-0039.1995.tb02464.x PG 5 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA QZ010 UT WOS:A1995QZ01000008 PM 7652742 ER PT J AU MILLER, JB BOYCE, FM AF MILLER, JB BOYCE, FM TI GENE-THERAPY BY AND FOR MUSCLE-CELLS SO TRENDS IN GENETICS LA English DT Editorial Material ID LONG-TERM CORRECTION; MEDIATED TRANSFER; MYOBLASTS; INVIVO RP MILLER, JB (reprint author), MASSACHUSETTS GEN HOSP,NEUROMUSCULAR LAB,149 13TH ST,BOSTON,MA 02129, USA. NR 20 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD MAY PY 1995 VL 11 IS 5 BP 163 EP 165 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA QU867 UT WOS:A1995QU86700002 PM 7785070 ER PT J AU BARRY, MJ OLEARY, MP AF BARRY, MJ OLEARY, MP TI THE DEVELOPMENT AND CLINICAL UTILITY OF SYMPTOM SCORES SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID BENIGN PROSTATIC HYPERPLASIA; AMERICAN-UROLOGICAL-ASSOCIATION; INDEX; QUALITY; QUESTIONNAIRE; PROSTATECTOMY; SPECIFICITY; VALIDATION; AGE AB Urinary symptom severity can be documented objectively among men with BPH using validated instruments such as the AUA Symptom Index. The AUA Index was developed to discriminate among BPH patients who are more or less bothered by their condition, and to measure change in symptom levels over time or with treatment. The AUA Index is reliable and valid for these purposes, and can be useful in both clinical practice and research. The role of symptom measurement in general and the AUA Index in particular in the diagnosis of BPH is unclear, and may be limited. Additional research is needed to maximize the utility of symptom measurement in urology. C1 HARVARD UNIV,SCH MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT SURG,DIV UROL,BOSTON,MA 02115. RP BARRY, MJ (reprint author), MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,HLTH SERV RES PROGRAM,50 STANIFORD ST,9TH FLOOR,BOSTON,MA 02114, USA. FU AHRQ HHS [HS 08397] NR 41 TC 33 Z9 33 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD MAY PY 1995 VL 22 IS 2 BP 299 EP 307 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA QZ977 UT WOS:A1995QZ97700007 PM 7539176 ER PT J AU RIEHMANN, M KNES, JM HEISEY, D MADSEN, PO BRUSKEWITZ, RC AF RIEHMANN, M KNES, JM HEISEY, D MADSEN, PO BRUSKEWITZ, RC TI TRANSURETHRAL RESECTION VERSUS INCISION OF THE PROSTATE - A RANDOMIZED, PROSPECTIVE-STUDY SO UROLOGY LA English DT Article ID TRANS-URETHRAL RESECTION; BLADDER NECK INCISION; CANCER AB Objectives, To evaluate longer term effects of transurethral resection (TURF) and incision (TUIP) of the prostate in randomized patients. Methods, In a randomized, prospective study, 120 patients with symptoms of bladder outlet obstruction caused by smaller benign prostates (estimated resectable weight less than 20 g) were assigned to TURF or TUIP, Patients were evaluated preoperatively and at intervals postoperatively as to urinary symptoms (Madsen's questionnaire), sexual function, and uroflowmetry. Overall evaluation of outcome of surgery was also assessed at follow-up visits. Results, Fifty-six patients received a TURF and 61 a TUIP, Three patients refused to participate in the project after randomization, and 5 patients were lost to or excluded from follow-up. A group of 1 12 patients were obtainable for postoperative evaluation with a mean follow-up time of 34 months (1 to 82 months). Improvements in mean urinary peak flow rates were seen in both groups throughout the study period. The peak flow rates generally were higher (but not statistically so) in the TURF group. Postoperative irritative, obstructive, as well as total symptom scores decreased significantly at all followup visits after both TURF and TUIP (P less than or equal to 0.034). Preoperatively and at all postoperative follow-up there was no statistically significant difference in irritative, obstructive, or total symptom scores between TURF and TUIP. The patients indicated an overall subjective improvement at all follow-ups in both groups, with no statistically significant difference be tween the treatment groups. Fifteen of 22 (68%) patients receiving TURF and 8 of 23 (35%) in the TUIP group who were sexually active before and after surgery developed postoperative retrograde ejaculation (P = 0.020), Postoperatively, 9 (16%) of the patients in the TURF and 14 (23%) in the TUIP group received further treatment for benign prostatic hyperplasia (BPH)-related infravesical obstruction. This difference was not statistically significant (P = 0.908). Conclusions. In small prostates TURF and TUIP were generally equally effective in relieving bladder outlet obstruction secondary to BPH. Most surgically treated BPH cases can be well managed by the incision technique, which is an underutilized procedure. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,DIV UROL,MADISON,WI. RP RIEHMANN, M (reprint author), UNIV WISCONSIN HOSP & CLIN,DEPT SURG,DIV UROL,MADISON,WI 53792, USA. NR 30 TC 58 Z9 61 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD MAY PY 1995 VL 45 IS 5 BP 768 EP 775 DI 10.1016/S0090-4295(99)80081-8 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA QW467 UT WOS:A1995QW46700011 PM 7538238 ER PT J AU TOGAWA, K RUSTGI, AK AF TOGAWA, K RUSTGI, AK TI A NOVEL HUMAN PAPILLOMAVIRUS SEQUENCE BASED ON L1 GENERAL PRIMERS SO VIRUS RESEARCH LA English DT Article DE HUMAN PAPILLOMAVIRUS; L1 REGION; NOVEL SEQUENCE ID POLYMERASE CHAIN-REACTION; P53 AB Over 65 human papillomaviruses (HPVs) have been identified. The majority have been isolated on the basis of cloning systems in bacteria. Recently, general consensus or degenerate primers from the L1 region have been used in PCR to identify novel genotypes. In this fashion, we employed general primers in the L1 region followed by DNA sequencing to identify a novel HPV sequence in association with esophageal squamous cell carcinoma. RP TOGAWA, K (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,JACKSON 904,50 BLOSSOM ST,BOSTON,MA 02114, USA. NR 21 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD MAY PY 1995 VL 36 IS 2-3 BP 293 EP 297 DI 10.1016/0168-1702(95)00011-E PG 5 WC Virology SC Virology GA QW562 UT WOS:A1995QW56200015 PM 7653107 ER PT J AU NATHAN, DM AF NATHAN, DM TI MANAGEMENT OF DIABETES-MELLITUS AFTER THE DCCT - WHATS NEXT SO WESTERN JOURNAL OF MEDICINE LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP, MALLINCKRODT GEN CLIN RES CTR, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. RP NATHAN, DM (reprint author), MASSACHUSETTS GEN HOSP, DIABET RES CTR, DIABET CLIN, BOSTON, MA 02114 USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU B M J PUBLISHING INC PI SAN FRANCISCO PA 221 MAIN ST, PO BOX 7690, SAN FRANCISCO, CA 94120-7690 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD MAY PY 1995 VL 162 IS 5 BP 469 EP 470 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QY992 UT WOS:A1995QY99200017 PM 7785269 ER PT J AU KOCHER, MS AF KOCHER, MS TI HISTORY OF REPLANTATION - FROM MIRACLE TO MICROSURGERY SO WORLD JOURNAL OF SURGERY LA English DT Article AB Severed body parts, from fingers to extremities, are now being routinely reattached at medical centers around the world. The dream of replantation traces its rich history from miracles and legends to early laboratory experiments and clinical attempts, culminating in today's commonplace procedure. RP KOCHER, MS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ORTHOPED SURG,FRUIT ST,BOSTON,MA 02114, USA. NR 49 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD MAY-JUN PY 1995 VL 19 IS 3 BP 462 EP 467 PG 6 WC Surgery SC Surgery GA RD004 UT WOS:A1995RD00400029 PM 7639007 ER PT J AU SHIPLEY, WU VERHEY, LJ MUNZENRIDER, JE SUIT, HD URIE, MM MCMANUS, PL YOUNG, RH SHIPLEY, JW ZIETMAN, AL BIGGS, PJ HENEY, NM GOITEIN, M AF SHIPLEY, WU VERHEY, LJ MUNZENRIDER, JE SUIT, HD URIE, MM MCMANUS, PL YOUNG, RH SHIPLEY, JW ZIETMAN, AL BIGGS, PJ HENEY, NM GOITEIN, M TI ADVANCED PROSTATE-CANCER - THE RESULTS OF A RANDOMIZED COMPARATIVE TRIAL OF HIGH-DOSE IRRADIATION BOOSTING WITH CONFORMAL PROTONS COMPARED WITH CONVENTIONAL-DOSE IRRADIATION USING PHOTONS ALONE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE CARCINOMA OF THE PROSTATE; PROTON IRRADIATION; CONFORMAL RADIATION THERAPY; RADIATION TOLERANCE; RANDOMIZED COMPARATIVE TRIALS ID BEAM RADIATION-THERAPY; LOCAL-CONTROL; METASTATIC DISSEMINATION; X-RAY; CARCINOMA; BIOPSY; ADENOCARCINOMA; RADIOTHERAPY AB Purpose: Following a thorough Phase I/II study, we evaluated by a Phase III trial high versus conventional dose external beam irradiation as mono-therapy for patients with Stage T3-T4 prostate cancer. Patient outcome following standard dose radiotherapy or following a 12.5% increase in total dose to 75.6 Cobalt Gray Equivalent (CGE) using a conformal perineal proton boost was compared for local tumor control, disease-free survival, and overall survival. Methods and Materials: Stage T3-T4, Nx, NO-2, MO patients received 50.4 Gy by four-field photons and were randomized to receive either an additional 25.2 CGE by conformal protons (arm 1-the high dose arm, 103 patients, total dose 75.6 CGE) or an additional 16.8 Gy by photons (arm 2-the conventional dose arm, 99 patients, total dose 67.2 Gy). Actuarial overall survival (OS), disease-specific survival (DSS), total recurrence-free survival (TRFS), (clinically free, prostate specific antigen (PSA) less than 4ng/ml and a negative prostate rebiopsy, done in 38 patients without evidence of disease) and local control (digital rectal exam and rebiopsy negative) were evaluated. Results: The protocol completion rate was 90% for arm 1 and 97% for arm 2. With a median follow-up of 61 months (range 3 to 139 months) 135 patients are alive and 67 have died, 20 from causes other than prostate cancer. We found no significant differences in OS, DSS, TRFS or local control between the two arms. Among those completing randomized treatment (93 in arm 1 and 96 in arm 2), the local control at 5 and 8 years for arm 1 is 92% and 77%, respectively and is 80% and 60%, respectively for arm 2 (p = .089) and there are no significant differences in OS, DSS, and TRFS. The local control for the 57 patients ,vith poorly differentiated (Gleason 4 or 5 of 5) tumors at 5 and 8 years for arm 1 is 94% and 84% and is 64% and 19% on arm 2 (p = 0.0014). In patients whose digital rectal exam had normalized following treatment and underwent prostate rebiopsy there was a lower positive rebiopsy rate for arm 1 versus arm 2 patients (28 vs. 45%) and also for those with well and moderately differentiated tumors versus poorly differentiated tumors (32 and 50%). These differences were not statistically significant. Grade 1 and 2 rectal bleeding is higher (32 vs. 12%, p = 0.002) as may be urethral stricture (19 vs. 8%, p = 0.07) in the arm 1 versus arm 2. Conclusions: An increase in prostate tumor dose by external beam of 12.5% to 75.6 CGE by a conformal proton boost compared to a conventional dose of 67.2 Gy by a photon boost significantly improved local control only in patients with poorly differentiated tumors, It has increased late radiation sequelae, and as yet, has not increased overall survival, disease-specific survival, or total recurrence-free survival in any subgroup. These results have led us to test by a subsequent Phase III trial the potential beneficial effect on local control and disease-specific survival of a 12.5% increase in total dose relative to conventional dose in patients with T1, T2a, and T2b tumors. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR CANC,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR CANC,SCH MED,DEPT UROL,BOSTON,MA 02114. RP SHIPLEY, WU (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR CANC,SCH MED,DEPT RADIAT ONCOL,32 FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-221239] NR 28 TC 261 Z9 269 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 30 PY 1995 VL 32 IS 1 BP 3 EP 12 DI 10.1016/0360-3016(95)00063-5 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA QU490 UT WOS:A1995QU49000001 PM 7721636 ER PT J AU WILLETT, CG WARLAND, G COEN, J SHELLITO, PC COMPTON, CC AF WILLETT, CG WARLAND, G COEN, J SHELLITO, PC COMPTON, CC TI RECTAL-CANCER - THE INFLUENCE OF TUMOR PROLIFERATION ON RESPONSE TO PREOPERATIVE IRRADIATION SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE RECTAL CANCER; TUMOR PROLIFERATION; PREOPERATIVE IRRADIATION; KI-67; PROLIFERATING CELL NUCLEAR ANTIGEN ID CELL NUCLEAR ANTIGEN; DNA POLYMERASE-DELTA; RADIATION-THERAPY; GROWTH FRACTION; PARAFFIN SECTIONS; MONOCLONAL-ANTIBODIES; AUXILIARY PROTEIN; EMBEDDED TISSUES; CYCLIN PCNA; KI-67 INDEX AB Purpose: Regression of rectal carcinoma after preoperative irradiation is variable, likely reflecting differences in the physical and biologic properties of these tumors, This study examines the association between the pathologic response of rectal cancer after irradiation and its pretreatment proliferative state as assayed by the activity of the proliferative dependent antigens (Ki-67, PCNA) and mitotic counts. Methods and Materials: One hundred and twenty-two patients with locally advanced rectal cancer received preoperative irradiation followed by surgery, Pretreatment tumor biopsies were scored for the extent of Ki-67 and PCNA immunostaining and the number of mitoses per 10 high-powered fields, Postirradiation surgical specimens were examined for extent of residual disease. Results: The tumors of 38 of 122 patients (31%) exhibited marked pathologic downstaging (no residual tumor or cancer confined to the rectal wall) after preoperative irradiation, Two features were associated with the likelihood of marked pathologic regression after preoperative irradiation: tumor proliferative activity and lesion size, When stratified by lesion size, marked tumor regression occurred most frequently in smaller tumors with high Ki-67, PCNA, and mitotic activity compared to larger tumors with lower Ki-67, PCNA, and mitotic activity, Intermediate downstaging rates were seen for small or large tumors with moderate Ki-67, PCNA, and mitotic activity. Conclusion: Tumor Ki-67, PCNA, and mitotic activity predicts the likelihood of response to irradiation, which may aid in formulating treatment policies for patients with rectal cancer. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR CANC,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR CANC,SCH MED,DEPT GEN SURG,BOSTON,MA 02114. RP WILLETT, CG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR CANC,SCH MED,DEPT RADIAT ONCOL,COX BLDG,100 BLOSSOM ST,BOSTON,MA 02114, USA. NR 26 TC 53 Z9 54 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 30 PY 1995 VL 32 IS 1 BP 57 EP 61 DI 10.1016/0360-3016(94)00457-V PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA QU490 UT WOS:A1995QU49000007 PM 7721640 ER PT J AU HUANG, PG ALLAM, A PEREZ, LA TAGHIAN, A FREEMAN, J SUIT, HD AF HUANG, PG ALLAM, A PEREZ, LA TAGHIAN, A FREEMAN, J SUIT, HD TI THE EFFECT OF COMBINING RECOMBINANT HUMAN TUMOR-NECROSIS-FACTOR-ALPHA WITH LOCAL RADIATION ON TUMOR-CONTROL PROBABILITY OF A HUMAN GLIOBLASTOMA-MULTIFORME XENOGRAFT IN NUDE-MICE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE RHUTNF-ALPHA; HUMAN TUMOR XENOGRAFT; GLIOBLASTOMA MULTIFORME; TCD50 ID FRACTIONATED-IRRADIATION; ENDOTHELIAL-CELLS; CYTO-TOXICITY; RADIOTHERAPY; SENSITIVITY; CARCINOMA; HYPERTHERMIA; INTERFERON AB Purpose: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha)) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-alpha with local radiation on the tumor control probability of this tumor model. Methods and Materials: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm(3), mice were randomly assigned to treatment: rHuTNF-alpha alone compared with normal saline control; or local radiation plus rHuTNF-alpha vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-alpha on this tumor. The TCD50 (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-alpha with local radiation. Results: Tumor growth in mice treated with a dose of 150 mu g/kg body weight rHuTNF-alpha, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-alpha also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNP-alpha starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD50 from the control value of 60.9 Gy to 50.5 Gy (p < 0.01). Conclusion: rHuTNF-alpha exhibits an antitumor effect against U87 xenograft in nude mice, as evidenced by an increased delay in tumor growth as well as cell loss factor. Also, there was an augmentation of tumor curability when given in combination with radiotherapy, resulting in a significantly lower TCD50 value in the treatment vs. the control groups. RP HUANG, PG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,EDWIN L STEELE RADIAT BIOL,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. RI Perez-Romasanta, Luis/B-7771-2016 OI Perez-Romasanta, Luis/0000-0001-8117-5459 FU NCI NIH HHS [CA13311] NR 29 TC 11 Z9 11 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 30 PY 1995 VL 32 IS 1 BP 93 EP 98 DI 10.1016/0360-3016(94)00492-4 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA QU490 UT WOS:A1995QU49000012 PM 7721643 ER PT J AU TAGHIAN, A DUBOIS, W BUDACH, W BAUMANN, M FREEMAN, J SUIT, H AF TAGHIAN, A DUBOIS, W BUDACH, W BAUMANN, M FREEMAN, J SUIT, H TI IN-VIVO RADIATION SENSITIVITY OF GLIOBLASTOMA-MULTIFORME SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE GLIOBLASTOMA MULTIFORME; IN VIVO; XENOGRAFTS; NUDE MICE; RADIATION SENSITIVITY; TCD50 ID COMBINED IMMUNODEFICIENT MICE; SQUAMOUS-CELL CARCINOMA; NCR/SED-NU/NU NUDE; MURINE TUMORS; XENOGRAFTS; TRANSPLANTABILITY; IRRADIATION; BRAIN; RADIOSENSITIVITY AB Purpose: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF2 values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD50 (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD50 of the xenografts and the sensitivity of the corresponding cell lines in vitro. Methods and Materials: The TCD50 assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. Results: The TCD50 values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 +/- 13.1 Gy. The TCD50 values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 +/- 6.4. The difference between the average TCD50, of GBM and SCC was not significant. The STS and CC xenografts had TCD50 values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD50 in vivo and the SF2 or D-0 in vitro. Conclusions: Our data on GBM xenografts showed a wide range of sensitivities to single dose irradiation in vivo, which does not correlate with the almost invariably fatal clinical outcome of these patients. No correlation was observed between the TCD50 in vivo and the in vitro SF2/D-0 of the corresponding cell lines. Our in vivo and in vitro data on GBM suggest that radiation sensitivity alone does not explain the cause of the poor clinical response of GBM to radiation, and other factors could contribute to this response. C1 BOSTON UNIV,MED CTR,DEPT RADIAT ONCOL,BOSTON,MA. DR DANIEL DENHOED CLIN,DEPT RADIAT THERAPY,3075 EA ROTTERDAM,NETHERLANDS. UNIV ESSEN GESAMTHSCH,DEPT RADIAT THERAPY,D-45122 ESSEN,GERMANY. UNIV HAMBURG,HOSP EPPENDORF,DEPT RADIAT THERAPY,D-20246 HAMBURG,GERMANY. RP TAGHIAN, A (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB RADIAT BIOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA13311] NR 27 TC 53 Z9 53 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 30 PY 1995 VL 32 IS 1 BP 99 EP 104 DI 10.1016/0360-3016(94)00494-6 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA QU490 UT WOS:A1995QU49000013 PM 7721644 ER PT J AU ALLAM, A PEREZ, LA HUANG, PG TAGHIAN, A AZINOVIC, I FREEMAN, J DUFFY, M EFIRD, J SUIT, HD AF ALLAM, A PEREZ, LA HUANG, PG TAGHIAN, A AZINOVIC, I FREEMAN, J DUFFY, M EFIRD, J SUIT, HD TI THE EFFECT OF THE OVERALL TREATMENT TIME OF FRACTIONATED-IRRADIATION ON THE TUMOR-CONTROL PROBABILITY OF A HUMAN SOFT-TISSUE SARCOMA XENOGRAFT IN NUDE-MICE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE TCD50; OVERALL TREATMENT TIME; REPOPULATION; T-POT ID SQUAMOUS-CELL CARCINOMA; LOCAL-CONTROL; RADIOTHERAPY; REPOPULATION; RADIATION; LARYNX; REOXYGENATION; CANCER; NUMBER AB Purpose: To study the impact of the overall treatment time of fractionated irradiation on the tumor control probability (TCP) of a human soft tissue sarcoma xenograft growing in nude mice, as well as to compare the pretreatment potential doubling time (T-pot) of this tumor to the effective doubling time (T-eff) derived from three different schedules of irradiation using the same total number of fractions with different overall treatment times. Methods and Materials: The TCP was assessed using the TCD50 value (the 50% tumor control dose) as an end point. A total of 240 male nude mice, 7-8 weeks old were used in three experimental groups that received the same total number of fractions (30 fractions) with different overall treatment times. In group 1, the animals received three equal fractions/day for 10 consecutive days, in group 2 they received two equal fractions/day for 15 consecutive days, and in group 3 one fraction/day for 30 consecutive days. All irradiations were given under normal blood flow conditions to air breathing animals. The mean tumor diameter at the start of irradiation was 7-8 mm. The mean interfraction intervals were from 8-24 h. The T-pot was measured using Iododeoxyuridine (IudR) labeling and flow cytometry and was compared to T-eff. Results: The TCD50 values of the three different treatment schedules were 58.8 Gy, 63.2 Gy, and 75.6 Gy for groups 1, 2, and 3, respectively. This difference in TCD50 values was significant (p < 0.05) between groups 1 and 2 (30 fractions/10 days and 30 fractions/15 days) vs. group 3 (30 fractions/30 days). The loss in TCP due to the prolongation of the overall treatment time from 10 days to 30 days was found to be 1.35-1.4 Gy/day. The pretreatment T-pot (2.4 days) was longer than the calculated T-eff in groups 2 and 3 (1.35 days). Conclusion: Our data show a significant loss in TCP with prolongation of the overall treatment time. This is most probably due to an accelerated repopulation of tumor clonogens. The pretreatment T-pot of this tumor model does not reflect the actual doubling of the clonogens in a protracted regimen. RP ALLAM, A (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB RADIAT BIOL,BOSTON,MA 02114, USA. RI Perez-Romasanta, Luis/B-7771-2016 OI Perez-Romasanta, Luis/0000-0001-8117-5459 FU NCI NIH HHS [CA13311] NR 28 TC 25 Z9 26 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 30 PY 1995 VL 32 IS 1 BP 105 EP 111 DI 10.1016/0360-3016(95)00511-V PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA QU490 UT WOS:A1995QU49000014 PM 7721606 ER PT J AU SMITH, AR GERBER, RL HUGHES, DB KLINE, RW KUTCHER, G LING, C OWEN, JB HANLON, A WALLACE, M HANKS, GE AF SMITH, AR GERBER, RL HUGHES, DB KLINE, RW KUTCHER, G LING, C OWEN, JB HANLON, A WALLACE, M HANKS, GE TI TREATMENT PLANNING STRUCTURE AND PROCESS IN THE UNITED-STATES - A PATTERNS OF CARE STUDY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE FACILITY SURVEY; TREATMENT PLANNING; PATTERNS OF CARE; RADIATION THERAPY FACILITIES; RADIATION ONCOLOGY AB Purpose: To conduct a study of the structure and process of treatment planning in the United States. Methods and Materials: A Patterns of Care treatment planning consensus committee developed a survey form that was used to gather data for 106 items relating to the structure and process of treatment planning. These questions were general in nature and not specific to any particular disease site. Seventy-three facilities were randomly selected for site visits from the 1321 radiation therapy facilities in the United States: 21 academic, 26 hospital, and 26 free-standing. During the site visit the facility physicist, assisted by the site-visit physicist, completed the form. Results: Twenty-nine percent of facilities have cobalt-60 machines; 25% have 4 MV linacs; 75% have photon energies in the range of 5-8 MV; and less than 10% have energies greater than 20 MV. Academic facilities led hospital and free-standing facilities by about 30 percentage points in the availability of all electron energies (88 vs. 58%, approximately, in the range 4-13 MeV and scaling downward to about 60 vs. 30% at the highest energies). The national averages for the availability of Cs-137, Ir-192, and I-125 were 87, 73, and 44%, respectively. Computerized tomography (CT) scanning is not available or not used in 15% of hospital and free-standing facilities. Ninety-six percent of facilities have treatment planning computers; at 10% of facilities physicians do not participate in treatment planning. The estimated national averages of facilities having formal quality assurance (QA) programs for treatment planning systems, simulators, film processors, and blocking systems are 44, 79, 62, and 55%, respectively. Sixty-three percent of facilities obtain independent machine calibrations. Conclusion: This is the first patterns of treatment planning study carried out in the United States and the results reported here will establish a baseline for future studies. The present study has identified some elements that were unexpected, such as the percentage of facilities lacking formal QA programs for treatment planning systems; however, it has not established any impact of such findings. It is recommended that future studies include the availability of new technologies such as multileaf collimation, dynamic wedges, digital portal imaging, and CT simulation. With the increasing nationwide concern with the cost of health care, we must continue to monitor the implementation, use, and impact on treatment outcome of new and expensive technologies. C1 MALLINCKRODT INST RADIOL,ST LOUIS,MO. ST VINCENT HOSP,PORTLAND,OR. MAYO CLIN,ROCHESTER,MN. MEM HOSP,NEW YORK,NY. AMER COLL RADIOL,RESTON,VA. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. RP SMITH, AR (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,COX BLDG,RM 342,BOSTON,MA 02114, USA. FU NCI NIH HHS [N01-CM-87275] NR 2 TC 10 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 30 PY 1995 VL 32 IS 1 BP 255 EP 262 DI 10.1016/0360-3016(94)00472-W PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA QU490 UT WOS:A1995QU49000034 PM 7721625 ER PT J AU FORTENBERRY, SC CHIRGWIN, JM AF FORTENBERRY, SC CHIRGWIN, JM TI THE PROPEPTIDE IS NONESSENTIAL FOR THE EXPRESSION OF HUMAN CATHEPSIN-D SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LYSOSOMAL-ENZYME PHOSPHORYLATION; PROTEIN RECOGNITION DETERMINANTS; HAMSTER KIDNEY-CELLS; ACTIVE HUMAN RENIN; PROCATHEPSIN-D; ASPARTIC PROTEINASES; PORCINE PEPSINOGEN; TARGETING SIGNAL; CRYSTAL-STRUCTURES; SITE AB When the 44-amino acid propeptide of human procathepsin D was deleted by mutagenesis in vitro, the mature protein was stably expressed and secreted from transfected mammalian cells. The secreted protein was correctly folded as judged by its binding to pepstatinyl-agarose. We were unable to detect lysosomal targeting of the propeptide-deleted protein, and targeting was not restored by the substitution of the propeptides from pepsin or renin. We conclude that its propeptide is not essential for the folding of nascent cathepsin D. Efficient lysosomal targeting in mammalian cells appears to require the precursor form of the molecule. C1 UNIV TEXAS, HLTH SCI CTR, DEPT MED, DIV ENDOCRINOL & METAB, SAN ANTONIO, TX 78284 USA. UNIV TEXAS, HLTH SCI CTR, DEPT BIOCHEM, SAN ANTONIO, TX 78284 USA. AUDIE L MURPHY MEM VET ADM MED CTR, RES SERV, SAN ANTONIO, TX 78284 USA. NR 61 TC 24 Z9 24 U1 0 U2 1 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 APR 28 PY 1995 VL 270 IS 17 BP 9778 EP 9782 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QV417 UT WOS:A1995QV41700015 PM 7730356 ER PT J AU WADE, M BLAKE, MC JAMBOU, RC HELIN, K HARLOW, E AZIZKHAN, JC AF WADE, M BLAKE, MC JAMBOU, RC HELIN, K HARLOW, E AZIZKHAN, JC TI AN INVERTED REPEAT MOTIF STABILIZES BINDING OF E2F AND ENHANCES TRANSCRIPTION OF THE DIHYDROFOLATE-REDUCTASE GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADENOVIRUS-INFECTED CELLS; HUMAN MYC PROMOTER; DNA-BINDING; TRANS-ACTIVATION; E4 GENE; COOPERATIVE BINDING; COMPLEX-FORMATION; GROWTH-REGULATION; CELLULAR GENES; MESSENGER-RNA AB An overlapping inverted repeat sequence that binds the eukaryotic transcription factor E2F is 100% conserved near the major transcription start sites in the promoters of three mammalian genes encoding dihydrofolate reductase, and is also found in the promoters of several other important cellular and viral genes. This element, 5' TTTCGCGCCAAA-3', is comprised of two overlapping, oppositely oriented sites which match the consensus E2F site (5'-TTT(C/G) (C/G)CGC-3'). Recent work has shown that E2F binding activity is composed of at least six related cellular polypeptides which are capable of forming DNA-binding home- and heterodimers. We have investigated the binding of cellular E2F activity and of home- and heterodimers of cloned E2F proteins to the inverted repeat E2F element. We have demonstrated that mutations in this element that abolish its inverted repeat nature, while preserving a single consensus E2F site, significantly decrease the binding stability of all of the forms of E2F tested. The rate of association of E2F-1/DP-1 heterodimers with the inverted repeat wild type site was not significantly different from those with the two single site mutated probes, Furthermore, the mutations decrease in vitro transcription and transient reporter gene expression 2-5-fold, an effect equivalent to that of abolishing E2F binding altogether. These data suggest a functional role that may explain the conservation of inverted repeat E2F elements among the DHFR promoters and several other cellular and viral promoters. C1 ROSWELL PK CANC INST,DEPT EXPTL THERAPEUT,BUFFALO,NY 14263. UNIV N CAROLINA,LINEBERGER CANC RES CTR,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CURRICULUM GENET & MOLEC BIOL,CHAPEL HILL,NC 27599. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA. NR 59 TC 30 Z9 30 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 APR 28 PY 1995 VL 270 IS 17 BP 9783 EP 9791 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QV417 UT WOS:A1995QV41700016 PM 7730357 ER PT J AU JEFFREY, PD SCHILDBACH, JF CHANG, CYY KUSSIE, PH MARGOLIES, MN SHERIFF, S AF JEFFREY, PD SCHILDBACH, JF CHANG, CYY KUSSIE, PH MARGOLIES, MN SHERIFF, S TI STRUCTURE AND SPECIFICITY OF THE ANTIDIGOXIN ANTIBODY-40-50 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE X-RAY CRYSTALLOGRAPHY; FAB COMPLEX; HAPTEN; CARDIAC GLYCOSIDE ID 3-DIMENSIONAL STRUCTURE; VARIABLE REGION; CRYSTAL-STRUCTURE; HIGH-AFFINITY; FAB FRAGMENT; ANTIDIGOXIN ANTIBODIES; MONOCLONAL-ANTIBODY; PROTEIN-STRUCTURE; PEPTIDE ANTIGEN; COMPLEX AB We determined the sequence, specificity for structurally related cardenolides, and three-dimensional. structure of the anti-digoxin antibody 40-50 Fab in complex with ouabain. The 40-50 antibody does not share close sequence homology with other high-affinity anti-digoxin antibodies. Measurement of the binding constants of structurally distinct digoxin analogs indicated a well-defined specificity pattern also distinct from other anti-digoxin antibodies. The 40-50-ouabain Fab complex crystallizes in space group C2 with cell dimensions of a = 93.7 Angstrom, b = 84.8 Angstrom, c = 70.1 Angstrom, beta = 128.0 degrees. The structure of the complex was determined by X-ray crystallography and refined at a resolution of 2.7 Angstrom. The hapten is bound in a pocket extending as a groove from the center of the combining site across the light chain variable domain, with five of the six complementarity-determining regions involved in interactions with the hapten. Approximately three-quarters of the hapten surface area is buried in the complex; two hydrogen bonds are formed between the antibody and hapten. The surface area of the antibody combining site buried by ouabain is contributed equally by the Light and heavy chain variable domains. Over half of the surface area buried on the Fab consists of the aromatic side-chains. The surface complementarity between hapten and antibody is sufficient to make the complex specific for only one lactone ring conformation in the hapten. The crystal structure of the 40-50-ouabain complex allows qualitative explanation of the observed fine specificities of 40-50, including that for the binding of haptens substituted at the 16 and 12 positions. Comparison of the crystal structures of 40-50 complexed with ouabain and the previously determined 26-10 anti-digoxin Fab complexed with digoxin, demonstrates that the antibodies bind these structurally related haptens in different orientations, consistent with their different fine specificities. These results demonstrate that the immune system can generate antibodies that provide diverse structural solutions to the binding of even small molecules. C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MACROMOLEC CRYSTALLOG,PRINCETON,NJ 08543. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. FU NHLBI NIH HHS [P01 HL19259, R01 HL47415] NR 69 TC 65 Z9 65 U1 0 U2 2 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 28 PY 1995 VL 248 IS 2 BP 344 EP 360 DI 10.1016/S0022-2836(95)80055-7 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QV413 UT WOS:A1995QV41300014 PM 7739045 ER PT J AU FAVA, M RAPPE, SM WEST, J HERZOG, DB AF FAVA, M RAPPE, SM WEST, J HERZOG, DB TI ANGER ATTACKS IN EATING DISORDERS SO PSYCHIATRY RESEARCH LA English DT Article DE ANOREXIA NERVOSA; BULIMIA NERVOSA; AFFECTIVE DISORDER; AGGRESSION ID ANOREXIA-NERVOSA; BULIMIA-NERVOSA; FLUOXETINE TREATMENT; UNIPOLAR DEPRESSION; CEREBROSPINAL-FLUID; SEROTONIN ACTIVITY; RESPONSES; BEHAVIOR; ABNORMALITIES; RECOVERY AB As central nervous system serotonergic dysregulation has been postulated to exist in both eating and aggression disorders, we hypothesized that anger attacks would be more common among patients with eating disorders than among control subjects. In addition, we wanted to examine possible relationships between the presence of anger attacks and the type or severity of the eating disorder. Subjects were 39 normal female volunteers and 132 female outpatients with anorexia nervosa, bulimia nervosa, or both. Forty-one (31%) of the patients met criteria for anger attacks compared with four (10%) of the control subjects. Bulimic patients reported the highest prevalence of anger attacks, although the difference was not statistically significant. Among bulimic patients, there was a trend for anger attacks to be associated with greater severity of illness. In addition, patients with eating disorders who have anger attacks had significantly more depressive symptoms than patients without these attacks. Central serotonergic function is involved in such diverse processes as feeding behavior, mood regulation, and anger and aggression. The higher prevalence of anger attacks among patients than among control subjects may reflect central hyposerotonergic function, found in previous studies to be present in both eating disorders and pathologic aggression. Supporting this interpretation is the finding that the prevalence of anger attacks increased, although nonsignificantly, with the severity of bulimia, which has previously been shown to be inversely correlated with central serotonergic activity. RP FAVA, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,ACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 31 TC 46 Z9 46 U1 3 U2 6 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD APR 28 PY 1995 VL 56 IS 3 BP 205 EP 212 DI 10.1016/0165-1781(95)02577-J PG 8 WC Psychiatry SC Psychiatry GA RG374 UT WOS:A1995RG37400001 PM 7568542 ER PT J AU FAVA, M GIANNELLI, A RAPISARDA, V PATRALIA, A GUARALDI, GP AF FAVA, M GIANNELLI, A RAPISARDA, V PATRALIA, A GUARALDI, GP TI RAPIDITY OF ONSET OF THE ANTIDEPRESSANT EFFECT OF PARENTERAL S-ADENOSYL-L-METHIONINE SO PSYCHIATRY RESEARCH LA English DT Note DE AFFECTIVE DISORDER; ANTIDEPRESSANT, NOVEL; SAME AB A possible method of reducing the delay in antidepressant response is to use S-adenosyl-L-methionine (SAMe), a naturally occurring compound that appears to have a rapid onset of effect in the treatment of depression. In this open, multicenter study, 195 patients were given 400 mg of SAMe, administered parenterally, for 15 days. Depressive symptoms remitted after both 7 and 15 days of treatment with SAMe, and no serious adverse events were reported. Further studies with a double-blind design are needed to confirm this preliminary indication that SAMe is a relatively safe and fast-acting antidepressant. C1 CA GRANDA NIGUARDA HOSP,DEPT PSYCHIAT,MILAN,ITALY. UNIV CATANIA,SCH MED,DEPT PSYCHIAT,I-95125 CATANIA,ITALY. UNIV MODENA,SCH MED,DEPT PSYCHIAT,I-41100 MODENA,ITALY. RP FAVA, M (reprint author), MASSACHUSETTS GEN HOSP,DEPRESS RES PROGRAM,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114, USA. NR 9 TC 28 Z9 33 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD APR 28 PY 1995 VL 56 IS 3 BP 295 EP 297 DI 10.1016/0165-1781(95)02656-H PG 3 WC Psychiatry SC Psychiatry GA RG374 UT WOS:A1995RG37400011 PM 7568552 ER PT J AU LEWIS, BS AF LEWIS, BS TI EFFICACY AND SAFETY OF NISOLDIPINE COAT CORE IN THE MANAGEMENT OF ANGINA-PECTORIS, SYSTEMIC HYPERTENSION, AND ISCHEMIC VENTRICULAR DYSFUNCTION SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Left Ventricular Dysfunction, Calcium Antagonism, and Nisoldipine CY JUN 23-26, 1994 CL AMSTERDAM, NETHERLANDS SP BAYER AG, LEVERKUSEN ID CONGESTIVE-HEART-FAILURE; CALCIUM-CHANNEL BLOCKER; MYOCARDIAL-INFARCTION; DOUBLE-BLIND; WALL-MOTION; NIFEDIPINE; THERAPY; ABNORMALITIES; ANTAGONISTS; HIBERNATION AB The effects of the long-acting dihydropyridine calcium antagonist nisoldipine coat core (CC) have been investigated in >3,500 patients with angina pectoris, hypertension, and ischemic ventricular dysfunction. in patients with angina pectoris, nisoldipine CC improved total treadmill exercise duration (p = 0.027), delayed the onset of angina pectoris (p = 0.009), and increased time to exercise-induced ST-segment depression (p = 0.061). In general, nisoldipine 20-40 mg was effective, and the dose-response curve flattened thereafter. in patients with hypertension, 10-40 mg once daily as monotherapy reduced blood pressure (p < 0.05), with a fall in diastolic pressure of greater than or equal to 10 mm Hg or a final diastolic pressure of <90 mm Hg in 35-63% of patients. In most patients followed for a year, nisoldipine CC was continued as monotherapy. Efficacy was similar in patients <65 and >65 years of age. In the Doppler Flow and Echocardiography in Functional Cardiac Insufficiency: Assessment of Nisoldipine Therapy (DEFIANT-I) study of patients recovering from myocardial infarction, nisoldipine CC had a salutary effect on diastolic ventricular function, with a higher transmitral early filling velocity and shorter isovolumic relaxation time than in patients receiving placebo. Bicycle exercise capacity was greater (by 12 W; 95% confidence interval, 0.8-23.3) and exercise-induced ischemia occurred less frequently, The nisoldipine CC data pool (3,679 patients) showed that the drug was well tolerated with a low incidence of side effects. Angina pectoris, chest pain, and dyspnea occurred less frequently with nisoldipine CC, and mortality was slightly lower in patients taking the drug (0.28% vs 0.37%). The absence or very low incidence of acute vasodilatory effects may indicate that complications associated with sharp peak and trough effects of drug (reflex sympathetic stimulation, catecholamine release, activation of the renin-angiotensin system) may be less frequent with long-acting calcium antagonists. C1 UNIV CALIF LOS ANGELES, LOS ANGELES, CA USA. W LOS ANGELES VET AFFAIRS MED CTR, DIV CARDIOL, LOS ANGELES, CA 90073 USA. NR 28 TC 18 Z9 18 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 27 PY 1995 VL 75 IS 13 BP E46 EP E53 DI 10.1016/S0002-9149(99)80448-2 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QU980 UT WOS:A1995QU98000009 PM 7726125 ER PT J AU WILSON, C SZOSTAK, JW AF WILSON, C SZOSTAK, JW TI IN-VITRO EVOLUTION OF A SELF-ALKYLATING RIBOZYME SO NATURE LA English DT Article ID RNA AB RNA enzymes are postulated to have catalysed all chemical reactions in the earliest living cells. This idea is now investigated in a search for alkyl transferases from a pool of random sequence RNAs. Selection for self-biotinylation yields a transfer RNA-like ribozyme that efficiently catalyses carbon-nitrogen bond formation. Ribozymes can thus promote reactions other than those involving the RNA sugar-phosphate backbone, suggesting that RNA may be capable of a broad range of catalytic activities. C1 MASSACHUSETTS GEN HOSP,DEPT BIOL MOLEC,BOSTON,MA 02114. NR 19 TC 176 Z9 181 U1 1 U2 11 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD APR 27 PY 1995 VL 374 IS 6525 BP 777 EP 782 DI 10.1038/374777a0 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QV315 UT WOS:A1995QV31500035 PM 7723823 ER PT J AU WECKER, H GRUSBY, MJ AUCHINCLOSS, H AF WECKER, H GRUSBY, MJ AUCHINCLOSS, H TI EFFECTOR-CELLS MUST RECOGNIZE ANTIGENS EXPRESSED IN THE GRAFT TO CAUSE EFFICIENT SKIN-GRAFT REJECTION IN SCID MICE SO TRANSPLANTATION LA English DT Note ID II-DEFICIENT MICE; T-CELLS; MOUSE C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,GEN SURG SERV,TRANSPLANTAT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL36372] NR 14 TC 29 Z9 29 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 APR 27 PY 1995 VL 59 IS 8 BP 1223 EP 1227 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA QW262 UT WOS:A1995QW26200028 PM 7732570 ER PT J AU HARRIS, RA MCQUILKIN, SJ PAYLOR, R ABELIOVICH, A TONEGAWA, S WEHNER, JM AF HARRIS, RA MCQUILKIN, SJ PAYLOR, R ABELIOVICH, A TONEGAWA, S WEHNER, JM TI MUTANT MICE LACKING THE GAMMA-ISOFORM OF PROTEIN-KINASE-C SHOW DECREASED BEHAVIORAL ACTIONS OF ETHANOL AND ALTERED FUNCTION OF GAMMA-AMINOBUTYRATE TYPE-A RECEPTORS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SHORT-SLEEP MICE; CEREBELLAR PURKINJE NEURONS; RECOMBINANT INBRED STRAINS; ACID-INDUCED DEPRESSIONS; CENTRAL-NERVOUS-SYSTEM; GATED ION CHANNELS; LONG-SLEEP; CHLORIDE CHANNELS; GABA(A) RECEPTOR; A RECEPTOR AB Calcium/phospholipid-dependent protein kinase (protein kinase C, PKC) has been suggested to play a role in the sensitivity of gamma-aminobutyrate type A (GABA(A)) receptors to ethanol. We tested a line of null mutant mice that lacks the gamma isoform of PKC (PKC gamma) to determine the role of this brain-specific isoenzyme in ethanol sensitivity. We found that the mutation reduced the amount of PKC gamma immunoreactivity in cerebellum to undetectable levels without altering the levels of the alpha, beta(I), or beta(II) isoforms of PKC. The mutant mice display reduced sensitivity to the effects of ethanol on loss of righting reflex and hypothermia but show normal responses to flunitrazepam or pentobarbital. Likewise, GABA(A) receptor function of isolated,brain membranes showed that the mutation abolished the action of ethanol but did not alter actions of flunitrazepam or pentobarbital. These studies show the unique interactions of ethanol with GABA(A) receptors and suggest protein kinase isoenzymes as possible determinants of genetic differences in response to ethanol. C1 UNIV COLORADO, HLTH SCI CTR, DEPT PHARMACOL, DENVER, CO 80262 USA. UNIV COLORADO, INST BEHAV GENET, BOULDER, CO 80309 USA. UNIV COLORADO, SCH PHARM, BOULDER, CO 80309 USA. MIT, CTR CANC RES, CAMBRIDGE, MA 02139 USA. MIT, DEPT BIOL, CAMBRIDGE, MA 02139 USA. MIT, CTR CANC RES, HOWARD HUGHES MED INST, CAMBRIDGE, MA 02139 USA. MIT, DEPT BIOL, CAMBRIDGE, MA 02139 USA. RP UNIV COLORADO, HLTH SCI CTR, DENVER VET AFFAIRS MED CTR, 4200 E 9TH AVE, DENVER, CO 80262 USA. FU NIAAA NIH HHS [AA03527, AA00141, AA06399] NR 45 TC 212 Z9 215 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 25 PY 1995 VL 92 IS 9 BP 3658 EP 3662 DI 10.1073/pnas.92.9.3658 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QV930 UT WOS:A1995QV93000005 PM 7731960 ER PT J AU SALAZAR, M LEONG, T TU, N GELMAN, RS WATSON, ALM BRONSON, R IGLESIAS, A MANN, M GOOD, RA YUNIS, EJ AF SALAZAR, M LEONG, T TU, N GELMAN, RS WATSON, ALM BRONSON, R IGLESIAS, A MANN, M GOOD, RA YUNIS, EJ TI LIFE-SPAN, T-CELL RESPONSES, AND INCIDENCE OF LYMPHOMAS IN CONGENIC MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SURVIVAL; LYMPH CELL CANCERS; AGING; IMMUNODEFICIENCY ID HISTOCOMPATIBILITY COMPLEX; INFLUENCE LONGEVITY; IMMUNODEFICIENCY; SURVIVAL; TRAITS; CANCER AB Survival, T-cell functions, and postmortem histopathology were studied in H-2 congenic strains of mice bearing H-2(b), H-2(k), and H-2(d) haplotypes. Males lived longer than females in all homozygous and heterozygous combinations except for H-2(d) homozygotes, which showed no differences between males anti females. Association of heterozygosity with longer survival Iras observed only with H-2(b)/H-2(b) and H-2(b)/H-2(d) mice, Analysis using classification and regression trees (CART) showed that both males and females of H-2(b) homozygous and H-2(k)/H-2(b) mice had the shortest life-span of the strains studied. In histopathological analyses, lymphomas were noted to be more frequent in females, while hemangiosarcomas and hepatomas were more frequent in males, Lymphomas appeared earlier than hepatomas or hemangiosarcomas, The incidence of lymphomas was associated with the H-2 haplotype-e.g., H-2(b) homozygous mice had more lymphomas than did mice of the H-2(d) haplotype. More vigorous T-cell function was maintained with age (27 months) in H-2(d), H-2(b)/H-2(d), and H-2(d)/H2(k) mice as compared with H-2(b), H-2(k), and H-2(b)/H-2(k) mice, which shelved a decline of T-cell responses with age. C1 AMER RED CROSS,DEDHAM,MA 02026. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. TUFTS UNIV VET MED,GRAFTON,MA 01536. UNIV S FLORIDA,ALL CHILDRENS HOSP,DEPT PEDIAT,ST PETERSBURG,FL 33701. RP SALAZAR, M (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-06516]; NIA NIH HHS [AG05633-10]; PHS HHS [R01-A602329-1J] NR 22 TC 14 Z9 14 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 APR 25 PY 1995 VL 92 IS 9 BP 3992 EP 3996 DI 10.1073/pnas.92.9.3992 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QV930 UT WOS:A1995QV93000073 PM 7732019 ER PT J AU KANG, JX XIAO, YF LEAF, A AF KANG, JX XIAO, YF LEAF, A TI FREE, LONG-CHAIN, POLYUNSATURATED FATTY-ACIDS REDUCE MEMBRANE ELECTRICAL EXCITABILITY IN NEONATAL RAT CARDIAC MYOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ACTION POTENTIAL; THRESHOLD; AUTOMATICITY; OMEGA-3 AND OMEGA-6 FATTY ACIDS; ANTIARRHYTHMICS ID SMOOTH-MUSCLE CELLS; ARACHIDONIC-ACID; POTASSIUM CHANNELS; CALCIUM CHANNELS; K+ CHANNELS; CURRENTS; HEART; PHOSPHOLIPIDS; MODULATION; MYOCARDIUM AB Because previous studies showed that polyunsaturated fatty acids can reduce the contraction rate of spontaneously beating heart cells and have antiarrhythmic effects, we examined the effects of the fatty acids on the electrophysiology of the cardiac cycle in isolated neonatal rat cardiac myocytes. Exposure of cardiomyocytes to 10 mu M eicosapentaenoic acid for 2-5 min markedly increased the strength of the depolarizing current required to elicit an action potential (from 18.0 +/- 2.4 pA to 26.8 +/- 2.7 pA, P < 0.01) and the cycle length of excitability (from 525 ms to 1225 ms, Delta = 700 +/- 212, P < 0.05), These changes were due to an increase in the threshold for action potential (from -52 mV to -43 mV, Delta = 9 +/- 3, P < 0.05) and a more negative resting membrane potential (from -52 mV to -57 mV, Delta = 5 +/- 1, P < 0.05), There was a progressive prolongation of intervals between spontaneous action potentials and a slowed rate of phase 4 depolarization. Other polyunsaturated fatty acids-including docosahexaenoic acid, linolenic acid, linoleic acid, arachidonic acid, and its nonmetabolizable analog eicosatetraynoic acid, but neither the monounsaturated oleic acid nor the saturated stearic acid-had similar effects. The effects of the fatty acids could be reversed by washing with fatty acid-free bovine serum albumin, These results show that free polyunsaturated fatty acids can reduce membrane electrical excitability of heart cells and provide an electrophysiological basis for the antiarrhythmic effects of these fatty acids. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, RENAL UNIT, BOSTON, MA 02114 USA. BROCKTON W ROXBURY VET AFFAIRS MED CTR, BOSTON, MA 02132 USA. FU NIDDK NIH HHS [R01-DK 38165] NR 29 TC 185 Z9 189 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 25 PY 1995 VL 92 IS 9 BP 3997 EP 4001 DI 10.1073/pnas.92.9.3997 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QV930 UT WOS:A1995QV93000074 PM 7732020 ER PT J AU SGROI, D KORETZKY, GA STAMENKOVIC, I AF SGROI, D KORETZKY, GA STAMENKOVIC, I TI REGULATION OF CD45 ENGAGEMENT BY THE B-CELL RECEPTOR CD22 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BETA-GALACTOSIDE ALPHA-2,6-SIALYLTRANSFERASE; TYROSINE PHOSPHATASE CD45; ANTIGEN RECEPTOR; T-CELLS; PHOSPHOLIPASE C-GAMMA-1; PROTEIN; PHOSPHORYLATION; STIMULATION; EXPRESSION; ADHESION AB The B-cell receptor CD22 binds sialic acid linked alpha-2-6 to terminal galactose residues on N-linked oligosaccharides associated with several cell-surface glycoproteins. The first of these sialoglycoproteins to be identified was the receptor-linked phosphotyrosine phosphatase CD45, which is required for antigen/CD3-induced T-cell activation. In the present work we examine the effect of interaction between the extracellular domain of CD45 and CD22 on T-cell activation. Using soluble CD22-immunoglobulin fusion proteins acid T cells expressing wild-type and chimeric CD45 forms, we show that engagement of CD45 by soluble CD22 can modulate early T-cell signals in antigen receptor/CD3-mediated stimulation. We also show that addition of sialic acid by beta-galactoside alpha-2,6-sialyltransferase to the CD22 molecule abrogates interactions between CD22 and its ligands. Together, these observations provide direct evidence for a functional role of the interaction between the extracellular domain of CD45 and a natural ligand and suggest another regulatory mechanism for CD22-mediated ligand engagement. C1 MASSACHUSETTS GEN HOSP EAST,DEPT PATHOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP EAST,CTR CANC,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP EAST,PATHOL RES LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. UNIV IOWA,COLL MED,DEPT INTERNAL MED,IOWA CITY,IA 52242. UNIV IOWA,COLL MED,DEPT PHYSIOL & BIOPHYS,IOWA CITY,IA 52242. FU PHS HHS [K08] NR 30 TC 78 Z9 78 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 25 PY 1995 VL 92 IS 9 BP 4026 EP 4030 DI 10.1073/pnas.92.9.4026 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QV930 UT WOS:A1995QV93000080 PM 7537381 ER PT J AU LAUHON, CT SZOSTAK, JW AF LAUHON, CT SZOSTAK, JW TI RNA APTAMERS THAT SHOW REDOX SELECTIVITY WITH NICOTINAMIDE COFACTORS SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1422 EP A1422 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401054 ER PT J AU LORSCH, JR SZOSTAK, JW AF LORSCH, JR SZOSTAK, JW TI IN-VITRO EVOLUTION OF POLYNUCLEOTIDE KINASE RIBOZYMES SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1422 EP A1422 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27401053 ER PT J AU SPRINGER, TA ALON, R HAMMER, DA AF SPRINGER, TA ALON, R HAMMER, DA TI THE EFFECT OF FORCE ON BOND LIFETIMES - ARE SELECTINS AND INTEGRINS SPECIALIZED FOR HIGH-TENSILE STRENGTH SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. UNIV ROCHESTER,MED CTR,DEPT BIOPHYS,ROCHESTER,NY 14642. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1995 VL 9 IS 6 BP A1389 EP A1389 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QV274 UT WOS:A1995QV27400865 ER PT J AU SANDS, BE OGATA, H LYNCHDEVANEY, K DEBEAUMONT, M EZZELL, RM PODOLSKY, DK AF SANDS, BE OGATA, H LYNCHDEVANEY, K DEBEAUMONT, M EZZELL, RM PODOLSKY, DK TI MOLECULAR-CLONING OF THE RAT INTESTINAL TREFOIL FACTOR GENE - CHARACTERIZATION OF AN INTESTINAL GOBLET CELL-ASSOCIATED PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; SPASMOLYTIC POLYPEPTIDE PSP; SUCRASE-ISOMALTASE GENE; PROTEIN-KINASE-C; REPORTER GENE; TRANSCRIPTIONAL ELEMENTS; RESPONSIVE ELEMENT; SEQUENCE-ANALYSIS; MESSENGER-RNA; P-DOMAIN AB Intestinal trefoil factor (ITF) is a small peptide bearing the unique motif of intrachain disulfide bonds characteristic of the trefoil family, Previous work had localized expression of ITF primarily within goblet cells in the small and large bowel, making it a candidate gene for the study of the molecular basis of intestinal and goblet cell-specific gene expression, In order to study the regulation of ITF expression, we have cloned the rat ITF gene and sequenced 1.7 kilobases of the 5'-flanking region, RNase protection analysis demonstrated a single transcriptional start site, Various lengths of the 5'-flanking region were linked to the reporter gene luciferase and transfected into the colon cancer cell lines LS174T and Caco-2, representing, respectively, cells with and without goblet cell-like phenotype, Expression in the goblet cell-like LS174T colon cancer cell line was nearly 10-fold greater than expression in Caco-2 cells which exhibit columnar enterocyte-like phenotype, The pattern of goblet cell-associated selective transcription required only 153 base pairs of the rat ITF 5'-flanking sequence, Transfection of a construct of human growth hormone under the control of the rat ITF promoter in the N2 subclone of HT-29 cells demonstrated expression of the reporter gene only in those cells exhibiting a goblet cell phenotype as assessed by expression of immuno-reactive mucin, These initial studies of the 5' flanking region of the ITF gene demonstrate the presence of cis-regulatory elements capable of directing goblet cell specific expression. C1 MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SURG RES LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Ogata, Haruhiko/B-3964-2014 FU NIDDK NIH HHS [DK43351, DK46906] NR 51 TC 43 Z9 48 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 APR 21 PY 1995 VL 270 IS 16 BP 9353 EP 9361 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QU089 UT WOS:A1995QU08900047 PM 7721858 ER PT J AU LI, CJ FRIEDMAN, DJ WANG, CL METELEV, V PARDEE, AB AF LI, CJ FRIEDMAN, DJ WANG, CL METELEV, V PARDEE, AB TI INDUCTION OF APOPTOSIS IN UNINFECTED LYMPHOCYTES BY HIV-1 TAT PROTEIN SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROGRAMMED CELL-DEATH; T-CELLS; PERIPHERAL-BLOOD; ACTIVATION; AIDS; INDIVIDUALS; EXPRESSION; INFECTION; CD4 AB Infection by human immunodeficiency virus-type 1 (HIV-1) is typified by the progressive depletion of CD4 T lymphocytes and deterioration of immune function in most patients. A central unresolved issue in acquired immunodeficiency syndrome (AIDS) pathogenesis is the mechanism underlying this T cell depletion. HIV-1 Tat protein was shown to induce cell death by apoptosis in a T cell line and in cultured peripheral blood mononuclear cells from uninfected donors, This Tat-induced apoptosis was inhibitable by growth factors and was associated with enhanced activation of cyclin-dependent kinases. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. WORCESTER FDN EXPTL BIOL INC,SHREWSBURY,MA 01545. RP LI, CJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,44 BINNEY ST,BOSTON,MA 02115, USA. RI Metelev, Valeri/I-3238-2012 FU NIAID NIH HHS [AI-35511] NR 47 TC 499 Z9 505 U1 1 U2 10 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 21 PY 1995 VL 268 IS 5209 BP 429 EP 431 DI 10.1126/science.7716549 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QU572 UT WOS:A1995QU57200044 PM 7716549 ER PT J AU KASINATH, BS AF KASINATH, BS TI EFFECT OF INSULIN ON HIGH-GLUCOSE MEDIUM-INDUCED CHANGES IN RAT GLOMERULAR EPITHELIAL-CELL METABOLISM OF GLYCOCONJUGATES SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE PROTEOGLYCANS; DIABETIC NEPHROPATHY; BASEMENT MEMBRANE; INSULIN ID HEPARAN-SULFATE PROTEOGLYCAN; STREPTOZOTOCIN DIABETIC RATS; BASEMENT-MEMBRANE; EXTRACELLULAR-MATRIX; INCREASED PERMEABILITY; REICHERTS MEMBRANE; GLYCOSAMINOGLYCANS; NEPHROPATHY; PREVENTION; COMPONENTS AB We have previously reported that incubation of rat glomerular epithelial cells in vitro for 8 days with 30 mM glucose without insulin results in reduction in the synthesis of a cell layer heparan sulfate proteoglycan (HSPG) species that has hydrodynamic size and antigenic characteristics of glomerular basement membrane HSPG (1994, Arch, Biochem, Biophys 309, 149-159). In these studies, reduction in HSPG synthesis could be attributed either to high-glucose medium or to insulin deficiency. In this study we investigated the effects of insulin replacement on changes in glomerular epithelial cell metabolism of glycoconjugates induced by high-glucose medium. Addition of pharmacologic concentrations of insulin prevented the following changes induced by 30 mM glucose: (a) increment in (SO4)-S-35 incorporation into macromolecules in cell layer and medium, (b) increment in the synthesis of low anionic macromolecules, probably glycoproteins, in both cell layer and medium, (c) increment in synthesis of small-sized glycosaminoglycans (K-av 0.75 on Sephrose CL-4B) associated with the cell layer. Insulin was unable to correct the 30 mM glucose-induced reduction in the synthesis of cell layer HSPG that resembles glomerular basement membrane HSPG. Physiologic concentrations of insulin did not affect any of the changes in glycopeptide metabolism induced by 30 mM glucose, These findings suggest that (a) inhibition of glomerular epithelial cell synthesis of (SO4)-S-35-labeled low anionic macromolecules, probably glycoproteins, may be involved in insulin-induced reversal of glomerular hypertrophy seen in early diabetes, and (b) mechanisms other than insulin lack are involved in reduction in the synthesis of glomerular basement membrane HSPG in diabetic nephropathy. (C) 1995 Academic Press, Inc. C1 UNIV TEXAS,AUDIE L MURPHY MEM VET HOSP,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. FU NIDDK NIH HHS [DK41517] NR 47 TC 13 Z9 14 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD APR 20 PY 1995 VL 318 IS 2 BP 286 EP 294 DI 10.1006/abbi.1995.1232 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QV624 UT WOS:A1995QV62400006 PM 7733656 ER PT J AU MORADPOUR, D WANDS, JR AF MORADPOUR, D WANDS, JR TI UNDERSTANDING HEPATITIS-B VIRUS-INFECTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SEVERE MALARIA; LIVER-DISEASE; REPLICATION; MUTANT RP MORADPOUR, D (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129, USA. NR 16 TC 27 Z9 30 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 APR 20 PY 1995 VL 332 IS 16 BP 1092 EP 1093 DI 10.1056/NEJM199504203321610 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QT187 UT WOS:A1995QT18700010 PM 7898530 ER PT J AU ISHIOKA, C ENGLERT, C WINGE, P YAN, YX ENGELSTEIN, M FRIEND, SH AF ISHIOKA, C ENGLERT, C WINGE, P YAN, YX ENGELSTEIN, M FRIEND, SH TI MUTATIONAL ANALYSIS OF THE CARBOXY-TERMINAL PORTION OF P53 USING BOTH YEAST AND MAMMALIAN-CELL ASSAYS IN-VIVO SO ONCOGENE LA English DT Article DE P53; CELL CYCLE ARREST; TUMOR SUPPRESSOR GENE ID WILD-TYPE P53; CYCLIN-DEPENDENT KINASES; DNA-BINDING; TRANSCRIPTIONAL ACTIVATION; GENE AMPLIFICATION; PROTEIN; APOPTOSIS; CANCER; LINE; TRANSFORMATION AB Increasing evidence indicates that p53 is a transcriptional tuans-activator through its sequence-specific DNA binding domain. Tumor-derived p53 mutations disrupt the tuans-activation ability mainly due to loss of its sequence-specific DNA binding, Using both yeast and mammalian cell assays, the effect of p53 mutations in the carboxy terminal portion was investigated in order to address how p53 mutations outside of the DNA binding domain affect p53 function, The p53 cDNA in the carboxy-terminus was randomly mutagenized by error-prone polymerase chain reactions and the amplified cDNA was screened for the ability to trans-activate using a yeast assay, Four p53 mutations, including two missense and two nonsense mutations located in the carboxy-terminal oligomerization domain, were further analysed for trans-activation, cell cycle arrest and colony formation in a human osteosarcoma cell line, Saos-2. These functional properties of p53 were disrupted by the missense mutations. Surprisingly, one of the nonsense mutations disrupts the trans-activation function and the ability to G1 arrest but shows a strong inhibition of colony formation, These results confirm that mutations in the oligomerization domain can inactivate p53 function and also indicate that p53-mediated cell growth inhibition does not necessarily depend on the ability to arrest cell cycle. C1 MASSACHUSETTS GEN HOSP,CTR CANC,DIV MOLEC GENET,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. CHILDRENS HOSP,DANA FARBER INST,DIV HEMATOL ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP ISHIOKA, C (reprint author), TOHOKU UNIV,INST DEV AGING & CANC,DEPT CLIN ONCOL,SENDAI,MIYAGI 980,JAPAN. NR 57 TC 80 Z9 81 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 20 PY 1995 VL 10 IS 8 BP 1485 EP 1492 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA QU681 UT WOS:A1995QU68100003 PM 7731702 ER PT J AU VOSS, G LI, J MANSON, K WYAND, M SODROSKI, J LETVIN, NL AF VOSS, G LI, J MANSON, K WYAND, M SODROSKI, J LETVIN, NL TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN-SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN SIMIAN-HUMAN IMMUNODEFICIENCY VIRUS-INFECTED RHESUS-MONKEYS SO VIROLOGY LA English DT Article ID HIV-1; CHIMPANZEES; GP120; CELL; DETERMINANTS; REPLICATION; PROTECTION; MACAQUES; TROPISM; DOMAIN AB Because of the importance of the envelope glycoprotein (Env) in determining the pathogenicity of HIV-1 and the importance of the immune response to Env in controlling virus spread, attempts are being made to study HIV-1 Env-directed immunity in primate models. To date HIV-1 Env-specific effector T lymphocyte responses have not been demonstrated in virus-infected nonhuman primates. We have previously reported that cynomolgus monkeys can develop a persistent infection with a chimeric simian-human immunodeficiency virus (SHIV) composed of SIVmac239 carrying the HIV-1 env, tat, rev, and vpu genes. We now demonstrate that SHIV-infection of another macaque species, the rhesus monkey, generates persistent, HIV-1 Env-specific cytolytic T lymphocyte (CTL) responses. These CTL are CD8(+) and major histocompatibility complex (MHC) class I-restricted. The induction of CTL was correlated neither to the virus load nor to the MHC class I haplotypes of the monkeys. The SHIV-infected rhesus monkey can, therefore, now be employed for studying effector T lymphocyte recognition of HIV-1 Env. (C) 1995 Academic Press, Inc. C1 DANA FARBER CANC INST,HUMAN RETROVIROL LAB,BOSTON,MA 02115. TSI MASON LABS,WORCESTER,MA 01608. RP VOSS, G (reprint author), HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV VIRAL PATHOLGENESIS,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NIAID NIH HHS [AI35478, AI29333, AI33832] NR 22 TC 25 Z9 25 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 0042-6822 J9 VIROLOGY JI Virology PD APR 20 PY 1995 VL 208 IS 2 BP 770 EP 775 DI 10.1006/viro.1995.1209 PG 6 WC Virology SC Virology GA QZ400 UT WOS:A1995QZ40000039 PM 7747449 ER PT J AU DUBINETT, SM HUANG, M DHANANI, S ECONOMOU, JS WANG, J LEE, P SHARMA, S DOUGHERTY, GJ MCBRIDE, WH AF DUBINETT, SM HUANG, M DHANANI, S ECONOMOU, JS WANG, J LEE, P SHARMA, S DOUGHERTY, GJ MCBRIDE, WH TI DOWN-REGULATION OF MURINE FIBROSARCOMA TRANSFORMING GROWTH-FACTOR-BETA-1 EXPRESSION BY INTERLEUKIN-7 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ACTIVATED KILLER-CELLS; HUMAN PERIPHERAL-BLOOD; FACTOR-BETA; ADOPTIVE IMMUNOTHERAPY; TUMOR REJECTION; LYMPHOCYTES-T; TGF-BETA; INHIBITION; CANCER; IL-7 AB Background: Cytokine genes encode proteins that modulate immune system responses, Modification of tumor cells by the introduction of cytokine genes has been used as a strategy to augment host immunity. Interleukin 7 (IL-7) gene transfer enhances the immune response to tumor cells and can result in tumor regression. Transforming growth factor-beta 1 (TGF-beta 1) is a potent immunosuppressive cytokine produced by many tumors. We have previously reported that recombinant IL-7 decreases the expression of TGF-beta 1 by murine macrophages. Purpose: This study investigates the inhibition of tumor-derived TGF-beta 1 production as a possible mechanism for the enhanced antitumor immunity that accompanies IL-7 gene transfer. Methods: A fibrosarcoma cell line (FSA-JmIL-7) genetically modified to produce IL-7 was used to evaluate the effects of IL-7 on tumor production of TGF-beta 1. The control cell line (FSA-Jneo) originated from the same parental fibrosarcoma cell line (FSA) and was produced by transduction with the same retroviral vector without the IL-7 gene. FSA-Jneo and FSA-JmIL-7 tumor cells were evaluated for the expression of TGF-beta 1 messenger RNA (mRNA). To determine if the observed change in TGF-beta 1 mRNA was associated with an alteration in protein secretion, we compared supernatants from tumor cell cultures for TGF-beta 1 production. Specific anti-TGF-beta 1 monoclonal antibody (MAb) was used to confirm the role of TGF-beta 1 in these assays. Results: Compared with FSA parental and FSA-Jneo cells, FSA-JmIL-7 cells expressed TGF-beta 1 mRNA at a lower level. Compared with supernatants from FSA-Jneo cells, FSA-JmIL-7 supernatants contained consistently lower levels of TGF-beta 1 activity (P<.05). In addition, FSA-Jneo supernatants suppressed lymphocyte proliferation to a significantly greater degree than supernatants from FSA-JmIL-7 cells (P<.05). Studies with anti-TGF-beta 1 MAb added to the supernatants confirmed the role of TGF-beta 1 in inhibition of lymphocyte proliferation. Conclusion: These findings suggest that IL-7 gene transfer inhibits the production of TGF-beta 1 by tumor cells and thus may enhance the efficacy of the host's antitumor immune response. Implication: The regulation of endogenous tumor-derived cytokines in response to cytokine gene transfer may contribute to altered immune responses in the tumor microenvironment and thus may be an important additional parameter to assess in gene therapy. C1 UNIV CALIF LOS ANGELES,JONSSON CANC CTR,DEPT SURG ONCOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,JONSSON CANC CTR,DEPT RADIAT ONCOL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,MED RES SERV,LOS ANGELES,CA. BRITISH COLUMBIA CANC RES CTR,TERRY FOX LAB,VANCOUVER,BC V5Z 1L3,CANADA. RP DUBINETT, SM (reprint author), UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS,WADSWORTH PULM IMMUNOL LAB,LOS ANGELES,CA 90073, USA. FU NCI NIH HHS [CA5932601, CA09120, CA5899301] NR 38 TC 33 Z9 35 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 APR 19 PY 1995 VL 87 IS 8 BP 593 EP 597 DI 10.1093/jnci/87.8.593 PG 5 WC Oncology SC Oncology GA QT131 UT WOS:A1995QT13100012 PM 7752257 ER PT J AU MAYNARD, KI YANEZ, P OGILVY, CS AF MAYNARD, KI YANEZ, P OGILVY, CS TI NITRIC-OXIDE MODULATES LIGHT-EVOKED COMPOUND ACTION-POTENTIALS IN THE INTACT RABBIT RETINA SO NEUROREPORT LA English DT Article DE NITRIC OXIDE; GUANYLATE CYCLASE; RETINA; NEUROTRANSMISSION; NEUROMODULATION; RABBIT ID NADPH-DIAPHORASE; GUANYLATE-CYCLASE; BIPOLAR CELLS; SYNTHASE; LOCALIZATION; NEURONS; EYE AB THIS study examines the effects of alterations in nitric oxide (NO) production on rabbit retinal function. NG-nitro-L-arginine (L-NA) and L-arginine (L-Arg) inhibited the light-evoked compound action potentials (CAPs) from the optic nerve, but not the electroretinogram (ERG), in a concentration-dependent manner, whereas D-arginine had no effect. L-Arg partially reversed the L-NA-induced inhibitory effect, and L-NA prevented the L-Arg-induced attenuation of the CAPs. Sodium nitroprusside reduced both the CAPs and the ERG, whilst potassium ferricyanide did not affect the CAPs, and potentiated the ERG. We conclude that, independent of the vasculature, endogenous NO modulates neurotransmission (i.e. light-evoked CAPs), but probably not phototransduction (i.e. light-evoked ERG) in this intact in vitro central nervous system preparation. RP MAYNARD, KI (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,EDWARDS 414,32 FRUIT ST,BOSTON,MA 02114, USA. NR 21 TC 17 Z9 17 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 19 PY 1995 VL 6 IS 6 BP 850 EP 852 DI 10.1097/00001756-199504190-00006 PG 3 WC Neurosciences SC Neurosciences & Neurology GA QV173 UT WOS:A1995QV17300006 PM 7612868 ER PT J AU DREYER, EB ZHANG, DX LIPTON, SA AF DREYER, EB ZHANG, DX LIPTON, SA TI TRANSCRIPTIONAL OR TRANSLATIONAL INHIBITION BLOCKS LOW-DOSE NMDA-MEDIATED CELL-DEATH SO NEUROREPORT LA English DT Article DE N-METHYL-D-ASPARTATE; RETINAL GANGLION CELLS; APOPTOSIS; EXCITOTOXICITY; GLUTAMATE; CELL DEATH ID RETINAL GANGLION-CELLS; AMYOTROPHIC-LATERAL-SCLEROSIS; CALCIUM-CHANNEL ANTAGONISTS; NEUROTOXICITY; GLUTAMATE; RAT; RECEPTOR; CULTURE AB GLUTAMATE toxicity in nerve cells has been well documented and may play a role in a broad spectrum of neurological and ophthalmic diseases. Recent work in several laboratories has suggested that an apoptotic-like mechanism may be implicated in glutamate toxicity under certain circumstances. We therefore studied the effects of transcriptional and translational inhibition on glutamate-mediated cell death in retinal ganglion cells. We now report that either cycloheximide or actinomycin D can, even when added 2 h after the initial excitotoxic insult, save retinal ganglion cells from low dose glutamate toxicity. However, cycloheximide or actinomycin D are unable to prevent glutamate-mediated death at higher concentrations of excitotoxin. This result indicates that at low doses, the neurotoxic effects of glutamate may develop through an apoptotic-like mechanism. C1 HARVARD UNIV,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,CHILDRENS HOSP,SCH MED,MOLEC & CELLULAR NEUROBIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. CHILDRENS HOSP,DEPT NEUROL,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT NEUROL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02115. RP DREYER, EB (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [R01 EY05477]; NICHD NIH HHS [P01 HD29587]; PHS HHS [R01 10009] NR 20 TC 49 Z9 49 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 19 PY 1995 VL 6 IS 6 BP 942 EP 944 DI 10.1097/00001756-199504190-00029 PG 3 WC Neurosciences SC Neurosciences & Neurology GA QV173 UT WOS:A1995QV17300029 PM 7612888 ER PT J AU WEAVER, DR ROCA, AL REPPERT, SM AF WEAVER, DR ROCA, AL REPPERT, SM TI C-FOS AND JUN-B MESSENGER-RNAS ARE TRANSIENTLY EXPRESSED IN FETAL RODENT SUPRACHIASMATIC NUCLEUS FOLLOWING DOPAMINERGIC STIMULATION SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Note DE SUPRACHIASMATIC NUCLEUS; COCAINE; SKF 38393; C-FOS; JUN-B; FETUS; CIRCADIAN RHYTHM ID GENE MESSENGER-RNAS; CIRCADIAN-CLOCK; SUBSTANTIA-NIGRA; SYRIAN-HAMSTER; PHASE ADVANCES; CELL-DEATH; LIGHT; RAT; INDUCE; OSCILLATOR AB We examined the time-course of expression of c-fos and jun-B mRNAs in the fetal rat suprachiasmatic nuclei (SCN) following maternal cocaine injection on gestational day 20. Both c-fos and jun-B mRNA levels increased within 20 min, peaked at 40 min and declined to baseline by 120 min after cocaine treatment (30 mg/kg). In mice, the D-1-dopamine agonist, SKF 38393, induced c-fos and jun-B mRNAs in the fetal SCN and striatum. Regulated expression of immediate early genes in the fetal SCN may play a role in entrainment of the fetal dock. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. RP WEAVER, DR (reprint author), MASSACHUSETTS GEN HOSP,CHILDRENS SERV,DEV CHRONOBIOL LAB,GRJ 1226,BOSTON,MA 02114, USA. NR 31 TC 35 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD APR 18 PY 1995 VL 85 IS 2 BP 293 EP 297 DI 10.1016/0165-3806(95)00016-7 PG 5 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA QT130 UT WOS:A1995QT13000019 ER PT J AU LAH, TT HAWLEY, M ROCK, KL GOLDBERG, AL AF LAH, TT HAWLEY, M ROCK, KL GOLDBERG, AL TI GAMMA-INTERFERON CAUSES A SELECTIVE INDUCTION OF THE LYSOSOMAL PROTEASES, CATHEPSIN-B AND CATHEPSIN-L, IN MACROPHAGES SO FEBS LETTERS LA English DT Article DE ANTIGEN-PRESENTING CELL; CATHEPSIN B, L, D; MHC CLASS II; MACROPHAGE; GAMMA-INTERFERON ID ANTIGEN-PRESENTING CELLS; CLASS-II; MHC; ACIDIFICATION; INHIBITORS; GENERATION; PROTEINS; EPITOPES; PEPTIDES AB Previous studies have indicated that acid-optimal cysteine proteinase(s) in the endosomal-lysosomal compartments, cathepsins, play a critical role in the proteolytic processing of endocytosed proteins to generate the antigenic peptides presented to the immune system on major histocompatibility complex (MHC) class II molecules. The presentation of these peptides and the expression of MHC class II molecules by macrophages and lymphocytes are stimulated by gamma-interferon (gamma-LFN). We found that treatment of human U-937 monocytes with gamma-IFN increased the activities and the content of the two major lysosomal cysteine proteinases, cathepsins B and L. Assays of protease activity, enzyme-linked immunosorbant assays (ELISA) and immunoblotting showed that this cytokine increased the amount of cathepsin B 5-fold and cathepsin L 3-fold in the lysosomal fraction. By contrast, the aspartic proteinase, cathepsin D, in this fraction was not significantly altered by gamma-IFN treatment. An induction of cathepsins B and L was also observed in mouse macrophages, but not in HeLa cells. These results suggest coordinate regulation in monocytes of the expression of cathepsins B and L and MHC class II molecules. Presumably, this induction of cysteine proteases contributes to the enhancement of antigen presentation by gamma-IFN. C1 ALBERT EINSTEIN MED CTR,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19141. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI20248]; NIGMS NIH HHS [5 RO1 GM46147-03] NR 36 TC 60 Z9 60 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 17 PY 1995 VL 363 IS 1-2 BP 85 EP 89 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA QU314 UT WOS:A1995QU31400021 PM 7729559 ER PT J AU DOWDY, SF EWEN, ME AF DOWDY, SF EWEN, ME TI HOT PAPERS - CELL BIOLOGY - PHYSICAL INTERACTION OF THE RETINOBLASTOMA PROTEIN WITH HUMAN D-CYCLINS BY DOWDY,S.F., HINDS,P.W., LOUIE,K., REED,S.I., ARNOLD,A., WEINBURG,R.A. - COMMENT SO SCIENTIST LA English DT Editorial Material C1 HOWARD HUGHES MED INST,ST LOUIS,MO. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP DOWDY, SF (reprint author), WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63110, USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD APR 17 PY 1995 VL 9 IS 8 BP 15 EP 15 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA QT426 UT WOS:A1995QT42600013 ER PT J AU LARSON, RA DODGE, RK BURNS, CP LEE, EJ STONE, RM SCHULMAN, P DUGGAN, D DAVEY, FR SOBOL, RE FRANKEL, SR HOOBERMAN, AL WESTBROOK, CA ARTHUR, DC GEORGE, SL BLOOMFIELD, CD SCHIFFER, CA AF LARSON, RA DODGE, RK BURNS, CP LEE, EJ STONE, RM SCHULMAN, P DUGGAN, D DAVEY, FR SOBOL, RE FRANKEL, SR HOOBERMAN, AL WESTBROOK, CA ARTHUR, DC GEORGE, SL BLOOMFIELD, CD SCHIFFER, CA TI A 5-DRUG REMISSION INDUCTION REGIMEN WITH INTENSIVE CONSOLIDATION FOR ADULTS WITH ACUTE LYMPHOBLASTIC-LEUKEMIA - CANCER AND LEUKEMIA GROUP-B STUDY-8811 SO BLOOD LA English DT Article ID ACUTE LYMPHOCYTIC-LEUKEMIA; DISEASE-FREE SURVIVAL; PROGNOSTIC FACTORS; RANDOMIZED TRIAL; FOLLOW-UP; HIGH-RISK; THERAPY; CHEMOTHERAPY; DAUNORUBICIN; CHILDREN AB The goal of this phase II multicenter clinical trial was to evaluate a new intensive chemotherapy program for adults with untreated acute lymphoblastic leukemia (ALL) and to examine prospectively the impact of clinical and biologic characteristics on the outcome. One hundred ninety-seven eligible and evaluable patients (16 to 80 years of age; median, 32 years of age) received cyclophosphamide, daunorubicin, vincristine, prednisone, and L-asparaginase; 167 patients (85%) achieved a complete remission (CR), 13 (7%) had refractory disease, and 17 (9%) died during induction. A higher CR rate was observed in younger patients (94% for those <30 years old, 85% for those 30 to 59 years old, and 39% for those greater than or equal to 60 years old, P < .001) and in those who had a mediastinal mass (100%) or blasts with a T-cell immunophenotype. Eighty percent of B-lineage and 97% of T-cell ALL patients achieved a CR (P = .01). The coexpression of myeloid antigens did not affect the response rate or duration. Seventy percent of those with cytogenetic or molecular evidence of the Philadelphia (Ph) chromosome and 84% of those without such evidence achieved a CR (P = .11). Patients in remission received multiagent consolidation treatment, central nervous system prophylaxis, late intensification, and maintenance chemotherapy for a total of 24 months. After a median follow-up time of 43 months, the median survival for all 197 patients is 36 months; the median remission duration for the 167 CR patients is 29 months. Favorable pretreatment characteristics relative to remission duration or survival are younger age, the presence of a mediastinal mass or lymphadenopathy, a white blood cell count (WBC) less than 30,000/mu L, L1 morphology, T or TMy immunophenotype, and the absence of the Ph chromosome. The estimates of the proportion surviving at 3 years are 69% for patients less than 30 years old, 39% for those 30 to 59 years old, 89% for those who had a mediastinal mass, 59% with WBC less than 30,000/mu L, 63% with L1 morphology, 69% for T or TMy antigen expression, and 62% for those who lack the Ph chromosome. Fifteen patients (8%) had no unfavorable prognostic factors and have an estimated probability of survival at 5 years of 100% (95% confidence interval, 77% to 100%). This intensive chemotherapy regimen produces a high remission rate and a high proportion of durable remissions in adults with ALL. (C) 1995 by The American Society of Hematology. C1 CALGB STAT CTR, DURHAM, NC USA. UNIV IOWA, IOWA CITY, IA USA. UNIV MARYLAND, CTR CANC, BALTIMORE, MD 21201 USA. DANA FARBER CANC INST, BOSTON, MA 02115 USA. N SHORE UNIV HOSP, MANHASSET, NY USA. SUNY HLTH SCI CTR, SYRACUSE, NY USA. UNIV CALIF SAN DIEGO, SAN DIEGO, CA 92103 USA. ROSWELL PK CANC INST, BUFFALO, NY USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. CALGB, LEBANON, NH USA. RP LARSON, RA (reprint author), UNIV CHICAGO, MED CTR, 5841 S MARYLAND AVE, MC2115, CHICAGO, IL 60637 USA. OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA31946, CA33601, CA37027] NR 47 TC 382 Z9 398 U1 2 U2 6 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 APR 15 PY 1995 VL 85 IS 8 BP 2025 EP 2037 PG 13 WC Hematology SC Hematology GA QU092 UT WOS:A1995QU09200006 PM 7718875 ER PT J AU PASQUALUCCI, L WASIK, M TEICHER, BA FLENGHI, L BOLOGNESI, A STIRPE, F POLITO, L FALINI, B KADIN, ME AF PASQUALUCCI, L WASIK, M TEICHER, BA FLENGHI, L BOLOGNESI, A STIRPE, F POLITO, L FALINI, B KADIN, ME TI ANTITUMOR-ACTIVITY OF ANTI-CD30 IMMUNOTOXIN (BER-H2 SAPORIN) IN-VITRO AND IN SEVERE COMBINED IMMUNODEFICIENCY DISEASE MICE XENOGRAFTED WITH HUMAN CD30(+) ANAPLASTIC LARGE-CELL LYMPHOMA SO BLOOD LA English DT Article ID RICIN-A-CHAIN; RIBOSOME-INACTIVATING PROTEINS; NON-HODGKINS-LYMPHOMA; REED-STERNBERG CELLS; MONOCLONAL-ANTIBODIES; KI-1 LYMPHOMA; ALKALINE-PHOSPHATASE; EXPRESSION; ANTIGEN; RESISTANT AB To develop a novel adjunctive therapy for CD30 (Ki-1)(+) anaplastic large-cell lymphoma (ALCL), we investigated in preclinical studies the antitumor activity of an immunotoxin (IT) constructed by coupling the plant ribosome-inactivating protein saporin (SO6) to the monoclonal antibody (MoAb) Ber-H2 that is directed against the CD30 molecule, a new member of the tumor necrosis factor receptor (TNFR) superfamily. The activity of Ber-H2/SO6 lT was tested both in vitro against the CD30(+) ALCL-derived cell line JB6 and in vivo using our severe combined immunodeficiency disease (SCID) mouse model of human xenografted CD30(+) ALCL, In vitro, the Ber-H2/SO6 IT was selectively and highly toxic to the JB6 cell line [50% inhibiting concentration (IC50), 3.23 x 10(-12) mol/L as SO6]. In vivo, a 3-day treatment with nontoxic doses of Ber-H2/SO6 (50% of LD(50)) induced lasting complete remissions (CR) in 80% of mice when started 24 hours after tumor transplantation. In contrast, injection of the IT at later stages of tumor growth (mice bearing subcutaneous tumors of 40- to 60-mm(3) volume), induced CR in only 6 of 21 (approximately 30%) mice and significantly delayed tumor growth rate (P<.01). This finding suggests that maximum effect of the anti-CD30 IT is observed when tumor cell burden is small. Persistent tumors from IT-treated mice consisted of CD30(+) cells, thus excluding the possibility that selection of CD30-negative mutant clones during IT therapy was responsible for resistance to treatment. We conclude that Ber-H2/SO6 IT is an effective agent against CD30(+) ALCL growing in SCID mice, suggesting its possible role as adjuvant therapy in patients with CD30(+) ALCL refractory to standard treatments. (C) 1995 by The American Society of Hematology. C1 BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA. UNIV BOLOGNA,DEPT EXPTL PATHOL,I-40126 BOLOGNA,ITALY. RP PASQUALUCCI, L (reprint author), UNIV PERUGIA,IST EMATOL,MONTELUCE POLICLIN,I-06100 PERUGIA,ITALY. OI Polito, Letizia/0000-0001-8051-4981 NR 52 TC 68 Z9 69 U1 1 U2 5 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 APR 15 PY 1995 VL 85 IS 8 BP 2139 EP 2146 PG 8 WC Hematology SC Hematology GA QU092 UT WOS:A1995QU09200020 PM 7718885 ER PT J AU POWELL, SN DEFRANK, JS CONNELL, P EOGAN, M PREFFER, F DOMBKOWSKI, D TANG, W FRIEND, S AF POWELL, SN DEFRANK, JS CONNELL, P EOGAN, M PREFFER, F DOMBKOWSKI, D TANG, W FRIEND, S TI DIFFERENTIAL SENSITIVITY OF P53(-) AND P53(+) CELLS TO CAFFEINE-INDUCED RADIOSENSITIZATION AND OVERRIDE OF G(2) DELAY SO CANCER RESEARCH LA English DT Note ID WILD-TYPE P53; DNA-DAMAGE; CYCLE ARREST; CHECKPOINT; PROTEIN; GENE; FIBROBLASTS; REDUCTION; LINES AB Most drug discovery efforts have focused on finding new DNA-damaging agents to kill tumor cells preferentially. An alternative approach is to find ways to increase tumor-specific killing by modifying tumor-specific responses to that damage. In this report, we ask whether cells lacking the G(1)-S arrest in response to X-rays are more sensitive to X-ray damage when treated with agents that override G(2)-M arrest. Mouse embryonic fibroblasts genetically matched to be (+) or (-) p53 and rat embryonic fibroblasts (+) or (-) for wild-type p53 function were irradiated with and without caffeine, a known checkpoint inhibitor. At low doses (500 phr), caffeine caused selective radiosensitization in the p53((-)) cells. At this low dose (where no effect was seen in p53((+)) cells), the p53((-)) cells showed a 50% reduction in the size of the G(2)-M arrest. At higher doses (2 mM caffeine), where sensitization was seen in both p53((+)) and p53((-)) cells, the radiosensitization and the G(2)-M override were more pronounced in the p53((-)) cells, The greater caffeine-induced radiosensitization in p53((-)) . cells suggests that p53, already shown to control the G(1)-S checkpoint, may also influence aspects of G(2)-M arrest. These data indicate an opportunity for therapeutic gain by combining DNA-damaging agents with compounds that disrupt G(2)-M arrest in tumors lacking functional p53. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. RP POWELL, SN (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,COX 302,100 BLOSSOM ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [R01-CA58985] NR 23 TC 309 Z9 319 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 APR 15 PY 1995 VL 55 IS 8 BP 1643 EP 1648 PG 6 WC Oncology SC Oncology GA QR973 UT WOS:A1995QR97300010 PM 7712468 ER PT J AU NUNAIN, SO ROELKE, M TROUTON, T OSSWALD, S KIM, YH SOSASUAREZ, G BROOKS, DR MCGOVERN, B GUY, M TORCHIANA, DF VLAHAKES, GJ GARAN, H RUSKIN, JN AF NUNAIN, SO ROELKE, M TROUTON, T OSSWALD, S KIM, YH SOSASUAREZ, G BROOKS, DR MCGOVERN, B GUY, M TORCHIANA, DF VLAHAKES, GJ GARAN, H RUSKIN, JN TI LIMITATIONS AND LATE COMPLICATIONS OF 3RD-GENERATION AUTOMATIC CARDIOVERTER-DEFIBRILLATORS SO CIRCULATION LA English DT Article DE PACING; DEFIBRILLATORS; ARRHYTHMIA; DEFIBRILLATION ID MALIGNANT VENTRICULAR ARRHYTHMIAS; CARDIAC-ARREST; HEART-FAILURE; LEAD SYSTEM; THERAPY; EXPERIENCE; DEVICE; MANAGEMENT; SHOCKS; IMPLANTATION AB Background This study examines the limitations and complex management problems associated with the use of tiered-therapy, implantable cardioverter-defibrillators (ICDs). Methods and Results The study group comprises the first 154 patients undergoing implantation of tiered-therapy ICDs at our institution. Pulse generators from three different manufacturers were used. In 39 patients, a complete nonthoracotomy lead system was used. The perioperative mortality was 1.3%. Of these 154 patients, 37% experienced late postoperative problems. Twenty-one patients required system revision within 36.5 months (mean, 8.57+/-11.3) of surgery. Reasons for revision were spurious shocks due to electrode fractures (3) or electrode adapter malfunction (2), inadequate signal from endocardial rate-sensing electrodes (3), superior vena cava or right ventricular coil migration (5), failure to correct tachyarrhythmias due to a postimplant rise in defibrillation threshold (5), or pulse generator failure (3). One of these patients required system removal for infection after revision of an endocardial lead. A further 32 patients received inappropriate shocks for atrial fibrillation with a rapid ventricular response or sinus tachycardia. Two of these patients also received shocks for ventricular tachycardia initiated by antitachycardia pacing triggered by atrial fibrillation. Ventricular pacing for bradycardia was associated with inappropriate shocks due to excessive autogain in 2 patients. Conclusions Despite the major diagnostic and therapeutic advantages of tiered-therapy ICDs, a significant proportion of patients continue to experience hardware-related complications or receive inappropriate shocks. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CARDIAC ARRHYTHMIA SERV,BOSTON,MA. HARVARD UNIV,SCH MED,CARDIAC SURG SERV,BOSTON,MA. NR 25 TC 104 Z9 104 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 APR 15 PY 1995 VL 91 IS 8 BP 2204 EP 2213 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QR285 UT WOS:A1995QR28500016 PM 7697850 ER PT J AU AGEMATSU, K KOBATA, T SUGITA, K HIROSE, T SCHLOSSMAN, SF MORIMOTO, C AF AGEMATSU, K KOBATA, T SUGITA, K HIROSE, T SCHLOSSMAN, SF MORIMOTO, C TI DIRECT CELLULAR COMMUNICATIONS BETWEEN CD45RO AND CD45RA T-CELL SUBSETS VIA CD27/CD70 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR RECEPTOR; HUMAN LYMPHOCYTES-B; MOLECULAR-CLONING; SURFACE-ANTIGEN; ACTIVATION ANTIGEN; BIOLOGICAL CHARACTERIZATION; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODY; ADHESION MOLECULES AB The engagement of CD27 with its ligand CD70 is considered to play an important role in T cell costimulation. In the present study, we investigated both the kinetics of CD70 expression and the contribution of its interaction with CD27 in T cell immune responses:CD70 was found to be expressed almost equally on both activated CD4 and CD8 T cells. On subsets of CD4 T cells, however, CD70 expression was induced preferentially on the CD45RO T cell population after activation, whereas its expression was not noted on CD45RA T cells for almost 2 wk following activation. In long-term culture with media containing T cell growth factor (TCGF) and rIL-2, the expression of CD70 was increased markedly on CD45RO T cells and minimally expressed on CD45RA T cells. In addition, strong surface expression of CD70 was observed on T cell clones originally derived from CD45RO(+) CD4 T cells, whereas T cell clones originally derived from CD45RA(+) CD4 T cells showed tower levels of expression. The addition of irradiated, activated CD45RO T cells to CD45RA T cells caused a down-regulation of CD27 expression and an up-regulation of CD25 expression. These changes were blocked by addition of the anti-CD70 mAb, suggesting that direct contact between CD45RO T cells and CD45RA T cells via CD27/CD70 occurred, leading to the activation of CD45RA T cells as measured by CD25 expression. These observations strongly support the notion that the engagement of CD27 plays an important regulatory role in the communication of subsets of CD45RO and CD45RA T cells. The Journal of Immunology, 1995, 154: 3627-3635. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIAID NIH HHS [AI 12609, AI 29530]; NIAMS NIH HHS [AR 33713] NR 58 TC 52 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 APR 15 PY 1995 VL 154 IS 8 BP 3627 EP 3635 PG 9 WC Immunology SC Immunology GA QR070 UT WOS:A1995QR07000001 PM 7706706 ER PT J AU BOMALASKI, JS FORD, T HUDSON, AP CLARK, MA AF BOMALASKI, JS FORD, T HUDSON, AP CLARK, MA TI PHOSPHOLIPASE A(2)-ACTIVATING PROTEIN INDUCES THE SYNTHESIS OF IL-1 AND TNF IN HUMAN MONOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; PHOSPHOLIPASE-A2-ACTIVATING PROTEIN; RHEUMATOID-ARTHRITIS; PROSTAGLANDIN BIOSYNTHESIS; ACTIVATING PROTEIN; FATTY-ACIDS; INTERLEUKIN-1; CELLS; STIMULATION; CYTOKINES AB Phospholipase A(2)-activating protein (PLAP) is an important mediator of eicosanoid generation. PLAP can also be found in high concentrations in synovial fluid from patients with rheumatoid arthritis, and injection of PLAP into animal joints results in an inflammatory, rheumatoid-like lesion. We have demonstrated previously that TNF-alpha and IL-1 beta stimulate formation of PLAP before phospholipase A(2) (PLA(2)) enzyme activation and production of eicosanoids. To further explore the mechanisms found in the inflammatory response, we examined the ability of PLAP to stimulate release of TNF and IL-1 from human peripheral blood monocytes. TNF and IL-1 protein levels were measured by ELISA, and IL-1 and TNF mRNA were determined by Northern blotting. PLAP, PLAP peptide, and melittin, a bee venom PLA(2) activator with homology with PLAP, all increased IL-1 and TNF production in a time- and dose-dependent manner. Heat-denatured PLAP and actin (an irrelevant protein) failed to exert this effect. PLAP stimulation of TNF and IL-1 could be enhanced with co-treatment of cells with free fatty acids, such as arachidonic or linoleic acid, but it was not blocked completely by PLA(2) inhibitors. These results demonstrate not only that synthesis of PLAP can be stimulated by cytokines, but also that PLAP may regulate cytokine synthesis and thus perpetuate an immune or inflammatory response. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. SCHERING PLOUGH CORP,RES INST,KENILWORTH,NJ 07033. RP BOMALASKI, JS (reprint author), MED COLL PENN,DEPT MED,DIV RHEUMATOL,129 ANN PRESTON HALL,PHILADELPHIA,PA 19129, USA. FU NIAMS NIH HHS [AR 39382] NR 34 TC 33 Z9 33 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 APR 15 PY 1995 VL 154 IS 8 BP 4027 EP 4031 PG 5 WC Immunology SC Immunology GA QR070 UT WOS:A1995QR07000044 PM 7706741 ER PT J AU KELLER, ET ERSHLER, WB AF KELLER, ET ERSHLER, WB TI EFFECT OF IL-6 RECEPTOR ANTISENSE OLIGODEOXYNUCLEOTIDE ON IN-VITRO PROLIFERATION OF MYELOMA CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-BREAST-CARCINOMA; MULTIPLE-MYELOMA; GENE-EXPRESSION; INTERLEUKIN-6 PRODUCTION; GROWTH-INHIBITION; AUTOCRINE GROWTH; BONE-MARROW; RNASE-H; LINES; INVITRO AB IL-6 stimulates proliferation of various tumors, including lymphoma and myeloma; thus, inhibiting IL-6 may decrease the growth of these tumors. Accordingly, we examined the effect of IL-6 and IL-6R antisense phospho-rothioated oligodeoxynucleotides (ODNs) on proliferation of IL-6 responsive (U266) and nonresponsive (RPMI 8226) myeloma cell lines. Cells were grown in the presence or absence of IL-6, with added antisense to either IL-6 or IL-6R. Cells were evaluated for proliferation ([H-3]thymidine uptake) and steady state levels of both IL-6 and IL-6R mRNA by competitive PCR (C-PCR). Proliferation of U266 cells was decreased markedly by IL-6 antisense ODN in the absence of IL-6, but not in its presence. In contrast, IL-6R antisense ODN inhibited proliferation of U266 cells in both the presence and absence of IL-6. As anticipated, neither IL-6 nor IL-6R antisense ODN had an effect on RPMI 8226 proliferation. C-PCR demonstrated a marked and specific decrease of IL-6 and IL-6R mRNA in cells exposed to IL-6 ODN and IL-6R ODN, respectively. These results suggest that IL-6R antisense ODN may be a more effective inhibitor of IL-6-stimulated cells than IL-6 antisense in a therapeutic setting. C1 UNIV WISCONSIN,INST AGING,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,MADISON,WI 53705. RI Keller, Evan/M-1446-2016 OI Keller, Evan/0000-0002-7592-7535 FU NIA NIH HHS [T32 AG00213] NR 70 TC 37 Z9 37 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 APR 15 PY 1995 VL 154 IS 8 BP 4091 EP 4098 PG 8 WC Immunology SC Immunology GA QR070 UT WOS:A1995QR07000052 PM 7706747 ER PT J AU SALEEM, A YUAN, ZM TANEJA, N RUBIN, E KUFE, DW KHARBANDA, SM AF SALEEM, A YUAN, ZM TANEJA, N RUBIN, E KUFE, DW KHARBANDA, SM TI ACTIVATION OF SERINE/THREONINE PROTEIN-KINASES AND EARLY GROWTH-RESPONSE-1 GENE-EXPRESSION BY TUMOR-NECROSIS-FACTOR IN HUMAN MYELOID-LEUKEMIA CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID C-MYC EXPRESSION; FACTOR-ALPHA; MONOCYTIC DIFFERENTIATION; SIGNAL-TRANSDUCTION; HL-60 CELLS; SPHINGOMYELIN TURNOVER; KAPPA-B; FOS; PHOSPHORYLATION; CERAMIDE AB The early growth response 1 (EGR-1) gene is induced by mitogenic and differentiating signals in diverse cell types. The present studies have examined the effects of TNF-alpha on the induction of EGR-1 expression in human myeloid leukemia cells and the potential cytoplasmic signaling cascades that transduce TNF-induced signals to the nucleus. The results demonstrate that treatment of HL-60 cells with TNF is associated with the transient induction of the EGR-1 gene. The results also demonstrate that TNF treatment is associated with activation of the serine/threonine kinase, pp90(rsk), which acts upstream to EGR-1 gene induction. Partial purification of pp90(rsk) by affinity chromatography demonstrated an increase in S6 peptide phosphorylation in response to TNF treatment. Because TNF activates sphingomyelin hydrolysis, we also studied the effects of sphingomyelinase (SMase) on induction of EGR-1 and pp90(rsk). The results demonstrate that SMase also activates pp90(rsk) and induces EGR-1 gene expression. Previous work has demonstrated that mitogen-activated protein (MAP) kinase activates pp90(rsk). The present studies further show that treatment with TNF or SMase is associated with induction of both the pp42/44 MAP and the related Jun kinases. Induction of pp42/44 MAP kinase activity is temporally related to activation of pp90(rsk) and the EGR-1 gene. These findings support the involvement of an MAP kinase/pp90(rsk)/EGR-1 cascade in the response of myeloid leukemia cells to TNF. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA-42802] NR 46 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1995 VL 154 IS 8 BP 4150 EP 4156 PG 7 WC Immunology SC Immunology GA QR070 UT WOS:A1995QR07000058 PM 7706752 ER PT J AU IIDAKLEIN, A GUO, J XIE, LY JUPPNER, H POTTS, JT KRONENBERG, HM BRINGHURST, FR ABOUSAMRA, AB SEGRE, GV AF IIDAKLEIN, A GUO, J XIE, LY JUPPNER, H POTTS, JT KRONENBERG, HM BRINGHURST, FR ABOUSAMRA, AB SEGRE, GV TI TRUNCATION OF THE CARBOXYL-TERMINAL REGION OF THE RAT PARATHYROID-HORMONE (PTH)/PTH-RELATED PEPTIDE RECEPTOR ENHANCES PTH STIMULATION OF ADENYLYL-CYCLASE BUT NOT PHOSPHOLIPASE-C SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN KINASE-C; VASOACTIVE-INTESTINAL-PEPTIDE; OSTEOBLAST-LIKE CELLS; EXPRESSION CLONING; INOSITOL TRISPHOSPHATE; MOLECULAR-CLONING; SARCOMA CELLS; CALCIUM; CAMP; POLYPEPTIDE AB The functional role of the rat parathyroid hormone(PTH)/PTH-related peptide (PTHrP) receptor's carboxyl-terminal region was characterized by comparing the binding and signaling properties of receptors that have 78 and 111 amino acid deletions (R513 and R480, respectively), with those of the 591-amino acid wild-type (WT) receptor. R480 and R513 have 4- and 1.5-fold lower apparent K-d values for rat PTH-(1-34) (rPTH), compared with the WT receptor (WT, 1.81 +/- 0.19 nM; R513, 1.24 +/- 0.12 nM; R480, 0.48 +/- 0.05 nM, mean +/- S.E.). PTH (100 nM) stimulated cAMP accumulation and polyphosphoinositide hydrolysis both correlated positively with receptor expression. However, whereas PTH-stimulated polyphosphoinositide hydrolysis was indistinguishable among WT and either truncated mutant at comparable levels of expressed receptors, maximal PTH-stimulated cAMP accumulation was 4-6- and 2-3-fold higher in cells expressing R480 and R513, respectively. Furthermore, pretreatment of COS-7 cells with 100 ng/ml of pertussis toxin (PTX) enhanced PTH-stimulated cAMP accumulation in cells expressing the WT receptor, but failed to do so in cells expressing either R480 or R513. Thus, sequences in the PTH/PTHrP receptor's carboxyl-terminal tail lower the affinity of the WT receptor for agonist; directly interact with, or indirectly facilitate the interaction of the receptor with a PTX-sensitive G protein that inhibits adenylyl cyclase; and decrease the efficacy with which the receptor interacts with G(s). C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [DK11794, DK47034, 1-F32-DK08751] NR 42 TC 80 Z9 81 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 14 PY 1995 VL 270 IS 15 BP 8458 EP 8465 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT448 UT WOS:A1995QT44800017 PM 7721741 ER PT J AU ARYSTARKHOVA, E GIBBONS, DL SWEADNER, KJ AF ARYSTARKHOVA, E GIBBONS, DL SWEADNER, KJ TI TOPOLOGY OF THE NA,K-ATPASE - EVIDENCE FOR EXTERNALIZATION OF A LABILE TRANSMEMBRANE STRUCTURE DURING HEATING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-SUBUNIT; ALPHA-SUBUNIT; CYTOPLASMIC SURFACE; CATALYTIC SUBUNIT; EXTRACELLULAR DOMAIN; CATION OCCLUSION; PROTEIN-KINASE; OUTER MEDULLA; NA+/K+-ATPASE; NA/K-ATPASE AB The topological organization of the Na,K-ATPase alpha subunit is controversial. Detection of extracellular proteolytic cleavage sites would help define the topology, and so attempts were made to find conditions and proteases that would permit digestion of Na,K-ATPase in sealed right-side-out vesicles from renal medulla, The beta subunit is predominantly extracellular and could mask the surface of the alpha subunit, Most of the tested proteases cleaved beta, and some digested it extensively, However, without further disruption of structure, there was still no digestion of the alpha subunit. Reduction (at 50 degrees C) of disulfide bonds that might stabilize the beta subunit fragments, or heating alone at 55 degrees C, permitted tryptic digestion of alpha at a site close to the C terminus, while simultaneously increasing digestion of beta. A 90-kDa N-terminal fragment of alpha was recovered, but the C-terminal fragment was further digested. Heating and reduction resulted in the extracellular exposure of a protein kinase A phosphorylation site, Ser-938, and the C terminus, both of which have been proposed to be located on the intracellular surface. At the same time, access to a distant protein kinase C phosphorylation site was not increased. The data suggest that the harsh treatment simultaneously resulted in alteration of the beta subunit and the extrusion of a segment of alpha that normally spans the membrane, without causing complete denaturation or opening the sealed vesicles. Preincubation with Rb+ was protective, consistent with prior evidence that it stabilizes the protein segments in the C-terminal third of alpha. We conclude that this portion of the alpha subunit contains a transmembrane structure with unique lability to heating. C1 MASSACHUSETTS GEN HOSP,MEMBRANE BIOL LAB,BOSTON,MA 02129. FU NHLBI NIH HHS [HL 36271] NR 67 TC 50 Z9 50 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 APR 14 PY 1995 VL 270 IS 15 BP 8785 EP 8796 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT448 UT WOS:A1995QT44800063 PM 7721785 ER PT J AU CHUNG, DC BRAND, SJ TILLOTSON, LG AF CHUNG, DC BRAND, SJ TILLOTSON, LG TI MUTUALLY EXCLUSIVE INTERACTIONS BETWEEN FACTORS BINDING TO ADJACENT SP1 AND AT-RICH ELEMENTS REGULATE GASTRIN GENE-TRANSCRIPTION IN INSULINOMA CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA POLYMERASE-II; DEVELOPMENTAL EXPRESSION; ACCURATE TRANSCRIPTION; PROMOTER; PROTEINS; ENHANCER; LINES; SITE; NESIDIOBLASTOSIS; HOMEODOMAIN AB The gastrin gene is transiently expressed in fetal pancreatic islets during islet neogenesis but then switched off after birth when islet cells become fully differentiated. Previous studies identified a cis-regulatory sequence between -109 and -75 in the human gastrin promoter which binds islet cell-specific activators and a nonspecific repressor and thus may act as a molecular switch. The present study identified another cis-regulatory sequence ((-163)ACACTAAATGAAAGGGCGGGGCAG(-140)) which bound two islet nuclear proteins in a mutually exclusive manner, as defined by gel shift competition, methylation interference, and DNase I footprinting assays. The general transactivator Sp1 recognized the downstream GGGCGGGG sequence, but Sp1 binding was prevented when another islet factor bound to the adjacent AT-rich sequence (CTAAATGA). This gastrin AT-rich element is nearly identical to the binding site (ATAAATGA) for the islet-specific transcription factor beta TF-1. However, the gastrin AT-binding factor appeared to differ from beta TF-1 in its gel mobility shift pattern. Transfections of rat insulinoma cells revealed that mutations which blocked binding to the AT-rich element but allowed Sp1 binding up-regulated transcriptional activity. These results suggest that the gastrin AT-binding factor blocks transactivation by Sp1 and may have a role in the repression of gastrin transcription seen at the end of islet differentiation. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP CHUNG, DC (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,JACKSON 7,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK42147, DK01410, DK07191] NR 47 TC 21 Z9 21 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 APR 14 PY 1995 VL 270 IS 15 BP 8829 EP 8836 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT448 UT WOS:A1995QT44800068 PM 7721790 ER PT J AU BURKE, TR BARCHI, JJ GEORGE, C WOLF, G SHOELSON, SE YAN, XJ AF BURKE, TR BARCHI, JJ GEORGE, C WOLF, G SHOELSON, SE YAN, XJ TI CONFORMATIONALLY CONSTRAINED PHOSPHOTYROSYL MIMETICS DESIGNED AS MONOMERIC SRC HOMOLOGY-2 DOMAIN INHIBITORS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TYROSINE-PHOSPHORYLATED PEPTIDES; SH2 DOMAIN; BINDING; RECOGNITION; P56(LCK); TARGETS; KINASE AB Inhibitors of specific src homology 2 (SH2) domain binding interactions could potentially afford new therapeutic approaches toward a variety of diseases, including several cancers. To date SH2 domain inhibitors have been confined to small phosphotyrosyl (pTyr)-containing peptides that appear to bind along the surface of SH2 domains with specific recognition features protruding into the protein. Among these protrusions is the pTyr residue itself, which is inserted into a well-formed binding pocket. In the present study monomeric pTyr mimetics were prepared having key aspects of their structure constrained to conformations of the bound pTyr residue observed in the previously reported X-ray structure of a pTyr-peptide bound to the Lck SH2 domain. The resulting constrained pTyr mimetics were examined for inhibitory potency ih six SH2 domain constructs: Lck, Src, Grb2, and the C-terminal SH2 domains of PLC gamma (PLC gamma-C) and the p85 subunit of PI-3 kinase (p85-C), as well as the N-terminal SH2 domain of SH PTP2. Although inhibition constants were in the millimolar range, it was observed that capping pTyr as its N-alpha-acetyl carboxamide [(L)-1] provided a roughly 2-3-fold increase in potency relative to free pTyr. Diastereomeric indanylglycine-based analogues (+/-)-3a,b were essentially inactive. Of note was methanobenzazocine (+/-)-2. While being racemic and a partial pTyr structure, this analogue retained full binding potency of the enantiomerically pure N-alpha-acetyl pTyr amide (L)-1. Modification and elaboration of 2 could potentially result in small molecule inhibitors having greater potency. C1 USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RP BURKE, TR (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BLDG 37,ROOM 5C06,BETHESDA,MD 20892, USA. RI Barchi Jr., Joseph/N-3784-2014; Burke, Terrence/N-2601-2014 NR 47 TC 62 Z9 62 U1 0 U2 1 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 APR 14 PY 1995 VL 38 IS 8 BP 1386 EP 1396 DI 10.1021/jm00008a017 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA QU380 UT WOS:A1995QU38000017 PM 7537333 ER PT J AU ABRAHAM, SA HANSEN, KK DINSMORE, RE KING, ME AF ABRAHAM, SA HANSEN, KK DINSMORE, RE KING, ME TI A 39-YEAR-OLD MAN WITH CHRONIC-RENAL-FAILURE, AORTIC REGURGITATION, AND A CALCIFIED MASS AROUND THE AORTIC ROOT - CHRONIC INFECTIVE ENDOCARDITIS DUE TO STAPHYLOCOCCUS-EPIDERMIDIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID SYSTEMIC LUPUS-ERYTHEMATOSUS; NONBACTERIAL THROMBOTIC ENDOCARDITIS; Q-FEVER ENDOCARDITIS; VALVE-REPLACEMENT; VALSALVA; SINUS; MANIFESTATIONS; ANEURYSMS; DISEASE; BLOCK C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP ABRAHAM, SA (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 47 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 13 PY 1995 VL 332 IS 15 BP 1015 EP 1022 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA QT737 UT WOS:A1995QT73700008 ER PT J AU HOLT, JC CAULFIELD, JB NORTON, P CHANTLER, PD SLAYTER, HS MARGOSSIAN, SS AF HOLT, JC CAULFIELD, JB NORTON, P CHANTLER, PD SLAYTER, HS MARGOSSIAN, SS TI HUMAN CARDIAC MYOSIN LIGHT-CHAINS - SEQUENCE COMPARISONS BETWEEN MYOSIN LC1 AND LC2 FROM NORMAL AND IDIOPATHIC DILATED CARDIOMYOPATHIC HEARTS SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE CARDIAC MYOSIN; REGULATORY LIGHT CHAIN; ESSENTIAL LIGHT CHAIN; PRIMARY STRUCTURE; AMINO ACID SEQUENCE; IDIOPATHIC DILATED CARDIOMYOPATHY ID AMINO-ACID-SEQUENCE; VENTRICULAR MYOSIN; MUSCLE MYOSIN; SKELETAL-MUSCLES; HUMAN ATRIAL; GENE; IDENTIFICATION; HYPERTROPHY; SUBUNITS; PROTEINS AB The primary structures of light chains isolated from the human myocardium with idiopathic dilated cardiomyopathy (IDC) were determined and compared with the sequence structures of myosin light chains obtained from control human heart myosin. Sequences were determined by chemical analysis and the identity of N-terminal residues established by mass spectrometry. The N-terminal residues in essential (ELC) and regulatory (RLC) light chains were blocked and were identified to be trimethyl alanine, The amino acid sequences of ELC and RLC from control human myosin revealed a high degree of homology with those purified from rat and chicken cardiac myosin, Comparison with a published partial chemical sequence of the human heart myosin light chains revealed significant variations, However, there was very good agreement with published sequences obtained by molecular biological techniques. Sequences of the light chains from cardiomyopathic myosin revealed no difference in the primary structures when compared with control human heart myosin light chains indicating IDC had no influence on, nor was caused by, altered myosin light chain gene expression. C1 ALBANY MED COLL,CARDIAC BIOCHEM & BIOPHYS LAB,DIV MOLEC & CELLULAR MED A175,ALBANY,NY 12208. RHONE POULENC RORER CENT RES,KING OF PRUSSIA,PA 19406. UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. UNIV LONDON,UNIV LONDON ROYAL VET COLL,MOLEC & CELLULAR BIOL UNIT,LONDON,ENGLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. MONTEFIORE MED CTR,DEPT BIOCHEM,BRONX,NY 10467. MONTEFIORE MED CTR,ORTHOPED RES LABS,BRONX,NY 10467. ALBERT EINSTEIN COLL MED,BRONX,NY 10467. FU NHLBI NIH HHS [HL-49597, HL-33014, HL-35358] NR 42 TC 5 Z9 5 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD APR 12 PY 1995 VL 145 IS 1 BP 89 EP 96 DI 10.1007/BF00925718 PG 8 WC Cell Biology SC Cell Biology GA QU410 UT WOS:A1995QU41000013 PM 7659082 ER PT J AU PETERS, R KING, CY UKIYAMA, E FALSAFI, S DONAHOE, PK WEISS, MA AF PETERS, R KING, CY UKIYAMA, E FALSAFI, S DONAHOE, PK WEISS, MA TI AN SRY MUTATION CAUSING HUMAN SEX REVERSAL RESOLVES A GENERAL MECHANISM OF STRUCTURE-SPECIFIC DNA RECOGNITION - APPLICATION TO THE 4-WAY DNA JUNCTION SO BIOCHEMISTRY LA English DT Article ID TESTIS-DETERMINING FACTOR; HMG BOX; DETERMINING REGION; MINOR-GROOVE; GONADAL-DYSGENESIS; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; BINDING DOMAIN; XY FEMALES; FACTOR-I AB SRY, a genetic ''master switch'' for male development in mammals, exhibits two biochemical activities: sequence-specific recognition of duplex DNA and sequence-independent binding to the sharp angles of four-way DNA junctions. Here, we distinguish between these activities by analysis of a mutant SRY associated with human sex reversal (46, XY female with pure gonadal dysgenesis). The substitution (I68T in human SRY) alters a nonpolar side chain in the minor-groove DNA recognition or-helix of the HMG box [Haqq, C. M., King, C.-Y., Ukiyama, E., Haqq, T. N., Falsalfi, S., Donahoe, P. K., and Weiss, M. A. (1994) Science 266, 1494-1500]. The native (but not mutant) side chain inserts between specific base pairs in duplex DNA, interrupting base stacking at a site of induced DNA bending. Isotope-aided H-1-NMR spectroscopy demonstrates that analogous side-chain insertion occurs on binding of SRY to a four-way junction, establishing a shared mechanism of sequence- and structure-specific DNA binding. Although the mutant DNA-binding domain exhibits >50-fold reduction in sequence-specific DNA recognition, near wild-type affinity for four-way junctions is retained. Our results (i) identify a shared SRY-DNA contact at a site of either induced or intrinsic DNA bending, (ii) demonstrate that this contact is not required to bind an intrinsically bent DNA target, and (iii) rationalize patterns of sequence conservation or diversity among HMG boxes. Clinical association of the I68T mutation with human sex reversal supports the hypothesis that specific DNA recognition by SRY is required for male sex determination. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NICHD NIH HHS [HD30812, P30 HD28138]; NIGMS NIH HHS [GM51558] NR 57 TC 41 Z9 42 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 11 PY 1995 VL 34 IS 14 BP 4569 EP 4576 DI 10.1021/bi00014a009 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT032 UT WOS:A1995QT03200009 PM 7718558 ER PT J AU THIM, L WOLDIKE, HF NIELSEN, PF CHRISTENSEN, M LYNCHDEVANEY, K PODOLSKY, DK AF THIM, L WOLDIKE, HF NIELSEN, PF CHRISTENSEN, M LYNCHDEVANEY, K PODOLSKY, DK TI CHARACTERIZATION OF HUMAN AND RAT INTESTINAL TREFOIL FACTOR PRODUCED IN YEAST SO BIOCHEMISTRY LA English DT Article ID PANCREATIC SPASMOLYTIC POLYPEPTIDE; XENOPUS-LAEVIS SKIN; HUMAN-BREAST CANCER; P-DOMAIN; MUCOSAL ULCERATION; MESSENGER-RNA; CELL LINEAGE; EXPRESSION; PS2; SECRETION AB Intestinal trefoil factor (ITF) from human (hITF) and rat (rITF) have been produced in Saccharomyces cerevisiae. The DNA encoding the two peptides were cloned by polymerase chain reactions (PCR) from a human normal colon library and a rat small intestinal epithelial cell library. Recombinant plasmids were constructed to encode a fusion protein consisting of a hybrid leader sequence and the rat and human ITF sequences, respectively. The leader sequence used serves to direct the fusion protein into the secretory (and processing) pathway of the cell. The secreted recombinant hITF was found in a monomer and a dimer form, whereas the rITF was only secreted as a dimer. The secreted peptides were purified by a combination of ionic exchange chromatography and preparative HPLC. From 8 L of yeast fermentation broth, 256 mg of hITF (monomer) and 133 mg of hITF (dimer) were isolated, and from 8.7 L of fermentation broth, 236 mg of rITF (dimer) was isolated. The structure of hITF (monomer), hITF (dimer), and rITF (dimer) was determined by amino acid analyses, peptide mapping. sequence analyses, and electrospray mass spectrometry analyses. In hITF (monomer) six of the seven cysteines are disulfide-linked to form 3 disulfide bridges. Mass analysis indicated that the last cysteine residue (Cys-57) did not exist as free (-SH) cysteine, but have reacted with cysteine to form an S-S linked cystine. Sequence and mass spectrometry analyses as well as peptide mapping showed that the dimer form of both hITF and rITF is mediated by a disulfide bridge between Cys-57 residues of two monomers. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. RP THIM, L (reprint author), NOVO NORDISK AS,BIOSCI,DK-2880 BAGSVAERD,DENMARK. FU NIDDK NIH HHS [DK 43351, DK 46906] NR 43 TC 89 Z9 97 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 11 PY 1995 VL 34 IS 14 BP 4757 EP 4764 DI 10.1021/bi00014a033 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QT032 UT WOS:A1995QT03200033 PM 7718582 ER PT J AU RICHARDSON, JH SODROSKI, JG WALDMANN, TA MARASCO, WA AF RICHARDSON, JH SODROSKI, JG WALDMANN, TA MARASCO, WA TI PHENOTYPIC KNOCKOUT OF THE HIGH-AFFINITY HUMAN INTERLEUKIN-2 RECEPTOR BY INTRACELLULAR SINGLE-CHAIN ANTIBODIES AGAINST THE ALPHA-SUBUNIT OF THE RECEPTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTI-TAC; ADULT T-CELL LEUKEMIA; GENE THERAPY ID T-CELL GROWTH; MONOCLONAL-ANTIBODY; IL-2 RECEPTOR; TAC ANTIGEN; EXPRESSION; PROTEINS; COMPLEX; TARGET; GENES AB The experimental manipulation of peptide growth hormones and their cellular receptors is central to understanding the pathways governing cellular signaling and growth control. Previous work has shown that intracellular antibodies targeted to the endoplasmic reticulum (ER) can be used to capture specific proteins as they enter the ER, preventing their transport to the cell surface. Here we have used this technology to inhibit the cell surface expression of the alpha subunit of the high-affinity interleukin 2 receptor (IL-2R alpha). A single chain variable-region fragment of the anti-Tac monoclonal antibody was constructed with a signal peptide and a C-terminal ER retention signal. Intracellular expression of the single-chain antibody was found to completely abrogate cell surface expression of IL-2R alpha in stimulated Jurkat T cells, IL-2R alpha was detectable within the Jurkat cells as an immature 40-kDa form that was sensitive to endoglycosidase H, consistent with its retention in a pre- or early Golgi compartment. A single-chain antibody lacking the ER retention signal was also able to inhibit cell surface expression of IL-2R alpha although the mechanism appeared to involve rapid degradation of the receptor chain within the ER. These intracellular antibodies will provide a valuable tool for examining the role of IL-2R alpha in T-cell activation, IL-2 signal transduction, and the deregulated growth of leukemic cells which overexpress IL-2R alpha. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115. NCI,METAB BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [AI28785, P30 AI28691] NR 36 TC 88 Z9 89 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 11 PY 1995 VL 92 IS 8 BP 3137 EP 3141 DI 10.1073/pnas.92.8.3137 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR968 UT WOS:A1995QR96800014 PM 7724529 ER PT J AU MCLAUGHLIN, ME EHRHART, TL BERSON, EL DRYJA, TP AF MCLAUGHLIN, ME EHRHART, TL BERSON, EL DRYJA, TP TI MUTATION SPECTRUM OF THE GENE ENCODING THE BETA-SUBUNIT OF ROD PHOSPHODIESTERASE AMONG PATIENTS WITH AUTOSOMAL RECESSIVE RETINITIS-PIGMENTOSA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN RETINAL DEGENERATION; PHOTORECEPTOR CGMP PHOSPHODIESTERASE; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; PERIPHERIN-RDS GENE; RHODOPSIN GENE; GUANOSINE MONOPHOSPHATE; NONSENSE MUTATION; GMP ACCUMULATION; POINT MUTATION; CONE DYSPLASIA AB Mutations in the gene encoding the beta subunit of rod cGMP phosphodiesterase are known causes of photoreceptor degeneration in two animal models of retinitis pigmentosa, the rd (retinal degeneration) mouse and the Irish setter dog with rod/cone dysplasia. Here we report a screen of 92 unrelated patients with autosomal recessive retinitis pigmentosa for defects in the human homologue of this gene. We identified seven different mutations that cosegregate with the disease. They were found among four patients with each patient heterozygously carrying two mutations. All of these mutations are predicted to affect the putative catalytic domain, probably leading to a decrease in phosphodiesterase activity and an increase in cGMP levels within rod photoreceptors. Mutations in the gene encoding the beta subunit of rod phosphodiesterase are the most common identified cause of autosomal recessive retinitis pigmentosa, accounting for approximate to 4% of cases in North America. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HOWE LAB OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. FU NEI NIH HHS [EY00169, EY08683] NR 42 TC 213 Z9 217 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 11 PY 1995 VL 92 IS 8 BP 3249 EP 3253 DI 10.1073/pnas.92.8.3249 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR968 UT WOS:A1995QR96800037 PM 7724547 ER PT J AU WETZLER, M TALPAZ, M YEE, G STASS, SA VANETTEN, RA ANDREEFF, M GOODACRE, AM KLEINE, HD MAHADEVIA, RK KURZROCK, R AF WETZLER, M TALPAZ, M YEE, G STASS, SA 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 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BCR; ABL; BCR-ABL; LEUKEMIA ID CHRONIC MYELOGENOUS LEUKEMIA; C-ABL PROTEIN; KINASE-ACTIVITY; SIGNAL TRANSDUCTION; TYROSINE KINASE; GENE-PRODUCTS; CDC2 KINASE; PHOSPHORYLATION; ENCODES; IDENTIFICATION AB The disruption of the BCR gene and its juxtaposition to and consequent activation of the ABL gene has been implicated as the critical molecular defect in Philadelphia chromosome-positive leukemias. The normal BCR protein is a multifunctional molecule with domains that suggest its participation in phosphokinase and GTP-binding pathways. Taken together with its localization to the cytoplasm of uncycled cells, it is therefore presumed to be involved in cytoplasmic signaling. By performing a double aphidicolin block for cell cycle synchronization, we currently demonstrate that the subcellular localization of BCR shifts from being largely cytoplasmic in interphase cells to being predominantly perichromosomal in mitosis. Furthermore, with the use of immunogold labeling and electron microscopy, association of BCR with DNA, in particular heterochromatin, can be dem onstrated even in quiescent cells. Results were similar in cell lines of lymphoid or myeloid origin. These observations suggest a role for BCR in the phosphokinase interactions linked to condensed chromatin, a network previously implicated in cell cycle regulation. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT HEMATOL,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT LAB MED,HOUSTON,TX 77030. ROSWELL PK CANC INST,DEPT MED,BUFFALO,NY 14263. CTR BLOOD RES,BOSTON,MA 02115. UNIV MARYLAND,MED SYST,DEPT PATHOL,BALTIMORE,MD 21201. RP WETZLER, M (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CLIN INVEST,BOX 302,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. FU NCI NIH HHS [CA-16672] NR 33 TC 18 Z9 18 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 11 PY 1995 VL 92 IS 8 BP 3488 EP 3492 DI 10.1073/pnas.92.8.3488 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR968 UT WOS:A1995QR96800086 PM 7724587 ER PT J AU LI, TS FRANSON, WK GORDON, JW BERSON, EL DRYJA, TP AF LI, TS FRANSON, WK GORDON, JW BERSON, EL DRYJA, TP TI CONSTITUTIVE ACTIVATION OF PHOTOTRANSDUCTION BY K296E OPSIN IS NOT A CAUSE OF PHOTORECEPTOR DEGENERATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DOMINANT RETINITIS-PIGMENTOSA; MONOCLONAL-ANTIBODIES; TRANSDUCIN ACTIVATION; TRANSGENIC MICE; RETINAL RODS; S-ANTIGEN; RHODOPSIN; PROTEIN; ARRESTIN; BINDING AB The missense mutation Lys-296 --> Glu (K296E) in the rhodopsin gene produces an opsin with no chromophore binding site and therefore is not activated by light. Nevertheless, the mutant opsin constitutively activates transducin in vitro and causes photoreceptor degeneration in vivo, possibly by continuously activating the phototransduction cascade, analogous to constant exposure to environmental light. We studied the K296E mutation in eight lines of transgenic mice. Each line developed photoreceptor degeneration with the rate of degeneration increasing monotonically as the ratio of mutant:wild-type opsin mRNA increased. At no time in the course of degeneration was there endogenous light adaptation in the retina as measured by the electroretinogram. The mutant opsin was found to be invariably phosphorylated and stably bound to arrestin. Light-independent activation of transducin was demonstrated only after the removal of arrestin and dephosphorylation of K296E opsin, Thus, K296E opsin in vivo does not activate the phototransduction cascade because it is shut off by photoreceptor inactivation mechanisms, Our data show that the K296E mutation does not cause photoreceptor degeneration by continuous activation of phototransduction. C1 HARVARD UNIV, MASSACHUSETTS EYE & EAR INFIRM, SCH MED, HOWE LAB OPHTHALMOL, BOSTON, MA 02114 USA. CUNY MT SINAI SCH MED, DEPT OBSTET & GYNECOL, NEW YORK, NY 10029 USA. RP LI, TS (reprint author), HARVARD UNIV, MASSACHUSETTS EYE & EAR INFIRM, SCH MED, BERMAN GUND LAB STUDY RETINAL DEGENERAT, BOSTON, MA 02114 USA. FU NEI NIH HHS [EY10581, EY10309] NR 34 TC 109 Z9 112 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 11 PY 1995 VL 92 IS 8 BP 3551 EP 3555 DI 10.1073/pnas.92.8.3551 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR968 UT WOS:A1995QR96800099 PM 7724596 ER PT J AU HYMAN, BT WEST, HL REBECK, GW BULDYREV, SV MANTEGNA, RN UKLEJA, M HAVLIN, S STANLEY, HE AF HYMAN, BT WEST, HL REBECK, GW BULDYREV, SV MANTEGNA, RN UKLEJA, M HAVLIN, S STANLEY, HE TI QUANTITATIVE-ANALYSIS OF SENILE PLAQUES IN ALZHEIMER-DISEASE - OBSERVATION OF LOG-NORMAL SIZE DISTRIBUTION AND MOLECULAR EPIDEMIOLOGY OF DIFFERENCES ASSOCIATED WITH APOLIPOPROTEIN-E GENOTYPE AND TRISOMY-21 (DOWN-SYNDROME) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMYLOID-BETA-PROTEIN; PRECURSOR PROTEIN; PEPTIDE; DEPOSITION; FREQUENCY; MUTATION; BINDING AB The discovery that the epsilon 4 allele of the apolipoprotein E (apoE) gene is a putative risk factor for Alzheimer disease (AD) in the general population has highlighted the role of genetic influences in this extremely common and disabling illness. It has long been recognized that another genetic abnormality, trisomy 21 (Down syndrome), is associated with early and severe development of AD neuropathological lesions. It remains a challenge, however, to understand how these facts relate to the pathological changes in the brains of AD patients. We used computerized image analysis to examine the size distribution of one of the characteristic neuropathological lesions in AD, deposits of A beta peptide in senile plaques (SPs), Surprisingly, we find that a log-normal distribution fits the SP size distribution quite well, motivating a porous model of SP morphogenesis. We then analyzed SP size distribution curves in genotypically defined subgroups of AD patients. The data demonstrate that both apoE epsilon 4/AD and trisomy 21/AD lead to increased amyloid deposition, but by apparently different mechanisms. The size distribution curve is shifted toward larger plaques in trisomy 21/AD, probably reflecting increased A beta production, In apoE epsilon 4/AD, the size distribution is unchanged but the number of SP is increased compared to apoE epsilon 3, suggesting increased probability of SP initiation, These results demonstrate that subgroups of AD patients defined on the basis of molecular characteristics have quantitatively different neuropathological phenotypes. C1 BOSTON UNIV, CTR POLYMER STUDIES, DEPT PHYS, BOSTON, MA 02215 USA. BAR ILAN UNIV, DEPT PHYS, RAMAT GAN, ISRAEL. RP MASSACHUSETTS GEN HOSP, NEUROL SERV, BOSTON, MA 02114 USA. RI Mantegna, Rosario/H-3652-2014; Buldyrev, Sergey/I-3933-2015 OI Mantegna, Rosario/0000-0003-4177-171X; FU NIA NIH HHS [AG08487, P050AG05134] NR 36 TC 172 Z9 175 U1 3 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 11 PY 1995 VL 92 IS 8 BP 3586 EP 3590 DI 10.1073/pnas.92.8.3586 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR968 UT WOS:A1995QR96800106 PM 7724603 ER PT J AU KANOFSKY, JR SIMA, PD AF KANOFSKY, JR SIMA, PD TI SINGLET OXYGEN GENERATION FROM THE REACTION OF OZONE WITH PLANT-LEAVES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ASCORBIC-ACID; BIOMOLECULES; DEPOSITION; CELLS AB Aqueous extracts of the intercellular fluid from Sedum album L. leaves generated singlet oxygen chemiluminescence at 1270 nm when exposed to a nitrogen gas stream containing ozone at 21 +/- 2 ppm. The concentration of ascorbic acid in the intercellular fluid extracts was 310 +/- 40 mu M. The intensity of the singlet oxygen chemiluminescence from the intercellular fluid extracts was comparable with the chemiluminescence from a control solution containing 300 mu M ascorbic acid. The intensity of the singlet oxygen emission from intercellular fluid treated with ascorbate oxidase was 0.19 +/- 0.07 of the intensity of the singlet oxygen chemiluminescence from untreated samples of intercellular fluid extract. The simplest explanation for the effect of ascorbate oxidase is that ascorbic acid is the major ozone target generating singlet oxygen. Much weaker singlet oxygen chemiluminescence was detected at 1270 nm when intact S. album L. plant tips were exposed to a nitrogen gas stream containing ozone at 22 +/- 5 ppm. Various explanations for the relatively low intensity of the singlet oxygen chemiluminescence from intact S. album L. plant tips are discussed. C1 US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,RES SERV,HINES,IL 60141. LOYOLA UNIV,STRITCH SCH MED,DEPT MED,MAYWOOD,IL 60153. LOYOLA UNIV,STRITCH SCH MED,DEPT MOLEC & CELLULAR BIOCHEM,MAYWOOD,IL 60153. RP KANOFSKY, JR (reprint author), US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,MED SERV,BOX 278,HINES,IL 60141, USA. NR 23 TC 55 Z9 55 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 7 PY 1995 VL 270 IS 14 BP 7850 EP 7852 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QR526 UT WOS:A1995QR52600012 PM 7713876 ER PT J AU SYMES, AJ RAJAN, P CORPUS, L FINK, JS AF SYMES, AJ RAJAN, P CORPUS, L FINK, JS TI C/EBP-RELATED SITES IN ADDITION TO A STAT SITE ARE NECESSARY FOR CILIARY NEUROTROPHIC FACTOR-LEUKEMIA FACTOR-DEPENDENT TRANSCRIPTIONAL ACTIVATION BY THE VASOACTIVE-INTESTINAL-PEPTIDE CYTOKINE RESPONSE ELEMENT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING PROTEINS; ACUTE-PHASE RESPONSE; NEUROBLASTOMA CELL-LINE; INHIBITORY FACTOR; TYROSINE PHOSPHORYLATION; NUCLEAR FACTOR; ONCOSTATIN-M; SIGNAL-TRANSDUCTION; LEUCINE ZIPPER; CNTF RECEPTOR AB The neuropoietic cytokines ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) regulate VIP gene expression through a cytokine response element (CyRE) which interacts with members of the STAT transcription factor family. The CyRE STAT site is, however, insufficient to mediate full transcriptional activation by CNTF/LIF, suggesting that other sequences and nuclear proteins are also important. As C/EBP proteins participate in the transcriptional effects of the related cytokine, interleukin-6, we investigated the role of possible C/EBP-binding sites in the response of the VIP CyRE to CNTF/LIF. Using DNase I footprinting, transactivation studies, DNA mobility shift assays, and mutational analysis, three sites within the VIP CyRE were identified as C/EBP-related binding sites and shown to be important to CNTF/LIF-mediated transcriptional activation. The CyRE C/EBP-related sites interact with nuclear proteins from the human neuroblastoma cell Line, NBFL, including a novel, protein synthesis-dependent, nuclear protein complex, induced by CNTF treatment, These nuclear proteins are not, however, recognized by antisera to known C/EBP proteins, Therefore, other nuclear proteins regulated by independent pathways act in concert with the JAK-STAT pathway to mediate CNTF/LIF regulation of VIP gene expression through the CyRE. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,MOLEC NEUROBIOL LAB,BOSTON,MA 02114. RI Symes, Aviva/S-7471-2016 OI Symes, Aviva/0000-0003-2557-9939 FU NINDS NIH HHS [NS27514] NR 76 TC 27 Z9 27 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 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 7 PY 1995 VL 270 IS 14 BP 8068 EP 8075 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QR526 UT WOS:A1995QR52600046 PM 7713908 ER PT J AU SCHIPANI, E KRUSE, K JUPPNER, H AF SCHIPANI, E KRUSE, K JUPPNER, H TI A CONSTITUTIVELY ACTIVE MUTANT PTH-PTHRP RECEPTOR IN JANSEN-TYPE METAPHYSEAL CHONDRODYSPLASIA SO SCIENCE LA English DT Article ID RHODOPSIN; MUTATIONS; GENE AB A single heterozygous nucleotide exchange in exon M2 of the gene encoding the parathyroid hormone-parathyroid hormone-related peptide (PTH-PTHrP) receptor was identified in a patient with Jansen-type metaphyseal chondrodysplasia, which changes a strictly conserved histidine residue at position 223 in the receptor's first intracellular loop to arginine. Constitutive, ligand-independent adenosine 3',5'-monophosphate accumulation was observed in COS-7 cells expressing the mutant PTH-PTHrP receptor but not in cells expressing the wild-type receptor. This finding explains the severe ligand-independent hypercalcemia and hypophosphatemia, and most likely the abnormal formation of endochondral bone, in this rare form of short-limbed dwarfism. C1 MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV LUBECK,PADIATRIE KLIN,D-23538 LUBECK,GERMANY. FU PHS HHS [R01 46718] NR 27 TC 439 Z9 450 U1 0 U2 4 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 7 PY 1995 VL 268 IS 5207 BP 98 EP 100 DI 10.1126/science.7701349 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR454 UT WOS:A1995QR45400034 PM 7701349 ER PT J AU RENARD, E GRIGORESCU, F LAVABRE, C KAHN, CR AF RENARD, E GRIGORESCU, F LAVABRE, C KAHN, CR TI INSULIN-DEPENDENT PHOSPHATIDYLINOSITOL 3'-KINASE ACTIVITY CO-PRECIPITATES WITH INSULIN-RECEPTOR IN HUMAN CIRCULATING MONONUCLEAR-CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SIGNAL TRANSDUCTION; INTACT-CELLS; IRS-1; ACTIVATION; PHOSPHORYLATION; SUBSTRATE-1; ASSOCIATION; MONOCYTES; TRANSPORT; 3-KINASE AB In order to establish a working cellular model for the study of post-receptor signaling events, insulin-dependent phosphatidylinositol 3' (PtdIns 3')-kinase activity was investigated in circulating mononuclear cells from normal subjects. The p85 alpha regulatory subunit of PtdIns 3'-kinase co-precipitated with activated insulin receptor as revealed by immunoblotting. Whereas insulin receptor substrate-1 was weakly detected, insulin increased 5.5+/-1.5-fold (mean+/-SD) PtdIns 3'-kinase activity in receptor immunoprecipitates. We conclude that insulin-stimulated PtdIns 3'-kinase activity is measurable in circulating mononuclear cells which may constitute an easily available cellular model for the detection of post-receptor defects in insulin-resistant states. (C) 1995 Academic Press, Inc. C1 UNIV MONTPELLIER 1,CRBM,CNRS,UPR 9008,INSERM,U249,F-34033 MONTPELLIER,FRANCE. ST ELOI HOSP,HAEMATOL LAB,MONTPELLIER,FRANCE. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,ELLIOTT P JOSLIN LAB,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 31036] NR 29 TC 4 Z9 4 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 APR 6 PY 1995 VL 209 IS 1 BP 234 EP 241 DI 10.1006/bbrc.1995.1494 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QQ914 UT WOS:A1995QQ91400034 PM 7726840 ER PT J AU MEREDITH, M RABAGLIA, M METZ, S AF MEREDITH, M RABAGLIA, M METZ, S TI CYTOSOLIC BIOSYNTHESIS OF GTP AND ATP IN NORMAL RAT PANCREATIC-ISLETS SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE PURINE NUCLEOTIDE INSULIN SECRETION; GTP BIOSYNTHESIS; ATP BIOSYNTHESIS; (RAT PANCREATIC ISLET) ID HUMAN NORMAL LYMPHOCYTES; MYCOPHENOLIC-ACID; IMP DEHYDROGENASE; INSULIN RELEASE; INOSINATE DEHYDROGENASE; CELLS; GUANINE; INTACT; INHIBITION; COMPARTMENTATION AB GTP and ATP are necessary for glucose-induced insulin secretion; however, the biosynthetic pathways of purine nucleotides have not been studied in pancreatic islets. The present work examines the cytosolic pathways of purine nucleotide synthesis using intact rat islets cultured overnight in RPMI 1640 medium containing either [C-14]glycine (to label the de novo pathway) or [H-3]hypoxanthine (to mark the salvage pathway), with or without mycophenolic acid or L-alanosine (selective inhibitors of cytosolic GTP and ATP synthesis, respectively). Addition of mycophenolic acid decreased total GTP content (mass) by 73-81%; although the incorporation of labeled hypoxanthine into GTP also fell by 87%, the incorporation of glycine did not change. Similarly, L-alanosine decreased ATP mass by 26-33% in the presence of either label; whereas the incorporation of hypoxanthine into ATP fell 59%, the incorporation of glycine was again not significantly decreased. Thus, both the de novo and salvage purine nucleotide biosynthetic pathways are present in rat islets; however, the salvage pathway appears to be quantitatively the more important source of nucleotides. This conclusion was supported by additional studies of the effects on nucleotide content and insulin secretion of various site-specific inhibitors of purine synthesis. These findings have potential relevance to the processes of mitogenesis, cell proliferation and differentiation of islet cells, as well as for the control of insulin secretion. C1 UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI 53792. UNIV WISCONSIN,SCH MED,ENDOCRINOL SECT,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. FU NIDDK NIH HHS [DK 37312] NR 36 TC 11 Z9 11 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD APR 6 PY 1995 VL 1266 IS 1 BP 16 EP 22 DI 10.1016/0167-4889(94)00235-7 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT136 UT WOS:A1995QT13600003 PM 7718617 ER PT J AU ZHANG, H WANG, J HWANG, I GOODMAN, HM AF ZHANG, H WANG, J HWANG, I GOODMAN, HM TI ISOLATION AND EXPRESSION OF AN ARABIDOPSIS 14-3-3-LIKE PROTEIN GENE SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Note DE 14-3-3 PROTEIN; ARABIDOPSIS; CELL-SIGNALING; PROTEIN KINASE C INHIBITOR ID KINASE-C INHIBITOR; BINDING COMPLEX; BRAIN; ACTIVATORS; CLONING; HOMOLOG; FAMILY AB We have isolated an Arabidopsis gene, AFT1, which encodes a 14-3-3-like protein (AFT1). The wide distribution of the 14-3-3 protein family in eukaryotes and the high steady-state mRNA levels of the AFT1 gene in most tissues throughout Arabidopsis growth and development suggest that AFT1 plays an important role(s) in Arabidopsis. DNA blot analysis indicates that AFT1 is a single copy gene, therefore AFT1 should be a good target for studies involving antisense or sense RNA technologies as a means to determine AFT1's function in vivo. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 25 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD APR 6 PY 1995 VL 1266 IS 1 BP 113 EP 116 DI 10.1016/0167-4889(95)00006-E PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT136 UT WOS:A1995QT13600015 PM 7718616 ER PT J AU ALON, R HAMMER, DA SPRINGER, TA AF ALON, R HAMMER, DA SPRINGER, TA TI LIFETIME OF THE P-SELECTIN-CARBOHYDRATE BOND AND ITS RESPONSE TO TENSILE FORCE IN HYDRODYNAMIC FLOW SO NATURE LA English DT Article ID NEUTROPHIL ADHESION; GLYCOPROTEIN LIGAND; MYELOID CELLS; SHEAR-FLOW; BINDING; IDENTIFICATION; RECOGNITION; DETACHMENT; VENULES AB SELECTINS tether to the blood vessel wall leukocytes that are flowing in the bloodstream and support subsequent labile rolling interactions as the leukocytes are subjected to hydrodynamic drag forces(1,2). To support this rolling, selectins have been proposed to have rapid bond association and dissociation rate constants, and special mechanical properties linking tensile forces and bond dissociation(3-6). We have visualized transient tethering and release of neutrophils in hydrodynamic flow on lipid bilayers containing densities of P-selectin below those required to support rolling. We report here that transient tethers had first-order kinetics and other characteristics suggesting a unimolecular interaction between P-selectin and its glycoprotein ligand (PSGL-1). The unstressed dissociation constant (off rate) was 1s(-1) Hydrodynamic shear stresses of up to 1.1 dyn cm(-2), corresponding to a force on the bond of up to 110 pN, increased the off rate only modestly, to 3.5 s(-1). The data was adequately matched by a proposed equation(7) relating off rate to the exponential of tensile force on the bond and the bond interaction distance, and gave a bond interaction distance of 0.5 Angstrom. This distance is compatible with hydrogen and metal coordination bonds between P-selectin and PSGL-1. Fast on and off rates, together with the high tensile strength of the selectin bond, appear necessary to support rolling at physiological shear stresses. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CORNELL UNIV,SCH CHEM ENGN,ITHACA,NY 14853. NR 30 TC 530 Z9 544 U1 5 U2 32 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD APR 6 PY 1995 VL 374 IS 6522 BP 539 EP 542 DI 10.1038/374539a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QR069 UT WOS:A1995QR06900051 PM 7535385 ER PT J AU LIPTON, SA GENDELMAN, HE AF LIPTON, SA GENDELMAN, HE TI DEMENTIA ASSOCIATED WITH THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID RECEPTOR-MEDIATED NEUROTOXICITY; TUMOR-NECROSIS-FACTOR; VASOACTIVE-INTESTINAL-PEPTIDE; VIRUS-INFECTED MACROPHAGES; PRIMARY CORTICAL CULTURES; BLOOD-BRAIN-BARRIER; HIV COAT PROTEIN; NITRIC-OXIDE; CEREBROSPINAL-FLUID; ARACHIDONIC-ACID C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,VIRAL PATHOGENESIS LABF,OMAHA,NE. UNIV NEBRASKA,MED CTR,DEPT MED,OMAHA,NE 68105. UNIV NEBRASKA,MED CTR,EPPLEY INST RES CANC & ALLIED DIS,OMAHA,NE. RP LIPTON, SA (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT NEUROL,CELLULAR & MOLEC NEUROSCI LAB,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 76 TC 407 Z9 418 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 6 PY 1995 VL 332 IS 14 BP 934 EP 940 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA QP893 UT WOS:A1995QP89300007 PM 7877652 ER PT J AU HABER, DA AF HABER, DA TI TELOMERES, CANCER, AND IMMORTALITY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HUMAN FIBROBLASTS RP HABER, DA (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02129, USA. NR 7 TC 21 Z9 26 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 APR 6 PY 1995 VL 332 IS 14 BP 955 EP 956 DI 10.1056/NEJM199504063321412 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QP893 UT WOS:A1995QP89300012 PM 7877656 ER PT J AU DAVIS, PJ GREGERMAN, RI AF DAVIS, PJ GREGERMAN, RI TI PARSE ANALYSIS .2. A REVISED MODEL THAT ACCOUNTS FOR PHI SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP DAVIS, PJ (reprint author), ALBANY MED COLL,ALBANY,NY 12208, USA. NR 1 TC 4 Z9 4 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 APR 6 PY 1995 VL 332 IS 14 BP 965 EP 966 DI 10.1056/NEJM199504063321421 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QP893 UT WOS:A1995QP89300034 PM 7877668 ER PT J AU BARNARD, D DIAZ, B HETTICH, L CHUANG, E ZHANG, XF AVRUCH, J MARSHALL, M AF BARNARD, D DIAZ, B HETTICH, L CHUANG, E ZHANG, XF AVRUCH, J MARSHALL, M TI IDENTIFICATION OF THE SITES OF INTERACTION BETWEEN C-RAF-1 AND RAS-GTP SO ONCOGENE LA English DT Article DE ONCOGENES; RAS; RAF; PROTEIN INTERACTIONS ID KINASE SIGNALING PATHWAY; MAP KINASE; PROTEIN-KINASE; HA-RAS; ACTIVATION; TARGET; RAF-1; ASSOCIATION; INHIBITION; P21(RAS) AB Specific sites of protein-protein interaction were identified in the 51-149 region of c-Raf-1 using contact epitope scanning and site-directed mutagenesis. Nineteen overlapping peptides based upon the primary sequence of the Ras binding domain of c-Raf-1 were tested for the ability to competitively inhibit complex formation between Ras-GTP and the c-Raf-1 N-terminus, A peptide containing c-Raf-1 residues 91-105 as well as five overlapping peptides covering a region extending from residues 118 to 143 interfered with Ras association, defining these sites as potential contact surfaces with Ras, Alanine scanning mutagenesis was used as a second probe for sites of Ras interaction with the c-Raf-1 N-terminus, Raf residues 64-67 and 80-103 were demonstrated as important for association with Ras-GTP with residues 66, 67, 84, 87, 89 and 91 identified as the most critical individual points of contact with the Ras protein, Alanine substitution of residues between 118-143 suggested only one potentially weak site of interaction defined by residues 120-125, The combined results of both peptide and mutagenic analyses suggest that the primary site of c-Raf-1 interaction,vith Ras maps to Raf residues 80-103, with secondary interactions occurring with residues 66 and 67 and possibly 120-125, Contact epitope scanning of the Ras effector region found maximum inhibition of Ras/Raf association with a peptide corresponding to Ras amino acids 37-51, A model is proposed for the GTP-dependent association of Ras and Raf. C1 INDIANA UNIV,DEPT MED,DIV HEMATOL & ONCOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,SCH MED,DEPT MED,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,SCH MED,DIABET UNIT,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,SCH MED,MED SERV,BOSTON,MA 02129. FU NIDDK NIH HHS [DK07519] NR 36 TC 50 Z9 50 U1 1 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 6 PY 1995 VL 10 IS 7 BP 1283 EP 1290 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA QR651 UT WOS:A1995QR65100004 PM 7731678 ER PT J AU LORENZO, MJ ENG, C MULLIGAN, LM STONEHOUSE, TJ HEALEY, CS PONDER, BAJ SMITH, DP AF LORENZO, MJ ENG, C MULLIGAN, LM STONEHOUSE, TJ HEALEY, CS PONDER, BAJ SMITH, DP TI MULTIPLE MESSENGER-RNA ISOFORMS OF THE HUMAN RET PROTOONCOGENE GENERATED BY ALTERNATE SPLICING SO ONCOGENE LA English DT Article DE RET; RECEPTOR TYROSINE KINASE; ALTERNATE SPLICING ID TYROSINE KINASE; TRANSFORMING GENE; SOLUBLE RECEPTOR; II ONCOGENE; CELL-LINE; PROTOONCOGENE; SEQUENCE; CLONING; RNA; CARCINOMAS AB The RET proto-oncogene encodes a receptor tyrosine kinase. We and others have recently shown that distinct germline mutations of the BET proto-oncogene account for the majority of cases of the dominantly inherited multiple endocrine neoplasia (MEN) type 2 syndromes, and can cause a dominantly inherited form of Hirschsprung disease, a disorder of development of the autonomic innervation of the gut. RET is also oncogenically activated in some sporadic thyroid and adrenal tumours. Here we report the characterisation of multiple mRNA isoforms of RET generated by alternate splicing. Two isoforms are predicted to encode membrane-spanning receptors with a truncated extracellular ligand-binding domain. A third isoform is predicted to encode a soluble, secreted form of the receptor, These mRNA isoforms are expressed in both normal and tumour tissues. C1 UNIV CAMBRIDGE,DEPT PATHOL,CRC,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 1QP,ENGLAND. HARVARD UNIV,SCH MED,DEPT MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. QUEENS UNIV,DEPT PAEDIAT,KINGSTON,ON K7L 3N6,CANADA. OI Eng, Charis/0000-0002-3693-5145 NR 42 TC 44 Z9 45 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 6 PY 1995 VL 10 IS 7 BP 1377 EP 1383 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA QR651 UT WOS:A1995QR65100015 PM 7731689 ER PT J AU WILLIAMS, JW HOLLEMAN, DR SAMSA, GP SIMEL, DL AF WILLIAMS, JW HOLLEMAN, DR SAMSA, GP SIMEL, DL TI RANDOMIZED CONTROLLED TRIAL OF 3 VS 10 DAYS OF TRIMETHOPRIM-SULFAMETHOXAZOLE FOR ACUTE MAXILLARY SINUSITIS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ANTIMICROBIAL RESISTANCE; AMOXICILLIN-CLAVULANATE; HAEMOPHILUS-INFLUENZAE; COMPARATIVE EFFICACY; CEFUROXIME AXETIL; THERAPY; CLARITHROMYCIN; EQUIVALENCE; AMOXYCILLIN; BOOTSTRAP AB Objective.-To compare 14-day outcomes and relapse and recurrence rates among patients with acute maxillary sinusitis randomized to 3-day (3D) vs 10-day (10D) treatment with trimethoprim/sulfamethoxazole (TMP/SMX). Setting.-University-affiliated Veterans Affairs general medical and acute care clinics. Patients.-Consecutive patients with sinus symptoms and radiographic evidence of maxillary sinusitis (complete opacity, air-fluid level, or greater than or equal to 6 mm of mucosal thickening). Patients were excluded for antibiotic use within the past week, TMP/ SMX allergy, symptoms for more than 30 days, or previous sinus surgery. Methods.-All subjects (n=80) received oxymetazoline nasal spray 0.05%, two sprays twice daily for 3 days. Subjects were randomly assigned to TMP/SMX double strength: one tablet twice daily for 10 days or one tablet twice daily for 3 days followed by 7 days of placebo, At 7 and 14 days, patients rated their overall sinus symptoms on a Likert scale. Radiographs were scored at baseline and 14 days by radiologists masked to clinical symptoms and treatment assignment. The primary outcome was number of days to ''cure'' or ''much improvement'' in sinus symptoms. Patients who were clinical successes by day 14 were assessed for symptomatic relapse or recurrence at 30 and 60 days, respectively, Results.-Groups were comparable at randomization: male, 100%; black, 53%; median age, 48 years (interquartile range, 41 to 63 years); symptom duration, 10 days (interquartile range, 6 to 17 days); bilateral maxillary disease, 51%; and radiograph score, 4 (interquartile range, 2 to 4). Outcome assessment was completed in 95% of patients at day 14(n=76). Medication side effects and use of nonstudy sinus medications were equal between groups. By 14 days, 77% of 3D subjects and 76% of 10D subjects rated their sinus symptoms as cured or much improved (95% confidence interval for difference, -15% to 17%). Median days to cure/much improvement were 5.0 and 4.5 for the 3D and 10D groups, respectively; distributions of time to cure were not different (P=.34). Radiograph scores improved in both groups compared with baseline (2 points; P<.001), but improvement did not differ between groups (P=.31). Eight percent of 3D subjects and 13% of 10D subjects missed work due to sinus symptoms. Of the 52 patients who were clinical successes at 14 days and completed follow-up, three (11%) of 27 3D subjects and one (4%) of 25 10D subjects relapsed symptomatically by day 30; one (4%) of 27 3D subjects and one (4%) of 25 10D subjects suffered symptomatic recurrence between days 30 and 60 (P=.45 for the relapse and recurrence rates combined). Conclusion.-At the 2-week follow-up, clinical symptoms and radiograph scores improved equally following 3 or 10 days of TMP/SMX plus oxymetazoline nasal spray. Symptomatic relapse and recurrence were similar between groups. Three days of antibiotics were as effective as 10 days and, because of the high disease prevalence, hold the potential for substantial cost savings. C1 AUDIE L MURPHY MEM VET ADM MED CTR,DIV GEN INTERNAL MED,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. LEXINGTON VET HOSP,MED SERV,LEXINGTON,KY. LEXINGTON VET HOSP,DIV GEN INTERNAL MED,LEXINGTON,KY. UNIV KENTUCKY,LEXINGTON,KY. VET AFFAIRS MED CTR,HLTH SERV RES FIELD PROGRAM,DURHAM,NC. VET AFFAIRS MED CTR,DIV GEN INTERNAL MED,DURHAM,NC. DUKE UNIV,MED CTR,DURHAM,NC. RP WILLIAMS, JW (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,AMBULATORY CARE SERV 11C,7400 MERTON MINTON BLVD,SAN ANTONIO,TX 78284, USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 48 TC 93 Z9 93 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 APR 5 PY 1995 VL 273 IS 13 BP 1015 EP 1021 DI 10.1001/jama.273.13.1015 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA QP890 UT WOS:A1995QP89000031 PM 7897784 ER PT J AU LUO, H HANRATTY, WP DEAROLF, CR AF LUO, H HANRATTY, WP DEAROLF, CR TI AN AMINO-ACID SUBSTITUTION IN THE DROSOPHILA HOP(TUM-L) JAK KINASE CAUSES LEUKEMIA-LIKE HEMATOPOIETIC DEFECTS SO EMBO JOURNAL LA English DT Article DE DROSOPHILA; HEMATOPOIESIS; HOP(TUM-L); JAK KINASE ID NF-KAPPA-B; PROTEIN-TYROSINE KINASE; MELANOTIC TUMOR-FORMATION; DNA-BINDING; SIGNAL-TRANSDUCTION; IMMUNE-REACTIONS; MELANOGASTER; GENE; RECEPTOR; EXPRESSION AB Proteins of the Jak family of non-receptor kinases play important roles in mammalian hematopoietic signal transduction. They mediate the cellular response to a wide range of cytokines and growth factors. A dominant mutation in a Drosophila Jak kinase, hopscotch(Tumorous-lethal) (hop(Tum-l)), causes hematopoietic defects. Here we conduct a molecular analysis of hop(Tum-l). We demonstrate that the hop(Tum-l) hematopoietic phenotype is caused by a single amino acid substitution of glycine to glutamic acid at residue 341. We generate a true revertant of the hop(Tum-l) mutation, in which both the molecular lesion and the mutant hematopoietic phenotype revert back to wild type. We also examine the effects of the G341E substitution in transgenic flies. The results indicate that a mutant Jak kinase can cause leukemia-like abnormalities. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DEV GENET GRP, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT RADIAT ONCOL, BOSTON, MA 02115 USA. INDIANA UNIV, DEPT BIOL, BLOOMINGTON, IN 47405 USA. FU NHLBI NIH HHS [HL 48823] NR 73 TC 216 Z9 217 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD APR 3 PY 1995 VL 14 IS 7 BP 1412 EP 1420 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QU574 UT WOS:A1995QU57400014 PM 7729418 ER PT J AU MHASHILKAR, AM BAGLEY, J CHEN, SY SZILVAY, AM HELLAND, DG MARASCO, WA AF MHASHILKAR, AM BAGLEY, J CHEN, SY SZILVAY, AM HELLAND, DG MARASCO, WA TI INHIBITION OF HIV-1 TAT-MEDIATED LTR TRANSACTIVATION AND HIV-1 INFECTION BY ANTI-TAT SINGLE-CHAIN INTRABODIES SO EMBO JOURNAL LA English DT Article DE AIDS; CD4(+); GENE THERAPY; INTRACELLULAR IMMUNIZATION; T CELLS ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; LONG TERMINAL REPEAT; RNA-BINDING PROTEIN; GENE-EXPRESSION; CHLORAMPHENICOL ACETYLTRANSFERASE; MUTATIONAL ANALYSIS; NUCLEAR-PROTEIN; BASIC DOMAIN; NASCENT RNA AB Genes encoding the rearranged immunoglobulin heavy and light chain variable regions of anti-HIV-l Tat, exon 1 or exon 2 specific monoclonal antibodies have been used to construct single chain intracellular antibodies 'intrabodies' for expression in the cytoplasm of mammalian cells. These anti-Tat single chain intrabodies (anti-Tat sFvs) are additionally modified with a C-terminal human C-kappa domain to increase cytoplasmic stability and/or the C-terminal SV40 nuclear localization signal to direct the nascent intrabody to the nuclear compartment, respectively. The anti-Tat sFvs with specific binding activity against the N-terminal activation domain of Tat, block Tat-mediated transactivation of HIV-1 LTR as well as intracellular trafficking of Tat in mammalian cells. As a result, the transformed lymphocytes expressing anti-Tat sFvs are resistant to HIV-1 infection. Thus, these studies demonstrate that stably expressed single chain intrabodies and their modified forms can effectively target molecules in the cytoplasm and nuclear compartments of eukaryotic cells. Furthermore, these studies suggest that anti-Tat sFvs used either alone or in combination with other genetically based strategies may be useful for the gene therapy of HIV-1 infection and AIDS. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIROL,BOSTON,MA 02115. UNIV BERGEN,BERGEN HIGH TECHNOL CTR,NATL CTR RES VIROL,BERGEN,NORWAY. FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [AI28785, P30 AI28691] NR 77 TC 152 Z9 158 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD APR 3 PY 1995 VL 14 IS 7 BP 1542 EP 1551 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QU574 UT WOS:A1995QU57400027 PM 7537216 ER PT J AU TESTA, CM STANDAERT, DG LANDWEHRMEYER, GB PENNEY, JB YOUNG, AB AF TESTA, CM STANDAERT, DG LANDWEHRMEYER, GB PENNEY, JB YOUNG, AB TI DIFFERENTIAL EXPRESSION OF MGLUR5 METABOTROPIC GLUTAMATE-RECEPTOR MESSENGER-RNA BY RAT STRIATAL NEURONS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE IN SITU HYBRIDIZATION; ENKEPHALIN; SOMATOSTATIN; CHOLINERGIC; NEOSTRIATUM ID INSITU HYBRIDIZATION HISTOCHEMISTRY; CENTRAL-NERVOUS-SYSTEM; PREPROENKEPHALIN MESSENGER-RNA; IN-SITU HYBRIDIZATION; SUBSTANCE-P; HUNTINGTONS-DISEASE; BASAL GANGLIA; GENE-EXPRESSION; CHOLINERGIC NEURONS; IMMUNOHISTOCHEMICAL LOCALIZATION AB Metabotropic glutamate receptors (mGluRs) mediate the effects of glutamate neurotransmission on intracellular second messenger systems. Among the seven distinct mGluR receptor isoforms currently identified, the mGluR5 isoform is expressed particularly prominently in the striatum, where it may contribute to neuronal plasticity, motor behaviors, and excitotoxic injury. mGluR5 mRNA expression in striatal enkephalinergic, somatostatinergic, and cholinergic neurons was examined using double label in situ hybridization techniques. mGluR5 expression is abundant in a large number of medium-sized striatal cells but is absent in a significant minority of neurons. Double label in situ hybridization with S-35-dATP- and digoxygenin-dUTP-tailed oligonucleotide probes demonstrated that mGluR5 message is highly expressed by enkephalinergic striatal neurons but is not detectable in cholinergic or somatostatin interneurons. In addition, some nonenkephalin, presumably substance P, neurons were also strongly labeled for mGluR5. The differential expression of mGluR5 in striatal projection neurons vs. interneurons may contribute to the selective vulnerability of these neurons to disease processes. (C) 1995 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIA NIH HHS [AG08671]; NINDS NIH HHS [NS31579, NS19613] NR 95 TC 148 Z9 150 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 3 PY 1995 VL 354 IS 2 BP 241 EP 252 DI 10.1002/cne.903540207 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA QM557 UT WOS:A1995QM55700006 PM 7782501 ER PT J AU BURKE, TR YE, B AKAMATSU, M YAN, XJ KOLE, HK WOLF, G SHOELSON, SE ROLLER, PP AF BURKE, TR YE, B AKAMATSU, M YAN, XJ KOLE, HK WOLF, G SHOELSON, SE ROLLER, PP TI NON-PHOSPHORUS-CONTAINING PHOSPHOTYROSYL MIMETICS AMENABLE TO PRODRUG DERIVATIZATION AND THEIR USE IN SOLID-PHASE SYNTHESIS OF SH2 DOMAIN AND PHOSPHATASE INHIBITORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIA,GRC,LCP,DIABET UNIT,BALTIMORE,MD 21224. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. NCI,MED CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 14 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203207 ER PT J AU SLECKMAN, BP ALT, FW AF SLECKMAN, BP ALT, FW TI GENETIC-ANALYSIS OF IMMUNE-SYSTEM DEVELOPMENT SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 20 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23200302 ER PT J AU ROSENZWEIG, AC NORDLUND, P LIPPARD, SI FREDERICK, CA AF ROSENZWEIG, AC NORDLUND, P LIPPARD, SI FREDERICK, CA TI X-RAY CRYSTALLOGRAPHIC STUDIES OF THE HYDROXYLASE PROTEIN OF METHANE MONOOXYGENASE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 HARVARD UNIV,DANA FARBER CANC INST,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. UNIV STOCKHOLM,DEPT MOLEC BIOL,S-10691 STOCKHOLM,SWEDEN. MIT,DEPT CHEM,CAMBRIDGE,MA 02139. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 210 EP INOR PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23202809 ER PT J AU YUAN, JY AF YUAN, JY TI THE GENES THAT CONTROL PROGRAMMED CELL-DEATH - FROM WORM TO MAMMAL SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1995 VL 209 BP 243 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA QP232 UT WOS:A1995QP23203435 ER PT J AU WYSS, DF CHOI, JS DAYIE, KT REINHERZ, EL WAGNER, G AF WYSS, DF CHOI, JS DAYIE, KT REINHERZ, EL WAGNER, G TI GLYCOPROTEIN STRUCTURE OF THE ADHESION DOMAIN OF THE HUMAN T-CELL RECEPTOR CD2 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 PROCEPT INC,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. RI Dayie, T Kwaku/E-6868-2011 OI Dayie, T Kwaku/0000-0002-7119-4362 NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 40 EP 40 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500124 ER PT J AU ZHOU, MM LOGAN, TM MEADOWS, RP YOON, HS RAICHANDRAN, KS BURAKOFF, SJ FESIK, SW AF ZHOU, MM LOGAN, TM MEADOWS, RP YOON, HS RAICHANDRAN, KS BURAKOFF, SJ FESIK, SW TI SOLUTION STRUCTURE OF THE SHC SH2 DOMAIN COMPLEXED WITH A TYROSINE-PHOSPHORYLATED PEPTIDE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 ABBOTT LABS,DIV PHARMACEUT DISCOVERY,ABBOTT PK,IL 60064. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. RI Yoon, Ho Sup/A-2193-2011 NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 41 EP 41 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500126 ER PT J AU ROSES, A SAUNDERS, A CORDER, E RISCH, N HAINES, J PERICAKVANCE, M HAN, SH EINSTEIN, G HULETTE, C SCHMECHEL, D GOEDERT, M WEISGRABER, K HUANG, D STRITTMATTER, W AF ROSES, A SAUNDERS, A CORDER, E RISCH, N HAINES, J PERICAKVANCE, M HAN, SH EINSTEIN, G HULETTE, C SCHMECHEL, D GOEDERT, M WEISGRABER, K HUANG, D STRITTMATTER, W TI APOLIPOPROTEIN E4 AND E2 ARE SUSCEPTIBILITY GENES THAT AFFECT THE RATE OF ALZHEIMER-DISEASE EXPRESSIVITY SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,JOSEPH & KATHLEEN BRYAN ALZHEIMERS DIS RES CTR,DURHAM,NC 27710. YALE UNIV,NEW HAVEN,CT 06520. MASSACHUSETTS GEN HOSP,BOSTON,MA. MRC,MOLEC BIOL LAB,CAMBRIDGE,ENGLAND. UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,SAN FRANCISCO,CA 94143. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 86 EP 86 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500288 ER PT J AU TANZI, RE ROMANO, DM PETTINGELL, W JONDRO, P SCHMIDT, S CROWLEY, AC RARADIS, M MURRELL, J BUCKLER, A WASCO, W AF TANZI, RE ROMANO, DM PETTINGELL, W JONDRO, P SCHMIDT, S CROWLEY, AC RARADIS, M MURRELL, J BUCKLER, A WASCO, W TI MOLECULAR-GENETIC STRATEGIES FOR ISOLATING THE MAJOR EARLY-ONSET FAD GENE ON CHROMOSOME-14 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 HARVARD UNIV,MASS GEN HOSP,SCH MED,GENET & AGING LAB,BOSTON,MA 02129. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 86 EP 86 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500290 ER PT J AU BEAL, MF AF BEAL, MF TI OXIDATIVE DAMAGE IN HUNTINGTON DISEASE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT NEUROCHEM,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 89 EP 89 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500297 ER PT J AU BOHN, MC YOSHIMOTO, Y LIN, Q COLLIER, TJ FRIM, DM BREAKEFIELD, XO AF BOHN, MC YOSHIMOTO, Y LIN, Q COLLIER, TJ FRIM, DM BREAKEFIELD, XO TI EX-VIVO GENE-THERAPY WITH BRAIN-DERIVED NEUROTROPHIC FACTOR NBDNF) IMPROVES BEHAVIOR IN A RAT MODEL OF PARKINSONS-DISEASE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 UNIV ROCHESTER,MED CTR,DEPT NEUROBIOL & ANAT,ROCHESTER,NY 14642. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 109 EP 109 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500370 ER PT J AU CUNNINGHAM, LA LOPEZCOLBERG, I KROBERT, K BREAKEFIELD, XO FRIM, D AF CUNNINGHAM, LA LOPEZCOLBERG, I KROBERT, K BREAKEFIELD, XO FRIM, D TI USE OF RETROVIRALLY TRANSDUCED ASTROCYTES TO DELIVER RECOMBINANT BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) TO MIDBRAIN DOPAMINE NEURONS IN CULTURE - IMPLICATIONS FOR GENE-THERAPY IN PARKINSONS-DISEASE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 UNIV NEW MEXICO,HLTH SCI CTR,DEPT PHARMACOL,ALBUQUERQUE,NM 87131. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. NR 1 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 109 EP 109 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500372 ER PT J AU IMBALZANO, AN KINGSTON, RE AF IMBALZANO, AN KINGSTON, RE TI FACILITATION OF TRANSCRIPTION FACTOR-BINDING TO NUCLEOSOMAL DNA BY HUMAN SWI SNF SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 159 EP 159 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500523 ER PT J AU YODH, JG IMBALZANO, AN KINGSTON, RE AF YODH, JG IMBALZANO, AN KINGSTON, RE TI EFFECT OF HISTONE ACETYLATION ON TRANSCRIPTION FACTOR-BINDING SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 1 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 163 EP 163 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500539 ER PT J AU SAKIHAMA, T SMOLYAR, A REINHERZ, EL AF SAKIHAMA, T SMOLYAR, A REINHERZ, EL TI OLIGOMERIZATION OF CD4 IS REQUIRED FOR STABLE BINDING TO CLASS-II MHC PROTEINS BUT NOT FOR INTERACTION WITH HIV-1 GP120 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract ID TOXIC LYMPHOCYTES-T; SOLUBLE CD4; MONOCLONAL-ANTIBODY; FUNCTIONAL SUBSETS; ATOMIC-STRUCTURE; ANTIGEN; RETROVIRUS; MOLECULES; RECEPTOR; DELINEATION C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 26 TC 0 Z9 0 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 180 EP 180 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500594 ER PT J AU TUDORWILLIAMS, G BANDA, NK COTTON, MF BABA, TW RUPRECHT, R DUPFER, A AF TUDORWILLIAMS, G BANDA, NK COTTON, MF BABA, TW RUPRECHT, R DUPFER, A TI APOPTOSIS OCCURS PREDOMINANTLY IN BYSTANDER CELLS AND NOT IN PRODUCTIVELY INFECTED-CELLS OF HIV-INFECTED AND SIV-INFECTED LYMPH-NODES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NATL JEWISH CTR IMMUNOL & RESP MED,DENVER,CO. NCI,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 182 EP 182 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500600 ER PT J AU RUPRECHT, RM BABA, TW JEONG, YS BRONSON, R PENNINCK, D GREENE, MF AF RUPRECHT, RM BABA, TW JEONG, YS BRONSON, R PENNINCK, D GREENE, MF TI DIFFERENTIAL PATHOGENICITY OF MULTIPLY DELETED SIV IN ADULT AND NEONATAL RHESUS-MONKEYS - IMPLICATIONS FOR LIVE-ATTENUATED VIRUS-VACCINE STRATEGIES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. TUFTS UNIV,SCH MED,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. TUFTS UNIV,SCH VET MED,BOSTON,MA 02111. NR 1 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 183 EP 183 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500604 ER PT J AU WYATT, R NIXON, C ACCOLA, M DESJARDINS, E ALLEN, R SODROSKI, J AF WYATT, R NIXON, C ACCOLA, M DESJARDINS, E ALLEN, R SODROSKI, J TI IMMUNOLOGICAL ANALYSIS OF VARIABLE AND CONSERVED REGION DELETED HIV-1 GP120 GLYCOPROTEINS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 229 EP 229 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500785 ER PT J AU KESTLER, HW PREMKUMAR, D HIRSCH, M MA, XZ SALKOWITZ, JR CHAKRABARTI, BK AF KESTLER, HW PREMKUMAR, D HIRSCH, M MA, XZ SALKOWITZ, JR CHAKRABARTI, BK TI THE UNIQUE NATURE OF NEF QUASI-SPECIES FROM A LONG-TERM SURVIVOR OF HIV-INFECTION - IMPLICATIONS FOR FUNCTION COMPARISON WITH OTHER ISOLATES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 CLEVELAND CLIN EDUC FDN,DEPT MOLEC BIOL,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI chakrabarti, bikas/F-4825-2013 NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 2 PY 1995 SU 21B BP 237 EP 237 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT865 UT WOS:A1995QT86500814 ER PT J AU BHAVANI, K DELAMONTE, S BROWN, NV XU, YY SASAKI, Y WANDS, JR AF BHAVANI, K DELAMONTE, S BROWN, NV XU, YY SASAKI, Y WANDS, JR TI EFFECT OF ETHANOL ON P36 PROTEIN-KINASE SUBSTRATE AND INSULIN-RECEPTOR SUBSTRATE-1 EXPRESSION AND TYROSYL PHOSPHORYLATION IN HUMAN HEPATOCELLULAR-CARCINOMA CELLS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ETHANOL; P36; IRS-1; TYROSYL PHOSPHORYLATION ID HEPATOCYTE DNA-SYNTHESIS; REGENERATING RAT-LIVER; HEPATIC REGENERATION; HEAVY-CHAIN; CALPACTIN-I; INHIBITION; GENE; ANNEXINS; CALCIUM AB Ethanol inhibits insulin (IN) and epidermal growth factor (EGF)-induced hepatocyte DNA synthesis. Growth factor receptor kinases, such as IN and EGF, phosphorylate insulin receptor substrate (IRS-1) and p36 protein kinase substrate, respectively, on tyrosine residues. IRS-1 and p36 are thought to be important intracellular signal transduction molecules involved in the regulation of cell growth. These investigations explored the effect of ethanol additions on the expression and tyrosyl phosphorylation (TP) of p36 and IRS-1 in a human hepatocellular carcinoma cell line (FOCUS) in relationship to cell proliferation induced by IN and serum growth factor stimulation. It was found that p36 was constitutively and highly expressed in serum-starved cells and protein, and mRNA levels did not change with cell proliferation induced by growth factors, However, exposure of FOCUS cells to ethanol additions substantially inhibited TP of p36. The early TP of IRS-1 induced by IN stimulation was also reduced by ethanol additions, Finally, there was a parallel decrease of FOCUS cell proliferation in ethanol-exposed cultures. These studies suggest that one possible mechanism of ethanol inhibitory effect on cell proliferation is through reduced TP of putative intracellular signal transduction molecules, such as p36 and IRS-1. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02129. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666, AA-01864] NR 35 TC 18 Z9 19 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 1995 VL 19 IS 2 BP 441 EP 446 DI 10.1111/j.1530-0277.1995.tb01528.x PG 6 WC Substance Abuse SC Substance Abuse GA QT750 UT WOS:A1995QT75000027 PM 7542850 ER PT J AU WURTMAN, J SAYEAH, R SCHIFF, I SPIERS, P MCDERMOTT, J WURTMAN, R AF WURTMAN, J SAYEAH, R SCHIFF, I SPIERS, P MCDERMOTT, J WURTMAN, R TI CHO-RICH BEVERAGE IMPROVES PREMENSTRUAL CHANGES IN MOOD AND APPETITE SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract C1 MIT,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1995 VL 61 IS 4 BP 903 EP 903 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA QQ342 UT WOS:A1995QQ34200092 ER PT J AU POUSSAINT, TY SIFFERT, J BARNES, PD POMEROY, SL GOUMNEROVA, LC ANTHONY, DC SALLAN, SE TARBELL, NJ AF POUSSAINT, TY SIFFERT, J BARNES, PD POMEROY, SL GOUMNEROVA, LC ANTHONY, DC SALLAN, SE TARBELL, NJ TI HEMORRHAGIC VASCULOPATHY AFTER TREATMENT OF CENTRAL-NERVOUS-SYSTEM NEOPLASIA IN CHILDHOOD - DIAGNOSIS AND FOLLOW-UP SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE BRAIN, EFFECTS OF IRRADIATION ON; BRAIN NEOPLASMS; CEREBRAL HEMORRHAGE; CHILDREN, NEOPLASMS ID INTRACEREBRAL HEMORRHAGE; COMPLICATION; THERAPY AB PURPOSE: To review the clinical data, imaging findings, and intermediate outcomes of a series of children with hemorrhagic vasculopathy after treatment for intracranial neoplasia. METHODS: We retrospectively analyzed the medical records and imaging examinations of 20 pediatric patients (ages 1 to 15 years) with intracranial neoplasia in whom delayed intracranial hemorrhage developed after cranial irradiation or radiation combined with systemic or intrathecal chemotherapy. Patients with intracranial hemorrhage from other identifiable causes were excluded. Histopathologic analysis was available in four patients. RESULTS: Twenty patients with delayed intracranial hemorrhage received cranial irradiation alone (n=9) or combined radiation and chemotherapy (n=11) for primary brain tumors (n=13), leukemia (n=6), or lymphoma (n=1). Imaging findings were consistent with hemorrhages of varying ages. The hemorrhages were not associated with tumor recurrence nor second tumors. Except for location of the hemorrhage, no significant relationship was established between outcome and original diagnosis, radiation dose (range, 1800 to 6000 centigray), chemotherapeutic agent or dosage, age at treatment, or interval between therapy and hemorrhage (mean, 8.1 years). Only brain stem hemorrhage was associated with a poor outcome. CONCLUSION: In children with central nervous system neoplasia who have undergone cranial irradiation, or radiation combined with chemotherapy, delayed intracranial hemorrhage may develop. C1 CHILDRENS HOSP,JOINT CTR RADIAT THERAPY,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,DEPT NEUROL,BOSTON,MA 02115. CHILDRENS HOSP,JOINT CTR RADIAT THERAPY,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,DEPT NEUROSURG,BOSTON,MA 02115. CHILDRENS HOSP,JOINT CTR RADIAT THERAPY,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,DEPT NEUROPATHOL,BOSTON,MA 02115. CHILDRENS HOSP,JOINT CTR RADIAT THERAPY,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,DEPT MED,BOSTON,MA 02115. CHILDRENS HOSP,JOINT CTR RADIAT THERAPY,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. RP POUSSAINT, TY (reprint author), CHILDRENS HOSP,JOINT CTR RADIAT THERAPY,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,DEPT RADIOL,BOSTON,MA 02115, USA. OI Anthony, Douglas/0000-0002-3815-2240 NR 11 TC 71 Z9 71 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 APR PY 1995 VL 16 IS 4 BP 693 EP 699 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA QT334 UT WOS:A1995QT33400012 PM 7611024 ER PT J AU PROVENZALE, JM BARBORIAK, DP SIMS, K AF PROVENZALE, JM BARBORIAK, DP SIMS, K TI NEURORADIOLOGIC FINDINGS IN FUCOSIDOSIS, A RARE LYSOSOMAL STORAGE DISEASE SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE BRAIN, METABOLISM; DEGENERATIVE DISEASE; PEDIATRIC NEURORADIOLOGY ID MRI AB Fucosidosis is a rare lysosomal storage disorder with the clinical features of mental retardation, cardiomegaly, dysostosis multiplex, progressive neurologic deterioration, and early death. The neuroradiologic findings in two patients are reported, and include abnormalities within the globus pallidus (both patients) and periventricular white matter (one patient). C1 SHIELDS HLTH CARE,BROCKTON,MA. MASSACHUSETTS GEN HOSP EAST,MOLEC NEUROGENET LAB,BOSTON,MA. RP PROVENZALE, JM (reprint author), DUKE UNIV,MED CTR,DEPT RADIOL,BOX 3808,DURHAM,NC 27710, USA. NR 14 TC 21 Z9 21 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 APR PY 1995 VL 16 IS 4 SU S BP 809 EP 813 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA QT868 UT WOS:A1995QT86800001 PM 7611045 ER PT J AU PINNOLIS, MK FOXWORTHY, D KEMP, B AF PINNOLIS, MK FOXWORTHY, D KEMP, B TI TREATMENT OF PROGRESSIVE OUTER RETINAL NECROSIS WITH SORIVUDINE SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Note ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME AB PURPOSE/METHODS: We examined a patient with progressive outer retinal necrosis, which is presumably caused by the varicella-zoster virus in patients with the acquired immunodeficiency syndrome. RESULTS/CONCLUSIONS: The patient was successfully treated with a combination of intravitreal ganciclovir and oral sorivudine. Treatment for progressive outer retinal necrosis has been disappointing; both acyclovir and ganciclovir have had only limited success, Sorivudine, a new antiviral medication with activity against varicella-zoster virus, may represent an effective alternative treatment for retinal necrosis. C1 HARVARD UNIV,COMMUNITY HLTH PLAN,DEPT VISUAL SERV,BOSTON,MA 02115. HARVARD UNIV,COMMUNITY HLTH PLAN,DEPT INTERNAL MED,BOSTON,MA 02115. HARVARD UNIV,COMMUNITY HLTH PALN,DEPT ONCOL,BOSTON,MA 02115. RP PINNOLIS, MK (reprint author), MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 5 TC 17 Z9 17 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 APR PY 1995 VL 119 IS 4 BP 516 EP 517 PG 2 WC Ophthalmology SC Ophthalmology GA QR237 UT WOS:A1995QR23700018 PM 7709980 ER PT J AU WELLENREUTHER, R KRAUS, JA LENARTZ, D MENON, AG SCHRAMM, J LOUIS, DN RAMESH, V GUSELLA, JF WIESTLER, OD VONDEIMLING, A AF WELLENREUTHER, R KRAUS, JA LENARTZ, D MENON, AG SCHRAMM, J LOUIS, DN RAMESH, V GUSELLA, JF WIESTLER, OD VONDEIMLING, A TI ANALYSIS OF THE NEUROFIBROMATOSIS-2 GENE REVEALS MOLECULAR VARIANTS OF MENINGIOMA SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Note ID CHROMOSOME-22; LOCUS; PCR AB There is evidence from cytogenetic and loss of heterozygosity studies for the involvement of a tumor suppressor gene on chromosome 22 in the formation of meningiomas. Recently, the NF2 gene, which causes neurofibromatosis type 2 and which is located in the affected region on chromosome 22, has been identified A previous study on 8 of the 17 exons of the NF2 gene described mutations in 16% of meningiomas. We have analyzed the entire coding region of the NF2 gene in 70 sporadic meningiomas and identified 43 mutations in 41 patients. These reszrlted predominantly in immediate truncation, splicing abnormalities, or an altered reading frame of the predicted protein product. Although there was no evidence for distinct hotspots, all mutations occurred in the first 13 exons, the region of homology with the filopodial proteins moesin, ezrin, and radixin. The association of loss of heterozy gosity on chromosome 22 with mutations in the NF2 gene was significant. These data suggest that NF2 represents the meningioma locus on chromosome 22, NF2 mutations occurred significantly more frequently in fibroblastic meningioma (70%) and transitional meningioma (83%) than in meningiothelial meningioma (25%), thus indicating a differential molecular pathogenesis of these meningioma variants. C1 UNIV BONN,MED CTR,DEPT NEUROPATHOL,W-5300 BONN,GERMANY. UNIV BONN,MED CTR,NEUROSURG CLIN,W-5300 BONN,GERMANY. NEUROSURG CLIN COLOGNE MERBEIM,COLOGNE,GERMANY. UNIV CINCINNATI,MED CTR,DEPT MOLEC GENET BIOCHEM & MICROBIOL,CINCINNATI,OH 45267. MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BOSTON,MA 02114. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X FU NINDS NIH HHS [NS24279] NR 20 TC 191 Z9 194 U1 0 U2 4 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 APR PY 1995 VL 146 IS 4 BP 827 EP 832 PG 6 WC Pathology SC Pathology GA QR984 UT WOS:A1995QR98400004 PM 7717450 ER PT J AU SCHWEICKHARDT, C SABOLIC, I BROWN, D BURCKHARDT, G AF SCHWEICKHARDT, C SABOLIC, I BROWN, D BURCKHARDT, G TI ECTO-ADENOSINE-TRIPHOSPHATASE IN RAT SMALL-INTESTINAL BRUSH-BORDER MEMBRANES SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE SMALL INTESTINE; CELL-CAM105; C-CAM1; ADHESION MOLECULE; APYRASE; ADENOSINE TRIPHOSPHATE DIPHOSPHOHYDROLASE; ALKALINE PHOSPHATASE ID CELL-ADHESION MOLECULE; HEPATOCYTE PLASMA-MEMBRANE; CANALICULAR MEMBRANE; ATPASE; LOCALIZATION; VESICLES; TRANSPORT; ISOFORMS; TISSUES; PROTEIN AB Antibodies against the hole ecto-adenosmetriphosphatase (ATPase) of rat liver and antibodies against COOH-terminal peptides of the long isoform of this enzyme reacted in Western blots with a 105-kDa band from small intestinal brush-border membranes. Indirect immunofluorescence revealed reactive proteins predominantly at the apical surface of enterocytes with some staining of basolateral membranes and of vascular endothelium. Similar results were obtained with monoclonal antibodies against HA4, a protein from rat liver closely related to the ecto-ATPase. Since these results suggested the presence of an ecto-ATPase, ATP hydrolysis was studied in intact, right-side-out brush-border membrane vesicles. Nearly half of ATP hydrolysis was caused by alkaline phosphatase (AP). Besides purine and pyrimidine trinucleotides, AP also hydrolyzed ADP, AMP, pyrophosphate, and 4-nitrophenylphosphate. Inactivation of AP by cleavage of its membrane anchor and by removal of the Zn2+ necessary for its function left the ecto-ATPase that was activated by Ca2+ and Mg2+ and hydrolyzed purine and pyrimidine trinucleotides and dinucleotides, but not AMP, pyrophosphate, and 4-nitrophenylphosphate. These features are characteristic of an ATP diphosphohydrolase (EC 3.6.1.5, also called apyrase). The physiological role of the small intestinal ecto-ATPase may be the degradation of nutrient nucleotides. C1 ZENTRUM PHYSIOL, D-37073 GOTTINGEN, GERMANY. INST MED RES & OCCUPAT HLTH, ZAGREB 41001, CROATIA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, RENAL UNIT, BOSTON, MA 02129 USA. FU NIDDK NIH HHS [DK-38452] NR 36 TC 11 Z9 11 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 APR PY 1995 VL 268 IS 4 BP G663 EP G672 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA QR813 UT WOS:A1995QR81300014 PM 7733291 ER PT J AU KAWAI, N BLOCH, DB FILIPPOV, G RABKINA, D SUEN, HC LOSTY, PD JANSSENS, SP ZAPOL, WM DELAMONTE, S BLOCH, KD AF KAWAI, N BLOCH, DB FILIPPOV, G RABKINA, D SUEN, HC LOSTY, PD JANSSENS, SP ZAPOL, WM DELAMONTE, S BLOCH, KD TI CONSTITUTIVE ENDOTHELIAL NITRIC-OXIDE SYNTHASE GENE-EXPRESSION IS REGULATED DURING LUNG DEVELOPMENT SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE NITRIC OXIDE; PULMONARY VASCULAR RESISTANCE; NEWBORN; RAT ID PULMONARY BLOOD-FLOW; RELAXING FACTOR; NEWBORN; CLONING; BIRTH; CELLS; VASODILATION; CIRCULATION; ARTERIES; PROTEINS AB Nitric oxide (NO), a potent vasodilator, is a free-radical gas synthesized from L-arginine by nitric oxide synthases (NOS). NO appears to have an important role in perinatal changes in pulmonary vascular resistance. We previously identified mRNA encoding the constitutive endothelial NOS (ceNOS) isoform in human pulmonary tissue. To begin investigating functions of this enzyme in perinatal pulmonary development, we measured ceNOS mRNA and immunoreactivity in the developing rat lung. With the use of RNA blot hybridization, abundant pulmonary ceNOS mRNA was detected during the late fetal and postnatal period. The highest levels were detected within 24 h after birth, and elevated mRNA levels persisted for 16 days. In contrast, much lower levels of ceNOS mRNA were found in adult rat lung. With the use of immunoblot techniques, ceNOS protein levels were found to be correlated with mRNA levels. To identify the pulmonary cell types expressing the ceNOS gene, in situ hybridization with a digoxigenin-labeled cRNA probe was performed on sections from lungs of 1-day-old and adult rats. In lungs from 1-day-old rats, ceNOS mRNA was detected in alveolar and serosal epithelial cells as well as in endothelial cells lining small and medium-sized blood vessels. In contrast, in adult lungs, ceNOS gene transcripts were detected in rare endothelial cells. These observations suggest that ceNOS gene expression is regulated during lung development and that ceNOS is available to participate in the postnatal reduction of pulmonary vascular resistance. ceNOS gene expression in nonendothelial cells in the neonatal rat lung suggests that NO may also contribute to nonvascular functions in the developing lung. C1 MASSACHUSETTS GEN HOSP, CARDIOVASC RES CTR, DEPT ANESTHESIA, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, MED SERV, MOLEC HEPATOL UNIT, ARTHRIT UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, PEDIAT SURG SERV, PEDIAT SURG RES LABS, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. FU NHLBI NIH HHS [HL-42397]; NIAMS NIH HHS [AR-01866]; NINDS NIH HHS [NS-00425] NR 39 TC 49 Z9 50 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD APR PY 1995 VL 268 IS 4 BP L589 EP L595 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA QT313 UT WOS:A1995QT31300008 PM 7537461 ER PT J AU GOLOMB, M FAVA, M ABRAHAM, M ROSENBAUM, JF AF GOLOMB, M FAVA, M ABRAHAM, M ROSENBAUM, JF TI GENDER DIFFERENCES IN PERSONALITY-DISORDERS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID III AXIS-II; DSM-III; PREVALENCE; CRITERIA; SITES AB Objective: The aim of this study was to assess gender differences in personality disorders. Since heterogeneity of axis I diagnoses could introduce variability in the assessment of axis II diagnoses, the authors studied a group of patients with a primary diagnosis of major depression. Method: A total of 316 patients were evaluated with the Personality Diagnostic Questionnaire-Revised, a self-rating measure, or the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II), a clinician-rated instrument, or both. Axis II disorders were assessed with the Personality Diagnostic Questionnaire-Revised for 288 patients with major depression. The SCID-II was administered to 117 subjects, with an additional 95 subjects receiving the SCID-II for cluster B diagnoses only. Results: The mean 17-item Hamilton Depression Rating Scale scores for 108 men (mean age=39.28 years) and 208 women (mean age=39.11) were 19.0 (SD=3.8) and 19.6 (SD=6.9), respectively. Men were significantly more likely than women to meet criteria for narcissistic, antisocial, and obsessive-compulsive personality disorders as measured by the Personality Diagnostic Questionnaire-Revised and for narcissistic and obsessive-compulsive Personality disorders as measured by the SCID-II. Conclusions: These findings are consistent with those of previous studies showing a greater prevalence of antisocial and narcissistic personality disorders in men. In contrast with other investigations, however, neither the Personality Diagnostic Questionnaire-Revised nor the SCID-II revealed a higher prevalence of any Personality disorder in women. C1 MASSACHUSETTS GEN HOSP,DEPRESS RES PROGRAM,BOSTON,MA 02114. NR 18 TC 84 Z9 84 U1 5 U2 15 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 1995 VL 152 IS 4 BP 579 EP 582 PG 4 WC Psychiatry SC Psychiatry GA QQ116 UT WOS:A1995QQ11600013 PM 7694907 ER PT J AU CENTORRINO, F BALDESSARINI, RJ FLOOD, JG KANDO, JC FRANKENBURG, FR AF CENTORRINO, F BALDESSARINI, RJ FLOOD, JG KANDO, JC FRANKENBURG, FR TI RELATION OF LEUKOCYTE COUNTS DURING CLOZAPINE TREATMENT TO SERUM CONCENTRATIONS OF CLOZAPINE AND METABOLITES SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Note AB Objective: This study was done to test the hypothesis that serum concentration of norclozapine is a risk factor for leukopenia during treatment with clozapine. Method: Maximum decreases in leukocyte counts in 44 unselected patients treated with clozapine were determined and then correlated with drug doses and serum concentrations of clozapine, norclozapine, and clozapine-N-oxide. Results: White cell and granulocyte counts decreased by zip to 60%-73%, but there were no positive correlations between these decrements and drug dose, drug level, ratio of drug level to drug dose, or ratio of norclozapine level to clozapine level, nor were the decreases related to age or gender. Conclusions: While these results do not suggest in vivo hemotoxicity of norclozapine, further study of patients with clinically significant leukopenia is required. C1 MCLEAN HOSP,MAILMAN RES CTR,BELMONT,MA 02178. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,NEUROSCI PROGRAM,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MCLEAN HOSP,PSYCHOT DISORDERS PROGRAM,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,CLIN CHEM LAB,BOSTON,MA 02114. FU NIMH NIH HHS [MH-47370, MH-31154] NR 10 TC 22 Z9 22 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 1995 VL 152 IS 4 BP 610 EP 612 PG 3 WC Psychiatry SC Psychiatry GA QQ116 UT WOS:A1995QQ11600019 PM 7694912 ER PT J AU BALLARD, RD CLOVER, CW SUH, BY AF BALLARD, RD CLOVER, CW SUH, BY TI INFLUENCE OF SLEEP ON RESPIRATORY-FUNCTION IN EMPHYSEMA SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; NON-REM SLEEP; VENTILATORY RESPONSE; OXYGEN DESATURATION; LUNG-VOLUME; OCCLUSION PRESSURE; ASTHMATIC-PATIENTS; CHRONIC-BRONCHITIS; MUSCLE-ACTIVITY; NORMAL HUMANS AB To assess the influence of sleep on respiratory function, five patients with chronic obstructive pulmonary disease (COPD) with laboratory evidence of emphysema were monitored during sleep in a horizontal body plethysmograph. Neither lung volume nor lower airway resistance (Rla) changed in association with sleep. Upper airway resistance (Rua) increased during sleep and was highest during rapid eye movement (REM) sleep (Rua = 5.9 +/- 1.1, 9.6 +/- 2.1, 11.2 +/- 1.5, and 15.6 +/- 4.1 cm H2O/L/s during wakefulness, Stages 2, 3-4, and REM, respectively, p < 0.05). Tidal volume (VT) decreased during sleep, resulting in a sleep-associated decrement in minute ventilation (VI = 8.69 +/- 0.46, 7.64 +/- 0.65, 7.08 +/- 0.70, and 5.62 +/- 0.47 L during wakefulness, Stages 2, 3-4, and REM, respectively, p < 0.05). Respiratory neuromuscular output was also reduced during sleep (esophageal occlusion pressure [P-0.1] = 2.69 +/- 0.39, 2.02 +/- 0.27, 1.90 +/- 0.27, and 1.63 +/- 0.25 cm H2O during wakefulness, Stages 2, 3-4, and REM, respectively, p = 0.005). We conclude that in patients with emphysema (1) sleep does not alter lung volume or increase lower airway resistance, (2) sleep is associated with a decrease in VT and VI, and (3) sleep is associated with an increase in Rua and a reduction in P-0.1 that may contribute to the sleep-associated decrease in VI. RP BALLARD, RD (reprint author), UNIV COLORADO,DENVER VET AFFAIRS MED CTR,HLTH SCI CTR,DEPT MED,DIV PULM SCI & CRIT CARE MED,DENVER,CO 80220, USA. NR 37 TC 40 Z9 45 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 APR PY 1995 VL 151 IS 4 BP 945 EP 951 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA QQ888 UT WOS:A1995QQ88800005 PM 7697271 ER PT J AU MONTGOMERY, AB FEIGAL, DW SATTLER, F MASON, GR CATANZARO, A EDISON, R MARKOWITZ, N JOHNSON, E OGAWA, S ROVZAR, M UDEM, SA EDEN, E HYSLOP, N CHEUNG, TW KESSLER, H MILDVAN, D GIRON, JA ETTINGER, N CRUMPACKER, C FRAME, P STEIGBIGEL, N VANDERHORST, C HIRSCH, M LEDERMAN, MM HEWITT, RG FALLAT, R FARBER, HW SACKS, HS EISMAN, SA LUCE, JM BOYLAN, T ADAMS, M FEINBERG, J HOPEWELL, PC AF MONTGOMERY, AB FEIGAL, DW SATTLER, F MASON, GR CATANZARO, A EDISON, R MARKOWITZ, N JOHNSON, E OGAWA, S ROVZAR, M UDEM, SA EDEN, E HYSLOP, N CHEUNG, TW KESSLER, H MILDVAN, D GIRON, JA ETTINGER, N CRUMPACKER, C FRAME, P STEIGBIGEL, N VANDERHORST, C HIRSCH, M LEDERMAN, MM HEWITT, RG FALLAT, R FARBER, HW SACKS, HS EISMAN, SA LUCE, JM BOYLAN, T ADAMS, M FEINBERG, J HOPEWELL, PC TI PENTAMIDINE AEROSOL VERSUS TRIMETHOPRIM-SULFAMETHOXAZOLE FOR PNEUMOCYSTIS-CARINII IN ACQUIRED-IMMUNE-DEFICIENCY-SYNDROME SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID IMMUNODEFICIENCY-SYNDROME; RANDOMIZED TRIAL; INTRAVENOUS PENTAMIDINE; PNEUMONIA; THERAPY; AIDS; CORTICOSTEROIDS; COSTS AB Pneumocystis carinii pneumonia remains one of the most common opportunistic infections in patients with acquired immune deficiency syndrome (AIDS). Treatment with either intravenous pentamidine or trimethoprim-sulfamethoxazole (TMP-SMX) is frequently complicated by serious adverse reactions. This study was a prospective, blinded comparison of 600 mg/d of pentamidine as an aerosol versus 15 mg/kg/d of trimethoprim plus 75 mg/kg/d of sulfamethoxazole for patients with mild or moderately severe P. carinii pneumonia (alveolar arterial oxygen difference of less than 55 mm Hg). Of 367 participants who were randomized to receive study therapies, 287 had proven and 16 had presumed Pneumocystis pneumonia. There were 29 deaths within 35 d of study initiation: 12 in the aerosolized pentamidine group and 17 in the TMP-SMX groups (log rank p = 0.28). The difference in mortality was 3.4% (95% CI = - 3.5, 10.8%). Ninety-four patients treated with aerosolized pentamidine had to have their study therapy changed because of lack of efficacy, compared with 22 patients treated with TMP-SMX(p = 0.002). In addition PaO2 improved faster in patients treated with TMP-SMX. However, aerosolized pentamidine was discontinued less often than TMP-SMX because of toxicity (9.4 versus 40% p < 0.001). Rash (0.6 versus 14.9%), nausea and vomiting (1.7 versus 12.2%), and abnormalities of liver function tests (1.7 versus 12.2%) were the most common adverse effects necessitating treatment discontinuation. During 6-mo follow-up there was no difference in mortality. Recurrences of P. carinii pneumonia were more frequent in patients treated with aerosolized pentamidine. Although aerosolized pentamidine was better tolerated than TMP-SMX, patients treated with TMP-SMX showed treatment failure, less often showed more rapidly improved oxygenation, and relapsed C1 UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA. UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92103. UNIV SO CALIF,DEPT MED,TORRANCE,CA. UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,DEPT MED,TORRANCE,CA 90509. HENRY FORD HOSP,DEPT MED,DETROIT,MI 48202. ST MICHAELS HOSP,DEPT MED,NEWARK,NJ. KINGS CTY MED CTR,DEPT MED,BROOKLYN,NY. ST MARYS HOSP,DEPT MED,LONG BEACH,CA. UNIV MED & DENT NEW JERSEY,DEPT MED,NEWARK,NJ 07103. ST LUKES ROOSEVELT HOSP,DEPT MED,NEW YORK,NY. TULANE UNIV,DEPT MED,NEW ORLEANS,LA 70118. CHARITY HOSP,NEW ORLEANS,LA. QUEENS MED CTR,DEPT MED,JAMAICA,NY. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT MED,CHICAGO,IL 60612. BETH ISRAEL MED CTR,DEPT MED,NEW YORK,NY 10003. FLUSHING HOSP & MED CTR,MED CTR,DEPT MED,FLUSHING,NY. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. UNIV CINCINNATI,DEPT MED,CINCINNATI,OH 45221. MONTEFIORE MED CTR,DEPT MED,NEW YORK,NY. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. CASE WESTERN RESERVE UNIV,SCH MED,DEPT MED,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,SCH MED,DEPT MED,CLEVELAND,OH 44106. SUNY BUFFALO,DEPT MED,BUFFALO,NY. PACIFIC PRESBYTERIAN MED CTR,DEPT MED,SAN FRANCISCO,CA 94120. BOSTON UNIV,SCH MED,CTR PULM,BOSTON,MA 02118. MT SINAI MED CTR,DEPT MED,NEW YORK,NY. RP MONTGOMERY, AB (reprint author), SAN FRANCISCO GEN HOSP,DIV PULM & CRIT CARE MED,MED SERV,RM 5K1,1001 POTRERO AVE,SAN FRANCISCO,CA 94110, USA. FU NCRR NIH HHS [RR00046]; NIAID NIH HHS [AI 25868] NR 23 TC 20 Z9 21 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 APR PY 1995 VL 151 IS 4 BP 1068 EP 1074 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA QQ888 UT WOS:A1995QQ88800024 PM 7697233 ER PT J AU SOTOARAPE, I BURTON, MD KAZEMI, H AF SOTOARAPE, I BURTON, MD KAZEMI, H TI CENTRAL AMINO-ACID NEUROTRANSMITTERS AND THE HYPOXIC VENTILATORY RESPONSE SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID GAMMA-AMINOBUTYRIC-ACID; SUSTAINED HYPOXIA; VENTRAL SURFACE; GLUTAMIC-ACID; BRAIN; MEDULLA; CAT; DEPRESSION; RECEPTORS; DOGS AB Acute sustained hypoxia causes an early rise in ventilation, followed by a reduction in ventilation (''roll off'') after several minutes to levels below the peak but above baseline. The underlying mechanism(s) of this biphasic response is unclear. Hypoxia induces changes in the release and metabolic turnover of glutamate and gamma aminobutyric acid (GABA). These endogenous neuroactive agents may play a role in mediating the biphasic hypoxic ventilatory response. Therefore, their role was studied in anesthetized (isoflurane), isocapnic, mechanically ventilated rats. Hypoxia alone (FIO2 = 0.1) produced the characteristic biphasic response in the phrenic neurogram (n = 6). When the glutamate receptor was blocked with application of two different N-methyl-D-aspartate (NMDA) antagonists, MK-801 or AP-5, to the ventrolateral medullary surface (VMS), the phrenic output fell by 90% during normoxia and demonstrated no response to hypoxia (n = 6 for each group). There was a rise of 60% in phrenic nerve output during normoxia when GABA antagonist bicuculline was applied to the VMS, and with hypoxia it rose another 15%, and no fall off was seen during hypoxia (n = 6). These findings suggest that during hypoxia the initial hyperventilation has a glutamatergic component and the subsequent fall off is mediated by GABAergic mechanisms. C1 MASSACHUSETTS GEN HOSP,DEPT MED,PULM & CRIT CARE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NHLBI NIH HHS [5 RO1 HL43819-03] NR 35 TC 61 Z9 64 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 APR PY 1995 VL 151 IS 4 BP 1113 EP 1120 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA QQ888 UT WOS:A1995QQ88800031 PM 7697240 ER PT J AU LEWANDROWSKI, K LEE, J SOUTHERN, J CENTENO, B WARSHAW, A AF LEWANDROWSKI, K LEE, J SOUTHERN, J CENTENO, B WARSHAW, A TI CYST FLUID ANALYSIS IN THE DIFFERENTIAL-DIAGNOSIS OF PANCREATIC CYSTS - A NEW APPROACH TO THE PREOPERATIVE ASSESSMENT OF PANCREATIC CYSTIC LESIONS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CARCINOEMBRYONIC ANTIGEN; CYSTADENOCARCINOMA; CYSTADENOMAS; PSEUDOCYSTS; NEOPLASMS; TUMORS AB Pancreatic cysts include pseudocysts, serous tumors, and mucinous tumors, some of which are malignant. The clinical and radiologic features of these lesions may not permit a preoperative diagnosis. Analysis of percutaneous cyst fluid aspirates for cytologic findings, tumor markers, enzymes, and viscosity has been proposed as an aid to differential diagnosis. The combination of cytologic findings, carcinoembryonic antigen level, and viscosity will usually differentiate mucinous from nonmucinous cysts, whereas cytologic findings and levels of tumor markers CA 15-3 and CA 72-4 are useful to predict malignancy. Pseudocysts can be identified by a combination of cytologic features; levels of tumor markers, including NB/70K; and levels of enzymes, including amylase isoenzymes and leukocyte esterase. Serous tumors are a diagnosis of exclusion, although in 50% of cases the cytologic findings will indicate a serous tumor. When compared with conventional methods of differentiating pancreatic cysts, cyst fluid analysis is a promising new approach to the evaluation of these diagnostically difficult lesions. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. RP LEWANDROWSKI, K (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,GRAY 5,BOSTON,MA 02114, USA. NR 15 TC 67 Z9 71 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 APR PY 1995 VL 164 IS 4 BP 815 EP 819 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QN207 UT WOS:A1995QN20700004 PM 7537015 ER PT J AU HESS, D BURNS, E ROMAGNOLI, D KACMAREK, RM AF HESS, D BURNS, E ROMAGNOLI, D KACMAREK, RM TI WEEKLY VENTILATOR CIRCUIT CHANGES - A STRATEGY TO REDUCE COSTS WITHOUT AFFECTING PNEUMONIA RATES SO ANESTHESIOLOGY LA English DT Article DE COMPLICATIONS, VENTILATOR-ASSOCIATED PNEUMONIA; ECONOMICS, HEALTH CARE COSTS; LUNG(S), MECHANICAL VENTILATION, RESPIRATORY THERAPY ID CONTINUOUS MECHANICAL VENTILATION; NOSOCOMIAL PNEUMONIA; GASTRIC COLONIZATION; MOISTURE EXCHANGERS; INFECTION; PATIENT; HEAT AB Background: Mechanical ventilator circuits are commonly changed at 48-h intervals. This frequency may be unnecessary because ventilator-associated pneumonia often results from aspiration of pharyngeal secretions and not from the ventilator circuit, We compared the ventilator-associated pneumonia rates and costs associated with 48-h and 7-day circuit changes. Methods: Ventilator circuits were changed at 48-h intervals during the control period (November 1992 to April 1993) and at 7-day intervals during the study period (June 1993 to November 1993). Nosocomial pneumonias were prospectively identified using the criteria of the Centers for Disease Control and Prevention, The annual cost difference of changing circuits at 48-h and 7-day intervals was calculated using the distribution of ventilator days for the control and study periods. Results: There were 1,708 patients, 9,858 ventilator days, and a pneumonia rate of 9.64 per 1,000 ventilator days in the control group (48-h circuit changes), There were 1,715 patients, 9,160 ventilator days, and 8.62 pneumonias per 1,000 ventilator days when circuits were changed at 1-week intervals (study group), Using a logistic regression model, there were significantly greater odds of developing a ventilator-associated pneumonia in surgical patients (odds ratio 1.77, P = 0.02) and patients in critical care units (odds ratio 1.54, P = 0.05), but no significant risk of ventilator-associated pneumonia in patients in whom circuits were changed at 1-week intervals (odds ratio 0.82, P = 0.22). Changing circuits at 7-day intervals resulted in a 76.6% ($111,530) reduction in the annual cost for materials and salaries. Conclusions: We found no difference in pneumonia rates with ventilator circuit changes at 48-h and 7-day intervals. Ventilator circuits can be safely changed at weekly intervals, resulting in large cost savings. C1 MASSACHUSETTS GEN HOSP,DEPT RESP CARE,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA. NR 30 TC 54 Z9 58 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 1995 VL 82 IS 4 BP 903 EP 911 DI 10.1097/00000542-199504000-00013 PG 9 WC Anesthesiology SC Anesthesiology GA QR223 UT WOS:A1995QR22300014 PM 7717562 ER PT J AU SICKLES, EA KOPANS, DB AF SICKLES, EA KOPANS, DB TI MAMMOGRAPHIC SCREENING FOR WOMEN AGED 40 TO 49 YEARS - THE PRIMARY-CARE PRACTITIONERS DILEMMA SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID NONPALPABLE BREAST-LESIONS; PROBABLY BENIGN LESIONS; FOLLOW-UP; CANCER; BIOPSY; MORTALITY; APPRAISAL; CARCINOMA; PROGRAM; TRIALS AB The data from population-based, randomized trials of the mammographic screening of women aged 40 to 49 years are limited by retrospective subgroup analysis, low statistical power, and the use of older mammographic techniques. Nonetheless, meta-analysis involving the most recently reported data from all similarly designed trials shows a 21% mortality reduction in women who have had mammographic screening compared with those in control groups, a statistically significant difference (upper bound of 95% CI, 0.98). Evidence from modern mammography demonstration projects (which are limited by a lack of control groups and the unavailability of mortality results) also shows that the tumor size, axillary lymph node status, and stage of screening-detected breast cancers in women aged 40 to 49 years indicate that screening is at least as beneficial for these women as it is for those aged 50 to 64 years, for whom mammographic screening is widely accepted. Overall, the evidence suggests that screening will benefit women aged 40 to 49 years, but some argue that the level of proof provided is not rigorous enough to establish the efficacy of screening. In the United States, more than 10 000 deaths per year occur among women who develop breast cancer between the ages of 40 and 49. Thousands of lives are probably lost each year because women are not being screened. We believe that it is much more prudent to endorse mammographic screening now, risking the unlikely subsequent determination that the effort was ineffective, than to withhold screening until it is determined whether ''proof'' of efficacy will be obtained, risking the loss of so many lives. We urge primary care practitioners to recommend routine mammography for women aged 40 to 49 years. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP SICKLES, EA (reprint author), UNIV CALIF SAN FRANCISCO,SCH MED,DEPT RADIOL,BOX 0628,SAN FRANCISCO,CA 94143, USA. NR 59 TC 34 Z9 34 U1 2 U2 2 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 APR 1 PY 1995 VL 122 IS 7 BP 534 EP 538 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA QP008 UT WOS:A1995QP00800010 PM 7872590 ER PT J AU NITSCH, RM REBECK, GW DENG, MH RICHARDSON, UI TENNIS, M SCHENK, DB VIGOPELFREY, C LIEBERBURG, I WURTMAN, RJ HYMAN, BT GROWDON, JH AF NITSCH, RM REBECK, GW DENG, MH RICHARDSON, UI TENNIS, M SCHENK, DB VIGOPELFREY, C LIEBERBURG, I WURTMAN, RJ HYMAN, BT GROWDON, JH TI CEREBROSPINAL-FLUID LEVELS OF AMYLOID BETA-PROTEIN IN ALZHEIMERS-DISEASE - INVERSE CORRELATION WITH SEVERITY OF DEMENTIA AND EFFECT OF APOLIPOPROTEIN-E GENOTYPE SO ANNALS OF NEUROLOGY LA English DT Article ID PRECURSOR DERIVATIVES; SOLUBLE DERIVATIVES; SENILE PLAQUES; PEPTIDE; DEPOSITION; ACTIVATION; RELEASE; CELLS AB Alzheimer's disease (AD) is characterized by formation in brain of neurofibrillary tangles and of amyloid deposits. The major protein component of the former is tau, while the latter are composed of amyloid beta-peptides (A beta), which are derived by proteolytic cleavage of the amyloid beta-protein precursor (APP). Both tau and various secretory APP derivatives including A beta and APP(S) are present in human cerebrospinal fluid (CSF). To investigate whether clinical signs of AD are paralleled by changes in CSF levels of these proteins, we correlated quantitative measures of dementia severity with CSF concentrations of A beta, of APP(S), and of tau. We found that levels of A beta in CSF of AD patients were inversely correlated both to cognitive and to functional measures of dementia severity. In contrast, levels of APP(S) and of tau did not correlate with dementia severity. Apolipoprotein E (apoE) genotype did not influence CSF levels of A beta, APP(S), or tau, which were similar among AD patients with Apo E epsilon 3/3, epsilon 3/4, and epsilon 4/4 alleles. These data indicate that CSF levels of A beta decrease with advancing severity of dementia in AD and suggest that they are independent of a patient's Apo E genotype. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. ATHENA NEUROSCI INC,S SAN FRANCISCO,CA. MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. FU NCRR NIH HHS [RR-01066]; NIA NIH HHS [2P50 AG-01534]; NIMH NIH HHS [NIMH 28783] NR 33 TC 98 Z9 100 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 1995 VL 37 IS 4 BP 512 EP 518 DI 10.1002/ana.410370414 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RD290 UT WOS:A1995RD29000013 PM 7717688 ER PT J AU SEECK, M SCHOMER, D MAINWARING, N IVES, J DUBUISSON, D BLUME, H COSGROVE, R RANSIL, BJ MESULAM, MM AF SEECK, M SCHOMER, D MAINWARING, N IVES, J DUBUISSON, D BLUME, H COSGROVE, R RANSIL, BJ MESULAM, MM TI SELECTIVELY DISTRIBUTED-PROCESSING OF VISUAL OBJECT RECOGNITION IN THE TEMPORAL AND FRONTAL LOBES OF THE HUMAN BRAIN SO ANNALS OF NEUROLOGY LA English DT Article ID NEURONS; MEMORY; CORTEX; FACES; DISSOCIATION; AMYGDALA AB Evoked potentials to visually driven cognitive tasks were recorded through depth electrodes placed bilaterally within the amygdala, hippocampus, midtemporal and inferotemporal cortex, and lateral frontal cortex of 6 epileptic patients. Task-related differential response patterns were used to identify the recording sites engaged by specific aspects of visual encoding, In this group of 6 patients, the amygdala was most frequently engaged in encoding the familiarity of faces; midtemporal and inferotemporal cortex, in encoding perceptual identity and object categorization; and lateral frontal cortex, in holding visual object information in working memory. The two aspects of encoding that most frequently engaged the hippocampal region were related to working memory and object categorization. The processing of complex visual knowledge is thus anatomically distributed but regionally specialized. These experiments also showed that identical input and output parameters can engage different areas of the brain depending on the nature of the instructional set. C1 NORTHWESTERN UNIV,SCH MED,CTR BEHAV & COGNIT NEUROL,CHICAGO,IL 60611. NORTHWESTERN UNIV,SCH MED,DEPT NEUROL,ALZHEIMER PROGRAM,CHICAGO,IL 60611. NORTHWESTERN UNIV,SCH MED,DEPT PSYCHIAT,CHICAGO,IL 60611. UNIV MUNICH,DEPT NEUROL,MUNICH,GERMANY. BETH ISRAEL HOSP,DEPT NEUROL,BOSTON,MA. BETH ISRAEL HOSP,DEPT SURG,DIV NEUROSURG,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,BOSTON,MA. NR 22 TC 38 Z9 40 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 1995 VL 37 IS 4 BP 538 EP 545 DI 10.1002/ana.410370417 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RD290 UT WOS:A1995RD29000016 PM 7717691 ER PT J AU WEIZER, G MALONE, RS NETSCHER, DT WALKER, LE THORNBY, J AF WEIZER, G MALONE, RS NETSCHER, DT WALKER, LE THORNBY, J TI UTILITY OF MAGNETIC-RESONANCE-IMAGING AND ULTRASONOGRAPHY IN DIAGNOSING BREAST IMPLANT RUPTURE SO ANNALS OF PLASTIC SURGERY LA English DT Article ID COMPLICATIONS; MAMMOGRAPHY; US AB We prospectively evaluated 81 patients (with 160 implants) who subsequently had implants removed to determine sensitivity and specificity of both magnetic resonance imaging and ultrasonography. Positive and negative predictive values were also calculated to determine whether a statistically beneficial interaction existed when ultrasonography and magnetic resonance imaging were used in combination to examine an implant. Finally, the misdiagnoses were retrospectively evaluated to identify the pitfalls of the investigations. Positive diagnostic criteria were described. The sensitivity and specificity of ultrasonography were 47% and 83%, respectively, and of MRI, 46% and 88%, respectively. On retrospective review by the radiologist, the sensitivity and specificity of ultrasonography were 70% and 90%, respectively, and of magnetic resonance imaging, 75.6% and 94%, respectively. Although definite conclusions could not be obtained, there did not seem to be an additive benefit from using both ultrasonography and magnetic resonance imaging. C1 BAYLOR COLL MED,DIV DIAGNOST RADIOL,HOUSTON,TX 77030. BAYLOR COLL MED,DIV PLAST SURG,HOUSTON,TX 77030. DEPT VET AFFAIRS MED CTR,HOUSTON,TX. NR 10 TC 17 Z9 18 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD APR PY 1995 VL 34 IS 4 BP 352 EP 361 DI 10.1097/00000637-199504000-00003 PG 10 WC Surgery SC Surgery GA QT734 UT WOS:A1995QT73400003 PM 7793779 ER PT J AU MITHOFER, K FERNANDEZDELCASTILLO, C FRICK, TW FOITZIK, T BASSI, DG LEWANDROWSKI, KB RATTNER, DW WARSHAW, AL AF MITHOFER, K FERNANDEZDELCASTILLO, C FRICK, TW FOITZIK, T BASSI, DG LEWANDROWSKI, KB RATTNER, DW WARSHAW, AL TI INCREASED INTRAPANCREATIC TRYPSINOGEN ACTIVATION IN ISCHEMIA-INDUCED EXPERIMENTAL PANCREATITIS SO ANNALS OF SURGERY LA English DT Article ID CARDIOPULMONARY BYPASS; HEMORRHAGIC-SHOCK; INJURY; PEPTIDES; RAT; MICROCIRCULATION; PATHOGENESIS; REPERFUSION; MECHANISMS; ALLOGRAFTS AB Objective The potential of pancreatic ischemia to cause acute pancreatitis as indicated by morphologic changes and ectopic trypsinogen activation was investigated. Background Experimental evidence has shown that pancreatic ischemia is important in the evolution of severe pancreatitis, but whether ischemia can initiate pancreatitis has been disputed. Methods Pancreatic ischemia was induced in rats by hemorrhagic hypotension (30 mm Hg for 30 min; n = 64). Changes of pancreatic microcirculatory perfusion were studied using diffuse reflectance spectroscopy. Serum amylase, trypsinogen activation peptide (TAP) in serum and pancreatic tissue, wet/dry weight ratio, and histology were determined over 24 hours and compared with sham-operated control subjects (n = 35). Results In control animals, serum amylase (47.9 +/- 2.1 units/L), serum (7.9 +/- 0.7 nmol/L) and tissue TAP (63.0 +/- 5.4 nmol/L X g), wet/dry weight ratio (2.8 +/- 0.1), and histology remained unchanged. Temporary hypotension markedly decreased pancreatic perfusion with incomplete recovery after reperfusion. Pancreatic isoamylase activity increased within 1 hour (110 +/- 5 units/L, p < 0.05) and further to 151 +/- 18 units/L at 24 hours. Tissue TAP was elevated at 1 hour(134 +/- 16 nmol/L X g, p < 0.05)and increased to 341 +/- 43 nmol/L X g (p < 0.001) after 24 hours, whereas serum TAP remained unchanged (8.3 +/- 0.5 nmol/L). Morphologic alterations included elevated wet/dry weight ratio (4.1 +/- 0.3, p < 0.01) and increased histologic scores for edema (p < 0.05) and acinar necrosis (p < 0.05) at 24 hours. Trypsinogen activation preceded the development of pancreatic necrosis. Conclusions In addition to its potentiating role, severe pancreatic ischemia can play a pathogenetic role in the initiation of acute pancreatitis. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 45 TC 47 Z9 49 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD APR PY 1995 VL 221 IS 4 BP 364 EP 371 DI 10.1097/00000658-199504000-00006 PG 8 WC Surgery SC Surgery GA QR531 UT WOS:A1995QR53100006 PM 7537036 ER PT J AU BEALL, AC LAFUENTE, JA JONES, JW AF BEALL, AC LAFUENTE, JA JONES, JW TI WEDGE RESECTION OF LUNG WITHOUT STAPLES ON SPECIMEN SO ANNALS OF THORACIC SURGERY LA English DT Note AB A technique for wedge resection of the lung using a linear cutter stapler without staples on the specimen is presented. C1 BAYLOR COLL MED,CORA WEBB DEPT SURG,HOUSTON,TX 77030. RP BEALL, AC (reprint author), HOUSTON VET AFFAIRS MED CTR,SURG SERV 112,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 1995 VL 59 IS 4 BP 1026 EP 1026 DI 10.1016/0003-4975(94)00018-3 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA QP487 UT WOS:A1995QP48700052 PM 7695384 ER PT J AU WEISSLEDER, R POSS, K WILKINSON, R ZHOU, C BOGDANOV, A AF WEISSLEDER, R POSS, K WILKINSON, R ZHOU, C BOGDANOV, A TI QUANTITATION OF SLOW DRUG-RELEASE FROM AN IMPLANTABLE AND DEGRADABLE GENTAMICIN CONJUGATE BY IN-VIVO MAGNETIC-RESONANCE-IMAGING SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MICROSPHERES; DELIVERY; ALBUMIN; ABSCESS AB A biodegradable model hydrogel containing a covalently bound aminoglycoside in which drug release can be monitored by magnetic resonance imaging (MRI) in vivo was developed, The hydrogel consists of the bis-hydroxysuccinimide ester of polyethylene glycol disuccinate cross-linked albumin, to which gentamicin and Gd-diethylenetriaminepentaacetic acid are covalently attached in stochiometric quantities. MRI allowed us to depict the three-dimensional structure of implanted gels, to accurately calculate their volumes, and thus to calculate the concentration of hydrogel-bound gentamicin. The correlation coefficient for the concentration of released gentamicin and the hydrogel volume was 0.965, Free and hydrogel-released gentamicin conjugates had similar antibiotic efficacies when tested in microbiological agar diffusion assays. In vivo, hydrogel-released gentamicin had a longer half-life in plasma than unaltered gentamicin (5.6 versus 0.7 h), presumably because of residual bound polyethylene glycol residues, Hydrogel implants into rats resulted in a prolonged (7 to 10 days) release of gentamicin and a decreased 24-h mortality in mice infected with a lethal dose of Pseudomonas aeruginosa. The results indicate the feasibility of imaging and quantitating therapeutic drug concentrations in vivo by MRI. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP WEISSLEDER, R (reprint author), MASSACHUSETTS GEN HOSP,MR PHARMACEUT PROGRAM,DEPT RADIOL,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NCI NIH HHS [1RO1 CA59649-01] NR 26 TC 16 Z9 16 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 1995 VL 39 IS 4 BP 839 EP 845 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA QQ123 UT WOS:A1995QQ12300008 PM 7785981 ER PT J AU GRAYBILL, JR NAJVAR, LK HOLMBERG, JD LUTHER, MF AF GRAYBILL, JR NAJVAR, LK HOLMBERG, JD LUTHER, MF TI FLUCONAZOLE, D0870, AND FLUCYTOSINE TREATMENT OF DISSEMINATED CANDIDA-TROPICALIS INFECTIONS IN MICE SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article AB D0870 is a recently developed triazole with characteristics of a broad spectrum of activity and slow clearance by nonrenal mechanisms. Herein we have evaluated the efficacy of D0870, alone and combined with flucytosine, in a murine model of disseminated Candida tropicalis infection. Four isolates of C. tropicalis were evaluated. Two were highly susceptible in vitro to fluconazole, and two were resistant to fluconazole. All were highly susceptible to flucytosine and D0870. Animals were pretreated with 5-fluorouracil 1 day before infection because C. tropicalis has reduced virulence in immunocompetent mice. This was done to render them neutropenic for >10 days. Mice were infected intravenously and treated orally with D0870 or fluconazole, alone or combined with flucytosine. Survival and tissue burden of the spleen and kidneys were used to evaluate the efficacy of antifungal therapy. Fluconazole was less effective for treatment of resistant C. tropicalis than susceptible C. tropicalis. D0870 was more potent than fluconazole and was effective in fluconazole-resistant isolates. Flucytosine was consistently effective when used alone but did not consistently add to the benefit of D0870 or fluconazole. D0870 has potential in treatment of candidiasis caused by C. tropicalis, including fluconazole-resistant isolates. RP GRAYBILL, JR (reprint author), UNIV TEXAS,AUDIE L MURPHY MEM VET HOSP,HLTH SCI CTR,DIV INFECT DIS 111F,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 10 TC 29 Z9 29 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 APR PY 1995 VL 39 IS 4 BP 924 EP 929 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA QQ123 UT WOS:A1995QQ12300024 PM 7785997 ER PT J AU PARK, SS DAMICO, DJ PATON, B BAKER, S AF PARK, SS DAMICO, DJ PATON, B BAKER, S TI TREATMENT OF EXOGENOUS CANDIDA ENDOPHTHALMITIS IN RABBITS WITH ORAL FLUCONAZOLE SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMPHOTERICIN-B; CRYPTOCOCCAL MENINGITIS; FUNGAL ENDOPHTHALMITIS; FLUCYTOSINE; THERAPY; AIDS; PENETRATION; MANAGEMENT; ALBICANS; EFFICACY AB We investigated the efficacy of oral fluconazole, alone or in combination with oral flucytosine (5FC), in treating Candida endophthalmitis using a rabbit model. Albino rabbits were infected with an intravitreal inoculation of 1,000 CFU of susceptible Candida albicans and randomized 5 days later to receive treatment with oral fluconazole alone (80 mg/kg of body weight per day), a combination of fluconazole and 5FC (100 mg/kg/12 h), or no treatment. The treatment effect was assessed at 2 and 4 weeks after therapy by funduscopy, quantitative vitreous culture, and histopathology. Intravitreal levels of fluconazole, 2 to 24 h after the first dose, were measured to be >10 the MIC of the drug for C. albicans. Among rabbits treated with fluconazole for 2 weeks, 67% had a >90% reduction in fungal load (P < 0.05) and 75% were sterile (P = 0.01). This treatment effect was unchanged 4 weeks after discontinuation of fluconazole. Among rabbits treated with fluconazole and 5FC for 2 weeks, 67% died during therapy. Among the surviving rabbits, 75% had a >90% reduction in fungal load (P < 0.05) and 25% were sterile. We conclude that oral fluconazole may be useful for treatment of Candida endophthalmitis. Addition of 5FC was associated with high toxicity and minimal additional antifungal effect in our rabbit model. C1 MASSACHUSETTS EYE & EAR INFIRM,INFECT DIS SERV,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,PORTER MICROBIOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. NR 43 TC 17 Z9 19 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 APR PY 1995 VL 39 IS 4 BP 958 EP 963 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA QQ123 UT WOS:A1995QQ12300030 PM 7786003 ER PT J AU HYMAN, BT WEST, HL REBECK, GW LAI, F MANN, DMA AF HYMAN, BT WEST, HL REBECK, GW LAI, F MANN, DMA TI NEUROPATHOLOGICAL CHANGES IN DOWNS-SYNDROME HIPPOCAMPAL-FORMATION - EFFECT OF AGE AND APOLIPOPROTEIN-E GENOTYPE SO ARCHIVES OF NEUROLOGY LA English DT Article ID SPORADIC ALZHEIMERS-DISEASE; AMYLOID-BETA-PEPTIDE; PATHOLOGICAL-CHANGES; NEUROFIBRILLARY TANGLES; SENILE PLAQUES; TYPE-4 ALLELE; DEMENTIA; PROTEIN; BINDING; IMMUNOREACTIVITY AB Background: The neuropathological changes of Alzheimer's disease occur universally in individuals with Down's syndrome as they reach middle age and worsen with increasing age. Thus, evaluation of patients of various ages with Down's syndrome allows one to construct a life history of the development of neuropathological changes associated with Alzheimer's disease at various points in the disease process. Methods: We have used semiquantitative scales and quantitative computerized image analysis techniques to analyze the characteristics of neurofibrillary tangle formation and A beta amyloid deposition in the hippocampal formation and inferior temporal gyrus in 36 individuals with Down's syndrome ranging in age from 4 to 73 years. Results: Neurofibrillary tangles occur in a hierarchical distribution in a circumscribed set of neuronal fields, affecting the entorhinal cortex, area CAl/subiculum, then other hippocampal subfields. Although amyloid deposition occurs more evenly in a more widespread distribution, it also accumulates over the years 30 to 50. Surprisingly, examination of the patients available older than 50 years showed no trend toward continued increased deposition of amyloid. Within this group, however, individuals who had inherited the apolipoprotein E (Ape E) epsilon 4 genotype contained more than twice the amyloid burden of individuals who did not inherit the Apo E epsilon 4 genotype. Comment: This large series of cases confirms earlier observations that had suggested early vulnerability of entorhinal cortex and CAl/subiculum for neurofibrillary tangles and a more widespread but specific topography of AP deposition. Moreover, it demonstrates quantitatively that the lesions increase to a certain level and then apparently reach a plateau. The level of amyloid deposition in Down's syndrome is higher than in sporadic Alzheimer's disease. Inheritance of the Apo E epsilon 4 genotype appears to be an additional (independent) risk factor for developing higher levels of amyloid accumulation. C1 EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,WALTHAM,MA. UNIV MANCHESTER,DEPT PATHOL SCI,MANCHESTER M13 9PL,LANCS,ENGLAND. RP HYMAN, BT (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,FRUIT ST,BOSTON,MA 02114, USA. FU NIA NIH HHS [AG08487] NR 37 TC 96 Z9 97 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 1995 VL 52 IS 4 BP 373 EP 378 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA QR986 UT WOS:A1995QR98600012 PM 7710373 ER PT J AU FOITZIK, T FERNANDEZDELCASTILLO, C RATTNER, DW KLAR, E WARSHAW, AL AF FOITZIK, T FERNANDEZDELCASTILLO, C RATTNER, DW KLAR, E WARSHAW, AL TI ALCOHOL SELECTIVELY IMPAIRS OXYGENATION OF THE PANCREAS SO ARCHIVES OF SURGERY LA English DT Article ID BLOOD-FLOW; REFLECTANCE SPECTROPHOTOMETRY; INTRINSIC REGULATION; ETHANOL; HEMODYNAMICS; CONSUMPTION; CIRCULATION; PERFUSION; DOGS AB Background: Alcohol predisposes to acute pancreatitis by an unknown mechanism and is known to reduce regional pancreatic blood flow. Objective: To investigate whether increased blood alcohol causes functional impairment of pancreatic microperfusion as indicated by reduced tissue oxygenation. Design: Prospective, randomized, controlled study. Setting: University hospital laboratory. Subjects: Forty adult female Wistar rats. Interventions: Intravenous infusion of ethanol (2 g/kg) or saline over 60 minutes. Tissue hemoglobin oxygenation saturation and hemoglobin content were measured using reflectance spectroscopy in the pancreas, stomach, and kidney at baseline and at 10-minute intervals for 1 hour. Results: Blood ethanol levels (mean+/-SEM) peaked at 1810+/-94 mg/L. Compared with saline controls, pancreatic hemoglobin oxygen saturation in ethanol-treated rats had significantly decreased by 40 minutes and remained depressed, while pancreatic hemoglobin content was unchanged. The magnitude of the depression was at least as great as that previously observed in acute experimental pancreatitis of moderate severity. Neither hemoglobin oxygen saturation nor hemoglobin content was affected in the stomach or kidney by ethanol. Conclusion: A raised blood ethanol level was associated with acutely decreased hemoglobin oxygen saturation in the pancreas but not in the stomach or kidney. This observation of provoked hypoxia provides a possible mechanism by which alcohol contributes to pancreatic injury. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV HEIDELBERG,DEPT SURG,W-6900 HEIDELBERG,GERMANY. NR 28 TC 23 Z9 23 U1 0 U2 1 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 APR PY 1995 VL 130 IS 4 BP 357 EP 361 PG 5 WC Surgery SC Surgery GA QR402 UT WOS:A1995QR40200001 PM 7710332 ER PT J AU JOHNSON, EM BERK, DA JAIN, RK DEEN, WM AF JOHNSON, EM BERK, DA JAIN, RK DEEN, WM TI DIFFUSION AND PARTITIONING OF PROTEINS IN CHARGED AGAROSE GELS SO BIOPHYSICAL JOURNAL LA English DT Article ID SPATIAL FOURIER-ANALYSIS; LOW IONIC-STRENGTH; COEFFICIENT MEASUREMENTS; POLY-ELECTROLYTES; PROBE DIFFUSION; MEMBRANES; CHROMATOGRAPHY; FRACTIONATION; OPTIMIZATION; SEPARATION AB The effects of electrostatic interactions on the diffusion and equilibrium partitioning of fluorescein-labeled proteins in charged gels were examined using fluorescence recovery after photobleaching and gel chromatography, respectively. Measurements were made with BSA, ovalbumin, and lactalbumin in SP-Sepharose (6% sulfated agarose), in phosphate buffers at pH 7 and ionic strengths ranging from 0.01 to 1.0 M. Diffusivities in individual gel beads (D) and in the adjacent bulk solution (D-infinity) were determined from the spatial Fourier transform of the digitized two-dimensional fluorescence recovery images. Equilibrium partition coefficients (Phi) were measured by recirculating protein solutions through a gel chromatography column until equilibrium was reached, and using a mass balance. Diffusion in the gel beads was hindered noticeably, with D/D-infinity = 0.4-0.5 in each case. There were no effects of ionic strength on BSA diffusivities, but with the smaller proteins (ovalbumin and lactalbumin) D-infinity increased slightly and D decreased at the lowest ionic strength. in contrast to the modest changes in diffusivity, there were marked effects of ionic strength on the partition coefficients of these proteins. We conclude that for diffusion of globular proteins through gel membranes of like charge, electrostatic effects on the effective diffusivity (D-eff = Phi D) are likely to result primarily from variations in Phi with only small contributions from the intramembrane diffusivity. C1 MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Berk, David/A-4863-2012 OI Berk, David/0000-0002-3855-6886 FU NCI NIH HHS [R35-CA-J6591]; NIDDK NIH HHS [DK20368] NR 43 TC 143 Z9 144 U1 3 U2 20 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 1995 VL 68 IS 4 BP 1561 EP 1568 PG 8 WC Biophysics SC Biophysics GA RD163 UT WOS:A1995RD16300033 PM 7787041 ER PT J AU HIRAYAMA, F LYMAN, SD CLARK, SC OGAWA, M AF HIRAYAMA, F LYMAN, SD CLARK, SC OGAWA, M TI THE FLT3 LIGAND SUPPORTS PROLIFERATION OF LYMPHOHEMATOPOIETIC PROGENITORS AND EARLY B-LYMPHOID PROGENITORS SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; TYROSINE KINASE RECEPTOR; STEM-CELL FACTOR; MULTIPOTENTIAL HEMATOPOIETIC PROGENITORS; C-KIT; GROWTH-FACTOR; INTERLEUKIN-3-DEPENDENT PROLIFERATION; DIFFERENTIATION ANTIGENS; SYNERGISTIC INTERACTIONS; MURINE HEMATOPOIESIS AB We have examined the effects of the murine ligand (FL) for the flt3/flk2 tyrosine kinase receptor on the proliferation of murine lymphohematopoietic progenitors as well as committed myeloid and B-cell progenitors. In the presence of erythropoietin, FL alone supported scant colony formation from enriched marrow cells of normal mice. However, when it was combined with interleukin-3 (IL-3), steel factor (SF), or IL-11, FL significantly enhanced colony formation. When tested on enriched marrow cells from 5-fluorouracil (5-FU)-treated mice, FL neither enhanced IL-3-dependent colony formation nor synergized with SF in support of colony formation. However, FL synergized with IL-6, IL-11, or granulocyte-colony stimulating factor (G-CSF) in support of formation of various types of colonies, including multilineage colonies. Approximately 30% of these colonies yielded pre-B-cell colonies when replated in secondary cultures containing SF and IL-7, indicating that 2-cytokine combinations, including FL and IL-6, IL-11, or G-CSF can support the proliferation of primitive lymphohematopoietic progenitors. FL, by itself and in synergy with IL-7 or SF, supported the proliferation of B-cell progenitors. These results show that FL has a wide range of activities in early hematopoiesis and B lymphopoiesis. (C) 1995 by The American Society of Hematology. C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. GENET INST INC,CAMBRIDGE,MA. IMMUNEX CORP,SEATTLE,WA. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29401. FU NIDDK NIH HHS [DK 32294] NR 53 TC 147 Z9 147 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 APR 1 PY 1995 VL 85 IS 7 BP 1762 EP 1768 PG 7 WC Hematology SC Hematology GA QP613 UT WOS:A1995QP61300010 PM 7703483 ER PT J AU INHORN, RC ASTER, JC ROACH, SA SLAPAK, CA SOIFFER, R TANTRAVAHI, R STONE, RM AF INHORN, RC ASTER, JC ROACH, SA SLAPAK, CA SOIFFER, R TANTRAVAHI, R STONE, RM TI A SYNDROME OF LYMPHOBLASTIC LYMPHOMA, EOSINOPHILIA, AND MYELOID HYPERPLASIA MALIGNANCY ASSOCIATED WITH T(8-13) (P11-Q11) - DESCRIPTION OF A DISTINCTIVE CLINICOPATHOLOGICAL ENTITY SO BLOOD LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOBLASTIC-LEUKEMIA; TRANSLOCATION; GENE; EXPRESSION AB We report two patients with a distinctive biphenotypic hematologic disorder characterized by lymphoblastic lymphoma (LBL), eosinophilia, and myeloid malignancy and/or hyperplasia associated with a t(8;13)(p11;q11) chromosomal translocation in both bone marrow and lymph node specimens. Both patients presented with lymphadenopathy pathologically classified as LBL with a T-cell immunophenotype, myeloid hyperplasia of the bone marrow, and peripheral blood eosinophilia. The first patient achieved clinical complete remission after receiving several regimens of chemotherapy and remains disease-free 16 months after undergoing allogeneic bone marrow transplantation. The second patient developed progressive lymphadenopathy despite several courses of chemotherapy directed against non-Hodgkin's lymphoma. Eight months after his initial presentation, he developed acute myelogenous leukemia that was refractory to therapy. Comparison of these patients with four similar cases recently reported in the literature suggests that this constellation of findings constitutes a distinctive clinicopathologic syndrome. Molecular analysis of the t(8;13) translocation breakpoint may identify genes located in this region and provide insight into the pathogenesis of this interesting biphenotypic hematologic malignancy. (C) 1995 by The American Society of Hematology. C1 DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 27 TC 112 Z9 114 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 APR 1 PY 1995 VL 85 IS 7 BP 1881 EP 1887 PG 7 WC Hematology SC Hematology GA QP613 UT WOS:A1995QP61300025 PM 7661940 ER PT J AU URASHIMA, M CHAUHAN, D UCHIYAMA, H FREEMAN, GJ ANDERSON, KC AF URASHIMA, M CHAUHAN, D UCHIYAMA, H FREEMAN, GJ ANDERSON, KC TI CD40 LIGAND TRIGGERED INTERLEUKIN-6 SECRETION IN MULTIPLE-MYELOMA SO BLOOD LA English DT Article ID B-CELL DIFFERENTIATION; MARROW STROMAL CELLS; HUMAN-BONE-MARROW; ADHESION MOLECULES; AUTOCRINE GROWTH; GENE-EXPRESSION; LYMPHOMA-CELLS; SERUM LEVELS; LINES; LEUKEMIA AB Previous studies have suggested that interleukin-6 (IL-6) may mediate growth of multiple myeloma (MM) in either an autocrine or paracrine growth mechanism. However, those molecules which can trigger IL-6 secretion either by tumor cells or non-MM marrow cells are not well characterized. In the present study, we have examined the expression and functional significance of CD40 on MM and plasma cell leukemia (PCL) cells and derived cell lines, as well as long-term bone marrow stromal cells (BMSCs) and derived cell lines. CD40 was expressed on the majority of MM cells (>90%) and BMSCs (>70%). Triggering via CD40 using NIH3T3 CD40 ligand transfectant (CD40LT) cells increased (>30%) cell surface CD80, CD18, CD11a, CD11b, and CD11c expression on MM cell lines. Culture with either fresh or paraformaldehyde fixed NIH3T3 CD40LT cells upregulates IL-6 secretion in MM cells and MM-derived cell lines, as well as normal and MM bone marrow mononuclear cells (BMMCs), BMSCs, and BMSC lines; this effect can be specifically blocked by anti-CD40 monoclonal antibody (MoAb). BMMCs and BMSCs from patients with MM secreted significantly more IL-6 than those from healthy donors (n = 3, P < .001); moreover, after stimulation using CD40L, IL-6 secretion was fourfold greater (n = 3, P < .001) from MM BMMCs and BMSCs than from normal BMMCs and BMSCs. Myeloma (CD38(+)CD45RA(-)) cells and non-MM (CD38(+)CD45RA(+), CD38(-)CD45RA(+), and CD38(-)CD45RA(-)) BMMCs were separated by dual fluorescence cell sorting. The latter secreted fourfold more IL-6 than the former (n = 2, P < .001). Increased IL-6 secretion (up to 28-fold) and proliferation (Stimulation Index 10) by CD38(+)CD45RA(-)MM cells was triggered by culture with NIH3T3 CD40LT cells. Finally, anti-CD40 MoAb partially (30%) blocked tumor cell to BMSC adhesion-induced IL-6 secretion. These studies support the view that CD40L may trigger IL-6 secretion by both MM cells and BMSCs and that IL-6-mediated autocrine and paracrine growth mechanisms may be possible in MM. (C) 1995 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. FU NCI NIH HHS [CA 50947] NR 49 TC 134 Z9 136 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 APR 1 PY 1995 VL 85 IS 7 BP 1903 EP 1912 PG 10 WC Hematology SC Hematology GA QP613 UT WOS:A1995QP61300028 PM 7535594 ER PT J AU SPITZER, TR CIRENZA, E MCAFEE, S FOELBER, R ZARZIN, J CAHILL, R MAZUMDER, A AF SPITZER, TR CIRENZA, E MCAFEE, S FOELBER, R ZARZIN, J CAHILL, R MAZUMDER, A TI PHASE I-II TRIAL OF HIGH-DOSE CYCLOPHOSPHAMIDE, CARBOPLATIN AND AUTOLOGOUS BONE-MARROW OR PERIPHERAL-BLOOD STEM-CELL RESCUE SO BONE MARROW TRANSPLANTATION LA English DT Article DE PHASE I-II TRIAL; CYCLOPHOSPHAMIDE; CARBOPLATIN ID METASTATIC MALIGNANT-MELANOMA; ADVANCED BREAST-CANCER; SOLID TUMORS; TRANSPLANTATION; CHEMOTHERAPY; THIOTEPA; THERAPY; SUPPORT; MELPHALAN; CARCINOMA AB In an effort to evaluate the toxicities and anti-tumor efficacy of the combination of high-dose cyclophosphamide (CY) and carboplatin, we undertook a phase I-II trial with autologous bone marrow (BM) or peripheral blood stem cell (PBSC) rescue for patients with solid tumors, Forty three patients, 39 of whom had either high risk stage II or III or metastatic breast cancer were treated with escalating doses of carboplatin 1200-1800 mg/m(2) and cyclophosphamide 4800-6000 mg/m(2) over 3 days followed by autologous BM or PBSC infusion, No life-threatening or fatal toxicities were observed, Reversible congestive heart failure was seen in two patients, Transient hepatotoxicity, characterized primarily by elevation of transaminase levels, and nausea and vomiting, adequately managed with anti-emetic therapy, were seen in 39 and 40 of 43 patients, respectively, The 14 month post-transplant probability of relapse-free survival for 26 patients with high risk II-III breast cancer was 79%; for 13 patients with metastatic disease, the 22 month relapse-free survival probability was 23%. High-dose carboplatin and CY at maximally administered doses of 1800mg/m2 and 6000 mg/m(2) is a well tolerated preparative transplant regimen for autologous BM or PBSC transplantation. It appears to have similar anti-tumor activity and an improved safety profile when compared with other commonly employed transplant preparative regimens. C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. RP SPITZER, TR (reprint author), MASSACHUSETTS GEN HOSP,BONE MARROW TRANSPLANTAT PROGRAM,COX 3,BOSTON,MA 02114, USA. NR 25 TC 25 Z9 25 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 1995 VL 15 IS 4 BP 537 EP 542 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA RB319 UT WOS:A1995RB31900008 PM 7655378 ER PT J AU LOUIS, DN VONDEIMLING, A AF LOUIS, DN VONDEIMLING, A TI HEREDITARY TUMOR SYNDROMES OF THE NERVOUS-SYSTEM - OVERVIEW AND RARE SYNDROMES SO BRAIN PATHOLOGY LA English DT Article ID GORLIN SYNDROME; SUPPRESSOR GENES; RETINOBLASTOMA; MUTATIONS; ASSOCIATION; CANCER; POLYPOSIS; DISEASE AB Hereditary tumor syndromes of the nervous system are a varied group of conditions that include neurofibromatosis 1, neurofibromatosis 2, tuberous sclerosis, and von Hippel-Lindau disease, as well as the retinoblastoma susceptibility, Li-Fraumeni, familial glioma, Turcot, Gorlin, Cowden and multiple endocrine neoplasia syndromes. For many of these conditions, the responsible genes have been localized or identified. Such studies have elucidated the genetic basis of both hereditary cancer predisposition and sporadic nervous system tumors. The first four hereditary tumor syndromes have been extensively studied and are discussed in detail in the four subsequent articles. The other syndromes have also been subject to both pathological and molecular genetic inquiries. In this introductory overview, we discuss the features common to the hereditary tumor syndromes of the nervous system, and review some of the rarer conditions. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,MOLEC NEUROONCOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV BONN,MED CTR,DEPT NEUROPATHOL,D-53105 BONN,GERMANY. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X NR 52 TC 42 Z9 42 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI ZURICH PA ISN JOURNAL PO BOX, CH-8033 ZURICH, SWITZERLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD APR PY 1995 VL 5 IS 2 BP 145 EP 151 DI 10.1111/j.1750-3639.1995.tb00588.x PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA RC531 UT WOS:A1995RC53100003 PM 7670655 ER PT J AU SHORT, MP RICHARDSON, EP HAINES, JL KWIATKOWSKI, DJ AF SHORT, MP RICHARDSON, EP HAINES, JL KWIATKOWSKI, DJ TI CLINICAL, NEUROPATHOLOGICAL AND GENETIC-ASPECTS OF THE TUBEROUS SCLEROSIS COMPLEX SO BRAIN PATHOLOGY LA English DT Article ID DIAGNOSTIC-CRITERIA; LINKAGE; HETEROGENEITY; LOCUS; DISORDERS; AUTISM; CELLS AB Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome in which patients develop hamartomatous lesions in the nervous system and a host of other organs. While considerable experience has been gained in defining the clinical spectrum of TSC, a number of nosological questions remain. Neuropathological studies have continued to refine our knowledge of the nervous system abnormalities that characterize TSC. Molecular genetic studies have implicated two chromosomal regions in the genesis of TSC, one on chromosome 9q and the other on chromosome 16p. The chromosome 16p gene, designated TSC2, has been cloned, although its function remains speculative. The identification of the TSC? gene on chromosome 9q, along with functional studies and mutational analyses of both TSC genes, will likely provide fascinating insights into the pathogenesis of TSC. C1 MASSACHUSETTS GEN HOSP, DEPT NEUROL, MOLEC NEUROGENET UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CS KUBIK LAB NEUROPATHOL, BOSTON, MA 02114 USA. BRIGHAM & WOMENS HOSP, DIV EXPTL MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02129 USA. RI Haines, Jonathan/C-3374-2012 NR 55 TC 35 Z9 35 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 EI 1750-3639 J9 BRAIN PATHOL JI Brain Pathol. PD APR PY 1995 VL 5 IS 2 BP 173 EP 179 DI 10.1111/j.1750-3639.1995.tb00591.x PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA RC531 UT WOS:A1995RC53100006 PM 7670658 ER PT J AU KRAMER, R WEBER, TK ARCECI, R RAMCHURREN, N KASTRINAKIS, WV STEELE, G SUMMERHAYES, IC AF KRAMER, R WEBER, TK ARCECI, R RAMCHURREN, N KASTRINAKIS, WV STEELE, G SUMMERHAYES, IC TI INHIBITION OF N-LINKED GLYCOSYLATION OF P-GLYCOPROTEIN BY TUNICAMYCIN RESULTS IN A REDUCED MULTIDRUG-RESISTANCE PHENOTYPE SO BRITISH JOURNAL OF CANCER LA English DT Article DE P-GLYCOPROTEIN; GLYCOSYLATION; TUNICAMYCIN; MDR PHENOTYPE ID PROTEIN-KINASE; HUMAN MDR1; CARCINOMA-CELLS; KB CELLS; PHOSPHORYLATION; EXPRESSION; MODULATION AB Characterisation of altered glycosylation of P-glycoprotein (P-gp) found associated with the absence of a multidrug resistance (MDR) phenotype in cell lines prompted an investigation to assess the role of post-translational processing in establishing P-gp efflux pump functionality. The clone A cell line used in this study displays a strong MDR phenotype mediated by high constitutive levels of expression of P-gp. Incubation of clone A cells with tunicamycin for different periods resulted in a time-dependent increase in daunorubicin accumulation, reflecting a reduction in P-gp function. Parallel experiments conducted with verapamil resulted in no loss of P-gp functionality in clone A cells. Reduction in surface-associated P-gp following exposure to tunicamycin was established by FAGS analysis, Western blot analysis and immunoprecipitation of surface-iodinated P-gp. In addition, immunoprecipitation of P-gp from P-32-orthophosphate-labelled cells demonstrated reduced phosphorylation of P-gp associated with tunicamycin exposure. From these studies we conclude that glycosylation of P-gp is required to establish the cellular MDR phenotype. C1 NEW ENGLAND DEACONESS HOSP,DEPT SURG,CANC BIOL LAB,BOSTON,MA 02115. AMER CYANAMID CO,DIV MED RES,PEARL RIVER,NY 10965. DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. FU NCI NIH HHS [CA42944, CA44704] NR 20 TC 46 Z9 55 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR PY 1995 VL 71 IS 4 BP 670 EP 675 DI 10.1038/bjc.1995.133 PG 6 WC Oncology SC Oncology GA QQ312 UT WOS:A1995QQ31200004 PM 7710927 ER PT J AU FIDIAS, P CAREY, RW GROSSBARD, ML AF FIDIAS, P CAREY, RW GROSSBARD, ML TI NON-HODGKINS-LYMPHOMA PRESENTING WITH BILIARY-TRACT OBSTRUCTION - A DISCUSSION OF 7 PATIENTS AND A REVIEW OF THE LITERATURE SO CANCER LA English DT Article DE NON-HODGKINS LYMPHOMA; CHOLESTASIS; CHEMOTHERAPY; BILIARY NEOPLASMS ID BILE-DUCT OBSTRUCTION; PANCREATIC LYMPHOMA; JAUNDICE SECONDARY; DIAGNOSIS; CHEMOTHERAPY; INVOLVEMENT; MANAGEMENT; GUIDELINES; CT AB Background. Biliary tract obstruction is a rare manifestation of non-Hodgkin's lymphoma (NHL). Because of the small numbers of patients studied, management of this condition has been inconsistent. Most patients have been treated with biliary diversion, and doxorubicin frequently has been withheld from initial therapy. Methods. Seven patients with NHL presenting with malignant biliary tract obstruction were identified at the Massachusetts General Hospital. Relevant clinical characteristics, laboratory values, treatment, and outcome are reported for ail patients. Thirty-eight additional patients were identified through a MEDLINE search; and the management and results of the patients reported here are discussed with reference to those patients. Results. Biliary tract obstruction was the presenting symptom in 0.8% of the patients with NHL. Bilirubin values at presentation ranged from 5.0-23.2 mg/dl. One patient had localized pancreatic lymphoma. Four of the seven patients had advanced-stage disease. The tumor was intermediate or high grade in five patients. Four patients underwent placement of a biliary stent or drainage catheter, Six patients received combination chemotherapy without doxorubicin in the initial cycle. Hyperbilirubinemia resolved in all patients within 3 months, regardless of use of a stent. Six patients responded to chemotherapy and one patient had progressive disease. Two of the six responders died, one with relapsed lymphoma. Conclusions. NHL presenting with biliary tract obstruction can be effectively treated with chemotherapy, with or without a procedure for biliary diversion. The use of doxorubicin in the presence of hyperbilirubinemia secondary to biliary tract obstruction remains controversial, and its omission from the initial cycles of chemotherapy for NHL may not influence outcome. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP FIDIAS, P (reprint author), MASSACHUSETTS GEN HOSP,HEMATOL ONCOL UNIT,COX 315,BOSTON,MA 02114, USA. NR 29 TC 27 Z9 27 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 APR 1 PY 1995 VL 75 IS 7 BP 1669 EP 1677 DI 10.1002/1097-0142(19950401)75:7<1669::AID-CNCR2820750718>3.0.CO;2-3 PG 9 WC Oncology SC Oncology GA QN813 UT WOS:A1995QN81300017 PM 8826926 ER PT J AU CHER, LM HOCHBERG, FH TERUYA, J NITSCHKE, M VALENZUELA, RF SCHMAHMANN, JD HERBERT, M ROSAS, HD STOWELL, C AF CHER, LM HOCHBERG, FH TERUYA, J NITSCHKE, M VALENZUELA, RF SCHMAHMANN, JD HERBERT, M ROSAS, HD STOWELL, C TI THERAPY FOR PARANEOPLASTIC NEUROLOGIC SYNDROMES IN 6 PATIENTS WITH PROTEIN-A COLUMN IMMUNOADSORPTION SO CANCER LA English DT Article DE PARANEOPLASTIC SYNDROMES; OPSOCLONUS; LIMBIC ENCEPHALITIS; PARANEOPLASTIC CEREBELLAR DEGENERATION; THERAPY; PROTEIN A IMMUNOADSORPTION ID CEREBELLAR DEGENERATION; A-IMMUNOADSORPTION; THROMBOCYTOPENIC PURPURA; OPSOCLONUS-MYOCLONUS; CARCINOMA; CANCER; ENCEPHALOPATHY; PLASMAPHERESIS; PATHOGENESIS; ANTIBODIES AB Background. Paraneoplastic neurologic syndromes, although rare, cause significant morbidity and mortality. They are thought to be immunologically mediated, but to date those involving the central nervous system (CNS) have not been particularly responsive to immunologic therapy. The use of the novel immunomodulator, protein A immunoadsorption, was explored to address this question. Methods. Six patients with neurologic paraneoplastic syndromes were treated with this technique, using the ''off line'' method. Two hundred fifty mi of plasma was perfused through a column containing protein A covalently attached to a silica matrix. The plasma was then returned to the patient. Results. Five of the patients responded to the therapy, with complete and durable responses in three patients with opsoclonus-myoclonus, objective, though transient, improvement in one patient with paraneoplastic brainstem encephalitis associated with a Merkel cell tumor, and stabilization and partial improvement in one patient with paraneoplastic limbic encephalitis. The patient without response developed a cutaneous vasculitis after the second treatment, and therapy was discontinued. Conclusions. This therapy appears beneficial for a number of paraneoplastic syndromes, most dramatically in the opsoclonus/myoclonus syndrome. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BLOOD TRANSFUS SERV,BOSTON,MA 02114. NR 33 TC 64 Z9 65 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 APR 1 PY 1995 VL 75 IS 7 BP 1678 EP 1683 DI 10.1002/1097-0142(19950401)75:7<1678::AID-CNCR2820750719>3.0.CO;2-2 PG 6 WC Oncology SC Oncology GA QN813 UT WOS:A1995QN81300018 PM 8826927 ER PT J AU DEALY, MF PAZOLA, K HEISLEIN, DM AF DEALY, MF PAZOLA, K HEISLEIN, DM TI CARE OF THE ADOLESCENT UNDERGOING AN ALLOGRAFT PROCEDURE SO CANCER NURSING LA English DT Article DE ALLOGRAFTS; ADOLESCENTS ID ADJUVANT CHEMOTHERAPY; OSTEOGENIC-SARCOMA AB During the last 25 years, substantial progress has been made in the detection and treatment of bone tumors in adolescents and young adults. Due to more effective chemotherapy treatments, patients are now surviving these illnesses and living quality lives. In the past, the only surgical option for treatment of these tumors was amputation. Today, however, limbsparing procedures such as allograft implantation, together with effective chemotherapy treatments, provide patients with another treatment option. The allograft procedure includes removing the tumor and affected bone and replacing it with bone procured from deceased donors. During the following 2 years, the body does the work of incorporating the allograft and replacing it, at least in part, with new host bone. After a long rehabilitation process, the patient will have a functioning limb. Nursing care of the adolescent undergoing allograft procedure encompasses meeting important physical and psychosocial needs. Adolescents are often still dealing with the emotional and physical stress of having cancer and chemotherapy or chemotherapy side effects at the time of surgery. They are concerned not only with their immediate recovery but also with their long-term prognosis. All treatment modalities, including allograft surgery, impinges on the normal developmental tasks of adolescents. The nursing challenge is to help the adolescent balance the limits of their illness and recovery with normal developmental needs. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 22 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD APR PY 1995 VL 18 IS 2 BP 130 EP 137 PG 8 WC Oncology; Nursing SC Oncology; Nursing GA QN810 UT WOS:A1995QN81000006 PM 7720051 ER PT J AU DATTA, R MANOME, Y TANEJA, N BOISE, LH WEICHSELBAUM, R THOMPSON, CB SLAPAK, CA KUFE, D AF DATTA, R MANOME, Y TANEJA, N BOISE, LH WEICHSELBAUM, R THOMPSON, CB SLAPAK, CA KUFE, D TI OVEREXPRESSION OF BCL-X(L) BY CYTOTOXIC DRUG EXPOSURE CONFERS RESISTANCE TO IONIZING RADIATION-INDUCED INTERNUCLEOSOMAL DNA FRAGMENTATION SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; PROGRAMMED CELL-DEATH; MYELOID-LEUKEMIA CELLS; C-MYC; BCL-2 PROTOONCOGENE; THYMOCYTE APOPTOSIS; GENE-EXPRESSION; P-GLYCOPROTEIN; FACTOR-ALPHA; HL-60 CELLS AB Acquired resistance to diverse chemotherapeutic agents has been associated with overexpression of the P-glycoprotein. We have selected human U-937 cells for clones resistant to the cytotoxic agents doxorubicin (U-A20) and vincristine (U-V20). The results demonstrate that P-glycoprotein-positive U-A20 and U-V20 cells exhibit resistance to inducers of internucleosomal DNA fragmentation. Although parental U-937 cells responded to ionizing radiation with the DNA laddering characteristic of physiological cell death, the drug-resistant lines were insensitive to this effect. The U-A20 and U-V20 clones were also resistant to endonucleolytic DNA cleavage associated with exposure to tumor necrosis factor or ceramide. Previous work has demonstrated that physiological cell death is inhibited by overexpression of the Bcl-2 protein. However, analysis of Bcl-2 revealed similar levels in the parental and drug-resistant cells. In contrast, we show that U-A20 and U-V20 cells overexpress the Bcl-2-related protein, Bcl-x(L). Moreover, studies with a U-937 cell line transfected with a Bcl-x(L) expression vector confirm resistance to ionizing radiation-induced DNA fragmentation and cell killing. These findings suggest that, unlike Bcl-2, Bcl-x(L) may be constitutively overexpressed as a result of selection for cytotoxic drug resistance and that Bcl-x(L) participates in an acquired form of multimodality resistance to chemotherapeutic agents and radiation. C1 UNIV CHICAGO,HOWARD HUGHES MED INST,DEPT MED,CHICAGO,IL 60637. UNIV CHICAGO,HOWARD HUGHES MED INST,DEPT MOLEC GENET & CELL BIOL,CHICAGO,IL 60637. UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. RP DATTA, R (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA55241] NR 53 TC 124 Z9 124 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD APR PY 1995 VL 6 IS 4 BP 363 EP 370 PG 8 WC Cell Biology SC Cell Biology GA QR290 UT WOS:A1995QR29000002 PM 7794804 ER PT J AU HYMAN, SE COLE, RL KONRADI, C KOSOFSKY, BE AF HYMAN, SE COLE, RL KONRADI, C KOSOFSKY, BE TI DOPAMINE REGULATION OF TRANSCRIPTION FACTOR-TARGET INTERACTIONS IN RAT STRIATUM SO CHEMICAL SENSES LA English DT Article ID C-FOS; CYCLIC-AMP; SOMATOSTATIN GENE; RESPONSE-ELEMENT; COCAINE; PHOSPHORYLATION; EXPRESSION; DYNORPHIN; BINDING; CREB AB Transcriptional regulation is an important mechanism by which neurons adapt to environmental stimuli. The indirect dopamine agonists, amphetamine and cocaine have been shown to induce expression of immediate early genes, such as c-fos, and neuropeptide genes, such as prodynorphin in the rat striatum. Here we show that phosphorylation of transcription factor CREB is a critical early event coupling dopamine stimulation to gene regulation. CREB interacts with functional regulatory elements in both the c-fos and prodynorphin genes, and is phosphorylated in response to dopamine in a D1 dopamine receptor-dependent manner. In addition, we show by intra-striatal injection of antisense oligonucleotides directed against CREB mRNA, that CREB protein is required for c-fos induction by amphetamine. C1 HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP HYMAN, SE (reprint author), MASSACHUSETTS GEN HOSP,MOLEC & DEV NEUROSCI LAB,CNY-2,149 13TH ST,BOSTON,MA 02129, USA. NR 24 TC 23 Z9 24 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD APR PY 1995 VL 20 IS 2 BP 257 EP 260 DI 10.1093/chemse/20.2.257 PG 4 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA QX812 UT WOS:A1995QX81200012 PM 7583020 ER PT J AU LEVINE, SM BRYAN, CL AF LEVINE, SM BRYAN, CL TI BRONCHIOLITIS OBLITERANS IN LUNG-TRANSPLANT RECIPIENTS - THE THORN IN THE SIDE OF LUNG TRANSPLANTATION SO CHEST LA English DT Editorial Material ID ALLOGRAFTS; REJECTION C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV PULM DIS CRIT CARE MED,SAN ANTONIO,TX. RP LEVINE, SM (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PULM DIS SECT 111 E,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 15 TC 17 Z9 17 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD APR PY 1995 VL 107 IS 4 BP 894 EP 897 DI 10.1378/chest.107.4.894 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA QR617 UT WOS:A1995QR61700005 PM 7705149 ER PT J AU HOLMES, DR TOPOL, EJ CALIFF, RM BERDAN, LG LEYA, F BERGER, PB WHITLOW, PL SAFIAN, RD ADELMAN, AG KELLETT, MA TALLEY, JD SHANI, J GOTTLIEB, RS PINKERTON, CA LEE, KL KEELER, GP ELLIS, SG FRANCO, I DEBOWEY, D LINCOFF, M KEREIAKES, D ABBOTTSMITH, C KENT, K LEON, M PICHARD, A SATLER, L POPMA, J HINOHARA, T KOSINSKI, E SIMONTON, C BERSIN, RM CEDARHOLM, J WILSON, B MCKEEVER, LS MARTIN, F CHAPEKIS, A GEORGE, BS COWLEY, M PINKERTON, C PETERS, T COHEN, M JACOBS, A FAXON, DP LEVINE, G KELLETT, M KING, S MASDEN, R MOONEY, M WHITE, CJ HOFLING, B WILLIAMS, D TALLEY, D WHITE, H BRINKER, J STEWART, DK CHAMBERS, J AU, P PALACIOS, I KUNTZ, R SAFIAN, R IVANHOE, R PUEL, J RAYBUCK, B BONAN, R PEARSON, C LAIRD, JR BURWELL, L CARNEY, RJ BELLINGER, R RICCI, D SPOKOJNY, A MARTYAK, TE COHEN, E ADELMAN, A LEWIS, S WEBB, J TRABOULSI, D REEN, B NIESS, G SLATER, J MARQUIS, JF BUSH, HS MOSES, JW HEUSER, R AYRES, M APFELBAUM, MA BLEICH, S ROUBIN, G STEIN, R HARTMAN, CW DENARDO, R LINDSEY, D CORIN, W UNTERECKER, B STILLABOWER, M MICK, M SHARMA, S COHEN, H BARBEAU, G GRIFFIN, J ARNOLD, A CALIFF, R AF HOLMES, DR TOPOL, EJ CALIFF, RM BERDAN, LG LEYA, F BERGER, PB WHITLOW, PL SAFIAN, RD ADELMAN, AG KELLETT, MA TALLEY, JD SHANI, J GOTTLIEB, RS PINKERTON, CA LEE, KL KEELER, GP ELLIS, SG FRANCO, I DEBOWEY, D LINCOFF, M KEREIAKES, D ABBOTTSMITH, C KENT, K LEON, M PICHARD, A SATLER, L POPMA, J HINOHARA, T KOSINSKI, E SIMONTON, C BERSIN, RM CEDARHOLM, J WILSON, B MCKEEVER, LS MARTIN, F CHAPEKIS, A GEORGE, BS COWLEY, M PINKERTON, C PETERS, T COHEN, M JACOBS, A FAXON, DP LEVINE, G KELLETT, M KING, S MASDEN, R MOONEY, M WHITE, CJ HOFLING, B WILLIAMS, D TALLEY, D WHITE, H BRINKER, J STEWART, DK CHAMBERS, J AU, P PALACIOS, I KUNTZ, R SAFIAN, R IVANHOE, R PUEL, J RAYBUCK, B BONAN, R PEARSON, C LAIRD, JR BURWELL, L CARNEY, RJ BELLINGER, R RICCI, D SPOKOJNY, A MARTYAK, TE COHEN, E ADELMAN, A LEWIS, S WEBB, J TRABOULSI, D REEN, B NIESS, G SLATER, J MARQUIS, JF BUSH, HS MOSES, JW HEUSER, R AYRES, M APFELBAUM, MA BLEICH, S ROUBIN, G STEIN, R HARTMAN, CW DENARDO, R LINDSEY, D CORIN, W UNTERECKER, B STILLABOWER, M MICK, M SHARMA, S COHEN, H BARBEAU, G GRIFFIN, J ARNOLD, A CALIFF, R TI A MULTICENTER, RANDOMIZED TRIAL OF CORONARY ANGIOPLASTY VERSUS DIRECTIONAL ATHERECTOMY FOR PATIENTS WITH SAPHENOUS-VEIN BYPASS GRAFT LESIONS SO CIRCULATION LA English DT Article DE ANGIOPLASTY; REVASCULARIZATION ID TRANS-LUMINAL ANGIOPLASTY; AORTOCORONARY BYPASS; BALLOON ANGIOPLASTY; FOLLOW-UP; RESTENOSIS; SURGERY; ATHEROSCLEROSIS; EXPERIENCE; STENOSIS; ARTERIES AB Background Directional coronary atherectomy and percutaneous transluminal coronary angioplasty have both been used in symptomatic patients with coronary saphenous vein bypass graft stenoses. The relative merits of plaque excision and removal versus balloon dilatation remain uncertain. We compared outcomes after directional coronary atherectomy or angioplasty in patients with de novo bypass graft stenoses. Methods and Results Fifty-four North American and European sites randomized 305 patients with de novo vein graft lesions to atherectomy (n=149) or angioplasty (n=156). Quantitative coronary angiography at a core laboratory assessed initial and 6-month results. Initial angiographic success was greater with atherectomy (89.2% versus 79.0%), as was initial luminal gain (1.45 versus 1.12 mm, P<.001). Distal embolization was increased with atherectomy (P=.012), and a trend was shown toward more non-Q-wave myocardial infarction (P=.09). Although the 6-month net minimum luminal diameter gain was 0.68 mm for atherectomy and 0.50 mm for angioplasty, the restenosis rates were similar, 45.6% for atherectomy and 50.5% for angioplasty (P=.491). At 6 months, there was a trend toward decreased repeated target-vessel interventions for atherectomy (P=.092); in addition, 13.2% of patients treated with atherectomy versus 22.4% of the angioplasty patients (P=.041) required repeated percutaneous intervention of the initial target lesion. Conclusions Atherectomy of de novo vein graft lesions was associated with improved initial angiographic success and luminal diameter but also with increased distal embolization. There was no difference in 6-month restenosis rates, although primary atherectomy patients tended to require fewer target-vessel revascularization procedures. C1 CLEVELAND CLIN FDN,CLEVELAND,OH 44195. DUKE UNIV,MED CTR,DURHAM,NC. LOYOLA MED CTR,CHICAGO,IL. WILLIAM BEAUMONT ROYAL OAK HOSP,ROYAL OAK,MI. UNIV LOUISVILLE,LOUISVILLE,KY 40292. MAINE MED CTR,PORTLAND,ME 04102. MAIMONIDES HOSP,BROOKLYN,NY. GRAD HOSP PHILADELPHIA,PHILADELPHIA,PA 19146. TORONTO GEN HOSP,TORONTO,ON,CANADA. ST VINCENTS HOSP,INDIANAPOLIS,IN. CHRIST HOSP,CINCINNATI,OH 45219. CARDIOL CTR,WASHINGTON,DC. SEQUOIA HOSP,REDWOOD CITY,CA. ST VINCENTS MED CTR,BRIDGEPORT,CT. CAROLINAS MED CTR,CHARLOTTE,NC 28203. CAROLINAS HEART INST,CHARLOTTE,NC 28232. MIDWEST HEART RES FDN,LOMBARD,IL. METHODIST HOSP,MEMPHIS,TN. RIVERSIDE METHODIST HOSP,COLUMBUS,OH 43214. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. ST FRANCIS HOSP,BEECH GROVE,IN. BOSTON UNIV,MED CTR,BOSTON,MA. EMORY HOSP,ATLANTA,GA. JEWISH HOSP,LOUISVILLE,KY. MINNEAPOLIS HEART INST,MINNEAPOLIS,MN. OCHSNER FDN HOSP,NEW ORLEANS,LA. UNIV MUNICH,KLINIKUM GROSSHADERN,W-8000 MUNICH,GERMANY. RHODE ISL HOSP,PROVIDENCE,RI 02902. SW CARDIOL ASSOCIATES,ALBUQUERQUE,NM. GRAD CARDIOL CONSULTANTS,PHILADELPHIA,PA. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD. LOYOLA MED CTR,MAYWOOD,IL. UNIV WASHINGTON,SEATTLE,WA 98195. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BETH ISRAEL HOSP,BOSTON,MA 02215. FLORIDA HOSP,ORLANDO,FL. CHU RANGUEIL,F-31054 TOULOUSE,FRANCE. FAIRFAX HOSP,ANNANDALE,VA. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. UNIV VIRGINIA,CHARLOTTESVILLE,VA. MOTHER FRANCES,TYLER,TX. SUTTER HOSP,SACRAMENTO,CA. HAHNEMANN UNIV,PHILADELPHIA,PA. VANCOUVER GEN HOSP,VANCOUVER,BC,CANADA. CORNELL UNIV,MED CTR,NEW YORK HOSP,NEW YORK,NY 10021. HENRICO HOSP,FREDERICKSBURG,VA. TORONTO GEN HOSP,N YORK,ON,CANADA. MT SINAI HOSP,TORONTO,ON M5G 1X5,CANADA. CARLESTON MED CTR,CHARLESTON,WV. ST PAULS HOSP,VANCOUVER,BC V6Z 1Y6,CANADA. FOOTHILLS PROV GEN HOSP,CALGARY,AB,CANADA. PRESBYTERIAN HOSP,CHARLOTTE,NC. ST LUKES ROOSEVELT HOSP,NEW YORK,NY 10025. OTTAWA HEART,OTTAWA,ON,CANADA. CLEVELAND CLIN FLORIDA,FT LAUDERDALE,FL. LENOX HILL HOSP,NEW YORK,NY 10021. HEALTHWEST REG MED CTR,PHOENIX,AZ. FT SANDERS REG MED CTR,KNOXVILLE,TN. COLUMBIA PRESBYTERIAN MED CTR,NEW YORK,NY 10032. E JEFFERSON HOSP,METAIRIE,LA. UNIV ALABAMA,BIRMINGHAM,AL. SENTARA NORFOLK GEN HOSP,NORFOLK,VA. ST MARYS HOSP,SAGINAW,MI. SHADYSIDE HOSP,PITTSBURGH,PA 15232. PRESBYTERIAN MED CTR,PHILADELPHIA,PA 19104. MED CTR DELAWARE,NEWARK,DE. METHODIST HOSP INDIANA,INDIANAPOLIS,IN 46202. MT SINAI MED CTR,NEW YORK,NY 10029. ST JOHNS HOSP,SANTA MONICA,CA. LAVAL HOSP,ST FOY,PQ,CANADA. VIRGINIA BEACH GEN HOSP,VIRGINIA BEACH,VA. OLYMPIA FIELDS HOSP 3,OLYMPIA FIELDS,IL. MCLAREN REG MED CTR,FLINT,MI. RP HOLMES, DR (reprint author), MAYO CLIN & MAYO FDN,CARDIAC CARE UNIT,200 1ST ST SW,ROCHESTER,MN 55905, USA. RI White, Christopher/J-6686-2012; OI White, Christopher/0000-0001-8618-7539; Topol, Eric/0000-0002-1478-4729 NR 37 TC 160 Z9 161 U1 2 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 1 PY 1995 VL 91 IS 7 BP 1966 EP 1974 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QP542 UT WOS:A1995QP54200014 PM 7895354 ER PT J AU LEWANDOWSKI, ED WHITE, LT AF LEWANDOWSKI, ED WHITE, LT TI PYRUVATE-DEHYDROGENASE INFLUENCES POSTISCHEMIC HEART FUNCTION SO CIRCULATION LA English DT Article DE MYOCARDIUM; REPERFUSION; NMR SPECTROSCOPY ID FATTY-ACID METABOLISM; ISCHEMIC RAT-HEART; STUNNED MYOCARDIUM; C-13 NMR; RABBIT HEARTS; GLUCOSE; DICHLOROACETATE; OXIDATION; RECOVERY; COMPARTMENTATION AB Background The pyruvate dehydrogenase (PDH) enzyme complex determines the extent of carbohydrate oxidation in the myocardium. PDH is in a largely inactive state during early reperfusion of postischemic myocardium. The resultant decrease in pyruvate oxidation in postischemic hearts has been documented with C-13 nuclear magnetic resonance (NMR) spectroscopy. This study demonstrates that counteracting depressed pyruvate oxidation can enhance contractile recovery in the absence of increases in either glycolytic activity or glucose oxidation. The findings indicate that increased incorporation of carbon units from pyruvate into the intermediates of the oxidative pathways by PDH influences the metabolic efficiency and mechanical work of postischemic hearts. Methods and Results Isolated rabbit hearts were situated in an NMR magnet and perfused or reperfused (10 minutes of ischemia) with 2.5 mmol/L [3-C-13]pyruvate as sole substrate to target PDH directly and bypass the glycolytic pathway. Hearts were observed with or without activation of PDH with dichloroacetate. Mechanical function and oxygen consumption (MV over dot o(2)) were monitored. C-13 and P-31 NMR spectroscopy allowed observations of pyruvate oxidation and bioenergetic state in intact, functioning hearts. Metabolite content and C-13 enrichment levels were then determined with in vitro NMR spectroscopy and biochemical assay. PDH activation did not affect performance of normal hearts. Postischemic hearts with augmented pyruvate oxidation (dichloroacetate-treated) sustained improved mechanical function throughout 40 minutes of reperfusion. Rate-pressure-product (RPP) increased from 8300+/-1800 (mean+/-SEM) in untreated postischemic hearts to 21 300+/-2400 in hearts treated with dichloroacetate (P<.05). Oxygen use per unit work [MV over dot o(2), multiplied by 10(4) divided by RPP] was improved from 1.50+/-0.13 to 1.14+/-0.11 (P<.05) without differences in high-energy phosphate content between treated and untreated hearts. Values of dP/dt were also consistently higher, by as much as 185%, during reperfusion with dichloroacetate. Postischemic hearts displayed reduced pyruvate oxidation from the incorporation of C-13 into the tissue glutamate pool. With the tissue alanine level as a marker of C-13-enriched pyruvate availability in the cell, the ratio of labeled glutamate to alanine was only 58% of the control value during early reperfusion. With dichloroacetate, that ratio was 167% greater than that of untreated hearts (P<.05). By the end of the reperfusion period, the C-13 enrichment of the tissue glutamate pool by pyruvate oxidation was elevated from dichloroacetate treatment (untreated, 62+/-7%; DCA-treated, 81+/-6%; P<.05), but glycogen content was similar in both groups and C-13 enrichment of tissue alanine remained unchanged, near 60%, indicating no increases in glycolytic end-product formation. Conclusions Metabolic reversal of contractile dysfunction was achieved in isolated hearts by counteracting depressed PDH activity in the postischemic myocardium. Improved cardiac performance did not result from, nor require, increased glycolysis secondary to the activation of PDH. Rather, restoring carbon flux through PDH alone was sufficient to improve mechanical work by postischemic hearts. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NMR CTR,DEPT RADIOL,BOSTON,MA. FU NHLBI NIH HHS [R01-HL-49244] NR 35 TC 103 Z9 104 U1 2 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 1 PY 1995 VL 91 IS 7 BP 2071 EP 2079 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QP542 UT WOS:A1995QP54200027 PM 7895366 ER PT J AU WOODGETT, JR AVRUCH, J KYRIAKIS, JM AF WOODGETT, JR AVRUCH, J KYRIAKIS, JM TI REGULATION OF NUCLEAR TRANSCRIPTION FACTORS BY STRESS SIGNALS SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY LA English DT Article; Proceedings Paper CT IUPHAR 1994 Satellite Symposium on In Vitro Neurotoxicology CY JUL, 1994 CL VAL MORIN, CANADA DE GENE EXPRESSION; ISCHEMIA; PHOSPHORYLATION; SIGNAL TRANSDUCTION; STRESS; TRANSCRIPTION; UV ID GLYCOGEN-SYNTHASE KINASE-3; ACTIVATED PROTEIN-KINASES; C-JUN; DNA-BINDING; PHOSPHORYLATION; CELLS; TAU AB 1. A diverse array of stressful stimuli induces changes in gene expression via post-translational modification of transcription factors. 2. Study of activator protein (AP-1) transcription factor regulation has revealed a novel family of protein-serine kinases. Molecular cloning and expression of these proteins have demonstrated their specific activation by stress stimuli such as UV irradiation, heat, ischaemia/reperfusion and metabolic toxins. 3. Dissection of the regulation of the stress-activated protein kinases has revealed a similar but distinct mechanism to mitogen-activated protein kinases suggesting that cellular responses to stress may partially overlap with normal growth responses and have common nuclear targets. C1 MASSACHUSETTS GEN HOSP EAST,MED SERV,DIABET RES LAB,BOSTON,MA. RP WOODGETT, JR (reprint author), ONTARIO CANC INST,500 SHERBOURNE ST,TORONTO,ON M4X 1K9,CANADA. RI Woodgett, Jim/F-1087-2010 OI Woodgett, Jim/0000-0003-3731-5797 NR 24 TC 31 Z9 31 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL AUSTR PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON 3053, AUSTRALIA SN 0305-1870 J9 CLIN EXP PHARMACOL P JI Clin. Exp. Pharmacol. Physiol. PD APR PY 1995 VL 22 IS 4 BP 281 EP 283 DI 10.1111/j.1440-1681.1995.tb01995.x PG 3 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA QY588 UT WOS:A1995QY58800008 PM 7671441 ER PT J AU CARUS, NH RAIZMAN, MB WILLIAMS, DL BAKER, AS AF CARUS, NH RAIZMAN, MB WILLIAMS, DL BAKER, AS TI RELAPSE OF MYCOBACTERIUM-LEPRAE INFECTION WITH OCULAR MANIFESTATIONS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; LEPROSY; BLINDNESS; THERAPY AB A case of ocular leprosy as the manifestation of persistent or relapsed Mycobacterium leprae infection similar to 20 years following treatment is reported. The clinical and pathological features of this case are described, and the molecular methods needed to arrive at the definitive diagnosis are examined, If blindness is to be averted, clinicians must have a high index of suspicion for the diagnosis of ocular leprosy when anterior segment changes are noted during ophthalmologic examination of a patient from an area in which M. leprae is endemic. The indolent nature of ocular leprosy may require lifelong surveillance and therapy to insure sight preservation. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,IMMUNOL & INFECT DIS SERV,BOSTON,MA. LOUISIANA STATE UNIV,GILLIS W LONG HANSENS DIS CTR,LAB RES BRANCH,BATON ROUGE,LA. NR 26 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 1995 VL 20 IS 4 BP 776 EP 780 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QP662 UT WOS:A1995QP66200007 PM 7795073 ER PT J AU NORLING, LL GOMEZ, RA INAGAMI, T AF NORLING, LL GOMEZ, RA INAGAMI, T TI CHARACTERIZATION OF A SYNTHETIC PEPTIDE ANTIBODY RECOGNIZING RAT-KIDNEY RENIN AND PRORENIN SO CLINICAL NEPHROLOGY LA English DT Article DE ANTIBODY; SYNTHETIC PEPTIDE; RENIN; PRORENIN; RAT KIDNEY ID INACTIVE RENIN; PROTEINS AB A fourteen amino acid peptide from the cDNA predicted rat renin amino acid sequence was synthesized and used to produce a polyclonal antibody, The ability of this antibody to recognize rat renin was characterized and compared to that of a previously tested polyclonal anti-rat renin antibody raised against purified rat renin to verify its usefulness as a reagent in renin processing. The anti-renin peptide antibody and anti-rat renin antibody were evaluated for specificity of recognition of rat renin by immunohistochemical staining and immunoblotting. The ability of the anti-renin peptide antibody to inhibit renin enzymatic activity and to immunoprecipitate rat recombinant protein was also tested. Anti-renin peptide antibody and anti-rat renin antibody had identical recognition of rat renin and prorenin in immunohistochemical stains of rat kidney section and immunoblots. However the anti-renin peptide antibody does not inhibit renin enzymatic activity nor does it immunoprecipitate recombinant rat prorenin. We have produced and characterized an antirenin peptide antibody which recognizes denaturated rat renin and prorenin in a way that is identical to that of an antibody raised against native rat renin. The anti-renin peptide antibody does not recognize nondenatured renin because it did not inhibit renin enzymatic activity nor was it able to immunoprecipitate renin or prorenin. The technique of using synthetic peptides to produce antibody recognizing at renin is useful because low yields of native renin purified from rat kidney are generally insufficient for antibody production, This limits the widespread availability of antibodies that recognize rat renin. Alternative ways of producing antibodies which recognize rat renin and prorenin will help to facilitate renin angiotensin research. C1 UNIV VIRGINIA,DEPT PEDIAT,CHARLOTTESVILLE,VA. VANDERBILT UNIV,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37240. RP NORLING, LL (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT NEPHROL UNIT,ACC 709,15 PARKMAN ST,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [K08-DK02048, P50-DK44765] NR 13 TC 4 Z9 4 U1 0 U2 2 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD APR PY 1995 VL 43 IS 4 BP 232 EP 236 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA QT393 UT WOS:A1995QT39300005 PM 7541738 ER PT J AU KRANE, SM AF KRANE, SM TI IS COLLAGENASE (MATRIX METALLOPROTEINASE-1) NECESSARY FOR BONE AND OTHER CONNECTIVE-TISSUE REMODELING SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Conference on Marrow Stromal Cell Differentiation CY JUL, 1993 CL OXFORD, ENGLAND SP BRIT BONE & TOOTH SOC, UNIV OXFORD ID HUMAN NEUTROPHIL COLLAGENASE; HUMAN FIBROBLAST COLLAGENASE; OP OP MOUSE; CYSTEINE SWITCH; ACTIVE-SITE; C-FOS; GENE; OSTEOPETROSIS; SPECIFICITY; PROTOONCOGENE AB In physiologic remodeling of bone and other connective tissues, proteinases such as the matrix metalloproteinases (MMPs) which can cleave Type I collagen play a critical role. In bone, MMP-1 is secreted by stromal fibroblasts, osteoblasts, and osteoclasts. Only the collagenases (MMP-1 and MMP-8) cleave native undenatured collagen at neutral pH. The cleavage is site specific at a single locus in the alpha 1(I) chain between Gl(775)/Ile(776). The authors have altered the amino acid sequences around the collagenase cleavage site by site-directed mutagenesis of the murine Col1a-I gene, introducing Pro for Gln(774), Pro for Ala(777), and Met for Ile(776). The mutant Col1a-I gene has been expressed in Mov13 fibroblasts, and secreted Type I collagen molecules have been found to be resistant to cleavage at Gly(775)/Ile(776) by MMP-1 or MMP-8. This subtle mutation was introduced recently into the endogenous Col1a-I gene by homologous recombination in embryonic stem cells to determine the role of collagenase in vivo. Chimaeric mice derived from blastocysts injected with these embryonic stem cells transmitted the mutant Col1a-I gene to their offspring. Surprisingly, homozygous mutant mice reproduce and appear to develop normally. The mechanisms of collagen resorption in remodeling of bone and soft tissues in these mice are being examined currently. Information should be derived that will be useful in interpreting human disorders characterized by increased collagen deposition, such as osteopetrosis and dermal fibrosis. C1 MASSACHUSETTS GEN HOSP,MED SERV,ARTHRITIS UNIT,BOSTON,MA 02114. RP KRANE, SM (reprint author), HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114, USA. FU NIAMS NIH HHS [AR-03564, AR-07258] NR 46 TC 17 Z9 19 U1 0 U2 1 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 APR PY 1995 IS 313 BP 47 EP 53 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA QR805 UT WOS:A1995QR80500007 PM 7641497 ER PT J AU NATOWICZ, MR STOLER, JM PRENCE, EM LISCUM, L AF NATOWICZ, MR STOLER, JM PRENCE, EM LISCUM, L TI MARKED HETEROGENEITY IN NIEMANN-PICK DISEASE, TYPE-C - CLINICAL AND ULTRASTRUCTURAL FINDINGS SO CLINICAL PEDIATRICS LA English DT Article ID LOW-DENSITY LIPOPROTEIN; HEXOSAMINIDASE-A DEFICIENCY; METACHROMATIC LEUKODYSTROPHY; CHOLESTEROL ESTERIFICATION; HUMAN CHROMOSOME-18; GM2 GANGLIOSIDOSIS; DIAGNOSIS; SPHINGOMYELINASE; FIBROBLASTS; SIBSHIP AB Niemann-Pick disease type C (NP-C) is an autosomal recessive lysosomal lipid storage disorder of unknown etiology, Diagnosis of NP-C is based on characteristic clinical findings and reduced fibroblast esterification of LDL-derived cholesterol. We describe three patients who demonstrate the NP-C spectrum of clinical heterogeneity in age of onset, presenting signs, pattern of organ system involvement, and natural history. In addition, electron microscopic analysis of skin biopsy specimens from these patients revealed marked variability in the extent and cellular distribution of intralysosomal storage and was suggestive of the correct diagnosis in only one case. These cases demonstrate both the limitations of electron microscopy for diagnosis of NP-C and the marked clinical variability in patients with this disorder. Practical clinical guidelines for appropriate suspicion of NP-C are presented. C1 EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV BIOMED SCI,WALTHAM,MA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. TUFTS UNIV,SCH MED,DEPT PHYSIOL,BOSTON,MA 02111. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV MED GENET,WALTHAM,MA 02254. FU NIDDK NIH HHS [DK 36505]; NIGMS NIH HHS [5T32GM07748] NR 31 TC 8 Z9 8 U1 0 U2 1 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD APR PY 1995 VL 34 IS 4 BP 190 EP 197 DI 10.1177/000992289503400404 PG 8 WC Pediatrics SC Pediatrics GA QR600 UT WOS:A1995QR60000004 PM 7789012 ER PT J AU BOLAND, GW LEE, MJ SILVERMAN, S MUELLER, PR AF BOLAND, GW LEE, MJ SILVERMAN, S MUELLER, PR TI INTERVENTIONAL RADIOLOGY OF THE PLEURAL SPACE SO CLINICAL RADIOLOGY LA English DT Review ID GUIDED CATHETER DRAINAGE; INTRACAVITARY UROKINASE; THORACIC EMPYEMA; PARAPNEUMONIC EFFUSIONS; PERCUTANEOUS CATHETER; FLUID COLLECTIONS; PNEUMOTHORAX; MANAGEMENT; TUBE; CHEST C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 45 TC 18 Z9 18 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 APR PY 1995 VL 50 IS 4 BP 205 EP 214 DI 10.1016/S0009-9260(05)83471-3 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QT144 UT WOS:A1995QT14400001 PM 7729115 ER PT J AU CHUNG, RT JAFFE, DL FRIEDMAN, LS AF CHUNG, RT JAFFE, DL FRIEDMAN, LS TI COMPLICATIONS OF CHRONIC LIVER-DISEASE SO CRITICAL CARE CLINICS LA English DT Review AB Important emergencies in the patient with chronic liver disease include bleeding gastroesophageal varices, massive ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy. In addition to careful hemodynamic management and appropriate antibiotic treatment, care of the patient should be directed toward specific pharmacologic and endoscopic interventions to decrease portal hypertension and its sequelae. Recently introduced approaches include endoscopic sclerotherapy and variceal band ligation, a growing array of portal antihypertensive drugs, and transjugular intrahepatic portosystemic shunt placement under radiologic guidance. In carefully selected patients, liver transplantation may be appropriate and life saving. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. NR 0 TC 4 Z9 4 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0749-0704 J9 CRIT CARE CLIN JI Crit. Care Clin. PD APR PY 1995 VL 11 IS 2 BP 431 EP 463 PG 33 WC Critical Care Medicine SC General & Internal Medicine GA QV562 UT WOS:A1995QV56200011 PM 7788540 ER PT J AU WHITE, K AF WHITE, K TI MORPHOGENESIS - CELL-DEATH RETURNS TO ITS ROOTS SO CURRENT BIOLOGY LA English DT Note ID NEURAL CREST CELLS; HINDBRAIN AB Cell-death researchers are looking back at an old question, as interest is revived in exploring the role of cell death in morphogenesis. RP WHITE, K (reprint author), MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129, USA. NR 13 TC 4 Z9 4 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 1 PY 1995 VL 5 IS 4 BP 371 EP 372 DI 10.1016/S0960-9822(95)00075-3 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT007 UT WOS:A1995QT00700012 PM 7627550 ER PT J AU VANDERGEER, P WILEY, S LAI, VKM OLIVIER, JP GISH, GD STEPHENS, R KAPLAN, D SHOELSON, S PAWSON, T AF VANDERGEER, P WILEY, S LAI, VKM OLIVIER, JP GISH, GD STEPHENS, R KAPLAN, D SHOELSON, S PAWSON, T TI A CONSERVED AMINO-TERMINAL SHC DOMAIN BINDS TO PHOSPHOTYROSINE MOTIFS IN ACTIVATED RECEPTORS AND PHOSPHOPEPTIDES SO CURRENT BIOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASES; GUANINE-NUCLEOTIDE EXCHANGE; GROWTH-FACTOR RECEPTORS; SIGNAL TRANSDUCTION; V-SRC; TRANSFORMING PROTEIN; ADAPTER PROTEIN; HIGH-AFFINITY; EGF RECEPTOR; GRB2 AB Background: Signal transduction by growth factor receptor protein-tyrosine kinases is generally initiated by autophosphorylation on tyrosine residues following ligand binding. Phosphotyrosines within activated receptors form binding sites for the Src homology 2 (SH2) domains of cytoplasmic signalling proteins. One such protein, Shc, is tyrosine phosphorylated in response to a large number of growth factors and cytokines. Phosphorylation of Shc on tyrosine residue Y317 allows binding to the SH2 domain of Grb2, and hence stimulation of the Ras pathway. Shc is therefore implicated as an adaptor protein able to couple normal and oncogenic protein-tyrosine kinases to Ras activation. Shc itself contains an SH2 domain at its carboxyl terminus, but the function of the amino-terminal half of the protein is unknown. Results: We have found that the Shc amino-terminal region binds to a number of tyrosine-phosphorylated proteins in v-src-transformed cells. This domain also bound directly to the activated epidermal growth factor (EGF) receptor. A phosphotyrosine (pY)-containing peptide modeled after the Shc-binding site in polyoma middle T antigen (LLSNPTpYSVMRSK) was able to compete efficiently with the activated EGF receptor for binding to the Shc amino terminus. This competition was dependent on phosphorylation of the tyrosine residue within the peptide, and was abrogated by deletion of the leucine residue at position -5. The Shc amino-terminal domain also bound to the autophosphorylated nerve growth factor receptor (Trk), but bound significantly less well to a mutant receptor in which tyrosine Y490 in the receptor's Shc-binding site had been substituted by phenylalanine. Conclusion: These data implicate the amino-terminal region of Shc in binding to activated receptors and other tyrosine-phosphorylated proteins. Binding appears to be specific for phosphorylated tyrosine residues within the sequence NPXpY, which is conserved in many Shc-binding sites. The Shc amino-terminal region bears only very limited sequence identity to known SH2 domains, suggesting that it represents a new class of phosphotyrosine-binding modules. Consistent with this view, the amino-terminal Shc domain is highly conserved in a Drosophila Shc homologue. Binding of Shc to activated receptors through its amino terminus could leave the carboxy-terminal SH2 domain free for other interactions. In this way, Shc may Function as an adaptor protein to bring two tyrosine-phosphorylated proteins together. C1 MT SINAI HOSP,SAMUEL LUNENFELD RES INST,PROGRAM MOLEC BIOL & CANC,TORONTO,ON M5G 1X5,CANADA. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Pawson, Tony/E-4578-2013; Gish, Gerald/C-7228-2017 NR 52 TC 159 Z9 160 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 1 PY 1995 VL 5 IS 4 BP 404 EP 412 DI 10.1016/S0960-9822(95)00081-9 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QT007 UT WOS:A1995QT00700018 PM 7542991 ER PT J AU YUAN, JY AF YUAN, JY TI MOLECULAR CONTROL OF LIFE AND DEATH SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; INTERLEUKIN-1-BETA CONVERTING ENZYME; CAENORHABDITIS-ELEGANS; C-ELEGANS; GENE CED-3; APOPTOSIS; BCL-2; ENCODES; CLONING; PROTEASE AB Recent evidence has shown that two of the three key genes in the programmed cell death pathway of Caenorhabditis elegans, ced-9 (a cell death suppressor) and ced-3 (a cell death inducer), encode proteins that share structural and functional similarities with the mammalian proto-oncogene product Bcl-2 and interleukin-1 beta converting enzyme, respectively. These findings reveal key molecules that control lire and death decisions in vertebrates. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP YUAN, JY (reprint author), MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,149 13TH ST,4TH FLOOR,BOSTON,MA 02129, USA. NR 35 TC 81 Z9 89 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 APR PY 1995 VL 7 IS 2 BP 211 EP 214 DI 10.1016/0955-0674(95)80030-1 PG 4 WC Cell Biology SC Cell Biology GA QP349 UT WOS:A1995QP34900010 PM 7612273 ER PT J AU LIANG, P PARDEE, AB AF LIANG, P PARDEE, AB TI RECENT ADVANCES IN DIFFERENTIAL DISPLAY SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID MESSENGER-RNAS; PCR; IDENTIFICATION; CLONING; CELLS; GENE; DNA AB Differential display and RNA arbitrary primed polmerase chain reaction are methods recently designed to identify and isolate differentially expressed genes. Methodological modifications have since been introduced to streamline the techniques. The major effort has centered on how to eliminate false positives as approached from a variety of angles, ranging from RNA sample preparation, northern blot confirmation, primer length variation, to better experimental design. RP LIANG, P (reprint author), DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 61232] NR 41 TC 218 Z9 231 U1 0 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 1995 VL 7 IS 2 BP 274 EP 280 DI 10.1016/0952-7915(95)80015-8 PG 7 WC Immunology SC Immunology GA QX634 UT WOS:A1995QX63400015 PM 7546389 ER PT J AU DAVIES, JE SICZKOWSKI, M SWEENEY, FP QUINN, PA KROLEWSKI, B KROLEWSKI, AS NG, LL AF DAVIES, JE SICZKOWSKI, M SWEENEY, FP QUINN, PA KROLEWSKI, B KROLEWSKI, AS NG, LL TI GLUCOSE-INDUCED CHANGES IN TURNOVER OF NA+/H+ EXCHANGER OF IMMORTALIZED LYMPHOBLASTS FROM TYPE-I DIABETIC-PATIENTS WITH NEPHROPATHY SO DIABETES LA English DT Article ID PROTEIN-KINASE-C; ANTIPORT ACTIVITY; HYPERTENSION; CELLS; MELLITUS; SUSCEPTIBILITY; PREDISPOSITION; DISEASE; CULTURE; CLONING AB Increased cellular Na+/H+ exchanger (NHE) activity has been demonstrated in type I diabetic patients with nephropathy. Such patients also have a previous history of poor glycemic control. The interaction between hyperglycemia and changes in NHE activity remains obscure. Therefore, we examined the effects of media containing 5 and 25 mmol/l glucose on the increased NHE activity and turnover number in Epstein-Barr virus-transformed lymphoblasts from patients with diabetic nephropathy compared with normoalbuminuric diabetic and nondiabetic control subjects. NHE activity was determined fluorometrically, and MIE isoform 1 (NHE-1) density was measured with specific polyclonal antibodies. In the presence of 5 mmol/l glucose, cells from patients with diabetic nephropathy exhibited higher NHE activity with intracellular pH clamped to 6.0 compared with diabetic and nondiabetic control subjects (P < 0.005 for both), due to a higher turnover number of NHE-1. Incubation in 25 mmol/l glucose for 48 h caused an increase in NHE activity (P < 0.001) and turnover number (P < 0.01) in the diabetic nephropathy group only with no significant change in the diabetic or nondiabetic control groups. The rate constants for cell proliferation and NHE activity or turnover number were correlated when cells were cultured in 5 mmol/l glucose (r = 0.34 and 0.32, respectively; P < 0.05) or 25 mmol/l glucose media (r = 0.66 and 0.65, respectively; P < 0.001). We conclude that only lymphoblasts from the diabetic nephropathy group show an increase in NHE activity and turnover number under conditions mimicking hyperglycemia. Thus, high glucose levels exaggerate the differences in NHE activity, turnover number, and cell proliferation rate already present between cells from diabetic nephropathy patients and those from diabetic and nondiabetic control subjects. C1 LEICESTER ROYAL INFIRM,DEPT MED & THERAPEUT,LEICESTER,LEICS,ENGLAND. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. JOSLIN DIABET CTR,BOSTON,MA 02215. FU NIDDK NIH HHS [DK-41526, DK-36836]; Wellcome Trust NR 24 TC 19 Z9 19 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 1995 VL 44 IS 4 BP 382 EP 388 DI 10.2337/diabetes.44.4.382 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QZ335 UT WOS:A1995QZ33500003 PM 7698504 ER PT J AU CLARKE, WL COX, DJ GONDERFREDERICK, LA JULIAN, D SCHLUNDT, D POLONSKY, W AF CLARKE, WL COX, DJ GONDERFREDERICK, LA JULIAN, D SCHLUNDT, D POLONSKY, W TI REDUCED AWARENESS OF HYPOGLYCEMIA IN ADULTS WITH IDDM - A PROSPECTIVE-STUDY OF HYPOGLYCEMIC FREQUENCY AND ASSOCIATED SYMPTOMS SO DIABETES CARE LA English DT Article ID DIABETIC-PATIENTS; UNAWARENESS; NEUROENDOCRINE; RESPONSES; FEAR AB OBJECTIVE-To prospectively evaluate the frequency and severity of hypoglycemic episodes in IDDM subjects who declare themselves to have reduced awareness of hypoglycemia, to validate their self-designations in their natural environment, and to determine objectively the presence or absence of autonomic and neuroglycopenic symptoms associated with their low blood glucose (BG) levels. RESEARCH DESIGN AND METHODS-A total of 78 insulin-dependent diabetes mellitus (IDDM) subjects (mean age 38.3 +/- 9.2 years; duration of diabetes 19.3 +/- 10.4 years) completed two sets of assessments separated by 6 months. The assessments included reports of frequency and severity of low BG, symptoms associated with low BG, and a BG symptom/estimation trial using a hand-held computer (HHC). Diaries of hypoglycemic episodes were kept for the intervening 6 months. HbA(1) levels were determined at each assessment. RESULTS-Of the subjects, 39 declared themselves as having reduced awareness of hypoglycemia (reduced-awareness subjects). There were no differences between these reduced-awareness subjects and aware subjects with regard to age, sex, disease duration, insulin dose, or HbA(1). During the HHC trials, reduced-awareness subjects were significantly less accurate in detecting BG <3.9 mmol/l (33.2 +/- 47 vs. 47.6 +/- 50% detection, P = 0.001) and had significantly fewer autonomic (0.41 +/- 0.82 vs. 1.08 +/- 1.22, P = 0.006, reduced-awareness vs. aware) and neuroglycopenic (0.44 +/- 0.85 vs. 1.18 +/- 1.32, P = 0.004, reduced-awareness vs. aware) symptoms per subject. Prospective diary records revealed that reduced-awareness subjects experienced more moderate (351 vs. 238, P = 0.026) and severe (50 vs. 17, P = 0.0062) hypoglycemic events. The second assessment results were similar to the first and verified the reliability of the data. CONCLUSIONS-IDDM subjects who believe they have reduced awareness of hypoglycemia are generally correct. They have a history of more moderate and severe hypoglycemia, are less accurate at detecting BG <3.9 mmol/l, and prospectively experience more moderate and severe hypoglycemia than do aware subjects. Neither disease duration nor level of glucose control explains their reduced awareness of hypoglycemia. Reduced-awareness individuals may benefit from interventions designed to teach them to recognize all of their potential early warning symptoms. C1 UNIV VIRGINIA, HLTH SCI CTR, DEPT PSYCHIAT MED, CHARLOTTESVILLE, VA USA. VANDERBILT UNIV, CTR DIABET RES & TRAINING, NASHVILLE, TN USA. JOSLIN DIABET CTR, BOSTON, MA 02215 USA. RP CLARKE, WL (reprint author), UNIV VIRGINIA, HLTH SCI CTR, DEPT PEDIAT, BOX 386, CHARLOTTESVILLE, VA 22908 USA. NR 22 TC 198 Z9 199 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 1995 VL 18 IS 4 BP 517 EP 522 DI 10.2337/diacare.18.4.517 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QQ216 UT WOS:A1995QQ21600013 PM 7497862 ER PT J AU COX, D GONDERFREDERICK, L POLONSKY, W SCHLUNDT, D JULIAN, D CLARKE, W AF COX, D GONDERFREDERICK, L POLONSKY, W SCHLUNDT, D JULIAN, D CLARKE, W TI A MULTICENTER EVALUATION OF BLOOD-GLUCOSE AWARENESS TRAINING .2. SO DIABETES CARE LA English DT Article ID INSULIN-DEPENDENT DIABETICS; DISCRIMINATION; IDDM AB OBJECTIVE-Blood glucose awareness training (BGAT) teaches individuals with insulin-dependent diabetes to more accurately estimate/detect their blood glucose (BG) fluctuations. It has not, however, consistently resulted in improved ability to detect low BG. To assess an enhanced version of BGAT (BGAT-II), with more focus on increasing sensitivity to low BG events, a multicenter study was undertaken. Following up on previous findings that BGAT is most effective with individuals who are least accurate in estimating BG, this study explicitly recruited subjects who did and did not report reduced awareness of hypoglycemia. RESEARCH DESIGN AND METHODS-Seventy-eight subjects from three research sites participated in a repeated baseline design. Subjects' BG estimation accuracy and BG profiles were assessed 6 months before, immediately before, and immediately after BGAT-II. RESULTS-Post-treatment, BGAT-II led to better overall accuracy in detecting BG fluctuations and better detection of both low and high BG levels. This was achieved while the number of low readings of self-monitoring of blood glucose (SMBG) was reduced. Reduction in the number of low SMBG events was significant only for subjects reporting awareness of hypoglycemia. Detection of low BG was significant only for subjects reporting reduced awareness of hypoglycemia. Both groups demonstrated equivalent improvements in detection of high BG levels. CONCLUSIONS-BGAT may be an effective behavioral strategy for reversing hypoglycemic unawareness and an adjunct to intensive insulin therapy to reduce the occurrence of severe hypoglycemia. C1 JOSLIN DIABET CTR,BOSTON,MA 02215. VANDERBILT UNIV,SCH MED,NASHVILLE,TN 37212. RP COX, D (reprint author), UNIV VIRGINIA,HLTH SCI CTR,BOX 223,CHARLOTTESVILLE,VA 22908, USA. FU NCRR NIH HHS [RR-00847]; NIDDK NIH HHS [R01-DK-28288] NR 16 TC 69 Z9 73 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 1995 VL 18 IS 4 BP 523 EP 528 DI 10.2337/diacare.18.4.523 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QQ216 UT WOS:A1995QQ21600014 PM 7497863 ER PT J AU FAUSTMAN, DL AF FAUSTMAN, DL TI ALTERED MHC CLASS-I EXPRESSION - A ROLE FOR TRANSPLANTATION AND IDDM AUTOIMMUNITY SO DIABETES-METABOLISM REVIEWS LA English DT Article RP FAUSTMAN, DL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,SCH MED,IMMUNOBIOL LAB,BLDG 149,13TH ST,CNY-3,BOSTON,MA 02129, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0742-4221 J9 DIABETES METAB REV JI Diabetes-Metab. Rev. PD APR PY 1995 VL 11 IS 1 BP 1 EP 19 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QR199 UT WOS:A1995QR19900001 PM 7600904 ER PT J AU SPIRO, MJ HE, Q DAUTILIA, ML AF SPIRO, MJ HE, Q DAUTILIA, ML TI EFFECT OF HIGH GLUCOSE ON FORMATION OF EXTRACELLULAR-MATRIX COMPONENTS BY CULTURED RAT-HEART ENDOTHELIAL-CELLS SO DIABETOLOGIA LA English DT Article DE RAT HEART ENDOTHELIAL CELLS; TYPE VI COLLAGEN; TYPE IV COLLAGEN; TYPE I COLLAGEN; FIBRONECTIN; GLUT1; HIGH GLUCOSE ID IV COLLAGEN PRODUCTION; VI COLLAGEN; BASEMENT-MEMBRANE; HEXOSE-TRANSPORT; MESANGIAL CELLS; PROTEIN; EXPRESSION; RNA AB In an attempt to define the basis for the microvascular changes observed in diabetic myocardium, a study was undertaken on the effect of elevated glucose on the synthesis by rat heart endothelial cells of the extracellular matrix components, types VI, IV and I collagen, as well as fibronectin. Confluent cultures of these cells, isolated by fluorescence-activated cell sorting after treatment with rhodamine-labelled acetylated low density lipoprotein, showed a three to fivefold enhancement in the synthesis of type VI collagen after exposure for 48 h to high glucose (20 to 30 mmol/l), as determined by immunoblot analysis. Increased production of type IV collagen and fibronectin was also observed, but the change was smaller and no effect on type I collagen was found. Measurement of mRNA levels by hybridization with cDNA probes indicated that 48-h exposure to high glucose significantly increased the level of transcripts for type VI and IV collagens but not for type I collagen. While glucose consumption by endothelial cells in high glucose doubled in the initial 24-h period, utilization returned to normal by 48 h, concomitant with a reduction in GLUT1 transcript levels, suggesting that signals for stimulation of collagen synthesis must be active during the initial period of exposure to elevated glucose levels. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM, BOSTON, MA 02115 USA. RP JOSLIN DIABET CTR, 1 JOSLIN PL, BOSTON, MA 02215 USA. FU NHLBI NIH HHS [HL31315]; NIDDK NIH HHS [DK36836] NR 33 TC 23 Z9 23 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD APR PY 1995 VL 38 IS 4 BP 430 EP 436 DI 10.1007/BF00410280 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QN462 UT WOS:A1995QN46200007 PM 7796983 ER PT J AU RHO, JP YOSHIKAWA, TT AF RHO, JP YOSHIKAWA, TT TI THE COST OF INAPPROPRIATE USE OF ANTIINFECTIVE AGENTS IN OLDER PATIENTS SO DRUGS & AGING LA English DT Article ID ADVERSE DRUG-REACTIONS; SKILLED-NURSING FACILITIES; ANTIBIOTIC USE; ANTIMICROBIAL RESISTANCE; GERIATRIC-PATIENTS; HOME RESIDENTS; MEDICATION; USAGE; COMMUNITY; AMINOGLYCOSIDES C1 US DEPT VET AFFAIRS,OFF GERIATR & EXTENDED CARE,WASHINGTON,DC 20420. GEORGE WASHINGTON UNIV,SCH MED,DEPT HLTHCARE SCI,WASHINGTON,DC. UNIV SO CALIF,SCH PHARM,DEPT CLIN PHARM,LOS ANGELES,CA. NR 43 TC 5 Z9 5 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PD APR PY 1995 VL 6 IS 4 BP 263 EP 267 DI 10.2165/00002512-199506040-00001 PG 5 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA QR191 UT WOS:A1995QR19100001 PM 7613015 ER PT J AU CLOUSTON, PD KIERS, L MENKES, D SANDER, H CHIAPPA, K CROS, D AF CLOUSTON, PD KIERS, L MENKES, D SANDER, H CHIAPPA, K CROS, D TI MODULATION OF MOTOR-ACTIVITY BY CUTANEOUS INPUT - INHIBITION OF THE MAGNETIC MOTOR EVOKED-POTENTIAL BY DIGITAL ELECTRICAL-STIMULATION SO ELECTROMYOGRAPHY AND MOTOR CONTROL-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE TRANSCRANIAL MAGNETIC STIMULATION; DIGITAL STIMULATION; INHIBITION; MOTOR EVOKED POTENTIAL ID PERIPHERAL-NERVE STIMULATION; DORSAL INTEROSSEOUS MUSCLE; TASK-DEPENDENT CHANGES; LONG-LATENCY REFLEXES; SILENT PERIOD; UPPER-LIMB; TRANSCRANIAL STIMULATION; AFFERENT STIMULATION; CORTEX STIMULATION; UNIT RESPONSES AB We examined the inhibitory effect of a brief train of digital (D2) electrical stimuli at 4 times perception threshold on transcranial magnetic motor evoked potentials (MEPs) recorded from abductor pollicis brevis (APE) and flexor carpi radialis (FCR) muscles ipsilateral to the side of D2 stimulation. We compared this to the inhibitory effect of ipsilateral D2 stimulation on averaged rectified EMG recorded at 10% maximum voluntary contraction and on F-responses and H-reflexes recorded from these same muscles. We also compared MEPs recorded following D2 stimulation just above perception threshold to MEPs following higher intensity D2 stimulation. As well, we assessed the effect of preceding D2 stimulation on MEPs recorded from a relaxed versus tonically contracted hand muscle. D2 stimulation elicited a triphasic response of modest MEP facilitation followed by inhibition and further facilitation. The duration and onset of MEP inhibition correlated with those of the initial period of rectified EMG inhibition, however, the magnitude of MEP inhibition was generally less than the magnitude of EMG inhibition, consistent with a greater inhibitory effect of digital afferents on smaller motor neurons. MEPs were not facilitated during the rebound of EMG activity (the E2 period) that usually followed the initial period of EMG inhibition (I1 period). The behavior of H-reflexes and F-responses following ipsilateral D2 stimulation suggested that inhibition of both EMG and MEPs is not mediated via presynaptic inhibition of Ia afferents, and that inhibition is augmented by descending rather than segmental input to spinal motor neurons. Tonic contraction of the target muscle during D2 stimulation decreased the inhibitory effect of the preceding digital stimulus possibly due to recruitment of larger spinal motor neurons less likely to be inhibited by cutaneous input. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. NR 49 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0924-980X J9 ELECTROMYOGR MOTOR C JI Electromyogr. Mot. Control-Electroencephalogr. Clin. Neurophysiol. PD APR PY 1995 VL 97 IS 2 BP 114 EP 125 DI 10.1016/0924-980X(94)00310-4 PG 12 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA QU966 UT WOS:A1995QU96600006 PM 7537203 ER PT J AU KIERS, L CLOUSTON, P CHIAPPA, KH CROS, D AF KIERS, L CLOUSTON, P CHIAPPA, KH CROS, D TI ASSESSMENT OF CORTICAL MOTOR OUTPUT - COMPOUND MUSCLE ACTION-POTENTIAL VERSUS TWITCH FORCE RECORDING SO ELECTROMYOGRAPHY AND MOTOR CONTROL-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE TRANSCRANIAL MAGNETIC STIMULATION; MOTOR EVOKED POTENTIAL (MEP) AMPLITUDE; TWITCH FORCE ID MAGNETIC STIMULATION; CORTEX STIMULATION; TRANSCRANIAL STIMULATION; ELECTRICAL-STIMULATION; VOLUNTARY CONTRACTION; INTACT MAN; RESPONSES; FACILITATION; PATHWAYS; VOLLEYS AB To determine whether motor evoked potential (MEP) amplitude and area are accurate measurements of the magnitude of response to magnetic cortical stimulation, we simultaneously recorded the twitch and MEP in the first dorsal interosseous muscle of 8 normal subjects. Consecutive stimuli were delivered at increasing stimulus intensities (SI) or with increasing levels of background voluntary muscle contraction (BVC). There was stimulus to stimulus variability in MEP amplitude, area and twitch force. At low SI and at low levels of background contraction, there was a good correlation between twitch amplitude and MEP amplitude and area (r = 0.6-0.96, P < 0.005). Increasing either variable caused the correlation to decrease significantly (r = 0.02-0.31, P > 0.01). With increasing SI, MEP amplitude and area plateaued but twitch force continued to increase. A similar pattern was observed with higher levels of background muscle contraction although in some subjects a second increase in MEP amplitude and area was seen. Collision experiments demonstrated that the amplitude of the EMG activity resulting from repetitive motoneuron firing increased as SI was increased. This is due to multiple descending volleys which result in repetitive firing of some spinal motoneurons. Rapid, repetitive firing of some motor units is likely to result in phase cancellation and, therefore, the MEP amplitude, and to a lesser extent area, do not accurately reflect the net motor output. C1 MASSACHUSETTS GEN HOSP,CLIN NEUROPHYSIOL LABS,EMG LAB,BOSTON,MA 02114. NR 26 TC 27 Z9 27 U1 0 U2 3 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0924-980X J9 ELECTROMYOGR MOTOR C JI Electromyogr. Mot. Control-Electroencephalogr. Clin. Neurophysiol. PD APR PY 1995 VL 97 IS 2 BP 131 EP 139 DI 10.1016/0924-980X(94)00325-2 PG 9 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA QU966 UT WOS:A1995QU96600008 PM 7729346 ER PT J AU CHEATHAM, B KAHN, CR AF CHEATHAM, B KAHN, CR TI INSULIN ACTION AND THE INSULIN SIGNALING NETWORK SO ENDOCRINE REVIEWS LA English DT Review ID GROWTH-FACTOR-I; TYROSINE KINASE-ACTIVITY; HAMSTER OVARY CELLS; POLYACRYLAMIDE GEL-ELECTROPHORESIS; RECEPTOR TRANSMEMBRANE DOMAIN; GLUCOSE-TRANSPORTER GLUT4; XENOPUS-LAEVIS OOCYTES; HUMAN SKELETAL-MUSCLE; MEMBRANE ECTO-ATPASE; PROTEIN S6 KINASE C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RP CHEATHAM, B (reprint author), JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK33201, DK-31036] NR 276 TC 715 Z9 728 U1 0 U2 29 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD APR PY 1995 VL 16 IS 2 BP 117 EP 142 DI 10.1210/er.16.2.117 PG 26 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QT902 UT WOS:A1995QT90200001 PM 7781591 ER PT J AU TAKAHASHI, S REDDY, SV DALLAS, M DEVLIN, R CHOU, JY ROODMAN, GD AF TAKAHASHI, S REDDY, SV DALLAS, M DEVLIN, R CHOU, JY ROODMAN, GD TI DEVELOPMENT AND CHARACTERIZATION OF A HUMAN MARROW STROMAL CELL-LINE THAT ENHANCES OSTEOCLAST-LIKE CELL-FORMATION SO ENDOCRINOLOGY LA English DT Article ID HUMAN-BONE-MARROW; COLONY-STIMULATING FACTOR; MULTINUCLEATED CELLS; GROWTH-FACTOR; OSTEOPETROTIC MICE; OSTEOBLASTIC CELLS; MOLECULAR-CLONING; SIMIAN VIRUS-40; GENE-EXPRESSION; SPLEEN-CELLS AB We established a human bone marrow stromal cell line (Saka) by infecting marrow adherent cells from semisolid marrow cultures with a recombinant simian virus-40 (SV40) virus. The cells expressed SV40 large tumor antigen, had a fibroblast-like shape, and expressed fibronectin and vimentin. They did not contain detectable alkaline phosphatase activity; express myeloid, lymphoid, or factor VIII-associated antigens; or develop adipocyte-like characteristics with dexamethasone treatment. Polymerase chain reaction analysis of Saka cell RNA detected expression of messenger RNAs for interleukin-6 (IL-6), IL-1 beta, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, stem cell factor, and the 1,25-dihydroxyvitamin D-3 receptor. Coculture of Saka cells with human marrow mononuclear cells enhanced formation of osteoclast-like multinucleated cells (MNC) in long term human bone marrow cultures. These MNC expressed calcitonin receptors and formed resorption lacunae on dentine. In contrast, coculture of marrow mononuclear cells with other SV40-transformed human marrow stromal cell lines did not increase MNC formation. Conditioned medium from Saka cells or coculture of bone marrow and Saka cells separated by a Millipore membrane did not enhance MNC formation. Addition of a neutralizing antibody to IL-6 or IL-1 beta blocked the effects of Saka cells on MNC formation. These results suggest that marrow stromal cells enhance osteoclast formation in part through direct cell to cell contact and production of IL-6 and/or IL-1 beta. C1 AUDIE L MURPHY MEM VET ADM MED CTR, RES SERV 151, SAN ANTONIO, TX 78284 USA. UNIV TEXAS, HLTH SCI CTR, DEPT MED, SAN ANTONIO, TX 78284 USA. NIH, BETHESDA, MD 20892 USA. FU NCI NIH HHS [CA-40035]; NIADDK NIH HHS [AM-35188]; NIAMS NIH HHS [AR-39539] NR 44 TC 33 Z9 34 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 APR PY 1995 VL 136 IS 4 BP 1441 EP 1449 DI 10.1210/en.136.4.1441 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QP117 UT WOS:A1995QP11700017 PM 7534699 ER PT J AU LEECH, CA HOLZ, GG HABENER, JF AF LEECH, CA HOLZ, GG HABENER, JF TI PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE INDUCES THE VOLTAGE-INDEPENDENT ACTIVATION OF INWARD MEMBRANE CURRENTS AND ELEVATION OF INTRACELLULAR CALCIUM IN HIT-T15 INSULINOMA CELLS SO ENDOCRINOLOGY LA English DT Article ID BETA-CELLS; CYCLIC-AMP; RAT; RECEPTOR; PEPTIDE; CA-2+ AB The secretion of insulin by pancreatic beta-cells is controlled by synergistic interactions of glucose and hormones of the glucagon-related peptide family, of which pituitary adenylate cyclase-activating polypeptide (PACAP) is a member. Here we show by simultaneous recording of intracellular calcium ion ([Ca2+](i)) and membrane potential that both PACAP-27 and PACAP-38 depolarize HIT-T15 cells and raise [Ca2+](i). PACAP stimulation can result in membrane depolarization by two distinct mechanisms: 1) PACAP reduces the membrane conductance and increases membrane excitability; and 2) PACAP activates a pronounced inward current that is predominantly a Na+ current, blockable by La3+, and which exhibits a reversal potential of about -28 mV. Activation of this current does not require membrane depolarization, because the response is observed when cells are held under voltage clamp at -70 mV. This current may result from the cAMP-dependent activation of nonspecific cation channels because the current is also observed in response to forskolin or membrane-permeant analogs of cAMP. We also suggest that PACAP raises [Ca2+](i) and stimulates insulin secretion by three distinct mechanisms: 1) depolarization activates Ca2+ influx through L-type voltage-dependent calcium channels, 2) mobilization of intracellular Ca2+ stores, and 3) entry of Ca2+ via voltage-independent Ca2+ channels. These effects of PACAP may play an important role in a neuro-entero-endocrine loop regulating insulin secretion from pancreatic beta-cells during the transition period from fasting to feeding. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DIABET UNIT, BOSTON, MA 02114 USA. RP LEECH, CA (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, HOWARD HUGHES MED INST, MOLEC ENDOCRINOL LAB, BOSTON, MA 02114 USA. RI Holz, George/A-3386-2012 FU NIDDK NIH HHS [DK-30834, R01 DK030834, DK-30457, R01 DK045817, R01 DK045817-06A2] NR 29 TC 41 Z9 41 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 APR PY 1995 VL 136 IS 4 BP 1530 EP 1536 DI 10.1210/en.136.4.1530 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QP117 UT WOS:A1995QP11700029 PM 7895663 ER PT J AU SAAD, MJA FOLLI, F KAHN, CR AF SAAD, MJA FOLLI, F KAHN, CR TI INSULIN AND DEXAMETHASONE REGULATE INSULIN-RECEPTORS, INSULIN-RECEPTOR SUBSTRATE-1, AND PHOSPHATIDYLINOSITOL 3-KINASE IN FAO HEPATOMA-CELLS SO ENDOCRINOLOGY LA English DT Article ID TYROSINE KINASE-ACTIVITY; GLUCOSE-OXIDATION; RAT ADIPOCYTES; ANIMAL-MODELS; INTACT RAT; PROTEIN; MUSCLE; ASSOCIATION; BINDING; LIVER AB Insulin rapidly stimulates tyrosine kinase activity of its receptor, resulting in phosphorylation of the cytosolic substrate, insulin receptor substrate-1 (IRS-1), which, in turn, associates with phosphatidylinositol 3-kinase (PI 3-kinase), thus activating the enzyme. In the present study we have examined these three early postreceptor components of the insulin action pathway in rat hepatoma (Fao) cells and have determined the effects of two hormones that can induce insulin resistance, dexamethasone and insulin. Dexamethasone (1 mu M) induced a time- and dose-dependent increase in insulin receptor levels in Fao cells, reaching 135 +/- 3% of basal levels after 24 h (P < 0.05). There was a simultaneous increase in IRS-I protein to 255 +/- 66% of the control value (P < 0.05) and a parallel increase in IRS-1 phosphorylation. Insulin stimulation of IRS-1-associated PI 3-kinase was also increased by 70% in cells treated with dexamethasone despite only a minimal increase in PI 3-kinase protein, as determined by immunoblotting. Prolonged insulin treatment induced a time- and dose-dependent decrease in insulin receptor and IRS-1 protein levels, reaching nadirs of 40 +/- 4% (P < 0.01) and 15 +/- 6% (P < 0.005) of control levels, respectively, after 24 h with 100 nM insulin. There was also a decrease in the phosphorylation of insulin receptors and IRS-1, a marked decrease in the association between IRS-1 and PI 3-kinase, and an 82% decrease in insulin-stimulated PI 3-kinase activity without a significant change in PI S-kinase protein levels. When cells were exposed to both insulin and dexamethasone, the effect of insulin to reduce insulin receptor and IRS-1 levels and insulin-stimulated IRS-1 phosphorylation dominated. These data suggest that regulation of the insulin receptor, IRS-1, and PI 3-kinase contributes significantly to the insulin resistance induced by chronic hyperinsulinemia, but that glucocorticoid-induced insulin resistance is located beyond these early steps in insulin action. (Endocrinology 136: 1579-1588, 1995! C1 HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DEPT MED, BOSTON, MA 02215 USA. RP SAAD, MJA (reprint author), JOSLIN DIABET CTR, DIV RES, 1 JOSLIN PL, BOSTON, MA 02215 USA. OI folli, franco/0000-0001-9824-5222 FU NIDDK NIH HHS [DK-33201, DK-36836] NR 41 TC 48 Z9 50 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 1995 VL 136 IS 4 BP 1579 EP 1588 DI 10.1210/en.136.4.1579 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QP117 UT WOS:A1995QP11700037 PM 7895667 ER PT J AU HISNANICK, JJ KYER, BL AF HISNANICK, JJ KYER, BL TI ASSESSING A DISAGGREGATED ENERGY INPUT - USING CONFIDENCE-INTERVALS AROUND TRANSLOG ELASTICITY ESTIMATES SO ENERGY ECONOMICS LA English DT Article DE ENERGY; ELASTICITY ESTIMATES; AES ID SUBSTITUTION; DEMAND; GROWTH AB The role of energy in the production of manufacturing output has been debated extensively in the literature, particularly its relationship with capital and labor. In an attempt to provide some clarification in this debate, a two-step methodology was used. First, under the assumption of a five-factor production function specification, we distinguished between electric and non-electric energy and assessed each component's relationship with capital and labor. Second, we calculated both the Allen and price elasticities and constructed 95% confidence intervals around these values. Our approach led to the following conclusions: that the disaggregation of the energy input into electric and non-electric energy is justified; that capital and electric energy and capital and non-electric energy are substitutes, while labor and electric energy and labor and non-electric energy are complements in production; and that capital and energy are substitutes, while labor and energy are complements. C1 FRANCIS MARION COLL,FLORENCE,SC 29501. RP HISNANICK, JJ (reprint author), US DEPT VET AFFAIRS,NCVAS 008C12,810 VERMONT AVE NW,WASHINGTON,DC 20420, USA. NR 18 TC 13 Z9 14 U1 1 U2 4 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA LINACRE HOUSE JORDAN HILL, OXFORD, OXON, ENGLAND OX2 8DP SN 0140-9883 J9 ENERG ECON JI Energy Econ. PD APR PY 1995 VL 17 IS 2 BP 125 EP 132 DI 10.1016/0140-9883(95)00008-I PG 8 WC Economics SC Business & Economics GA RE974 UT WOS:A1995RE97400004 ER PT J AU CHRISTENSEN, EI NIELSEN, S MOESTRUP, SK BORRE, C MAUNSBACH, AB DEHEER, E RONCO, P HAMMOND, TG VERROUST, P AF CHRISTENSEN, EI NIELSEN, S MOESTRUP, SK BORRE, C MAUNSBACH, AB DEHEER, E RONCO, P HAMMOND, TG VERROUST, P TI SEGMENTAL DISTRIBUTION OF THE ENDOCYTOSIS RECEPTOR GP330 IN RENAL PROXIMAL TUBULES SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE KIDNEY; IMMUNOCYTOCHEMISTRY; LYSOSOMES; ENDOCYTOSIS; RECEPTORS ID DENSITY-LIPOPROTEIN RECEPTOR; FOLATE-BINDING PROTEIN; BRUSH-BORDER; HEYMANN NEPHRITIS; COATED PIT; RAT-KIDNEY; ULTRASTRUCTURAL-LOCALIZATION; MONOCLONAL-ANTIBODIES; EPITHELIAL-CELLS; PLASMA-MEMBRANE AB The subcellular distribution and segmental variations in location of gp330, a scavenger receptor for filtered proteins in renal proximal tubules, was analyzed. Kidney tissue from rats (4 differed strains), rabbits and humans were analyzed by light- and electron microscope immunocytochemistry, using cryosections or Lowicryl sections from cryosubstituted tissue. Gp330 was located mainly in apical coated pits, small and large endocytic vacuoles and in dense apical tubules in the proximal tubule cells. The labeling density was markedly higher in segments 1 and 2 as compared to segment 3 of the proximal tubule. In addition to the location in the early part of the endocytic pathway, gp330 was also present in lysosomes, especially in segments 1 and 2. The lysosomal labeling was not restricted to the membrane, but was also seen in the matrix. Localization of gp330 in lysosomes was ron firmed on sections from purified lysosomal fractions from rat renal cor tex. The brash border localization of gp330 in proximal tubules exhibited a characteristic segmental variation. In the initial part of segment 1, there was virtually no brush border labeling, In the remaining part of segment 1 and in segment 2, there was a distinct but sometimes patchy labeling of the brush border. In segment 3, groups of microvilli of approximately 10 as seen in sections were intensively labeled from bottom to tip and there were often more than one of these groups on a single cell, the remaining microvilli were unlabeled. No differences in the cellular and subcellular localization of gp330 were observed between species or rat strains. In conclusion, the present study demonstrates that in addition to its location in the early endocytic and recycling pathway, gp330 is also present in microvilli and the protein and degradation products thereof is present in lysosomes, consistent with its role as a protein scavenger receptor. C1 AARHUS UNIV,INST MED BIOCHEM,DK-8000 AARHUS,DENMARK. LEIDEN UNIV,DEPT PATHOL,LEIDEN,NETHERLANDS. HOP TENON,INSERM,U64,F-75970 PARIS,FRANCE. UNIV WISCONSIN HOSP & CLIN,WILLIAM S MIDDLETON MEM VET ADM HOSP,MADISON,WI 53792. RP CHRISTENSEN, EI (reprint author), AARHUS UNIV,INST ANAT,DEPT CELL BIOL,DK-8000 AARHUS C,DENMARK. RI Moestrup, Soren Kragh/A-1403-2014 OI Moestrup, Soren Kragh/0000-0003-3862-2107 FU NIDDK NIH HHS [DK 46117] NR 49 TC 118 Z9 118 U1 0 U2 2 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 APR PY 1995 VL 66 IS 4 BP 349 EP 364 PG 16 WC Cell Biology SC Cell Biology GA QT314 UT WOS:A1995QT31400005 PM 7656901 ER PT J AU CARMEL, R GOTT, PS WATERS, CH CAIRO, K GREEN, R BONDAREFF, W DEGIORGIO, CM CUMMINGS, JL JACOBSEN, DW BUCKWALTER, G HENDERSON, VW AF CARMEL, R GOTT, PS WATERS, CH CAIRO, K GREEN, R BONDAREFF, W DEGIORGIO, CM CUMMINGS, JL JACOBSEN, DW BUCKWALTER, G HENDERSON, VW TI THE FREQUENTLY LOW COBALAMIN LEVELS IN DEMENTIA USUALLY SIGNIFY TREATABLE METABOLIC, NEUROLOGIC AND ELECTROPHYSIOLOGIC ABNORMALITIES SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE COBALAMIN DEFICIENCY; METHYLMALONIC ACID; HOMOCYSTEINE; EVOKED POTENTIALS; ELECTROENCEPHALOGRAM; DEMENTIA MALABSORPTION ID DEOXYURIDINE SUPPRESSION TEST; LOW SERUM VITAMIN-B12; ALZHEIMERS-DISEASE; MEGALOBLASTIC-ANEMIA; DEFICIENCY STATES; PERNICIOUS-ANEMIA; SENILE DEMENTIA; FOLLOW-UP; SUBTLE; MANIFESTATIONS AB Cobalamin levels are frequently low in patients with dementia, but it is unclear if they represent definable deficiency and what the mechanisms are. Therefore, patients being evaluated for dementia who had low cobalamin levels but no obvious evidence of deficiency were studied hematologically, neurologically and with metabolic tests and were re-evaluated after cobalamin treatment. Abnormalities suggestive of or diagnostic for deficiency were documented in most of the 16 demented and nondemented patients. Metabolic results: 50% of patients tested had abnormal deoxyuridine suppression and 44% had increased serum methylmalonic acid and/or homocysteine levels; these test results correlated with each other. Neurologic results: 73% of patients had clinical abnormalities, primarily mild neuropathies, not attributable to other causes, 75% had electroencephalographic abnormalities, 77% had abnormal visual evoked potentials and 33% had abnormal somatosensory potentials. Metabolic and neurologic dysfunction were present together or absent together in all but 2 cases. Cobalamin therapy improved 50-100% of the various types of abnormalities, although it did not improve cognitive function in the 13 demented patients. Food-cobalamin malabsorption was found in 60% of the patients. Despite the absence of megaloblastic anemia and rarity of traditional malabsorption of free cobalamin, low cobalamin levels in demented patients frequently represent mild cobalamin deficiency and are often associated with food-cobalamin malabsorption. Perhaps most importantly, this is accompanied not only by metabolic changes but by evidence of mild neurologic dysfunction. Their frequent reversibility by cobalamin confirms that these defects indeed arise from cobalamin deficiency. Although the long-standing dementia does not improve, treating such patients with cobalamin has other concrete benefits. C1 UNIV SO CALIF,SCH MED,DEPT PATHOL,LOS ANGELES,CA 90033. UNIV SO CALIF,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90033. UNIV SO CALIF,LOS ANGELES CTY MED CTR,LOS ANGELES,CA 90033. CLEVELAND CLIN FDN,LAB HEMATOL SECT,CLEVELAND,OH 44195. UNIV CALIF LOS ANGELES,HLTH SCI CTR,DEPT NEUROL,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,HLTH SCI CTR,DEPT PSYCHIAT,LOS ANGELES,CA. UNIV SO CALIF,DEPT PSYCHOL,LOS ANGELES,CA 90089. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,LOS ANGELES,CA 90073. UNIV SO CALIF,ANDRUS GERONTOL CTR,LOS ANGELES,CA. RP CARMEL, R (reprint author), UNIV SO CALIF,SCH MED,DEPT MED,RMR 306,2025 ZONAL AVE,LOS ANGELES,CA 90033, USA. FU NCRR NIH HHS [MO1 RR-43]; NIA NIH HHS [AG-05142]; NIDDK NIH HHS [DK-32640] NR 51 TC 97 Z9 97 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD APR PY 1995 VL 54 IS 4 BP 245 EP 253 PG 9 WC Hematology SC Hematology GA RD188 UT WOS:A1995RD18800006 PM 7789470 ER PT J AU DEFOUGEROLLES, AR DIAMOND, MS SPRINGER, TA AF DEFOUGEROLLES, AR DIAMOND, MS SPRINGER, TA TI HETEROGENOUS GLYCOSYLATION OF ICAM-3 AND LACK OF INTERACTION WITH MAC-1 AND P150,95 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE ICAM-1; ICAM-3; LEUKOCYTE INTEGRINS; LFA-1; ADHESION ID INTERCELLULAR-ADHESION MOLECULE-3; FUNCTION-ASSOCIATED ANTIGEN-1; COUNTER-RECEPTOR; TRANSENDOTHELIAL MIGRATION; NEUTROPHIL AGGREGATION; COMPLEMENT RECEPTOR; L-SELECTIN; LFA-1; IMMUNOGLOBULIN; CLONING AB Intercellular adhesion molecule (ICAM)-1, ICAM-2, and ICAM-3 have been identified as counter-receptors for the leukocyte integrin lymphocyte function-associated antigen 1 (LFA-1). The other leukocyte integrins, Mac-1 and p150,95, also interact with ICAM-1. ICAM-1 and ICAM-3 are highly homologous, and an undefined ligand for Mac-1 is present on neutrophils where ICAM-3 is well expressed. In addition, glycosylation has been shown to affect the interaction of ICAM-1 with Mac-1. We therefore sought to characterize ICAM-3 heterogeneity and determine whether ICAM-3 was a ligand for either Mac-1 or p150,95. Despite extensive differences in N-linked glycosylation, ICAM-3 purified from lymphoid cells and from neutrophils supports adhesion of LFA-1-bearing cells equally well; however, neither supports adhesion of Mac-1 or p150,95-expressing chinese hamster ovary cell transfectants. Similarly, purified Mac-1 does not support adhesion of ICAM-2 or ICAM-3-expressing L cell transfectants. ICAM-3 on neutrophils does not participate in Mac-1-dependent homotypic aggregation. Thus, ICAM-3 is not a counter-receptor for either Mac-1 or p150,95. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA31798, CA31799] NR 35 TC 29 Z9 30 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 APR PY 1995 VL 25 IS 4 BP 1008 EP 1012 DI 10.1002/eji.1830250422 PG 5 WC Immunology SC Immunology GA QY508 UT WOS:A1995QY50800020 PM 7737271 ER PT J AU LAWRENCE, MB BERG, EL BUTCHER, EC SPRINGER, TA AF LAWRENCE, MB BERG, EL BUTCHER, EC SPRINGER, TA TI ROLLING OF LYMPHOCYTES AND NEUTROPHILS ON PERIPHERAL NODE ADDRESSIN AND SUBSEQUENT ARREST ON ICAM-1 IN SHEAR-FLOW SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE L-SELECTIN; CD62L; ROLLING ICAM-1; CD54 ID LEUKOCYTE ADHESION MOLECULE-1; ENDOTHELIAL CELL RECOGNITION; L-SELECTIN; HOMING RECEPTOR; T-CELLS; FUNCTIONAL-CHARACTERIZATION; VASCULAR ADDRESSIN; BINDING; VENULES; ACTIVATION AB We studied leukocyte interactions in shear now with peripheral lymph node addressin (PNAd), a mixture of glycoproteins expressed on high endothelial venules (HEV) that is required for lymphocyte homing and has been shown to contain a ligand for L-selectin. T lymphocytes and neutrophils tether and roll on plastic-immobilized PNAd and E-selectin at 1.8 dyn/cm(2) wall shear stress, but fail to interact with immobilized ICAM-1, a ligand for LFA-1 and Mac-1, at the same flow rate. Celts roll faster on PNAd than on P-selectin or E-selectin. L-selectin mAb inhibit T lymphocyte and neutrophil tethering to PNAd, but do not inhibit T lymphocyte tethering to purified E-selectin. If allowed to interact with ICAM-1 under static conditions, phorbol ester-treated T lymphocytes, but not resting T lymphocytes, are able to form stationary adhesions that withstand the detachment force generated by 36 dyn/cm(2) wall shear stress. In contrast, a wall shear stress of 7.3 dyn/cm(2) detaches 50% of resting T lymphocytes bound to PNAd. Incubating T lymphocytes on PNAd and ICAM-1 does not result in adhesion strengthening, suggesting that adhesion through PNAd by L-selectin does not stimulate lymphocyte LFA-1 avidity for ICAM-1. Chemoattractant stimulation of neutrophils or phorbol ester stimulation of lymphoblasts rolling on coimmobilized PNAd and ICAM-1 results in rapid arrest and firm sticking, extending the model of sequential selectin-mediated rolling and subsequent integrin-mediated firm arrest to lymphocytes and ligands expressed on HEV. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,DEPT PATHOL,BOSTON,MA 02115. STANFORD UNIV,SCH MED,DEPT PATHOL,STANFORD,CA 94305. RI Berg, Ellen/D-9076-2014 OI Berg, Ellen/0000-0001-5149-6665 FU NCI NIH HHS [CA31799, CA31798]; NHLBI NIH HHS [HL48675] NR 42 TC 105 Z9 106 U1 0 U2 3 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 APR PY 1995 VL 25 IS 4 BP 1025 EP 1031 DI 10.1002/eji.1830250425 PG 7 WC Immunology SC Immunology GA QY508 UT WOS:A1995QY50800023 PM 7537667 ER PT J AU SCHNEIDER, H CAI, YC PRASAD, KVS SHOELSON, SE RUDD, CE AF SCHNEIDER, H CAI, YC PRASAD, KVS SHOELSON, SE RUDD, CE TI T-CELL ANTIGEN CD28 BINDS TO THE GRB-2/SOS COMPLEX, REGULATORS OF P21(RAS) SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD28; CO-STIMULATION; GRB-2/SOS ID RECEPTOR TYROSINE KINASES; CTLA-4 COUNTER-RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; SH3 DOMAINS; SIGNAL TRANSDUCTION; MITOGENIC SIGNAL; LYMPHOCYTES-T; ZETA-CHAIN; PROTEIN; ACTIVATION AB The T cell molecule CD28 provides a co-stimulatory signal that is required for T cell proliferation, and has been implicated in the control of T cell anergy. An important clue to the signaling mechanism of CD28 is the finding that CD28 can bind to phosphatidylinositol 3-kinase (PI 3-kinase) by means of a cytoplasmic phospho-YMNM (pYMNM) motif. A remaining issue concerns whether CD28 can recruit other intracellular signaling molecules. In this study, we show that CD28 uses the same pYMNM motif to recruit a second intracellular protein, GRB-2. CD28-associated GRB-2, as detected by anti-GRB-2 immunoblotting, was found in human peripheral T cells, HPB-ALL and Jurkat cells. As in the case of PI 3-kinase, antibody-induced cross-linking of CD28 induces a time-dependent recruitment of GRB-2. Likewise, mutation of the pY-191 residue within the pYMNM motif reduces GRB-2 binding. Peptide binding studies show that the SH2 domain of GRB-2 binds to the pYMNM motif with an affinity comparable to GRB-2/SHC, but some 10- to 100-fold lower than the CD28/PI3-kinase. Despite this, CD28/GRB-2 and CD28/PI 3-kinase complexes are found to co-exist in peripheral T cells. Finally, immunoblotting shows that CD28 also associates with the gene product of the human homolog of the Drosophila Son of sevenless gene (SOS), a GRB-2-complexed guanine nucleotide exchange factor responsible for converting p21(ras) to a GTP-bound active state. CD28-associated GRB2/SOS is likely to serve an important link in the regulation of p21(ras) and lymphokine expression mediated by CD28. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 67 TC 117 Z9 120 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD APR PY 1995 VL 25 IS 4 BP 1044 EP 1050 DI 10.1002/eji.1830250428 PG 7 WC Immunology SC Immunology GA QY508 UT WOS:A1995QY50800026 PM 7737275 ER PT J AU BREWSTER, DC AF BREWSTER, DC TI THE ROLE OF ANGIOPLASTY TO IMPROVE INFLOW FOR INFRAINGUINAL BYPASSES SO EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1078-5884 J9 EUR J VASC ENDOVASC JI Eur. J. Vasc. Endovasc. Surg. PD APR PY 1995 VL 9 IS 3 BP 262 EP 266 DI 10.1016/S1078-5884(05)80128-5 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA QU179 UT WOS:A1995QU17900002 PM 7620950 ER PT J AU LATINA, MA PARK, C AF LATINA, MA PARK, C TI SELECTIVE TARGETING OF TRABECULAR MESHWORK CELLS - IN-VITRO STUDIES OF PULSED AND CW LASER INTERACTIONS SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE TRABECULAR MESHWORK; GLAUCOMA; PULSED LASER; LASER TRABECULOPLASTY; SELECTIVE TARGETING ID ND-YAG LASER; ULTRASTRUCTURAL-CHANGES; HUMAN-SKIN; ARGON; PHOTOTHERMOLYSIS; IRRADIATION; TRABECULOPLASTY; RADIATION; MONKEYS; WAVES AB The purpose of the present study was to selectively target pigmented trabecular meshwork cells without producing collateral damage to adjacent non-pigmented cells or structures. The ability to selectively target trabecular meshwork cells without coagulation, while preserving the structural integrity of the meshwork, could be a useful approach to study whether the biological response of non-coagulative damage to the trabecular meshwork and trabecular meshwork cells is similar to that seen with coagulative damage to the trabecular meshwork which occurs with argon laser trabeculoplasty. This approach also may be useful to non-invasively deplete trabecular meshwork cells while preserving the structural integrity of the trabecular meshwork in an animal model. A mixed cell culture of pigmented and non-pigmented trabecular meshwork cells were irradiated with Q-switched Nd-YAG and frequency-doubled Nd-YAG lasers, microsound pulsed dye-lasers, and an argon ion laser in order to define a regime where laser absorption would be confined to pigmented trabecular meshwork cells, thereby permitting selective targeting of these cells without producing collateral thermal damage to adjacent non-pigmented cells. Pulse durations ranged from 10 nsec to 0.1 sec. A fluorescent viability/cytotoxicity assay was used to evaluate laser effects and threshold energies, and cells were examined morphologically by light and TEM. Selective targeting of pigmented trabecular meshwork cells was achieved with pulse durations between 10 nsec and 1 mu sec and 1 mu sec without producing collateral thermal or structural damage to adjacent non-pigmented trabecular meshworks cells when examined by light and transmission electron microscopy. Pulse durations greater than 1 mu sec resulted in non-selective killing of non-pigmented trabecular meshwork cells. Threshold radiant exposures were as low as 18 mJ cm(-2), and increased at longer wavelengths, longer pulse durations and lower melanin contents within the cells. It is concluded that selective targeting of pigmented trabecular meshwork cells can be achieved using pulsed lasers with low threshold radiant exposures avoiding collateral thermal damage to adjacent nonpigmented trabecular meshwork cells, This approach can be readily applied in vivo. C1 SCHEPENS EYE RES INST,BOSTON,MA. RP LATINA, MA (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN LABS,BOSTON,MA 02114, USA. FU NEI NIH HHS [K11-EY-00292] NR 19 TC 146 Z9 182 U1 0 U2 9 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD APR PY 1995 VL 60 IS 4 BP 359 EP 371 DI 10.1016/S0014-4835(05)80093-4 PG 13 WC Ophthalmology SC Ophthalmology GA QR635 UT WOS:A1995QR63500003 PM 7789416 ER PT J AU SCHULZ, JB HENSHAW, DR MATTHEWS, RT BEAL, MF AF SCHULZ, JB HENSHAW, DR MATTHEWS, RT BEAL, MF TI COENZYME Q(10) AND NICOTINAMIDE AND A FREE-RADICAL SPIN TRAP PROTECT AGAINST MPTP NEUROTOXICITY SO EXPERIMENTAL NEUROLOGY LA English DT Note ID EXCITOTOXIC LESIONS; PARKINSONS-DISEASE; MITOCHONDRIAL; THERAPY; IMPAIRMENT; METABOLISM; UBIQUINONE; STRIATUM; TOXICITY; NEURONS AB l-Methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) produces Parkinsonism in both experimental animals and in man. MPTP is metabolized to 1-methyl-4-phenylpridinium, an inhibitor of mitochondrial complex I. MPTP administration produces ATP depletions in vivo, which may lead to secondary excitotoxicity and free radical generation. If this is the case then agents which improve mitochondrial function or free radical scavengers should attenuate MPTP neurotoxicity. In the present experiments three regimens of MPTP administration produced varying degrees of striatal dopamine depletion. A combination of coenzyme Q(10) and nicotinamide protected against both mild and moderate depletion of dopamine. In the MPTP regimen which produced mild dopamine depletion nicotinamide or the free radical spin trap N-tert-butyl-alpha-(2-sulfophenyl)-nitrone were also effective. There was no protection with a MPTP regimen which produced severe dopamine depletion. These results show that agents which improve mitochondrial energy production (coenzyme Q(10) and nicotinamide) and free radical scavengers can attenuate mild to moderate MPTP neurotoxicity. (C) 1995 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Schulz, Jorg/D-9786-2012 OI Schulz, Jorg/0000-0002-8903-0593 FU NINDS NIH HHS [NS 16367, NS 31579] NR 32 TC 93 Z9 93 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD APR PY 1995 VL 132 IS 2 BP 279 EP 283 DI 10.1016/0014-4886(95)90033-0 PG 5 WC Neurosciences SC Neurosciences & Neurology GA RD350 UT WOS:A1995RD35000015 PM 7789466 ER PT J AU ABEL, PE BOLAND, M DURAND, BA GEOLOT, DH GOODSON, JD ISHAM, GJ STEELE, LGF AF ABEL, PE BOLAND, M DURAND, BA GEOLOT, DH GOODSON, JD ISHAM, GJ STEELE, LGF TI WORK-FORCE AND COMMUNITY-HEALTH CARE NEEDS - A MODEL TO LINK SERVICE, EDUCATION, AND THE COMMUNITY SO FAMILY & COMMUNITY HEALTH LA English DT Article DE COMMUNITY; INTERDISCIPLINARY; WORK FORCE LINKAGES AB This article discusses a model of primary care delivery that was formulated through numerous discussions by a group of primary care policy fellows. This model considers the work force linkages of clinical practice and education of interdisciplinary providers as critical to the delivery of quality, cost-effective primary care. Work force linkages must be related to community health care needs. C1 IRISH COLL GEN PRACTITIONERS,LURRIGA SKIBEREEN,CORK,IRELAND. ARIZONA STATE UNIV,COLL NURSING,TEMPE,AZ. HLTH RESOURCES & SERV ADM,BUR HLTH PROFESS,DIV NURSING,ROCKVILLE,MD. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. INDIAN HLTH SERV,DIV MED SYST RES & DEV,TUCSON,AZ. HEALTHPARTNERS,MINNEAPOLIS,MN. RP ABEL, PE (reprint author), UNIV TEXAS,SCH NURSING,DIV COMMUNITY HLTH NURSING,AUSTIN,TX 78712, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21701 SN 0160-6379 J9 FAM COMMUNITY HEALTH JI Fam. Community Health PD APR PY 1995 VL 18 IS 1 BP 75 EP 79 PG 5 WC Family Studies; Public, Environmental & Occupational Health SC Family Studies; Public, Environmental & Occupational Health GA QM138 UT WOS:A1995QM13800009 ER PT J AU AMIR, I SHARMA, R BAUMAN, WA KORSTEN, MA AF AMIR, I SHARMA, R BAUMAN, WA KORSTEN, MA TI BOWEL CARE IN SPINAL-CORD INJURY PATIENTS - A COMPARISON OF 4 MODALITIES SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 BRONX VET AFFAIRS MED CTR,SPINAL CORD DAMAGE RES CTR,GASTROENTEROL SECT,BRONX,NY. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A562 EP A562 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302235 ER PT J AU BABYATSKY, MW ROSSITER, G PODOLSKY, DK AF BABYATSKY, MW ROSSITER, G PODOLSKY, DK TI TRANSFORMING GROWTH-FACTORS ALPHA AND BETA ARE DIFFERENTIALLY EXPRESSED IN CROHNS-DISEASE AND ULCERATIVE-COLITIS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MT SINAI MED CTR,GASTROINTESTINAL UNIT,NEW YORK,NY 10029. MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A775 EP A775 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86303089 ER PT J AU COHEN, J SAVIDES, TS JENSEN, DM AF COHEN, J SAVIDES, TS JENSEN, DM TI SURVIVAL OF PATIENTS WITH SEVERE UGI BLEEDING FROM GASTRIC ADENOCARCINOMA SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VAMC,CURE,LOS ANGELES,CA 90024. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A457 EP A457 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86301816 ER PT J AU DARMOUL, D HUTTNER, KM FREDERICK, DM OUELLETTE, AJ AF DARMOUL, D HUTTNER, KM FREDERICK, DM OUELLETTE, AJ TI THE MURINE CRYPTIDIN-4 GENE - STRUCTURE AND DIFFERENTIAL ACTIVITY IN CRYPTS ISOLATED ALONG THE LONGITUDINAL AXIS OF THE SMALL-INTESTINE SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. CHILDRENS HOSP MED CTR,JOINT PROGRAM NEONATOL,BOSTON,MA 02115. NR 2 TC 1 Z9 1 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A806 EP A806 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86303210 ER PT J AU DEA, SK YOUNG, SH ENNES, HS MAYER, EA AF DEA, SK YOUNG, SH ENNES, HS MAYER, EA TI SUBSTANCE-P PRODUCES OSCILLATIONS OF INTRACELLULAR CALCIUM ([CA](I)) IN MYOCYTES FROM LONGITUDINAL (L) BUT NOT CIRCULAR (C) COLONIC MUSCLE SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, DEPT PHYSIOL, CURE VA UCLA GASTROENTER BIOL CTR NEUROENTER BIOL, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, DEPT MED, LOS ANGELES, CA 90073 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A589 EP A589 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302344 ER PT J AU DIEHL, DL FULLERTON, S MAYER, EA AF DIEHL, DL FULLERTON, S MAYER, EA TI FUNCTIONAL BOWEL-DISEASE SYMPTOMS IN PATIENTS WITH CHRONIC FATIGUE SYNDROME (CFS) - PREVALENCE AND QUALITY-OF-LIFE SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, DEPT MED, CURE VA UCLA GASTROENTER BIOL CTR, LOS ANGELES, CA USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A592 EP A592 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302356 ER PT J AU FASS, R FULLERTON, S DIEHL, DL HIRSH, T MAYER, EA AF FASS, R FULLERTON, S DIEHL, DL HIRSH, T MAYER, EA TI SEXUAL DYSFUNCTION IN PATIENTS WITH IRRITABLE-BOWEL-SYNDROME (IBS) AND NONULCER DYSPEPSIA (NUD) SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, DEPT MED, CURE VA UCLA GASTROENTER BIOL CTR NEUROENTER BIOL, LOS ANGELES, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A596 EP A596 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302371 ER PT J AU FASS, R FULLERTON, S DIEHL, DL MAYER, EA AF FASS, R FULLERTON, S DIEHL, DL MAYER, EA TI SLEEP DISTURBANCE (SDE IN PATIENTS WITH FUNCTIONAL BOWEL DISORDERS (FBD) SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES, DEPT MED CURE VA UCLA GASTROENTER BIOL CTR NEUROEN, LOS ANGELES, CA 90073 USA. W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A596 EP A596 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302373 ER PT J AU FASS, R KAGAN, B FULLERTON, S MAYER, EA AF FASS, R KAGAN, B FULLERTON, S MAYER, EA TI THE PREVALENCE OF FUNCTIONAL GASTROINTESTINAL SYMPTOMS IN MALE-PATIENTS WITH POSTTRAUMATIC-STRESS-DISORDER (PTSD) SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA 90073 USA. CURE VA UCLA GASTROENTER BIOL CTR, NEUROENTER BIOL GRP, LOS ANGELES, CA 90073 USA. NR 1 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A597 EP A597 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302374 ER PT J AU FEINMAN, SV BLAJCHMAN, M BULL, S DIENSTAG, J HEATHCOTE, EJ MINUK, G SCHROEDER, E AF FEINMAN, SV BLAJCHMAN, M BULL, S DIENSTAG, J HEATHCOTE, EJ MINUK, G SCHROEDER, E TI HEPATITIS NON-ABC - IS THERE YET ANOTHER POST TRANSFUSION HEPATITIS (PTH) SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV TORONTO,MT SINAI HOSP,LIVER STUDY UNIT,TORONTO,ON M5G 1X5,CANADA. UNIV TORONTO,MT SINAI HOSP,LUNENFELD RES INST,TORONTO,ON M5G 1X5,CANADA. MCMASTER UNIV,DEPT PATHOL,HAMILTON,ON L8S 4L8,CANADA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. TORONTO HOSP,TORONTO,ON,CANADA. HLTH SCI CTR,WINNIPEG,MB R3E 0W1,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A1064 EP A1064 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86304236 ER PT J AU FOITZIK, T RYSCHICH, E FORGACS, B HOTZ, HG KLAR, E WARSHAW, AL BUHR, HJ AF FOITZIK, T RYSCHICH, E FORGACS, B HOTZ, HG KLAR, E WARSHAW, AL BUHR, HJ TI CORTICOSTEROIDS IMPROVE RATHER THAN AGGRAVATE ACUTE-PANCREATITIS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. UNIV HEIDELBERG,DEPT SURG,W-6900 HEIDELBERG,GERMANY. FREE UNIV BERLIN,DEPT SURG,W-1000 BERLIN 33,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A1220 EP A1220 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86304855 ER PT J AU FRICK, TW MITHOFER, K FERNANDEZDELCASTILLO, C RATTNER, DW WARSHAW, AL AF FRICK, TW MITHOFER, K FERNANDEZDELCASTILLO, C RATTNER, DW WARSHAW, AL TI INFLUENCE OF VERAPAMIL AND NIFEDIPINE ON CERULEIN, SECRETIN, AND A23187 STIMULATED RAT PANCREATIC ACINI - EFFECT OF ELEVATED EXTRACELLULAR CALCIUM SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. UNIV ZURICH,DEPT SURG,CH-8006 ZURICH,SWITZERLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A354 EP A354 DI 10.1016/0016-5085(95)24074-8 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86301405 ER PT J AU FULLERTON, S CONTEAS, C DONOVAN, J NALIBOFF, B MAYER, EA AF FULLERTON, S CONTEAS, C DONOVAN, J NALIBOFF, B MAYER, EA TI MEASURING SEVERITY OF ILLNESS FOR PATIENTS WITH FUNCTIONAL BOWEL-DISEASE USING SENSORY AND AFFECTIVE VERBAL DESCRIPTOR RATING-SCALES SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 SO CALIF PERMANENTE MED GRP, LOS ANGELES, CA USA. W LOS ANGELES VET AFFAIRS MED CTR, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, DEPT MED, CURE VA UCLA, GASTROENTER BIOL CTR NEUROENTER BIOL GRP, LOS ANGELES, CA 90073 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A602 EP A602 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302397 ER PT J AU FULLERTON, S MERTZ, H DIEHL, DL MAYER, EA AF FULLERTON, S MERTZ, H DIEHL, DL MAYER, EA TI A COMPARISON OF DIAGNOSTIC-CRITERIA FOR IRRITABLE-BOWEL-SYNDROME SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, DEPT MED, CURE VA UCLA GASTROENTER BIOL CTR NEUROENTER BIOL, LOS ANGELES, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A602 EP A602 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302395 ER PT J AU FURUNYAN, RD OHNO, Y MACDERMOTT, RP SANDERSON, IR AF FURUNYAN, RD OHNO, Y MACDERMOTT, RP SANDERSON, IR TI SHORT-CHAIN FATTY-ACIDS ENHANCE INTERLEUKIN-1-BETA INDUCED SECRETION OF INTERLEUKIN-8 BY CACO-2 CELLS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02114. LAHEY CLIN FDN,GASTROINTESTINAL SECT,BURLINGTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A726 EP A726 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302894 ER PT J AU HOCKER, M ZHANG, Z CHULAK, MB WANG, TC AF HOCKER, M ZHANG, Z CHULAK, MB WANG, TC TI GASTRIN REGULATES THE HISTIDINE-DECARBOXYLASE PROMOTER THROUGH A PKC-DEPENDENT PATHWAY SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A976 EP A976 DI 10.1016/0016-5085(95)28210-6 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86303888 ER PT J AU HOTZ, HG FOITZIK, T SCHMIDT, J KLAR, E WARSHAW, AL BUHR, HJ AF HOTZ, HG FOITZIK, T SCHMIDT, J KLAR, E WARSHAW, AL BUHR, HJ TI ISOVOLEMIC HEMODILUTION IN ACUTE EXPERIMENTAL PANCREATITIS - DEXTRAN IS SUPERIOR TO HYDROXYETHYL-STARCH SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. UNIV HEIDELBERG,DEPT SURG,W-6900 HEIDELBERG,GERMANY. FREE UNIV BERLIN,BENJAMIN FRANKLIN HOSP,DEPT SURG,W-1000 BERLIN 33,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A1223 EP A1223 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86304868 ER PT J AU JACOBY, RF VERMA, AK TUTSCH, KD MAMBY, CA LOVE, RR AF JACOBY, RF VERMA, AK TUTSCH, KD MAMBY, CA LOVE, RR TI PLACEBO-CONTROLLED RANDOMIZED TRIAL OF DFMO AS A CHEMOPREVENTIVE AGENT IN PATIENTS AT HIGH-RISK FOR COLORECTAL-CANCER SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV WISCONSIN,CTR COMPREHENS CANC,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,CTR COMPREHENS CANC,DEPT HUMAN ONCOL,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A485 EP A485 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86301930 ER PT J AU JACOBY, RF MARSHALL, DJ NOVAKOVIC, KR FRICK, T MOSER, AR DOVE, WF AF JACOBY, RF MARSHALL, DJ NOVAKOVIC, KR FRICK, T MOSER, AR DOVE, WF TI COLON-CANCER CHEMOPREVENTION STUDIES USING THE APC MUTANT MIN/+ ONCOMOUSE SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,DEPT ONCOL,MADISON,WI 53706. UNIV WISCONSIN,DEPT GENET,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A485 EP A485 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86301928 ER PT J AU KANAI, M ROSENBERG, I TSUNEKAWA, S PODOLSKY, DK AF KANAI, M ROSENBERG, I TSUNEKAWA, S PODOLSKY, DK TI CYTOKINES AND GROWTH-FACTORS MODULATE A DISTINCTIVE FIBROBLAST GROWTH-FACTOR RECEPTOR EXPRESSION IN COLONIC EPITHELIAL-CELL LINE SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02114. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A979 EP A979 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86303898 ER PT J AU KESHARVARIAN, A FUSUNYAN, RD DASTICE, M EIZNHAMER, D SANDERSON, JR MACDERMOTT, RP AF KESHARVARIAN, A FUSUNYAN, RD DASTICE, M EIZNHAMER, D SANDERSON, JR MACDERMOTT, RP TI RECTAL DIALYSATES FROM ACTIVE ULCERATIVE-COLITIS PATIENTS CONTAIN INCREASED IL-8 - A POSSIBLE OBJECTIVE MEASUREMENT OF COLONIC MUCOSAL INFLAMMATION AND DISEASE-ACTIVITY SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 LOYOLA UNIV,DIV GASTROINTESTINAL,MAYWOOD,IL 60153. LAHEY CLIN FDN,GASTROINTESTINAL SECT,BURLINGTON,MA. MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02114. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A848 EP A848 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86303376 ER PT J AU KIM, YI CHOI, SW SALOMON, RN GRAEMECOOK, F SMITH, D NADEAU, M DALLAL, G MASON, JB MAYER, J AF KIM, YI CHOI, SW SALOMON, RN GRAEMECOOK, F SMITH, D NADEAU, M DALLAL, G MASON, JB MAYER, J TI DIETARY-FOLATE PROTECTS AGAINST THE DEVELOPMENT OF MACROSCOPIC COLONIC NEOPLASMS IN A DOSE-RESPONSIVE MANNER IN THE DIMETHYLHYDRAZINE RAT MODEL SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. TUFTS UNIV,HUMAN NUTR RES CTR,BOSTON,MA 02111. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A489 EP A489 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86301946 ER PT J AU LLOYD, M HURLEY, C KORSMO, H OLSEN, W AF LLOYD, M HURLEY, C KORSMO, H OLSEN, W TI TRANS-ACTING NUCLEAR PROTEINS IN HUMAN LACTASE AND SUCRASE-ISOMALTASE REGULATION SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. NR 2 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A736 EP A736 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302935 ER PT J AU MA, A DATTA, MW MARGOSIAN, E HORAK, I ALT, FW AF MA, A DATTA, MW MARGOSIAN, E HORAK, I ALT, FW TI INFLAMMATORY BOWEL-DISEASE IN IL-2 DEFICIENT MICE REQUIRES T-LYMPHOCYTES, BUT NOT B-LYMPHOCYTES SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,HOWARD HUGHES MED 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A867 EP A867 DI 10.1016/0016-5085(95)27774-9 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86303452 ER PT J AU MAHIDA, YR GALVIN, A GRAY, T MAKH, S MCALINDON, M SEWELL, H PODOLSKY, DK AF MAHIDA, YR GALVIN, A GRAY, T MAKH, S MCALINDON, M SEWELL, H PODOLSKY, DK TI A NOVEL MODEL FOR STUDY AND ISOLATION OF INTESTINAL-CELLS - CULTURE OF INTESTINAL-MUCOSA DENUDED OF EPITHELIAL-CELLS LEADS TO MIGRATION OF LAMINA PROPRIA (LP) LYMPHOCYTES AND MACROPHAGES SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV NOTTINGHAM HOSP,DIV GASTROENTEROL,NOTTINGHAM NG7 2UH,ENGLAND. UNIV NOTTINGHAM HOSP,DIV PATHOL,NOTTINGHAM NG7 2UH,ENGLAND. UNIV NOTTINGHAM HOSP,DIV IMMUNOL,NOTTINGHAM NG7 2UH,ENGLAND. MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A868 EP A868 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86303458 ER PT J AU MASHIMO, H HE, XD HUANG, PL FISHMAN, MC GOYAL, RK AF MASHIMO, H HE, XD HUANG, PL FISHMAN, MC GOYAL, RK TI EVIDENCE FOR NITRIC-OXIDE AS AN NANC INHIBITORY NEUROTRANSMITTER - STUDIES USING MUTANT MICE WITH DISRUPTED NCNOS GENE SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02114. BETH ISRAEL HOSP,DEPT GASTROENTEROL,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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A990 EP A990 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86303941 ER PT J AU MASHIMO, H PODOLSKY, DK FISHMAN, MC AF MASHIMO, H PODOLSKY, DK FISHMAN, MC TI STRUCTURE AND EXPRESSION OF MURINE INTESTINAL TREFOIL FACTOR - HIGH EVOLUTIONARY CONSERVATION AND POSTNATAL EXPRESSION SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A738 EP A738 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302942 ER PT J AU MERTZ, H FULLERTON, S HIRSH, T MAYER, EA AF MERTZ, H FULLERTON, S HIRSH, T MAYER, EA TI CLASSIFICATION OF CONSTIPATION BY BIOLOGICAL PARAMETERS AND SYMPTOM CRITERIA SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,DEPT MED,CURE,GASTROENTER BIOL CTR,NEUROENTER BIOL GRP,LOS ANGELES,CA 90024. VANDERBILT UNIV,DEPT MED,NASHVILLE,TN 37240. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A648 EP A648 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302582 ER PT J AU MITHOFER, K FERNANDEZDELCASTILLO, C RATTNER, DW WARSHAW, AL AF MITHOFER, K FERNANDEZDELCASTILLO, C RATTNER, DW WARSHAW, AL TI SUBCELLULAR REDISTRIBUTION OF LYSOSOMAL-ENZYMES IN EXPERIMENTAL ACUTE-PANCREATITIS IS ASSOCIATED WITH INCREASED PROTEASE ACTIVATION IN THE INTRAACINAR ZYMOGEN COMPARTMENT SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT SURG,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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A376 EP A376 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86301492 ER PT J AU MITHOFER, K FRICK, TW FERNANDEZDELCASTILLO, C LEWANDROWSKI, KB RATTNER, DW WARSHAW, AL AF MITHOFER, K FRICK, TW FERNANDEZDELCASTILLO, C LEWANDROWSKI, KB RATTNER, DW WARSHAW, AL TI DOSE DEPENDENCE OF ECTOPIC PROTEASE ACTIVATION AND PANCREATIC INJURY IN HYPERCALCEMIA-INDUCED EXPERIMENTAL PANCREATITIS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A376 EP A376 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86301493 ER PT J AU MUNAKATA, J CHANG, L AN, C NALIBOFF, B MAYER, EA AF MUNAKATA, J CHANG, L AN, C NALIBOFF, B MAYER, EA TI REPETITIVE ACTIVATION OF SIGMOID MECHANORECEPTORS RESULTS IN THE DEVELOPMENT OF RECTAL HYPERALGESIA IN IBS PATIENTS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES, W LOS ANGELES VET AFFAIRS MED CTR, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, W LOS ANGELES VET AFFAIRS MED CTR, CURE VA UCLA GASTROENTER BIOL CTR NEUROBIOL GRP, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, HARBOR MED CTR, DEPT MED, LOS ANGELES, CA 90073 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A653 EP A653 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302599 ER PT J AU MUNAKATA, J NALIBOFF, B CHANG, L AN, C MAYER, EA AF MUNAKATA, J NALIBOFF, B CHANG, L AN, C MAYER, EA TI OCTREOTIDE INHIBITS THE DEVELOPMENT OF RECTAL HYPERALGESIA IN RESPONSE TO MECHANICAL SIGMOID SENSITIZATION IN IBS PATIENTS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES, HARBOR MED CTR, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, W LOS ANGELES VET AFFAIRS, MED CTR, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, W LOS ANGELES VET AFFAIRS MED CTR, CURE VA UCLA GASTROENTER BIOL, CTR NEUROENTEROL BIOL GRP, LOS ANGELES, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A652 EP A652 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302598 ER PT J AU NAKAGAWA, H WANG, TC TOGAWA, K ZUKERBERG, L ODZE, R WILSON, JB RUSTGI, AK AF NAKAGAWA, H WANG, TC TOGAWA, K ZUKERBERG, L ODZE, R WILSON, JB RUSTGI, AK TI ESOPHAGEAL SQUAMOUS EPITHELIAL CYCLIN-D1 ONCOGENE EXPRESSION USING AN EPSTEIN-BARR-VIRUS PROMOTER IN TRANSGENIC MICE SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. LUDWIG INST RES,GLASGOW,SCOTLAND. RI Wilson, Joanna/B-4466-2009 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A513 EP A513 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302041 ER PT J AU NALIBOFF, B HIRSH, T KODNER, A NIAZI, N MAYER, EA AF NALIBOFF, B HIRSH, T KODNER, A NIAZI, N MAYER, EA TI PHYSIOLOGICAL AND SYMPTOMATIC IMPROVEMENT FOLLOWING AN ANORECTAL BIOFEEDBACK TRAINING-PROGRAM FOR INCONTINENCE AND CONSTIPATION - COMPARISON OF PATIENTS WITH AND WITHOUT IBS SYMPTOMS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,CURE VA UCLA GASTROENTER BIOL CTR NEUROENTER BIOL GRP,LOS ANGELES,CA 90024. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A656 EP A656 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302613 ER PT J AU NISHIMURA, A MARTINEZ, O OGUCHI, S FUSUNYAN, RD MACDERMOTT, RP SANDERSON, IR AF NISHIMURA, A MARTINEZ, O OGUCHI, S FUSUNYAN, RD MACDERMOTT, RP SANDERSON, IR TI PROFILE OF IGF-BINDING PROTEINS SECRETED BY INTESTINAL EPITHELIAL-CELLS CHANGES WITH DIFFERENT NUTRIENTS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,DEV GASTROENTEROL LAB,BOSTON,MA 02114. LAHEY CLIN FDN,GASTROINTESTINAL SECT,BURLINGTON,MA. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A742 EP A742 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302958 ER PT J AU OGATA, H SANDS, BE PODOLSKY, DK AF OGATA, H SANDS, BE PODOLSKY, DK TI REGULATION OF EXPRESSION OF INTESTINAL TREFOIL FACTOR - ANALYSIS OF INTESTINAL GOBLET CELL-SPECIFIC TRANSCRIPTIONAL ELEMENTS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02114. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A312 EP A312 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86301237 ER PT J AU OHNO, Y FUSUNYAN, RD AOKI, N MACDERMOTT, RP SANDERSON, IR AF OHNO, Y FUSUNYAN, RD AOKI, N MACDERMOTT, RP SANDERSON, IR TI MACROPHAGE INFLAMMATORY PROTEIN-2 (MIP-2) - REGULATION IN RAT SMALL-BOWEL ENTEROCYTES SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02114. LAHEY CLIN FDN,GASTROINTESTINAL SECT,BURLINGTON,MA. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A887 EP A887 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86303532 ER PT J AU OISHI, AJ INOUE, Y SOUBA, WW SARR, MG AF OISHI, AJ INOUE, Y SOUBA, WW SARR, MG TI SELECTIVE DOWN-REGULATION OF GLUTAMINE TRANSPORT AFTER JEJUNOILEAL AUTOTRANSPLANTATION SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MAYO CLIN & MAYO FDN,DEPT SURG,ROCHESTER,MN 55905. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A1236 EP A1236 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86304918 ER PT J AU RALL, CJN RUSTGI, AK AF RALL, CJN RUSTGI, AK TI NOVEL CD44V6 ISOFORM OVEREXPRESSED IN METASTASES OF PANCREATIC ADENOCARCINOMA SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A385 EP A385 DI 10.1016/0016-5085(95)24199-X PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86301532 ER PT J AU RATTNER, DW FERNANDEZDELCASTILLO, C WARSHAW, AL AF RATTNER, DW FERNANDEZDELCASTILLO, C WARSHAW, AL TI PITFALLS OF DISTAL PANCREATECTOMY FOR RELIEF OF PAIN IN CHRONIC-PANCREATITIS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A1240 EP A1240 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86304934 ER PT J AU RATTNER, DW BRUGGE, W FERNANDEZDELCASTILLO, C WARSHAW, AL AF RATTNER, DW BRUGGE, W FERNANDEZDELCASTILLO, C WARSHAW, AL TI THE ROLE OF LOCAL RESECTION IN THE MANAGEMENT OF AMPULLARY TUMORS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT GASTROENTEROL,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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A1240 EP A1240 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86304933 ER PT J AU REINECKER, HC PODOLSKY, DK AF REINECKER, HC PODOLSKY, DK TI HUMAN INTESTINAL EPITHELIAL-CELLS EXPRESS FUNCTIONAL CYTOKINE RECEPTORS SHARING THE COMMON GAMMA-C-CHAIN OF THE INTERLEUKIN-2 RECEPTOR SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. LAHEY CLIN FDN,BURLINGTON,MA. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A901 EP A901 DI 10.1016/0016-5085(95)27911-3 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86303589 ER PT J AU REINECKER, HC MACDERMOTT, RP MIRAU, S KANAI, M PODOLSKY, DK AF REINECKER, HC MACDERMOTT, RP MIRAU, S KANAI, M PODOLSKY, DK TI HUMAN INTESTINAL EPITHELIAL-CELLS PRODUCE INTERLEUKIN-15 SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. LAHEY CLIN FDN,BURLINGTON,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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A749 EP A749 DI 10.1016/0016-5085(95)27308-5 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302986 ER PT J AU RIVERA, JA FERNANDEZDELCASTILLO, C RALL, CJN GRAEMECOOK, F WARSHAW, AL RUSTGI, AK AF RIVERA, JA FERNANDEZDELCASTILLO, C RALL, CJN GRAEMECOOK, F WARSHAW, AL RUSTGI, AK TI ANALYSIS OF K-RAS MUTATIONS IN CHRONIC-PANCREATITIS WITH DUCTAL HYPERPLASIA SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A386 EP A386 DI 10.1016/0016-5085(95)24203-1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86301536 ER PT J AU SHIFFMAN, ML BRUGGE, WR MALET, PF KHANDELWAL, M MOORE, EW AF SHIFFMAN, ML BRUGGE, WR MALET, PF KHANDELWAL, M MOORE, EW TI URSODEOXYCHOLIC ACID (UDCA) REDUCES MUCIN CONCENTRATION IN THE GALLBLADDER (GB) BILE OF PATIENTS WITH GALLSTONES (GS) SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. UNIV PENN,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A1169 EP A1169 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86304654 ER PT J AU TENNER, S DELCASTILLO, CF WARSHAW, AL STEINBERG, W HERMONTAYLOR, J VALENZUELA, JE HARIRI, M BANKS, PA AF TENNER, S DELCASTILLO, CF WARSHAW, AL STEINBERG, W HERMONTAYLOR, J VALENZUELA, JE HARIRI, M BANKS, PA TI URINARY TRYPSINOGEN ACTIVATION PEPTIDE (TAP) PREDICTS SEVERITY IN ACUTE-PANCREATITIS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. UNIV SO CALIF,LOS ANGELES,CA 90089. ST GEORGE HOSP,LONDON,ENGLAND. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A395 EP A395 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86301570 ER PT J AU TOGAWA, K RUSTGI, AK AF TOGAWA, K RUSTGI, AK TI A NOVEL SERINE-THREONINE KINASE IS EXPRESSED IN INTESTINAL CRYPT CELLS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A547 EP A547 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86302175 ER PT J AU TORBEY, C KORSMO, H OLSEN, WA AF TORBEY, C KORSMO, H OLSEN, WA TI REGULATION OF LACTASE EXPRESSION IN A HUMAN INTESTINAL-CELL LINE AND IN RATS IS INDEPENDENT OF PUTATIVE TRANSCRIPTION FACTOR NF-LPH1 SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,GASTROENTEROL RES LAB,MADISON,WI 53705. UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. NR 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A758 EP A758 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86303019 ER PT J AU WASA, M BODE, B SOUBA, W AF WASA, M BODE, B SOUBA, W TI ADAPTIVE REGULATION OF AMINO-ACID-TRANSPORT IN NUTRIENT-DEPRIVED HUMAN HEPATOMAS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A1250 EP A1250 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86304973 ER PT J AU WELCH, G RICHTER, J KAWACHI, I BACHWICH, D AF WELCH, G RICHTER, J KAWACHI, I BACHWICH, D TI THE SF-36 QUALITY-OF-LIFE MEASURE IN INFLAMMATORY BOWEL-DISEASE - AN EVALUATION OF ITS RELIABILITY AND VALIDITY SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH PUBL HLTH,JOSLIN DIABET CTR,BOSTON,MA 02114. UNIV PENN,MED CTR,PHILADELPHIA,PA 19104. NR 0 TC 6 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A940 EP A940 DI 10.1016/0016-5085(95)28064-2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86303742 ER PT J AU XAVIER, R ROMEO, C KOLANUS, W SEED, B AF XAVIER, R ROMEO, C KOLANUS, W SEED, B TI ROLE FOR NONRECEPTOR TYROSINE KINASES IN T-CELL ACTIVATION SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,GASTROINTESTINAL UNIT,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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A945 EP A945 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86303763 ER PT J AU YANG, JM SOUTHERN, JF WARSHAW, AL LEWANDROWSKI, KB AF YANG, JM SOUTHERN, JF WARSHAW, AL LEWANDROWSKI, KB TI TISSUE POLYPEPTIDE ANTIGEN IN PANCREATIC CYST FLUID - A PROLIFERATION ANTIGEN THAT DISTINGUISHES MALIGNANT MUCINOUS CYSTADENOCARCINOMAS FROM BENIGN CYSTIC TUMORS AND PSEUDOCYSTS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1995 VL 108 IS 4 SU S BP A1252 EP A1252 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT863 UT WOS:A1995QT86304982 ER PT J AU BRUGGE, WR CAREY, RW MATHISEN, DJ LEE, MJ AF BRUGGE, WR CAREY, RW MATHISEN, DJ LEE, MJ TI WHAT IS THE MOST ACCURATE EUS METHOD FOR TUMOR STAGING OF ESOPHAGEAL CANCER SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1995 VL 41 IS 4 BP 299 EP 299 DI 10.1016/S0016-5107(05)80052-5 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT419 UT WOS:A1995QT41900016 ER PT J AU JAFFE, DL BRUGGE, WR AF JAFFE, DL BRUGGE, WR TI ENDOSCOPIC ULTRASONOGRAPHY IS USEFUL IN EVALUATING ISOLATED GASTRIC VARICES SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1995 VL 41 IS 4 BP 306 EP 306 DI 10.1016/S0016-5107(05)80077-X PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT419 UT WOS:A1995QT41900041 ER PT J AU KOZAREK, RA RALTZ, S BRUGGE, WR SHAPIRO, RH BOYCE, WH BAILLIE, J BRANCH, S LIGHTDALE, C STEVENS, P LEHMAN, G BENJAMIN, S MARCON, N AF KOZAREK, RA RALTZ, S BRUGGE, WR SHAPIRO, RH BOYCE, WH BAILLIE, J BRANCH, S LIGHTDALE, C STEVENS, P LEHMAN, G BENJAMIN, S MARCON, N TI PROSPECTIVE MULTICENTER TRIAL UTILIZING ESOPHAGEAL Z(R) STENT FOR DYSPHAGIA AND TE FISTULAS SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 VIRGINIA MASON MED CTR,SEATTLE,WA 98101. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV S FLORIDA,TAMPA,FL 33620. DUKE UNIV,DURHAM,NC 27706. COLUMBIA UNIV,NEW YORK,NY 10027. INDIANA UNIV,BLOOMINGTON,IN 47405. GEORGETOWN UNIV,WASHINGTON,DC 20057. WELLESLEY COLL HOSP,TORONTO,ON,CANADA. NR 0 TC 7 Z9 8 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1995 VL 41 IS 4 BP 353 EP 353 DI 10.1016/S0016-5107(05)80267-6 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QT419 UT WOS:A1995QT41900231 ER PT J AU VAIRO, G LIVINGSTON, DM GINSBERG, D AF VAIRO, G LIVINGSTON, DM GINSBERG, D TI FUNCTIONAL INTERACTION BETWEEN E2F-4 AND P130 - EVIDENCE FOR DISTINCT MECHANISMS UNDERLYING GROWTH SUPPRESSION BY DIFFERENT RETINOBLASTOMA PROTEIN FAMILY MEMBERS SO GENES & DEVELOPMENT LA English DT Article DE E2F; CELL CYCLE; TRANSCRIPTION FACTOR; G(0); P130; RB FAMILY ID TRANSCRIPTION FACTOR E2F; CELL-CYCLE; GENE-PRODUCT; COMPLEX-FORMATION; SUSCEPTIBILITY GENE; VIRAL ONCOPROTEINS; BINDING PROTEIN; P107; RB; TRANSACTIVATION AB Little is known of the mechanisms controlling the G(0)/G(1) transition of the cell cycle. The induction of immediate early gene expression, thought to be important for this process, suggests that the key factors controlling this transition preexist in quiescent cells. The E2F family of transcription factors likely play an important role in this process, because E2F DNA-binding activity exists in quiescent cells, and the induction of at least some immediate early genes requires intact E2F regulatory promoter sites. Here, we show that the major G(0) E2F activity of primary human T cells, E2F-4, is stably bound to the p130 pocket protein in association with a DP heterodimerization partner. p130-E2F-4 binding has functional implications because p130 effectively suppressed E2F-4-mediated trans-activation, and coexpression of E2F-4 overcame p130-mediated G(1) arrest more efficiently than RB-induced G(1) blockade. Conversely, E2F-1 overrode an RB-induced G(1) block more efficiently than E2F-4. Thus, p130 and RB appear to induce cell cycle arrest via biochemically distinct mechanisms that involve different E2F family members. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 62 TC 291 Z9 291 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 APR 1 PY 1995 VL 9 IS 7 BP 869 EP 881 DI 10.1101/gad.9.7.869 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA QT898 UT WOS:A1995QT89800009 PM 7705662 ER PT J AU RUNGGERBRANDLE, E ALLIOD, C FOUQUET, B MESSERLI, MM AF RUNGGERBRANDLE, E ALLIOD, C FOUQUET, B MESSERLI, MM TI BEHAVIOR OF MACROGLIAL CELLS, AS IDENTIFIED BY THEIR INTERMEDIATE FILAMENT COMPLEMENT, DURING OPTIC-NERVE REGENERATION OF XENOPUS TADPOLE SO GLIA LA English DT Review DE GLIA; ASTROCYTES; AMPHIBIA; INJURY; CYTOSKELETON; IMMUNOCYTOCHEMISTRY; CONFOCAL MICROSCOPY ID FIBRILLARY ACIDIC PROTEIN; WALLERIAN DEGENERATION; GFA PROTEIN; GLIAL-CELL; NEUROFILAMENT ANTISERA; AXONAL REGENERATION; NEURITE OUTGROWTH; EPITHELIAL-CELLS; LAEVIS EPIDERMIS; VISUAL PATHWAY AB Assessment of glial cell behaviour during optic nerve (ON) regeneration in Xenopus tadpoles is hampered by the lack of classical cellular markers that distinguish different glial cells in mammals. We thus have characterized the intermediate filament (IF) complement of tadpole glial cells and used it to follow the fate of glial cell subsets during the first 10 days after ON crush. Glial cells synthesize a restricted number of cytokeratin (CK) species and vimentin. This pattern remains essentially unchanged during metamorphosis and regeneration. However, vimentin turnover is specifically enhanced after injury. The expression of CKs and vimentin has been followed immunocytochemically in situ and in isolated cells recovered from dissociated ON segments. In the normal nerve, 79% of ramified glial cells express both CK and vimentin, 1% CK and 4% vimentin only, whereas 16% express neither IF protein. We tentatively classified CK expressing cells as mature astrocytes and those without IF proteins as oligodendrocytes. In the regenerating ON, the relative number of oligodendrocytes is decreased, while the astrocytic subset becomes accordingly larger but is decreased by day 10 already in favour of cells expressing vimentin only. Astrocytes invade the lesion site soon after crush, arrange into a central core within the distal nerve segment and establish a peripheral scaffold that is readily crossed by axons. Unlike mammalian astrocytes that remain absent from the lesion site but form a scar at some distance to it, amphibian astrocytes appear to provide active guidance to axons growing through the lesion site. (C) 1995 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,BOSTON,MA. ETH ZURICH,INST CELL BIOL,ZURICH,SWITZERLAND. UNIV GENEVA,EYE CLIN,GENEVA,SWITZERLAND. NR 101 TC 4 Z9 4 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 0894-1491 J9 GLIA JI Glia PD APR PY 1995 VL 13 IS 4 BP 255 EP 271 DI 10.1002/glia.440130403 PG 17 WC Neurosciences SC Neurosciences & Neurology GA QV542 UT WOS:A1995QV54200002 PM 7542224 ER PT J AU YOUNG, RH OLIVA, E SCULLY, RE AF YOUNG, RH OLIVA, E SCULLY, RE TI UNTITLED SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material ID SMALL-CELL-CARCINOMA; OVARY; HYPERCALCEMIA RP YOUNG, RH (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114, USA. NR 9 TC 16 Z9 16 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 1995 VL 57 IS 1 BP 7 EP 8 DI 10.1006/gyno.1995.1092 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA QR144 UT WOS:A1995QR14400003 PM 7705703 ER PT J AU BLUMENTHAL, D MORT, E EDWARDS, J AF BLUMENTHAL, D MORT, E EDWARDS, J TI THE EFFICACY OF PRIMARY-CARE FOR VULNERABLE POPULATION GROUPS SO HEALTH SERVICES RESEARCH LA English DT Article DE EFFICACY; PRIMARY CARE; LITERATURE REVIEW ID NEIGHBORHOOD HEALTH-CENTER; IMPROVING ACCESS; RANDOMIZED TRIAL; RURAL-COMMUNITY; MEDICAL-CARE; PROGRAMS; SERVICES; COMMUNICATION; TERMINATION; CONTINUITY AB This article reviews the existing literature on the efficacy of primary care with an emphasis on the evaluation of primary care for vulnerable populations: groups whose demographic, geographic, or economic characteristics impede or prevent their access to health care services. A significant portion of the literature derives from studies of poor and underserved populations. However, to construct a more complete evaluation of primary care services, the authors cite literature that: has examined both advantaged and disadvantaged populations. Even then the literature is incomplete, at best. The article describes a definition of primary care suitable for policy analysis and formulation, reviews evidence on the efficacy of care that meets that definition, and concludes that widespread use of primary care services is likely to result in improved patient satisfaction and health status. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. RP BLUMENTHAL, D (reprint author), MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,BOSTON,MA 02114, USA. NR 70 TC 81 Z9 81 U1 3 U2 6 PU HEALTH ADMINISTRATION PRESS PI MELROSE PARK PA C/O FOUNDATION AMER COLL HEALTHCARE EXECUTIVES 1951 CORNELL AVE, MELROSE PARK, IL 60160 SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 1995 VL 30 IS 1 BP 253 EP 273 PN 2 PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA RB542 UT WOS:A1995RB54200009 PM 7721596 ER PT J AU WIEDERHOLD, ML YAMASHITA, M LARSEN, KA BATTEN, JS KOIKE, H ASASHIMA, M AF WIEDERHOLD, ML YAMASHITA, M LARSEN, KA BATTEN, JS KOIKE, H ASASHIMA, M TI DEVELOPMENT OF THE OTOLITH ORGANS AND SEMICIRCULAR CANALS IN THE JAPANESE RED-BELLIED NEWT, CYNOPS-PYRRHOGASTER SO HEARING RESEARCH LA English DT Article DE OTOCONIA; OTOLITH; UTRICLE; SACCULE; SEMICIRCULAR CANALS; DEVELOPMENT ID X-RAY-DIFFRACTION; OTOCONIA AB The sequence in which the otoliths and semicircular canals and their associated sensory epithelia appear and develop in the newt are described. Three-dimensional reconstruction of serial sections through the otic vesicle of newt embryos from stages 31 through 58 demonstrate the first appearance, relative position and growth of the otoliths. A single otolith is first seen in stage 33 embryos (approximately 9 days old); this splits into separate utricular and saccular otoliths at stage 40 (13 days). The lateral semicircular canal is the first to appear, at stage 41 (14 days). The anterior and posterior canals appear approximately one week later and the vestibular apparatus is essentially fully formed at stage 58 (approximately 5 weeks). The data reported here will serve as ground-based controls for fertilized newt eggs flown on the International Microgravity Laboratory-2 Space Shuttle night, to investigate the influence of microgravity on the development of the gravity-sensing organs. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. INST SPACE & ASTRONAUT SCI,SAGAMIHARA,KANAGAWA 229,JAPAN. UNIV TOKYO,TOKYO,JAPAN. RP WIEDERHOLD, ML (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT OTOLARYNGOL HEAD & NECK SURG,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 25 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD APR PY 1995 VL 84 IS 1-2 BP 41 EP 51 DI 10.1016/0378-5955(95)00012-S PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA QV812 UT WOS:A1995QV81200005 PM 7642454 ER PT J AU STEYGER, PS WIEDERHOLD, ML BATTEN, J AF STEYGER, PS WIEDERHOLD, ML BATTEN, J TI THE MORPHOGENIC FEATURES OF OTOCONIA DURING LARVAL DEVELOPMENT OF CYNOPS-PYRRHOGASTER, THE JAPANESE RED-BELLIED NEWT SO HEARING RESEARCH LA English DT Article DE OTOCONIA; VESTIBULAR; MORPHOGENESIS; BIOMINERALIZATION; EXTRACELLULAR MATRIX ID ENDOLYMPHATIC SAC; CRYSTAL-GROWTH; PROTEIN; STATOCONIA; MEMBRANE AB Otoconia are calcified protein matrices within the gravity-sensing organs of the vertebrate vestibular system. Mammalian otoconia are barrel-shaped with triplanar facets at each end. Reptilian otoconia are commonly prismatic or fusiform in shape. Amphibians have all three otoconial morphologies, barrel-shaped otoconia within the utricle, with prismatic and fusiform otoconia in the saccule. Scanning electron microscopy revealed a sequential appearance of all three otoconial morphologies during larval development of the newt, Cynops pyrrhogaster. The first otoconia appear within a single, developing otolith, and some resemble adult barrel-shaped otoconia. As the larvae hatch, around stages 39-42, the single otolith divides into two anatomically separate regions, the utricle and saccule, and both contain otoconia similar to those seen in the single otolith. Throughout development, these otoconia may have variable morphologies, with serrated surfaces, or circumferential striations with either separated facets or adjacent facets in the triplanar end-regions. small fusiform otoconia occur later, at stage 51, and only in the saccule. Prismatic otoconia appear later still, at stage 55, and again only in the saccule. Thus, although prismatic otoconia are the most numerous in adult newts, it is the last vestibular otoconial morphology to be expressed. C1 UNIV TEXAS,HLTH SCI CTR,DEPT OTOLARYNGOL HEAD & NECK SURG,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 50 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD APR PY 1995 VL 84 IS 1-2 BP 61 EP 71 DI 10.1016/0378-5955(95)00013-T PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA QV812 UT WOS:A1995QV81200007 PM 7642456 ER PT J AU TEICHER, BA AF TEICHER, BA TI PHYSIOLOGICAL-MECHANISMS OF THERAPEUTIC RESISTANCE - BLOOD-FLOW AND HYPOXIA SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID FLUOSOL-DA 20-PERCENT; CHEMOTHERAPEUTIC ALKYLATING-AGENTS; MAGNETIC-RESONANCE SPECTROSCOPY; BOVINE HEMOGLOBIN PREPARATION; MELPHALAN ANTITUMOR-ACTIVITY; TUMOR SUBPOPULATIONS INVIVO; SQUAMOUS-CELL CARCINOMA; O2 TENSION MEASUREMENTS; GRADE BRAIN-TUMORS; RADIATION-THERAPY AB The tools now are available to characterize oxygenation/hypoxia in the clinic. The clinical investigations conducted thus far have shown that significant regions of hypoxia exist in solid tumors in patients. Of the various strategies developed in the laboratory for reducing (or eliminating) hypoxia in tumors, the intravenous administration of nontoxic oxygen-carrying materials is probably the most generally applicable in a clinical setting. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA. RP TEICHER, BA (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 169 TC 63 Z9 63 U1 1 U2 2 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 APR PY 1995 VL 9 IS 2 BP 475 EP 506 PG 32 WC Oncology; Hematology SC Oncology; Hematology GA QT664 UT WOS:A1995QT66400013 PM 7642474 ER PT J AU WEI, MX TAMIYA, T HURFORD, RK BOVIATSIS, EJ TEPPER, RI CHIOCCA, EA AF WEI, MX TAMIYA, T HURFORD, RK BOVIATSIS, EJ TEPPER, RI CHIOCCA, EA TI ENHANCEMENT OF INTERLEUKIN-4-MEDIATED TUMOR-REGRESSION IN ATHYMIC MICE BY IN-SITU RETROVIRAL GENE-TRANSFER SO HUMAN GENE THERAPY LA English DT Article ID BRAIN-TUMORS; CELLS; IMMUNOTHERAPY; THERAPY; BROMODEOXYURIDINE; GLIOBLASTOMA; LYMPHOCYTES; POTENT; INSITU; GLIOMA AB Intratumoral grafting of genetically engineered cells that produce interleukin-4 (IL-4) has been shown to produce tumor regression as well as prolong survival of mice harboring intracerebral gliomas. We sought to determine whether retroviral-mediated gene delivery into tumor cells in situ resulted in enhanced tumor regression by IL-4. Two mouse fibroblast lines were obtained: they both secreted similar levels of IL-4 but one produced a retrovirus vector bearing the IL-4 gene (CRE-MFG-IL-4 cells), whereas the other did not (NIH3T3-IL-4 cells). In mixed transplantation assays in the subcutaneous flanks of athymic mice, CRE-MFG, IL-4 cells were more effective than NIH3T3-IL-4 cells in inhibiting the growth of rat C6 glioma cells (p < 0.005, ANOVA). Subcutaneous tumors injected with fibroblasts that produced a control retrovirus vector without producing IL-4 (CRE-MFG-LacZ cells) did not inhibit subcutaneous tumor growth. An intracranial assay was used to evaluate survival of athymic mice harboring intracranial gliomas. Three days after implanting rat C6 glioma cells into the right frontal lobes of athymic mice, NIH3T3-IL-4 cells (n = 10) or CRE-MFG-IL-4 cells (n = 10) were stereotactically inoculated into the tumor bed. The average survival of mice treated with CRE-MFG-IL-4 cells was 38 days (+/-2.4, SE), whereas that of mice treated with NIH3T3-IL-4 cells was 31 days (+/-0.8, SE) (p < 0.005, ANOVA; p < 0.001, log-rank analysis). The mean survival of control mice treated with CRE-MFG-LacZ cells was only 25 days (+/-0.7, SE) (p < 0.0001, compared to CRE-MFG-IL-4-treated mice). Histologic analysis of animals' tumors revealed extensive eosinophilic infiltrates in mice treated with the IL-4-producing cells (both NIH3T3-IL-4 and CRE-MFG-IL-4) but not in mice treated with IL-4 nonproducing cells (CRE-MFG-LacZ). This infiltrate started to decrease 3 weeks after fibroblast implantation, implying that its maintenance was needed for prolonged tumor regression. This study demonstrates that in situ retroviral mediated transfer of the IL-4 gene enhances the anticancer effect of cells that produce the cytokine. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,MOLEC NEUROGENET LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,MGH CANC CTR,BOSTON,MA 02114. FU NINDS NIH HHS [NS24279-08] NR 37 TC 51 Z9 52 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD APR PY 1995 VL 6 IS 4 BP 437 EP 443 DI 10.1089/hum.1995.6.4-437 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA QU204 UT WOS:A1995QU20400005 PM 7612701 ER PT J AU KUPRYJANCZYK, J BELL, DA DIMEO, D BEAUCHAMP, R THOR, AD YANDELL, DW AF KUPRYJANCZYK, J BELL, DA DIMEO, D BEAUCHAMP, R THOR, AD YANDELL, DW TI P53 GENE ANALYSIS OF OVARIAN BORDERLINE TUMORS AND STAGE-I CARCINOMAS SO HUMAN PATHOLOGY LA English DT Article DE P53 GENE; OVARY; BORDERLINE TUMORS; EARLY OVARIAN CANCER; CLONALITY ID SUPPRESSOR PROTEIN; CANCER; MUTATIONS; ACCUMULATION; ORIGIN; PROGNOSIS; SPECTRUM AB Mutations of the p53 gene are common in human ovarian carcinomas; however, their role in the early development of ovarian cancer is unclear. Twelve ovarian borderline tumors (BTs; eight of them p53 immunopositive) and 10 stage I carcinomas (four of them p53 immunopositive) were studied for genetic alterations in the p53 gene. The study was based on single-strand conformation polymorphism (SSCP) analysis and DNA sequencing of exons 2 through 11 of the p53 gene using DNA preparations from microdissected tumors. Mutations were found in 40% of the carcinomas (including a borderline component adjacent to carcinoma in one lesion) but in none of the pure BTs. These findings suggest that p53 mutations may not be commonly associated with the borderline phenotype of ovarian epithelial tumors but may occur during malignant transformation. HUM PATHOL 26:387-392. Copyright (C) 1995 by W.B. Saunders Company C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. UNIV VERMONT,DEPT PATHOL,BURLINGTON,VT 05405. FU NCI NIH HHS [CA44-768] NR 28 TC 62 Z9 63 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD APR PY 1995 VL 26 IS 4 BP 387 EP 392 DI 10.1016/0046-8177(95)90138-8 PG 6 WC Pathology SC Pathology GA QT413 UT WOS:A1995QT41300006 PM 7705816 ER PT J AU GOODFRIEND, TL BALL, DL ELLIOTT, ME SHACKLETON, C AF GOODFRIEND, TL BALL, DL ELLIOTT, ME SHACKLETON, C TI LEAD INCREASES ALDOSTERONE PRODUCTION BY RAT ADRENAL-CELLS SO HYPERTENSION LA English DT Article; Proceedings Paper CT 48th Annual Fall Conference and Scientific Sessions of the Council-for-High-Blood-Pressure-Research CY SEP 27-30, 1994 CL CHICAGO, IL SP COUNCIL HIGH BLOOD PRESSURE RES DE LEAD; BLOOD PRESSURE; ALDOSTERONE; HYPERTENSION, MINERALOCORTICOID; CORTICOSTERONE; ADRENAL GLANDS ID BLOOD-PRESSURE; ANGIOTENSIN; EXPOSURE AB Exposure to lead has been postulated to contribute to elevated blood pressure in humans and has been shown to raise blood pressure in animals. The mechanism of action of lead on blood pressure is unknown. We fed lead to rats in their drinking water and then examined the production of aldosterone by their adrenal cells in vitro. We also measured excretion of aldosterone and corticosterone by intact rats stimulated with corticotropin, with and without lead treatment. At a dose (273 ppm) that raised blood levels to 30 to 40 mu g/dL, comparable to blood levels in exposed humans, lead induced increased aldosterone secretion in vitro and in vivo. The effect of lead was most evident when cells or animals were stimulated with aldosterone secretagogues. Experiments in vitro indicate that exposure to lead in vivo increases activity of one or more steps in the late pathway of aldosterone biosynthesis. The results suggest that the hypertensive effect of lead involves relative hyperaldosteronism and may be most evident when secretion of this hormone is stimulated. C1 UNIV WISCONSIN,DEPT PHARMACOL,MADISON,WI. UNIV WISCONSIN,DEPT MED,MADISON,WI. CHILDRENS HOSP RES INST,OAKLAND,CA. RP GOODFRIEND, TL (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. FU NIDDK NIH HHS [DK34400] NR 14 TC 16 Z9 16 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD APR PY 1995 VL 25 IS 4 BP 785 EP 789 PN 2 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QT942 UT WOS:A1995QT94200025 PM 7721433 ER PT J AU WEBER, GF ABROMSONLEEMAN, S CANTOR, H AF WEBER, GF ABROMSONLEEMAN, S CANTOR, H TI A SIGNALING PATHWAY COUPLED TO T-CELL RECEPTOR LIGATION BY MMTV SUPERANTIGEN LEADING TO TRANSIENT ACTIVATION AND PROGRAMMED CELL-DEATH SO IMMUNITY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INCOMPATIBLE STRAIN C3H; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; ARACHIDONIC-ACID; CONVENTIONAL ANTIGEN; APOPTOTIC THYMOCYTES; HUMAN-LYMPHOCYTES; GENE-EXPRESSION; MICE AB Stimulation of T cells by retroviral and bacterial superantigens is followed by specific T cell elimination, in contrast with stimulation of T cells by peptide, which is usually associated with clonal expansion. We show here that this differential response phenotype is apparent at the level of individual T cell clones following TCR ligation with peptide or MTV antigen. We exploited selective coupling of apoptosis to TCR ligation by MTV7 to examine some of the intracellular biochemical events that underlie this response. MTV-dependent activation resulting in apoptosis was associated with activation of phospholipase Aa and the generation of reactive oxygen intermediates. Inhibition of these biochemical events prevented both MTV-dependent activation and apoptosis without affecting the peptide-dependent response of the same T cell clones. These results indicate that clonal expansion or programmed cell death following TCR ligation may be consequences of distinct TCR-coupled signaling pathways. C1 HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. RP DANA FARBER CANC INST, IMMUNOPATHOL LAB, BOSTON, MA 02115 USA. FU NIAID NIH HHS [AI36105, AI13600, AI12184] NR 56 TC 32 Z9 32 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD APR PY 1995 VL 2 IS 4 BP 363 EP 372 DI 10.1016/1074-7613(95)90144-2 PG 10 WC Immunology SC Immunology GA QU616 UT WOS:A1995QU61600006 PM 7719939 ER PT J AU SHINKAI, Y MA, A CHENG, HL ALT, FW AF SHINKAI, Y MA, A CHENG, HL ALT, FW TI CD3-EPSILON AND CD3-XI CYTOPLASMIC DOMAINS CAN INDEPENDENTLY GENERATE SIGNALS FOR T-CELL DEVELOPMENT AND FUNCTION SO IMMUNITY LA English DT Article ID RECEPTOR ZETA-CHAIN; ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODIES; MUTANT MICE; B-CELLS; EXPRESSION; ACTIVATION; COMPLEX; LACKING; TAIL AB To determine whether CD3 epsilon and CD3 zeta proteins have unique roles in TCR-dependent functions, chimeric genes encoding the extracellular and transmembrane domains of the human IL-2 receptor alpha chain (Tac) fused to a cytoplasmic domain of either the CD3 epsilon or CD3 zeta chain were introduced as transgenes into both normal and RAG2-deficient (RAG2(-/-)) mice. Developmental arrest of T lineage cells at the CD4, CD8 double-negative stage in the transgenic RAG2(-/-) thymus was released to the CD4, CD8 double-positive (DR) stage by in vivo cross-linking of TT epsilon or TT zeta with anti-Tac antibody. In TT epsilon(+) or TT zeta(+), RAG2(-/-) mice, in vitro cross-linking of TT epsilon and TT zeta induced DP thymocyte cell death and proliferation of mature single-positive T cells. Overall, no qualitative differences were observed between TT epsilon- and TT zeta-mediated functions, suggesting that different CD3 components deliver qualitatively similar signals in inducing TCR-dependent functions. C1 CHILDRENS HOSP,HOWARD HUGHES MED INST,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RP SHINKAI, Y (reprint author), CHILDRENS HOSP,HOWARD HUGHES MED INST,DEPT GENET,BOSTON,MA 02115, USA. RI Shinkai, Yoichi/N-3909-2014 OI Shinkai, Yoichi/0000-0002-6051-2484 FU NCI NIH HHS [CA42335]; PHS HHS [A120047, U01 A131541] NR 39 TC 70 Z9 71 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 1995 VL 2 IS 4 BP 401 EP 411 PG 11 WC Immunology SC Immunology GA QU616 UT WOS:A1995QU61600010 PM 7719942 ER PT J AU SALAZAR, M DEULOFEUT, H GRANJA, C DEULOFEUT, R YUNIS, DE MARCUSBAGLEY, D AWDEH, Z ALPER, CA YUNIS, EJ AF SALAZAR, M DEULOFEUT, H GRANJA, C DEULOFEUT, R YUNIS, DE MARCUSBAGLEY, D AWDEH, Z ALPER, CA YUNIS, EJ TI NORMAL HBSAG PRESENTATION AND T-CELL DEFECT IN THE IMMUNE-RESPONSE OF NONRESPONDERS SO IMMUNOGENETICS LA English DT Article ID HEPATITIS-B VACCINE; HAPLOTYPE CONTROLS NONRESPONSIVENESS; MAJOR HISTOCOMPATIBILITY COMPLEX; SURFACE-ANTIGEN HBSAG; IMMUNOGENIC PEPTIDES; CLONAL ELIMINATION; GENETIC-REGULATION; LYMPHOCYTES-T; RECOGNITION; BINDING AB Lymphocytes from nonresponders to HBsAg fail to proliferate in vitro in the presence of HBsAg-pulsed antigen presenting cells. We studied four pairs of major histocompatibility complex (MHC)-matched, mixed lymphocyte reaction-negative individuals discordant for HBsAg response. For each pair, responder lymphocytes proliferated in the presence of nonresponder antigen pulsed antigen presenting cells. Responder and nonresponder antigen presenting cells were equally effective. There was no evidence for inhibition of responder T-cell proliferation by nonresponder lymphocytes or antigen presenting cells, The defect is thus in the helper T cells of nonresponders and not in the antigen processing or binding of processed peptides to MHC molecules on antigen presenting cells. C1 CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. AMER RED CROSS,DEDHAM,MA 02026. FU NHLBI NIH HHS [HL-29583]; NIAID NIH HHS [AI-14157]; NICHD NIH HHS [HD-17461] NR 46 TC 54 Z9 57 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD APR PY 1995 VL 41 IS 6 BP 366 EP 374 DI 10.1007/BF00163994 PG 9 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA QW712 UT WOS:A1995QW71200005 PM 7759133 ER PT J AU ABDI, K ROGERS, RA LI, XP LOPEZ, P RAWN, J MENTZER, SJ AF ABDI, K ROGERS, RA LI, XP LOPEZ, P RAWN, J MENTZER, SJ TI IN-SITU FLUORESCENCE LABELING OF SHEEP LUNG MICROVASCULAR ENDOTHELIUM SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE LUNG; ENDOTHELIUM; MICROVESSELS; LIPOSOMES; FLUORESCENCE; SHEEP ID LOW-DENSITY LIPOPROTEIN; CELLS; CULTURES; HETEROGENEITY; JUNCTIONS; ANTIBODY AB Endothelial cells are intimately involved in a variety of biological processes such as inflammatory disorders, wound healing, and tumor invasion. The finding of endothelial heterogeneity in various tissues has led to major efforts to isolate and culture microvascular endothelial cells in human and animal tissue. In this report we have used phosphatidyl ethanolamine (PE)-labeled liposomes to fluorescently label the sheep lung microvasculature in situ. Using normotensive perfusion pressure, the PE-labeled liposomes did not extravasate into extravascular lung tissue. Mechanical and enzymatic digestion of the lung tissue demonstrated that the PE-labeled liposomes provided a stable label of the vascular lining cells during ex vivo processing. After digestion, the overwhelming majority of the fluorescent label appeared in cellular aggregates, Approximately 80% of these cells demonstrated an in vitro phenotype consistent with microvascular endothelium. A novel monoclonal antibody selective for sheep endothelial cells was developed to confirm the presence of lung endothelium in the fluorescently labeled cellular aggregates. We conclude that in situ fluorescence labeling of vascular lining cells provides an anatomic marker for relevant vascular lining cells and an opportunity to study these cells in vitro. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,RESP BIOL PROGRAM,BOSTON,MA 02115. FU NHLBI NIH HHS [HL47078] NR 22 TC 9 Z9 9 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI LARGO PA 9315 LARGO DR WEST, STE 25, LARGO, MD 20774 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD APR PY 1995 VL 31 IS 4 BP 310 EP 315 PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA QP273 UT WOS:A1995QP27300013 PM 7795850 ER PT J AU JOSHI, PC PATHAK, MA AF JOSHI, PC PATHAK, MA TI PHOTOPHYSICAL AND PHOTOBIOLOGICAL PROPERTIES OF 3-CARBETHOXYPSORALEN SO INDIAN JOURNAL OF BIOCHEMISTRY & BIOPHYSICS LA English DT Article ID 4',5' REACTION SITE; 3,4 AND-OR; SINGLET OXYGEN; YEAST; 8-METHOXYPSORALEN; SENSITIZATION; DERIVATIVES; PSORALENS AB 3-Carbethoxypsoralen (3-CP), a linear tricyclic psoralen, known for its photoreaction with DNA to form monofunctional cyclobutane adducts with pyrimidine bases, was found to produce a highly reactive cytotoxic species, singlet oxygen (O-1(2)) to a greater extent than several other linear psoralens such as psoralen, 8-MOP, 5-MOP or angular psoralens (angelicin). 3-CP also produced superoxide radicals (O-2-radical-anion) at a rate slower than psoralens in the following order:psoralen > angelicin > 3-CP > 8-MOP > 5-MOP. O-1(2) produced by photoactivated 3-CP was found td oxidize tyrosine and Dopa to Dopachrome, and subsequently their conversion to melanin. It also induced photooxidation of 2'-deoxyguanosine. Reactive oxygen species produced by 3-CP also induced lipid peroxidation. The rate of dopachrome formation to promote its conversion to melanin and lipid peroxidation by 3-CP and other linear and angular psoralens and hematoporphyrin derivatives may be related to their skin photosensitizing ability and the rate of O-1(2) production. Topically applied 3-CP on hairless mice exposed to UVA radiation was found to be a nonphotocarcinogenic agent in contrast to 8-MOP, which under similar conditions produced a 70% tumour yield (squamous cell carcinoma) in 65 weeks. 3-CP was observed to be a photolabile compound and was converted to a dihydro-form as previously reported by other investigators. The photoconversion of 3-CP to 4',5'-dihydro-3-CP was enhanced under N-2, whereas, under O-2 atmosphere, lesser degree of photoconversion was observed, thus, indicating that reduction takes place via an anoxic or Type I mechanism. The significance of these observations are discussed in relation to the skin photosensitizing, nonphotocarcinogenic, and photochemotherapeutic potential of 3-CP. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02114. NR 35 TC 4 Z9 4 U1 0 U2 0 PU COUNCIL SCIENTIFIC INDUSTRIAL RESEARCH PI NEW DELHI PA PUBL & INFO DIRECTORATE, NEW DELHI 110012, INDIA SN 0301-1208 J9 INDIAN J BIOCHEM BIO JI Indian J. Biochem. Biophys. PD APR PY 1995 VL 32 IS 2 BP 63 EP 73 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RL792 UT WOS:A1995RL79200001 PM 7642202 ER PT J AU CAROZZA, SE OLSHAN, AF FAUSTMAN, EM GULA, MJ KOLONEL, LN AUSTIN, DF WEST, ED WEISS, NS SWANSON, GM LYON, JL HEDLEYWHYTE, T GILLES, FH ASCHENBRENER, C LEVITON, A AF CAROZZA, SE OLSHAN, AF FAUSTMAN, EM GULA, MJ KOLONEL, LN AUSTIN, DF WEST, ED WEISS, NS SWANSON, GM LYON, JL HEDLEYWHYTE, T GILLES, FH ASCHENBRENER, C LEVITON, A TI MATERNAL EXPOSURE TO N-NITROSATABLE DRUGS AS A RISK FACTOR FOR CHILDHOOD BRAIN-TUMORS SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID NITROSO-COMPOUNDS; TUMORS; CHILDREN; PRODUCTS; NITRITE; SMOKING; CANCER; DIET AB Background. Animal models suggest that compounds containing a nitrosyl group (N-nitroso compounds (NNO)) can act as potent transplacental carcinogens. Many common drug formulations have the potential to undergo nitrosation in vivo. The association between maternal use of nitrosatable drugs during pregnancy and development of brain tumours in the offspring was examined in a SEER-based case-control study. Methods. Maternal exposure to nitrosatable drugs during pregnancy was compared among 361 childhood brain tumour cases and 1083 matched controls recruited through random-digit dialling. Results. There was no increase in risk observed for childhood brain tumours overall (OR = 1.15; 95% CI : 0.69-1.94) or for astrocytomas individually (OR = 1.16; 95% CI : 0.50-2.69). A slight elevation in risk was noted for medulloblastomas (OR = 1.47; 95% CI : 0.28-7.62) and 'other' tumours (OR = 1.27; 95% CI : 0.56-2.86), however, both estimates were based on small numbers. Conclusions. Our findings suggest that no increased risk of childhood brain tumours was associated with maternal exposure to nitrosatable drugs. The study results should be Viewed with caution given the imprecision of the point estimates as well as the lack of data on specific timing and dosage of exposure and degree of nitrosatability of drugs taken. C1 UNIV WASHINGTON,DEPT ENVIRONM HLTH,SEATTLE,WA 98195. UNIV PITTSBURGH,DEPT BIOSTAT,PITTSBURGH,PA 15261. CANC RES CTR HAWAII,PROGRAM EPIDEMIOL,HONOLULU,HI. CALIF DEPT HLTH SERV,CANC EPIDEMIOL UNIT,EMERYVILLE,CA. NO CALIFORNIA CANC REGISTRY,ALAMEDA,CA. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. MICHIGAN STATE UNIV,CTR COMPREHENS BREAST CANC,E LANSING,MI. UNIV UTAH,DEPT FAMILY & COMMUNITY MED,SALT LAKE CITY,UT. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA. CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. UNIV SO CALIF,LOS ANGELES,CA. UNIV NEBRASKA,MED CTR,OMAHA,NE. CHILDRENS HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RP CAROZZA, SE (reprint author), UNIV N CAROLINA,DEPT EPIDEMIOL,CHAPEL HILL,NC 27599, USA. FU NCI NIH HHS [CA-21819] NR 25 TC 20 Z9 20 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 1995 VL 24 IS 2 BP 308 EP 312 DI 10.1093/ije/24.2.308 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA032 UT WOS:A1995RA03200007 PM 7635590 ER PT J AU GANS, JS RUTAN, JS WILCOX, N AF GANS, JS RUTAN, JS WILCOX, N TI T-GROUPS (TRAINING GROUPS) IN PSYCHIATRIC RESIDENCY PROGRAMS - FACTS AND POSSIBLE IMPLICATIONS SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article AB The authors studied T-groups offered in psychiatric residency programs in the United States in 1992. A 32-item questionnaire was sent to the residency training directors of 297 psychiatric programs and 34% responded. Results of the questionnaire are presented and their possible implications are discussed. These include: (1) programs that offer T-group value it as indicated by the time allotted to it, the quality of the T-group leaders, and the objectives within the residency program it seeks to accomplish; (2) 45% of respondents not offering T-groups cite negative attitudes toward T-groups (theirs or their residents) as a reason for this decision; (3) T-group, often equated with psychodynamic process, may have suffered the same recent deemphasis as has the teaching of psychodynamic psychotherapy; (4) and T-group, by its very nature, has educational as well as therapeutic features, a combination that creates tensions with regard to the T-group contract, especially the items having to do with confidentiality and attendance. The authors suggest group therapy will be a primary treatment modality in the coming years of economic constraint. They also recommend making a case to residency training directors for T-group and its inclusion in psychiatric curricula. C1 MASSACHUSETTS GEN HOSP,CTR GRP PSYCHOTHERAPY,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. NR 12 TC 4 Z9 4 U1 0 U2 0 PU GUILFORD PRESS PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD APR PY 1995 VL 45 IS 2 BP 169 EP 183 PG 15 WC Psychology, Clinical SC Psychology GA RB270 UT WOS:A1995RB27000007 PM 7759178 ER PT J AU HUGHESDAVIES, L GALANOPOULOS, T HARRISON, L MAXWELL, M ANTONIADES, HN DEMPLE, B AF HUGHESDAVIES, L GALANOPOULOS, T HARRISON, L MAXWELL, M ANTONIADES, HN DEMPLE, B TI EXPRESSION OF THE HUMAN APURINIC ENDONUCLEASE GENE (APE) IN NORMAL AND MALIGNANT-TISSUES SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE APURINIC ENDONUCLEASE GENE; ASTROCYTOMA; MENINGIOMA ID DNA-REPAIR; EXONUCLEASE-III; MUTAGENESIS; CLONING AB Apurinic/apyrimidinic endonucleases initiate repair at sites of base loss produced by many carcinogens and maintain genetic stability by repairing abasic sites produced spontaneously. We examined whether expression of the main apurinic endonuclease of human cells, encoded by the APE gene, might be decreased in malignant cells and thus potentiate an elevated mutation rate. Northern blotting and in situ hybridisation were used to quantitate the level of APE mRNA in various normal tissues and in 24 different brain tumors. There were no differences in APE expression among the normal tissues, or between malignant astrocytomas and meningiomas and the surrounding normal brain tissues. This suggests that diminished expression of the apurinic endonuclease does not underly the induction of these cancers, or explain clinical variations in presentation and response to treatment. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT MOLEC & CELLULAR TOXICOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 15 TC 6 Z9 6 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD APR PY 1995 VL 6 IS 4 BP 749 EP 752 PG 4 WC Oncology SC Oncology GA QN715 UT WOS:A1995QN71500002 PM 21556598 ER PT J AU KOURY, ME REGEZI, JA PERROTT, DH KABAN, LB AF KOURY, ME REGEZI, JA PERROTT, DH KABAN, LB TI ATYPICAL FIBROOSSEOUS LESIONS - DIAGNOSTIC CHALLENGES AND TREATMENT CONCEPTS SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article DE FIBROOSSEOUS LESIONS; JAW TUMORS ID JUVENILE OSSIFYING FIBROMA; OSTEOSARCOMATOSIS; JAWS AB The term fibro-osseous lesion is a generic designation of a group of jaw disorders (ranging from inflammatory to neoplastic) that microscopically exhibit, a connective-tissue matrix and islands/trabeculae of bone. Although the histologic appearance, and frequently the clinical and radiographic features, may be similar for many of these lesions, they demonstrate a wide range of biologic behavior. Treatment therefore is varied, and there are few well-established guidelines to help the surgeon. Five fibro-osseous lesions with atypical features are presented to demonstrate the diagnostic difficulties associated with these lesions and to show the need for accurate classification in order to help direct treatment and predict outcome. Final diagnoses for ''atypical'' fibro-osseous lesions included: multiple ossifying fibromas, unclassifiable fibro-osseous lesion, osteosarcoma with concomitant multiple ossifying fibromas, juvenile or psammomatoid ossifying fibroma, and central low-grade osteosarcoma. ''Fibro-osseous lesion'' should be viewed as a working diagnosis, and a definitive diagnosis should be actively sought; the addition of ''atypical'' to this designation suggests the likelihood of an aggressive lesion. Treatment of lesions having atypical and nonclassical microscopic features must be based on the biologic behavior of the tumor. C1 UNIV CALIF SAN FRANCISCO,DEPT ORAL & MAXILLOFACIAL SURG,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,SCH DENT,SAN FRANCISCO,CA. UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA. HARVARD UNIV,SCH DENT MED,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA. NR 22 TC 32 Z9 33 U1 0 U2 3 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 APR PY 1995 VL 24 IS 2 BP 162 EP 169 DI 10.1016/S0901-5027(06)80094-9 PG 8 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA RA037 UT WOS:A1995RA03700010 PM 7608584 ER PT J AU BERGMAN, S SELIG, M COLLINS, MD FARROW, JAE BARON, EJ DICKERSIN, GR RUOFF, KL AF BERGMAN, S SELIG, M COLLINS, MD FARROW, JAE BARON, EJ DICKERSIN, GR RUOFF, KL TI STREPTOCOCCUS-MILLERI STRAINS DISPLAYING A GLIDING TYPE OF MOTILITY SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID COAGULASE-NEGATIVE STAPHYLOCOCCI; CLINICAL SPECIMENS; RECOGNITION; SLIME AB Isolates belonging to the ''Streptococcus milleri'' species group that appear to exhibit a gliding type of motility, which is expressed as spreading growth on certain types of agar media, are described. These strains resembled a biotype of ''S. milleri'' that is usually isolated from genitourinary sources and is notable for its ability to ferment a wide array df carbohydrates. This biotype, which is currently included in the species Streptococcus anginosus, has been implicated in cases of neonatal infection. The ''S. milleri'' isolates which we studied lacked any observable organelles of motility and gave negative results when they were tested in conventional motility test medium stab cultures, Colonies growing on certain agar media, however, spread over the surfaces of plates and increased in area with increasing time of incubation. Chocolate agar supported maximum spreading, while this characteristic was barely discernible on blood agar. Electron microscopy studies revealed that there was more production of extracellular glycocalyx by motile strains than by a nonmotile isolate having a similar biotype. The results of an analysis of 16S rRNA gene sequences suggested that the motile strains are closely related to S. anginosus and represent a distinct rRNA population within the ''S. milleri'' species complex. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MICROBIOL LAB,BOSTON,MA 02114. BBSRC,INST FOOD RES,READING RG6 2EF,BERKS,ENGLAND. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. NR 18 TC 19 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD APR PY 1995 VL 45 IS 2 BP 235 EP 239 PG 5 WC Microbiology SC Microbiology GA QR834 UT WOS:A1995QR83400007 PM 7537057 ER PT J AU GONZALEZ, VH HU, LK THEODOSSIADIS, PG FLOTTE, TJ GRAGOUDAS, ES YOUNG, LHY AF GONZALEZ, VH HU, LK THEODOSSIADIS, PG FLOTTE, TJ GRAGOUDAS, ES YOUNG, LHY TI PHOTODYNAMIC THERAPY OF PIGMENTED CHOROIDAL MELANOMAS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE PHOTODYNAMIC THERAPY; CHOROIDAL MELANOMA; PHOTOSENSITIZER; RABBIT MODEL; PIGMENTED MELANOMAS ID CHLOROALUMINUM SULFONATED PHTHALOCYANINE; INTRAOCULAR MALIGNANT-MELANOMA; DIHEMATOPORPHYRIN ETHER; TUMOR DESTRUCTION; HYPERTHERMIA; CANCER; SKIN; MODEL; PHOTOSENSITIZERS; PHOTOTHERAPY AB Purpose. To evaluate the effectiveness of photodynamic therapy with chloroaluminum sulfonated phthalocyanine in the treatment of pigmented choroidal melanomas in a rabbit model. Methods. Pigment containing B16F10 murine melanoma cells were implanted transclerally into the subchoroidal space of 28 immunosuppressed New Zealand albino rabbits. The animals were treated with daily injections of cyclosporine and were followed up until tumors at least 2 mm in height were detected by ultrasonography. Twenty-four hours after the intravenous injection of chloroaluminum sulfonated phthalocyanine (CASPc, 5 mg/kg), tumors were irradiated at 675 nm through an argon-pumped dye laser at estimated total light doses of 25 to 70 J/cm(2). Control animals were treated with light only or photosensitizer only. The animals were followed up for 4 1/2 to 8 weeks with regular fundus examinations. Results. Twenty tumor-bearing rabbits were treated with light and dye. The tumor regressed in 12 animals. Five of these animals were followed up for at least 4 1/2 weeks and the other seven for 8 weeks after treatment. At light doses under 40 J/cm(2), tumor regrowth was observed in five animals within 10 days of treatment. In all central groups, the tumor-bearing eyes were filled with tumor cells by the third week after implantation. Histologic examination of tumors treated with photosensitizer and light revealed prominent vascular damage early after treatment that resulted in vascular occlusion. Tumor necrosis was evident within 24 hours of treatment. Conclusions. Results suggest that photodynamic therapy may have a role in the treatment of pigmented choroidal melanomas. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,RETINA SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA. NR 37 TC 15 Z9 17 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 1995 VL 36 IS 5 BP 871 EP 878 PG 8 WC Ophthalmology SC Ophthalmology GA QQ756 UT WOS:A1995QQ75600014 PM 7706035 ER PT J AU PARK, IW SODROSKI, J AF PARK, IW SODROSKI, J TI FUNCTIONAL-ANALYSIS OF THE VPX, VPR, AND NEF GENES OF SIMIAN IMMUNODEFICIENCY VIRUS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE SIMIAN IMMUNODEFICIENCY VIRUS; VPX GENE; VPR GENE; NEF GENE; POINT MUTATIONS; DELETION MUTATIONS ID VIRION-ASSOCIATED PROTEIN; MUTATIONAL ANALYSIS; CELL-LINE; TYPE-2; HIV-2; REPLICATION; MACROPHAGES; SEQUENCE; GENOME; SIV AB The role of the vpx, vpr, and nef genes in the replication of simian immunodeficiency virus (SIV) was investigated using point and deletion mutations in these genes. The effects on replication kinetics of single or combined mutants-vpx, vpr, vpx-vpr, vpx-nef, vpr-nef, and vpx-vpr-nef-in established lymphoid CEMx174 and MT-4 cells were negligible, except that the postinfection appearance of vpx-nef, vpr-nef, and vpx-vpr-nef progeny virus was slightly delayed in MT-4 cells. The vpx, but not the vpr, point mutation reverted to wild-type sequences within 12 days after infection, suggesting that stronger selection pressure for Vpx than for Vpr expression might exist in these established cell lines. In contrast to growth in the lymphoid cell lines, replication of vpx-deleted viruses in macaque peripheral blood mononuclear cells (PBMC) was severely impaired, indicating that Vpx is necessary for efficient replication in PBMC. In contrast, the vpr mutant exhibited different degrees of impairment depending on the donor animal used as a source of PBMC. A virus encoding a Vpx-Vpr fusion protein replicated in PBMC comparably to a vpr deletion mutant virus, whereas a frameshift deletion at the vpx-vpr junction of this mutant eliminated virus replication, suggesting that deletion of the C-terminal half of Vpx was partially compensated by the presence of the large Vpr portion in the fusion protein. Deletion of the nef gene did not affect SIVmac replication in PBMC. The Vpx and Vpr proteins expressed in COS-1 cells were detected in the extracellular medium and did not crossreact with Vpr- and Vpx-specific antisera, in spite of extensive amino acid similarity between these proteins. These studies indicate the importance of Vpx and Vpr in SIVmac infection and suggest that these proteins are antigenically and functionally distinct. 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 02115. FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [P30 AI28691, R01 AI29333] NR 28 TC 21 Z9 21 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 APR 1 PY 1995 VL 8 IS 4 BP 335 EP 344 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QL406 UT WOS:A1995QL40600003 PM 7882097 ER PT J AU BENNETT, CL ADAMS, J BENNETT, RL RODRIQUE, D GEORGE, L CASSILETH, B GILMAN, SC AF BENNETT, CL ADAMS, J BENNETT, RL RODRIQUE, D GEORGE, L CASSILETH, B GILMAN, SC TI THE LEARNING-CURVE FOR AIDS-RELATED PNEUMOCYSTIS-CARINII PNEUMONIA - EXPERIENCE FROM 3,981 CASES IN VETERANS AFFAIRS HOSPITALS 1987-1991 SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE PNEUMOCYSTIS CARINII PNEUMONIA; LEARNING CURVE; SELECTIVE REFERRAL ID ACQUIRED IMMUNODEFICIENCY SYNDROME; SURVIVAL; MORTALITY; PATTERNS AB Previous studies have found lower mortality rates for AIDS-related Pneumocystis carinii pneumonia (PCP) in hospitals with higher levels of experience with PCP. It is not known if patients are selectively referred to better hospitals or if there is a learning curve whereby outcomes improve as physicians gain experience in treating PCP. We assessed cases of PCP at 140 Veterans Administration (VA) Medical Centers in the United States. During 1987-1991, 3,981 patients were hospitalized with first-episode AIDS-related PCP. Mortality at 30 days after admission. For these 3,981 hospitalizations at the 140 study hospitals, the 30-day mortality was 19%. Logistic regression models indicate that older age, race, geographic area, earlier year of treatment, hospitalization in the previous 12 months, and lower levels of hospital experience with AIDS were significant predictors of mortality at 30 days after admission. Compared with hospitals that had treated three cases or fewer of first-episode PCP, the odds of mortality at 30 days at hospitals that treated >50 cases of first-episode PCP were 0.73 (95% confidence interval 0.58-0.91), after controlling for differences in characteristics of the patients, year, and region. Mortality of patients with AIDS-related PCP decreases as VA hospitals gain experience. Longitudinal analyses over a 5-year period suggest that a learning curve best explains this finding. 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,DEPT MED,DURHAM,NC. DUKE UNIV,CTR CANC,DURHAM,NC. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. RAND CORP,LONG BEACH,CA. VET ADM MED CTR,WESTERN REG SPECIAL STUDIES GRP,LONG BEACH,CA 90822. UNIV SO CALIF,DIV INFECT DIS,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. VET AFFAIRS MED CTR,LONG BEACH,CA. RI Bennett, Charles/C-2050-2008 FU AHRQ HHS [1R01HS06494-01] NR 17 TC 19 Z9 19 U1 0 U2 1 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 APR 1 PY 1995 VL 8 IS 4 BP 373 EP 378 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QL406 UT WOS:A1995QL40600008 PM 7882102 ER PT J AU HEFLE, SL HELM, RM BURKS, AW BUSH, RK AF HEFLE, SL HELM, RM BURKS, AW BUSH, RK TI COMPARISON OF COMMERCIAL PEANUT SKIN-TEST EXTRACTS SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE PEANUT ALLERGY; SKIN TESTING; ALLERGENIC EXTRACTS ID ATOPIC-DERMATITIS; ALLERGEN; PROTEINS; IDENTIFICATION AB Background: Skin prick testing is a major tool for diagnosing food allergy. Food allergen extracts have not been standardized; this may lead to great variability in the predictive accuracy of skin prick tests. Methods: Six commercial peanut skin test extracts were compared in vitro with RAST inhibition assays, ELISA, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting with sera from peanut-allergic adults and in vivo by skin prick testing. Results: ELISA showed that the content of peanut allergens Ara h I and Ara h II in the extracts ranged from 0.0015 to 0.0236 and 0.0001 to 0.0164 mg Eq/ml, respectively. RAST inhibition studies showed that the extracts produced curves of similar slope, suggesting conservation of allergenic epitopes. SDS-PAGE revealed differences in protein profiles because roasted extracts generally possessed the same number and proportion of major protein bands but raw extracts varied more in both respects. SDS-PAGE and immunoblotting showed that two of the extracts contained major IgE-binding protein bands that did not appear in the others. One roasted extract gave little protein banding and consequently little IgE binding. Conclusions: Skin testing results showed no differences in the ability of the extracts to provoke a positive skin test response in peanut-sensitive subjects. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. UNIV WISCONSIN,DEPT MED,MADISON,WI. ARKANSAS CHILDRENS HOSP,DEPT PEDIAT IMMUNOL & ALLERGY,LITTLE ROCK,AR 72202. NR 18 TC 31 Z9 31 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 1995 VL 95 IS 4 BP 837 EP 842 DI 10.1016/S0091-6749(95)70127-3 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA QT468 UT WOS:A1995QT46800009 PM 7722164 ER PT J AU ICHINOSE, F ADRIE, C HURFORD, WE ZAPOL, WM AF ICHINOSE, F ADRIE, C HURFORD, WE ZAPOL, WM TI PROLONGED PULMONARY VASODILATOR ACTION OF INHALED NITRIC-OXIDE BY ZAPRINAST IN AWAKE LAMBS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE GUANOSINE 3',5'-CYCLIC MONOPHOSPHATE PHOSPHODIESTERASE; PLASMA GUANOSINE 3',5-CYCLIC MONOPHOSPHATE LEVELS; PULMONARY HYPERTENSION; NITRIC OXIDE TOXICITY ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; VASCULAR SMOOTH-MUSCLE; RELAXING FACTOR; METHYLENE-BLUE; RABBIT AORTA; B 22948; RESPONSES; GMP; VASOCONSTRICTION; INHIBITION AB Inhaled nitric oxide (NO) has been shown to selectively dilate the pulmonary vasculature. Zaprinast, an inhibitor of guanosine 3',5'-cyclic monophosphate-specific phosphodiesterase, augments smooth muscle relaxation induced by endothelium-dependent vasodilators. The present study was designed to determine whether intravenous administration of Zaprinast potentiates the vasodilating effects or prolongs the duration of action of intermittent NO inhalation. Eight awake lambs with U-46619-induced pulmonary hypertension breathed three concentrations of NO (5, 10, and 20 ppm) in a random order before and during an intravenous Zaprinast infusion (0.1 mg . kg-1 . min-1). Inhaled NO decreased pulmonary arterial pressure (PAP) in a dose-dependent fashion, with mean PAP reduction at 5, 10, and 20 ppm NO inhalation of 6 +/- 1, 7 +/- 1, and 9 +/- 1 (SE) mmHg, respectively. Although the Zaprinast infusion did not change the magnitude of mean PAP reduction, it caused a statistically significant reduction of pulmonary vascular resistance and prolonged the duration of action of inhaled NO (half-times of vasodilator response to 5, 10, and 20 ppm NO inhalation: 1.9 +/- 0.1, 2.1 +/- 0.2, and 2.1 +/- 0.2 min, respectively; half-times of NO inhalation with Zaprinast: 9.7 +/- 1.7, 11.5 +/- 2.2, and 12.3 +/- 2.0, respectively). Plasma concentrations as well as the transpulmonary differences of guanosine 3',5'-cyclic monophosphate were increased by the Zaprinast infusion during NO inhalation. A stable level of pulmonary vasodilation was demonstrated in four additional lambs by combining intermittent NO breathing with an intravenous infusion of Zaprinast. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 FU NHLBI NIH HHS [HL-42397] NR 40 TC 62 Z9 63 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD APR PY 1995 VL 78 IS 4 BP 1288 EP 1295 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA QR546 UT WOS:A1995QR54600012 PM 7615435 ER PT J AU PILLUTLA, RC SHARER, JD GULATI, PS WU, E YAMASHITA, Y LERNER, CG INOUYE, M MARCH, PE AF PILLUTLA, RC SHARER, JD GULATI, PS WU, E YAMASHITA, Y LERNER, CG INOUYE, M MARCH, PE TI CROSS-SPECIES COMPLEMENTATION OF THE INDISPENSABLE ESCHERICHIA-COLI ERA GENE HIGHLIGHTS AMINO-ACID REGIONS ESSENTIAL FOR ACTIVITY SO JOURNAL OF BACTERIOLOGY LA English DT Note ID GTP-BINDING PROTEIN; RAS PROTEINS; RNC OPERON; GROWTH AB Era is an essential GTP binding protein in Escherichia coli. Two homologs of this protein, Sgp from Streptococcus mutans and Era from Coxiella burnetii, can substitute for the essential function of Era in E. coli. Site-specific and randomly generated Era mutants which may indicate regions of the protein that are of functional importance are described. C1 UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,PISCATAWAY,NJ 08854. DANA FARBER CANC INST,BOSTON,MA 02115. KYUSHU UNIV,DEPT PREVENT DENT,HIGASHI KU,FUKUOKA 812,JAPAN. FU NIGMS NIH HHS [GM40087, GM19043] NR 16 TC 25 Z9 25 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 1995 VL 177 IS 8 BP 2194 EP 2196 PG 3 WC Microbiology SC Microbiology GA QR556 UT WOS:A1995QR55600035 PM 7721709 ER PT J AU REDDY, SV HUNDLEY, JE WINDLE, JJ ALCANTARA, O LINN, R LEACH, RJ BOLDT, DH ROODMAN, GD AF REDDY, SV HUNDLEY, JE WINDLE, JJ ALCANTARA, O LINN, R LEACH, RJ BOLDT, DH ROODMAN, GD TI CHARACTERIZATION OF THE MOUSE TARTRATE-RESISTANT ACID-PHOSPHATASE (TRAP) GENE PROMOTER SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID HUMAN OSTEOCLASTOMAS; PURIFICATION; CLONING; TYPE-5; BONE; UTEROFERRIN; INHIBITION; EXPRESSION; SEQUENCE; REGION AB Tartrate-resistant acid phosphatase (TRAP) is an iron-binding protein that is highly expressed in osteoclasts. To characterize the regulation of TRAP gene expression, progressive 5' and 3' deletions of a 1.8 kb fragment containing the 5'-flanking sequence were fused to a luciferase reporter gene. Two nonoverlapping regions of this 1.8 kb fragment had promoter activity. The upstream promoter (P-1) was located within the region from -881 bp to -463 bp relative to the ATG, while the downstream promoter (P-2) was located between -363 bp to -1 bp in a region we have previously shown to be an intron in transcripts originating from the upstream promoter. A putative repressor region for the P-2 promoter at -1846 bp to -1240 bp and a putative enhancer region at -962 bp to -881 bp relative to the ATG were identified. PCR analysis of promoter-specific transcription of the TRAP gene in various murine tissues showed that both promoters were active in several tissues. Transferrin-bound iron increased P-1 promoter activity 2.5-fold and hemin decreased P-1 promoter activity, but neither had any effect on P-2 activity. These data show that the transcriptional regulation of the TRAP gene is complex and that iron may play a key role in TRAP gene regulation. C1 AUDIE L MURPHY MEM VET ADM MED CTR,HLTH SCI CTR,RES SERV 151,SAN ANTONIO,TX 78284. UNIV TEXAS,DEPT MED HEMATOL,SAN ANTONIO,TX. UNIV TEXAS,DEPT CELL & STRUCT BIOL,SAN ANTONIO,TX 78284. CANC THERAPY & RES CTR S TEXAS,SAN ANTONIO,TX. OI Windle, Jolene/0000-0001-6690-385X FU NIADDK NIH HHS [AM35188]; NIAMS NIH HHS [AR39539, AR41336] NR 22 TC 67 Z9 68 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 1995 VL 10 IS 4 BP 601 EP 606 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QQ479 UT WOS:A1995QQ47900012 PM 7610931 ER PT J AU RAD, MR PHAN, HL KIRCHRATH, L TAN, PK KIRCHHAUSEN, T HOLLENBERG, CP PAYNE, GS AF RAD, MR PHAN, HL KIRCHRATH, L TAN, PK KIRCHHAUSEN, T HOLLENBERG, CP PAYNE, GS TI SACCHAROMYCES-CEREVISIAE APL2P, A HOMOLOG OF THE MAMMALIAN CLATHRIN AP BETA-SUBUNIT, PLAYS A ROLE IN CLATHRIN-DEPENDENT GOLGI FUNCTIONS SO JOURNAL OF CELL SCIENCE LA English DT Article DE CLATHRIN; CLATHRIN-ASSOCIATED PROTEIN; ADAPTIN; GOLGI APPARATUS; YEAST ID VESICLE ASSEMBLY POLYPEPTIDES; MEMBRANE-PROTEIN RETENTION; PUTATIVE YEAST HOMOLOG; PLASMA-MEMBRANE; COATED PITS; SECRETORY PATHWAY; COMPLEX AP-2; ENDOCYTOSIS; TRANSPORT; ADAPTERS AB Clathrin-coated vesicles mediate selective intracellular protein traffic from the plasma membrane and the trans-Golgi network. At these sites, clathrin-associated protein (AP) complexes have been implicated in both clathrin coat assembly and collection of cargo into nascent vesicles, We have found a gene on yeast chromosome XI that encodes a homologue of the mammalian AP beta subunits, Disruptions of this gene, APL2, and a previously identified beta homologue, APL1, have been engineered in cells expressing wild-type (CHC1) or temperature sensitive (chc1-ts) alleles of the clathrin heavy chain gene. APL1 or APL2 disruptions (apl1 Delta or apl2 Delta) yield no discernable phenotypes in CHC1 strains, indicating that the Apl proteins are not essential for clathrin function, However, the apl2 Delta, but not the apl1 Delta, allele enhances the growth and alpha-factor pheromone maturation defects of chc1-ts cells, Disruption of APL2 also partially suppresses the vacuolar sorting defect that occurs in chc1-ts cells immediately after imposition of the non-permissive temperature, These Golgi-specific effects of apl2 Delta in chc1-ts cells provide evidence that Apl2p is a component of an AP complex that interacts with clathrin at the Golgi apparatus. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT BIOL CHEM, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, INST MOLEC BIOL, LOS ANGELES, CA 90024 USA. UNIV DUSSELDORF, INST MICROBIOL, D-40225 DUSSELDORF, GERMANY. HARVARD UNIV, SCH MED, DEPT CELL BIOL, BOSTON, MA 02115 USA. CTR BLOOD RES, BOSTON, MA 02115 USA. FU NIGMS NIH HHS [GM 36548, GM39040] NR 58 TC 54 Z9 55 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD APR PY 1995 VL 108 BP 1605 EP 1615 PN 4 PG 11 WC Cell Biology SC Cell Biology GA QV626 UT WOS:A1995QV62600027 PM 7615679 ER PT J AU BARTOLAZZI, A JACKSON, D BENNETT, K ARUFFO, A DICKINSON, R SHIELDS, J WHITTLE, N STAMENKOVIC, I AF BARTOLAZZI, A JACKSON, D BENNETT, K ARUFFO, A DICKINSON, R SHIELDS, J WHITTLE, N STAMENKOVIC, I TI REGULATION OF GROWTH ACID DISSEMINATION OF A HUMAN LYMPHOMA BY CD44 SPLICE VARIANTS SO JOURNAL OF CELL SCIENCE LA English DT Article DE CD44; SPLICE VARIANT; GLYCOSAMINOGLYCAN; SHEDDING; TUMOR GROWTH ID T-CELL ACTIVATION; EXTRACELLULAR DOMAIN; ADHESION MOLECULE; RECEPTOR; HYALURONATE; EXPRESSION; ISOFORMS; CONFERS; PROTEIN; MEMBER AB CD44 is a polymorphic cell surface glycoprotein, currently proposed to be the principal cell surface receptor for hyaluronan, However, different isoforms of CD44, expressed in human lymphoid tumor cells, appear to have distinct effects on the ability of the cells to attach to hyaluronan-coated surfaces and on their capacity to form tumors in vivo, In the present study, we address the mechanisms that may regulate CD44 isoform-dependent adhesion to hyaluronan. We use a human Burkitt lymphoma, stably transfected with six different alternatively spliced human CD44 isoforms, to determine their potential hyaluronan binding and tumor growth promoting roles, We show that transfectants expressing CD44 splice variants that contain variable exons 6-10, 7-10 and 8-10 adhere to hyaluronan-coated surfaces weakly and that corresponding tumor formation in vivo is delayed with respect to CD44-negative parental cell-derived tumors. Abundant shedding of these three isoforms may play a significant role in determining the rate of tumor development, Transfectants expressing variable exon 3, on the other hand, fail to display CD44-mediated adhesion to hyaluronan, but form bone marrow tumors rapidly following intravenous injection. These observations suggest that different mechanisms regulate CD44-mediated adhesion and tumor growth, and provide evidence that expression of exon v3 may confer novel ligand-binding properties. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. MGH E,BOSTON,MA 02129. JOHN RADCLIFFE HOSP,INST MOLEC MED,MOLEC IMMUNOL GRP,OXFORD OX3 9DU,ENGLAND. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. CANTAB PHARMACEUT LTD,CAMBRIDGE CB4 4GN,ENGLAND. RP BARTOLAZZI, A (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NCI NIH HHS [R01CA55735] NR 28 TC 60 Z9 60 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 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD APR PY 1995 VL 108 BP 1723 EP 1733 PN 4 PG 11 WC Cell Biology SC Cell Biology GA QV626 UT WOS:A1995QV62600038 PM 7542258 ER PT J AU HERLIHY, JP VERMEULEN, MW JOSEPH, PM HALES, CA AF HERLIHY, JP VERMEULEN, MW JOSEPH, PM HALES, CA TI IMPAIRED ALVEOLAR MACROPHAGE FUNCTION IN SMOKE-INHALATION INJURY SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; AGING NEUTROPHILS; APOPTOSIS; DIFFERENTIATION; PHAGOCYTOSIS; RECOGNITION; MODULATION; CYTOKINES; MONOCYTES; EXPOSURE AB The high incidence of both bacterial pneumonia and the adult respiratory distress syndrome (ARDS) associated with smoke inhalation injury (SII) may result, at least in part, from smoke-induced injury to the alveolar macrophage (AM). Specifically, we hypothesized that AM antimicrobial function, ability to phagocytose apoptotic PMNs, and capacity to prevent apoptosis in PMNs are impaired by smoke. To test these hypotheses, AMs were harvested by bronchoalveolar ravage from sheep before and after the animal was exposed to cotton smoke. The two populations of AMs were incubated with Pseudomonas aeruginosa (PSA) in vitro. Normal AMs (NAMs) phagocytosed a mean of 99 +/- 11% of the PSA placed in their wells, whereas smoke-exposed AMs (SAMs) ingested only 60 +/- 8%. NAMs killed 80 +/- 8% of PSA ingested, whereas SAMs killed only 56 +/- 16% (P < 0.05). When sheep PMNs, allowed to undergo apoptosis, were incubated with the two AM populations, 66 +/- 3% of the NAMs and 40 +/- 6% of the SAMs demonstrated phagocytosis of these apoptotic PMNs (P < 0.05). Fresh sheep PMNs were incubated in unconditioned media, NAM and SAM-conditioned media, and followed over 48 hr for the development of apoptosis and maintenance of viability. The NAM-conditioned media markedly prevented apoptosis and augmented PMN survival relative to the unconditioned and SAM-conditioned media (P < 0.05). The poor antimicrobial function known to be characteristic of apoptotic PMNs, together with the directly impaired antimicrobial function of AMs, may contribute to the infectious complications of SII. If the PMNs recruited to the lung in SII are not properly supported by the AMs following smoke injury, large numbers may undergo apoptosis. if not properly disposed of by these SAMs, the apoptotic PMNs could eventually lyse, releasing tissue toxins, resulting in escalation of lung injury and leading to ARDS. (C) 1995 Wiiey-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,PULM & CRIT CARE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02174. FU NHLBI NIH HHS [HL36829, 1 F32 HL09017-01] NR 30 TC 22 Z9 28 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD APR PY 1995 VL 163 IS 1 BP 1 EP 8 DI 10.1002/jcp.1041630102 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA QN686 UT WOS:A1995QN68600001 PM 7896885 ER PT J AU BELL, NH AF BELL, NH TI VITAMIN-D METABOLISM, AGING, AND BONE LOSS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID SENILE OSTEOPOROSIS; FRACTURES; WOMEN; AGE; DEFICIENCY; CALCIUM C1 MED UNIV S CAROLINA, RALPH H JOHNSON VET AFFAIRS MED CTR, DEPT PHARMACOL, CHARLESTON, SC 29425 USA. RP BELL, NH (reprint author), MED UNIV S CAROLINA, RALPH H JOHNSON VET AFFAIRS MED CTR, DEPT MED, CHARLESTON, SC 29425 USA. NR 14 TC 21 Z9 22 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1995 VL 80 IS 4 BP 1051 EP 1051 DI 10.1210/jc.80.4.1051 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QR243 UT WOS:A1995QR24300002 PM 7714064 ER PT J AU KHOURY, RH WANG, QF CROWLEY, WF HALL, JE SCHNEYER, AL TOTH, T MIDGLEY, AR SLUSS, PM AF KHOURY, RH WANG, QF CROWLEY, WF HALL, JE SCHNEYER, AL TOTH, T MIDGLEY, AR SLUSS, PM TI SERUM FOLLISTATIN LEVELS IN WOMEN - EVIDENCE AGAINST AN ENDOCRINE FUNCTION OF OVARIAN FOLLISTATIN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; MESSENGER-RIBONUCLEIC-ACID; ACTIVIN-BINDING PROTEIN; GRANULOSA-CELLS; ESTROUS-CYCLE; GROWTH-FACTOR; RAT OVARY; INHIBIN; EXPRESSION; SECRETION AB Follistatin is a monomeric protein first identified in and isolated from ovarian follicular fluid. Evidence that follistatin might be an ovarian endocrine hormone functioning in a negative feedback fashion to modulate pituitary FSH production is based primarily on in vitro experiments. To examine the possible role of follistatin as an endocrine agent in vivo, we sought to relate circulating levels of follistatin to ovarian activity in women. Therefore, we developed a specific and sensitive homologous RIA using antiserum generated against recombinant human follistatin for the measurement of total follistatin in the presence or absence of activin. Follistatin was measured quantitatively (106 +/- 6% recovery) using calibration standards ranging from 0.4-25 ng/tube and up to 400 mu L/tube serum. Furthermore, all of the endogenous follistatin measured in human serum could be removed by adsorption to activin-coated plates. Using this homologous RIA, human follicular fluid (100-600 ng/mL; n = 75) contained 3-150 times more follistatin than serum (4-35 ng/mL), an observation consistent with the notion that serum follistatin originates from the gonad. However, further studies of follistatin levels across the normal menstrual cycle (mean +/- SE, 8.09 +/- 0.73; n = 72 daily samples from 4 women), in pregnant women (17.49 +/- 1.34; n = 8), in daily samples from 20 women undergoing ovarian stimulation by exogenous FSH (9.90 +/- 0.62; n = 119), in postmenopausal women including two ovariectomized individuals (9.57 +/- 0.43; n = 8), and in GnRH-deficient women (9.85 +/- 0.50; n = 6) failed to support the hypothesis that serum levels of follistatin reflect ovarian activity in women. Levels of follistatin measured in serum collected across normal menstrual cycles did not fluctuate. However, the roughly nanomolar concentrations of follistatin measured suggest a physiological role for this protein. Follistatin at nanomolar concentrations may be capable of binding and inactivating circulating activin and perhaps in this way limiting the biological activity of activin to local autocrine or paracrine mechanisms. Measurement of peripheral levels of follistatin apparently represents only a first, albeit crucial, step in the study of the physiological significance of this protein in human reproduction. C1 MASSACHUSETTS GEN HOSP, REPROD ENDOCRINE UNIT, BOSTON, MA 02114 USA. FU NICHD NIH HHS [P30-HD-28138, R01-HD-15080, U54-HD-29164] NR 43 TC 61 Z9 64 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1995 VL 80 IS 4 BP 1361 EP 1368 DI 10.1210/jc.80.4.1361 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QR243 UT WOS:A1995QR24300058 PM 7714112 ER PT J AU MILLER, GM ALEXANDER, JM BIKKAL, HA KATZNELSON, L ZERVAS, NT KLIBANSKI, A AF MILLER, GM ALEXANDER, JM BIKKAL, HA KATZNELSON, L ZERVAS, NT KLIBANSKI, A TI SOMATOSTATIN RECEPTOR SUBTYPE GENE-EXPRESSION IN PITUITARY-ADENOMAS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ANALOG OCTREOTIDE; SUBUNIT SECRETION; TUMORS; CLONING; GROWTH; ALPHA; INHIBITION; INVITRO; CYCLASE; HORMONE AB Somatostatin (SRIF) exerts its diverse biological effects through a family of membrane receptors. In addition to inhibiting GH secretion, SRIF has antiproliferative effects and has been used clinically in the treatment of pituitary tumors. SRIF receptor (SSTR) expression has recently been identified in pituitary adenomas, and it is unknown whether differential expression of SSTR subtypes predicts clinical responses to SRIF analogs. We therefore determined which SSTR subtype messenger RNAs (mRNAs) are expressed in pituitary adenoma phenotypes and in normal human pituitary tissue using reverse transcriptase-polymerase chain reaction and tested whether expression of specific SSTR subtype mRNA is necessary for SRIF inhibition of GH secretion in human somatotroph adenomas in vitro. Expression of SSTR subtypes 1, 2, and 5 mRNA was identified in all pituitary adenoma types and normal pituitary tissue. In contrast, SSTR3 mRNA was detected in only one somatotroph adenoma as well as in control insulinoma tissue, a tissue known to express SSTR3 mRNA, and was not detected in normal pituitary tissue. SSTR4 mRNA was not detected in any human pituitary tissue. To determine whether specific SSTR subtype mRNA expression is required for SRIF inhibition of GH secretion, five somatotroph adenomas were treated with 10(-7) mol/L SRIF in vitro, and significant inhibition of GH release occurred ed in all adenomas. All five tumors expressed SSTR2 mRNA and SSTR5 mRNA, and three expressed SSTR1 mRNA. The absence of SSTR1 mRNA expression did not affect the ability of SRIF to suppress GH secretion. We conclude that: 1) human pituitary adenomas and normal pituitary express multiple SSTR gene transcripts; 2) SSTR5 mRNA which has not been reported in other human endocrine tumor types, is expressed in neoplastic and normal pituitary tissue; and 3) SSTR2 mRNA, SSTR5, mRNA, and variable SSTR1 mRNA are expressed in GH-secreting tumors, which are responsive to SRIF in vitro. Further understanding of SSTR gene expression in pituitary adenomas will facilitate our understanding of the pathogenetic mechanisms of tumorigenesis and may provide a rationale for the use of specific SRIF analogs for clinical application. C1 MASSACHUSETTS GEN HOSP, DEPT MED, NEUROENDOCRINE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROSURG, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-01066]; NIDDK NIH HHS [DK-07028, DK-40947] NR 33 TC 178 Z9 180 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1995 VL 80 IS 4 BP 1386 EP 1392 DI 10.1210/jc.80.4.1386 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QR243 UT WOS:A1995QR24300062 PM 7714115 ER PT J AU DILLER, L SEXSMITH, E GOTTLIEB, A LI, FP MALKIN, D AF DILLER, L SEXSMITH, E GOTTLIEB, A LI, FP MALKIN, D TI GERMLINE P53 MUTATIONS ARE FREQUENTLY DETECTED IN YOUNG-CHILDREN WITH RHABDOMYOSARCOMA SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE LI-FRAUMENI SYNDROME; RHABDOMYOSARCOMA; P53 TUMOR SUPPRESSOR GENE; GERMLINE MUTATION ID TUMOR-SUPPRESSOR GENE; LI-FRAUMENI SYNDROME; SOFT-TISSUE SARCOMAS; BREAST-CANCER; PROTEIN; FAMILY; IDENTIFICATION; AMPLIFICATION; LOCALIZATION; POLYMORPHISM AB We investigated the possibility that a proportion of children with sporadic rhabdomyosarcoma (RMS) carry constitutional mutations of the p53 tumor suppressor gene, 33 patients with sporadic RMS at two large outpatient pediatric oncology clinics submitted blood samples. Genomic DNA was extracted from peripheral blood leukocytes and PCR was used to amplify exons 2-11 of the p53 gene, Amplified genomic DNA was screened for the presence of germline p53 mutations using single-strand conformation polymorphism (SSCP) analysis, The DNA sequence of those samples that showed aberrant migration of bands on SSCP analysis was determined to identify the precise nature of the gene mutations. Patient records were reviewed to assess clinical correlates of the mutant p53 carrier state. Heterozygous constitutional mutations were detected in 3/33 patient samples screened. Two of these missense mutations are located in exon 7 and one in exon 8 of the p53 gene. The presence of mutations was not correlated with tumor histology, stage, or site. However, an association between young age at diagnosis and presence of a constitutional p53 mutation was noted: 3/13 children under the age of 3 yr at diagnosis carried mutations, whereas none of 20 children over 3 yr of age at diagnosis harbored a detectable constitutional mutation. These results in children with RMS corroborates previous findings in other clinical settings suggesting that the mutant p53 carrier state may predispose individuals to malignancy at an early age. Although this study did not assess whether the mutations were preexisting or new germline alterations, assessment of close relatives of RMS patients for cancer risk and predictive genetic testing may be indicated. C1 UNIV TORONTO,HOSP SICK CHILDREN,DEPT PEDIAT,DIV ONCOL,TORONTO,ON M5G 1X8,CANADA. HARVARD UNIV,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,DANA FARBER CANC INST,DIV EPIDEMIOL & CANC CONTROL,BOSTON,MA 02115. FU NCI NIH HHS [5K07CA1648-02] NR 52 TC 120 Z9 122 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 1995 VL 95 IS 4 BP 1606 EP 1611 DI 10.1172/JCI117834 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QQ596 UT WOS:A1995QQ59600025 PM 7706467 ER PT J AU TRIAL, JA BIRDSALL, HH HALLUM, JA CRANE, ML RODRIGUEZBARRADAS, MC DEJONG, AL KRISHNAN, B LACKE, CE FIGDOR, CG ROSSEN, RD AF TRIAL, JA BIRDSALL, HH HALLUM, JA CRANE, ML RODRIGUEZBARRADAS, MC DEJONG, AL KRISHNAN, B LACKE, CE FIGDOR, CG ROSSEN, RD TI PHENOTYPIC AND FUNCTIONAL-CHANGES IN PERIPHERAL-BLOOD MONOCYTES DURING PROGRESSION OF HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION - EFFECTS OF SOLUBLE IMMUNE-COMPLEXES, CYTOKINES, SUBCELLULAR PARTICULATES FROM APOPTOTIC CELLS, AND HIV-1-ENCODED PROTEINS ON MONOCYTE PHAGOCYTIC FUNCTION, OXIDATIVE BURST, TRANSENDOTHELIAL MIGRATION, AND CELL-SURFACE PHENOTYPE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE HIV; MONOCYTE; PHAGOCYTOSIS; ANTIGEN-ANTIBODY COMPLEX; APOPTOSIS ID STAPHYLOCOCCUS-AUREUS; ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODY; ADHESION MOLECULE; TYPE-1 INFECTION; HIV-INFECTION; FC-RECEPTORS; T-CELLS; AIDS; MACROPHAGES AB We postulated that changes in the cell surface display of molecules that facilitate cell-cell and cell-matrix adhesions may reflect the changing immunosurveillance capacity of blood monocytes during progression of human immunodeficiency virus (HIV) infections, In Centers for Disease Control (CDC) stage A patients, whose monocytes' ability to phagocytose bacteria and generate reactive oxygen intermediates is often increased, the frequency of monocytes expressing CD49d, HLA-DP, HLA-DQ, and an activation epitope of CD11a/CD18 was increased and monocyte transendothelial migration was unimpaired, In CDC stage B/C patients, whose monocytes' ability to phagocytose bacteria and migrate across confluent endothelial monolayers was diminished, surface expression of CD49e and CD62L and the percentage of monocytes expressing CD18, CD11a, CD29, CD49e, CD54, CD58, CD31, and HLA-I were significantly decreased. Incubating normal donor monocytes with immune complexes in vitro reproduced the phenotypic and functional abnormalities seen in stage B/C patients, By contrast, in vitro stimulation with subcellular particulates released by apoptotic lymphocytes reproduced changes seen in stage A patients' monocytes, Although circulating monocytes appear to be activated at all stages, these data suggest that the high levels of circulating immune complexes, found predominantly in the later stages of HIV infection, may be particularly instrumental in reducing the monocyte's capacity to maintain surveillance against infection. C1 HOUSTON VET AFFAIRS MED CTR,IMMUNOL RES LAB,HOUSTON,TX 77030. HOUSTON VET AFFAIRS MED CTR,LAB SERV,HOUSTON,TX 77030. NETHERLANDS CANC INST,AMSTERDAM,NETHERLANDS. BAYLOR COLL MED,DEPT OTORHINOLARYNGOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PATHOL,HOUSTON,TX 77030. GREENVILLE HOSP SYST,DIV MED EDUC & RES,GREENVILLE,NC 27835. RP TRIAL, JA (reprint author), HOUSTON VET AFFAIRS MED CTR,AIDS & HIV RELATED INFECT RES CTR,BLDG 109,RM 147,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. RI Figdor, Carl/A-4232-2010 FU NIAID NIH HHS [R01 AI28071, UO1 AI33236]; NINDS NIH HHS [R01 NS32583] NR 54 TC 46 Z9 46 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 1995 VL 95 IS 4 BP 1690 EP 1701 DI 10.1172/JCI117845 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QQ596 UT WOS:A1995QQ59600036 PM 7706478 ER PT J AU FUNG, CY FISHER, DE AF FUNG, CY FISHER, DE TI P53 - FROM MOLECULAR MECHANISMS TO PROGNOSIS IN CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID NEGATIVE BREAST-CANCER; WILD-TYPE P53; CELL-PROLIFERATION; APOPTOSIS; PROTEIN; OVEREXPRESSION; ASSOCIATION; EXPRESSION; MARKER C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP FUNG, CY (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. NR 19 TC 31 Z9 32 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1995 VL 13 IS 4 BP 808 EP 811 PG 4 WC Oncology SC Oncology GA QQ608 UT WOS:A1995QQ60800002 PM 7707105 ER PT J AU MAUCH, PM CANELLOS, GP SHULMAN, LN SILVER, B TARBELL, NJ COME, S RABIN, MS COLEMAN, CN AF MAUCH, PM CANELLOS, GP SHULMAN, LN SILVER, B TARBELL, NJ COME, S RABIN, MS COLEMAN, CN TI MANTLE IRRADIATION ALONE FOR SELECTED PATIENTS WITH LAPAROTOMY-STAGED IA TO IIA HODGKINS-DISEASE - PRELIMINARY-RESULTS OF A PROSPECTIVE TRIAL SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROGNOSTIC FACTORS; COMBINED-MODALITY; THERAPY; RADIOTHERAPY; MOPP; MANAGEMENT; EXPERIENCE; PATTERNS; ADJUVANT; LYMPHOMA AB Purpose: To determine the feasibility of omitting prophylactic paraaortic irradiation in selected patients with laparotomy-staged (pathologically staged [PS]) IA to IIA Hodgkin's disease. Patients and Methods: We initiated a prospective single-arm trial in October 1988 to study the role of mantle irradiation alone in selected PS IA to IIA patients with Hodgkin's disease. A total of 37 patients have been entered onto this trial. Entrance criteria included nodular sclerosis (NS) or lymphocyte predominance (LP) histology, absence of B symptoms, disease limited above the carina, and a negative laparotomy. Results of treatment of 23 patients in the prospective trial, monitored off treatment for greater than or equal to 1 year, are presented. Twenty-three additional PS IA to IIA patients, treated with mantle irradiation alone from 1970 to 1987, were analyzed as a comparison group. The median follow-up durations were 32 and 113 months, respectively, for the two groups. Results: The 4-year actuarial rates of freedom from relapse and overall survival are 83% and 100%, respectively, for the prospective trial. The 10-year actuarial rates of freedom from relapse and overall survival ore 83% and 89%, respectively, for retrospectively studied patients. There have been five recurrences among 46 patients who received mantle irradiation alone, all with a component of relapse below the diaphragm. Conclusion: These early results support the use of mantle irradiation alone in selected PS IA to IIA patients with NS or LP histology. Relapses, although rare, have occurred predominantly below the diaphragm. This suggests the need for continued long-term surveillance of abdominal and pelvic nodes in this group of treated patients. J Clin Oncol 13:947-952. (C) 1995 by American Society of Clinical Oncology. C1 DANA FARBER CANC INST,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,COMMUNITY HLTH PLAN,BOSTON,MA 02115. HARVARD UNIV,COLLABORATIVE ONCOL GRP,BOSTON,MA 02115. RP MAUCH, PM (reprint author), HARVARD UNIV,JOINT CTR RADIAT THERAPY,SCH MED,DEPT RADIAT THERAPY,50 BINNEY ST,BOSTON,MA 02115, USA. NR 32 TC 16 Z9 16 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 APR PY 1995 VL 13 IS 4 BP 947 EP 952 PG 6 WC Oncology SC Oncology GA QQ608 UT WOS:A1995QQ60800021 PM 7707123 ER PT J AU MANGHAM, DC CANNON, A LI, XQ KOMIYA, S GEBHARDT, MC SPRINGFIELD, DS ROSENBERG, AE MANKIN, HJ AF MANGHAM, DC CANNON, A LI, XQ KOMIYA, S GEBHARDT, MC SPRINGFIELD, DS ROSENBERG, AE MANKIN, HJ TI P53 OVEREXPRESSION IN EWINGS-SARCOMA PRIMITIVE NEUROECTODERMAL TUMOR IS AN UNCOMMON EVENT SO JOURNAL OF CLINICAL PATHOLOGY-CLINICAL MOLECULAR PATHOLOGY EDITION LA English DT Article DE P53; EWINGS SARCOMA; IMMUNOHISTOCHEMISTRY ID SOFT-TISSUE SARCOMAS; HUMAN BREAST-CANCER; LUNG-CANCER; COLORECTAL CARCINOMAS; GENE; MUTATIONS; EXPRESSION; ONCOGENE; SPECTRUM; TRANSFORMATION AB Aim-To determine the presence of p53 overexpression in Ewing's sarcoma/primitive neuroectodermal tumours (ETs) and to assess whether p53 accumulation has any prognostic value. Methods-From a prospectively compiled database of 76 patients with ETs, suitable tumour tissue was available for 38. The monoclonal antibody pAb1801 was used to detect p53 nuclear protein overexpression. Results-Nuclear staining was detected in the tumours of three (8%) of the 38 patients. Where tumours stained positively, over 10% of the tumour nuclei were postively stained. All three patients whose tumours overexpressed p53 died and in a relatively short time compared with the patients who did not overexpress p53 (mean 3.7 months compared with a mean of 38.7 months in the p53 negative group). Conclusion-Overexpression of p53 in ETs is an uncommon event. Overexpression of p53 has repeatedly been shown to correlate closely with p53 point missense mutations and therefore this oncogenic event appears not to be of primary pathogenic importance in ETs. There is a tentative indication that those uncommon ETs in which p53 overexpression can be detected may behave more aggressively. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,ORTHOPAED RES LABS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 30 TC 10 Z9 10 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 1355-2910 J9 J CLIN PATHOL-CL MOL JI J. Clin. Pathol.-Clin. Mol. Pathol. Ed. PD APR PY 1995 VL 48 IS 2 BP M79 EP M82 PG 4 WC Pathology SC Pathology GA RL044 UT WOS:A1995RL04400004 ER PT J AU ASTIN, MC OGLANDHAND, SM COLEMAN, EM FOY, DW AF ASTIN, MC OGLANDHAND, SM COLEMAN, EM FOY, DW TI POSTTRAUMATIC-STRESS-DISORDER AND CHILDHOOD ABUSE IN BATTERED WOMEN - COMPARISONS WITH MARITALLY DISTRESSED WOMEN SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Note ID VIOLENCE AB In the present study, posttraumatic stress disorder (PTSD) prevalence rates were compared among 50 battered women and 37 maritally distressed women who had not experienced battering (N = 87). Participants were administered R. Spitzer and I. B. S. Williams's (1985) Structured Clinical Interview for the DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders [3rd ed., rev.]) to assess PTSD status and previous traumatic experiences in addition to other standardized measures of PTSD and violence exposure. Battered women exhibited significantly higher rates of PTSD than maritally distressed women (58% vs. 18.9%). Although both groups had similar rates of previous trauma experiences, women with a PTSD-positive status(both battered women and maritally distressed women) were significantly more likely to have experienced self-reported childhood sexual abuse and a higher overall number of previous traumas than those with a PTSD-negative status. Battering exposure and childhood sexual abuse predicted 37% of the variance in overall PTSD intensity levels. C1 FULLER GRAD SCH PSYCHOL,PASADENA,CA. PEPPERDINE UNIV,GRAD SCH EDUC PSYCHOL,MALIBU,CA 90265. W LOS ANGELES VET AFFAIRS MED CTR,BRENTWOOD DIV,LOS ANGELES,CA. NR 16 TC 100 Z9 101 U1 2 U2 2 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 APR PY 1995 VL 63 IS 2 BP 308 EP 312 DI 10.1037//0022-006X.63.2.308 PG 5 WC Psychology, Clinical SC Psychology GA QR238 UT WOS:A1995QR23800016 PM 7751492 ER PT J AU THYEN, U AF THYEN, U TI MOTOR-ASSESSMENT OF THE DEVELOPING INFANT - PIPER,MC, DARRAH,J SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Book Review RP THYEN, U (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD APR PY 1995 VL 16 IS 2 BP 116 EP 117 PG 2 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA QT662 UT WOS:A1995QT66200014 ER PT J AU IRIE, HY RAVICHANDRAN, KS BURAKOFF, SJ AF IRIE, HY RAVICHANDRAN, KS BURAKOFF, SJ TI CD8-BETA CHAIN INFLUENCES CD8-ALPHA CHAIN-ASSOCIATED LCK KINASE-ACTIVITY SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TYROSINE-PROTEIN-KINASE; T-CELL RECEPTOR; SURFACE EXPRESSION; GENE-TRANSFER; BETA-CHAIN; HUMAN CD8; COMPLEX; P56LCK; RECOGNITION; SELECTION AB The CD8 molecule plays an important role in the differentiation of CD8(+) T cells in the thymus and in their normal function in the periphery. CD8 exists on the cell surface in two forms, the alpha alpha homodimer and the alpha beta heterodimer. Recent studies indicate an important role for the CD8 beta chain in thymic development of CD8(+) T cells and suggest that signaling via CD8 alpha beta may be distinct from CD8 alpha alpha. To better understand these differences, we introduced the CD8 beta gene into a T cell hybridoma which only expressed the CD8 alpha alpha homodimer. In the parent hybridoma, cross-linking of the CD8 alpha chain led to minimal enhancement of CD8-associated Lck tyrosine kinase activity. In the CD8 beta(+) transfectants, several observations suggested that CD8 beta modifies CD8 alpha-associated Lck tyrosine kinase activity: (a) in in vitro kinase assays, antibody-mediated crosslinking of CD8 alone, or CD8 cross-linking with the TCR, resulted in 10-fold greater activation of Lck kinase activity, compared to cells expressing CD8 alpha alpha alone; (b) in vivo, markedly enhanced tyrosine phosphorylation of several intracellular proteins was observed upon CD8 cross-linking with the TCR in CD8 alpha beta-expressing cells, compared to cells expressing CD8 alpha alpha alone; and (c) Lck association with CD8 alpha was stabilized by the coexpression of CD8 beta. Thus, the differential Lck kinase activation and tyrosine phosphorylation seen with CD8 alpha alpha vs. CD8 alpha beta may reflect the unique signaling capabilities of the CD8 beta molecule. These differences in signaling may, in part, account for the diminished ability to generate CD8 single positive thymocytes in mice bearing a homozygous disruption of the CD8 beta gene. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. FU NIAID NIH HHS [AI-17258]; NIGMS NIH HHS [T32 GM007753, T32 GM07753] NR 29 TC 51 Z9 51 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 1 PY 1995 VL 181 IS 4 BP 1267 EP 1273 DI 10.1084/jem.181.4.1267 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA QQ192 UT WOS:A1995QQ19200001 PM 7699318 ER PT J AU XIA, WJ PINTO, CE KRADIN, RL AF XIA, WJ PINTO, CE KRADIN, RL TI THE ANTIGEN-PRESENTING ACTIVITIES OF IA(+) DENDRITIC CELLS SHIFT DYNAMICALLY FROM LUNG TO LYMPH-NODE AFTER AN AIRWAY CHALLENGE WITH SOLUBLE-ANTIGEN SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN ALVEOLAR MACROPHAGES; T-CELLS; ACCESSORY CELLS; RESPONSES; RAT; LYMPHOCYTES; DISPLAY; HYPERSENSITIVITY; IMMUNOGENICITY; POPULATIONS AB Dendritic cells (DC) are widely distributed in the lung where they are distinguished by their morphology and class II major histocompatibility complex (Ia) antigen expression. Although a role for DC as pulmonary antigen-presenting cell (APC) has been suggested, little is currently known concerning how these cells respond to inhaled antigens in vivo. Hen-egg lysozyme (HEL) was injected intratracheally into Lewis rats; DC were subsequently purified from the lung and regional lymph nodes (LN) at intervals of up to 14 d and examined for their ability to stimulate the proliferation of HEL-immune T cells in vitro in the absence of added HEL. Pulmonary DC displayed APC activities at 3 h and for up to 7 d after the injection of antigen. Dendritic cells in the draining hilar LN showed APC activities that appeared at 24 h, peaked at day 3, and then diminished progressively. After the primary sensitization, HEL-immune T cells were detected in hilar LN but not in the lung. A second airway challenge with HEL at day 14 yielded an antigen-specific pulmonary immune response, characterized histologically by the accumulation of mononuclear cells around lung venules. We conclude that APC activities shift from lung to lymph node during the response to inhaled antigen. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. FU NHLBI NIH HHS [HL48385] NR 36 TC 134 Z9 136 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 1 PY 1995 VL 181 IS 4 BP 1275 EP 1283 DI 10.1084/jem.181.4.1275 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA QQ192 UT WOS:A1995QQ19200002 PM 7699319 ER PT J AU LEAF, DA NEIGHBOR, WE SCHAAD, D SCOTT, CS AF LEAF, DA NEIGHBOR, WE SCHAAD, D SCOTT, CS TI A COMPARISON OF SELF-REPORT AND CHART AUDIT IN STUDYING RESIDENT PHYSICIAN ASSESSMENT OF CARDIAC RISK-FACTORS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE RESIDENTS; PERFORMANCE ASSESSMENT; CARDIAC RISK FACTORS; PHYSICIAN PERCEPTION; CHART AUDIT AB OBJECTIVE: To examine the relationship between resident physicians' perceptions of their preventive cardiology practices and a chart audit assessment of their documented services. DESIGN: A criterion standard comparison of two methods used to assess resident physicians' practices: self-report and chart audit. SETTING: Physician ambulatory care in a residency program. PATIENTS AND OTHER PARTICIPANTS: Coronary artery disease (CAD) risk factor assessment was evaluated by self-report for 72 resident physicians and by chart audit of randomly selected records of 544 of their patients who did not have CAD or a debilitating chronic disease during a one-year period. INTERVENTION: Measurements of the residents' perceived CAD risk factor assessment practice by self-report, and chart audit assessments of their recorded care. MAIN OUTCOME: The relationship between self-reported and chart audit assessments of CAD risk factors. RESULTS: Chart audit assessment of CAD risk factor management was highly significantly (p < 0.01) lower than self-reported behaviors for evaluation of cigarette smoking, diet, physical activity, stress, plasma cholesterol, blood pressure, and body weight/obesity. CONCLUSIONS: Three different interpretations of these findings are apparent. 1) Physician self-report is a poor tool for the measurement of clinical behavior, and therefore research of physician behavior should not rely solely on self-reported data; 2) physicians' chart recording of their clinical practice is insufficient to reflect actual care; or 3) neither is an accurate measure of actual practice. RP LEAF, DA (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,DIV GEN INTERNAL MED 691111G,WILSHIRE & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. FU NHLBI NIH HHS [HL 30564] NR 0 TC 39 Z9 39 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 APR PY 1995 VL 10 IS 4 BP 194 EP 198 DI 10.1007/BF02600254 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA QT151 UT WOS:A1995QT15100003 PM 7790980 ER PT J AU JENIKE, MA AF JENIKE, MA TI POSTTRAUMATIC-STRESS-DISORDER IN THE ELDERLY - A 3-YEAR FOLLOW-UP OF THE LOCKERBIE DISASTER SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 3 TC 1 Z9 1 U1 0 U2 1 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON ST, PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD APR PY 1995 VL 8 IS 2 BP 137 EP 137 PG 1 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA QR239 UT WOS:A1995QR23900013 ER PT J AU SEN, J VENKATARAMAN, L SHINKAI, Y PIERCE, JW ALT, FW BURAKOFF, SJ SEN, R AF SEN, J VENKATARAMAN, L SHINKAI, Y PIERCE, JW ALT, FW BURAKOFF, SJ SEN, R TI EXPRESSION AND INDUCTION OF NUCLEAR FACTOR-KAPPA-B-RELATED PROTEINS IN THYMOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; CULTURED FETAL THYMUS; POSITIVE SELECTION; CYCLOSPORINE-A; INTERLEUKIN-2 PROMOTER; MONOCLONAL-ANTIBODIES; TRANSCRIPTION FACTORS; SURFACE EXPRESSION; ORGAN-CULTURES; LYMPHOCYTES-T AB Thymocytes mature in response to the cues from the thymic micro-environment, which regulate stage-specific gene expression during development. We find that several proteins that bind the kappa B sequence in vitro are constitutively activated in freshly isolated thymocytes. These include the rel-related p50 homodimers, p50/p65 heterodimers, low levels of c-rel, and two other factors that may be thymus specific. Disruption of the thymic micro-environment resulted in loss of DNA-binding, suggesting that lymphocyte-stromal cell interactions induce and maintain these proteins in a DNA-binding form. Phorbol ester and ionomycin treatment induced p50, p65, and p68 c-rel kappa B DNA-binding activity. Expression of p68 c-rel protein, but not p50 or p65, was suppressed by the immunosuppressive drug FK506. Because FK506 specifically inhibits the appearance of mature single-positive thymocytes, gene expression regulated by p68 c-rel may play a role in selection and maturational signals involved in the double-positive to single-positive transition. C1 BRANDEIS UNIV,ROSENSTIEL BASIC MED SCI RES CTR,WALTHAM,MA 02254. BRANDEIS UNIV,DEPT BIOL,WALTHAM,MA 02254. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. RI Shinkai, Yoichi/N-3909-2014 OI Shinkai, Yoichi/0000-0002-6051-2484 FU NIAID NIH HHS [R01 AI 17258]; NIGMS NIH HHS [GM 00563, GM 43874] NR 63 TC 56 Z9 56 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 APR 1 PY 1995 VL 154 IS 7 BP 3213 EP 3221 PG 9 WC Immunology SC Immunology GA QN459 UT WOS:A1995QN45900018 PM 7534792 ER PT J AU WONG, YW KUSSIE, PH PARHAMISEREN, B MARGOLIES, MN AF WONG, YW KUSSIE, PH PARHAMISEREN, B MARGOLIES, MN TI MODULATION OF ANTIBODY-AFFINITY BY AN ENGINEERED AMINO-ACID SUBSTITUTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; PARA-AZOPHENYLARSONATE ANTIBODIES; CROSS-REACTIVE IDIOTYPE; ARS-A ANTIBODIES; IMMUNE-RESPONSE; 3-DIMENSIONAL STRUCTURE; BINDING-SITE; ARSONATE IDIOTYPE; SOMATIC MUTATIONS; ENHANCED AFFINITY AB The crystal model of the complex of the somatically mutated anti-p-azophenylarsonate (Ars) Ab 36-71 F(ab) with phenylarsonate reveals that six residues (Asn35, Trp47, Tyr50, Ser99, and Tyr106 in the H chain and Arg96 in the L chain) contact hapten. Further study of this model suggested that H chain Phe108, which forms the base of the combining cavity, also affects Ars binding. We predicted that Trp with a bulkier aromatic side chain might be accommodated in this position and increase Ars affinity. The substitution of Phe by Trp using in vitro mutagenesis at position 108 enhanced affinity 10-fold in the germline-encoded Ab 36-65. However, the same mutation in Ab 36-71 abolished the binding. Phe108 was then mutated to different amino acids in both Abs. The results indicated that except for the Trp substitution in 36-65, all other substitutions at position 108 decrease or abolish Ars binding in both Abs. It was shown previously that the 200-fold difference in affinity between 36-65 and 36-71 could be reproduced by changing only three V-H amino acids. Because the mutation of Phe108 to Trp has never been observed during in vivo affinity maturation, we constructed mutants of 36-65 in which Trp108 was combined with one or more of the ''favorable'' mutations of 36-71, to determine whether the mutations were additive. The results indicate that it is possible to maintain an affinity significantly higher than wild-type by such combined mutations. Thus, the failure to observe Trp108 in vivo is not due to structural idiosyncrasy, but may simply be due to codon usage at Phe108 in the germline sequence. Such limited ''adaptability'' of a germline sequence indicates that it is possible to achieve higher affinity Abs through protein engineering via routes that are constrained during in vivo selection. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. COLUMBIA UNIV,COLL PHYS & SURG,DIV MOLEC MED,NEW YORK,NY 10032. FU NCI NIH HHS [R01 CA24432] NR 48 TC 20 Z9 21 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1995 VL 154 IS 7 BP 3351 EP 3358 PG 8 WC Immunology SC Immunology GA QN459 UT WOS:A1995QN45900032 PM 7897218 ER PT J AU SHARMA, CP EZZELL, RM ARNAOUT, MA AF SHARMA, CP EZZELL, RM ARNAOUT, MA TI DIRECT INTERACTION OF FILAMIN (ABP-280) WITH THE BETA-2-INTEGRIN SUBUNIT CD18 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIN-BINDING PROTEIN; AMINO-ACID-SEQUENCE; LEUKOCYTE ADHESION MOLECULES; INTEGRIN-BETA-SUBUNIT; MEMBRANE GLYCOPROTEIN-IB; CYTOPLASMIC DOMAIN; ALPHA-ACTININ; FIBRONECTIN RECEPTOR; SECONDARY-STRUCTURE; FOCAL CONTACTS AB beta 2-Integrins mediate leukocyte extravasation into inflamed tissues, phagocytosis, and target cell killing, functions that require an intact actin cytoskeleton. Previous studies have focused on elucidating interactions of the cytoplasmic tails of integrins with the cytoskeleton at focal contacts in stationary cells. As integrins are also located at other types of cell-substratum junctions, such as the leading edge of migrating cells, additional cytosolic proteins abundant at these sites may also interact with integrins. In this study, we have identified the actin-binding protein, filamin (ABP-280), as a major cytoskeletal protein that binds to the cytoplasmic tail of the beta 2-integrin subunit CD18. Filamin bound to cytoplasmic CD18 directly and specifically, co-immunoprecipitated with beta 2-integrins in detergent cell lysate and co-immunolocalized with cross-linked beta 2-integrins in intact cells. The filamin binding site in CD18 was localized to the N-terminal (amino acids (aa) 724 to 747) but not to the C-terminal (aa 743 to 769) half of cytoplasmic CD18. Filamin did not bind to the major cr-actinin binding site (aa 733 to 742), however, suggesting that these two cytoskeletal proteins bind to distinct but overlapping sites. Given the conservation of the filamin binding region among P-integrin subunits, these findings suggest the presence of similar associations between filamin and other integrins. These associations may be important in the spreading and extension of lamellipodia at the leading edge during cell movement and, if interrupted, may contribute to the dramatic decrease in cell locomotion observed in genetic deletions involving filamin or integrins. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG RES LAB,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02129. RP SHARMA, CP (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,RENAL UNIT,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,BOSTON,MA 02129, USA. FU NIAID NIH HHS [AI-21963]; NIDDK NIH HHS [DK-48549] NR 57 TC 193 Z9 193 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1995 VL 154 IS 7 BP 3461 EP 3470 PG 10 WC Immunology SC Immunology GA QN459 UT WOS:A1995QN45900044 PM 7534799 ER PT J AU MAYTIN, EV AF MAYTIN, EV TI HEAT-SHOCK PROTEINS AND MOLECULAR CHAPERONES - IMPLICATIONS FOR ADAPTIVE RESPONSES IN THE SKIN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Review DE THERMOTOLERANCE; ULTRAVIOLET LIGHT; GLUCOCORTICOIDS; REVIEW ID GLUCOCORTICOID-RECEPTOR COMPLEXES; SYSTEMIC LUPUS-ERYTHEMATOSUS; CULTURED HUMAN KERATINOCYTES; CHINESE-HAMSTER FIBROBLASTS; AMINO-ACID-ANALOGS; STRESS PROTEINS; MAMMALIAN-CELLS; EPIDERMAL-KERATINOCYTES; ULTRAVIOLET-LIGHT; SODIUM-ARSENITE AB Recent advances in the biology of heat-shock proteins (hsps) are reviewed. These abundant and evolutionarily highly conserved proteins (also called stress proteins) act as molecular escorts. Hsps bind to other cellular proteins, help them to fold into their correct secondary structures, and prevent misfolding and aggregation during stress. Cytoplasmic hsp70 and hsp60 participate in complicated protein-folding pathways during the synthesis of new polypeptides. Close relatives of hsp70 and hsp60 assist in the transport and assembly of proteins inside intracellular organelles. Hsp90 may have a unique role, binding to the glucocorticoid receptor in a manner essential for proper steroid hormone action. Hsps may also be essential for thermotolerance and for prevention and repair of damage caused by ultraviolet B light. A unique class of T lymphocytes, the gamma delta T cells, exhibits a restricted specificity against hsps. These T cells may constitute a general, nonspecific immune mechanism directed against the hsps within invading organisms or against very similar hsps expressed by infected (stressed) keratinocytes. Immunologic cross-reactivity between hsps of foreign organisms and of the host may play a role in some autoimmune diseases. Although hsps are expressed in the skin, many questions remain about their role during injury, infection, and other types of cutaneous pathophysiology. C1 HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. RP MAYTIN, EV (reprint author), MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,DEPT MED ENDOCRINOL,WELLMAN 3,BOSTON,MA 02114, USA. NR 110 TC 67 Z9 68 U1 0 U2 1 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 APR PY 1995 VL 104 IS 4 BP 448 EP 455 DI 10.1111/1523-1747.ep12605702 PG 8 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200004 PM 7706757 ER PT J AU VAILLY, J PULKKINEN, L MIQUEL, C CHRISTIANO, AM GERECKE, D BURGESON, RE UITTO, J ORTONNE, JP MENEGUZZI, G AF VAILLY, J PULKKINEN, L MIQUEL, C CHRISTIANO, AM GERECKE, D BURGESON, RE UITTO, J ORTONNE, JP MENEGUZZI, G TI IDENTIFICATION OF A HOMOZYGOUS ONE-BASEPAIR DELETION IN EXON-14 OF THE LAMB3 GENE IN A PATIENT WITH HERLITZ JUNCTIONAL EPIDERMOLYSIS-BULLOSA AND PRENATAL-DIAGNOSIS IN A FAMILY AT RISK FOR RECURRENCE SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE LAMININ-5; NICEIN; KALININ; BASEMENT MEMBRANE; DERMAL EPIDERMAL JUNCTION; HEMIDESMOSOME ID DERMAL-EPIDERMAL JUNCTION; MONOCLONAL-ANTIBODY GB3; BASEMENT-MEMBRANES; HUMAN-SKIN; HEMIDESMOSOMES; COMPONENTS; EXPRESSION; ACID AB Herlitz junctional epidermolysis bullosa, a severe epidermal blistering disorder, is inherited in an autosomal recessive manner. It has recently been shown that, in kindreds with junctional epidermolysis bullosa, the disorder results from mutations in the gamma 2 chain of laminin-5, a basement membrane protein synthesized by the basal cells of stratifying squamous epithelia. In this report we describe a mutation identified in the beta 3 chain gene of laminin-5 in a family with Herlitz junctional epidermolysis bullosa. The disease is caused by a homozygous deletion of 1 bp that leads to a frameshift and premature termination codon. The segregation of the mutated allele in the family is consistent with the pathogenic role of the mutation. We also report a direct DNA-based prenatal exclusion of Herlitz junctional epidermolysis bullosa in a pregnancy at risk using a chorionic villus biopsy and allele-specific oligomer hybridization from polymerase chain reaction-amplified genomic DNA. C1 UFR MED,INSERM,U385,NICE,FRANCE. HOP LOUIS PASTEUR,SERV DERMATOL,F-06002 NICE,FRANCE. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT DERMATOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19107. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA. FU NIAMS NIH HHS [AR35689, P01-AR38923] NR 31 TC 62 Z9 64 U1 0 U2 1 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 APR PY 1995 VL 104 IS 4 BP 462 EP 466 DI 10.1111/1523-1747.ep12605898 PG 5 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200006 PM 7706759 ER PT J AU BEISSERT, S KUHN, R MULLER, W RAJEWSKY, K HOSOI, J GRANSTEIN, RD AF BEISSERT, S KUHN, R MULLER, W RAJEWSKY, K HOSOI, J GRANSTEIN, RD TI INTERLEUKIN-10 GENE-TARGETED (KNOCK-OUT) MICE ARE RESISTANT TO UVB RADIATION-INDUCED INHIBITION OF THE INDUCTION OF DELAYED-TYPE HYPERSENSITVITY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,HARVARD CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV COLOGNE,INST GENET,W-5000 COLOGNE,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 555 EP 555 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200029 ER PT J AU ASAHINA, A MORO, O HOSOI, J GRANSTEIN, RD AF ASAHINA, A MORO, O HOSOI, J GRANSTEIN, RD TI CALCITONIN-GENE-RELATED PEPTIDE (CGRP) HAS SPECIFIC EFFECTS ON CAMP LEVELS, B7-2 EXPRESSION AND FUNCTION OF ANTIGEN-PRESENTING CELLS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,HARVARD CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 566 EP 566 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200094 ER PT J AU KRUEGER, GG JORGENSEN, CM LI, HL MORGAN, JR PETERSEN, MJ AF KRUEGER, GG JORGENSEN, CM LI, HL MORGAN, JR PETERSEN, MJ TI EPIDERMAL STEM-CELLS - PROOF-OF-CONCEPT USING KERATINOCYTES CARRYING THE TRANSGENE LACZ IN AN IN-VIVO SETTING SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV UTAH,DIV DERMATOL,SALT LAKE CITY,UT. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SHRINERS BURN INST,SURG SERV,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 573 EP 573 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200132 ER PT J AU AMANO, S GERECKE, D NISHIYAMA, T BURGESON, RE AF AMANO, S GERECKE, D NISHIYAMA, T BURGESON, RE TI THE UP-REGULATION OF LAMININ-5 (KALININ) PRODUCTION BY HUMAN KERATINOCYTES BY SERUM AND TGFS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HARVARD CUTANEOUS BIOL RES CTR,BOSTON,MA. RI Nishiyama, Toshio/C-5434-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 579 EP 579 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200171 ER PT J AU FINI, ME BARTLETT, JD GUPTA, R RINEHART, WB SADOW, PM WESTMAYS, JA WILLIAMS, T ZIESKE, JD AF FINI, ME BARTLETT, JD GUPTA, R RINEHART, WB SADOW, PM WESTMAYS, JA WILLIAMS, T ZIESKE, JD TI GELATINASE-B GENE-EXPRESSION BY KERATINOCYTES IS REGULATED BY TRANSCRIPTION FACTOR AP-2 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA. YALE UNIV,DEPT BIOL,NEW HAVEN,CT. SCHEPENS EYE RES INST,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 580 EP 580 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200176 ER PT J AU NISHIYAMA, T TSUNENAGA, M AKUTSU, N CHAMPLIAUD, MF ROUSSELLE, P AMANO, S BURGESON, RE AF NISHIYAMA, T TSUNENAGA, M AKUTSU, N CHAMPLIAUD, MF ROUSSELLE, P AMANO, S BURGESON, RE TI LAMININ-5 (KALININ) PROMOTES HUMAN KERATINOCYTE MIGRATION SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 SHISEIDO RES CTR,YOKOHAMA,KANAGAWA,JAPAN. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HARVARD CUTANEOUS BIOL RES CTR,BOSTON,MA. RI Nishiyama, Toshio/C-5434-2013 NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 589 EP 589 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200230 ER PT J AU EMING, SA LEE, J SNOW, RG YARMUSH, ML TOMPKINS, RG MORGAN, JR AF EMING, SA LEE, J SNOW, RG YARMUSH, ML TOMPKINS, RG MORGAN, JR TI EXPRESSION OF PLATELET-DERIVED GROWTH-FACTOR (PDGF) FROM GENETICALLY-MODIFIED KERATINOCYTES SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SHRINERS BURNS INST,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 596 EP 596 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200273 ER PT J AU NGUYEN, BC ANDERSON, RR KOCHEVAR, JE AF NGUYEN, BC ANDERSON, RR KOCHEVAR, JE TI EFFECT OF RELATIVE-HUMIDITY ON DHA STAINING OF SKIN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 614 EP 614 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200381 ER PT J AU RAJADHYAKSHA, M GROSSMAN, M WEBB, RH ANDERSON, RR AF RAJADHYAKSHA, M GROSSMAN, M WEBB, RH ANDERSON, RR TI VIDEO-RATE CONFOCAL SCANNING LASER MICROSCOPY OF LIVE HUMAN SKIN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,DEPT DERMAT,BOSTON,MA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 618 EP 618 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200405 ER PT J AU GERECKE, DR NISHIYAMA, T AMANO, S BURGESON, RE AF GERECKE, DR NISHIYAMA, T AMANO, S BURGESON, RE TI LAMININ-5 IS UP-REGULATED BY KERATINOCYTES DURING PROLIFERATION AND MIGRATION - EXAMINATION OF LAMININS-1 AND LAMININ-5 BY IMMUNOFLUORESENCE, IMMUNOPRECIPITATION AND RT-PCR SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA. RI Nishiyama, Toshio/C-5434-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 624 EP 624 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200442 ER PT J AU LIN, GC GONZALEZ, S TOPE, WD ROSS, V ANDERSON, RR KOLLIAS, N AF LIN, GC GONZALEZ, S TOPE, WD ROSS, V ANDERSON, RR KOLLIAS, N TI NATIVE FLUORESCENCE OF BASAL-CELL CARCINOMA IS PREDICTIVE OF EPIDERMAL PROLIFERATIVE ACTIVITY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 634 EP 634 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200497 ER PT J AU BADEN, HP RAFTERY, LA ANDERSON, RR AF BADEN, HP RAFTERY, LA ANDERSON, RR TI UVC RADIATION PRODUCES IMMEDIATE WRITHING RESPONSE IN DROSOPHILA-MELANOGASTER LARVAE SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,CUTANEOUS BIOL RES CTR,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA. RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 643 EP 643 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200554 ER PT J AU HIBINO, T LEUTHARDT, D TAKAHASHI, T BACIU, P GOETINCK, PF AF HIBINO, T LEUTHARDT, D TAKAHASHI, T BACIU, P GOETINCK, PF TI MECHANISM OF KERATINOCYTE GROWTH-STIMULATION BY UROKINASE PLASMINOGEN-ACTIVATOR (UPA) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. SHISEIDO RES CTR,YOKOHAMA,KANAGAWA,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 645 EP 645 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200564 ER PT J AU HONG, JJ STILLER, MJ MENN, E SMITH, SL GILLES, R DRAKE, LA AF HONG, JJ STILLER, MJ MENN, E SMITH, SL GILLES, R DRAKE, LA TI A PILOT-STUDY TO DETERMINE THE BIOPSYCHOSOCIAL EFFECTS OF ONYCHOMYCOSIS ON A NORTHEASTERN AMERICAN SUBPOPULATION SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,DERMATOL CLIN INVEST UNIT,BOSTON,MA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 APR PY 1995 VL 104 IS 4 BP 668 EP 668 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200701 ER PT J AU TSAY, A BHAWAN, J MORAN, M KOCHEVAR, IE AF TSAY, A BHAWAN, J MORAN, M KOCHEVAR, IE TI IN-SITU HYBRIDIZATION OF TROPOELASTIN MESSENGER-RNA IN PHOTOAGED MURINE SKIN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 BOSTON UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02118. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 670 EP 670 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200713 ER PT J AU JORGENSEN, CM MORGAN, JR PETERSEN, MJ KWAN, MK KRUEGER, GG AF JORGENSEN, CM MORGAN, JR PETERSEN, MJ KWAN, MK KRUEGER, GG TI COMPARISON OF THE SURVIVAL OF PRE-SENESCENT WITH SENESCENT HUMAN FIBROBLASTS IN-VIVO USING A GENE MARKER (LACZ) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV UTAH,DIV DERMATOL,SALT LAKE CITY,UT. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SHRINERS BURNS INST,SURG SERV,BOSTON,MA. ADV TISSUE SCI,LA JOLLA,CA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 676 EP 676 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200753 ER PT J AU KADUNCE, DP LIIMATTA, A JORGENSEN, C MORGAN, J KRUEGER, GG AF KADUNCE, DP LIIMATTA, A JORGENSEN, C MORGAN, J KRUEGER, GG TI HUMAN GROWTH-HORMONE BINDING-ANTIBODIES IN NUDE-MICE SECONDARY TO GENE-THERAPY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SHRINERS BURNS INST,BOSTON,MA. UNIV UTAH,DIV DERM,SALT LAKE CITY,UT. NR 0 TC 0 Z9 0 U1 0 U2 5 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 APR PY 1995 VL 104 IS 4 BP 676 EP 676 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200750 ER PT J AU GRANSTEIN, RD MCAULIFFE, D DRAKE, L DWYER, DS AF GRANSTEIN, RD MCAULIFFE, D DRAKE, L DWYER, DS TI RUTHENIUM RED (RR) INHIBITS THE INDUCTION AND THE ELICITATION OF CONTACT HYPERSENSITIVITY (CHS) IN MICE SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. PROCEPT INC,CAMBRIDGE,MA 02139. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 679 EP 679 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200770 ER PT J AU QURESHI, AA ASAHINA, A GRANSTEIN, RD LERNER, EA AF QURESHI, AA ASAHINA, A GRANSTEIN, RD LERNER, EA TI IMMUNOMODULATORY EFFECTS OF MAXADILAN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,DEPT DERMATOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 679 EP 679 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200768 ER PT J AU SMITH, SL KOLLIAS, N GILLIES, R STILLER, MJ HONG, JJ MUCCINI, JA PHILLIPS, SB DRAKE, LA AF SMITH, SL KOLLIAS, N GILLIES, R STILLER, MJ HONG, JJ MUCCINI, JA PHILLIPS, SB DRAKE, LA TI IMPROVEMENT OF PSORIATIC PLAQUES TREATED WITH CALCIPOTRIOL IS BETTER VISUALIZED USING POLARIZED-LIGHT PHOTOGRAPHY SPECTROSCOPY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. NR 0 TC 3 Z9 3 U1 0 U2 0 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 APR PY 1995 VL 104 IS 4 BP 689 EP 689 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200829 ER PT J AU LIN, GC LEE, MS TSOUKAS, MM GONZALEZ, S ANDERSON, RR KOLLIAS, N AF LIN, GC LEE, MS TSOUKAS, MM GONZALEZ, S ANDERSON, RR KOLLIAS, N TI TOWARD A MECHANISTIC UNDERSTANDING OF BPD-MA INDUCED PHOTOTOXICITY IN NORMAL SKIN - THE CORRELATION WITH PHARMACOKINETICS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 694 EP 694 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200856 ER PT J AU STILLER, MJ HONG, JJ HILLSON, EM KOLLIAS, N SMITH, SL MENN, E DRAKE, LA AF STILLER, MJ HONG, JJ HILLSON, EM KOLLIAS, N SMITH, SL MENN, E DRAKE, LA TI DECREASED VELLOUS HAIR COUNTS AFTER APPLICATION OF TOPICAL TRETINOIN 0.025-PERCENT SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,DERMATOL CLIN INVEST UNIT,BOSTON,MA. NORTHEASTERN UNIV,DEPT STAT,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1995 VL 104 IS 4 BP 694 EP 694 PG 1 WC Dermatology SC Dermatology GA QR532 UT WOS:A1995QR53200862 ER PT J AU RAO, A AF RAO, A TI NFATP, A CYCLOSPORINE-SENSITIVE TRANSCRIPTION FACTOR IMPLICATED IN CYTOKINE GENE INDUCTION SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT 30th National Meeting of the Society-for-Leukocyte-Biology on Molecular Mechanism of Host Resistance CY SEP 21-24, 1994 CL TUCSON, AZ SP SOC LEUKOCYTE BIOL DE CYCLOSPORINE; NFAT(P); TRANSCRIPTION; CYTOKINE GENES ID ACTIVATED T-CELLS; FACTOR-ALPHA GENE; NUCLEAR FACTOR; SIGNAL-TRANSDUCTION; FK506; CALCINEURIN; PROMOTER; IDENTIFICATION; LYMPHOCYTE; BINDING AB The transcription factor NFATp (nuclear factor of activated T cells, preexisting) is likely to regulate the cyclosporin-sensitive transcription of cytokine genes and other activation-associated genes during the immune response. NFATp is the first identified member of a new family of transcription factors, whose DNA binding domains show a weak sequence similarity to those of the Rel (NF-kappa B) family of proteins. NFATp, is expressed in several types of immune cells as a cytosolic protein that translocates to the nucleus following activation. The nuclear translocation is regulated by calcium and calcineurin and inhibited by cyclosporin A and FK506. In the nucleus, NFATp cooperates with Fos-Jun dimers and possibly with other transcription factors at composite elements in the regulatory regions of cytokine genes. The potential roles of NFATp, and a related family member, NFATc, in cytokine gene transcription are discussed. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP RAO, A (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,ROOM B465,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA42471]; NIAID NIH HHS [AI35297]; NIGMS NIH HHS [GM46227] NR 48 TC 62 Z9 64 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD APR PY 1995 VL 57 IS 4 BP 536 EP 542 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA QU085 UT WOS:A1995QU08500004 PM 7722411 ER PT J AU TOGAWA, K RUSTGI, AK AF TOGAWA, K RUSTGI, AK TI HUMAN PAPILLOMAVIRUS-16 AND PAPILLOMAVIRUS-18 REPLICATION IN ESOPHAGUS SQUAMOUS CANCER CELL-LINES DOES NOT REQUIRE HETEROLOGOUS E1 AND E2 PROTEINS SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HUMAN PAPILLOMAVIRUS; ESOPHAGUS SQUAMOUS CANCER; VIRAL REPLICATION ID GROWTH-FACTOR RECEPTOR; EPITHELIAL DIFFERENTIATION; BOVINE PAPILLOMAVIRUS; E5 GENE; TYPE-16; INVITRO; ORIGIN AB Human papillomaviruses (HPVs) are double-stranded DNA viruses that replicate in the nuclei of squamous epithelial cells. HPVs can be classified into high-risk (e.g., types 16, 18, 31, and 33) or low-risk (e.g., types 6, 11, and 30), depending on their association with benign or malignant tumors. We recently described the association of HPV-16 and -18 with esophagus squamous cell cancer. HPV replication was studied in representative cell lines derived from esophagus cancers. HPV-16 and -18 genomes were independently transiently transfected into HCE-4 and HCE-7 cell lines with and without E1 and E2 genes under heterologous promoters. Southern blot analysis demonstrated that these cell lines support viral replication. However, heterologous El and E2 are not required for HPV replication. These findings suggest that specific host nuclear factors in esophageal squamous epithelial cells may support HPV replication. (C) 1995 Wiley-Liss, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. NR 20 TC 10 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD APR PY 1995 VL 45 IS 4 BP 435 EP 438 PG 4 WC Virology SC Virology GA QQ263 UT WOS:A1995QQ26300013 PM 7666044 ER PT J AU THOMAS, DM ROGERS, SD SLEEMAN, MW PASQUINI, GM BRINGHURST, FR NG, KW ZAJAC, JD BEST, JD AF THOMAS, DM ROGERS, SD SLEEMAN, MW PASQUINI, GM BRINGHURST, FR NG, KW ZAJAC, JD BEST, JD TI MODULATION OF GLUCOSE-TRANSPORT BY PARATHYROID-HORMONE AND INSULIN IN UMR-106-01, A CLONAL RAT OSTEOGENIC-SARCOMA CELL-LINE SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID DEPENDENT PROTEIN-KINASE; L6 MUSCLE-CELLS; MESSENGER-RNA; CYCLIC-AMP; OSTEOBLASTIC CELLS; RIBONUCLEIC-ACID; GENE-EXPRESSION; GLUT4 GENE; UMR-106-01; SYSTEM AB This study characterizes the actions of insulin and parathyroid hormone (PTH) on the glucose transport system in the rat osteogenic sarcoma cell line UMR 106-01, which expresses a number of features of the osteoblast phenotype. Using [1,2-H-3]2-deoxyglucose (2-DOG) as a label, UMR 106-01 cells were shown to possess a glucose transport system which was enhanced by insulin. In contrast, PTH influenced glucose transport in a biphasic manner with a stimulatory effect at 1 h and a more potent inhibitory effect at 16 h on basal and insulin-stimulated 2-DOG transport. To explore the mechanism of PTH action, a direct agonist of cAMP-dependent protein kinase (PKA) was tested. 8-Bromo-cAMP had no acute stimulatory effect but inhibited basal and insulin-stimulated 2-DOG transport at 16 h. This result suggested that the prolonged, but not the acute, effect of PTH was mediated by the generation of cAMP. Further studies with the cell line UMR 4-7, a UMR 106-01 clone stably transfected with an inducible mutant inactive regulatory subunit of PKA, confirmed that the inhibitory but not the stimulatory effect of PTH was mediated by the PKA pathway. Northern blot data indicated that the prolonged inhibitory effects of PTH and 8-bromo-cAMP on glucose transport were likely to be mediated in part by reduction in the levels of GLUT1 (HepG2/brain glucose transporter) mRNA. C1 ROYAL MELBOURNE HOSP,DEPT MED,MELBOURNE,VIC 3050,AUSTRALIA. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. RP THOMAS, DM (reprint author), UNIV MELBOURNE,ST VINCENTS HOSP,DEPT MED,41 VICTORIA PARADE,FITZROY,VIC 3065,AUSTRALIA. NR 46 TC 21 Z9 23 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD APR PY 1995 VL 14 IS 2 BP 263 EP 275 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QU527 UT WOS:A1995QU52700012 PM 7619214 ER PT J AU MATTAMMAL, MB STRONG, R LAKSHMI, VM CHUNG, HD STEPHENSON, AH AF MATTAMMAL, MB STRONG, R LAKSHMI, VM CHUNG, HD STEPHENSON, AH TI PROSTAGLANDIN-H SYNTHETASE-MEDIATED METABOLISM OF DOPAMINE - IMPLICATION FOR PARKINSONS-DISEASE SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE ARACHIDONIC ACID; PROSTAGLANDINS; DOPAMINE; COOXIDATION; NEURONS; PARKINSONS DISEASE ID CARCINOGEN-DNA ADDUCTS; OXYGEN FREE-RADICALS; ACUTE LUNG INJURY; LIPID-PEROXIDATION; SUBSTANTIA-NIGRA; ARACHIDONIC-ACID; HUMAN-BRAIN; OXIDATION; SYNTHASE; ACTIVATION AB Differences in prostaglandin H synthetase (PHS) activity in the substantia nigra of age- and postmortem interval-matched parkinsonian, Alzheimer's, and normal control brain tissue were assessed. Prostaglandin E(2) (PGE(2), an index of PHS activity) was higher in substantia nigra of parkinsonian brain tissue than Alzheimer's or control tissue. Incubation of substantia nigra slices with arachidonic acid (AA) increased PGE(2) synthesis. Dopamine stimulated PHS synthesis of PGE(2). [H-3]Dopamine was activated by PHS to electrophilic intermediate(s) that covalently bound to DNA, microtubulin protein, bovine serum albumin, and sulfhydryl reagents. When AA was replaced by hydrogen peroxide, PHS/H2O2-supported binding proceeded at rates similar to those observed with PHS/AA. Indomethacin and aspirin inhibited AA-mediated cooxidation of dopamine but not H2O2-mediated metabolism. PHS-mediated metabolism of dopamine was not affected by monoamine oxidase inhibitors. Substrate requirements and effects of specific inhibitors suggest cooxidation of dopamine is mediated by the hydroperoxidase activity of PHS. P-32-postlabeling was used to detect dopamine-DNA adducts. PHS/AA activation of dopamine in the presence of DNA resulted in the formation of five dopamine-DNA adducts, i.e., 23, 43, 114, 70, and 270 amol/mu g DNA. DNA adduct formation was PHS, AA, and dopamine dependent. PHS catalyzed cooxidation of dopamine in dopaminergic neuronal degeneration is discussed. C1 VET ADM MED CTR, CLIN LAB SERV, ST LOUIS, MO 63125 USA. ST LOUIS UNIV, CTR HLTH SCI, DIV GERIATR MED, ST LOUIS, MO 63103 USA. ST LOUIS UNIV, CTR HLTH SCI, DIV PATHOL, ST LOUIS, MO 63103 USA. ST LOUIS UNIV, CTR HLTH SCI, DIV PHARMACOL & PHYSIOL SCI, ST LOUIS, MO 63103 USA. AUDIE L MURPHY MEM VET ADM MED CTR, CTR GERIATR RES EDUC & CLIN, SAN ANTONIO, TX 78284 USA. UNIV TEXAS, HLTH SCI CTR, DEPT CELLULAR & STRUCT BIOL, SAN ANTONIO, TX USA. UNIV TEXAS, HLTH SCI CTR, DEPT PHARMACOL, SAN ANTONIO, TX 78284 USA. RP VET ADM MED CTR, GRECC 11G, JEFFERSON BARRACKS, ST LOUIS, MO 63125 USA. FU NCRR NIH HHS [RR-00954]; NIA NIH HHS [AG09557]; NIADDK NIH HHS [AM-20579] NR 53 TC 114 Z9 117 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 1995 VL 64 IS 4 BP 1645 EP 1654 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA QN150 UT WOS:A1995QN15000026 PM 7891092 ER PT J AU PAN, ZH LIPTON, SA AF PAN, ZH LIPTON, SA TI MULTIPLE GABA RECEPTOR SUBTYPES MEDIATE INHIBITION OF CALCIUM INFLUX AT RAT RETINAL BIPOLAR CELL TERMINALS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GABA; GABA RECEPTORS; CALCIUM; 3-AMINO-PROPYL(METHYL)PHOSPHINIC ACID; SYNAPTIC TRANSMISSION; BIPOLAR CELLS; RETINA; RAT ID GAMMA-AMINOBUTYRIC-ACID; SINGLE SYNAPTIC TERMINALS; XENOPUS OOCYTES; GANGLION-CELLS; PHARMACOLOGY; CURRENTS; RHO-1; MOUSE; RESPONSES; NEURONS AB Inhibitory effects of GABA on K+-evoked Ca2+ influx into rat retinal bipolar cell terminals were studied using calcium imaging methods. Application of high K+ evokes a sustained, reversible increase in [Ca2+](i) at bipolar cell terminals, which occurs mainly via dihydropyridine-sensitive (L-type) Ca2+ channels. There are at least two GABA receptor subtypes coexisting at bipolar cell terminals: a conventional GABA(A) receptor and a bicuculline/baclofen-insensitive GABA receptor. Activation of either GABA receptor inhibited the K+-evoked Ca2+ response. However, these two GABA receptor subtypes have distinct properties. GABA(A) receptors suppress the Ca2+ response only at relatively high concentrations of agonist, and with fas(+) kinetics and a narrow dynamic range. In contrast, the bicuculline/baclofen-insensitive GABA receptors produce inhibition on the Ca2+ response at a much lower concentration of agonist, and with slow onset and a wider dynamic range. The pharmacologic profile of the bicuculline/baclofen-insensitive GABA receptor at bipolar cell terminals is most similar to the GABA(C) receptor reported by Feigenspan et al. (1993). Unlike the GABA(C) receptors described in other species, it is extremely insensitive to picrotoxin. Therefore, it may be appropriate to refer to this receptor as a picrotoxin-insensitive GABA(C) receptor. 3-Aminopropyl(methyl)phosphinic acid (3-APMPA) and 3-aminopropylphosphonic (3-APA), two phosphate analogs of GABA, selectively antagonize the picrotoxin-insensitive GABA(C) receptors but not the GABA(A) receptors in this system. These results imply a functional role for multiple GABA receptors in regulating synaptic transmission at bipolar cell terminals. C1 HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. BETH ISRAEL HOSP,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02115. RP PAN, ZH (reprint author), HARVARD UNIV,CHILDRENS HOSP,DEPT NEUROL,BOSTON,MA 02115, USA. FU NEI NIH HHS [R01EY05477] NR 42 TC 119 Z9 125 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 APR PY 1995 VL 15 IS 4 BP 2668 EP 2679 PG 12 WC Neurosciences SC Neurosciences & Neurology GA QT913 UT WOS:A1995QT91300007 PM 7722621 ER PT J AU TOOTELL, RBH REPPAS, JB KWONG, KK MALACH, R BORN, RT BRADY, TJ ROSEN, BR BELLIVEAU, JW AF TOOTELL, RBH REPPAS, JB KWONG, KK MALACH, R BORN, RT BRADY, TJ ROSEN, BR BELLIVEAU, JW TI FUNCTIONAL-ANALYSIS OF HUMAN MT AND RELATED VISUAL CORTICAL AREAS USING MAGNETIC-RESONANCE-IMAGING SO JOURNAL OF NEUROSCIENCE LA English DT Review DE FUNCTIONAL MRI; AREA MT; HUMAN VISUAL CORTEX; MOTION PERCEPTION; CONTRAST SENSITIVITY; COLOR ID LATERAL GENICULATE-NUCLEUS; SUPERIOR TEMPORAL SULCUS; MACAQUE STRIATE CORTEX; RECEPTIVE-FIELD PROPERTIES; RETINAL GANGLION-CELLS; CONTRAST SENSITIVITY; HUMAN BRAIN; CORTICOCORTICAL CONNECTIONS; TOPOGRAPHIC ORGANIZATION; VISUOTOPIC ORGANIZATION AB Using noninvasive functional magnetic resonance imaging (fMRI) techniques, we analyzed the responses in human area MT with regard to visual motion, color, and luminance contrast sensitivity, and retinotopy, As in previous PET studies, we found that area MT responded selectively to moving (compared to stationary) stimuli. The location of human MT in the present fMRI results is consistent with that of MT in earlier PET and anatomical studies. In addition we found that area MT has a much higher contrast sensitivity than that in several other areas, including primary visual cortex (V1). Functional MRI half-amplitudes in V1 and MT occurred at approximately 15% and 1% luminance contrast, respectively. High sensitivity to contrast and motion in MT have been closely associated with magnocellular stream specialization in nonhuman primates, Human psychophysics indicates that visual motion appears to diminish when moving color-varying stimuli are equated in luminance. Electrophysiological results from macaque MT suggest that the human percept could be due to decreases in firing of area MT cells at equiluminance. We show here that fMRI activity in human MT does in fact decrease at and near individually measured equiluminance. Tests with visuotopically restricted stimuli in each hemifield produced spatial variations in fMRI activity consistent with retinotopy in human homologs of macaque areas V1, V2, V3, and VP. Such activity in area MT appeared much less retinotopic, as in macaque. However, it was possible to measure the interhemispheric spread of fMRI activity in human MT (half amplitude activation across the vertical meridian = similar to 15 degrees). C1 HARVARD UNIV, MIT, DIV HLTH SCI & TECHNOL, BOSTON, MA 02115 USA. RP TOOTELL, RBH (reprint author), MASSACHUSETTS GEN HOSP, CTR NMR, 149 13TH ST, BOSTON, MA 02129 USA. RI Li, Chong/F-4265-2015; OI Born, Richard/0000-0003-4360-427X FU NEI NIH HHS [EY07980]; NHLBI NIH HHS [R01 HL39810]; NIMH NIH HHS [R01 MH 50054] NR 122 TC 969 Z9 978 U1 5 U2 53 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR PY 1995 VL 15 IS 4 BP 3215 EP 3230 PG 16 WC Neurosciences SC Neurosciences & Neurology GA QT913 UT WOS:A1995QT91300055 PM 7722658 ER PT J AU SORENSEN, G BEDER, B PRIBLE, CR PINNEY, J AF SORENSEN, G BEDER, B PRIBLE, CR PINNEY, J TI REDUCING SMOKING AT THE WORKPLACE - IMPLEMENTING A SMOKING BAN AND HYPNOTHERAPY SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CIGARETTE CONSUMPTION; CESSATION; PREVALENCE; ATTITUDES; POLICY AB Smoking cessation programs may be an important component in the implementation of worksite smoking policies. This study examines the impact of a smoke-free policy and the effectiveness of an accompanying hypnotherapy smoking cessation program, Participants in the 90-minute smoking cessation seminar were surveyed 12 months after the program was implemented (n = 2642; response rate = 76%). Seventy-one percent of the smokers participated in the hypnotherapy program. Fifteen percent of survey respondents quit and remained continuously abstinent. A survey to assess attitudes toward the policy was conducted 1 year after policy implementation (n = 1256; response rate = 64%), Satisfaction was especially high among those reporting high compliance with the policy. These results suggest that hypnotherapy may be an. attractive alternative smoking cessation method particularly when used in conjunction with a smoke-free worksite policy that offers added incentive for smokers to think about quitting. C1 BOSTON UNIV,SCH PUBL HLTH,BOSTON,MA. BEDER HLTH ASSOCIATES,BRAINTREE,MA. NEW ENGLAND TELEPHONE,BOSTON,MA. RP SORENSEN, G (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 24 TC 15 Z9 15 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD APR PY 1995 VL 37 IS 4 BP 453 EP 460 DI 10.1097/00043764-199504000-00017 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QT048 UT WOS:A1995QT04800010 PM 7670901 ER PT J AU DONOFF, RB AF DONOFF, RB TI EXPERIMENTAL TOPICAL TETRACYCLINE-INDUCED NEURITIS IN THE RAT - DISCUSSION SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Discussion RP DONOFF, RB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD APR PY 1995 VL 53 IS 4 BP 434 EP 434 DI 10.1016/0278-2391(95)90719-X PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA QQ668 UT WOS:A1995QQ66800017 ER PT J AU RODGERS, JA RODGERS, WB AF RODGERS, JA RODGERS, WB TI MARGINAL MANDIBULAR NERVE PALSY DUE TO COMPRESSION BY A CERVICAL HARD COLLAR SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Note DE CERVICAL SPINE; IMMOBILIZATION; CERVICAL COLLAR AB A case history of a trauma patient who developed a palsy of the marginal mandibular nerve from compression by a cervical spine hard collar is presented. After clinical and radiographic screening found no evidence of occult cervical spine pathology, the collar was removed; the palsy resolved uneventfully during the next 2 days. C1 NEW ENGLAND DEACONESS HOSP,DIV PLAST SURG,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114. NR 0 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD APR PY 1995 VL 9 IS 2 BP 177 EP 179 DI 10.1097/00005131-199504000-00015 PG 3 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA QQ253 UT WOS:A1995QQ25300015 PM 7776040 ER PT J AU COLLINS, JJ GRIER, HE KINNEY, HC BERDE, CB AF COLLINS, JJ GRIER, HE KINNEY, HC BERDE, CB TI CONTROL OF SEVERE PAIN IN CHILDREN WITH TERMINAL MALIGNANCY SO JOURNAL OF PEDIATRICS LA English DT Article ID NEUROPATHIC PAIN; PATIENT AB Objective: To identify the characteristics of the subset of children with malignancy in whom massive opioid infusions are needed during the terminal phase. Design: Retrospective review of the records of the 199 patients who died of malignancy after treatment at Children's Hospital, Boston, from March 1989 to July 1993, identifying characteristics of patients who required massive opioid infusions (operationally defined as infusion of >3 mg/kg per hour of morphine dose equivalent) during the terminal phase. Results: Twelve patients (6%) required massive opioid infusions, and eight of these patients required extraordinary measures (epidural or subarachnoid infusion and/or sedation) to achieve adequate analgesia. The duration of epidural or subarachnoid infusions in three patients ranged from 3 to 9 days, and minimal complications occurred. The duration of sedation ranged from 1 to 15 days. Maximal intravenous opioid dosing ranged from 3.8 to 518 mg/kg per hour of morphine equivalent. The maximal infusion rate (exceeding all previous published reports) occurred in an infant with an isolated metastasis in the periaqueductal gray matter, a brain-stem site linked to mediating analgesia and defense reactions. The need for massive opioid dosing in 11 of 12 patients was associated with tumor spread to the spinal nerve roots, nerve plexus, large peripheral nerve, or spinal cord compression. Conclusions: Standard dosing of opioids adequately treats most cancer pain in children; however, a significant group requires more extensive management. These problems occur more commonly among patients with solid tumors metastatic to spine and major nerves. C1 CHILDRENS HOSP, DIV HEMATOL ONCOL, PAIN TREATMENT SERV, BOSTON, MA 02115 USA. CHILDRENS HOSP, DEPT ANESTHESIA, BOSTON, MA 02115 USA. CHILDRENS HOSP, DEPT MED, BOSTON, MA 02115 USA. CHILDRENS HOSP, DEPT PATHOL, BOSTON, MA 02115 USA. DANA FARBER CANC INST, DEPT PEDIAT ONCOL, BOSTON, MA USA. HARVARD UNIV, SCH MED, DEPT ANESTHESIA, BOSTON, MA USA. HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA USA. NR 18 TC 81 Z9 82 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 1995 VL 126 IS 4 BP 653 EP 657 DI 10.1016/S0022-3476(95)70370-5 PG 5 WC Pediatrics SC Pediatrics GA QR212 UT WOS:A1995QR21200027 PM 7535354 ER PT J AU FRUEH, BC LEVERETT, JP KINDER, BN AF FRUEH, BC LEVERETT, JP KINDER, BN TI INTERRELATIONSHIP BETWEEN MMPI-2 AND RORSCHACH VARIABLES IN A SAMPLE OF VIETNAM VETERANS WITH PTSD SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; COMBAT VETERANS; SYMPTOMS AB We examined interrelationships between theoretically related MMPI-2 and Rorschach variables in a sample of Veterans Affairs outpatients with Posttraumatic Stress Disorder (PTSD). Subjects were 20 White Vietnam combat veterans diagnosed with PTSD who completed the Rorschach and MMPI-2 as part of a comprehensive evaluation. Correlations were calculated for variables in three groups: validity, depression and anxiety, and thought disturbance. Results showed strong relationships between m, MOR, and the Dramatic special score of the Rorschach and MMPI-2 indices of distress. Positive relationships were also found for some indicators of thought disturbance, whereas correlations for other depressive indicators were not significant. Findings are discussed with regard to implications for the clinical assessment of combat-related PTSD and future directions for assessment research. C1 UNIV S FLORIDA,TAMPA,FL 33620. RP FRUEH, BC (reprint author), MED UNIV S CAROLINA,RALPH H JOHNSON VET AFFAIRS MED CTR,DEPT PSYCHIAT & BEHAV SCI,CHARLESTON,SC 29401, USA. NR 19 TC 5 Z9 5 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD APR PY 1995 VL 64 IS 2 BP 312 EP 318 DI 10.1207/s15327752jpa6402_10 PG 7 WC Psychology, Clinical; Psychology, Social SC Psychology GA QP364 UT WOS:A1995QP36400010 PM 7722856 ER PT J AU WILLIAMS, JW HOLLEMAN, DR SIMEL, DL AF WILLIAMS, JW HOLLEMAN, DR SIMEL, DL TI MEASURING SHOULDER FUNCTION WITH THE SHOULDER PAIN AND DISABILITY INDEX SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE HEALTH STATUS MEASURE; FUNCTIONAL STATUS; QUALITY OF LIFE; SHOULDER FUNCTION ID HEALTH ASSESSMENT QUESTIONNAIRE; DOUBLE-BLIND; RESPONSIVENESS; PHYSIOTHERAPY; INSTRUMENTS; INJECTIONS; ARTHRITIS; VALIDITY; THERAPY; TRIAL AB Objective. To extend the validity of the Shoulder Pain and Disability Index (SPADI) by (1) making it suitable for telephone administration; (2) determining its convergent validity with other health status measures; and (3) assessing the responsiveness of the SPADI to clinical change. Methods, Consecutive primary care patients with shoulder discomfort were followed for 3 months. At enrollment, a detailed shoulder specific history was obtained by a trained research assistant, and the Health Assessment Questionnaire (HAQ), the Medical Outcomes Study SF-20 (SF-20), and numeric and visual analog versions of the SPADI were completed by the patient. At 2, 4, and 12 weeks the numeric scaled SPADI was administered by telephone and patients rated globally the change in shoulder discomfort. Results, One hundred and two subjects were enrolled; 96 completed at least one followup assessment and 75 completed all followup assessments. Subjects were men (98%), predominantly white (73%), with a median age of 60 years, and the majority had experienced shoulder discomfort for >3 months (66%). At baseline the visual analog (VAS) and numeric scaled SPADI were highly concordant (intraclass correlation coefficient = 0.86), and the SPADI correlated substantially with the HAQ (r = 0.61) and the physical functioning (r = -0.50) and pain (r = -0.43) domains of the SF-20, The SPADI(triangle) (baseline - followup) discriminated accurately between subjects who improved versus those who stayed the same or worsened [receiver operating characteristic cure, (ROC) = 0.91, likelihood ratio for improvement = 34]. Conclusion. The numerically scaled SPADI is highly correlated with the original VAS version of the SPADI and other measures of health status. The SPADI is responsive to change and accurately discriminates among patients who are improved or worsened. C1 UNIV TEXAS,HLTH SCI CTR,DIV GEN INTERNAL MED,SAN ANTONIO,TX 78284. UNIV KENTUCKY,DIV MED GENET,MED SERV,LEXINGTON,KY 40506. VET ADM MED CTR,CTR AMBULATORY CARE,LEXINGTON,KY 40511. VET ADM MED CTR,CTR HLTH SERV RES PRIMARY CARE,DURHAM,NC 27705. DUKE UNIV,MED CTR,DIV GEN INTERNAL MED,DURHAM,NC 27710. UNIV TEXAS,AUDIE L MURPHY MEM VET HOSP,HLTH SCI CTR,DIIV GEN INTERNAL MED,AMBULATORY CARE SERV,SAN ANTONIO,TX 78285. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 33 TC 153 Z9 158 U1 1 U2 4 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 APR PY 1995 VL 22 IS 4 BP 727 EP 732 PG 6 WC Rheumatology SC Rheumatology GA QU120 UT WOS:A1995QU12000029 PM 7791172 ER PT J AU HUANG, PG ALLAM, A TAGHIAN, A RUKA, W FREEMAN, J DUFFY, M SUIT, HD AF HUANG, PG ALLAM, A TAGHIAN, A RUKA, W FREEMAN, J DUFFY, M SUIT, HD TI QUANTITATIVE COMPARISON OF XENOTRANSPLANTATION OF A HUMAN SOFT-TISSUE SARCOMA INTO THE SUBCUTANEOUS TISSUE OF NORMAL, POSTINCISION, AND POSTINCISION PLUS INDOMETHACIN-TREATED NUDE-MICE SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE HUMAN XENOGRAFTS; TD50; ANGIOGENESIS; SURGICAL WOUND; NUDE MICE ID TUMOR-GROWTH; INDUCED ANGIOGENESIS; INHIBITION; RECURRENCE; WOUNDS AB The purpose of this study was to test the hypotheses that (1) surgical wounding can enhance the xenotransplantability of a human soft tissue sarcoma (HSTS26T) into subcutaneous (s.c.) tissue of nude mice, and (2) Indomethacin may reduce the xenotransplantability of this human tumor in the surgical wounding animal model by suppressing angiogenesis. The experimental method was to employ the quantitative transplantation assays (TD50, the number of tumor cells that, on average, would be expected to induce a tumor in 50% of the recipients). After an incisional wound (1.0-1.2 cm long) was made on the right leg of each experimental mouse, tumor cells were inoculated into the surgical wound, or into the contralateral leg at 24 and 72 hr postincision, and in another group tumor cells were inoculated into the wound at 72 hr postincision, plus daily s.c. injection of indomethacin, 2 mg/kg body weight for 8 consecutive days in a separate experiment. Nonincisional mice received the same inoculation as the control groups. The TD(50)s of surgically wounded groups were 3.5-10.7 times lower than that of the control groups. Significantly lower TD50 values were found in groups of cells inoculated into the surgical wound at 72 hr postincision (P < 0.05 or P < 0.01) and into the contralateral leg at 24 hr postincision (P = 0.05). No significant difference was found between the TD50 values in mice that received cells inoculated at 72 hr postincision plus indomethacin treatment, and those with no wound controls. Our conclusion is that the surgical wound can enhance the xenotransplantability of HSTS26T in nude mice. Indomethacin can decrease this enhancing effect level similar to that in no-wound controls and may prevent tumor recurrence in a surgical wound. (C) 1995 Wiley-Liss, Inc. RP HUANG, PG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB RADIAT BIOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA13311] NR 24 TC 1 Z9 2 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 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD APR PY 1995 VL 58 IS 4 BP 257 EP 262 DI 10.1002/jso.2930580412 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA QU857 UT WOS:A1995QU85700011 PM 7723370 ER PT J AU BIEDERMAN, J WOZNIAK, J KIELY, K ABLON, S FARAONE, S MICK, E MUNDY, E KRAUS, I AF BIEDERMAN, J WOZNIAK, J KIELY, K ABLON, S FARAONE, S MICK, E MUNDY, E KRAUS, I TI CBCL CLINICAL-SCALES DISCRIMINATE PREPUBERTAL CHILDREN WITH STRUCTURED INTERVIEW-DERIVED DIAGNOSIS OF MANIA FROM THOSE WITH ADHD SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE CHILD BEHAVIOR CHECKLIST; MANIA; ATTENTION-DEFICIT HYPERACTIVITY; DISORDER; CHILDREN; COMORBIDITY ID DEPRESSIVE VARIANT SYNDROME; ATTENTION-DEFICIT DISORDER; THERAPEUTIC CONSIDERATIONS; PSYCHIATRIC DIAGNOSES; BEHAVIOR CHECKLIST; BIPOLAR DISORDER; CONVERGENCE; ADOLESCENT; CHILDHOOD; COMORBIDITY AB Objective: To evaluate the discriminative ability of the Child Behavior Checklist (CBCL) to identify children with structured interview-derived diagnosis of bipolar disorder. Method: We evaluated the convergence of CBCL scales with the diagnosis of mania in 31 children with mania, 120 children with attention-deficit hyperactivity disorder, and 77 prepubertal normal control children aged 12 years or younger. We evaluated the strength of association between each CBCL scale and structured interview-derived diagnoses with total predictive value and the odds ratio. Results: Excellent convergence was found between the CBCL scales of Delinquent Behavior, Aggressive Behavior, Somatic Complaints, Anxious/Depressed, and Thought Problems and the diagnosis of mania. Conclusions: These findings indicate that the CBCL could serve as a rapid and useful screening instrument to identify manic children in clinical settings. C1 HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,COMMUNITY HLTH PLAN,DEPT PEDIAT,BOSTON,MA. RP BIEDERMAN, J (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,ACC 725,FRUIT ST,BOSTON,MA 02114, USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 47 TC 192 Z9 194 U1 2 U2 13 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 1995 VL 34 IS 4 BP 464 EP 471 DI 10.1097/00004583-199504000-00013 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA QP335 UT WOS:A1995QP33500015 PM 7751260 ER PT J AU DISALVO, TG MATHIER, M SEMIGRAN, MJ DEC, GW AF DISALVO, TG MATHIER, M SEMIGRAN, MJ DEC, GW TI PRESERVED RIGHT-VENTRICULAR EJECTION FRACTION PREDICTS EXERCISE CAPACITY AND SURVIVAL IN ADVANCED HEART-FAILURE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID IDIOPATHIC DILATED CARDIOMYOPATHY; CORONARY-ARTERY DISEASE; PEAK EXERCISE; CARDIAC TRANSPLANTATION; PLASMA NOREPINEPHRINE; ANAEROBIC THRESHOLD; OXYGEN-CONSUMPTION; SYSTOLIC PRESSURE; PROGNOSTIC VALUE; MORTALITY AB Objectives. This study was undertaken to determine which exercise and radionuclide ventriculographic variables predict prognosis in advanced heart failure. Background. Although cardiopulmonary exercise testing is frequently used to predict prognosis in patients with advanced heart failure, little is known about the prognostic significance of ventriculographic variables. Methods. The results of maximal symptom-limited cardiopulmonary exercise testing and first pass radionuclide ventriculography in patients with advanced heart failure referred for evalu tion for cardiac transplantation were analyzed. Results. Sixty seven patients with advanced heart failure (mean [+/-SD]; age 51 +/- 10 years, New York Heart Association functional classes III (58%) and IV (18%); mean left ventricular ejection fraction 0.22 +/- 0.07) underwent simultaneous upright bicycle ergometric cardiopulmonary exercise testing and first-pass rest/exercise radionuclide ventriculography. Mean peak oxygen consumption (Vo(2)) was 11.8 +/- 4.2 ml/kg per min, and mean peak age- and gender-adjusted percent predicted oxygen consumption (%Vo(2)) was 38 +/- 11.9%. Univariate predictors of overall survival included right ventricular ejection fraction greater than or equal to 0.35 at rest and greater than or equal to 0.35 at exercise and %Vo(2), greater than or equal to 45% (all p < 0.05). In a multivariate proportional hazards survival model, right ventricular ejection fraction greater than or equal to 0.35 at exercise (p < 0.01) and %Vo(2) greater than or equal to 45% (p = 0.01) were selected as independent predictors of overall survival. Univariate predictors of event-free survival included right ventricular ejection fraction greater than or equal to 0.35 at rest (p = 0,01) and greater than or equal to 0.35 at exercise (p < 0.01), functional class II (p < 0.05) and %Vo(2) greater than or equal to 45% (p = 0.05). Right ventricular ejection fraction greater than or equal to 0.35 at exercise (p = 0.01) was the only independent predictor of event-free survival in a multivariate proportional hazards model. Cardiac index at rest, Vo(2), left ventricular ejection fraction at rest, and exercise-related increase or decrease >0.05 in left or right ventricular ejection fraction were not predictive of overall or event-free survival in any univariate or multivariate analysis. Conclusions. 1) Right ventricular ejection fraction greater than or equal to 0.35 at rest and exercise is a more potent predictor of survival in advanced heart failure than Vo(2) or %Vo(2); 2) %Vo, rather than Vo(2) predicts survival in advanced heart failure; 3) neither %Vo(2) nor Vo(2) predicts survival to the combined end point of death or admission for inotropic or mechanical support in patients with advanced heart failure. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP DISALVO, TG (reprint author), MASSACHUSETTS GEN HOSP,CTR HEART FAILURE,DEPT MED,CARDIAC UNIT,BULFINCH 211,BOSTON,MA 02114, USA. NR 46 TC 408 Z9 413 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR PY 1995 VL 25 IS 5 BP 1143 EP 1153 DI 10.1016/0735-1097(94)00511-N PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QP930 UT WOS:A1995QP93000027 PM 7897128 ER PT J AU NADEL, AS BROMLEY, B FRIGOLETTO, FD BENACERRAF, BR AF NADEL, AS BROMLEY, B FRIGOLETTO, FD BENACERRAF, BR TI CAN THE PRESUMED RISK OF AUTOSOMAL TRISOMY BE DECREASED IN FETUSES OF OLDER WOMEN FOLLOWING A NORMAL SONOGRAM SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article ID SERUM ALPHA-FETOPROTEIN; CHOROID-PLEXUS CYSTS; DOWNS-SYNDROME; CHROMOSOMAL-ABNORMALITIES; 2ND-TRIMESTER FETUS; FETAL PYELECTASIS; SCREENING TOOL; 2ND TRIMESTER; AMNIOCENTESIS; ASSOCIATION AB Previous studies showed that a sonographic scoring system can be used to identify women under age 35 who are at an increased risk for a fetal autosomal trisomy. We propose to use the same scoring system to select women over age 35 who are at a decreased risk of a fetal autosomal trisomy because the ultrasonogram is normal. We reviewed the sonographic scores of 97 trisomic and 694 normal control fetuses from two previously published consecutive series designed to identify women at increased risk for an affected fetus. Using the same scoring index in this study, we calculated the sensitivity and specificity of a score = 0 zero for identifying fetuses with autosomal trisomy. We then applied Bayes' theorem to determine the probability of an autosomal trisomy at various maternal ages, given a sonographic score of 0. Of the 97 fetuses with an autosomal trisomy, 83 had a score of greater-than-or-equal-to 1, for a sensitivity of 86% (95% CI 77-92%). Of the 694 control fetuses with normal karyotype, 606 had a score of 0, for a specificity of 87% (95% CI 83-89%). A 42 year old woman's probability of an autosomal trisomy if the sonographic score is 0 becomes equivalent to the age-specific probability for a 35 year old woman. Using the lower limit of the CIs for sensitivity and specificity, we calculated that the probability of having a fetus with an autosomal trisomy falls from 18.8 in 1000 to 5.3 in 1000 for a 40 year old woman with a sonographic score of 0. Our data show that ultrasonography and maternal age provide a more accurate estimation of risk of fetal autosomal trisomy than maternal age alone. The approach described in this report may further define the candidates for karyotyping such that fewer amniocenteses would be necessary for close to the same number of chromosomally abnormal fetuses identified. This approach would result in a decrease in cost as well as morbidity and mortality for normal fetuses being tested. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET GYNECOL,BOSTON,MA 02114. NR 26 TC 62 Z9 62 U1 0 U2 0 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 APR PY 1995 VL 14 IS 4 BP 297 EP 302 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA QT457 UT WOS:A1995QT45700012 PM 7602689 ER PT J AU BROMLEY, B BENACERRAF, BR AF BROMLEY, B BENACERRAF, BR TI DIFFICULTIES IN THE PRENATAL-DIAGNOSIS OF MICROCEPHALY SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE MICROCEPHALY; FETUS; PRENATAL DIAGNOSIS ID FETAL AB Our objective was to determine whether the diagnosis of microcephaly present at birth is apparent using standard biometry in the second trimester. Fetuses with prenatally suspected microcephaly (biparietal diameter greater-than-or-equal-to 3 standard deviations below mean) who had a first sonogram prior to 22 weeks' gestation and a confirmation of microcephaly after birth were included in the study. We excluded all fetuses who had neural tube defects or other major associated abnormality that would lead to a suspicion of microcephaly. We therefore included fetuses who either had normal-appearing brains sonographically or intracranial calcifications as the only sonographic abnormality seen prior to 22 weeks' gestation. Seven fetuses met these criteria. One fetus was diagnosed as having microcephaly prior to 22 weeks' gestation. The other six fetuses had a normal head size prior to 22 weeks' gestation and were diagnosed as having microcephaly at 27 weeks' gestation and later. Only one of the seven fetuses had a karyotypic abnormality. We conclude that the prenatal diagnosis of microcephaly is not excluded by normal biometry on second trimester sonography. C1 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. 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. NR 6 TC 23 Z9 24 U1 0 U2 3 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 APR PY 1995 VL 14 IS 4 BP 303 EP 305 PG 3 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA QT457 UT WOS:A1995QT45700013 PM 7602690 ER PT J AU MCDOUGAL, WS AF MCDOUGAL, WS TI OBSTRUCTIVE UROPATHY - COMMENTARY SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP MCDOUGAL, WS (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 1995 VL 153 IS 4 BP 1084 EP 1084 DI 10.1016/S0022-5347(01)67515-3 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA QL361 UT WOS:A1995QL36100001 ER PT J AU MULUK, SC GINNS, LC SEMIGRAN, MJ KAUFMAN, JA GERTLER, JP AF MULUK, SC GINNS, LC SEMIGRAN, MJ KAUFMAN, JA GERTLER, JP TI KLIPPEL-TRENAUNAY-SYNDROME WITH MULTIPLE PULMONARY EMBOLI - AN UNUSUAL CAUSE OF PROGRESSIVE PULMONARY DYSFUNCTION SO JOURNAL OF VASCULAR SURGERY LA English DT Note AB A 32-year-old man with progressive dyspnea and congenital lymphedema was transferred to our hospital for evaluation as a lung transplant candidate with the suspected diagnosis of primary pulmonary hypertension. Evaluation revealed the additional history of previous limb-shortening procedures for the left leg, the presence of syndactyly, long-standing bilateral (left to right) lower extremity varices, as well as soft tissue asymmetry with the left leg and arm larger than the right-sided counterparts. A diagnosis of Klippel-Trenaunay syndrome was made on the basis of these findings. Because of the deep venous malformations known to occur in this syndrome, we sought evidence of recurrent pulmonary emboli as an explanation for the patient's progressive dyspnea, despite negative pulmonary arteriography and ventilation-perfusion scanning results at another institution. Repeat pulmonary arteriography demonstrated evidence of chronic and subacute pulmonary emboli. The patient is presently being treated with warfarin anticoagulation, with plans for placement of a caval filter if anticoagulation alone is insufficient to prevent further embolism. Klippel-Trenaunay syndrome is a rare cause of chronic pulmonary emboli, and this entity should be considered when the characteristic historical and physical findings are present. A case report and review of the syndrome, with particular focus on the aspects relevant to the vascular surgeon, are presented. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,DIV VASC SURG,PULM & CRIT CARE UNIT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GEN MED SERV,DIV CARDIOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA. RP MULUK, SC (reprint author), MASSACHUSETTS GEN HOSP,CTR AMBULATORY CARE,SUITE 464,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 18 TC 31 Z9 31 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 APR PY 1995 VL 21 IS 4 BP 686 EP 690 DI 10.1016/S0741-5214(95)70199-0 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA QT922 UT WOS:A1995QT92200014 PM 7707572 ER PT J AU MAIA, M TAKAHASHI, H ADLER, K GARLICK, RK WANDS, JR AF MAIA, M TAKAHASHI, H ADLER, K GARLICK, RK WANDS, JR TI DEVELOPMENT OF A 2-SITE IMMUNO-PCR ASSAY FOR HEPATITIS-B SURFACE-ANTIGEN SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE 2-SITE; SENSITIVE; IMMUNO-PCR; DETECTION; HBV; ANTIGEN ID POLYMERASE CHAIN-REACTION; MONOCLONAL-ANTIBODIES; VIRUS-DNA; IDENTIFICATION; TRANSMISSION; SYSTEM; SERUM AB Hepatitis B virus (HBV) gene transcription may occur at very low levels resulting in HBsAg concentrations in serum and liver below the limit of detection by currently available immunoassays. An assay has been developed that combines the specificity of two high affinity anti-HBs monoclonal antibodies (MAb) directed against distinct and separate determinants in the 'a' domain of HBsAg with the highly sensitive polymerase chain reaction (PCR) detection method. Following capture of HBsAg present in serum samples, the second anti-HBs MAb, which is biotinylated, is added. Binding of the second antibody allows the subsequent specific binding of streptavidin and a biotinylated linear DNA molecule derived from a bluetongue virus (BTV) gene. Presence of this DNA is then detected by PCR using BTV-specific primers. The PCR product is quantified by a liquid-phase oligonucleotide enzymatic assay, which further increases the sensitivity of the technique. The use of a two-site MAb capture and PCR detection system for HBsAg was shown to greatly enhance the specificity and sensitivity of the assay and detect as little as 0.5 pg of HBsAg in serum samples. It is suggested that the principles of this technique could be applied to measure other low level viral antigens in serum and biological samples. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP CANC CTR,MOLEC HEPATOL LAB,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA 02129. DUPONT CO INC,BOSTON,MA 02118. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-08169, AA-00048] NR 24 TC 43 Z9 48 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD APR PY 1995 VL 52 IS 3 BP 273 EP 286 DI 10.1016/0166-0934(94)00145-7 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA QR246 UT WOS:A1995QR24600004 PM 7601903 ER PT J AU LJUBIMOV, AV BURGESON, RE BUTKOWSKI, RJ MICHAEL, AF SUN, TT KENNEY, MC AF LJUBIMOV, AV BURGESON, RE BUTKOWSKI, RJ MICHAEL, AF SUN, TT KENNEY, MC TI HUMAN CORNEAL BASEMENT-MEMBRANE HETEROGENEITY - TOPOGRAPHICAL DIFFERENCES IN THE EXPRESSION OF TYPE-IV COLLAGEN AND LAMININ ISOFORMS SO LABORATORY INVESTIGATION LA English DT Article DE PERLECAN; ENTACTIN/NIDOGEN; FIBRONECTIN; KERATIN 3; IMMUNOFLUORESCENCE ID HEPARAN-SULFATE PROTEOGLYCAN; FIBROBLAST GROWTH-FACTOR; MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; KERATOCONUS CORNEAS; TISSUE DISTRIBUTION; NEUROMUSCULAR-JUNCTION; COMPONENTS; ANTIGEN; LOCALIZATION AB BACKGROUND: The corneal epithelium converges at the peripheral zone (limbus) with the conjunctival epithelium, forming a continuous sheet with phenotypically distinct regions-central, limbal, and conjunctival. The epithelial basement membrane (EBM) is important for corneal functions and cell adhesion, but its regional composition is poorly understood. Current literature is controversial as to the occurrence of type IV collagen in the cornea. The aim of this study was to investigate in detail corneal basement membrane (BM) composition and correlate it with the differentiation state of contributing cells. EXPERIMENTAL DESIGN: Adult human corneas (N = 8) were cryosectioned and analyzed by immunofluorescence with antibodies to 15 BM components and to keratin 3, a marker of corneal epithelial differentiation. RESULTS: A novel type of spatial heterogeneity (''horizontal'') in the EBM composition was found between the central cornea, limbus, and conjunctiva. Central EBM had type Dr collagen alpha 3-alpha 5 chains, whereas limbal and conjunctival EBM contained alpha 1-alpha 2 chains and also laminin alpha 2 and beta 2 chains. Limbal EBM in addition had alpha 5(IV) chain. Laminin-1 (alpha 1 beta 1 gamma 1), laminin-5 (alpha 3 beta 3 gamma 2), perlecan, fibronectin, entactin/nidogen, and type VII collagen were seen in the entire EBM. Another novel type of BM heterogeneity (''vertical'') was typical for the corneal Descemet's membrane: its stromal face had alpha 1(IV) and alpha 2(IV) chains and fibronectin, whereas alpha 3(IV)-alpha 5(IV) chains, entactin/nidogen, laminin-1, and perlecan were present on the endothelial face. CONCLUSIONS: Type N collagen controversy is the result of the shifts of isoforms in the limbus and conjunctiva. These shifts and the appearance of additional laminins in the limbus may be related to the differentiation state of corneal cells contributing to the EBM formation. Novel types of BM heterogeneity in the human cornea are described: regional (horizontal) in the EBM and vertical in the Descemet's membrane. The first one may be a common feature of converging complex epithelia, whereas the second one may be another unique property of the Descemet's membrane. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA. INCSTAR CORP,STILLWATER,MN. UNIV MINNESOTA,DEPT PEDIAT,MINNEAPOLIS,MN. NYU,SCH MED,NEW YORK,NY. RP LJUBIMOV, AV (reprint author), UNIV CALIF LOS ANGELES,CEDARS SINAI MED CTR,SCH MED,OPHTHALMOL RES LABS,DAVIS BLDG,ROOM 5069,LOS ANGELES,CA 90048, USA. RI Ljubimov, Alexander/E-5883-2013 NR 55 TC 198 Z9 201 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD APR PY 1995 VL 72 IS 4 BP 461 EP 473 PG 13 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA QV501 UT WOS:A1995QV50100012 PM 7723285 ER PT J AU GLIKLICH, RE METSON, R AF GLIKLICH, RE METSON, R TI TECHNIQUES FOR OUTCOMES RESEARCH IN CHRONIC SINUSITIS SO LARYNGOSCOPE LA English DT Article ID HEALTH SURVEY QUESTIONNAIRE; SF-36; MANAGEMENT AB Accurate assessment os patient outcome after sinus surgery requires the collection of valid and reliable data. Symptom-based surveys were administered in a prospective manner to 104 patients with chronic sinusitis. Test-retest reliability for the Chronic Sinusitis Survey based on duration of symptoms (0.86, P<.0001) was superior to that for a similar survey based on severity of symptoms (0.57, P<.0001). Results of the Chronic Sinusitis Survey also correlated significantly with subscales of a general health assessment in the extent to which chronic sinusitis limits physical activity (0.40, P<.01), interferes with work or other activities (0.36, P<.01), and affects patient perception of bodily pain (0.46, P<.001). The Chronic Sinusitis Survey is an efficient and reliable method to follow health status and health-related quality of life outcomes in patients with chronic sinusitis. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA. RP GLIKLICH, RE (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,CLIN OUTCOMES RES UNIT,243 CHARLES ST,BOSTON,MA 02114, USA. NR 18 TC 136 Z9 141 U1 0 U2 2 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 1995 VL 105 IS 4 BP 387 EP 390 DI 10.1288/00005537-199504000-00010 PN 1 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA QQ337 UT WOS:A1995QQ33700010 PM 7715384 ER PT J AU ASELTINE, RH CARLSON, KJ FOWLER, FJ BARRY, MJ AF ASELTINE, RH CARLSON, KJ FOWLER, FJ BARRY, MJ TI COMPARING PROSPECTIVE AND RETROSPECTIVE MEASURES OF TREATMENT OUTCOMES SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Conference on Measuring the Effects of Medical Treatment CY APR 21-22, 1994 CL MINNEAPOLIS, MN SP AGCY HLTH CARE POLICY & RES DE OUTCOMES; CHANGE IN HEALTH STATUS AB This study examines the correspondence between retrospective and prospective assessments of treatment outcomes among female patients treated for gynecologic symptoms (n = 800) and male patients having surgery for benign prostatic hyperplasia (n = 434). The overall health and symptom status of patients in both samples was assessed at enrollment and again 3 months after treatment; at the 3-month follow-up, patients also were asked to compare retrospectively their current health and how they were feeling with their condition before treatment. Findings indicate that prospective and retrospective measures of change do not yield the same results. Retrospective assessments consistently produce higher estimates of the benefits of treatment, although that pattern was clearer for overall health status than for measures of symptoms. Patients' posttreatment health and symptom status contributes as much to retrospective assessments of change as does prospectively measured change, although the retrospective assessments of female patients whose gynecologic symptoms were medically managed were more strongly related to prospective change than those of hysterectomy patients or prostate surgery patients. Overall, we conclude that these alternative measurement strategies yield divergent assessments of change, depending on the type of treatment a patient receives and, to some extent, what is being measured. C1 MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,BOSTON,MA 02114. RP ASELTINE, RH (reprint author), UNIV MASSACHUSETTS,10TH FLOOR HEALEY LIBRARY,100 MORRISSEY BLVD,BOSTON,MA 02125, USA. FU AHRQ HHS [HS 06121, HS 06336] NR 13 TC 44 Z9 44 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 1995 VL 33 IS 4 SU S BP AS67 EP AS76 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA QU755 UT WOS:A1995QU75500010 PM 7536868 ER PT J AU BARRY, MJ FOWLER, FJ OLEARY, MP BRUSKEWITZ, RC HOLTGREWE, HL MEBUST, WK AF BARRY, MJ FOWLER, FJ OLEARY, MP BRUSKEWITZ, RC HOLTGREWE, HL MEBUST, WK TI MEASURING DISEASE-SPECIFIC HEALTH-STATUS IN MEN WITH BENIGN PROSTATIC HYPERPLASIA SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Conference on Measuring the Effects of Medical Treatment CY APR 21-22, 1994 CL MINNEAPOLIS, MN SP AGCY HLTH CARE POLICY & RES DE HEALTH STATUS; PROSTATIC HYPERTROPHY; QUALITY OF LIFE ID SYMPTOM; PROSTATECTOMY; QUALITY AB In preparation for an outcomes study of benign prostatic hyperplasia (BPH), two measures of disease-specific health status were developed to supplement a symptom score and overall health status measures. The symptom problem index (SPI) captures how troublesome patients find their urinary symptoms. The BPH impact index (BII) measures how much their urinary problems affect various domains of health. A prospective revalidation of the refined instruments (N = 108 BPH patients and 50 controls) documented that both indices had good internal consistency (Cronbach's alpha = 0.88 and 0.79, respectively) and test-retest (r = 0.88 for both) reliabilities, correlated strongly with symptom scores (r = 0.86 and 0.77), and discriminated between BPH and control subjects (receiver-operating characteristic areas = 0.87 and 0.85, respectively). These indices were nearly as responsive as symptom scores in 50 men actively treated for BPH, and much more responsive than a non-disease-specific General Health Index (GHI), a Mental Health Index (MHI), and an Activity Index (AI). Finally, these measures capture most of the health status significance of BPH symptoms. In linear regression models constructed to predict scores on the GHI, MHI, and AI, symptom scores added little explanatory power to the SPI and, particularly, to the BII. These measures help clarify how BPH affects overall health status and function. Such measures have an important role to play in studies of the outcomes of treatment for BPH, and probably for other conditions that interfere with health status and function. C1 UNIV MASSACHUSETTS,CTR SURVEY RES,BOSTON,MA 02125. UNIV WISCONSIN,DEPT UROL,MADISON,WI 53706. BRIGHAM & WOMENS HOSP,DIV UROL,BOSTON,MA 02115. JOHNS HOPKINS UNIV,SCH MED,DEPT UROL,BALTIMORE,MD 21205. UNIV KANSAS,MED CTR,UROL SECT,KANSAS CITY,KS 66103. AMER UROL ASSOC,BALTIMORE,MD. RP BARRY, MJ (reprint author), MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,50 STANIFORD ST 9TH FLOOR,BOSTON,MA 02114, USA. NR 22 TC 137 Z9 138 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 1995 VL 33 IS 4 SU S BP AS145 EP AS155 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA QU755 UT WOS:A1995QU75500018 ER PT J AU STONE, RA OBROSKY, DS SINGER, DE KAPOOR, WN FINE, MJ HOUGH, L KARPF, M LAVE, J LI, YH MEDSGER, A REDMOND, C RICCI, E AF STONE, RA OBROSKY, DS SINGER, DE KAPOOR, WN FINE, MJ HOUGH, L KARPF, M LAVE, J LI, YH MEDSGER, A REDMOND, C RICCI, E TI PROPENSITY SCORE ADJUSTMENT FOR PRETREATMENT DIFFERENCES BETWEEN HOSPITALIZED AND AMBULATORY PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Conference on Measuring the Effects of Medical Treatment CY APR 21-22, 1994 CL MINNEAPOLIS, MN SP AGCY HLTH CARE POLICY & RES DE CAUSAL INFERENCE IN NONRANDOMIZED STUDIES; CLASSIFICATION TREES; STATISTICAL ADJUSTMENT FOR CONFOUNDING AB A primary goal of the Pneumonia Patient Outcomes Research Team (PORT) multicenter cohort study is to identify a subgroup of patients with community-acquired pneumonia (CAP) who could be safely treated on an ambulatory basis. The medical outcomes of inpatients and outpatients are to be compared. Propensity score adjustment provides a unified way to control for pretreatment differences in the analysis of all the outcomes in this nonrandomized study by defining ''comparable'' patients as those with the same propensity score (i.e., the same probability of hospitalization). Data for 747 patients (35.5% hospitalized) with CAP in the Pneumonia PORT study illustrate the development and assessment of a propensity score adjustment. A classification tree algorithm defined seven propensity score strata with hospitalization probabilities ranging from 6.5% to 76.5%. Statistically significant pretreatment imbalances favoring the outpatients were found for 29 of 44 baseline variables considered; after stratification on the propensity score, only 13 of the 29 imbalances remained statistically significant at the 0.05 level. Post hoc stratification on the estimated propensity score consistently reduced, but did not completely eliminate, systematic baseline differences between ambulatory and hospitalized patients with CAP. Regression adjustment can be used in conjunction with propensity score stratification to adjust further for the remaining identified imbalances. C1 MASSACHUSETTS GEN HOSP,GEN MED UNIT,BOSTON,MA 02114. UNIV PITTSBURGH,SCH MED,DEPT INTERNAL MED,PITTSBURGH,PA. RP STONE, RA (reprint author), UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT BIOSTAT,304 PARRAN HALL,PITTSBURGH,PA 15261, USA. FU AHRQ HHS [HS06468] NR 11 TC 49 Z9 49 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 1995 VL 33 IS 4 SU S BP AS56 EP AS66 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA QU755 UT WOS:A1995QU75500009 PM 7723462 ER PT J AU OLEARY, JF FAIRCLOUGH, DL JANKOWSKI, MK WEEKS, JC AF OLEARY, JF FAIRCLOUGH, DL JANKOWSKI, MK WEEKS, JC TI COMPARISON OF TIME-TRADEOFF UTILITIES AND RATING-SCALE VALUES OF CANCER-PATIENTS AND THEIR RELATIVES - EVIDENCE FOR A POSSIBLE PLATEAU RELATIONSHIP SO MEDICAL DECISION MAKING LA English DT Article DE TIME TRADEOFF; UTILITY; RATING SCALE; CANCER; PATIENT PREFERENCES; QUALITY OF LIFE ID COST-EFFECTIVENESS; QUALITY; LIFE; PREFERENCES; ADJUSTMENT; OREGON AB Because they are easy to administer, rating Scales are often used as proxies for utility measures. The authors investigated the relationship between time-tradeoff utilities and rating scale values in two populations: 124 cancer patients asked to evaluate their current states of health and 102 relatives and close friends of cancer patients asked to evaluate health-state scenarios. None of the models tested effectively described the relationship between individual patients' rating scale values and time-tradeoff utilities for their current states of health. In contrast, both a plateau and a power-function model explained the variability in the responses. of the relatives reasonably well (R(2) = 0.56 and R(2) = 0.58, respectively). Given that many respondents who were unwilling to trade off any time assigned rating scale values of well below 100, a plateau model may represent the best approach to adjusting rating scale values for health-state scenarios when it is not feasible to elicit time-tradeoff utilities. C1 DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA. NR 20 TC 64 Z9 64 U1 0 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD APR-JUN PY 1995 VL 15 IS 2 BP 132 EP 137 DI 10.1177/0272989X9501500205 PG 6 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA QQ674 UT WOS:A1995QQ67400005 PM 7783573 ER PT J AU HARPER, JW ELLEDGE, SJ KEYOMARSI, K DYNLACHT, B TSAI, LH ZHANG, PM DOBROWOLSKI, S BAI, C CONNELLCROWLEY, L SWINDELL, E FOX, MP WEI, N AF HARPER, JW ELLEDGE, SJ KEYOMARSI, K DYNLACHT, B TSAI, LH ZHANG, PM DOBROWOLSKI, S BAI, C CONNELLCROWLEY, L SWINDELL, E FOX, MP WEI, N TI INHIBITION OF CYCLIN-DEPENDENT KINASES BY P21 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CELL-CYCLE; RETINOBLASTOMA PROTEIN; SUBUNIT AB p21(Cip1) is a cyclin-dependent kinase (Cdk) inhibitor that is transcriptionally activated by p53 in response to DNA damage. We have explored the interaction of p21 with the currently known Cdks. p21 effectively inhibits Cdk2, Cdk3, Cdk4, and Cdk6 kinases (K-i 0.5-15 nM) but is much less effective toward Cdc2/cyclin B (K-i similar to 400 nM) and Cdk5/p35 (K-i > 2 mu M), and does not associate with Cdk7/cyclin H. Overexpression of p21 arrests cells in G1. Thus, p21 is not a universal inhibitor of Cdks but displays selectivity for G1/S Cdk/cyclin complexes. Association of p21 with Cdks is greatly enhanced by cyclin binding. This property is shared by the structurally related inhibitor p27, suggesting a common biochemical mechanism for inhibition. With respect to Cdk2 and Cdk4 complexes, p27 shares the inhibitory potency of p21 but has slightly different kinase specificities. In normal diploid fibroblasts, the vast majority of active Cdk2 is associated with p21, but this active kinase can be fully inhibited by addition of exogenous p21. Reconstruction experiments using purified components indicate that multiple molecules of p21 can associate with Cdk/cyclin complexes and inactive complexes contain more than one molecule of p21. Together, these data suggest a model whereby p21 functions as an inhibitory buffer whose levels determine the threshold kinase activity required for cell cycle progression. C1 BAYLOR COLL MED,VERNA & MARRS MCLEAN DEPT BIOCHEM,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MOLEC & HUMAN GENET,HOUSTON,TX 77030. BAYLOR COLL MED,HOWARD HUGHES MED INST,HOUSTON,TX 77030. MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC ONCOL LAB,BOSTON,MA 02129. NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,ALBANY,NY 12201. OI Swindell, Eric/0000-0002-1193-8200 FU NIA NIH HHS [AG-11085] NR 38 TC 756 Z9 771 U1 0 U2 8 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD APR PY 1995 VL 6 IS 4 BP 387 EP 400 PG 14 WC Cell Biology SC Cell Biology GA QW446 UT WOS:A1995QW44600003 PM 7626805 ER PT J AU MCGEHEE, RE HABENER, JF AF MCGEHEE, RE HABENER, JF TI DIFFERENTIATION-SPECIFIC ELEMENT-BINDING PROTEIN (DSEB) BINDS TO A DEFINED ELEMENT IN THE PROMOTER OF THE ANGIOTENSINOGEN GENE REQUIRED FOR THE IRREVERSIBLE INDUCTION OF GENE-EXPRESSION DURING DIFFERENTIATION OF 3T3-L1 ADIPOBLASTS TO ADIPOCYTES SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID REPLICATION FACTOR-C; TRANSCRIPTIONAL REGULATION; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; DNA-REPLICATION; CLONING; CELLS; ENHANCER; KINASES; LIGASE AB The differentiation-specific element (DSE) is a cis-acting transcriptional element located at nucleotide -1000 in the 5'-flanking promoter of the angiotensinogen gene. It is required for the irreversible and sustained increase in transcription of the angiotensinogen gene that occurs during differentiation of 3T3-L1 adipoblasts into adipocytes induced by a 3-day hormonal pulse. We report here the cloning of 3T3-L1 adipocyte cDNA encoding a 150 kilodalton protein designated Differentiation Specific Element Binding Protein (DSEB) that exhibits sequence-specific binding to a DSE oligonucleotide. Two DSEB mRNAs (3.6 and 4.2 kilobases) are observed in adipose, brain, kidney, testis, liver, and lung. Both DSEB mRNA and protein are induced during, and remain elevated after, 3T3-L1 cell adipogenesis. Analysis of adipoblasts by immunocytochemistry with an antiserum directed to bacterial expressed DSEB reveals that DSEB is localized to the nucleus and is induced during differentiation. DNA-binding assays show that binding is specific and exhibits high affinity and specificity for the DSE. Deletional analyses of bacterial expressed recombinant DSEB identifies a DNA-binding domain of 120 amino acids that contains two predicted helical regions. A sequence of 72 amino acids within the DNA-binding domain of DSEB is 60% identical to domains found in the sequences of several bacterial ligases. Further, DSEB is homologous to several proteins reported recently that are proposed to be a component(s) of the DNA replication-C complex raising the possibility that DSEB may be both a transcription factor and a DNA-replication factor. C1 MASSACHUSETTS GEN HOSP, HOWARD HUGHES MED INST, MOLEC ENDOCRINOL LAB, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. NR 46 TC 20 Z9 20 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD APR PY 1995 VL 9 IS 4 BP 487 EP 501 DI 10.1210/me.9.4.487 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QT366 UT WOS:A1995QT36600012 PM 7659092 ER PT J AU JAIN, RK JANDA, KD SALTZMAN, WM AF JAIN, RK JANDA, KD SALTZMAN, WM TI DRUG DISCOVERY AND DELIVERY - EXPLOITING BIOLOGICAL DIVERSITY - LIBRARIES AND MUTATIONS FOR RESEARCH AND DRUG DEVELOPMENT, LA-JOLLA, CA, USA, 26-27 JANUARY 1995 - DRUG-DELIVERY - BARRIERS TO DRUG TRANSPORT AND THE DESIGN OF NOVEL THERAPEUTIC TARGETS, HILTON HEAD ISLAND, SC, USA, 7-13 JANUARY 1995 SO MOLECULAR MEDICINE TODAY LA English DT Editorial Material C1 Scripps Res Inst, DEPT CHEM, LA JOLLA, CA 92037 USA. SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA. JOHNS HOPKINS UNIV, DEPT CHEM ENGN, BALTIMORE, MD 21218 USA. RP JAIN, RK (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT RADIAT ONCOL, FRUIT ST, BOSTON, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD APR PY 1995 VL 1 IS 1 BP 4 EP 4 DI 10.1016/1357-4310(95)80005-0 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RP374 UT WOS:A1995RP37400008 PM 9415129 ER PT J AU SCHNEIDER, KA PATENAUDE, AF GARBER, JE AF SCHNEIDER, KA PATENAUDE, AF GARBER, JE TI TESTING FOR CANCER GENES - DECISIONS, DECISIONS SO NATURE MEDICINE LA English DT Editorial Material ID OVARIAN-CANCER; GENETICS; BREAST; SUSCEPTIBILITY; PHYSICIANS; KNOWLEDGE RP SCHNEIDER, KA (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 13 TC 8 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 1995 VL 1 IS 4 BP 302 EP 303 DI 10.1038/nm0495-302 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RN098 UT WOS:A1995RN09800022 PM 7585056 ER PT J AU LANDAU, WM DAUBE, JR AMINOFF, MJ BREY, RL BROOKS, BR DEUEL, RK GALABURDA, AM PORTER, JA ROSENBAUM, RB WHITHAM, RH WIGGS, JW AF LANDAU, WM DAUBE, JR AMINOFF, MJ BREY, RL BROOKS, BR DEUEL, RK GALABURDA, AM PORTER, JA ROSENBAUM, RB WHITHAM, RH WIGGS, JW TI NEUROREALITY .1. DEDICATED DEMOLITION OF THE DECADE OF THE BRAIN - THE GENUINE THREAT TO NEUROLOGIC RESEARCH FROM THE ANIMAL RADICAL RIGHT SO NEUROLOGY LA English DT Editorial Material C1 WASHINGTON UNIV,SCH MED,DEPT NEUROL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT PEDIAT,ST LOUIS,MO 63110. MAYO CLIN & MAYO FDN,DEPT NEUROL,ROCHESTER,MN 55905. UNIV CALIF SAN FRANCISCO,DEPT NEUROL,SAN FRANCISCO,CA 94143. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV WISCONSIN HOSP & CLIN,WILLIAM S MIDDLETON MEM VET ADM HOSP,NEUROL SERV,MADISON,WI 53792. BETH ISRAEL HOSP,BEHAV NEUROL UNIT,BOSTON,MA 02215. OREGON HLTH SCI UNIV,DEPT NEUROL,PORTLAND,OR 97201. NR 0 TC 4 Z9 4 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 APR PY 1995 VL 45 IS 4 BP 609 EP 610 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA QT454 UT WOS:A1995QT45400002 PM 7723943 ER PT J AU BEJAOUI, K HIRABAYASHI, K HENTATI, F HAINES, JL BENHAMIDA, C BELAL, S MILLER, RG MCKENNAYASEK, D WEISSENBACH, J ROWLAND, LP GRIGGS, RC MUNSAT, TL BENHAMIDA, M ARAHATA, K BROWN, RH AF BEJAOUI, K HIRABAYASHI, K HENTATI, F HAINES, JL BENHAMIDA, C BELAL, S MILLER, RG MCKENNAYASEK, D WEISSENBACH, J ROWLAND, LP GRIGGS, RC MUNSAT, TL BENHAMIDA, M ARAHATA, K BROWN, RH TI LINKAGE OF MIYOSHI MYOPATHY (DISTAL AUTOSOMAL RECESSIVE MUSCULAR-DYSTROPHY) LOCUS TO CHROMOSOME 2P12-14 SO NEUROLOGY LA English DT Article ID RIMMED VACUOLE FORMATION; ONSET; DISEASE AB Miyoshi myopathy (MM) is a young-adult-onset, autosomal recessive distal muscular dystrophy initially affecting the plantar flexors. We analyzed 12 MM families, five with consanguineous marriage, for chromosomal linkage using polymorphic microsatellite DNA markers to map the MM gene. A significant lod score was obtained with the 2p12-14 locus D2S291 (Z(max) = 15.3 at theta = 0). Two additional 2p12-14 markers, D2S286 (Z = 10.7 at theta = 0) and D2S292 (Z = 7.2 at theta = 0.05), also gave significant lod scores. These markers will be useful for diagnosis of symptomatic and presymptomatic patients, prenatal and carrier diagnosis of family members carrying MM, and ultimately identification of a gene responsible for MM. C1 MASSACHUSETTS GEN HOSP,DAY NEUROMUSCULAR RES LAB,BOSTON,MA 02114. NCNP,NATL INST NEUROSCI,DEPT NEUROMUSCULAR RES,TOKYO,JAPAN. NCNP,NATL INST NEUROSCI,DEPT CELL BIOL,TOKYO,JAPAN. INST NATL NEUROL,TUNIS,TUNISIA. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. CALIF PACIFIC MED CTR,GERALDINE BRUSH CANC RES INST,DEPT NEUROL,SAN FRANCISCO,CA 94115. COLUMBIA UNIV,DEPT NEUROL,NEW YORK,NY 10027. UNIV ROCHESTER,MED CTR,DEPT NEUROL,ROCHESTER,NY 14642. TUFTS UNIV,NEW ENGLAND MED CTR,DEPT NEUROL,BOSTON,MA 02111. RI Haines, Jonathan/C-3374-2012 FU NINDS NIH HHS [NS24279] NR 30 TC 129 Z9 129 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 APR PY 1995 VL 45 IS 4 BP 768 EP 772 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA QT454 UT WOS:A1995QT45400028 PM 7723968 ER PT J AU KANTER, DS HORENSKY, D SPERLING, RA KAPLAN, JD MALACHOWSKI, ME CHURCHILL, WH AF KANTER, DS HORENSKY, D SPERLING, RA KAPLAN, JD MALACHOWSKI, ME CHURCHILL, WH TI PLASMAPHERESIS IN FULMINANT ACUTE DISSEMINATED ENCEPHALOMYELITIS SO NEUROLOGY LA English DT Note AB We describe two patients with fulminant acute disseminated encephalomyelitis (ADEM) treated with plasmapheresis after they failed to improve on steroids. Both patients improved concomitant with the plasma exchange. These are the first reported cases of fulminant ADEM with extensive white matter abnormalities on imaging studies treated with a regimen of plasmapheresis and steroids. Plasmapheresis may be beneficial in this disorder. C1 BRIGHAM & WOMENS HOSP,NEUROL NEUROSURG INTENS CARE UNIT,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA. BRIGHAM & WOMENS HOSP,DIV PATHOL,BOSTON,MA 02115. SPAULDING REHAB HOSP,DEPT NEUROL,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP KANTER, DS (reprint author), BRIGHAM & WOMENS HOSP,DIV NEUROL,75 FRANCIS ST,BOSTON,MA 02115, USA. OI Kanter, Daniel/0000-0003-4929-4890 NR 10 TC 98 Z9 100 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 1995 VL 45 IS 4 BP 824 EP 827 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA QT454 UT WOS:A1995QT45400039 PM 7723979 ER PT J AU WELSH, DK LOGOTHETIS, DE MEISTER, M REPPERT, SM AF WELSH, DK LOGOTHETIS, DE MEISTER, M REPPERT, SM TI INDIVIDUAL NEURONS DISSOCIATED FROM RAT SUPRACHIASMATIC NUCLEUS EXPRESS INDEPENDENTLY PHASED CIRCADIAN FIRING RHYTHMS SO NEURON LA English DT Article ID CULTURED NEURONS; VASOPRESSIN RELEASE; HYPOTHALAMIC SLICE; ACTION-POTENTIALS; MAMMALIAN RETINA; INVITRO; CELLS; CLOCK; GABA; NEUROTRANSMITTER AB Within the mammalian hypothalamus, the suprachiasmatic nucleus (SCN) contains a circadian clock for timing of diverse neuronal, endocrine, and behavioral rhythms. By culturing cells from neonatal rat SCN on fixed microelectrode arrays, we have been able to record spontaneous action potentials from individual SCN neurons for days or weeks, revealing prominent circadian rhythms in firing rate. Despite abundant functional synapses, circadian rhythms expressed by neurons in the same culture are not synchronized. After reversible blockade of neuronal firing lasting 2.5 days, circadian firing rhythms re-emerge with unaltered phases. These data suggest that the SCN contains a large population of autonomous, single-cell circadian oscillators, and that synapses formed in vitro are neither necessary for operation of these oscillators nor sufficient for synchronizing them. C1 HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. CHILDRENS HOSP,DIV CARDIOL,BOSTON,MA 02115. HARVARD UNIV,DEPT MOLEC & CELLULAR BIOL,CAMBRIDGE,MA 02138. RP WELSH, DK (reprint author), MASSACHUSETTS GEN HOSP,DEV CHRONOBIOL LAB,BOSTON,MA 02114, USA. RI Welsh, David/G-2277-2011 NR 58 TC 879 Z9 896 U1 2 U2 42 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD APR PY 1995 VL 14 IS 4 BP 697 EP 706 DI 10.1016/0896-6273(95)90214-7 PG 10 WC Neurosciences SC Neurosciences & Neurology GA QU826 UT WOS:A1995QU82600004 PM 7718233 ER PT J AU NATHANSON, JA SCAVONE, C SCANLON, C MCKEE, M AF NATHANSON, JA SCAVONE, C SCANLON, C MCKEE, M TI THE CELLULAR NA+ PUMP AS A SITE OF ACTION FOR CARBON-MONOXIDE AND GLUTAMATE - A MECHANISM FOR LONG-TERM MODULATION OF CELLULAR-ACTIVITY SO NEURON LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE; GUANYLATE-CYCLASE; HEME OXYGENASE; ENZYMATIC-PROPERTIES; SODIUM-PUMP; CYCLIC-GMP; ACTIVATION; RECEPTORS; LOCALIZATION AB Carbon monoxide (CO) induces a long-lasting alteration in cerebellar alpha 3-Na,K-ATPase independent of [Na+] but linked to cGMP synthesis and localized to Purkinje neurons. The action of CO is absent in Purkinje neuron-deficient mice, mimicked by 8-Br-cGMP, and blocked by inhibition of PKG. Glutamate (Glu) and metabotropic agonists mimic the action of CO, an effect that requires PKC and is associated with CO synthesis. These data suggest that CO regulates Na,K-ATPase through cGMP and PKG, and that Glu regulates CO through mGluRs. This system is also modulated by NMDA agonists and nitric oxide, possibly via Glu release, as well as by free radicals. These findings offer a mechanism by which CO, Glu, and free radicals can exert specific effects on synaptic transmission (relevant to long-term changes in cell excitability), as well as more general actions on energy metabolism (relevant to the pathophysiology of excitotoxicity). C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. RP NATHANSON, JA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROPHARMACOL RES LAB,CNY-6,BOSTON,MA 02114, USA. OI Scavone, Cristoforo/0000-0002-1206-0882 FU PHS HHS [NEI 05077] NR 51 TC 111 Z9 115 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD APR PY 1995 VL 14 IS 4 BP 781 EP 794 DI 10.1016/0896-6273(95)90222-8 PG 14 WC Neurosciences SC Neurosciences & Neurology GA QU826 UT WOS:A1995QU82600012 PM 7718240 ER PT J AU COLE, RL KONRADI, C DOUGLASS, J HYMAN, SE AF COLE, RL KONRADI, C DOUGLASS, J HYMAN, SE TI NEURONAL ADAPTATION TO AMPHETAMINE AND DOPAMINE - MOLECULAR MECHANISMS OF PRODYNORPHIN GENE-REGULATION IN RAT STRIATUM SO NEURON LA English DT Article ID FREELY MOVING RATS; KAPPA-OPIOID RECEPTORS; NUCLEUS-ACCUMBENS; CYCLIC-AMP; C-FOS; INVIVO MICRODIALYSIS; DIFFERENTIAL EXPRESSION; BINDING PROTEIN; COCAINE; RELEASE AB Induction of prodynorphin gene expression by psychostimulant drugs may re present a compensatory adaptation to excessive dopamine stimulation and may contribute to the aversive aspects of withdrawal. We therefore investigated the molecular mechanisms by which dopamine psychostimulant drugs induce prodynorphin gene expression in vivo and in rat primary striatal cultures. We demonstrate that three recently described cAMP response elements (CREs), rather than a previously reported noncanonical AP-1 site, are critical for dopamine induction of the prodynorphin gene in striatal neurons. CRE-binding protein (CREB) binds to these CREs in striatal cell extracts and is phosphorylated on Ser-133 after dopamine stimulation in a D1 dopamine receptor-dependent manner. Surprisingly, following chronic administration of amphetamine, revels of phosphorylated CREB are increased above basal in rat striatum in vivo, whereas c-fos mRNA is suppressed below basal levels. D1 receptor-mediated CREB phosphorylation appears to mediate adaptations to psychostimulant drugs in the striatum. C1 HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02114. OREGON HLTH SCI UNIV,VOLLUM INST,PORTLAND,OR 97201. RP COLE, RL (reprint author), MASSACHUSETTS GEN HOSP,MOLEC & DEV NEUROSCI LAB,CNY-2,BOSTON,MA 02129, USA. FU NIDA NIH HHS [DA07282, DA07134, R01 DA007134, R01 DA007134-12, T32 DA007282]; NIMH NIH HHS [MH44160] NR 57 TC 281 Z9 291 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD APR PY 1995 VL 14 IS 4 BP 813 EP 823 DI 10.1016/0896-6273(95)90225-2 PG 11 WC Neurosciences SC Neurosciences & Neurology GA QU826 UT WOS:A1995QU82600015 PM 7718243 ER PT J AU BAUMAN, ML KEMPER, TL ARIN, DM AF BAUMAN, ML KEMPER, TL ARIN, DM TI MICROSCOPIC OBSERVATIONS OF THE BRAIN IN RETT-SYNDROME SO NEUROPEDIATRICS LA English DT Article; Proceedings Paper CT International Rett Symposium - Molecular and Neurobiology Aspects of Rett Syndrome CY OCT 01, 1994 CL PORTLAND, OR DE RETT SYNDROME; NEUROPATHOLOGY; BRAIN DEVELOPMENT ID NEUROPATHOLOGY AB Rett syndrome (RS) is a clinically defined disorder which appears to be unique to females and which is associated with apparent loss of cognitive and motor skills early in life. Using the technique of gapless serial section, microscopic analysis of the brains from three cases of RS and identically processed age-matched controls was conducted to determine the nature and extent of cerebral abnormality in this disorder. Small neuronal cell size and increased cell packing density were observed throughout the brain in all three cases, without evidence of gliosis or active degeneration. These findings are consistent with a curtailment of brain development which may begin before birth. Further, the brain abnormalities in RS appear to be more diffuse than previously appreciated and are in accord with the widespread neurological symptoms characteristic of this disorder. C1 BOSTON CITY HOSP,DEPT NEUROL,BOSTON,MA 02118. MASSACHUSETTS INST ALLIED HLTH PROFESS,BOSTON,MA 02114. RP BAUMAN, ML (reprint author), MASSACHUSETTS GEN HOSP,CHILDRENS NEUROL SERV,BOSTON,MA 02114, USA. FU NICHD NIH HHS [HD 24448-04] NR 25 TC 72 Z9 72 U1 0 U2 1 PU HIPPOKRATES VERLAG GMBH PI STITTGART PA PO BOX 30 05 04 RUDIGERSTRASSE 14, 70469 STITTGART, GERMANY SN 0174-304X J9 NEUROPEDIATRICS JI Neuropediatrics PD APR PY 1995 VL 26 IS 2 BP 105 EP 108 DI 10.1055/s-2007-979737 PG 4 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA RE344 UT WOS:A1995RE34400016 PM 7566446 ER PT J AU PAKZABAN, P DEACON, TW BURNS, LH DINSMORE, J ISACSON, O AF PAKZABAN, P DEACON, TW BURNS, LH DINSMORE, J ISACSON, O TI A NOVEL MODE OF IMMUNOPROTECTION OF NEURAL XENOTRANSPLANTS - MASKING OF DONOR MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I ENHANCES TRANSPLANT SURVIVAL IN THE CENTRAL-NERVOUS-SYSTEM SO NEUROSCIENCE LA English DT Article ID RAT-BRAIN; IMMUNOLOGICAL ASPECTS; ALLOGRAFT-REJECTION; MONOCLONAL-ANTIBODY; PARKINSONS-DISEASE; ANTIGEN EXPRESSION; TRANSGENIC MICE; IMMUNE-RESPONSE; 3RD VENTRICLE; CELL-ADHESION AB To determine the role of major histocompatibility complex (MHC) class I in immunological rejection of neural xenotransplants, F(ab')(2) fragments of a monoclonal antibody to porcine MHC class I were used to mask this complex on porcine fetal striatal cells transplanted into rat striata previously lesioned with quinolinic acid. Presence of MHC class I on the surface of porcine striatal cells was confirmed by fluorescence-activated cell sorting prior to F(ab')(2) treatment. At three to four months post-transplantation, survival of F(ab')(2)-treated xenografts was assessed by means of donor-specific immunostaining and compared to that of untreated xenografts in non-immunosuppressed rats and in rats immunosuppressed with cyclosporine A. In this study, masking of donor MHC class I by F(ab')(2) treatment resulted in enhanced xenografts Survival compared to the non-immunosuppressed controls (graft survival rates, 52% and 7%, respectively; P < 0.005) at survival:times up to four months. While xenograft survival in F(ab')(2)-treated animals was not significantly different from that in cyclosporine-treated rats (74% graft survival), mean graft volume in F(ab')(2)-treated animals was smaller than that in cyclosporine-treated animals (1.07 +/- 0.30 mm(3) versus 3.14 +/- 0.51 mm(3); P < 0.005). The cytoarchitectonic organization of the xenografts was similar in F(ab')(2)- and cyclosporine-treated animals, and grafts in both groups exhibited long distance target-directed axonal outgrowth. The pattern of immunoreactivity to porcine MHC class I in the xenografts corresponded to the regional distribution of donor glia. In xenografts undergoing rejection, infiltration with host inflammatory cells was restricted to necrotic graft remnants and spared the nearby host structures. We conclude that MHC class-I-restricted immune mechanisms Play an important role in neural xenograft rejection and that masking of this complex on donor cells may provide a useful strategy for immunoprotection of neural xenografts. C1 MCLEAN HOSP, NEUROGENERAT LAB, BELMONT, MA 02178 USA. MASSACHUSETTS GEN HOSP, NEUROSURG SERV, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, NEUROL SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02114 USA. DIACRIN INC, BOSTON, MA 02129 USA. FU NINDS NIH HHS [NS30064, 5T32 NS07340, NS29178] NR 54 TC 84 Z9 86 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD APR PY 1995 VL 65 IS 4 BP 983 EP 996 DI 10.1016/0306-4522(94)00626-G PG 14 WC Neurosciences SC Neurosciences & Neurology GA QR297 UT WOS:A1995QR29700007 PM 7617173 ER PT J AU KONRADI, C HECKERS, S AF KONRADI, C HECKERS, S TI HALOPERIDOL-INDUCED FOS EXPRESSION IN STRIATUM IS DEPENDENT UPON TRANSCRIPTION FACTOR CYCLIC-AMP RESPONSE ELEMENT-BINDING PROTEIN SO NEUROSCIENCE LA English DT Article ID NUCLEAR FACTOR CREB; C-FOS; RAT STRIATUM; MESSENGER-RNA; DIFFERENTIAL EXPRESSION; DOPAMINE-RECEPTORS; SOMATOSTATIN GENE; MOLECULAR-CLONING; PHOSPHORYLATION; D1 AB Haloperidol has been shown to induce rapid and transient expression of c-fos messenger RNA and Fos protein in striatal neurons via dopamine D-2 receptors. Regulation of the c-fos gene by cyclic AMP and Ca2+ has been shown to be dependent on a DNA regulatory element within its promoter that binds the constitutively expressed transcription factor cyclic AMP response element binding protein. Cyclic AMP response element binding protein binds to an oligonucleotide containing the calcium/cyclic AMP response element of the c-fos promoter sequence in striatal cell extracts; the amount of binding is not regulated by haloperidol treatment. We have previously shown that haloperidol induces cyclic AMP response element binding protein phosphorylation in the striatum. Here we show by intrastriatal injection of antisense oligonucleotides that haloperidol-induced Fos expression is dependent on cyclic AMP response element binding protein. Intrastriatal injections of phosphorothioate oligonucleotides, in antisense orientation to cyclic AMP response element binding protein messenger RNA, reduce levels of cyclic AMP response element binding protein and completely prevent haloperidol-mediated induction of Fos. Oligonucleotides in sense orientation have no such effect. We observed a markedly different time course of the Fos protein inhibition by cyclic AMP response element binding protein antisense oligonucleotides compared to c-fos antisense oligonucleotides. This most likely reflects the different half-lives of c-fos and cyclic AMP response element binding protein messenger RNA and proteins. Neither cyclic AMP response element binding protein nor c-fos antisense oligonucleotide injection reduced c-Jun immunostaining in the striatum. We conclude that haloperidol induces Fos via transcription factor cyclic AMP response element binding protein. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP KONRADI, C (reprint author), MASSACHUSETTS GEN HOSP,MOLEC & DEV NEUROSCI LAB,CNY 2,149 13TH ST,BOSTON,MA 02129, USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 44 TC 54 Z9 54 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR PY 1995 VL 65 IS 4 BP 1051 EP 1061 DI 10.1016/0306-4522(94)00546-H PG 11 WC Neurosciences SC Neurosciences & Neurology GA QR297 UT WOS:A1995QR29700012 PM 7617161 ER PT J AU YAMAKAWA, K PETERSON, JW SIBILIA, R ZERVAS, NT AF YAMAKAWA, K PETERSON, JW SIBILIA, R ZERVAS, NT TI EFFECT OF VASOCONSTRICTOR AGENTS ON DIACYLGLYCEROL CONTENT OF NORMAL AND VASOSPASTIC CANINE BASILAR ARTERIES IN-VITRO SO NEUROSURGERY LA English DT Article DE CEREBRAL ARTERY; CEREBRAL VASOSPASM; DIACYLGLYCEROL; VASOPRESSORS ID PROTEIN-KINASE-C; VASCULAR SMOOTH-MUSCLE; SWISS 3T3 CELLS; ANGIOTENSIN-II; HYPERTENSIVE RATS; PHOSPHATIDIC-ACID; GROWTH-FACTOR; CONTRACTION; CALCIUM; 1,2-DIACYLGLYCEROL AB A CAUSAL OR supportive relationship between 1,2-diacylglycerol (DAG) content and the maintenance of tonic vasoconstriction was sought in canine basilar arteries treated in vitro with various agents reported to increase DAG levels in other tissues (platelet-derived growth factor, vasopressin, angiotensin II, and endothelin-1) and, conversely, with agents known to activate sustained constriction (high K+, phorbol ester, hemolysate, and endothelin-1). Multiple segments from individual isolated arteries were prepared. Some segments were immediately frozen as controls and others incubated in physiological saline solution at 37 degrees C for either 5 minutes or 30 minutes in the presence or absence of different concentrations of the test materials, Segments were then quickly frozen until homogenized for lipid extraction and DAG assay. The DAG content of samples incubated up to 2 hours in physiological saline solution alone did not significantly differ from that of immediately frozen control samples. Resting DAG content expressed relative to total protein measured in each sample averaged 3.82 +/- 0.26 (standard error of the mean) pmol DAG/mu g of protein (74 samples from 37 arteries). Endothelin at 2 x 10(-7) mol/L led to a statistically significant increase in DAG content of approximately 40% of basal content at 5 and 30 minutes. A smaller increase in DAG attributable to hemolysate (similar to 25%) was statistically significant at 30 minutes, whereas vasopressin provoked a notable decrease in DAG content. The other agents had no effect. No differences in these results were noted between normal canine basilar arteries and arteries constricted in vivo by subarachnoid blood clot before isolation. The observed increases in DAC content with endothelin and hemolysate may be large enough to play a role in promoting sustained vasoconstriction. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. FU NHLBI NIH HHS [HL44554, HL22573] NR 37 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD APR PY 1995 VL 36 IS 4 BP 789 EP 796 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA QQ369 UT WOS:A1995QQ36900064 PM 7596511 ER PT J AU FRIM, DM OGILVY, CS AF FRIM, DM OGILVY, CS TI MUTISM AND CEREBELLAR DYSARTHRIA AFTER BRAIN-STEM SURGERY - CASE-REPORT SO NEUROSURGERY LA English DT Note DE CASE REPORT; CEREBELLAR DYSARTHRIA; MUTISM; PENS; POSTOPERATIVE AB TRANSIENT MUTISM RESOLVING to cerebellar speech after posterior fossa surgery is a well-recognized phenomenon, particularly in pediatric patients. The anatomic basis for this postoperative functional change is unclear but may reside in the dominant superior cerebellar hemisphere or the medial deep cerebellar nuclei. We report a case of an 8-year-old girl who presented for surgical resection of a cavernous malformation of the right pens (at the level of the middle cerebellar peduncle) after hemorrhage. Preoperatively, her complaints consisted of contralateral motor deficits. She had normal speech. Her lesion was resected through a subtemporal approach to the pens. She awoke unable to speak. She was able to communicate through a variety of verbal cues, including sign language. Her mutism lasted 12 days after which she underwent a prolonged period of slowly resolving cerebellar dysarthria. Her preoperative motor deficits also slowly resolved. This is the first reported case of mutism resolving to cerebellar dysarthria after a supratentorial approach to the brain stem. We discuss the anatomic basis for postoperative mutism in light of previous observations combined with the unusual finding of mutism after pontine surgery. In particular, reports of mutism after bilateral cerebellar hemispheric injury, bilateral or unilateral medial deep nuclear injury, and, now, pontine tegmental injury implicate the superior cerebellar hemispheres, the deep cerebellar nuclei, and the nuclear outflow through the superior cerebellar peduncle as the anatomic bases for cerebellar participation in the production of human speech. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. NR 11 TC 62 Z9 62 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD APR PY 1995 VL 36 IS 4 BP 854 EP 857 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA QQ369 UT WOS:A1995QQ36900095 PM 7596521 ER PT J AU TUGALTUTKUN, I AKOVA, YA FOSTER, CS AF TUGALTUTKUN, I AKOVA, YA FOSTER, CS TI PENETRATING KERATOPLASTY IN CICATRIZING CONJUNCTIVAL DISEASES SO OPHTHALMOLOGY LA English DT Article ID STEVENS-JOHNSON SYNDROME; TOXIC EPIDERMAL NECROLYSIS; ERYTHEMA MULTIFORME; KERATITIS AB Purpose: The outcome of successful penetrating keratoplasty (PK) typically is poor in eyes with end-stage chronic cicatrizing conjunctival diseases such as ocular cicatricial pemphigoid (OCP), Stevens-Johnson syndrome, and toxic epidermal necrolysis due to immunologically driven conjunctival inflammation associated with conjunctival cicatrization and lid abnormalities, severe dry eye, and extensive corneal neovascularization. The authors report the results of their experience with PK in 13 patients with OCP, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Methods: The authors reviewed the records of patients with OCP, Stevens-Johnson syndrome, or toxic epidermal necrolysis seen between 1976 and 1992. Patients who underwent PK were examined for the purpose of this study. Initial and final visual acuity, indications for PK, surgical procedure, postoperative therapy, complications, total number of repeat PKs, length of follow-up, and the final outcome were recorded. Results: Thirty-two PKs were performed in 16 eyes of 13 patients with advanced OCP (6 patients), OCP as a sequels of Stevens-Johnson syndrome (2 patients), Stevens-Johnson syndrome (3 patients), and toxic epidermal necrolysis (2 patients). The indications for the first PK were corneal perforation in six eyes (37.5%) and extensive corneal scarring in ten eyes (62.5%). Preoperative visual acuity was counting fingers in five eyes, hand motions in eight, and light perception in three. Preoperative therapy included systemic chemotherapy (8 patients), mucous membrane grafting (9 eyes), lamellar keratoplasty (2 eyes), superficial keratectomy (1 eye), and corneal dye laser photocoagulation (6 eyes). The mean follow-up period was 4.6 years (3 months-13 years). Eight eyes (50%) had clear grafts, and three eyes (18.7%) had 20/200 or better visual acuity at last visit. The major causes of graft failure were epithelial defect formation/persistence, stromal ulceration, perforation, and graft rejection. Conclusions: These results indicate that PK may be performed for tectonic reasons, but prospects for restoration of sight in patients with advanced cicatrizing conjunctival diseases, even after extensive preoperative medical and surgical therapy, are limited. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. ISTANBUL FAC MED,DEPT OPHTHALMOL,ISTANBUL,TURKEY. NR 20 TC 68 Z9 69 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 1995 VL 102 IS 4 BP 576 EP 585 PG 10 WC Ophthalmology SC Ophthalmology GA QR300 UT WOS:A1995QR30000014 PM 7724175 ER PT J AU REMULLA, HD RUBIN, PAD SHORE, JW SUTULA, FC TOWNSEND, DJ WOOG, JJ JAHRLING, KV AF REMULLA, HD RUBIN, PAD SHORE, JW SUTULA, FC TOWNSEND, DJ WOOG, JJ JAHRLING, KV TI COMPLICATIONS OF POROUS SPHERICAL ORBITAL IMPLANTS SO OPHTHALMOLOGY LA English DT Article ID CORALLINE HYDROXYAPATITE; POLYETHYLENE; ENUCLEATION AB Purpose: To determine the complications observed with using porous spherical orbital implants (hydroxyapatite and porous polyethylene) and the factors leading to their occurrence. Methods: A total of 101 cases of porous spherical orbital implantation by five ophthalmic surgeons were reviewed retrospectively. The demographic data, diagnosis, prior surgery, type and technique of surgery, implant characteristics and prosthesis fitting were described in patients with complications. Results: Eleven of the 101 patients had implant exposure. There were six male (1 with bilateral involvement) and four female patients, ranging in age from 2 to 71 years. Preoperative diagnosis included trauma in five patients, nontrauma in five, and tumor in one. Seven had prior eye surgeries. Three patients underwent evisceration, whereas eight underwent enucleation. Eight hydroxyapatite and three porous polyethylene implants were used with diameters of 16 to 20 mm. Three were unwrapped, six were wrapped in sclera, and two were wrapped in preserved fascia. Exposures, which generally occurred within 1 year, were grouped into small (1-5 mm), medium (6-10 mm), and large (>10 mm). One delayed case occurred after drilling. Small stable exposures were managed conservatively. Larger exposures were managed either by implant revision or replacement. All patients were fit ultimately with a prosthesis. Histopathologic findings of explanted spheres showed fibrovascularization limited to the periphery with moderate inflammatory reaction. Conclusion: Complications were significantly higher in cases of eviscerations than enucleations. Complicatations occurred in implants either unwrapped or wrapped in homologous grafts. None of the autologous wrapping had exposure. Secondary procedures may initiate exposure when fibrovascular status of implant is inadequate. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,EYE PLAST & ORBIT SERV,BOSTON,MA 02114. NEW ENGLAND EYE CTR,EYE PLAST & ORBIT SERV,BOSTON,MA. JAHRLING OCULAR PROSTHET,BOSTON,MA. NR 30 TC 133 Z9 159 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 1995 VL 102 IS 4 BP 586 EP 593 PG 8 WC Ophthalmology SC Ophthalmology GA QR300 UT WOS:A1995QR30000015 PM 7536909 ER PT J AU FRIEDMAN, E KRUPSKY, S LANE, AM OAK, SS FRIEDMAN, ES EGAN, K GRAGOUDAS, ES AF FRIEDMAN, E KRUPSKY, S LANE, AM OAK, SS FRIEDMAN, ES EGAN, K GRAGOUDAS, ES TI OCULAR BLOOD-FLOW VELOCITY IN AGE-RELATED MACULAR DEGENERATION SO OPHTHALMOLOGY LA English DT Article ID BRUCH MEMBRANE; ANGIOGRAPHY AB Background: Changes in the structure of the ocular blood vessels associated with age-related macular degeneration (AMD) have been described in some detail, but comparatively little is known of the concomitant circulatory changes. The goal of this study is to evaluate changes in the ocular circulation that may be associated with AMD. Methods: Ocular blood flow velocities and vessel pulsatilities were measured in volunteers with and without AMD using a color Doppler imaging unit. Spectral analyses were recorded from the ophthalmic artery, central retinal artery and vein, the temporal and nasal short posterior ciliary arteries, and the four vortex veins. Results: Adjusting for age, pulsatility indices of all arteries were higher in subjects with AMD (central retinal artery [P = 0.02]; temporal and nasal short posterior ciliary arteries [P = 0.06 and 0.002, respectively]; and ophthalmic artery [P = 0.24]). End-diastolic blood flow velocity of the short posterior ciliary arteries tended to decrease in the presence of AMD. Conclusions: The combination of increased pulsatility and decreased velocity of the short posterior ciliary arteries, observed in the presence of AMD, are interpreted as evidence of increased vascular resistance. The clinical signs of AMD may be related to degradation of the metabolic transport function of the retinal pigment epithelium, resulting from impaired choroidal perfusion. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP FRIEDMAN, E (reprint author), MASSACHUSETTS EYE & EAR INFIRM,243 CHARLES ST,BOSTON,MA 02114, USA. NR 31 TC 167 Z9 173 U1 0 U2 6 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 1995 VL 102 IS 4 BP 640 EP 646 PG 7 WC Ophthalmology SC Ophthalmology GA QR300 UT WOS:A1995QR30000023 PM 7724181 ER PT J AU DELAMAZA, MS FOSTER, CS JABBUR, NS AF DELAMAZA, MS FOSTER, CS JABBUR, NS TI SCLERITIS ASSOCIATED WITH SYSTEMIC VASCULITIC DISEASES SO OPHTHALMOLOGY LA English DT Article ID RHEUMATOID-ARTHRITIS; NECROTIZING SCLERITIS; EPISCLERITIS; THERAPY AB Purpose: Scleritis may occur associated with systemic vasculitic diseases. The detection of systemic vasculitic diseases in patients with scleritis is a sign of poor general prognosis because it indicates potentially lethal systemic complications. This study was undertaken to analyze the ocular prognosis of patients with scleritis and the different systemic vasculitic diseases. Methods: Patient characteristics, scleritis type, and ocular complications were evaluated in 82 patients with scleritis with systemic vasculitic diseases; comparisons were made between patients with scleritis with a specific systemic vasculitic diseases and patients with scleritis with the other systemic vasculitic diseases. Results: Patients with scleritis with Wegener granulomatosis had more necrotizing scleritis (79%, P = 0.0001), decrease in vision (79%, P = 0.014), and peripheral ulcerative keratitis (50%, P = 0.0139) than patients with scleritis with the other systemic vasculitic diseases. Patients with scleritis with spondyloarthropathies had less decrease in vision (8%, P = 0.001) and peripheral ulcerative keratitis (0%, P = 0.0256) than patients with scleritis with the other systemic vasculitic diseases. Patients with scleritis and systemic lupus erythematosus had less necrotizing scleritis (0%, P = 0.0412) than patients with scleritis with the other systemic vasculitic diseases. Conclusions: Ocular prognosis of scleritis with systemic vasculitic diseases varies depending on the specific systemic vasculitic diseases: scleritis in spondyloarthropathies or in systemic lupus erythematosus is usually a benign and self-limiting condition, whereas scleritis in Wegener granulomatosis is a severe disease that can lead to permanent blindness; scleritis in rheumatoid arthritis or relapsing polychondritis is a disease of intermediate severity, which should be monitored closely for the development of ocular complications. C1 HARVARD UNIV, SCH MED, MASSACHUSETTS EYE & EAR INFIRM, OCULAR IMMUNOL SERV, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, MASSACHUSETTS EYE & EAR INFIRM, HILLES IMMUNOL LAB, BOSTON, MA 02115 USA. NR 19 TC 66 Z9 71 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 1995 VL 102 IS 4 BP 687 EP 692 PG 6 WC Ophthalmology SC Ophthalmology GA QR300 UT WOS:A1995QR30000028 PM 7724185 ER PT J AU SCHOEMAN, RJ ROSE, DL AF SCHOEMAN, RJ ROSE, DL TI DESTRUCTIVE GINGIVAL MASS SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Discussion C1 UNIV MINNESOTA,SCH DENT,DEPT ENDODONT,MINNEAPOLIS,MN 55455. UNIV CALIF LOS ANGELES,CTR HLTH SCI,SCH DENT,ORAL & MAXILLOFACIAL SURG SECT,LOS ANGELES,CA 90024. RP SCHOEMAN, RJ (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 9 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD APR PY 1995 VL 79 IS 4 BP 407 EP 409 DI 10.1016/S1079-2104(05)80118-0 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA QT453 UT WOS:A1995QT45300005 PM 7614196 ER PT J AU HIRSCHFELD, S MORRIS, BK AF HIRSCHFELD, S MORRIS, BK TI REVIEW - PAIN ASSOCIATED WITH HIV-INFECTION SO PEDIATRIC AIDS AND HIV INFECTION-FETUS TO ADOLESCENT LA English DT Review RP HIRSCHFELD, S (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 0 TC 5 Z9 5 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1045-5418 J9 PEDIATR AIDS HIV INF JI Pediatr. AIDS HIV Infect.-Fetus Adolesc. PD APR PY 1995 VL 6 IS 2 BP 63 EP 74 PG 12 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA QZ808 UT WOS:A1995QZ80800002 PM 11361383 ER PT J AU ARMENTANO, ME AF ARMENTANO, ME TI ASSESSMENT, DIAGNOSIS, AND TREATMENT OF THE DUALLY DIAGNOSED ADOLESCENT SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID SUBSTANCE-ABUSE; PSYCHIATRIC-DISORDERS; DRUG-ABUSE; CLINICAL IMPLICATIONS; MENTAL-DISORDERS; ALCOHOLISM ONSET; PRIMARY CARE; RISK-FACTORS; PSYCHOPATHOLOGY; COMORBIDITY AB Because many adolescents in treatment for substance abuse present with other psychiatric diagnoses, it is important to recognize the disorders that the physician is likely to see and to formulate an integrated treatment plan. This article presents guidelines for management and consultation. C1 MASSACHUSETTS GEN HOSP,CHILD & ADOLESCENT PSYCHIAT SERV,BOSTON,MA. MASSACHUSETTS GEN HOSP,ADDICT SERV,BOSTON,MA. NR 58 TC 6 Z9 6 U1 2 U2 2 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 APR PY 1995 VL 42 IS 2 BP 479 EP 490 PG 12 WC Pediatrics SC Pediatrics GA QT960 UT WOS:A1995QT96000018 PM 7724271 ER PT J AU PATRICE, SJ TARBELL, NJ GOUMNEROVA, LC SHRIEVE, DC BLACK, PM LOEFFLER, JS AF PATRICE, SJ TARBELL, NJ GOUMNEROVA, LC SHRIEVE, DC BLACK, PM LOEFFLER, JS TI RESULTS OF RADIOSURGERY IN THE MANAGEMENT OF RECURRENT AND RESIDUAL MEDULLOBLASTOMA SO PEDIATRIC NEUROSURGERY LA English DT Article DE MEDULLOBLASTOMA; RADIOSURGERY; RADIOTHERAPY ID INTRACRANIAL ARTERIOVENOUS-MALFORMATIONS; STANDARD LINEAR-ACCELERATOR; STEREOTAXIC RADIOSURGERY; RADIATION-THERAPY; BRAIN-TUMORS; PATTERNS AB Between June 1989 and January 1994, 14 patients with recurrent (n = 11) or posttreatment residual (n = 3) medulloblastoma were enrolled in a program to evalute the efficacy and toxicity of stereotactic radiosurgery (SR). Initial treatment consisted of subtotal surgical resection in 12 patients and complete surgical resection in 2. Thirteen patients received systemic chemotherapy, and all had craniospinal irradiation prior to SR. SR was used as a technique for boosting sites of posttreatment residual disease in 3 patients (3 tumors) and as salvage therapy in 11 patients (14 tumors) with radiographically well-defined, discrete recurrent tumors. Patients underwent SR 1-97 (median 20) months after completing craniospinal irradiation. The median minimum peripheral tumor dose was 12 Gy. The median tumor volume at the time of SR was 6.9 cm(3). With a median follow-up period from diagnosis of 27 (range 8-39) months, all patients treated with SR as a boost to sites of residual disease are alive without evidence of disease. In contrast, 6 of 11 patients who underwent SR for treatment of recurrent disease have died of progressive medulloblastoma. The median survival from the time of SR for patients treated for recurrent disease was 10 (range 5-59+) months. The predominant site of failure after SR was distant within the central nervous system, with 6 patients (43%) failing outside the posterior fossa. No patient failed locally within the radiosurgical target volume. Two patients (14%) developed marginal recurrences. There was one transient acute complication (within 7 days of SR), two subacute complications requiring corticosteroid therapy for less than 6 months, and one long-term complication directly attributable to SR. No patient required reoperation for symptomatic mass effect after SR. Our initial experience suggests that SR is capable of controlling small, locally recurrent medulloblastomas in the majority of the patients. SR alone, however, will not be curative treatment for most of these patients. The high incidence of distant central nervous system failures indicates that SR must be used in conjunction with aggressive systemic therapy in order to impove the survival of patients with recurrent disease. For patients with a newly diagnosed medulloblastoma, our preliminary results suggest that SR is a safe and effective adjunct to craniospinal irradiation in the initial management of selected patients. C1 CHILDRENS HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROSURG,BOSTON,MA 02115. HARVARD UNIV,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,CTR BRAIN TUMOR,BOSTON,MA 02115. HARVARD UNIV,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. FU NINDS NIH HHS [P20 NS31110] NR 18 TC 40 Z9 40 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1016-2291 J9 PEDIATR NEUROSURG JI Pediatr. Neurosurg. PD APR PY 1995 VL 22 IS 4 BP 197 EP 203 DI 10.1159/000120901 PG 7 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA QY559 UT WOS:A1995QY55900005 PM 7619720 ER PT J AU BABA, TW JEONG, YS PENNINCK, D BRONSON, R GREENE, MF RUPRECHT, RM AF BABA, TW JEONG, YS PENNINCK, D BRONSON, R GREENE, MF RUPRECHT, RM TI IMMUNE DYSFUNCTION OCCURS IN NEONATAL RHESUS-MONKEYS EXPOSED ORALLY TO LIVE ATTENUATED SIMIAN IMMUNODEFICIENCY VIRUS DELETED IN NEF, VPR AND NE SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, VIRAL PATHOGENESIS LAB, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. TUFTS UNIV, SCH MED, DEPT PEDIAT, DIV NEWBORN MED, BOSTON, MA 02111 USA. TUFTS UNIV, SCH VET MED, DEPT RADIOL, MEDFORD, MA 02155 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT OBSTET & GYNECOL, BOSTON, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1995 VL 37 IS 4 BP A287 EP A287 PN 2 PG 1 WC Pediatrics SC Pediatrics GA QP082 UT WOS:A1995QP08201706 ER PT J AU CHAN, C MOLRINE, D GEORGE, S GOORIN, A TARBELL, N MAUCH, P DILLER, L PHILLIPS, N AMBROSINO, D AF CHAN, C MOLRINE, D GEORGE, S GOORIN, A TARBELL, N MAUCH, P DILLER, L PHILLIPS, N AMBROSINO, D TI HEPTAVALENT PNEUMOCOCCAL CONJUGATE VACCINE (7-OMPC) PRIMES FOR ANTIBODY-RESPONSE TO PURE POLYSACCHARIDE PNEUMOCOCCAL VACCINE FOLLOWING TREATMENT FOR HODGKINS-DISEASE SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, JOINT CTR RADIAT THERAPY, BOSTON, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1995 VL 37 IS 4 BP A171 EP A171 PN 2 PG 1 WC Pediatrics SC Pediatrics GA QP082 UT WOS:A1995QP08201014 ER PT J AU DEVINCENZO, JP SKORNIK, WA MURTHY, GGK BRAIN, JD MCIVER, J SIBER, GR AF DEVINCENZO, JP SKORNIK, WA MURTHY, GGK BRAIN, JD MCIVER, J SIBER, GR TI AEROSOL DELIVERY OF RESPIRATORY SYNCYTIAL VIRUS (RSV) ANTIBODY TO THE LUNGS OF COTTON RATS SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV, SCH PUBL HLTH, DANA FARBER CANC INST, CAMBRIDGE, MA 02138 USA. MASSACHUSETTS PUBL HLTH BIOL LABS, BOSTON, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1995 VL 37 IS 4 BP A173 EP A173 PN 2 PG 1 WC Pediatrics SC Pediatrics GA QP082 UT WOS:A1995QP08201023 ER PT J AU FUSUNVAN, RD MACDERMOTT, RP WALKER, WA SANDERSON, IR AF FUSUNVAN, RD MACDERMOTT, RP WALKER, WA SANDERSON, IR TI BACTERIAL PRODUCTS INDUCE SECRETION OF INTERLEUKIN-8 BY INTESTINAL EPITHELIAL-CELLS SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR, BOSTON, MA 02114 USA. LAHEY CLIN FDN, GASTROINTESTINAL SECT, BOSTON, MA 02215 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1995 VL 37 IS 4 BP A122 EP A122 PN 2 PG 1 WC Pediatrics SC Pediatrics GA QP082 UT WOS:A1995QP08200717 ER PT J AU GRABOWSKI, EF HUG, EB MUKAI, S AF GRABOWSKI, EF HUG, EB MUKAI, S TI COMBINATION CHEMOTHERAPY AND PROTON-BEAM RADIATION FOR HIGH-RISK INTRAOCULAR RETINOBLASTOMA SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS EYE & EAR INFIRM, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1995 VL 37 IS 4 BP A157 EP A157 PN 2 PG 1 WC Pediatrics SC Pediatrics GA QP082 UT WOS:A1995QP08200929 ER PT J AU GUERINA, NG WARE, J BURBRIDGE, J MEISSNER, HC LYNFIELD, R HSU, HW PASTERNACK, MS GRADY, GF AF GUERINA, NG WARE, J BURBRIDGE, J MEISSNER, HC LYNFIELD, R HSU, HW PASTERNACK, MS GRADY, GF TI NEURODEVELOPMENTAL (ND) OUTCOMES FOR INFANTS WITH CONGENITAL TOXOPLASMA INFECTION (CTI) FROM A NEWBORN SEROLOGIC SCREENING AND TREATMENT PROGRAM SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 STATE LAB INST, BOSTON, MA USA. TUFTS UNIV NEW ENGLAND MED CTR, FLOATING HOSP CHILDREN, BOSTON, MA 02111 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1995 VL 37 IS 4 BP A292 EP A292 PN 2 PG 1 WC Pediatrics SC Pediatrics GA QP082 UT WOS:A1995QP08201734 ER PT J AU HUFFMAN, JA WERT, SE DRANOFF, G MULLIGAN, RC WHITSETT, JA AF HUFFMAN, JA WERT, SE DRANOFF, G MULLIGAN, RC WHITSETT, JA TI MACROPHAGES ACCUMULATE IN LUNGS OF TRANSGENIC MICE BEARING A TISSUE-SPECIFIC SP-C-GM-CSF CHIMERIC GENE SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 WHITEHEAD INST, CAMBRIDGE, MA USA. CHILDRENS HOSP MED CTR, DIV PULM BIOL, CINCINNATI, OH 45229 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1995 VL 37 IS 4 BP A392 EP A392 PN 2 PG 1 WC Pediatrics SC Pediatrics GA QP082 UT WOS:A1995QP08202336 ER PT J AU INGELFINGER, JR HAVERAN, L BOUYOUNES, B SWINFORD, RD JUNG, FF AF INGELFINGER, JR HAVERAN, L BOUYOUNES, B SWINFORD, RD JUNG, FF TI ANGIOTENSINOGEN MESSENGER-RNA IS UP-REGULATED IN THE PREGNANT KIDNEY SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP, CHILDRENS SERV, BOSTON, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1995 VL 37 IS 4 BP A364 EP A364 PN 2 PG 1 WC Pediatrics SC Pediatrics GA QP082 UT WOS:A1995QP08202164 ER PT J AU KURTJONES, FA SATTLER, FA NOVITSKY, T FLEISHER, GR SIBER, GR AF KURTJONES, FA SATTLER, FA NOVITSKY, T FLEISHER, GR SIBER, GR TI ENDOTOXIN NEUTRALIZING PROTEIN BINDS TO CELLS AND INHIBITS LIPOPOLYSACCHARIDE MEDIATED RESPONSES IN-VITRO SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV, CHILDRENS HOSP, SCH MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. ASSOCIATES CAPE COD INC, WOODS HOLE, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1995 VL 37 IS 4 BP A181 EP A181 PN 2 PG 1 WC Pediatrics SC Pediatrics GA QP082 UT WOS:A1995QP08201070 ER PT J AU MOLRINE, DC GUINAN, EC PARSON, SK WEINSTEIN, HJ ANTIN, JH WHEELER, C PHILLIPS, NR KINSELLA, K DEANS, K CIAMARRA, A AMBROSINO, DM AF MOLRINE, DC GUINAN, EC PARSON, SK WEINSTEIN, HJ ANTIN, JH WHEELER, C PHILLIPS, NR KINSELLA, K DEANS, K CIAMARRA, A AMBROSINO, DM TI DONOR IMMUNIZATION AND ANTIBODY-RESPONSES TO POLYSACCHARIDE (PS)-CONJUGATE VACCINE IN BONE-MARROW TRANSPLANTATION SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1995 VL 37 IS 4 BP A184 EP A184 PN 2 PG 1 WC Pediatrics SC Pediatrics GA QP082 UT WOS:A1995QP08201089 ER PT J AU NORLING, LL FOX, JW AF NORLING, LL FOX, JW TI BASEMENT-MEMBRANE, GLYCATION, AND GLUCOSE REGULATE ENDOTHELIAL-CELL RESPONSE TO ATRIAL-NATRIURETIC-PEPTIDE (ANP) SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PEDIAT NEPHROL, BOSTON, MA 02114 USA. UNIV VIRGINIA, HLTH SCI CTR, DEPT MICROBIOL, CHARLOTTESVILLE, VA 22903 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1995 VL 37 IS 4 BP A367 EP A367 PN 2 PG 1 WC Pediatrics SC Pediatrics GA QP082 UT WOS:A1995QP08202183 ER PT J AU STACK, A SALADINO, R MARRA, M NOVITSKY, T SIBER, GR FLEISHER, GR AF STACK, A SALADINO, R MARRA, M NOVITSKY, T SIBER, GR FLEISHER, GR TI A COMPARISON OF A RECOMBINANT ENDOTOXIN NEUTRALIZING PROTEIN VERSUS A RECOMBINANT BACTERICIDAL PERMEABILITY-INCREASING PROTEIN VARIANT FOR THE TREATMENT OF ESCHERICHIA-COLI SEPSIS IN THE RAT SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 ASSOCIATES CAPE COD INC, WOODS HOLE, MA USA. INCYTE PHARMACEUT, PALO ALTO, CA USA. HARVARD UNIV, CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST, DIV EM MED, BOSTON, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1995 VL 37 IS 4 BP A188 EP A188 PN 2 PG 1 WC Pediatrics SC Pediatrics GA QP082 UT WOS:A1995QP08201115 ER EF